Datasets:

pdf2dataset
/

69347c28a4b70caf8b7d04cf6af062d2

Dataset card Viewer Files Files and versions Community

Split (1)

train · 944 rows

text stringlengths 3.88k 7.89k	source stringclasses 1 value
FLUNIXIN MEGLUMINE 401 Overdosage/Acute Toxicity No clinical case reports of ﬂunixin overdoses were discovered. It is suggested that acute overdosage be handled by using established protocols of emptying the gut (if oral ingestion and practical or possible) and treating the patient supportively. Drug Interactions Drug/drug interactions have not been appreciably studied for ﬂunixin and the label does not mention any drug interactions. However, the following drug interactions have either been reported or are theoretical in humans or animals receiving other NSAIDs and may be of signiﬁcance in veterinary patients receiving ﬂunixin: !TASPIRIN : When aspirin is used concurrently with NSAIDs, plasma levels of the NSAID could decrease and an increased likelihood of GI adverse effects (blood loss) could occur !TCYCLOSPORINE : NSAIDs may increase cyclosporine blood levels and increase the risk for nephrotoxicity !TDIGOXIN : NSAIDs may increase serum levels of digoxin; use with caution in patients with severe cardiac failure !TFUROSEMIDE & OTHER DIURETICS : NSAIDs may reduce the saluretic and diuretic effects of furosemide !TMETHOTREXATE : Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate; use together with caution !TNEPHROTOXIC AGENTS (e. g., amphotericin B, aminoglycosides, cispl-atin, etc. ): Potential for increased risk of nephrotoxicity if used with NSAIDs !TPROBENECID : May cause a signiﬁcant increase in serum levels and half-life of some NSAIDs !TWARFARIN : Use with NSAIDs may increase the risk for bleeding Doses !TDOGS: Note : Many of these doses are from a time when there were no approved NSAIDs for dogs; consider using approved drugs ﬁrst. a) 0. 5-2. 2 mg/kg IM or IV one time only (Jenkins 1987) b) As an antidiarrheal/antipyretic: 1 mg/kg IV (do not admin-ister more than once in an animal that has received corticos-teroids (Tams 1999) c) For ocular indications: 0. 25 mg/kg IV once daily for no more than 5 days at a time. May also be used preoperatively by in-jecting IV 30 minutes before ocular surgery. May dilute 1:9 (ﬂunixin: sterile water) in syringe to administer accurately to very small animals. (Wyman 1986) d) For ocular disease: 0. 5 mg/kg IV twice daily for 1-2 treat-ments For acute gastric dilatation: 1 mg/kg IV once For GI tract obstruction: 0. 5 mg/kg IV once to twice daily for 3 treatments (Morgan 1988) e) For surgical pain: 1 mg/kg IV, SC or IM initially once; 1 mg/ kg subsequent daily doses For pyrexia: 0. 25 mg/kg IV, SC or IM once, may be repeated in 12-24 hours if needed For ophtho procedures: 0. 25-1 mg/kg IV, IM or SC once; may be repeated in 12-24 hours if needed (Johnson 1996) !TCATS: a) As an antiinﬂammatory/analgesic: For surgical pain: 0. 25 mg/kg SC once; may be repeated once in 12-24 hours if needed; For pyrexia: 0. 25 mg/kg IV, SC or IM once, may be repeated once in 12-24 hours if needed (Johnson 1996) !TFERRETS: a) 0. 5-2 mg/kg PO or IM one time daily (Williams 2000) !TRABBITS/RODENTS/SMALL MAMMALS: a) Rabbits: 1. 1 mg/kg SC, IM, IV q12-24h (Ivey and Morrisey 2000) b) Rabbits: 1. 1 mg/kg SC or IM q12h Rodents: 2. 5 mg/kg SC or IM q12h (Huerkamp 1995) c) Chinchillas: 1-3 mg/kg SC q12h Guinea pigs: 2. 5-5 mg/ kg SC q12h Gerbils, Mice, Rats, Hamsters: 2. 5 mg/kg SC q12-24h (Adamcak and Otten 2000) !TCATTLE: a) For labeled indications: 1. 1-2. 2 mg/kg (1-2 m L per 100 lbs. BW) given slow IV either once a day as a single dose or di-vided into two doses q12h for up to 3 days. Avoid rapid IV administration. (Package Insert; Banamine®—Schering). b) As an analgesic: 1. 1-2. 2 mg/kg IV q6-12hours; recommend 72 hour milk withdrawal at this dose rate. (Walz 2006b) c) As an analgesic for visceral pain: 0. 25-1 mg/kg IV q12-24h. (Anderson 2006a) c) For treatment of radial nerve injury: 250-500 mg IV or IM twice daily, may need only one treatment; taper and discon-tinue usually after 2-3 days (Rebhun 1986) Note : See warn-ings for IM use in the Contraindications section above. d) For aseptic lameness in cattle: 1. 1 mg/kg; must be adminis-tered within 24 hrs after onset of symptoms to be effective (Berg 1986) e) 2. 2 mg/kg then 1. 1 mg/kg q8h IV (Jenkins 1987) !THORSES: (Note : ARCI UCGFS Class 4 Drug) a) Injectable: 1. 1 mg/kg IV or IM once daily for up to 5 days. For colic cases, use IV route and may redose when necessary. Oral Paste: 1. 1 mg/kg PO (see markings on syringe—cali-brated in 250 lb. weight increments) once daily. One syringe will treat a 1000 lb. horse for 3 days. Do not exceed 5 days of consecutive therapy. Oral Granules: 1. 1 mg/kg PO once daily. One packet will treat 500 lbs of body weight. May apply on feed. Do not exceed 5 consecutive days of therapy. (Package Inserts; Banamine®—Schering Animal Health) b) For adjunctive treatment of medical colic: 0. 25-1. 1 mg/kg IV q8-12h; usually 1. 1 mg/kg IV q12h. (Blikslager 2006b) c) T o decrease pain, inﬂammation, and edema in laminitis: 0. 5-1. 1 mg/kg IV or PO q8-12 hours. A dose of 0. 25 mg/kg can be administered IV q8h to interrupt eicosanoid produc-tion associated with endotoxemia. (Moore 2003) d) For adjunctive treatment of laminitis: 1. 1 mg/kg IM, IV or PO twice daily (Brumbaugh, Lopez et al. 1999) e) For adjunctive treatment of uveitis in foals: 0. 5-1 mg/kg (route not noted) twice daily (Cutler 2003) !TSWINE: a) T o control pyrexia associated with swine respiratory disease: 2. 2 mg/kg IM once, only in the neck musculature with a max-imum of 10 m L per site. (Label information; Banamine®-S— Schering-Plough) !TBIRDS: a) As an antiinﬂammatory analgesic: 1-10 mg/kg IM once daily. Note : Renal disease and death occur occasionally in psittacines after repeated doses of ﬂunixin. Use the lowest possible dose for the shortest duration of time. Recommend supplemental hydration. (Clyde and Paul-Murphy 2000)	pppbs.pdf
402 FLUOROURACIL TMonitoring T ! Analgesic/antiinﬂammatory/antipyretic effects T ! GI effects in dogs T ! CBC's, occult blood in feces with chronic use in horses Client Information T ! If injecting IM, do not inject into neck muscles. T ! he IM route is extra-label in cattle and should only be used when the IV route is not feasible for use. Longer withdrawal times would be required after IM use. T ! Flunixin should not be used in an attempt to ambulate cattle to be shipped for slaughter. Chemistry/Synonyms Flunixin meglumine, a nonsteroidal antiinﬂammatory agent is a highly substituted derivative of nicotinic acid, and is unique struc-turally when compared to other NSAIDs. It occurs as a white to off-white powder that is soluble in water and alcohol. The chemical name for ﬂunixin is 3-pyridine-carboxylic acid. Flunixin may also be known as 3-pyridine-carboxylic acid, ﬂunixin meglumine, Sch-14714, Banamine®, Flumeglumine®, and Finadyne®, Flu-Nix®D, Flunixamine®, Flunixiject®, Flunizine®, Prevail®, Suppressor®, and Vedagesic®. Storage/Stability/Compatibility All ﬂunixin products should be stored between 2-30°C (36-86°F). It has been recommended that ﬂunixin meglumine injection not be mixed with other drugs because of unknown compatibilities. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Note : Individual products may be approved and be labeled for differ-ent species, lactation status, different routes of administration (IV, IM). Flunixin is also approved only for use in horses not intended for food. Refer to the speciﬁc product label for more information Flunixin Meglumine for Injection: 50 mg/m L in 50 m L, 100 m L and 250 m L vials; At the time of writing, the following products are ap-proved for use in horses and use in beef and dairy cattle (not for use in dry dairy cows or veal calves): Banamine® (Schering-Plough), Flunixin Meglumine Injection (IVX, Vet T ek, Aspen), Flumeglumine® (Phoenix Pharmaceuticals), Flunixamine® (Fort Dodge), Flunixiject® (Butler), Prevail® (Vet One), Suppressor® Dairy (RXV), Flunizine® (Bimeda), Vedagesic® (Vedco); Flu-Nix®D (Agri Labs); (Rx). Depend-ing on product, when used as labeled: withdrawal (Cattle): Milk 36 hours; Slaughter 4 days. Flunixin Meglumine for Injection: 50 mg/m L in 100 m L vials; At the time of writing, the following product is approved for IM use in swine: Banamine®-S (Schering-Plough); (Rx) Withdrawal: Slaughter = 12 days. Flunixin Meglumine for Injection: 50 mg/m L in 100 m L vials; At the time of writing, the following product is approved for use in horses: Suppressor® (RXV); (Rx) Flunixin Meglumine Oral Paste: 1500 mg/syringe in 30 gram syringes in boxes of 6; Banamine® Paste (Schering-Plough); (Rx). Approved for use in horses. Flunixin Meglumine Oral Granules: 250 mg in 10 gram sachets in boxes of 50; 20 g sachets containing 500 mg ﬂunixin in boxes of 25; Banamine® Granules (Schering-Plough); (Rx) Approved for use in horses. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: None 5-Fluorocytosine—see Flucytosine FLUOROURACIL (5-FU) (ﬂure-oh-yoor-a-sill) Adrucil® ANTINEOPLASTIC AGENT Prescriber Highlights TT Antineoplastic agent used in dogs for susceptible tumors (see doses) & intralesionally in horses for skin tumors TT Contraindications: Do NOT use in any form on cats; Pa-tients hypersensitive to it, in poor nutritional states, de-pressed bone marrow, serious infections TT Known teratogen TT Adverse Effects: Dose-dependent myelosuppression, GI toxicity, & neurotoxicity Uses/Indications Chemotherapeutic agent used for canine mammary carcinoma (in combination with doxorubicin and cyclophosphamide—FAC pro-tocol), dermal squamous cell carcinoma and GI tract tumors. It is also used for intralesional injection with epinephrine into certain skin neoplasms (squamous cell carcinoma, melanoma, sarcoid) in horses. Pharmacology/Actions Fluorouracil is converted via intracellular mechanisms to active metabolites (ﬂuoruridine monophosphate—FUMP and ﬂuoruri-dine triphosphate—FUTP). FUMP inhibits the synthesis of deoxy-thymidine triphosphate thereby interfering with DNA synthesis. FUTP incorporates into RNA and inhibits cell function. Pharmacokinetics Fluorouracil is administered systemically via the IV route. It rapidly disappears from the systemic circulation (plasma half live is about 15 minutes in humans) and is primarily distributed into tumor cells, intestinal mucosa, liver, and bone marrow. While some of the drug is converted to active metabolites, (see Pharmacology above), the majority of it is metabolized by the liver. A small amount (about 15% of dose) is excreted unchanged into the urine. Contraindications/Precautions/Warnings Cats develop a severe, potentially fatal neurotoxicity when given ﬂuorouracil. It is contraindicated in cats in any form (including topical). 5-FU is contraindicated in patients hypersensitive to it, in poor nutritional states, with depressed or reduced bone marrow function or concurrent serious infections. Adverse Effects In dogs, 5-FU causes a dose-dependent myelosuppression, GI tox-icity (diarrhea, GI ulceration/sloughing, stomatitis), and neurotox-icity (seizures). Fluorouracil has a very narrow therapeutic index and should be used only by clinicians with experience using cancer chemotherapeutic agents.	pppbs.pdf
FLUOROURACIL 403 Reproductive/Nursing Safety The drug is a known teratogen and its use should be weighed against any risks to offspring. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fe-tal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) It is not known whether ﬂuorouracil is excreted in milk. Because ﬂuorouracil inhibits DNA, RNA and protein synthesis, milk replac-er should be considered if the dam requires 5-FU. Overdosage/Acute Toxicity While overdoses are possible with IV use, careful checking of dos-ages and preparation should minimize the risks. Oral ingestions of topical products have occurred with dogs. The lowest reported toxic dose at which dogs show adverse signs is 8. 6 mg/kg. Seizures and death have been reported at doses as low as 10. 3 mg/kg (APCC database). Signs at lower doses include mild GI irritation and vomiting. There were 332 exposures to 5-Fluorouracil reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases 319 were dogs with 65 show-ing clinical signs and the remaining 13 cases were cats with 3 show-ing clinical signs. Common ﬁndings in dogs recorded in decreas-ing frequency included vomiting, seizures, death, euthanasia, and ataxia. Common ﬁndings in cats recorded in decreasing frequency included ataxia, anemia, anorexia, blindness, and death. Should an oral ingestion occur, aggressive GI decontamination with GI protection should be employed and the patient monitored. Seizure control with diazepam is often unrewarding. A barbiturate or general anesthesia is often required. Control of pain is impor-tant. Use broad-spectrum antibiotics to prevent secondary bacte-rial infections. If bone marrow suppression develops, ﬁlgrastim (Neupogen®) can be used to stimulate bone marrow stem cell pro-liferation in dogs. Patients given an accidental parenteral overdose should undergo intensive hematologic monitoring for at least 4 weeks and be sup-ported as required. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ﬂuorouracil and may be of signiﬁcance in veterinary patients: !!LEUCOVORIN : May increase the GI toxic effects of 5-FU Laboratory Considerations !TFluorouracil may cause increases in alkaline phosphatase, serum transaminase, serum bilirubin, and lactic dehydrogenase Doses For more information on using 5-FU as part of chemotherapy pro-tocols, refer to the protocols found in the appendix or other dos-ages/protocols found in numerous references, including: Withrow and Mac Ewen's Small Animal Clinical Oncology, 4th Ed. (Withrow and Vail 2007); Canine and Feline Geriatric Oncology (Villalobos 2007); Small Animal Internal Medicine, 3rd Edition (Nelson and Couto 2003); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edition (Ettinger and Feldman 2005); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. (Tilley and Smith 2004). !TDOGS: a) For canine mammary carcinoma (in combination with dox-orubicin and cyclophosphamide—FAC protocol), dermal squamous cell carcinoma and GI tract tumors: 150 mg/m2 IV weekly, or 5-10 mg/kg IV weekly (Kitchell and Dhaliwal 2000) !TCATS: 5-FU is CONTRAINDICATED in cats in any form (including topical) !THORSES: a) For intratumoral injection with epinephrine into certain skin neoplasms (squamous cell carcinoma, melanoma, sarcoid): 0. 3 m L of 1:1000 epinephrine is added to each m L of 5-FU solution up to a maximum of 3 m L of epinephrine per total volume of 5-FU injected. Epinephrine may result in white hair growth and can cause transient excitation, tachycardia, and shaking if absorbed systemically in sufﬁcient quantities. (Moll 2002) Monitoring !TCBC's (nadirs usually occur between days 9-14 with recovery by day 30; no dog info located) !TGI and CNS adverse effects !TEfﬁcacy Client Information !TClients should understand the serious potential effects of the drug (including death) and be committed for follow-up monitoring Chemistry/Synonyms A pyrimidine antagonist antineoplastic agent, ﬂuorouracil (5-FU) occurs as a white, practically odorless, crystalline powder. It is spar-ingly soluble in water and slightly soluble in alcohol. The com-mercially available injection has its p H adjusted to 8. 6-9. 4 and may be colorless or slightly yellow in color. Fluorouracil may also be known as 5-ﬂuorouracil, ﬂuorouracilo, ﬂuorouracilum, 5-FU, NSC-19893, Ro-2-9757, and WR-69596; many trade names are available. Storage/Stability/Compatibility The injection should be stored between 15-30°C; avoid freezing and exposure to light. Slight color changes in the solution can be ig-nored. If a precipitate forms, the solution can be heated to 60°C and shaken vigorously to redissolve the drug. Cool to body tempera-ture before administering. If unsuccessful in redissolving the drug, it should not be used. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Fluorouracil Injection: 50 mg/m L in 10, 20, 50, & 100 m L vials and 10 m L amps; Adrucil® (Gensia Sicor); generic; (Rx) Also available in topical creams and solutions in concentrations ranging from 0. 5% to 5%. These are indicated in humans for treating multiple actinic or solar keratoses, and superﬁcial basal cell carcino-mas (5%) when other treatments are impractical.	pppbs.pdf
404 FLUOXETINE HCL FLUOXETINE HCL (ﬂoo-ox-e-teen) Prozac®, Reconcile® SELECTIVE SEROTONIN-REUPTAKE INHIBITOR (SSRI) Prescriber Highlights TT A selective-serotonin reuptake inhibitor antidepressant used in dogs & cats for a variety of behavior disorders TT Contraindications: Patients with known hypersensitivity or receiving monoamine oxidase inhibitors TT Caution: Patients with diabetes mellitus or seizure disor-ders; dosages may need to be reduced in patients with severe hepatic impairment TT Adverse Effects: DOGS: Anorexia, lethargy, GI effects, anxiety, irritability, insomnia/hyperactivity, or panting, & aggressive behavior in previously unaggressive dogs is possible; CAT S: May exhibit behavior changes (anxiety, irritability, sleep disturbances), anorexia, & changes in elimination patterns TT Drug Interactions Uses/Indications Fluoxetine may be beneﬁcial for the treatment of canine aggression, stereotypic behaviors (and other obsessive-compulsive behaviors), and anxiety. It may be useful in cats for the aforementioned behav-iors and, additionally, for inappropriate elimination. Pharmacology/Actions Fluoxetine is a highly selective inhibitor of the reuptake of sero-tonin in the CNS thereby potentiating the pharmacologic activity of serotonin. Fluoxetine apparently has little effect on other neu-rotransmitters (e. g., dopamine or norepinephrine). Pharmacokinetics Fluoxetine is apparently well absorbed after oral administration. In a study done in beagles, approximately 70% of an oral dose reached the systemic circulation. The presence of food altered the rate, but not the extent, of absorption. The oral capsules and oral liquid ap-parently are bioequivalent. Fluoxetine and its principal metabolite, norﬂuoxetine (active), are apparently distributed throughout the body with highest levels found in the lungs and the liver. CNS concentrations are detected within one hour of dosing. In humans, ﬂuoxetine is approximately 95% bound to plasma proteins. Fluoxetine crosses the placenta in rats, but it is unknown if it does so in other species. Fluoxetine en-ters maternal milk in concentrations about 20-30% of those found in plasma. Fluoxetine is primarily metabolized in the liver to a variety of metabolites, including norﬂuoxetine (active). Both ﬂuoxetine and norﬂuoxetine are eliminated slowly. In humans, the elimination half-life of ﬂuoxetine is about 2-3 days and norﬂuoxetine, about 7-9 days. In dogs, elimination half-life average for ﬂuoxetine is about 6+ hours and for norﬂuoxetine, about 2 days; wide interpa-tient variation does occur, however. Renal impairment does not ap-parently affect elimination rates substantially, but liver impairment will decrease clearance rates. Contraindications/Precautions/Warnings The labeling for the veterinary (canine) approved drug states that ﬂuoxetine should not be used in dogs with epilepsy or a history of seizures, and should not be given with drugs that lower the sei-zure threshold (e. g., acepromazine, chlorpromazine). Fluoxetine is contraindicated in patients with known hypersensitivity to it, as well as those receiving monoamine oxidase inhibitors (see Drug Interactions below). Fluoxetine should be used with caution in patients with diabetes mellitus as it may alter blood glucose. Dosages may need to be re-duced in patients with severe hepatic impairment. Adverse Effects In multi-site ﬁeld trials in dogs, seizures were reported in some of the dogs treated with ﬂuoxetine. Absolute causality and incidence rate has not been determined. Fluoxetine may cause lethargy, GI effects, anxiety, irritability, insomnia/hyperactivity, or panting. Anorexia is a common side-affect in dogs (usually transient and may be negated by temporarily increasing the palatability of food and/or hand feeding). Some dogs have persistent anorexia that pre-cludes further treatment. Aggressive behavior in previously unag-gressive dogs has been reported. Cats may exhibit behavior changes (anxiety, irritability, sleep disturbances), anorexia, and changes in elimination patterns. In humans, potential adverse effects are extensive and diverse, but most those most commonly noted include anxiety, nervous-ness, insomnia, drowsiness, fatigue, dizziness, anorexia, nausea, rash, diarrhea, and sweating; seizures or hepatotoxicity are possible. About 15% of human patients discontinue treatment due to ad-verse effects. Reproductive/Nursing Safety Fluoxetine's safety during pregnancy has not been established. The canine-approved product states that studies to determine the effects of ﬂuoxetine in breeding, pregnant, or lactating dogs or in patients less than 6 months of age have not been conducted. Preliminary studies done in rats demonstrated no overt teratogenic effects. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) The drug is excreted into milk (20-30% of plasma levels), so caution is advised in nursing patients. Clinical implications for nursing offspring are not clear. Overdosage/Acute Toxicity The LD 50 for rats is 452 mg/kg. Five of six dogs given an oral “tox-ic” dose developed seizures that immediately stopped after giving IV diazepam. The dog having the lowest plasma level of ﬂuoxetine that developed seizures had a level twice that expected of a human taking 80 mg day (highest recommended dose). There were 277 exposures to ﬂuoxetine reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org ) dur-ing 2005-2006. In these cases 225 were dogs with 18 showing clini-cal signs, 46 were cats with 5 showing clinical signs. The remaining reported cases were 3 birds, 2 ferrets, and 1 bovine none of which showed clinical signs. Common ﬁndings in dogs recorded in de-creasing frequency included lethargy, agitation, ataxia, hypersaliva-tion and tremors. Common ﬁndings in cats recorded in decreas-ing frequency included hypersalivation, lethargy, agitation and tail chasing. Treatment of ﬂuoxetine overdoses consists of symptomatic and supportive therapy. Gut emptying techniques should be employed when warranted and otherwise not contraindicated. Diazepam should be used to treat seizures.	pppbs.pdf
FLUTICASONE PROPIONATE 405 TDrug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ﬂuoxetine and may be of signiﬁcance in veterinary patients: T ! BUSPIRONE : Increased risk for serotonin syndrome T ! CYPROHEPTADINE : May decrease or reverse the effects of SSRIs T ! DIAZEPAM, ALPRAZOLAM : Fluoxetine may increase diazepam levels T ! DIURETICS : Increased risk for hyponatremia T ! INSULIN : May alter insulin requirements T ! ISONIAZID : Increased risk for serotonin syndrome T ! MAO INHIBITORS (including amitraz and potentially, selegiline ): High risk for serotonin syndrome; use contraindicated; in hu-mans, a 5 week washout period is required after discontinuing ﬂuoxetine and a 2 week washout period if ﬁrst discontinuing the MAO inhibitor T ! PENTAZOCINE : Serotonin syndrome-like adverse effects possible T ! PHENYTOIN : Increased plasma levels of phenytoin possible T ! PROPRANOLOL, METOPROLOL : Fluoxetine may increase these beta-blocker's plasma levels; atenolol may be safer to use if ﬂuoxetine required T ! TRICYCLIC ANTIDEPRESSANTS (e. g., clomipramine, amitriptyline ): Flu-oxetine may increase TCA blood levels and may increase the risk for serotonin syndrome T ! TRAZODONE : Increased plasma levels of trazodone possible T ! WARFARIN : Fluoxetine may increase the risk for bleeding Doses T ! DOGS: For the adjunctive treatment of behavior disorders (see Indica-tions above): a) For the treatment of canine separation anxiety in conjunc-tion with a behavior modiﬁcation plan: 1-2 mg/kg PO once daily (Label Information; Reconcile®—Lilly) b) 1 mg/kg PO once to twice daily for 6-8 weeks to start (Over-all 2000) c) 0. 5-1 mg/kg once daily (Line 2000); (Thompson 1999) d) 1-1. 5 mg/kg daily; Latency to effect is 1-4 weeks (Crowell-Davis 1999) e) 1-1. 5 mg/kg PO once daily (Seibert 2003) f) 1 mg/kg PO once daily (up to 3 mg/kg PO once daily) (Lands-Client Information T ! his medication is most effective when used with a behavior modiﬁcation program T ! Keep this medication away from children and other pets T ! Most commonly reported adverse effects with use of this medi-cation include: lethargy/depression, decreased appetite, vomiting, shaking, tremor, restlessness, diarrhea, and excessive vocalization (whining); if these are severe or persist, contact your veterinarian T ! Rarely, dogs may develop seizures (convulsion) while receiving this medication; contact veterinarian immediately should this occur Chemistry/Synonyms A member of the phenylpropylamine-derivative antidepressant group, ﬂuoxetine differs both structurally and pharmacologi-cally from either the tricyclic or monoamine oxidase inhibitor an-tidepressants. Fluoxetine HCl occurs as a white to off-white crystal-line solid. Approximately 50 mg are soluble in 1 m L of water. Fluoxetine may also be known as: ﬂuoxetini hydrochloridum, and LY-110140; many trade names are available. Storage/Stability Capsules and tablets should be stored in well-closed containers at room temperature. The oral liquid should be stored in tight, light-resistant containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Fluoxetine Chewable Tablets: 8 mg, 16 mg, 32 mg, & 64 mg; Recon-cile® (Lilly); (Rx). Approved for use in dogs. The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Fluoxetine HCl Tablets: 10 mg & 20 mg (as base); Prozac® (Eli Lilly/ Dista); generic; (Rx) Fluoxetine HCl Capsules: 10 mg, 20 mg, 40 mg (as base) and 90 mg (delayed-release); Prozac® Pulvules & Prozac® Weekly (Eli Lilly/Dista); Sarafem® Pulvules (Warner Chilcott); generic; (Rx) Fluoxetine HCl Oral Solution: 4 mg/m L (as base) in 120 m L & 473 m L; Prozac® (Eli Lilly/Dista); generic; (Rx) berg 2004) T ! CATS: T o help control urine marking or separation anxiety: a) 0. 5-1 mg/kg PO once daily (Neilson 2006b); (Neilson 2006a) T o control pruritus when other therapies have failed: a) 1-5 mg/cat PO once daily; advise obtaining baseline lab work. Assess therapy after 1-4 weeks. Taper off dose over 6-8 weeks. (Messinger 2000) b) 0. 5-1 mg/kg PO once daily (Overall 2000), (Seibert 2003), (Landsberg 2004) c) 0. 5-1 mg/kg, daily. Latency to effect is 1-4 weeks (Crowell-Davis 1999) Monitoring T ! Efﬁcacy T ! Adverse effects; including appetite (weight) FLUTICASONE PROPIONATE (ﬂoo-ti-ca-sone) Flovent® GLUCOCORTICOID, INHALED/TOPICAL Prescriber Highlights TT Glucocorticoid used most commonly in veterinary medi-cine as an inhaled aerosol TT Has shown efﬁcacy in treating feline asthma, dogs with chronic cough, & in horses for recurrent airway obstruc-tion or inﬂammatory airway disease TT May be useful as a nasally inhaled treatment for allergy-related rhinosinusitis TT Appears to be well tolerated; suppression of HPA axis possible TT Must be used with a species-appropriate delivery device TT Expense may be an issue	pppbs.pdf
406 FLUTICASONE PROPIONATE Uses/Indications While there are topical forms of ﬂuticasone, most veterinary inter-ests are in the inhaled versions of the drug. The aerosol for pulmo-nary inhalation appears to be effective in treating feline asthma, re-current airway obstruction (RAO, heaves) or inﬂammatory airway disease (IAD) in horses, and dogs with chronic tracheobronchial disease. While the majority of small animal use has been with ﬂuti-casone, there are several other aerosol corticosteroids for inhalation (beclomethasone dipropionate, ﬂunisolide, and triamcinolone ac-etonide) that theoretically could be used for the same purpose. The nasal inhalation corticosteroid products may be useful for allergy-related chronic rhinosinusitis in cats and dogs. Pharmacology/Actions Like other glucocorticoids, ﬂuticasone has potent antiinﬂamma-tory activity. Fluticasone has an afﬁnity 18X that of dexamethasone for human glucocorticoid receptors. For a more thorough discus-sion of glucocorticoid effects, refer to the Glucocorticoids, General Information monograph. Pharmacokinetics In humans, when ﬂuticasone aerosol is administered via the lung, about 30% is absorbed into the systemic circulation. In humans, a dose of 880 mcg (4 puffs of the 220 mg aerosol) showed peak plasma concentrations of 0. 1 to 1 ng/m L. Volume of distribution averages 4. 2 L/kg and it is 91% bound to human plasma proteins. Fluticasone is metabolized via cytochrome P450 3A4 isoenzymes to a metabolite with negligible pharmacologic activity. T erminal elimination half-life is about 8 hours. Most of the drug is excreted in the feces as parent drug and metabolites. Contraindications/Precautions/Warnings Fluticasone is contraindicated when patients are hypersensitive to it or during acute bronchospasm (status asthmaticus). Adverse Effects In humans, the most likely adverse effects are pharyngitis and up-per respiratory infections. While inhaled steroids generally cause signiﬁcantly fewer adverse effects than injectable or oral therapy, suppression of the HPA axis can occur. When transferring patients from systemic steroid therapy to inhaled steroids, wean slowly off systemic therapy to avoid acute adrenal insufﬁciency. Prepare to cover patients with additional steroid therapy during periods of acute stress, severe asthma attacks occurring during the withdrawal stage, or after transfer to inhaled steroids. Fluticasone is not useful for acute bronchospasm; cases of ﬂuticasone-induced bronchos-pasm have been reported in humans. Reproductive/Nursing Safety In humans, the FDA categorizes inhaled ﬂuticasone as a category C drug for use during pregnancy (Animal studies have shown an ad-verse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate stud-ies in humans). When given subcutaneously to laboratory animals, ﬂuticasone caused a variety of teratogenic effects, including growth retardation, cleft palate, omphalocele and retarded cranial ossiﬁca-tion. It should be used during pregnancy only when the beneﬁts clearly outweigh the risks of therapy. It is not known if the drug enters maternal milk; use with cau-tion in nursing dams. Overdosage/Acute Toxicity Acute overdoses of this medication are unlikely, but there have been reported cases of dogs puncturing canisters of albuterol and devel-oping adverse effects. A similar occurrence with ﬂuticasone would unlikely require treatment. Chronic overdoses could result in sig-niﬁcant HPA axis suppression and cushinoid effects. Drug Interactions While the manufacturer states that due to the low systemic plasma levels associated with inhalational therapy clinically signiﬁcant drug interactions are unlikely, use caution when used in conjunction with other drugs (such as ketoconazole ) that can inhibit CYP 3A4 isoenzymes; theoretically, ﬂuticasone levels could be increased. Laboratory Considerations No speciﬁc laboratory interactions or considerations were noted. Doses !TCATS: For treatment of feline asthma: a) For cats with signs of asthma that occur daily: Give prednisone at 1-2 mg/kg PO twice daily for 10-14 days. Once a beneﬁcial response to oral prednisone has been documented (usually within 3-5 days) begin inhaled ste-roids as you wean off oral prednisone. Use a delivery device (e. g., Aero Kat®) in combination with a spacer and 110 mcg ﬂuticasone metered dose inhaler. Attach MDI and the facemask to the spacer. Place facemask gently over cats mouth and nose and actuates the MDI to ﬁll the spacer with medication. The cat breathes in and out for 7-10 times with the mask in place. (Padrid 2006) !TDOGS: For adjunctive treatment of chronic tracheobronchial disease: a) In dogs with excessive side effects associated with oral ste-roids therapy: Use a delivery device (e. g., Aero Dawg®) in combination with either ﬂuticasone 220 mcg or 110 mcg (1 puff) twice daily. Ensure a tightly ﬁtting face mask and counting 7-10 respirations after actuating the MDI into the spacer is important for optimizing therapy. (Johnson 2007) !THORSES: Use a delivery device (e. g., Aeromask® or Equine-haler®) in com-bination with a metered dose inhaler: a) For the prototypical young racehorse with IAD: Weeks 1 and 2: Fluticasone 2200 mcg (10 puffs) twice daily or beclometha-sone HFA 1000 mg (5 puffs) twice daily with albuterol 450 mcg (5 puffs) prior to steroid inhaler and at approximately 30 minutes before exercise. Weeks 3 and 4: Fluticasone 2200 mcg (10 puffs) once daily or beclomethasone HFA 1000 mg (5 puffs) twice daily. Recheck in 4 weeks to determine further treatment. For the typical horse with moderate RAO (heaves): Begin stringent control of environment and a course of systemic prednisone therapy. ( Note : Reference does not state when oral prednisone should be discontinued. ) At week 3 add ﬂu-ticasone 2200 mcg (10 puffs) twice daily with salmeterol 210 mcg (10 puffs) twice daily. Week 4: ﬂuticasone 2200 mcg (10 puffs) once daily with salmeterol 210 mcg (10 puffs) once daily. If lung function shows a good response at end of 4 weeks: ﬂuticasone 2200 mcg (10 puffs) once every other day with salmeterol 210 mcg (10 puffs) once daily. (Mazan 2002); (Mazan 2003) Monitoring !TEfﬁcacy	pppbs.pdf
FLUVOXAMINE MALEATE 407 Client Information T ! Before using, shake well and, if possible, bring canister to room temperature. Do not puncture or incinerate can. Must be used with a spacer device appropriate for the species being treated. T ! Allow animal to breath with the mask on for 7-10 times before removing T ! One puff twice a day will last approximately 2 months Chemistry/Synonyms A triﬂuorinated glucocorticoid, ﬂuticasone propionate occurs as a white to off-white powder that is practically insoluble in water and slightly soluble in ethanol. Fluticasone may also be known as: CCI-18781, ﬂuticasoni pro-pionas, Advair Diskus®, Cutovate®, Flixotide®, Flixonase®, Flovent®, and Flutivate®. Storage/Stability/Compatibility Fluticasone propionate aerosol for inhalation (Flovent®) should be stored between 2-30°C (36-86°F); protect from freezing and di-rect sunlight. Store canister with the mouthpiece down. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Fluticasone Propionate aerosol for inhalation: 44 mcg per actuation, 110 mcg per actuation, 220 mcg per actuation in 7. 9 gram and 13 gram canisters. Each 7. 9 gram canister contains approximately 60-metered inhalations; 13 gram canister contains approximately 120-metered inhalations when used with the supplied aerosol actuator; Flovent® (Glaxo Smith Kline); (Rx) Note : Dosages referenced above FLUVOXAMINE MALEATE (ﬂoo-vox-a-meen) Luvox® SELECTIVE SEROTONIN-REUPTAKE INHIBITOR (SSRI) Prescriber Highlights TT A selective-serotonin reuptake inhibitor (SSRI) antide-pressant similar to ﬂuoxetine; used in dogs & cats for variety of behavior disorders TT Not commonly used TT Contraindications: Patients with known hypersensitivity or receiving MAOIs TT Must treat for 6-8 weeks before evaluating efﬁcacy TT Caution: Patients with severe cardiac, renal or hepatic disease; dosages may need to be reduced in patients with severe renal or hepatic impairment TT Adverse effect proﬁle not well established: Potentially, DOGS: Anorexia, lethargy, GI effects, anxiety, irritability, insomnia/hyperactivity, or panting; aggressive behavior in previously non-aggressive dogs possible. CAT S: May exhibit sedation, decreased appetite/anorexia, vomiting, diarrhea, behavior changes (anxiety, irritability, sleep dis-turbances), & changes in elimination patterns TT Drug-drug interactions use the 220 mcg/actuation product. Fluticasone is also available commercially as a Fluticasone Propi-onate/Salmeterol Powder for Inhalation: 100 mcg ﬂuticasone propi-onate, 50 mcg salmeterol; 250 mcg ﬂuticasone propionate, 50 mcg salmeterol; & 500 mcg ﬂuticasone propionate, 50 mcg salmeterol) in color-coded blisters; Advair Diskus® (Glaxo Smith Kline); (Rx) Nasal solutions, topical creams and ointments containing ﬂuticasone are also available. Uses/Indications Fluvoxamine may be considered for use in treating a variety of be-havior-related diagnoses in dogs and cats, including aggression and stereotypic behaviors (and other obsessive-compulsive behaviors). Pharmacology/Actions Fluvoxamine is a highly selective inhibitor of the reuptake of sero-tonin in the CNS thereby potentiating the pharmacologic activity of serotonin. Fluvoxamine apparently has little effect on dopamine or norepinephrine, and apparently no effect on other neurotrans-mitters. Pharmacokinetics There is limited data on the pharmacokinetics of ﬂuvoxamine in domestic animals. In dogs, ﬂuvoxamine appears to be completely absorbed; only about 10% of a dose is excreted unchanged in the urine. Half-life appears to be similar to humans (15 hours). In humans, ﬂuvoxamine is absorbed after oral administration, but bioavailability is only around 50%. Peak plasma concentrations occur between 3-8 hours post-dose. Food does not appear to affect the absorptive characteristics of the drug. Fluvoxamine is widely distributed in the body and about 80% bound to plasma proteins. The drug is extensively metabolized in the liver to non-active me-tabolites and eliminated in the urine. Plasma half-life is about 15 hours. Contraindications/Precautions/Warnings Fluvoxamine is contraindicated in patients hypersensitive to it or any SSRI or if the patient is receiving a monoamine oxidase inhibi-tor (MAOI) or cisapride. Consider using a lower dosage in patients with hepatic impairment or in geriatric patients.	pppbs.pdf
408 FLUVOXAMINE MALEATE TAdverse Effects The adverse effect proﬁle of ﬂuvoxamine in dogs or cats has not been well established. In dogs, SSRIs can cause lethargy, GI effects, anxiety, irritability, insomnia/hyperactivity, or panting. Anorexia is a common side effect in dogs (usually transient and may be negat-ed by temporarily increasing the palatability of food and/or hand feeding). Some dogs have persistent anorexia that precludes further treatment. Aggressive behavior in previously non-aggressive dogs has been reported. SSRIs in cats can cause sedation, decreased ap-petite/anorexia, vomiting, diarrhea, behavior changes (anxiety, ir-ritability, sleep disturbances), and changes in elimination patterns. In humans, common adverse reactions (>10%) include sexual side effects (abnormal ejaculation, anorgasmia), agitation/nervous-ness, insomnia, nausea, dry mouth, constipation/diarrhea, dyspep-sia, dizziness, headache, and somnolence Reproductive/Nursing Safety In humans, the FDA categorizes ﬂuvoxamine as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). In rats, ﬂuvoxamine reportedly increased pup mortality at birth and was associated with decreased birth weights. Fluvoxamine enters maternal milk, although it appears unlikely to be of signiﬁcant clinical concern. Overdosage/Acute Toxicity Limited data exists for animals. Reportedly, any dosage over 10 mg/kg can cause tremors and lethargy. Other signs associated with overdoses may include vomiting, somnolence/coma, diarrhea, hy-potension, heart rate/rhythm disturbances (bradycardia/tachycar-dia, ECG changes), seizures, etc. Cyproheptadine may be useful in the adjunctive treatment of serotonin syndrome. Fatalities have been reported in human overdoses; the highest reported dose where the patient survived was 10,000 mg. Treatment recommendations include standard protocols for drug adsorption/ removal from the GI for potentially dangerous overdoses and symp-tomatic and supportive therapy. Serotonin effects may be negated somewhat by administration (oral or rectal) with cyproheptadine at a dose of 1. 1 mg/kg. Seizures or other neurologic signs may be treated with diazepam. The drug has an elimination half-life of ap-proximately 15 hours in dogs. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ﬂuvoxamine and may be of signiﬁcance in veterinary patients: !TBUSPIRONE : Fluvoxamine may paradoxically decrease the clinical efﬁcacy of buspirone !TCISAPRIDE : Fluvoxamine may increase plasma levels of cisapride leading to toxicity !TCYPROHEPTADINE : May decrease or reverse the effects of SSRIs !TDIAZEPAM, ALPRAZOLAM, MIDAZOLAM : Fluvoxamine may increase diazepam levels !TDILTIAZEM : Fluvoxamine may increase the effects of diltiazem; bradycardia has been reported in humans taking this drug combination !TMAO INHIBITORS (including amitraz and potentially, selegiline ): High risk for serotonin syndrome; use contraindicated; in hu-mans, a 5 week washout period is required after discontinuing ﬂuvoxamine and a 2 week washout period if ﬁrst discontinuing the MAO inhibitor !TMETHADONE : Fluvoxamine may increase plasma levels of metha-done, leading to toxicity !TPHENYTOIN : Increased plasma levels of phenytoin possible !TPROPRANOLOL, METOPROLOL : Fluvoxamine may increase these beta-blocker's plasma levels; atenolol may be safer to use if ﬂuoxetine required !TTHEOPHYLLINE : Fluvoxamine may increase plasma levels of theophylline !TTRICYCLIC ANTIDEPRESSANTS (e. g., clomipramine, amitriptyline ): Flu-voxamine may increase TCA blood levels and may increase the risk for serotonin syndrome !TWARFARIN : Fluvoxamine may increase the risk for bleeding Laboratory Considerations No ﬂuvoxamine-related laboratory interactions noted. Doses !TDOGS: a) For treatment of compulsive disorders: 0. 5-2 mg/kg PO twice daily (Landsberg 2004) b) For treatment of behavioral diagnoses: 1 mg/kg PO q12-24h (once to twice a day); must treat for 3-5 weeks minimum to assess effects; then treat until “well” and either have no signs associated with diagnosis or some low, consistent level (a minimum of another 1-2 months). Continue to treat for another 1-2 months (minimum) so that reliability of assess-ment is reasonably assured. If weaning off the drug, do so over 3-5 weeks (or longer). Treatment should last for a min-imum 4-6 months once initiating therapy. (Overall 2001) !TCATS: a) For treatment of compulsive disorders: 0. 25-0. 5 mg/kg PO once daily (Landsberg 2004) b) For treatment of behavioral diagnoses: 0. 25-0. 5 mg/kg PO q24h (once a day); must treat for 3-5 weeks minimum to as-sess effects; then treat until “well” and either have no signs as-sociated with diagnosis or some low, consistent level (a mini-mum of another 1-2 months). Continue to treat for another 1-2 months (minimum) so that reliability of assessment is reasonably assured. If weaning off the drug, do so over 3-5 weeks (or longer). Treatment should last for a minimum 4-6 months once initiating therapy. (Overall 2001) c) For spraying: 0. 25 mg/kg PO q12h; avoid use with benzodi-azepines (Seksel 2006) Monitoring !TEfﬁcacy !TAdverse Effects; including appetite (weight) !TConsider doing baseline liver function tests and ECG and re-test as needed Client Information !This medication is most effective when used with a behavior modiﬁcation program !TKeep this medication away from children and other pets !TBecause there has not been widespread use of ﬂuvoxamine in dogs or cats, its adverse effect and efﬁcacy proﬁles have not been yet fully determined; clients should be briefed to report any sig-niﬁcant abnormal ﬁndings to the veterinarian. !TClients must understand that this drug is unlikely to have effect immediately or even in the short term, and must commit to using the drug for months so that an adequate trial can occur.	pppbs.pdf
FOLIC ACID 409 Chemistry/Synonyms A selective serotonin-reuptake inhibitor (SSRI), ﬂuvoxamine maleate occurs as a white to almost white crystalline powder. It is freely soluble in alcohol and sparingly soluble in water. Fluvoxamine may also be known as DU-23000, desiﬂuvoxamin, Dumirox®, Dumyrox®, Faverin®, Favoxil®, Felixsan®, Fevarin®, Flox-ex®, Floxyfral®, Fluvohexal®, Fluvosol®, Fluvoxadura®, Fluvoxin®, Luvox ®, and Maveral®. Storage/Stability/Compatibility The commercially available tablets should be stored in tight con-tainers at room temperatures of 15-30° C (59-86° F) and pro-tected from high humidity. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Fluvoxamine Tablets: 25 mg, 50 mg, & 100 mg; generic, (Rx) FOLIC ACID (foe-lik ass-id) Folate, Folacin WATER-SOLUBLE “B ” VITAMIN Prescriber Highlights TT “B” Vitamin necessary for nucleoprotein synthesis & nor-mal erythropoiesis TT Injectable or oral dosage forms TT Folic acid deﬁciency may be seen in animals (especially cats) with proximal or diffuse small intestinal inﬂamma-tory disease TT May be used when dihydrofolate reductase inhibitor drugs (e. g., trimethoprim, ormetoprim, pyrimethamine) are used for a prolonged period TT Very safe Uses/Indications Folic acid is used to treat folic acid deﬁciency in dogs, cats, and horses (theoretically in other animal species as well) often due to small intestinal disease. Cats with exocrine pancreatic insufﬁciency appear to be most at risk for folate and cobalamin deﬁciencies sec-ondary to malabsorption of folic acid in the diet. Dogs with exocrine pancreatic insufﬁciency often are noted to have increased folate lev-els secondary to overgrowths of folate-synthesizing bacteria in the proximal small intestine. Chronic administration of dihydrofolate reductase inhibiting drugs such as pyrimethamine, ormetoprim or trimethoprim can potentially lead to reduced activated folic acid (tetrahydrofolic acid); folic acid supplementation is sometimes pre-scribed in an attempt to alleviate this situation. Pharmacology/Actions Folic acid is required for several metabolic processes. It is reduced via dihydrofolate reductase in the body to tetrahydrofolate (5-m-ethyltetrahydrofolate) which acts as a coenzyme in the synthesis of purine and pyrimidine nucleotides that are necessary for DNA synthesis. Folic acid is also required for maintenance of normal erythropoiesis. Pharmacokinetics Therapeutically administered folic acid is primarily absorbed in the proximal small intestine via carrier-mediated diffusion. In humans, synthetic folic acid is nearly completely absorbed after oral admin-istration while folate in foodstuffs is about 50% bioavailable. Folic acid is converted to its active form, tetrahydrofolic acid, principally in the liver and plasma. Folate is distributed widely throughout the body and is stored in the liver. Erythrocyte and CSF levels can be signiﬁcantly higher than those found in serum. It can undergo enterohepatic recirculation and is excreted primarily in the urine either as metabolites or unchanged drug (when administered in ex-cess of body requirements). Contraindications/Precautions/Warnings Folic acid treatment is contraindicated only when known intoler-ance to the drug is documented. In humans, cobalamin (B-12) lev-els may be reduced with megaloblastic anemias; folic acid therapy may mask the signs associated with it. Folic acid doses in people above 0. 4 mg/day (except during pregnancy and lactation) are not to be used until pernicious anemia has been ruled out. As dogs may have increased, normal, or decreased folate levels associated with enteropathies, do not administer therapeutic doses until folate and cobalamin levels have been determined. Adverse Effects Folic acid is quite non-toxic and should not cause signiﬁcant ad-verse effects. Rarely in humans, folic acid tablets or injection have reportedly caused hypersensitivity reactions or gastrointestinal ef-fects. Very high oral doses in humans (15 mg/day) have occasionally caused CNS effects (e. g., difﬁculty sleeping, excitement, confusion, etc. ). Reproductive/Nursing Safety Folic acid is safe to use during pregnancy and in humans it is rou-tinely prescribed as part of prenatal vitamin supplementation as fo-late deﬁciency can increase the risk for fetal neural tube defects. In humans, the FDA categorizes this drug as category A for use during pregnancy (Adequate studies in pregnant women have not demon-strated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Folic acid is distributed into milk, but is safe. Folic acid require-ments may be increased in lactating animals. Overdosage/Acute Toxicity Folic acid is relatively non-toxic and no treatment should be re-quired if an inadvertent overdose occurs. Excess drug is metabo-lized or rapidly excreted unchanged in the urine. Drug Interactions The following drug interactions or have been reported in humans and may be of signiﬁcance in veterinary patients receiving folic acid or may alter patient folic acid requirements: T ! CHLORAMPHENICOL : May delay response to folic acid T ! METHOTREXATE, TRIMETHOPRIM, PYRIMETHAMINE (drugs that inhibit dihydrofolate reductase ): May interfere with folic acid utilization T ! PHENYTOIN : May decrease serum folate levels, and phenytoin dos-age may need to be increased; increased frequency in seizures can occur T ! SULFASALAZINE, BARBITURATES, NITROFURANTOIN, PRIMIDONE : May increase risk for folate deﬁciency	pppbs.pdf
410 FOMEPIZOLE Laboratory Considerations T ! Serum samples to be analyzed for cobalamin and/or folate should be protected from bright light and excessive heat T ! Hemolysis can cause falsely elevated serum concentrations of folate T ! Potentially, decreased cobalamin serum levels (B-12) can occur in patients receiving prolonged folic acid supplementation Doses T ! DOGS/CAT S: a) For severe folate deﬁciency: 0. 5-2 mg (total dose) once daily for 1 month. (Williams 2000) b) For cats with folate deﬁciency secondary to exocrine pancre-atic insufﬁciency: 400 mcg (0. 4 mg) PO once daily. (Steiner and Williams 2005) c) For cats on long-term use of high dose trimethoprim/sulfa (for treating Nocardia): 2 mg (total dose) PO once daily. (Wolf 2006a) d) For dogs with folate and cobalamin deﬁciency secondary to inﬂammatory bowel disease: folic acid at 5 mg (total dose) PO once daily for 1-6 months and cyanocobalamin 750 mcg (total dose) parenterally once per month. (Hoskins 2005a) T ! HORSES: a) Prolonged therapy with antifolate medications (e. g., trimethoprim, pyrimethamine): Sometimes recommend fo-lic acid at 20-40 mg (total dose) PO per day. Pregnant mares should routinely receive folic acid supplementation during treatment with antifolates. (Granstrom and Saville 1998) Monitoring T ! Small Animals: folate & cobalamin levels (serum); before and af-ter treatment T ! Clinical signs associated with deﬁciency T ! CBC, baseline and ongoing if abnormal Client Information T ! When used to treat folate deﬁciency associated with small intes-tinal disease or pancreatic insufﬁciency, lifelong monitoring and periodic replacement therapy may be required Chemistry/Synonyms Folic acid occurs as a yellow, yellow-brownish, or yellowish-orange, odorless crystalline powder. It is very slightly soluble in water and insoluble in alcohol. Commercially available folic acid is obtained synthetically. Folic acid may also be known as: folate, folacin, vitamin B 9, acidum folicum, pteroylglutamic acid, pteroylmonoglutamic acid, Folvite® and vitamin B 11. Storage/Stability Folic acid tablets should be stored in well-closed containers below 40°C (104°F), preferably between 15-30°C; protect from light and moisture. The injection should be stored protected from light be-low 40°C (104°F), preferably between 15-30°C. Do not allow to freeze. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None as sole ingredient products. There are many products available that contain folic acid as one of the ingredients. If using one of these products, be certain it has enough folic acid to treat folate deﬁciency without overdosing fat soluble vitamins A or D. HUMAN-LABELED PRODUCTS: Folic Acid Tablets: 400 mcg (0. 4 mg), & 800 mcg (0. 8 mg); generic; (depending on label either OTC or Rx) Folic Acid Tablets: 1 mg; generic; (Rx) Folic Acid Injection: 5 mg/m L in 10 m L vials; Folvite® (Lederle), ge-neric; (Rx) FOMEPIZOLE 4-METHYLPYRAZOLE (4-MP) (foe-me-pi-zole) Antizol-Vet® ANTIDOTE Prescriber Highlights TT Synthetic alcohol dehydrogenase inhibitor used to treat dogs for ethylene glycol poisoning TT May be efﬁcacious in cats at high dosages, if given within 3 hours of ingestion TT Adverse Effects: Rapid IV infusion may cause vein irrita-tion & phlebosclerosis; anaphylaxis is potentially possible TT Dilute as directed in the commercially available kit TT Monitor & treat acid/base, ﬂuid, electrolyte imbalances TT May inhibit elimination of ethanol (& vice versa) TT Expense & rapid availability may be issues Uses/Indications Fomepizole is used for the treatment of known or suspected ethyl-ene glycol toxicity in dogs (and humans). Fomepizole, at high dos-es, may be efﬁcacious in treating recent (within 3 hours) ingestion of ethylene glycol in cats. Pharmacology/Actions Ethylene glycol itself is only mildly toxic in dogs, but when it is me-tabolized to glycoaldehyde, glycolate, glyoxalic acid, and oxalic acid, the resultant metabolic acidosis and renal tubular necrosis can be fatal. Fomepizole is a competitive inhibitor of alcohol dehydroge-nase, the primary enzyme that converts ethylene glycol into glyco-aldehyde and other toxic metabolites. This allows ethylene glycol to be excreted primarily unchanged in the urine decreasing the mor-bidity and mortality associated with ethylene glycol ingestion. Pharmacokinetics Fomepizole is excreted primarily by the kidneys and apparently ex-hibits a dose-dependent accumulation of the drug over time; there-fore, a reduction in subsequent doses can safely occur. Contraindications/Precautions/Warnings There are no labeled contraindications to fomepizole's use. Fomepizole has been shown to be effective in treating ethylene gly-col in cats, but a high dosage is required. Adverse Effects Giving concentrated drug rapidly intravenously may cause vein irritation and phlebosclerosis. Dilute as directed in the commer-cially available kit. One dog during clinical trials was reported to develop anaphylaxis.	pppbs.pdf
FURAZOLIDONE 411 Use of fomepizole alone without adequate monitoring and ad-junctive supportive care (e. g., correction of acid/base, ﬂuid, elec-trolyte imbalances) may lead to therapeutic failure. If animal pres-ents within 1-2 hours post ingestion, consider inducing vomiting and/or gastric lavage with activated charcoal to prevent further absorption. Reproductive/Nursing Safety Fomepizole's safe use during pregnancy, lactation or in breeding animals has not been established. However, because of the mor-bidity and mortality associated with ethylene glycol toxicity, the beneﬁts of fomepizole should generally outweigh its risks. In hu-mans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether this drug is excreted in milk. Overdosage/Acute Toxicity Overdosage may cause signiﬁcant CNS depression. No speciﬁc treatment is recommended. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving fomepizole and may be of signiﬁcance in veterinary patients: T ! ETHANOL : Fomepizole inhibits alcohol dehydrogenase; ethanol metabolism is reduced signiﬁcantly and alcohol poisoning (CNS depression, coma, death) can occur. Use together is generally not recommended, but if both drugs are used, monitoring of ethanol blood levels is mandatory. Doses T ! DOGS: a) For treatment of ethylene glycol toxicity: Initially load at 20 mg/kg IV; at 12 hours post initial dose give 15 mg/kg IV; at 24 hours post initial dose give another 15 mg/kg IV and at 36 hours after initial dose give 5 mg/kg; may give additional 5 mg/kg doses as necessary (animal has not recovered or has additional ethylene glycol in blood). (Package Insert; Antizol-Vet®) T ! CATS: a) For treatment of ethylene glycol toxicity: Initially, 125 mg/ kg slow IV; at 12, 24, 36 hours give 31. 25 mg/kg IV. In addi-tion, treat supportively with supplemental ﬂuids. Cats must be treated within 3 hours of ingestion. Cats whose treatment began 4 hours post ethylene glycol had 100% mortality with either fomepizole or ETOH therapy. (Connally and Thrall 2002) Monitoring T ! Ethylene glycol blood levels (mostly important to document di-agnosis if necessary and to determine if therapy can be discontin-ued after 36 hours of treatment. ) T ! Blood gases and serum electrolytes T ! Hydration status T ! Renal function tests (e. g., Urine output and urinalysis; BUN or serum creatinine) T ! Cats: body temperature Client Information T ! Clients should be informed that treatment of serious ethylene glycol toxicity is an “intensive care” admission and that appropri-ate monitoring and therapy can be quite expensive, particularly when fomepizole is used in large dogs. T ! Because time is of the essence in this therapy, clients will need to make an informed decision rapidly. Dogs treated within 8 hours post ingestion have a signiﬁcantly better prognosis than those treated after 10-12 hours post ingestion. Cats must be treated within 3 hours of ingestion with high dosages. Chemistry/Synonyms A synthetic alcohol dehydrogenase inhibitor, fomepizole is com-monly called 4-methylpyrazole (4-MP). Its chemical name is 4-m-ethyl-1H-pyrazole. It has a molecular weight of 81; it is soluble in water and very soluble in ethanol. Fomepizole may also be known as: 4-methylpyrazole, 4-MP, fo-mepisol, fomepizolum, and Antizol®. Storage/Stability/Compatibility Commercially available solutions should be stored at room temper-ature. The concentrate for injection may solidify at temperatures less than 25°C. Should this occur, resolubolize by running warm water over the vial. Solidiﬁcation or resolubolization does not af-fect drug potency or stability. Store reconstituted vial at room tem-perature and discard after 72 hours. Reconstituted solutions may be further diluted in D 5W or normal saline for IV infusion. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Fomepizole 1. 5 g Kit for Injection; Antizol-Vet® (Jazz); (Rx). Ap-proved for use in dogs. Note : At recommended doses 1 kit will treat a 26 kg dog (up to 58 lb. ); larger dogs will require additional kits Preparation: If drug has solidiﬁed run warm water over vial; Add en-tire contents to 30 m L vial of 0. 9% Na Cl (in kit), mix well. Resultant solution is: 50 mg/m L HUMAN-LABELED PRODUCTS: Fomepizole Injection Concentrate (preservative free): 1 g/m L pre-servative free (must be diluted) in 1. 5 m L vials; Antizol® (Orphan Medical); (Rx) FURAZOLIDONE (fyoor-a-zoe-li-done) Furoxone® ANTIBACTERIAL/ANTIPROTOZOAL Prescriber Highlights TT Antibacterial/antiprotozoal nitrofuran used primarily in dogs & cats; availability is an issue TT Contraindications: Known hypersensitivity; food animals TT Adverse Effects: GI effects (anorexia, vomiting, cramping & diarrhea) possible TT May innocuously discolor urine to a dark yellow to brown color TT Drug Interactions Uses/Indications Furazolidone is usually a drug of second choice in small animals to treat enteric infections caused by the organisms listed below. Because it is no longer commercially available (in the USA), it may be difﬁcult to locate.	pppbs.pdf
412 FURAZOLIDONE Pharmacology/Actions Furazolidone interferes with susceptible bacterial enzyme sys-tems. Its mechanism against susceptible protozoa is not well deter-mined. Furazolidone has activity against Giardia, Vibrio cholerae, Trichomonas, Coccidia, and many strains of E. coli, Enterobacter, Campylobacter, Salmonella, and Shigella. Not all strains are sensitive, but resistance is usually limited and develops slowly. Furazolidone also inhibits monoamine oxidase. Pharmacokinetics Conﬂicting information on furazolidone's absorption characteris-tics are published. As colored metabolites are found in the urine, it is clearly absorbed to some extent. Because furazolidone is used to treat enteric infections, absorption becomes important only when discussing adverse reactions and drug interaction issues. Furazolidone reportedly distributes into the CSF. Absorbed fura-zolidone is rapidly metabolized in the liver and the majority of ab-sorbed drug is eliminated in the urine. Contraindications/Precautions/Warnings Furazolidone is contraindicated in patients hypersensitive to it. The FDA has prohibited the extralabel use of furazolidone in food animals. Adverse Effects Adverse effects noted with furazolidone are usually minimal. Anorexia, vomiting, cramping, and diarrhea may occasionally oc-cur. Some human patients are reported to be hypersensitive to the drug. Because furazolidone also inhibits monoamine oxidase it may, potentially, interact with several other drugs and foods (see Drug Interactions below). The clinical signiﬁcance of these interac-tions remains unclear, particularly in light of the drug's poor ab-sorptive characteristics. Reproductive/Nursing Safety While the safe use of furazolidone during pregnancy has not been established, neither were there any teratogenic issues located for it. However, one reference (Tams 2003b) states that furazolidone should not be used in pregnant queens. In humans, the FDA cat-egorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no ad-equate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is unknown if furazolidone enters maternal milk. Overdosage/Acute Toxicity No information was located; but moderate overdoses are unlikely to cause signiﬁcant toxicity. Gut emptying may be considered for large overdoses. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving furazolidone and may be of signiﬁcance in veterinary patients: !!ALCO H OL: With furazolidone may cause a disulﬁram-like reaction Because furazolidone inhibits monoamine oxidase, its use concur-rently with the following drugs is not recommended because dan-gerous hypertension could occur: !!AMITRAZ !!BUSPIRONE !!SELEGILINE !!SYMPATHOMIMETIC AMINES (phenylpropanolamine, ephedrine, etc. ) !!TRICYCLIC ANTIDEPRESSANTS !!FISH OR POULTRY (high tyramine content ) Laboratory Considerations !TFurazolidone may cause a false-positive urine glucose determina-tion when using the cupric sulfate solution test (e. g., Clinitest®). Doses !TDOGS: a) For amebic colitis: 2. 2 mg/kg PO q8h for 7 days; For coccidiosis: 8-20 mg/kg PO for one week (Sherding and Johnson 1994) b) For treatment of Giardia: 4 mg/kg PO twice daily (q12h) for 7 days For Cystoisospora spp. : 8-20 mg/kg PO q12-24h for 5 days (Lappin 2000) c) For coccidiosis: 8-20 mg/kg PO once daily for 7 days For entamebiasis: 2. 2 mg/kg PO q8h for 7 days (Greene and Watson 1998) !TCATS: a) For treatment of Giardia: 4 mg/kg PO twice daily (q12h) for 7-10 days; if re-treatment is required, elevated dosages or lengthened treatment regimens may provide better results. (Reinemeyer 1992) b) For treatment of Giardia: 4 mg/kg, PO twice daily (q12h) for 7 days For Cystoisospora spp. : 8-20 mg/kg PO q12-24h for 5 days (Lappin 2000) c) For coccidiosis: 8-20 mg/kg PO once daily for 7 days For giardiasis: 4 mg/kg PO q12h for 5-10 days For amebiasis: 2. 2 mg/kg PO q8h for 7 days (Greene and Watson 1998) d) For amebic colitis: 2. 2 mg/kg PO q8h for 7 days; For coccidi-osis: 8-20 mg/kg PO for one week; for Giardia: 4 mg/kg PO q12h for 5 days (Sherding and Johnson 1994) !THORSES: a) 4 mg/kg PO three times daily (Robinson 1992) Monitoring !TEfﬁcacy (stool exams for parasitic infections) Client Information !TFurazolidone may discolor urine to a dark yellow to brown color; this is not signiﬁcant. !THave clients report prolonged or serious GI effects. Chemistry/Synonyms A synthetic nitrofuran-derivative antibacterial/antiprotozoal, fura-zolidone occurs as a bitter-tasting, yellow, crystalline powder. It is practically insoluble in water. Furazolidone may also be known as: nifurazolidonum, Enterolidon®, Exofur®, Furasian®, Furion®, Furoxona®, Fuxol ®, Giarcid®, Giardil®, Giarlam®, Neo Furasil®, Nifuran®, Novafur®, Salmocide®, and Seforman®. Storage/Stability Store protected from light in tight containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: No systemic products are available; a 4% topical powder/spray is available. The FDA prohibits its use on food producing animals. HUMAN-LABELED PRODUCTS: None; the human product Furoxone® has apparently been withdrawn from the USA market. Preparations may be available from com-pounding pharmacies.	pppbs.pdf
FUROSEMIDE 413 FUROSEMIDE (fur-oh-se-mide) Lasix® LOOP DIURETIC Prescriber Highlights TT A loop diuretic commonly used in many species for treat-ment of congestive cardiomyopathy, pulmonary edema, udder edema, hypercalcuric nephropathy, uremia, as adjunctive therapy in hyperkalemia &, occasionally, as an antihypertensive agent TT Used in racehorses to prevent/reduce EIPH TT Contraindications: Patients with anuria, hypersensitivity, or seriously depleted electrolytes TT Caution: Patients with pre-existing electrolyte or water balance abnormalities, impaired hepatic function, & dia-betes mellitus TT Adverse Effects: Fluid & electrolyte (esp. hyponatremia) abnormalities, others included: ototoxicity, GI distress, he-matologic effects, ototoxicity, weakness, & restlessness TT Pre-renal azotemia if dehydration occurs TT Encourage normal food & water intake Uses/Indications Furosemide is used for its diuretic activity in all species. It is used in small animals for the treatment of congestive cardiomyopathy, pulmonary edema, hypercalcuric nephropathy, uremia, as adjunc-tive therapy in hyperkalemia and, occasionally, as an antihyper-tensive agent. In cattle, it is approved for use for the treatment of post-parturient udder edema. It has been used to help prevent or reduce epistaxis (exercise-induced pulmonary hemorrhage; EIPH) in racehorses. Pharmacology/Actions Furosemide reduces the absorption of electrolytes in the ascending section of the loop of Henle, decreases the reabsorption of both sodium and chloride and increases the excretion of potassium in the distal renal tubule, and directly effects electrolyte transport in the proximal tubule. The exact mechanisms of furosemide's effects have not been fully established. It has no effect on carbonic anhy-drase nor does it antagonize aldosterone. Furosemide increases renal excretion of water, sodium, potas-sium, chloride, calcium, magnesium, hydrogen, ammonium, and bicarbonate. In dogs, excretion of potassium is affected much less so than is sodium; hyponatremia may be more of a concern than hypokalemia. It causes some renal venodilation and transiently in-creases glomerular ﬁltration rates (GFR). Renal blood ﬂow is in-creased and decreased peripheral resistance may occur. While furo-semide increases renin secretion, due to its effects on the nephron, increases in sodium and water retention do not occur. Furosemide can cause hyperglycemia, but to a lesser extent than the thiazides. At high doses (10-12 mg/kg), thoracic duct lymph ﬂow is in-creased in dogs. In horses, guinea pigs and humans, furosemide has some bronchodilative effects. Cats are reportedly more sensitive than other species to the diuretic effects of furosemide. Pharmacokinetics The pharmacokinetics of furosemide have been studied in a limited fashion in domestic animals. In dogs, the oral bioavailability is ap-proximately 77% and the elimination half-life approximately 1-1. 5 hours. In humans, furosemide is 60-75% absorbed following oral ad-ministration. The diuretic effect takes place within 5 minutes af-ter IV administration and within one hour after oral dosing. Peak effects occur approximately 30 minutes after IV dosing, and 1-2 hours after oral dosing. The drug is approximately 95% bound to plasma proteins in both azotemic and normal patients. The serum half-life is about 2 hours, but prolonged in patients with renal fail-ure, uremia, CHF, and in neonates. Contraindications/Precautions/Warnings Furosemide is contraindicated in patients with anuria or who are hypersensitive to the drug. The manufacturer states that the drug should be discontinued in patients with progressive renal disease if increasing azotemia and oliguria occur during therapy. Furosemide should be used with caution in patients with preex-isting electrolyte or water balance abnormalities, impaired hepatic function (may precipitate hepatic coma), and diabetes mellitus. Patients with conditions that may lead to electrolyte or water bal-ance abnormalities (e. g., vomiting, diarrhea, etc. ) should be moni-tored carefully. Patients hypersensitive to sulfonamides may also be hypersensitive to furosemide (not documented in veterinary species). Adverse Effects Furosemide may induce ﬂuid and electrolyte abnormalities. Patients should be monitored for hydration status and electrolyte imbalances (especially potassium, calcium, magnesium and sodium). Prerenal azotemia may result if moderate to severe dehydration occurs. Hy-ponatremia is probably the greatest concern, but hypocalcemia, hy-pokalemia, and hypomagnesemia may all occur. Animals that have normal food and water intake are much less likely to develop water and electrolyte imbalances than those who do not. Other potential adverse effects include ototoxicity, especially in cats with high dose IV therapy. Dogs reportedly require dosages greater than 22 mg/kg IV to cause hearing loss. Other effects in-clude gastrointestinal disturbances, hematologic effects (anemia, leukopenia), weakness, and restlessness. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have un-covered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) Furosemide appears in milk; clinical signiﬁcance to nursing off-spring is unknown. Overdosage/Acute Toxicity The LD 50 in dogs after oral administration is >1000 mg/kg; after IV injection >300 mg/kg. Chronic overdosing at 10 mg/kg for six months in dogs led to development of calciﬁcation and scarring of the renal parenchyma. Acute overdosage may cause electrolyte and water balance prob-lems, CNS effects (lethargy to coma and seizures) and cardiovascu-lar collapse.	pppbs.pdf
414 FUROSEMIDE Treatment consists of emptying the gut after recent oral inges-tion, using standard protocols. Avoid giving concomitant cathartics as they may exacerbate the ﬂuid and electrolyte imbalances that can occur. Aggressively monitor and treat electrolyte and water balance abnormalities supportively. Additionally, monitor respiratory, CNS, and cardiovascular status. Treat supportively and symptomatically if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving furosemide and may be of signiﬁcance in veterinary patients: !TACE INHIBITORS (e. g., enalapril, benazepril ): Increased risks for hy-potension, particularly in patients who are volume or sodium depleted secondary to diuretics !TAMINOGLYCOSIDES (gentamicin, amikacin, etc. ): Increased risk for ototoxicity !TAMPHOTERICIN B: Loop diuretics may increase the risk for nephro-toxicity development; hypokalemia !TCORTICOSTEROIDS : Increased risk for GI ulceration; hypokalemia !TDIGOXIN : Furosemide-induced hypokalemia may increase the po-tential for digoxin toxicity !TINSULIN : Furosemide may alter insulin requirements !TMUSCLE RELAXANTS, NON-DEPOLARIZING (e. g., atracurium, tubocura-rine): Furosemide may prolong neuromuscular blockade !TPROBENECID : Furosemide can reduce uricosuric effects !TSALICYLATES : Loop diuretics can reduce the excretion of salicy-lates !TSUCCINYLCHOLINE : Furosemide may potentiate !TTHEOPHYLLINE : Pharmacologic effects of theophylline may be en-hanced when used with furosemide Doses !TDOGS & CAT S: As a general diuretic: a) 2. 5-5 mg/kg (lower dose suggested for cats) once or twice daily at 6-8 hour intervals PO, IV or IM (Package Insert; Salix®—Intervet) For cardiogenic or pulmonary edema: a) For adjunctive therapy of CHF: 0. 5-2 mg/kg PO per day. The goal is to ﬁnd the lowest dose of furosemide that will prevent development of effusion or edema. This may change over time. (Ware and Keene 2000) b) For severe pulmonary edema (parenteral dosing) Dogs: Up to 7. 7 mg/kg IV or IM every 1-2 hours until respi-ratory rate and/or respiratory character improves; Cats: Up to 4. 4 mg/kg IV or IM every 1-2 hours until respi-ratory rate and/or respiratory character improves; For heart failure (oral dosing; often in combination with an ACE inhibitor and digoxin): Dogs: Dosage ranges from 1. 1 mg/kg PO every other day for very mild heart failure to 4. 4 mg/kg PO q8h for severe heart failure; Cats: Dosage ranges from 1. 1 mg/kg PO every 2-3 days to 2. 2 mg/kg, q8-12h. (May require doses up to 6. 6. mg/kg q12h or 15. 4 mg/kg PO once a day for cats that are difﬁcult to treat orally). Animals must drink adequate amounts of water or severe de-hydration may result (Kittleson 2000) c) The credo for furosemide therapy is: “Use as much as the case requires, and as little as necessary. ” Prior to therapy, ob-tain serum chemistry and full urinalysis (or at least measure urine speciﬁc gravity). For severe pulmonary edema (parenteral dosing): Dogs: Up to 8 mg/kg IV every hour with adjunctive therapy (usually strict cage rest, O 2 therapy, topical NTG ointment and minimal restraint) until improved. For chronic maintenance therapy: Usually start at 2 mg/kg PO q12h, but will adjust as necessary. Rarely go above 4 mg/ kg PO q8h. If case requires more than this dosage, add hy-drochlorothiazide at 2-4 mg/kg PO q12h. However, at this point prognosis is becoming dismal. Encourage oral food and water intake. (T obias 2001) d) Using furosemide as a constant rate infusion (CRI): May di-lute 5% injection (50 mg/m L) in D5W to a concentration of 5 mg/m L or 10 mg/m L without precipitation occurring; give as a CRI and titrate dose to between 0. 1-1 mg/kg/hour. (Rush 2005a) For hypercalcemia/hypercalcuric nephropathy: a) For adjunctive treatment of moderate to severe hypercalce-mia: Volume expansion is necessary prior to use of furosemi-de; 2-4 mg/kg two to three times daily, IV, SC or PO. (Chew, Schenck et al. 2003) For acute oliguric renal failure: a) Initially 2 mg/kg IV; if no substantial diuresis develops in one hour, the dose may be doubled to 4 mg/kg. If this dose fails to induce diuresis, may increase to 6 mg/kg. If diuresis still does not ensue, very large doses of furosemide, an alternative diuretic (e. g., mannitol), or the combination of furosemide and dopamine may be considered. (Polzin 2005a) T o promote diuresis in hyperkalemic states: a) 2 mg/kg IV; attempted if mannitol is ineffective after one hour (Seeler and Thurmon 1985) As a diuretic for the treatment of ascites: a) 1-2 mg/kg PO, SC once to twice daily (Morgan 1988) !TFERRETS: For adjunctive therapy for heart failure: a) 2-3 mg/kg IM or IV initially for fulminant CHF; 1-2 mg/kg PO q12h for long-term maintenance therapy (Hoeffer 2000) b) 1-4 mg/kg PO, SC, IM or IV 2-3 times a day (Williams 2000) !TRABBITS/RODENTS/SMALL MAMMALS: a) Rabbits: For CHF: 2-5 mg/kg PO, SC, IM or IV q12h; For pulmonary edema: 1-4 mg/kg IV or IM q4-6h (Ivey and Morrisey 2000) b) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 5-10 mg/kg q12h (Adamcak and Otten 2000) !TCATTLE: a) 500 mg once daily or 250 mg twice daily; 2 grams PO once daily. Treatment not to exceed 48 hours post-partum (for ud-der edema). Package Insert; Lasix®-Hoechst) b) 2. 2-4. 4 mg/kg IV q12h (Howard 1986) !THORSES: (Note : Refer to state guidelines for use of furosemide in racing animals) As a diuretic: a) For adjunctive therapy for congestive heart failure: Initially, 1-2 mg/kg IM or IV q6-12h to control edema. Long-term therapy: 0. 5-2 mg/kg PO or IM q8-12h (Mogg 1999) b) For adjunctive therapy of acute renal failure: 2-4 mg/kg q6h (Jose-Cunilleras and Hinchcliff 1999)	pppbs.pdf
GABAPENTIN 415 For epistaxis prevention: a) 0. 3-0. 6 mg/kg 60-90 minutes prior to race (Robinson 1987) b) 250 mg IV 4 hours prior to racing (Foreman 1999) T ! BIRDS: As a diuretic: a) 0. 05 mg/300 gm IM twice daily ( Note : Lories are very sensi-tive to this agent and can be easily overdosed) (Clubb 1986) T ! REPTILES: For most species: a) 5 mg/kg IV or IM as needed (Gauvin 1993) Monitoring T ! Serum electrolytes, BUN, creatinine, glucose T ! Hydration status T ! Blood pressure, if indicated T ! Clinical signs of edema, patient weight, if indicated T ! Evaluation of ototoxicity, particularly with prolonged therapy or in cats Client Information T ! Clients should contact veterinarian if clinical signs of water or electrolyte imbalance occur, such as excessive thirst, lethargy, las-situde, restlessness, reduced urination, GI distress or fast heart rate. Chemistry/Synonyms A loop diuretic related structurally to the sulfonamides, furosemide occurs as an odorless, practically tasteless, white to slightly yellow, ﬁne, crystalline powder. Furosemide has a melting point between 203°-205°C with decomposition, and a p K a of 3. 9. It is practically insoluble in water, sparingly soluble in alcohol, and freely soluble in alkaline hydroxides. The injectable product has its p H adjusted to 8-9. 3 with sodium hydroxide. Furosemide may also be known as: frusemide, furosemidum, and LB-502; many trade names are available. Storage/Stability/Compatibility Furosemide tablets should be stored in light-resistant, well-closed containers. The oral solution should be stored at room temperature and protected from light and freezing. Furosemide injection should be stored at room temperature. A precipitate may form if the in-jection is refrigerated, but will resolubolize when warmed without alteration in potency. The human injection (10 mg/m L) should not be used if it has a yellow color. The veterinary injection (50 mg/m L) normally has a slight yellow color. Furosemide is unstable at an acid p H, but is very stable under alkaline conditions. Furosemide injection (10 mg/m L) is reportedly physically com-patible with all commonly used intravenous solutions and the fol-lowing drugs: amikacin sulfate, cimetidine HCl, kanamycin sulfate, tobramycin sulfate, and verapamil. It is reportedly physically incompatible with the following agents: ascorbic acid solutions, dobutamine HCl, epinephrine, gentamicin sulfate, netilmicin sulfate and tetracyclines. It should generally not be mixed with antihistamines, local anesthetics, alkaloids, hypnot-ics, or opiates. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Furosemide Tablets: 12. 5 mg, 50 mg; Salix® (Intervet); Disal® Tab-lets (Boehringer Ingelheim), Furotabs® (Butler); generic (Phoenix Pharmaceutical); (Rx). Products may be approved for use in dogs and cats. Furosemide Oral Solution (Syrup): 10 mg/m L in 60 m L; generic (IVX, First Priority); (Rx) Approved for use in dogs. Furosemide for Injection: 50 mg/m L (5%) in 50 m L and 100 m L vials; Disal® Injection (Boehringer Ingelheim), Salix® Injection (In-tervet), Furoject® (Butler), generic (Agri Labs, IVX, Vet T ek, Phoenix Pharmaceutical), (Rx). Products may be approved for use in dogs, cats and horses. HUMAN-LABELED PRODUCTS: Furosemide Tablets: 20 mg, 40 mg, & 80 mg; Lasix® (Aventis); ge-neric; (Rx) Furosemide Oral Solution: 10 mg/m L in 60 m L and 120 m L; 40 mg/5 m L in 500 m L and UD 5 m L and 10 m L; generic; (Rx) Furosemide Injection: 10 mg/m L in 2 m L, 4 m L and 10 m L single-dose vials and 10 m L multi-dose vial; generic; (Rx) GABAPENTIN (gab-ah-pen-tin) Neurontin® ANTICONVULSANT; NEUROPATHIC PAIN ANALGESIC Prescriber Highlights TT May be useful in dogs & cats as adjunctive therapy for refractory or complex partial seizures or the treatment of pain TT Caution in patients with diminished renal function, but dogs partially (30-40%) metabolize the drug (humans do not) TT Avoid use of xylitol-containing oral liquid in dogs TT Sedation most likely adverse effect, but adverse effect proﬁle not well-deﬁned for animals TT Expense may be a signiﬁcant issue, but may decrease as generics are now available Uses/Indications Gabapentin may be useful as adjunctive therapy for refractory or complex partial seizures, or in the treatment of chronic pain in dogs or cats. Pharmacology/Actions Gabapentin has analgesic effects and can prevent allodynia (sensa-tion of pain resulting from a normally non-noxious stimulus) or hyperalgesia (exaggerated response to painful stimuli). It also has anticonvulsant activity. The mechanism of action of gabapentin, for either its anticonvulsant or analgesic actions is not understood. While gabapentin is structurally related to GABA, it does not ap-pear to alter GABA binding, reuptake, or degradation, or serve as a GABA agonist in vivo. Pharmacokinetics In dogs, oral bioavailability is about 80% at a dose of 50 mg/kg. Peak plasma levels occur about 2 hours post dose. Elimination is primarily via renal routes, but gabapentin is partially metabolized to N-methyl-gabapentin. Elimination half-life is approximately 2-4 hours in dogs. No pharmacokinetic data for cats was located. In humans, gabapentin bioavailability decreases as dosage increas-es. At doses of 900 mg/day, 60% of the dose is absorbed. Percentage absorbed is reduced as doses are increased to a minimum of 27%	pppbs.pdf
416 GABAPENTIN Tof the dose being absorbed when 4800 mg/day is administered. Presence of food only marginally alters absorption rate and extent of absorption. Gabapentin is only minimally bound to plasma pro-teins; CSF levels are approximately 20% of those in plasma. The drug is not signiﬁcantly metabolized and is almost exclusively ex-creted unchanged into the urine. Elimination half-lives in humans are approximately 5-7 hours. Contraindications/Precautions/Warnings Gabapentin is considered contraindicated in patients hypersensi-tive to it. Because gabapentin is eliminated via renal routes (practi-cally 100% in humans), it should be used with caution in patients with renal insufﬁciency; if required, dosage adjustment should be considered. In dogs, the drug is also metabolized (30-40%) of a dose, so dosage adjustment may not be required in dogs with mild to moderate renal dysfunction. In general, avoid the use of the commercially available human oral solution (Neurontin®) in dogs as it reportedly contains 300 mg/ m L xylitol. As the threshold dose that can cause hypoglycemia in dogs is approximately 100 mg/kg, doses of up to 15 mg/kg in dogs using the solution should be safe, but further data is needed to con-ﬁrm this. Additionally, xylitol may be hepatotoxic in dogs. Doses of 500 mg/kg of xylitol are currently thought to be the threshold for this toxicity, but there have been anecdotal reports of it occurring at much lower doses. In cats, at the dosages used presently, xylitol toxicity does not appear to be a problem with gabapentin oral solu-tion, but use with caution. Adverse Effects Sedation is probably the most likely adverse effect seen in small ani-mals. Starting the dose at the lower end of the range and increasing with time, may alleviate this effect. In humans, the most common adverse effects associated with gabapentin therapy are dizziness, somnolence, and peripheral edema. Gabapentin was associated with an increased rate of pancreatic adenocarcinoma in male rats. It is unknown if this effect crosses into other species. Abrupt discontinuation of the drug has lead to withdrawal-pre-cipitated seizures. In humans, it is recommended to wean off the drug when it is used for epilepsy treatment. Reproductive/Nursing Safety In humans, the FDA categorizes gabapentin as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). At high dosages (at or above human maximum dosages), gabapen-tin was associated with a variety of fetotoxic and teratogenic effects (e. g., delayed ossiﬁcation, hydronephrosis, fetal loss) in rats, mice and rabbits. Gabapentin enters maternal milk. It has been calculated that a nursing human infant could be exposed to a maximum dosage of 1 mg/kg/day. This is 5-10% of the usual pediatric (>3 yrs old) thera-peutic dose. In veterinary patients, this appears unlikely to be of signiﬁcant clinical concern. Overdosage/Acute Toxicity In humans, doses of up to 49 grams have been reported without fatality. Most likely effects include ataxia, lethargy/somnolence, di-arrhea, etc. The commercially available oral solution contains 300 mg/m L; doses of 0. 33 m L/kg may cause hypoglycemia or liver toxicity in dogs. There were 256 exposures to gabapentin reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org ) dur-ing 2005-2006. In these cases 211 were dogs with 13 showing clinical signs and the remaining 45 cases were cats with 11 show-ing clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included lethargy, ataxia, sedate, vomiting and bulging eyes. Common ﬁndings in cats recorded in decreasing frequency included ataxia, lethargy, bradycardia, depression, and mydriasis. Treatment is basically supportive with general decontamination procedures including emesis, activated charcoal, and cathartics. The drug can be removed with hemodialysis. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving gabapentin and may be of signiﬁcance in veterinary patients: !TANTACIDS : Oral antacids given concurrently with gabapentin may decrease oral bioavailability by 20%; if antacids are required, sep-arate doses at least 2 hours from gabapentin !THYDROCODONE : Co-administration of gabapentin and hydro-codone may increase the AUC (area under the curve) of gabap-entin and increase the efﬁcacy and/or adverse effects of the drug. Gabapentin can reduce the AUC of hydrocodone, potentially re-ducing the drug's effectiveness. !TMORPHINE : May increase gabapentin levels Laboratory Considerations !There are reports of gabapentin causing false-positive urinary pro-tein readings on Ames N-Multistix SG dipstick tests. The use of a sulfosalicylic acid precipitation test to determine presence of urine protein is recommended for patients receiving gabapentin. Doses !TDOGS: For ancillary therapy of refractory seizures: a) 10-30 mg/kg PO q8-12h (Podell 2006a) b) 25-60 mg/kg/day PO divided q6-8h, the author initially uses 10 mg/kg PO q8h. (Dewey 2005b) c) 10-30 mg/kg PO q8h. Note : expensive and of limited beneﬁt (Berry 2003) As an analgesic: a) For adjunctive treatment of chronic or cancer pain: 3 mg/kg PO once a day (Lascelles 2003) b) 1. 25-10 mg/kg PO q24h (once daily) (Hardie 2006) !TCATS: For ancillary therapy of refractory seizures: a) 5 mg/kg PO three times daily (Pearce 2006b) b) 5-10 mg/kg PO q8-12h (Podell 2006a) c) 10-30 mg/kg PO q8h ( Note : expensive and of limited ben-eﬁt) (Berry 2003) As an analgesic: a) 1. 25-10 mg/kg PO q24h (once daily) (Hardie 2006) b) For adjunctive treatment of chronic or cancer pain: 3 mg/ kg PO once a day (Lascelles 2003), (Hardie, Lascelles et al. 2003) c) For adjunctive analgesia associated with neuropathic pain: While suggested range in cats is 2. 5-5 mg/kg PO q12h, this author starts at 5 mg/kg and increases (up to 10 mg/kg) if no effect seen in two hours. May be a higher requirement in cats for post-seizure or CPR vocalization and thrashing. Wean off slowly or patient may experience worse pain. Reduce in renal insufﬁciency. Usually the limit of dosing is reached when pa-tient is sedated. (Mathews 2006)	pppbs.pdf
GEMCITABINE HCL 417 Monitoring T ! Note : Gabapentin serum levels are not monitored at present. T ! Clinical efﬁcacy and adverse effects should be monitored. Client Information T ! Clients should report any signiﬁcant adverse effects such as ataxia or hypersomnolence Chemistry/Synonyms Gabapentin occurs as white to off-white crystalline solid that is freely soluble in water. It has a p Ka1 of 3. 7 and a p Ka2 of 10. 7. It is structurally related to GABA (gamma-aminobutyric acid). Gabapentin may also be known as: CI-945, GOE-3450, Aclonium®, Equipax®, Gantin®, Gabarone®, Neurontin®, Neurostil® and Progresse®. Storage/Stability/Compatibility The commercially available capsules and tablets should be stored at room temperature (25°C, 77°F); excursions permitted to 15-30°C (59-86°F). The oral liquid should be stored in the refrigerator at 2-8°C (36-46°F). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Gabapentin Capsules & Tablets: 100 mg, 300 mg, 400 mg; 600 mg, & 800 mg (ﬁlm-coated); Gabarone® or Gabapentin (Ivax); Neurontin® (Pﬁzer); generic, (Rx) Gabapentin Solution: 250 mg/5m L (50 mg/m L) in 470 m L; Neuront-in® (Pﬁzer); (Rx) Note : Contains xylitol. Use with caution in dogs. GEMCITABINE HCL (jem-site-ah-ben) Gemzar® ANTINEOPLASTIC Prescriber Highlights TT Antineoplastic agent that may potentially be useful for treating several cancers in dogs or cats TT Very limited clinical use & research performed thus far TT Myelosuppression most likely adverse effect TT Very expensive Uses/Indications Very limited clinical use and research performed with this drug to date have demonstrated limited clinical efﬁcacy. However, it poten-tially may be useful as a radiosensitizer for non-resectable tumors, as part of combination protocols, or as a single agent for tumors not amenable to more accepted therapies. Follow research reports for the most up-to-date information. In humans, gemcitabine has shown some efﬁcacy in treating pancreatic carcinoma, small-cell lung carcinoma, lymphoma, blad-der and other soft tissue carcinomas. Pharmacology/Actions Gemcitabine exhibits cell phase speciﬁcity and acts primarily on the S phase. It also inhibits cell progression through the G1/S-phase boundary. Gemcitabine is metabolized intracellularly to diﬂurodeoxy-cytidine monophosphate (d Fd CMP) that is then converted into diphosphate (d Fd CDP) and triphosphate (d Fd CTP) forms, the metabolites that give the drug its activity. The diphosphate inhibits ribonucleotide reductase. The triphosphate competes with deoxy-cytidine triphosphate (d TCP; the “normal” nucleotide) for incor-poration into DNA strands. Pharmacokinetics In dogs, gemcitabine exhibits ﬁrst order elimination and has a terminal half-life of about 1. 5-3. 2 hours. Volume of distribution (steady-state) is around 1 L/kg. In humans, gemcitabine levels achieve steady state in about 15 minutes during a 30 minute infusion. Protein binding is negligible. Volume of distribution is about 50 L/m 2. Less than 10% of the drug is excreted unchanged in the urine. Contraindications/Precautions/Warnings Gemcitabine is contraindicated in patients hypersensitive to it. It should be used with caution in patients with diminished renal or hepatic function. Adverse Effects Gemcitabine may cause myelosuppression and can affect red cell, white cell, and platelet cell lines, but neutrophils and platelets ap-pear to be most affected. Neutrophil nadirs usually occur 3-7 days post treatment. GI effects have been reported in animals receiving the drug, but are usually mild. Retinal hemorrhage could occur in animals receiving gemcitabine. In a pilot study (Kosarek, Kissabeth et al. 2005) in 19 dogs re-ceiving up to 675 mg/m2 biweekly demonstrated “minimal and ac-ceptable toxicity. ” Another study (Turner, Hahn et al. 2006) where dogs with lymphoma were given gemcitabine as single agent thera-py at 400 mg/m2 weekly for 3 weeks and then off one week, showed signiﬁcant decreases in neutrophils and platelets 7 days post treat-ment. 15 of the 21 dogs in the study required dosage reduction or delay in retreatment. Only 7 of the 21 dogs ﬁnished the initial 4 week cycle and a second cycle did not result in any objective thera-peutic response. Reproductive/Nursing Safety In pregnant humans, gemcitabine is designated by the FDA as a cat-egory D drug (There is evidence of human fetal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) It is unknown whether gemcitabine is excreted in maternal milk. Overdosage/Acute Toxicity There is no known antidote to gemcitabine in an overdose situation. Myelosuppression should be expected. Treatment is supportive. Drug Interactions No speciﬁc drug interactions were noted, but toxic effects (myelo-suppression, GI) could be additive when used with other drugs that also cause those effects.	pppbs.pdf
418 GEMFIBROZIL Laboratory Considerations No speciﬁc laboratory interactions or considerations noted. Doses T ! DOGS: a) For investigational use in pancreatic adenocarcinoma: Ini-tially 300 mg/m2 IV administered over 25-30 minutes weekly for 3-4 weeks, then a one week break. Follow moni-toring guidelines below. Consider adding an NSAID such as deracoxib, piroxicam or meloxicam, if renal and liver health is adequate. (de Lorimier 2004b) T ! CATS: a) For investigational use when other standards of care, and published options have been attempted and failed: 200 mg/ m2 in maintenance saline over 20 minutes. Follow monitor-ing guidelines (below) and do not administer if less than 2,500 neutrophils or less than 80,00 platelets. May give for 3-4 weeks in a row (if tolerated) and then skip one week. (de Lorimier 2004a) Monitoring T ! CBC before each treatment T ! Fundic exam weekly while on therapy T ! Prior to therapy, baseline renal and hepatic function and periodi-cally thereafter Client Information T ! Owners should understand that veterinary experience with this drug is limited and it must be considered an “investigational” treatment. Chemistry/Synonyms A synthetic pyrimidine nucleoside cytarabine analog antineoplastic agent, gemcitabine HCl occurs as white to off-white solid. It is sol-uble in water and practically insoluble in ethanol or polar organic solvents. Its chemical name is 2,2'-diﬂurodeoxycytidine. Gemcitabine may also be known as: d Fd C, LY-288022, Abine®, Antoril®, Gemcite®, or Gemtrol® and Gemzar®. Storage/Stability/Compatibility Store unreconstituted gemcitabine at controlled room temperature (20-25°C; 68-77°F). After reconstitution with 0. 9% sodium chlo-ride injection without preservatives, the resulting solution may be stored at room temperature for up to 24 hours. Reportedly, when frozen at-20°C, the reconstituted solution is stable for 7 days. Do not refrigerate or re-crystallization may occur. Reconstituted solu-tion should not be greater than 40 mg/m L (at least 5 m L of diluent for 200 mg vial; 25 m L diluent for 1 gram vial). Additional diluent may be added to yield concentrations as low as 0. 1 mg/m L. Gemcitabine injection is reportedly physically incompatible with the following medications when used via Y-site injection: acyclo-vir, amphotericin B, cefoperazone, cefotaxime sodium, furosemide, imipenem, methotrexate, methylprednisolone sodium succinate, mitomycin, piperacillin, and prochlorperazine. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Gemcitabine HCl lyophilized Powder for Injection: 200 mg (in 10 m L vial) and 1 g (in 50 m L vial); Gemzar® (Lilly); (Rx) GEMFIBROZIL (jem-ﬁh-broh-zil) Lopid® ORAL A NTIHYPERLIPIDEMIC Prescriber Highlights TT May be useful as adjunctive therapy (with low fat diet) to treat hypertriglyceridemia in dogs or cats TT Very limited experience & no published clinical studies in dogs or cats; efﬁcacy or safety is not established Uses/Indications Gemﬁbrozil may be useful to reduce serum triglycerides in those dogs or cats with hypertriglyceridemia and when diet modiﬁca-tions alone have been unsuccessful. One reference (Elliott 2005) suggests not adding drug therapy to treat hypertriglyceridemia un-less the serum triglyceride concentration exceeds 500 mg/d L with associated clinical signs. Pharmacology/Actions Gemﬁbrozil inhibits lipolysis in adipose issue and reduces hepatic uptake of plasma free fatty acids causing reduced production of triglycerides. Secondarily, gemﬁbrozil inhibits the synthesis of very low-density lipoprotein (VLDL) carrier apolipoprotein B, which reduces VLDL production and incorporation of long-chain fatty acids into triglycerides. Pharmacokinetics No pharmacokinetic data for dogs or cats was found. In humans, gemﬁbrozil is rapidly and completely absorbed from the GI tract. The rate and extent of absorption are greatest when administered 30 minutes before a meal. It is highly bound to plasma protein and highest concentrations of the drug are found in the liver and kid-neys. In the liver, 4 major metabolites are formed in humans, which are primarily excreted in the urine. Elimination half-life is about 1. 5 hours. Reductions in plasma VDL levels are noted within 5 days; peak reductions occur about 4 weeks after starting therapy. Contraindications/Precautions/Warnings Contraindications for using gemﬁbrozil in dogs or cats are not known. In humans, gemﬁbrozil is contraindicated in patients with severe hepatic or renal dysfunction or with known hypersensitivity to gemﬁbrozil. Use with caution in dogs or cats as very limited safety data is available for this medication. Adverse Effects Because no clinical studies have been published regarding gemﬁ-brozil use in dogs and cats and clinical use has been quite limited, an accurate adverse effect proﬁle is not known. Anecdotal reports are that the drug has been well tolerated in the few patients that have received the medication, but abdominal pain, vomiting, diar-rhea, and abnormal liver function tests have been reported. In humans, the most common adverse effects reported are GI related (dyspepsia, nausea, vomiting, diarrhea, etc. ) and CNS relat-ed (headache, paresthesias, somnolence, dizziness, fatigue). Other adverse effects reported include myositis, taste alterations, blurred vision, eczema and decreased libido/impotence. Rarely, hypersen-sitivity reactions, bone marrow depression, and increases in liver function test values (AST, ALT, Alk Phos, bilirubin) have been re-ported. Long-term studies in rats have demonstrated an increased	pppbs.pdf
GENTAMICIN SULFATE 419 rate of benign and malignant liver tumors when doses were approx-imately 1. 3X of the human dose. Reproductive/Nursing Safety Gemﬁbrozil administered to female rats prior to and during gesta-tion at 0. 6-2X the human dose, showed decreased fertility rates and their offspring had an increased incidence of skeletal abnor-malities. When given to pregnant rabbits at 1-3X the human dose, litter sizes were decreased and at the highest dose (3X), parietal bone variations were noted. In humans, the FDA categorizes gemﬁ-brozil as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no ad-equate studies in humans. ) It is not known if gemﬁbrozil enters milk and safe use during nursing cannot be assured. Overdosage/Acute Toxicity Limited information is available. One 7-year-old child ingested up to 9 grams and recovered with supportive treatment. The reported LD50 (oral) in rats is 1414 mg/kg. Consider gut-emptying protocols for recent large oral ingestions and support as required. Monitor for dehydration and electrolyte imbalance if vomiting and/or diar-rhea is severe or persists. Monitor liver function tests. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving gemﬁbrozil and may be of signiﬁcance in veterinary patients: T ! THIAZIDE DIURETICS, BETA-BLOCKERS, ESTROGENS : May possibly in-crease triglyceride concentrations T ! URSODIOL : May reduce effectiveness of gemﬁbrozil T ! WARFARIN : Gemﬁbrozil may potentiate anticoagulant effects Laboratory Considerations No speciﬁc concerns associated with gemﬁbrozil; see Monitoring Doses T ! DOGS/CAT S: For hypertriglyceridemia that has not been controlled with diet alone: a) Dogs: 150 mg-300 mg (total dose) PO q12h; Cats: 7. 5-10 mg/kg PO q12h (Jones 2003) b) Dogs: 200 mg (total dose) PO once daily; Cats: 10 mg/kg PO q12h (Elliott 2005) Monitoring T ! Plasma triglycerides; realistic goal for therapy is 400 mg/d L or less T ! Baseline and periodic: CBC, liver function tests T ! Adverse effects T ! If treatment is less effective than hoped, assure that clients have adhered to prescribed diet and dosing schedule before altering dosage Client Information T ! Clients must understand the use of this drug in animals is “inves-tigational”; although approved for use in people, little informa-tion is known about it for use in dogs or cats T ! Gemﬁbrozil is used in conjunction with diet modiﬁcation; lack of adherence to dietary recommendations will likely negate the beneﬁts of using this medication T ! Report any signiﬁcant adverse effects to the veterinarian, includ-ing changes in behavior, activity level, gastrointestinal effects (vomiting, diarrhea, lack of appetite), yellowish eyes or mucous membranes, etc. Chemistry/Synonyms Gemﬁbrozil is a ﬁbric acid derivative that occurs as a waxy, crys-talline solid that is practically insoluble in water, but soluble in alcohol. Gemﬁbrozil may also be known as: CI-719, gemﬁbrozilo, or gemﬁbrozilium; many international trade names are available. Storage/Stability Gemﬁbrozil tablets or capsules should be stored below 30°C in tight containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Gemﬁbrozil Tablets: 600 mg; Lopid® (Parke-Davis), generic; (Rx) Note: 300 mg capsules are available in Canada GENTAMICIN SULFATE (jen-ta-mye-sin) Gentocin®, Garamycin® AMINOGL YCOSIDE ANTIBIOTIC Prescriber Highlights TT Parenteral-aminoglycoside antibiotic that has “good” activity against a variety of bacteria, predominantly gram-negative aerobic bacilli, but also many staphylo-cocci strains TT Because of potential adverse effects, usually reserved for serious infections when given systemically TT Adverse effect proﬁle: Nephrotoxicity, ototoxicity, neuro-muscular blockade TT Cats may be more sensitive to toxic effects TT Risk factors for nephrotoxicity: Preexisting renal disease, age (both neonatal & geriatric), fever, sepsis, & dehydration TT Usually dosed once daily Uses/Indications The inherent toxicity of the aminoglycosides limit their systemic (parenteral) use to the treatment of serious gram-negative infec-tions when there is either a documented lack of susceptibility to other less toxic antibiotics or when the clinical situation dictates immediate treatment of a presumed gram-negative infection be-fore culture and susceptibility results are reported. Various gentamicin products are approved for parenteral use in dogs, cats, chickens, turkeys, and swine, although the injectable small animal products appear to be no longer marketed. Although routinely used parenterally in horses, gentamicin is only approved for intrauterine infusion in this species. Oral products are approved for gastrointestinal infections in swine and turkeys. For more infor-mation, refer to the Dosage section below. Pharmacology/Actions Gentamicin has a mechanism of action and spectrum of activity (primarily gram-negative aerobes) similar to the other aminogly-cosides. Like the other aminoglycoside antibiotics, it acts on suscep-	pppbs.pdf
420 GENTAMICIN SULFATE tible bacteria presumably by irreversibly binding to the 30S ribo-somal subunit thereby inhibiting protein synthesis. It is considered a bactericidal concentration-dependent antibiotic. Gentamicin's spectrum of activity includes coverage against many aerobic gram-negative and some aerobic gram-positive bacteria, including most species of E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Enterobacter, Serratia, and Shigella, Mycoplasma, and Staphylococcus. Several strains of Pseudomonas aeruginosa, Proteus, and Serratia that are resistant to gentamicin may still be treated with amikacin. Antimicrobial activity of the aminoglycosides is enhanced in an alkaline environment. The aminoglycoside antibiotics are inactive against fungi, virus-es and most anaerobic bacteria. Pharmacokinetics Gentamicin, like other aminoglycosides, is not appreciably absorbed after oral or intrauterine administration, but is absorbed from topi-cal administration (not skin or urinary bladder) when used in ir-rigations during surgical procedures. Patients receiving oral amin-oglycosides with hemorrhagic or necrotic enteritises may absorb appreciable quantities of the drug. After IM administration to dogs and cats, peak levels occur from H to 1 hour later. Subcutaneous injection results in slightly delayed peak levels and with more vari-ability than after IM injection. Bioavailability from extravascular injection (IM or SC) is greater than 90%. After absorption, aminoglycosides are distributed primarily in the extracellular ﬂuid. They are found in ascitic, pleural, pericardial, peritoneal, synovial and abscess ﬂuids and high levels are found in sputum, bronchial secretions and bile. Aminoglycosides are mini-mally protein bound (<20%, streptomycin 35%) to plasma pro-teins. Aminoglycosides do not readily cross the blood-brain barrier or penetrate ocular tissue. CSF levels are unpredictable and range from 0-50% of those found in the serum. Therapeutic levels are found in bone, heart, gallbladder and lung tissues after parenteral dosing. Aminoglycosides tend to accumulate in certain tissues, such as the inner ear and kidneys, which may help explain their toxicity. Volumes of distribution have been reported to be 0. 15-0. 3 L/kg in adult cats and dogs, and 0. 26-0. 58 L/kg in horses. Volumes of distri-bution may be signiﬁcantly larger in neonates and juvenile animals due to their higher extracellular ﬂuid fractions. Aminoglycosides cross the placenta, but one study showed no detectable levels in foals when gentamicin was administered to mares at term. In other species, fetal concentrations range from 15-50% of those found in maternal serum. Elimination of aminoglycosides after parenteral administration occurs almost entirely by glomerular ﬁltration. The elimination half-lives for gentamicin have been reported to be 1. 82-3. 25 hours in horses, 2. 2-2. 7 hours in calves, 2. 4 hours in sheep, 1. 8 hours in cows, 1. 9 hours in swine, 1 hour in rabbits, and 0. 5-1. 5 hours in dogs and cats. Patients with decreased renal function can have signiﬁcantly prolonged half-lives. In humans with normal renal function, elimination rates can be highly variable with the amino-glycoside antibiotics. Contraindications/Precautions/Warnings Aminoglycosides are contraindicated in patients who are hyper-sensitive to them. Because these drugs are often the only effective agents in severe gram-negative infections there are no other abso-lute contraindications to their use. However, they should be used with extreme caution in patients with preexisting renal disease with concomitant monitoring and dosage interval adjustments made. Other risk factors for the development of toxicity include age (both neonatal and geriatric patients), fever, sepsis and dehydration. Because aminoglycosides can cause irreversible ototoxicity, they should be used with caution in “working” dogs (e. g., “seeing-eye”, herding, dogs for the hearing impaired, etc. ). Aminoglycosides should be used with caution in patients with neuromuscular disorders (e. g., myasthenia gravis) due to their neu-romuscular blocking activity. Because aminoglycosides are eliminated primarily through re-nal mechanisms, they should be used cautiously, preferably with serum monitoring and dosage adjustment in neonatal or geriatric animals. Aminoglycosides are often considered contraindicated in rabbits as they adversely affect the GI ﬂora balance in these animals, but dosages are listed below. Use with caution. Adverse Effects The aminoglycosides are infamous for their nephrotoxic and oto-toxic effects. The nephrotoxic (tubular necrosis) mechanisms of these drugs are not completely understood, but are probably relat-ed to interference with phospholipid metabolism in the lysosomes of proximal renal tubular cells, resulting in leakage of proteolytic enzymes into the cytoplasm. Nephrotoxicity is usually manifested by increases in: BUN, creatinine, non-protein nitrogen in the se-rum, and decreases in urine speciﬁc gravity and creatinine clear-ance. Proteinuria and cells or casts may also be seen in the urine. Nephrotoxicity is usually reversible once the drug is discontinued. While gentamicin may be more nephrotoxic than the other amino-glycosides, the incidences of nephrotoxicity with all of these agents require equal caution and monitoring. Ototoxicity (8th cranial nerve toxicity) of the aminoglycosides can manifest by either auditory and/or vestibular clinical signs and may be irreversible. Vestibular clinical signs are more frequent with streptomycin, gentamicin, or tobramycin. Auditory clinical signs are more frequent with amikacin, neomycin, or kanamycin, but other forms can occur with any of the drugs. Cats are apparently very sensitive to the vestibular effects of the aminoglycosides. The aminoglycosides can also cause neuromuscular blockade, facial edema, pain/inﬂammation at injection site, peripheral neu-ropathy, and hypersensitivity reactions. Rarely, GI clinical signs, he-matologic and hepatic effects have been reported. Reproductive/Nursing Safety Aminoglycosides can cross the placenta and, while rare, may cause 8th cranial nerve toxicity or nephrotoxicity in fetuses. Because the drug should only be used in serious infections, the beneﬁts of ther-apy may exceed the potential risks. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ). In a separate system evaluating the safety of drugs in canine and fe-line pregnancy (Papich 1989), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should be used cau-tiously as a last resort when the beneﬁt of therapy clearly outweighs the risks. ) While small amounts of gentamicin may be excreted into milk, the risk to nursing offspring appears minimal. Overdosage/Acute Toxicity Should an inadvertent overdosage be administered, three treat-ments have been recommended. 1) Hemodialysis is very effective in reducing serum levels of the drug, but is not a viable option for most veterinary patients. 2) Peritoneal dialysis also will reduce se-rum levels, but is much less effective. 3) Complexation of drug with ticarcillin (12-20 g/day in humans) is reportedly nearly as effective as hemodialysis.	pppbs.pdf
GENTAMICIN SULFATE 421 Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving gentamicin and may be of signiﬁcance in veterinary patients: !TBETA-LACTAM ANTIBIOTICS (penicillins, cephalosporins ): May have synergistic effects against some bacteria; some potential for inac-tivation of aminoglycosides in vitro (do not mix together) and in vivo (patients in renal failure) !TCEPHALOSPORINS : The concurrent use of aminoglycosides with cephalosporins is somewhat controversial. Potentially, cepha-losporins could cause additive nephrotoxicity when used with aminoglycosides, but this interaction has only been well docu-mented with cephaloridine and cephalothin (both no longer marketed). !TDIURETICS, LOOP (e. g., furosemide, torsemide ) or OSMOTIC (e. g., man-nitol): Concurrent use with loop or osmotic diuretics may increase the nephrotoxic or ototoxic potential of the aminoglycosides !TNEPHROTOXIC DRUGS, OTHER (e. g., cisplatin, amphotericin b, polymyxin B, or vancomycin ): Potential for increased risk for nephrotoxicity !TNEUROMUSCULAR BLOCKING AGENTS & ANESTHETICS, GENERAL : Con-comitant use with general anesthetics or neuromuscular block-ing agents could potentiate neuromuscular blockade Laboratory Considerations !TGentamicin serum concentrations may be falsely decreased if the patient is also receiving beta-lactam antibiotics and the serum is stored prior analysis. It is recommended that if assay is delayed, samples be frozen and, if possible, drawn at times when the beta-lactam antibiotic is at a trough. Doses Note : Most infectious disease clinicians now agree that aminoglyco-sides should be dosed once a day in most patients (mammals). This dosing regimen yields higher peak levels with resultant greater bac-terial kill, and as aminoglycosides exhibit a “post-antibiotic effect”, surviving susceptible bacteria generally do not replicate as rapidly even when antibiotic concentrations are below MIC. Periods where levels are low may decrease the “adaptive resistance” (bacteria take up less drug in the presence of continuous exposure) that can oc-cur. Once daily dosing may also decrease the toxicity of aminogly-cosides as lower urinary concentrations may mean less-uptake into renal tubular cells. However, patients who are neutropenic (or oth-erwise immunosuppressed) may beneﬁt from more frequent dos-ing (q8h). !TDOGS: For susceptible infections: a) For sepsis: 6 mg/kg IV once daily (Hardie 2000) b) 6-8 mg/kg (route not speciﬁed) once daily (q24h). Neutro-penic or immunocompromised patients may still need to be dosed q8h (dose divided). (Trepanier 1999) c) 8 mg/kg once daily or 2-4 mg/kg q8h IV, IM or SC (Aucoin 2002b) d) For localized, urinary infections: First dose of 4. 4 mg/kg IM, SC and then 2. 2 mg/kg IM, SC once daily (q24h) for 7-10 days; For orthopedic and soft tissue infections: 4. 4-6. 6 mg/kg IV, IM, SC once daily (q24h) for <7 days. For bacteremia, sepsis: 6. 6 mg/kg IV, IM, SC once daily (q24h) for <7 days. Monitor renal function by urine sediment examination and serum urea nitrogen levels. (Greene, Hartmannn et al. 2006) e) For Brucellosis: Gentamicin 5 mg/kg SC once daily (q24h) for 7 days; 2-courses of treatment, treating on weeks one and four; plus Minocycline at 25 mg/kg PO once daily (q24h) for 4 weeks. Eventually, doxycycline can be substituted for minocycline at the same dosage to lower cost. Infected ani-mals may need to be treated for two or more 4-week courses. Sequential antibody tests at 3 to 6 monthly intervals are rec-ommended to monitor treatment. Monitor renal function secondary to gentamicin therapy. (Hartmannn and Greene 2005) !TCATS: For susceptible infections: a) For sepsis: 6 mg/kg IV once daily (Hardie 2000) b) 6-8 mg/kg (route not speciﬁed) once daily (q24h). Neutro-penic or immunocompromised patients may still need to be dosed q8h (dose divided). (Trepanier 1999) c) 8 mg/kg once daily or 2-4 mg/kg q8h IV, IM or SC (Aucoin 2002b) d) For localized, urinary infections: 2. 2 mg/kg IV, IM, SC once daily (q24h) for <7 days; For bacteremia, sepsis: 4. 4 mg/kg IV, IM, SC once daily (q24h) for <7 days. Monitor renal function by urine sediment examination and serum urea nitrogen levels. (Greene, Hartmannn et al. 2006) !TFERRETS: For susceptible infections: a) 5 mg/kg SC, IM q24h; use with caution or avoid use. (Mor-risey and Carpenter 2004) b) 4-8 mg/kg IM, SC, IV divided and given 2-3 times daily. Use only when culture and sensitivity dictates. (Williams 2000) !TRABBITS/RODENTS/SMALL MAMMALS: a) Rabbits: 5-8 mg/kg daily dose (may divide into q8h-q24h) SC, IM or IV. Increased efﬁcacy and decreased toxicity if giv-en once daily. If given IV, dilute into 4 m L/kg of saline and give over 20 minutes (Ivey and Morrisey 2000) b) Chinchillas, Gerbils, Guinea pigs, Hamsters, Mice, Rats: 2-4 mg/kg SC or IM q8-24h (Adamcak and Otten 2000) c) Chinchillas: 2-4 mg/kg SC, IM q8-24h (Hayes 2000) !TCATTLE: For susceptible infections: a) 4. 4-6. 6 mg/kg/day IM divided three times daily (Upson 1988) b) Intramammary: 100-150 mg q12h (Schultz 1986) !THORSES: For susceptible infections: a) Foals: 8-10 mg/kg q18-24 hours. Monitor levels to adjust dosage or dosing interval. (Furr 1999) b) Adults: 6. 6 mg/kg IV or IM once daily (q24h) (Foreman 1999), (Chafﬁn 2006a) c) For intrauterine infusion: 0. 5-2 grams. Little science is avail-able for recommending doses, volume infused, frequency, di-luents, etc. Most intrauterine treatments are commonly per-formed every day or every other day for 3-7 days. (Perkins 1999) d) Foals: 7 mg/kg IV or IM once daily (q24h) (Giguere 2003a) !TSWINE: For susceptible infections: a) For colibacillosis in neonates: 5 mg PO or IM once (Label di-rections; Garacin® Pig Pump and Piglet Injection—Schering)	pppbs.pdf
422 GENTAMICIN SULFATE b) For weanlings and other swine: Colibacillosis: 1. 1 mg/kg/day in drinking water (concentra-tion of 25 mg/gallon) for 3 days. Swine dysentery (Treponema hyodysenteriae): 2. 2 mg/kg/ day in drinking water (concentration of 50 mg/gallon) for 3 days (Label directions; Garacin® Soluble Powder and Oral Solution—Schering) !TBIRDS: For susceptible infections: a) For Pheasants and Cranes: 5 mg/kg IM three times daily for 5-10 days. For Quail, African Grey Parrots: 10 mg/kg IM three times daily. Blue and Gold Macaws: 10 mg/kg IM twice daily. Once or twice daily dosing may be effective in less seri-ous infections. (Clubb 1986) b) For gut sterilization/gut infections: 40 mg/kg PO 1-3 times a day for 2-3 days. (Clubb 1986) c) For pneumonia (with carbenicillin or tylosin given IM): 5-10 mg/kg intratracheally once daily (Clubb 1986) d) Ratites: 5 mg/kg IM once daily; Note : use only as a last resort as it causes visceral gout (Jenson 1998) !TREPTILES: For susceptible infections: a) For bacterial gastritis in snakes: gentamicin 2. 5 mg/kg IM every 72 hours with oral neomycin 15 mg/kg plus oral live lactobacillus. (Burke 1986) b) For bacterial shell diseases in turtles: 5-10 mg/kg daily in water turtles, every other day in land turtles and tortoises for 7-10 days. Used commonly with a beta-lactam antibiotic. Recommend beginning therapy with 20 m L/kg ﬂuid injec-tion. Maintain hydration and monitor uric acid levels when possible. (Rosskopf 1986) Monitoring (Parenteral use) !TEfﬁcacy (cultures, clinical signs associated with infection) !TRenal toxicity; baseline urinalysis, serum creatinine/BUN. Casts in the urine are often the initial sign of impending nephrotoxic-ity. Frequency of monitoring during therapy is controversial. Fre-quency of monitoring during therapy is controversial, but daily urinalysis and serum creatinine may not be too frequent. !TGross monitoring of vestibular or auditory toxicity is recommended !TSerum levels, if possible. Draw levels at 1, 2, and 4 hours post dose. Peak should be at least 20 mcg/m L and 4 hour sample should be less than 10 mcg/m L (Papich 2003c). Client Information !TWith appropriate training, owners may give subcutaneous injec-tions at home, but routine monitoring of therapy for efﬁcacy and toxicity must still be done. !TClients should un derstand that the potential exists for severe toxicity (nephrotoxicity, ototoxicity) developing from this medication. Chemistry/Synonyms An aminoglycoside obtained from cultures of Micromonaspora pur-purea, gentamicin sulfate occurs as a white to buff powder that is soluble in water and insoluble in alcohol. The commercial product is actually a combination of gentamicin sulfate C 1, C2, and C 3, but all these compounds apparently have similar antimicrobial activi-ties. Commercially available injections have a p H from 3-5. 5. Gentamicin may also be known as: gentamicin sulphate, gen-tamicini sulfas, NSC-82261, and Sch-9724; many trade names are available. Storage/Stability/Compatibility Gentamicin sulfate for injection and the oral solution should be stored at room temperature (15-30°C); freezing or temperatures above 40°C should be avoided. The soluble powder should be stored from 2-30°C. Do not store or offer medicated-drinking water in rusty containers or the drug may be destroyed. While the manufacturer does not recommend that gentamicin be mixed with other drugs, it is reportedly physically compatible and stable in all commonly used intravenous solutions and with the fol-lowing drugs: bleomycin sulfate, cefoxitin sodium, cimetidine HCl, clindamycin phosphate, methicillin sodium, metronidazole (with and without sodium bicarbonate), penicillin G sodium, and vera-pamil HCl. The following drugs or solutions are reportedly physically incompatible or only compatible in speciﬁc situations with gentami-cin: amphotericin B, ampicillin sodium, carbenicillin disodium, cefamandole naftate, cephalothin sodium, cephapirin sodium, do-pamine HCl, furosemide, and heparin sodium. Compatibility is de-pendent upon factors such as p H, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more speciﬁc information. In vitro inactivation of aminoglycoside antibiotics by beta-lac-tam antibiotics is well documented. Gentamicin is very susceptible to this effect and it is recommended to avoid mixing these com-pounds together. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Gentamicin Sulfate Injection: 100 mg/m L in 100 m L and 250 m L vi-als; Amtech® Gentamax 100 (IVX), Gentafuse® (Butler), Gentamax® 100 (Phoenix Pharmaceutical), Gentaved® 100 (Vedco), Gentozen® (Schering-Plough), Legacy® (Agri Labs); generic; (Rx). Approved for horses. Gentamicin Sulfate Injection: 100 mg/m L (poultry only) in 100 m L vials; Garasol® Injection (Schering-Plough); Amtech® Gentapoult (IVX); (OTC) For use in day-old chickens (slaughter withdrawal = 5 weeks) and 1-3 day-old turkeys (slaughter withdrawal=9 weeks) only. Gentamicin Sulfate Injection: 5 mg/m L in 250 m L vials; Garacin® Piglet Injection (Schering-Plough); (OTC). Approved for use in pig-lets up to 3 days of age. Slaughter (when used as labeled) = 40 days. Gentamicin Sulfate Oral Solution: 5 mg/m L in 118 m L bottles with pump applicator; Amtech® Gentamicin Sulfate Pig Pump Oral Solu-tion (IVX); (Rx); Approved for use in neonatal swine only. Slaughter withdrawal = 14 days. Gentamicin Soluble Powder: 333. 33 mg/g in 360 gram jars. Approved for use in weanling swine. Slaughter withdrawal = 10 days. Gen-Gard® Soluble Powder (Agri Labs); (OTC) Gentamicin Sulfate Soluble Powder: 2 g gentamicin/30 grams of powder in 360-gram jar; Garacin® Soluble Powder (Schering-Plough); (OTC). Approved for use in swine. Slaughter (when used as labeled) = 10 days. Veterinary-approved injections for chickens and turkeys plus a water additive for egg dipping may also be available. Ophthalmic, otic, and topical preparations are available with veterinary labeling. HUMAN-APPROVED PRODUCTS (partial listing): Gentamicin Sulfate Injection: 40 mg/m L (as sulfate) in 2 m L and 20 m L vials and 1. 5 m L and 2 m L cartridge-needle units; 10 mg/m L (as sulfate) in 2 m L vials & ADD-Vantage 60 mg, 80 mg & 100 mg vials; 0. 8 mg/m L, 0. 9 mg/m L, & 1 mg/m L (as gentamicin base) in 100 m L; 1. 2 mg/m L, 1. 4 mg/m L & 1. 6 mg/m L (as gentamicin base) in 50 m L;	pppbs.pdf
GLIMEPIRIDE 423 Pediatric Gentamicin Sulfate (Fujisawa); Gentamicin Sulfate in 0. 9% Sodium Chloride (Hospira); generic; (Rx) T opical, otic and ophthalmic labeled products are also available. GLIMEPIRIDE (glye-meh-per-ide) Amaryl® SULFONYLUREA ANTIDIABETIC AG ENT Prescriber Highlights TT Oral, once-daily, anti-hyperglycemic agent; could be use-ful in the adjunctive treatment of non-insulin dependent diabetes mellitus (NIDDM) in cats TT Very limited experience in cats TT Contraindicated: Patients hypersensitive to it or with dia-betic ketoacidosis TT Hypoglycemia may occur TT Potentially, signiﬁcant drug interactions TT Do not confuse glipizide, glimepiride & glyburide Uses/Indications Glimepiride may potentially be a useful adjunct in the treatment of non-insulin dependent diabetes mellitus (NIDDM) in cats. Its du-ration of action in humans allows it to be dosed once daily, which could be of beneﬁt in cats. It may also have fewer side effects than glipizide in cats. Pharmacology/Actions Glimepiride increases pancreatic release of insulin from function-ing beta cells and, with continued use, may also increase peripheral tissue sensitivity to insulin. The exact mechanism for these effects is not well understood. Pharmacokinetics No pharmacokinetic data for cats was located. In humans, glimepir-ide is completely absorbed from the GI tract. Peak levels occur in 2-3 hours; food delays the peak somewhat and lowers AUC by about 9%. Volume of distribution is 0. 11 L/kg; the drug is greater than 99% bound to plasma proteins. Glimepiride is hepatically me-tabolized to at least two major metabolites. One of these, M1, has activity at about N that of the parent compound; clearance is 48 m L/min and elimination half-life about 9 hours. Approximately 60% of the drug (as metabolites) are excreted into the urine and the remainder in the feces. The drug has a 24-hour duration of ac-tivity in humans. Contraindications/Precautions/Warnings Glimepiride is contraindicated in patients hypersensitive to it or with diabetic ketoacidosis. Adverse Effects Hypoglycemia has been reported in about 1% of human patients taking the drug. Dizziness and asthenia have been reported; rarely, liver function impairment, dermatologic reactions, or hematologic reactions have been reported in humans. Reproductive/Nursing Safety In humans, the FDA categorizes glimepiride as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). In rabbits and rats, glimepiride did not cause teratogenic effects when given at high dosages. There were some intrauterine deaths when maternal hypoglycemia was induced by the drug. Some glimepiride is excreted into maternal milk of rats. The manufacturer states to discontinue the drug in nursing, human mothers. Overdosage/Acute Toxicity Overdoses may result in hypoglycemia, ranging from mild to se-vere. Treatment consists of glucose administration and intensive monitoring. Because of the drug's long duration of activity, patients may need to be supported with glucose for a least 48 hours post-ingestion, even after apparent recovery. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving glimepiride and may be of signiﬁcance in veterinary patients: T ! ANTIFUNGALS, AZOLE (ketoconazole, itraconazole, ﬂuconazole ): May increase plasma levels of glimepiride T ! BETA-BLOCKERS : May potentiate hypoglycemic effect T ! CHLORAMPHENICOL : May displace glimepiride from plasma proteins T ! CORTICOSTEROIDS : May reduce efﬁcacy T ! DIURETICS, THIAZIDE : May reduce hypoglycemic efﬁcacy T ! ISONIAZID : May reduce hypoglycemic efﬁcacy T ! NIACIN : May reduce hypoglycemic efﬁcacy T ! PHENOTHIAZINES : May reduce hypoglycemic efﬁcacy T ! PHENYTOIN : May reduce hypoglycemic efﬁcacy T ! SULFONAMIDES : May displace glimepiride from plasma proteins T ! SYMPATHOMIMETIC AGENTS : May reduce hypoglycemic efﬁcacy T ! WARFARIN : May displace glimepiride from plasma proteins Laboratory Considerations No speciﬁc laboratory interactions or considerations were noted. Doses T ! CATS: For treatment of NIDDM: a) 2 mg (total dose) per cat once daily (Bruyette 2004) b) 1-2 mg (total dose per cat) PO once daily (Scherk 2005c) Monitoring T ! Efﬁcacy: Standard methods of monitoring efﬁcacy for diabetes treatment should be followed (e. g., fasting blood glucose, appe-tite, attitude, body condition, PU/PD resolution and, perhaps, serum fructosamine and/or glycosylated hemoglobin levels) T ! Adverse effects Client Information T ! Clients should understand the “investigational” nature of using this drug in cats and report any untoward effects to the veteri-narian. Chemistry/Synonyms A sulfonylurea antidiabetic agent, glimepiride occurs as a white to yellowish-white, crystalline, odorless to practically odorless pow-der. It is practically insoluble in water. Glimepiride may also be known as: HOE-490, Amarel®, Amaryl®, Amarylle®, Euglim®, Glimepil®, Solosa®, and Roname®.	pppbs.pdf
424 GLIPIZIDE Storage/Stability/Compatibility Glimepiride tablets should be stored between 15-30°C (59-86°F) in well closed containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Glimepiride Tablets: 1 mg, 2 mg, & 4 mg; Amaryl® (Aventis); generic; (Rx) GLIPIZIDE (glip-i-zide) Glucotrol® SULFONYLUREA ANTIDIABETIC AG ENT Prescriber Highlights TT Human oral antidiabetic agent (Type II) that may be use-ful in cats TT Contraindications: Severe burns/trauma/infection, dia-betic coma or other hypoglycemic conditions, major surgery, ketosis, ketoacidosis or other signiﬁcant acidotic conditions TT Caution: Untreated adrenal or pituitary insufﬁciency; thyroid, renal or hepatic function impairment; prolonged vomiting; high fever; malnourishment or debilitated condition TT Adverse Effects: CATS: GI (i. e., anorexia, vomiting), hypo-glycemia, liver toxicity TT Drug interactions TT Do not confuse glipizide, glimepiride & glyburide Uses/Indications Glipizide may be of beneﬁt in treating cats with type II diabetes if they have a population of functioning beta cells. It has been sug-gested that there are two situations when glipizide can be recom-mended, 1) If an owner refuses to consider using insulin usually due to a fear of needles, and 2) the cat appears to be relatively well controlled on quite small doses of insulin and the owner would strongly prefer to no longer give insulin (Feldman 2005b). While glipizide potentially could be useful in treating canine pa-tients with type II or III diabetes, however, by the time dogs present with hyperglycemia, they are absolutely or relatively insulinopenic and glipizide would unlikely be effective. Pharmacology/Actions Sulfonylureas lower blood glucose concentrations in both diabetics and non-diabetics. The exact mechanism of action is not known, but these agents are thought to exert the effect primarily by stimu-lating the beta cells in the pancreas to secrete additional endogenous insulin. Extrapancreatic effects include enhanced tissue sensitivity of circulating insulin. Ongoing use of the sulfonylureas appears to enhance peripheral sensitivity to insulin and reduce the production of hepatic basal glucose. The mechanisms causing these effects are yet to be fully explained, however. Pharmacokinetics Glipizide is rapidly and practically completely absorbed after oral administration. The absolute bioavailability reported in humans ranges from 80-100%. Food will alter the rate, but not the extent, of absorption. Glipizide is very highly bound to plasma proteins. It is primarily biotransformed in the liver to inactive metabolites that are then excreted by the kidneys. In humans, half-life is about 2-4 hours. Effects on insulin levels in cats tend to be short-lived. Effects peak in about 15 minutes and return to baseline after about 60 minutes. Contraindications/Precautions/Warnings Oral antidiabetic agents are considered contraindicated with the following conditions: severe burns, severe trauma, severe infection, diabetic coma or other hypoglycemic conditions, major surgery, ke-tosis, ketoacidosis or other signiﬁcant acidotic conditions. Glipizide should only be used when its potential beneﬁts outweigh its risks during untreated adrenal or pituitary insufﬁciency; thyroid, renal or hepatic function impairment; prolonged vomiting; high fever; malnourishment or debilitated condition is present. While glipizide may initially be effective, it may become ineffec-tive in weeks to months after starting therapy; insulin will then be required. Some patients with type II or type III diabetes may have their disease complicated by the production of excessive amounts of cor-tisol or growth hormone which may antagonize insulin's effects. These causes should be ruled out before initiating oral antidiabetic therapy. Adverse Effects Approximately 15% of cats receiving glipizide develop gastrointesti-nal adverse effects (i. e., anorexia, vomiting). Vomiting usually will subside in 2-5 days. If it persists or is severe, decrease dose or fre-quency and, if necessary, discontinue. Some cats receiving this drug have developed hypoglycemia, but severe hypoglycemia appears to be rare. Should hypoglycemia oc-cur, discontinue glipizide and recheck glucose in one week; may re-start at a lower dose or dosing frequency if hyperglycemia is noted. Effects on the liver have been reported. Serum hepatic enzymes should be checked every 1-2 weeks initially. Discontinue glipiz-ide in cats with elevated enzymes if they develop lethargy, anorexia, vomiting, or if ALT exceeds 500 IU/L; should icterus occur, discon-tinue glipizide and restart at a lower dose once icterus resolves; dis-continue use should icterus reoccur. Other adverse effects that are possible (noted in humans) in-clude: allergic skin reactions, and bone marrow suppression. Glipizide does not appear to be effective in cats demonstrating insulin resistance. Reproductive/Nursing Safety Safe use during pregnancy has not been established. Glipizide was found to be mildly fetotoxic in rats when given at doses at 5-50 mg/ kg; however, no other teratogenic effects were noted. Use in preg-nancy only when beneﬁts outweigh potential risks. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduc-tion studies and no adequate studies in humans. ) It is unknown if glipizide enters milk. Overdosage/Acute Toxicity Oral LD 50's are greater than 4 g/kg in all animal species tested. Pro-found hypoglycemia is the greatest concern after an overdose. Gut emptying protocols should be employed when warranted. Because of its shorter half-life than chlorpropamide, prolonged hypoglyce-mia is less likely with glipizide, but blood glucose monitoring and treatment with parenteral glucose may be required for several days. Massive overdoses may also require additional monitoring (blood gases, serum electrolytes) and supportive therapy.	pppbs.pdf
GLUCAGON 425 Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving glipizide and may be of signiﬁcance in veterinary patients: T ! ALCOHOL : A disulﬁram-like reaction (anorexia, nausea, vomiting) has been reported in humans who have ingested alcohol within 48-72 hours of receiving glipizide T ! ANTIFUNGALS, AZOLE (ketoconazole, itraconazole, ﬂuconazole ): May increase plasma levels of glipizide ! !BETA-BLOCKERS : May potentiate hypoglycemic effect ! !CHLORAMPHENICOL : May displace glipizide from plasma proteins ! !CIMETIDINE : May potentiate hypoglycemic effect ! !CORTICOSTEROIDS : May reduce efﬁcacy ! !DIURETICS, THIAZIDE : May reduce hypoglycemic efﬁcacy ! !ISONIAZID : May reduce hypoglycemic efﬁcacy ! !MOA INHIBITORS : May potentiate hypoglycemic effect ! !NIACIN : May reduce hypoglycemic efﬁcacy ! !PHENOTHIAZINES : May reduce hypoglycemic efﬁcacy ! !PHENYTOIN : May reduce hypoglycemic efﬁcacy ! !PROBENECID : May potentiate hypoglycemic effect ! !SULFONAMIDES : May displace glipizide from plasma proteins ! !SYMPATHOMIMETIC AGENTS : May reduce hypoglycemic efﬁcacy ! !THYROID AGENTS : May reduce hypoglycemic effect ! !WARFARIN : May displace glipizide from plasma proteins Doses T ! CATS: For diabetes mellitus: a) In non-ketotic cats that are relatively healthy: Initially moni-tor weight, urine/glucose/ketones, and several blood glucose measurements. Then give 2. 5 mg PO per cat twice daily in conjunction with a meal. After 2 weeks, monitor again and if adverse reactions have not occurred, increase dose to 5 mg twice daily and re-evaluate again in 2 weeks. (Nelson 2000), (Nelson 2005) b) 2. 5-5 mg per cat PO twice a day when combined with di-etary ﬁber therapy. Evaluate every one to two weeks for a pe-riod of 2-3 months. If fasting blood glucose decreases to less than 200 mg/dl, continue at same dosage and reevaluate in 3-6 months. If fasting blood glucose remains greater than 200 mg/dl after 2-3 months, discontinue and institute insu-lin therapy (Greco 1999); (Greco 2000) c) If cat is generally well, weight loss is mild, not ketoacidotic, and does not have peripheral neuropathy, may try glipizide at: 2. 5 mg (total dose) PO twice a day. (Daminet 2003) d) 5 mg per cat PO twice daily, may decrease dose if hypogly-cemia occurs or increase to 7. 5 mg (maximum) twice daily if not controlled. Slightly less than 50% of cats may tolerate the drug, have improved clinical signs and blood glucose lev-els. Response may be delayed, so it should be given for 4-8 weeks before deciding if it was efﬁcacious (owner opinion, body weight, blood glucose determinations over a one-day period every 4 weeks. ) (Feldman 2005b) Monitoring T ! Weekly exams during ﬁrst month of therapy, including PE, body weight, urine glucose/ketones, and several blood glucose exams. T ! Adverse effects (anorexia, vomiting, icterus), and occasional liver enzymes and CBC. Client Information T ! Clients should be informed of clinical signs to watch for that would indicate either hypoglycemia or hyperglycemia and be in-structed to report these to the veterinarian. T ! Compliance with dosing regimen should also be stressed. Chemistry/Synonyms A sulfonylurea antidiabetic agent, glipizide (also known as glydi-azinamide) occurs as a whitish powder. It is practically insoluble in water and has p K a of 5. 9. Glipizide may also be known as: CP-28720, glipizidum, glydiazi-namide, or K-4024; many international trade names are available. Storage/Stability Tablets should be stored in tight, light-resistant containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Glipizide Tablets: 5 mg, & 10 mg; Glucotrol® (Pﬁzer); generic (Rx) Glipizide Extended Release Tablets: 2. 5 mg, 5 mg, & 10 mg; Glucotrol XL® (Pﬁzer); generic; (Rx) Glipizide/Metformin Hydrochloride Tablets (ﬁlm-coated): 2. 5 mg/250 mg or 500 mg; 5 mg/500 mg; Metaglip® (Bristol-Myers S-quibb); generic (Sandoz); (Rx) GLUCAGON (gloo-ka-gon) Gluco Gen® HORMONAL A GENT Prescriber Highlights TT Hormone to increase blood glucose that may be useful for treating hypoglycemia in small animals & potentially fatty liver syndrome in dairy cows TT May be effective in treating beta-blocker or calcium chan-nel overdoses TT Must be parenterally administered TT When used as CRI, must be in a setting where blood glu-cose can be monitored TT Unlikely to cause adverse effects Uses/Indications In small animals, the primary use for glucagon is to increase blood glucose in patients with excessive insulin levels, either endogenous-ly produced (insulinoma) or exogenously administered (insulin overdose). Glucagon has potential in the treatment of fatty liver syndrome in dairy cattle. In human medicine, glucagon is used in treating the cardiac manifestations of beta-blocker and calcium-channel blocker over-doses. One study (Kerns, D et al. 1997) in dogs, however, demon-strated insulin to be superior to glucagon in treating experimental propranolol overdoses in dogs. Pharmacology/Actions Glucagon's main pharmacologic activities are to increase blood glu-cose and relax smooth muscle of the GI tract. It primarily increases blood glucose by stimulating hepatic glycogenolysis. The mecha-nisms of action for its GI effects are poorly understood.	pppbs.pdf
426 GLUCAGON Pharmacokinetics Glucagon must be administered parenterally; it is destroyed in the gut after oral dosing. After intravenous injection, maximum glu-cose levels are attained within 30 minutes; hyperglycemic effects persist up to 90 minutes after dosing. Glucagon is degraded in the plasma, liver and kidneys; in humans, plasma half-life is around 10 minutes. Contraindications/Precautions/Warnings Glucagon should usually not be used in patients with pheochro-mocytoma as catecholamines may be released leading to hyperten-sion. When used for insulinoma, it must be in a setting where blood glucose can be closely monitored. While glucagon may be useful for blood glucose elevation in insulinoma patients, in humans its use for this is cautioned as it can increase insulin production, leading to greater hypoglycemia once the drug is discontinued. Adverse Effects Glucagon is usually well tolerated, but potentially nausea and vom-iting could occur after administration. Hypokalemia and hypersen-sitivity reactions (very rare) are also possible. Reproductive/Nursing Safety In humans, glucagon is designated by the FDA as a category B drug (Animal studies have not demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus during the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) As an endogenously produced hormone, it is unlikely to cause signiﬁcant risk to offspring. It is unknown if glucagon enters maternal milk, but it is unlikely to cause harm to nursing offspring. Overdosage/Acute Toxicity Adverse effects seen with overdose include nausea, vomiting, di-arrhea, gastric hypotonicity and, possibly, hypokalemia. Because glucagon's elimination half-life is so short, treatment may not be necessary and would be symptomatic in nature. If the patient is also receiving beta-blockers, greater increases in blood pressure and heart rate may be seen. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving glucagon and may be of signiﬁcance in veterinary patients: !TANTICOAGULANTS : May have their effects increased when glucagon is concurrently administered; this effect may be delayed. It is sug-gested to monitor for bleeding and prothrombin activity if glu-cagon is necessary. Laboratory Considerations No glucagon-related laboratory interactions noted. Doses !TDOGS: a) For hypoglycemic (neuroglycopenic) crises in patients with “insulinomas”: 1 mg of glucagon is reconstituted per manu-facturer directions and then added to 1000 m L of 0. 9% Sodi-um Chloride; this results in a 1000 ng/m L (nanograms/m L) solution. [ Note : Some references state to not mix or dilute with saline solutions, but to use D5W only. ] Initially give a 50 ng/kg bolus IV and then administer at a constant rate infu-sion (CRI) using a suitable pump at a rate of 10-15 ng/kg/ minute. May need to increase up to 40 ng/kg/min to main-tain euglycemia. (Smith 2002c) b) For refractory hypoglycemic patients with insulinoma: Pre-pare solution as in “a” above. Give at an initial infusion rate of 5 ng/kg/min and increase as needed. (Garrett 2003) !TCATS: a) For hypoglycemic (neuroglycopenic) crises in patients with “insulinomas”: 1 mg of glucagon is reconstituted per manu-facturer directions and then added to 1000 m L of 0. 9% So-dium Chloride; this results in a 1000 ng/m L solution. [ Note : Some references state to not mix or dilute with saline solu-tions, but to use D5W only. ] Initially give a 50 ng/kg bolus IV and then administer at a constant rate infusion (CRI) using a suitable pump at a rate of 10-15 ng/kg/minute. May need to increase up to 40 ng/kg/min to maintain euglycemia. (Smith 2002c) !TCATTLE: a) For treatment of fatty liver in early lactation dairy cows older than 3. 5 years: 5 mg glucagon in 60 m L of normal saline SC q8h (15 mg/day) for 14 days (Bobe, Ametaj et al. 2003) Monitoring !TBlood glucose !TSerum potassium if used other than for acute treatment Client Information !TGlucagon could potentially be used for outpatient emergency initial treatment of hypoglycemia, but oral glucose is probably more appropriate for use by clients. !TGlucagon should be used as a CRI only in a setting where blood glucose can be adequately monitored. Chemistry/Synonyms A hormone secreted by the alpha2 cells of the pancreas, glucagon is a straight chain polypeptide that contains 29 amino acids whose sequence is consistent throughout mammalian species. It has a mo-lecular weight of 3483. When in crystalline form it is a white-to off-white powder that is relatively insoluble in water at physiologic p H, but is soluble at p H of less than 3 and greater than 9. 5. Glucagon may be expressed in terms of International Units (IU) or by weight. One IU is equivalent to one milligram of glucagon. Commercially available glucagon is now obtained via recombinant DNA sources. Glucagon may also be known as glucagonum or HGF, and Gluca Gen®. Storage/Stability/Compatibility The commercially available powder for reconstitution should be stored at room temperature between 20-25°C (68-77°F); avoid freezing and protect from light. Once reconstituted with the sup-plied diluent the solution should be clear with a water-like con-sistency and used immediately; any unused portion should be dis-carded. If the solution contains any gel formation or particles, it should be discarded. T o prepare glucagon for a continuous rate infusion, dilute 1 mg with the supplied diluent or sterile water; roll gently until dissolved, this may then be further diluted in D5W. May be given through a Y-tube or 3-way stopcock if a dextrose solution is running. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Glucagon powder for Injection: 1 mg (1 unit) with 1 m L diluent in vials & syringes; Gluca Gen® Diagnostic Kit & Gluca Gen Hypo Kit® (Novo Nordisk); Glucagon Emergency Kit® (Eli Lilly); (Rx)	pppbs.pdf
GLUCOCORTICOID AGENTS 427 GLUCOCORTICOID AGENTS, GENERAL INFORMATION drugs' vasoconstrictive properties and increased blood volume that may be produced. Cells : Glucocorticoids inhibit ﬁbroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lympho-cytes and the cellular response to mediators of inﬂammation. Glucocorticoid Comparison Table DRUG EQUIV. ANTI-INFLAMMATORY DOSE (MG) RELATIVE ANTI-INFLAMMATORY POTENCY RELATIVE MINERAL-CORTICOID ACTIVITY PLASMA HALF-LIFE DOGS (MIN) [HUMANS] DURATION OF ACTION AFTER ORAL/IV [IM] Hydrocortisone (Cortisol) 20 1 1-2 52-57 [90] <12 hrs Betamethasone Sod. Succ. / Sod. Phos. 0. 6 25 0 [300+] >48 hrs Dexamethasone Sod. Succ. / Sod. Phos. 0. 75 30 0 119-136 [200-300+] >48 hrs Flumethasone 1. 5 15-30 ? ? Isoﬂupredone 17 Methylpred- nisolone 4 5 0 91 [200] 12-36 hrs Prednisolone 5 4 1 69-197 [115-212] 12-36 hrs Prednisone 5 4 1 [60] 12-36 hrs Triamcinolone Acetonide 4 5 0 [200+] 12-36 hrs [weeks] Uses/Indications Glucocorticoids have been used in an attempt to treat practically every malady that afﬂicts man or animal, but there are three broad uses and dosage ranges for use of these agents. 1) Replacement of glucocorticoid activity in patients with adrenal insufﬁciency, 2) as an antiinﬂammatory agent, and 3) as an immunosuppressive. Among some of the uses for glucocorticoids include treatment of: endocrine conditions (e. g., adrenal insufﬁciency), rheumatic dis-eases (e. g., rheumatoid arthritis), collagen diseases (e. g., systemic lupus), allergic states, respiratory diseases (e. g., asthma), dermato-logic diseases (e. g., pemphigus, allergic dermatoses), hematologic disorders (e. g., thrombocytopenias, autoimmune hemolytic anemi-as), neoplasias, nervous system disorders (increased CSF pressure), GI diseases (e. g., ulcerative colitis exacerbations), and renal diseases (e. g., nephrotic syndrome). Some glucocorticoids are used topically in the eye and skin for various conditions or are injected intra-ar-ticularly or intra-lesionally. The above listing is certainly not com-plete. For speciﬁc dosages and indications refer to the Doses section for each glucocorticoid drug monograph. Pharmacology/Actions Glucocorticoids have effects on virtually every cell type and system in mammals. An overview of the effects of these agents follows: Cardiovascular System : Glucocorticoids can reduce capillary per-meability and enhance vasoconstriction. A relatively clinically in-signiﬁcant positive inotropic effect can occur after glucocorticoid administration. Increased blood pressure can result from both the Glucocorticoids stabilize lysosomal membranes. CNS/A utonomic Nervous System : Glucocorticoids can lower seizure threshold, alter mood and behavior, diminish the response to pyro-gens, stimulate appetite and maintain alpha rhythm. Glucocorticoids are necessary for normal adrenergic receptor sensitivity. Endocrine System : When animals are not stressed, glucocorticoids will suppress the release of ACTH from the anterior pituitary, thereby reducing or preventing the release of endogenous corticos-teroids. Stress factors (e. g., renal disease, liver disease, diabetes) may sometimes nullify the suppressing aspects of exogenously admin-istered steroids. Release of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), prolactin, and luteinizing hormone (LH) may all be reduced when glucocorticoids are ad-ministered at pharmacological doses. Conversion of thyroxine (T 4) to triiodothyronine (T 3) may be reduced by glucocorticoids; and plasma levels of parathyroid hormone increased. Glucocorticoids may inhibit osteoblast function. Vasopressin (ADH) activity is re-duced at the renal tubules and diuresis may occur. Glucocorticoids inhibit insulin binding to insulin-receptors and the post-receptor effects of insulin. Hematopoietic System : Glucocorticoids can increase the numbers of circulating platelets, neutrophils and red blood cells, but platelet aggregation is inhibited. Decreased amounts of lymphocytes (pe-ripheral), monocytes and eosinophils are seen as glucocorticoids can sequester these cells into the lungs and spleen and prompt de-creased release from the bone marrow. Removal of old red blood cells becomes diminished. Glucocorticoids can cause involution of lymphoid tissue. GI Tract and Hepatic System : Glucocorticoids increase the secre-tion of gastric acid, pepsin, and trypsin. They alter the structure of mucin and decrease mucosal cell proliferation. Iron salts and calcium absorption are decreased while fat absorption is increased. Hepatic changes can include increased fat and glycogen depos-its within hepatocytes, increased serum levels of alanine amin-otransferase (ALT), and gamma-glutamyl transpeptidase (GGT). Signiﬁcant increases can be seen in serum alkaline phosphatase levels. Glucocorticoids can cause minor increases in BSP (bromo-sulfophthalein) retention time. Immune System (also see Cells and Hematopoietic System): Glucocorticoids can decrease circulating levels of T-lymphocytes; inhibit lymphokines; inhibit neutrophil, macrophage, and mono-cyte migration; reduce production of interferon; inhibit phagocyto-sis and chemotaxis; antigen processing; and diminish intracellular killing. Speciﬁc acquired immunity is affected less than nonspeciﬁc immune responses. Glucocorticoids can also antagonize the com-plement cascade and mask the clinical signs of infection. Mast cells are decreased in number and histamine synthesis is suppressed. Many of these effects only occur at high or very high doses and there are species differences in response. Metabolic effects : Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body (e. g., abdomen) and adipose tissue can be redistributed away from the extremities to the trunk. Fatty acids are mobilized from tissues and their oxi-dation is increased. Plasma levels of triglycerides, cholesterol, and glycerol are increased. Protein is mobilized from most areas of the body (not the liver). Musculoskeletal : Glucocorticoids may cause muscular weakness (also caused if there is a lack of glucocorticoids), atrophy, and os-	pppbs.pdf
428 GLUCOCORTICOID AGENTS teoporosis. Bone growth can be inhibited via growth hormone and somatomedin inhibition, increased calcium excretion and inhibi-tion of vitamin D activation. Resorption of bone can be enhanced. Fibrocartilage growth is also inhibited. Ophthalmic : Prolonged corticosteroid use (both systemic or topically to the eye) can cause increased intraocular pressure and glaucoma, cataracts, and exophthalmos. Renal, Fluid, & Electrolytes : Glucocorticoids can increase potassium and calcium excretion, sodium and chloride reabsorption, and extra-cellular ﬂuid volume. Hypokalemia and/or hypocalcemia rarely oc-cur. Diuresis may develop following glucocorticoid administration. Skin: Thinning of dermal tissue and skin atrophy can be seen with glucocorticoid therapy. Hair follicles can become distended and alopecia may occur. Contraindications/Precautions/Warnings Systemic use of glucocorticoids is generally considered contrain-dicated in systemic fungal infections (unless used for replacement therapy in Addison's), when administered IM in patients with id-iopathic thrombocytopenia, and in patients hypersensitive to a particular compound. Use of sustained-release injectable gluco-corticoids is considered contraindicated for chronic corticosteroid therapy of systemic diseases. Animals that have received glucocorticoids systemically, other than with “burst” therapy, should be tapered off the drugs. Patients who have received the drugs chronically should be tapered off slowly as endogenous ACTH and corticosteroid function may re-turn slowly. Should the animal undergo a “stressor” (e. g., surgery, trauma, illness, etc. ) during the tapering process or until normal adrenal and pituitary function resume, additional glucocorticoids should be administered. Adverse Effects Adverse effects are generally associated with long-term administra-tion of these drugs, especially if given at high dosages or not on an alternate day regimen. Effects generally manifest as clinical signs of hyperadrenocorticism. When administered to young, grow-ing animals, glucocorticoids can retard growth. Many of the po-tential effects, adverse and otherwise, are outlined above in the Pharmacology section. In dogs, polydipsia (PD), polyphagia (PP), and polyuria (PU) may all be seen with short-term “burst” therapy as well as with al-ternate-day maintenance therapy on days when the drug is given. Adverse effects in dogs can include: dull, dry haircoat, weight gain, panting, vomiting, diarrhea, elevated liver enzymes, pancreatitis, GI ulceration, lipidemias, activation or worsening of diabetes mellitus, muscle wasting and behavioral changes (depression, lethargy, vi-ciousness). Discontinuation of the drug may be necessary; chang-ing to an alternate steroid may also alleviate the problem. With the exception of PU/PD/PP, adverse effects associated with short-term antiinﬂammatory therapy occur relatively uncommonly. Adverse effects associated with immunosuppressive doses are more com-mon and potentially more severe. Cats generally require higher dosages than dogs for clinical effect, but tend to develop fewer adverse effects. Occasionally, polydipsia, polyuria, polyphagia with weight gain, diarrhea, or depression can be seen. Long-term, high dose therapy can lead to “Cushingoid” ef-fects, however. Administration of dexamethasone or triamcinolone may play a role in the development of laminitis in horses. Reproductive/Nursing Safety Glucocorticoids are probably necessary for normal fetal develop-ment. They may be required for adequate surfactant production, myelin, retinal, pancreatic, and mammary development. Excessive dosages early in pregnancy may lead to teratogenic effects. In horses and ruminants, exogenous steroid administration may induce par-turition when administered in the latter stages of pregnancy. Glucocorticoids unbound to plasma proteins will enter milk. High dosages or prolonged administration to mothers may poten-tially inhibit the growth of nursing newborns. In humans, several studies suggest that amounts excreted in human breast milk are negligible with prednisone or prednisolone doses of 20 mg/day or less, or methylprednisolone doses less than or equal to 8 mg/day. Large doses for short periods may not harm the infant. Waiting 3-4 hours after the dose before nursing and using prednisolone rather than prednisone may result in a lower corticosteroid dose to offspring. Overdosage/Acute Toxicity Glucocorticoids when given short-term are unlikely to cause harm-ful effects, even in massive dosages. One incidence of a dog develop-ing acute CNS effects after accidental ingestion of glucocorticoids has been reported. Should clinical signs occur, use supportive treat-ment if required. Chronic usage of glucocorticoids can lead to serious adverse ef-fects. Refer to Adverse Effects above for more information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving glucocorticoids and may be of signiﬁcance in veterinary patients: !TAMPHOTERICIN B : When administered concomitantly with gluco-corticoids may cause hypokalemia !TANTICHOLINESTERASE AGENTS (e. g., pyridostigmine, neostigmine, etc. ): In patients with myasthenia gravis, concomitant glucocor-ticoid with these agents may lead to profound muscle weakness. If possible, discontinue anticholinesterase medication at least 24 hours prior to corticosteroid administration. !TASPIRIN (salicylates ): Glucocorticoids may reduce salicylate blood levels !TCYCLOPHOSPHAMIDE : Glucocorticoids may also inhibit the hepatic metabolism of cyclophosphamide; dosage adjustments may be required. !TCYCLOSPORINE : Concomitant administration of may increase the blood levels of each, by mutually inhibiting the hepatic metabo-lism of each other; clinical signiﬁcance of this interaction is not clear !TDIGOXIN : Secondary to hypokalemia, increased risk for arrhythmias !TDIURETICS, POTASSIUM-DEPLETING (furosemide, thiazides ): When administered concomitantly with glucocorticoids may cause hy-pokalemia !TEPHEDRINE : May increase metabolism !TESTROGENS : The effects of hydrocortisone, and possibly other glu-cocorticoids, may be potentiated by concomitant administration with estrogens !TINSULIN : Requirements may increase in patients receiving gluco-corticoids !TKETOCONAZOLE : May decrease metabolism !TMITOTANE : May alter the metabolism of steroids; higher than usu-al doses of steroids may be necessary to treat mitotane-induced adrenal insufﬁciency !TNSAIDS : Administration of other ulcerogenic drugs with gluco-corticoids may increase risk	pppbs.pdf
GLUCOSAMINE/CHONDROITIN 429 TT ! PHENOBARBITAL : May increase the metabolism of glucocorticoids T ! PHENYTOIN : May increase the metabolism of glucocorticoids T ! RIFAMPIN : May increase the metabolism of glucocorticoids T ! VACCINES : Patients receiving corticosteroids at immunosuppres-sive dosages should generally not receive live attenuated-virus vaccines as virus replication may be augmented; a diminished immune response may occur after vaccine, toxoid, or bacterin administration in patients receiving glucocorticoids Laboratory Considerations T ! Glucocorticoids may increase serum cholesterol and urine glucose levels. T ! Glucocorticoids may decrease serum potassium. T ! Glucocorticoids can suppress the release of thyroid stimulat-ing hormone (TSH) and reduce T3 & T4 values. Thyroid gland atrophy has been reported after chronic glucocorticoid admin-istration. Uptake of I131 by the thyroid may be decreased by glucocorticoids. T ! Reactions to skin tests may be suppressed by glucocorticoids. T ! False-negative results of the nitroblue tetrazolium test for systemic bacterial infection s may be induced by glucocorticoids. Monitoring Monitoring of glucocorticoid therapy is dependent on its reason for use, dosage, agent used (amount of mineralocorticoid activity), dosage schedule (daily versus alternate day therapy), duration of therapy, and the animal's age and condition. The following list may not be appropriate or complete for all animals; use clinical assess-ment and judgment should adverse effects be noted: T ! Weight, appetite, signs of edema T ! Serum and/or urine electrolytes T ! otal plasma proteins, albumin T ! Blood glucose T ! Growth and development in young animals T ! ACTH stimulation test if necessary Client Information T ! Clients should carefully follow the dosage instructions and should not discontinue the drug abruptly without consulting with vet-erinarian beforehand. T ! Clients should be briefed on the potential adverse effects that can be seen with these drugs and instructed to contact the veterinar-ian should these effects progress or become severe. GLUCOSAMINE/CHONDROITIN SULFATE (gloo-kose-a-meen/kon-droy-tin sul-fayt) Cosequin® NUTRITIONAL SUPPLEMENT Prescriber Highlights TT So-called nutraceutical that can be used as an adjunctive treatment for osteoarthritis or other painful conditions in horses, cats, dogs, etc; FLUTD in cats TT Well tolerated, but efﬁcacy is uncertain TT Not a regulated drug; choose products carefully; large variation in commercially available products Uses/Indications These compounds may be useful in treating osteoarthritis or other painful conditions in domestic animals, but large, well-designed controlled clinical studies proving efﬁcacy were not located. One study in dogs (Mc Carthy, O'Donovan et al. 2007) showed some pos-itive effect, but this study was not placebo controlled and compared responses versus carprofen. Another placebo-controlled, blinded study in dogs (Moreau, Dupuis et al. 2003), did not demonstrate statistically signiﬁcant improvement after 60 days of treatment. These compounds potentially could be of beneﬁt in cats with FLUTD (feline lower urinary tract disease) because of the presence of glycosaminoglycans as part of the protective layer of the urinary tract. Controlled studies have shown some positive effects in some cats, but overall did not appear to make a signiﬁcant difference. Pharmacology/Actions Cartilage cells use glucosamine to produce glycosaminoglycans and hyaluronan. Glucosamine also regulates synthesis of collagen and proteoglycans in cartilage and has mild antiinﬂammatory effects due to its ability to scavenge free radicals. Chondrocytes normally produce ample quantities of glucosamine from glucose and amino acids, but this ability may diminish with age, disease, or trauma. Exogenously administered glucosamine appears to be able to be utilized by chondrocytes. Chondroitin sulfate possesses several pharmacologic effects. It appears to inhibit destructive enzymes in joint ﬂuid and cartilage. Thrombi formation in microvasculature may be reduced. In joint cartilage, it stimulates the production of glycosaminoglycans and proteoglycans. While in vitro evidence exists, there is not solid evidence that using these compounds together improves clinical effect over either alone, but in vivo studies are ongoing. Pharmacokinetics The pharmacokinetics of these compounds are hard to evaluate due to the different salts, lack of standards, etc. Both glucosamine HCl and glucosamine sulfate are absorbed in the gut after the salt is cleaved in the stomach. There exists controversy as to whether either salt of glucosamine is superior to the other. Theoretically, if the amount of glucosamine base contained in the product is equiv-alent, the amount absorbed should be as well. Most clinical studies in veterinary species have been done with the HCl salt. Puriﬁed, low molecular weight chondroitin appears to be absorbed from the gut. Reported bioavailability in horses for chondroitin sulfate is about 25%; glucosamine, about 2%; bioavailability in dogs is reportedly about 5% for chondroitin sulfate and 12% for glucosamine. Onset of any clinical efﬁcacy may require 2-6 weeks of treatment. Contraindications/Precautions/Warnings No absolute contraindications were located for these compounds. As hypersensitivity reactions are a theoretical possibility, animals demonstrating prior hypersensitivity reactions to these compounds should not receive them. In humans, glucosamine may exacerbate symptoms associated with asthma. Although this has not yet been reported in veterinary patients, caution is advised in patients with bronchoconstrictive conditions. Adverse Effects These products appear to be very well tolerated in dogs, cats, and horses. Adverse effects could potentially include some minor gas-trointestinal effects (ﬂatulence, stool softening). Since these prod-ucts are often derived from natural sources, hypersensitivity reac-tions could occur.	pppbs.pdf
430 GLUCOSAMINE/CHONDROITIN Reproductive/Nursing Safety No studies on the safety of these compounds in pregnant or lactat-ing animals have been performed. Overdosage/Acute Toxicity Oral overdosage is unlikely to cause signiﬁcant problems. The LD50 for the combined compound in rats is greater than 5 g/kg. Gastrointestinal effects may result. Changes in coagulation param-eters could occur, but have not been documented to date. Products that contain manganese could lead to manganese tox-icity if given in very high dosages (above label recommendations) chronically. Drug Interactions No clinically signiﬁcant drug interactions have been reported to date. By reducing doxorubicin or etoposide inhibition of topoi-somerase II, glucosamine may induce resistance to these agents. High dose chondroitin sulfate and/or glucosamine potentially could enhance the effects of warfarin, heparin, or other drugs that affect coagulation. Again, clinically signiﬁcant interactions with ei-ther of these compounds have not been conﬁrmed. Laboratory Considerations !THigh dose chondroitin and glucosamine theoretically could in-crease International Normalized Ratio ( INR) in patients taking warfarin. Doses Note : Because of the variability in products available, it is recom-mended to choose a product that has been tested in the species for which it is marketed; consult the product label. !TDOGS: a) For adjunctive treatment of chronic pain: Glucosamine/ chondroitin: 13-15 mg/kg (of the chondroitin component) PO once daily (q24h). (Hardie, Lascelles et al. 2003) b) For adjunctive treatment of cancer pain: Glucosamine/chon-droitin: 15-30 mg/kg (of the chondroitin component) PO once daily (q24h) for 4-6 weeks then half the dose. (Las-celles 2003) c) For adjunctive treatment of chronic pain: Glucosamine/ chondroitin: 13-15 mg/kg (of the chondroitin compo-nent) PO once daily or every other day (q24-48h). (Hansen 2003b) d) Label Recommendation as a Dietary Supplement for Cosequin®: For Small Dogs (under 25 lbs): Initially, using Regular Strength capsules for cats and small dogs: under 10 lb. : H to 1 capsule daily; 10-24 lb. : 2 capsules daily (1 in AM/ 1 in PM). Mainte-nance Administration (after initial 4-6 week period): under 10 lb. can often have their dosage reduced to H capsule daily or 1 capsule every other day. 10 to 24 lb. can often have their dosage reduced to 1 capsule daily. For Medium and Large Dogs (>25 lbs. ): Initially, using Cosequin®DS (double strength) tablets or capsules: 25-49 lb. : 2 capsules daily (1 in AM/ 1 in PM); 50-100 lb. : 3 cap-sules daily (2 in AM/ 1 in PM); over 100 lb. : 4 capsules daily (2 in AM/ 2 in PM). Maintenance Administration (after ini-tial 4-6 week period): dogs can have their total daily dosage gradually lowered until maintenance level is reached. Amount can be increased at any time depending on the pet's needs. Tablets can be given as a treat or crumbled and mixed with the pet's food. The capsules can be pulled apart and the contents sprinkled on the pet's food. Wet or moist food works best. As an alternative, pets can be pilled or the capsules administered by wrapping in a small piece of food. (Label recommendations; Cosequin®—Nutramax) !TCATS: a) For adjunctive treatment of cancer pain: Glucosamine/chon-droitin: 15-30 mg/kg (of the chondroitin component) PO once daily (q24h) for 4-6 weeks then half the dose. (Las-celles 2003) b) For adjunctive treatment of chronic pain: Glucosamine/ chondroitin: 15-20 mg/kg (of the chondroitin compo-nent) PO once daily or every other day (q24-48h). (Hansen 2003b) c) Label Recommendation as a Dietary Supplement for Cose-quin® For Cats: Initially: under 10 lb. : 1 capsule sprinkled on food daily; over 10 lb. : 2 capsules sprinkled on food daily (1 in AM/ 1 in PM). Maintenance Administration (after initial 4-6 week period): once desired response is obtained, cap-sules may be administered every other day. Number of capsules can be increased at any time depending on the pet's needs. The capsules contain a ﬂavored powder. The capsules should be opened and the contents mixed with or sprinkled over the food. Dry food may be moistened with a small amount of water so that the powder sticks. Alterna-tively, the contents of the capsules may be mixed with a small amount (i. e., tablespoon) of wet or moist food. As an alterna-tive, cats can be pilled. (Label recommendations; Cosequin® For Cats—Nutramax) !THORSES: a) For navicular syndrome: Using Cosequin® Concentrated Pow-der labeled for horses: 16. 5 grams (5 scoops) in feed twice daily. (Hanson, Brawner et al. 2001) b) Label Recommendation as a Dietary Supplement for Cose-quin® Concentrated Powder: Initially: for horses under 600 lb., 2 scoops in AM and 2 scoops in PM; horses 600-1,200 lb., 3 scoops in AM and 3 scoops in PM; horses over 1,200 lb., 4 scoops in AM and 4 scoops in PM. The initial admin-istration period is 2 to 4 weeks; if horse shows little or no response, extend initial amount for two more weeks. Transition Period: Do not lower amount until horse has be-gun to respond. After achieving a good response, reduce total daily amount by one level scoop each week. Gradually re-ducing the amount will help ﬁnd an individual maintenance level. Suggested Maintenance Administration: horses under 600 lb., 1 scoop daily; horses 600-1,200 lb., 1-2 scoops daily; horses over 1,200 lb., 2 scoops daily. Amount can be increased at any time. May be top dressed on sweet feed. Add a small amount of water or molasses to get the powder to stick to dry feed. (La-bel and insert recommendations; Cosequin® Concentrated Powder—Nutramax Labs) Monitoring !TClinical efﬁcacy Client Information !TOnset of any clinical improvement may require 2-6 weeks of treatment. !TDo not switch brands from that prescribed without ﬁrst contact-ing your veterinarian. !TSide effects are unlikely, but mild gastrointestinal upset has been reported in small animals. Should this be troublesome, contact your veterinarian.	pppbs.pdf
GLUTAMINE 431 Chemistry/Synonyms Glucosamine is most often available as either glucosamine HCl or glucosamine sulfate. It is an amino sugar that is synthesized in vivo by animal cells from glucose and glutamine. Glucosamine (HCl or Sulfate) may also be known as: chito-samine,NSC-758,2-amino-2-deoxy-beta-D-glucopyranose,G6SD-glucosamine, glucose-6-phosphate, or amino monosaccharide. Chondroitin sulfate is an acid mucopolysaccharide/glycosamin-oglycan that is found in most cartilaginous tissues. It is a long chain compound that contains units of galactosamine and glucuronic acid. Chondroitin sulfate may also be known as chondroitin 4-sulfate, chondroitin sulfate A, chondroitin sulfate B, chondroitin sulfate C, chondroitin sulfate sodium, CSA, sodium chondroitin sulfate, chondroitin polysulfate, CDA, CSCSC, GAG, or galactosaminoglu-conoglycan sulfate. Storage/Stability Because of the multiple products and product formulations avail-able, check label for storage and stability (expiration date) informa-tion. Chondroitin sulfate is an extremely hygroscopic compound and, generally, these products should be stored in tight containers at room temperature. Avoid storing in direct sunlight. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None as pharmaceuticals. Supplements are available from a wide vari-ety of sources and dosage forms include tablets, capsules and powder in a variety of concentrations. There are speciﬁc products marketed for use in animals, including Cosequin®, Restor-A-Flex®, Oste O-3®, Arthri-Nu®, Pro Motion®, Seraquin®, Oste-O-Guard®, Caniﬂex®, Equi-Phar Flex®, etc. Glucosamine and chondroitin sulfate are considered nutritional sup-plements by the FDA. No standards have been accepted for potency, purity, safety or efﬁcacy by regulatory bodies. Bioequivalence between products cannot be assumed and indepen-dent analysis has shown a wide variation in products. HUMAN-LABELED PRODUCTS: None as pharmaceuticals GLUTAMINE (gloo-ta-meen) NUTRITIONAL Prescriber Highlights TT Amino acid that may be useful in preventing/treating GI epithelium damage TT Little documentation for efﬁcacy, but adverse effects unlikely Uses/Indications Glutamine has been used as a GI protectant and in an attempt to enhance GI healing in conditions where GI epithelium is damaged (Parvo enteritis, chemotherapy, etc. ). A study that evaluated the efﬁcacy of glutamine supplementa-tion in cats with methotrexate-induced enteritis found no differ-ence between cats supplemented with glutamine and those that were not. (Marks, Cook et al. 1999) Pharmacology/Actions Glutamine is a conditionally essential amino acid that is produced primarily in skeletal muscle and then released into the circulation. Glutamine is required for proper function of the immune system, GI tract, kidneys, and liver. Glutamine also serves as a precursor for glu-tathione, glutamate, purines, pyrimidines, and other amino acids. Glutamine's effects on the gastrointestinal tract are one of the primary areas of interest for its therapeutic use as an exogenously administered drug. When the body is under severe stress, it con-sumes more glutamine than it can produce and progressive muscle wasting occurs as it tries to meet glutamine requirements. There is some evidence that glutamine may have a role in intestinal cell proliferation and determination. When glutamine is depleted, in-testinal epithelium can atrophy, ulcerate, or become necrotic. In patients undergoing cancer chemotherapy or radiotherapy, dimin-ished glutamine levels in the gastrointestinal tract can cause in-creased GI toxicity. Supplementation of exogenous glutamine may help protect the GI from these effects. Pharmacokinetics Little information was located outside of what is described in the pharmacology section. Contraindications/Precautions/Warnings Because it is partially metabolized into ammonia and glutamate, use with caution in patients with severe hepatic insufﬁciency, severe behavior disorders or epilepsy. Adverse Effects Glutamine is well tolerated when used orally or intravenously. Potentially, it may have some CNS effects at high dosages. Reproductive/Nursing Safety There is insufﬁcient data available documenting the safe use of glu-tamine during pregnancy or nursing. Overdosage/Acute Toxicity Overdosages are unlikely to be harmful. Doses of up to 40 grams per day IV have been tolerated in humans without ill effects. Because glutamine is partially metabolized to ammonia, patients with he-patic insufﬁciency may be adversely affected. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving glutamine and may be of signiﬁcance in veterinary patients: T ! ANTICONVULSANT MEDICATIONS : Glutamine could potentially affect the efﬁcacy of antiseizure medications ( phenobarbital, potassium bromide, etc. ). It is partially converted into glutamate, which can act as an excitatory neurotransmitter. T ! LACTULOSE : Theoretically, glutamine may antagonize the effects of lactulose in patients with hepatic encephalopathy. Laboratory Considerations T ! Glutamine may increase serum ammonia or glutamate levels. Doses T ! DOGS & CAT S: For adjunctive treatment of GI inﬂammatory conditions: a) 0. 5 grams/kg PO daily (Wynn 2002) b) 0. 5 gram/kg/day PO divided twice a day in the water or food. (Silverstein 2003)	pppbs.pdf
432 GLYBURIDE Monitoring T ! Efﬁcacy Client Information T ! May be administered with food. Chemistry/Synonyms Glutamine is an aliphatic amino acid. It occurs as white crystals or crystalline powder and is soluble in water and practically insoluble in alcohol. Glutamine may also be known as: glutamic acid, GLN, gluta-mate, glutaminate, levoglutamide, levoglutamine, L-glutamic acid, L-glutamic acid 5-amide, l-glutamine, L-glutamine, and Q. Storage/Stability/Compatibility Glutamine tablets and powder should be stored in tight containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Glutamine is considered a nutrient. Glutamine may be purchased as L-glutamine 500 mg tablets, glutamine powder, or glutamic acid in 500 mg tablets, powder. Glutamic acid is rapidly degraded in the body to glutamine. Parenteral forms of glutamate may be available in other countries. GLYBURIDE (glye-byoor-ide) Dia Beta®, Micronase® SULFONYLUREA ANTIDIABETIC AG ENT Prescriber Highlights TT Human oral antidiabetic agent (Type II) that may be use-ful in cats TT Glipizide used more often; glyburide may be useful if glipizide unavailable or if once a day dosing is important TT Contraindications: Severe burns, severe trauma, severe infection, diabetic coma or other hypoglycemic condi-tions, major surgery, ketosis, ketoacidosis or other signiﬁ-cant acidotic conditions TT Caution: Untreated adrenal or pituitary insufﬁciency; thyroid, renal, or hepatic function impairment; prolonged vomiting; high fever; malnourishment or debilitated condition TT Adverse Effects: CATS: GI (i. e., vomiting), hypoglycemia, liver toxicity TT Drug interactions TT Do not confuse glipizide, glimepiride & glyburide Uses/Indications Glyburide is an alternative oral treatment for non-insulin depen-dent diabetes mellitus (NIDDM) in cats, particularly if glipizide is unavailable or if twice daily administration of glipizide is not toler-ated (by cat or owner). Pharmacology/Actions Like glipizide and other oral sulfonylureas, glyburide lowers blood glucose concentrations in both diabetic and normal patients. While it is unknown how glyburide precisely lowers glucose, it initially stimulates secretion of endogenous functional beta cells in the pan-creas. It also may enhance insulin activity at post receptor sites and reduce basal hepatic glucose production that may explain its effec-tiveness with long-term administration. Pharmacokinetics Glyburide appears to be well absorbed but bioavailability data is lacking. Food apparently does not have an effect on the absorptive characteristics of the drug. Glyburide is distributed throughout the body, including into the brain and across the placenta. Glyburide is apparently completely metabolized, presumably in the liver. Metabolites are excreted in both the feces and the urine. While its elimination half-life in cats is not known, once a day dosing appears to be effective in cats with NIDDM. Contraindications/Precautions/Warnings Oral antidiabetic agents are considered contraindicated with the following conditions: severe burns, severe trauma, severe infec-tion, diabetic coma or other hypoglycemic conditions, major sur-gery, ketosis, ketoacidosis or other signiﬁcant acidotic conditions. Glyburide should only be used when its potential beneﬁts outweigh its risks in patients with untreated adrenal or pituitary insufﬁcien-cy; thyroid, renal, or hepatic function impairment; prolonged vom-iting; high fever; malnourishment or in debilitated condition. Some patients with type II diabetes may have their disease complicated by the production of excessive amounts of cortisol or growth hormone that may antagonize insulin's effects. These causes should be ruled out before initiating oral antidiabetic therapy. Adverse Effects Experience with glyburide is limited in veterinary medicine. Hypo-glycemia, vomiting, icterus, and increased ALT (SGPT) levels are all potentially possible. Should toxicity develop, reinstitution of drug therapy may be attempted at a lower dosage after clinical signs resolve. Other adverse effects that are possible (noted in humans) in-clude: allergic skin reactions, arthralgia, bone marrow suppression, or cholestatic jaundice. Glyburide may not be effective in cats demonstrating insulin resistance. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is unknown if glyburide is excreted in milk. Overdosage/Acute Toxicity Profound hypoglycemia is the greatest concern after an overdose. In humans, severe hypoglycemia has occurred at relatively low dos-ages. Gut emptying protocols should be employed when warranted. Because its half-life is longer than glipizide, prolonged hypoglyce-mia may occur and blood glucose monitoring and treatment with parenteral glucose may be required for several days. Massive over-doses may also require additional monitoring (blood gases, serum electrolytes) and supportive therapy. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving glyburide and may be of signiﬁcance in veterinary patients: T ! ALCOHOL : A disulﬁram-like reaction (anorexia, nausea, vomiting) is possible	pppbs.pdf
GLYCERIN 433 T ! ANTIFUNGALS, AZOLE (ketoconazole, itraconazole, ﬂuconazole ): May increase plasma levels of glyburide T ! BETA-BLOCKERS : May potentiate hypoglycemic effect T ! CHLORAMPHENICOL : May displace glyburide from plasma proteins T ! CIMETIDINE : May potentiate hypoglycemic effect T ! CORTICOSTEROIDS : May reduce efﬁcacy T ! DIURETICS, THIAZIDE : May reduce hypoglycemic efﬁcacy T ! ISONIAZID : May reduce hypoglycemic efﬁcacy T ! MOA INHIBITORS : May potentiate hypoglycemic effect T ! NIACIN : May reduce hypoglycemic efﬁcacy T ! PHENOTHIAZINES : May reduce hypoglycemic efﬁcacy T ! PHENYTOIN : May reduce hypoglycemic efﬁcacy T ! PROBENECID : May potentiate hypoglycemic effect T ! SULFONAMIDES : May displace glyburide from plasma proteins T ! SYMPATHOMIMETIC AGENTS : May reduce hypoglycemic efﬁcacy T ! THYROID AGENTS : May reduce hypoglycemic effect T ! WARFARIN : May displace glyburide from plasma proteins Doses T ! CATS: For NIDDM: a) Initial dose at 0. 625 mg (H of a 1. 25 mg tablet) PO once daily (Nelson 2000) b) If cat is generally well, weight loss is mild, is not ketoacidotic, and does not have peripheral neuropathy, may try glyburide at: 2. 5 mg (total dose) PO twice a day (Daminet 2003) Monitoring T ! Weekly exams during ﬁrst month of therapy including PE, body weight, urine glucose/ketones and several blood glucose exams. T ! Adverse effects (vomiting, icterus), and occasional liver enzymes and CBC. Client Information T ! Clients should be informed of clinical signs to watch for that would indicate either hypoglycemia or hyperglycemia and be in-structed to report these to the veterinarian. T ! Compliance with dosing regimen should also be stressed. Chemistry/Synonyms An oral sulfonylurea antidiabetic agent, glyburide occurs as a white or nearly white, odorless or almost odorless, crystalline powder. As p H increases, solubility increases. At a p H of 4, solubility in water is about 4 mcg/m L and at a p H of 9, 600 mcg/m L. Glyburide has a p Ka of 6. 8. Glyburide may also be known as: glibenclamide, glibencl-amidum, glybenclamide, glybenzcyclamide, HB-419, and U-26452; many trade names are available. Storage/Stability Glyburide oral tablets should be stored in well-closed containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Glyburide Tablets: 1. 25 mg, 2. 5 mg, & 5 mg; micronized tablets: 1. 5 mg, 3 mg, 4. 5 mg and 6 mg; Micronase® & Glynase® Pres Tab (Pharma-cia & Upjohn); Dia Beta® (Hoechst Marion Roussel); generic; (Rx) Glyburide/Metformin HCl Tablets: 1. 25 mg/250 mg, 2. 5 mg/500 mg and 5 mg/500 mg; Glucovance® (Bristol-Myers Squibb); generic (PAR); (Rx) GLYCERIN, ORAL (gli-ser-in) Osmoglyn® OSMOTIC AG ENT Prescriber Highlights TT Oral osmotic that reduces intraocular & CSF pressure TT Contraindications: Patients with known hypersensitivity, anuria (well established), severe dehydration, severe car-diac decompensation, acute pulmonary edema. TT Caution: Hypovolemia, cardiac disease, or diabetes TT Adverse Effects: Vomiting (most common) Uses/Indications Oral glycerin is used primarily for the short-term reduction of IOP in small animals with acute glaucoma. It may also be considered for use to reduce increased CSF pressure. The IOP-lowering effect of glycerin may be more variable than with mannitol, but since it may be given orally, it may be more ad-vantageous to use in certain cases. Pharmacology/Actions Glycerin in therapeutic oral doses increases the osmotic pressure of plasma so that water from extracellular spaces is drawn into the blood. This can decrease intraocular pressure (IOP). The amount of decrease in IOP is dependent upon the dose of glycerin, and the cause and extent of increased IOP. Glycerin also decreases extracel-lular water content from other tissues and can cause dehydration and decreased CSF pressure. Pharmacokinetics Glycerin is rapidly absorbed from the GI tract; peak serum lev-els generally occur within 90 minutes and maximum decreases in IOP usually occur within an hour of dosing and persist for up to 8 hours. Glycerin is distributed throughout the blood and is pri-marily metabolized by the liver. About 10% of the drug is excreted unchanged in the urine. Serum half-life in humans is about 30-45 minutes. Contraindications/Precautions/Warnings Glycerin is contraindicated in patients hypersensitive to it. It is also contraindicated in patients with well-established anuria, that are severely dehydrated, severely cardiac decompensated, or with frank or impending acute pulmonary edema. Glycerin should be used with caution in animals when the blood:ocular barrier is not intact (hyphema, uveitis), and those with hypovolemia, cardiac disease, or diabetes. Acute urinary reten-tion should be avoided during the preoperative period. Adverse Effects Vomiting after dosing is the most common adverse effect seen with glycerin use. In humans, headache, nausea, thirst, and diarrhea have also been reported. Reproductive/Nursing Safety The safety of this drug in pregnant animals is unknown; use only when potential beneﬁts outweigh the risks of therapy. In humans, the FDA categorizes this drug as category C for use during preg-nancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal re-production studies and no adequate studies in humans. )	pppbs.pdf
434 GLYCOPYRROLATE No speciﬁc information on glycerin was located for lactation safety. Overdosage/Acute Toxicity No speciﬁc information was located, but cardiac arrhythmias, non-ketotic hyperosmolar coma, and severe dehydration have been re-ported with the drug. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving glycerin and may be of signiﬁcance in veterinary patients: T ! CARBONIC ANHYDRASE INHIBITORS (e. g., acetazolamide, dichlorphe-namide ): Concomitant administration of carbonic anhydrase in-hibitors or topical miotic agents may prolong the IOP-reducing effects of glycerin. T ! MIOTIC AGENTS, TOPICAL : Concomitant administration topical mi-otic agents may prolong the IOP-reducing effects of glycerin Doses T ! DOGS & CAT S: For acute glaucoma: a) 1-2 m L/kg (of 50% solution); may repeat in 8 hours if nec-essary; withhold water for 30-60 minutes after administra-tion (Brooks 1986), (Brooks 1990) b) 1-2 g/kg PO (Herring 2003) c) 1-2 m L/kg (of a 90% solution) PO usually as a single dose; withhold water for 3-4 hours after administration. Author uses glycerin often because it is quicker and easier to admin-ister than mannitol and is usually effective. (Collins 2006) Monitoring T ! IOP T ! Urine output T ! Hydration status Chemistry/Synonyms A trihydric alcohol, glycerin occurs as clear, sweet-tasting, syrupy, hygroscopic liquid that has a characteristic odor. It is miscible with water and alcohol, but not miscible in oils. Glycerin solutions are neutral to litmus. Glycerin may also be known as: E422, glycerol, glicerol, glycerin, glycerine, and glycerolum; many trade names are available. Storage/Stability Glycerin oral solution should be stored in tight containers at room temperature; protect from freezing. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None for systemic use. HUMAN-LABELED PRODUCTS: Glycerin Oral Liquid: 50% (0. 6 g glycerin/m L) in 220 m L; Osmoglyn® (Alcon); (Rx) Glycerin is also available in a topical ophthalmic solution and as sup-positories or liquid for rectal laxative use. USP glycerin 90% could be used for oral use in small animals (see doses above). Glyceryl Guaiacolate; GG —see Guaifenesin GLYCOPYRROLATE (glye-koe-pye-roe-late) Robinul® ANTICHOLINERGIC (ANTIMUSCARINIC) Prescriber Highlights TT Synthetic antimuscarinic agent similar to atropine avail-able both orally & parenterally; used for a variety of indi-cations (bradycardia, premed, antidote, etc. ) TT Contraindicated in conditions where anticholinergic ef-fects would be detrimental (e. g., narrow angle glaucoma, tachycardias, ileus, urinary obstruction, etc. ) TT Adverse effects are dose related & anticholinergic in nature, including: dry secretions; initial bradycardia, then tachycardia; slowing of gut & urinary tract motility; mydriasis/cycloplegia TT Drug interactions Uses/Indications Glycopyrrolate injection is approved for use in dogs and cats. The FDA approved indication for these species is as a preanesthetic an-ticholinergic agent. The drug is also used to treat sinus bradycardia, sinoatrial arrest, and incomplete A V block, where anticholinergic therapy may be beneﬁcial. When cholinergic agents such as neostig-mine or pyridostigmine are used to reverse neuromuscular block-ade due to non-depolarizing muscle relaxants, glycopyrrolate may be administered simultaneously to prevent the peripheral muscar-inic effects of the cholinergic agent. Pharmacology/Actions An antimuscarinic with similar actions as atropine, glycopyrrolate is a quaternary ammonium compound and, unlike atropine, does not cross appreciably into the CNS. It, therefore, should not exhibit the same extent of CNS adverse effects that atropine possesses. For further information, refer to the atropine monograph. Pharmacokinetics Quaternary anticholinergic agents are not completely absorbed after oral administration, but quantitative data reporting the rate and extent of absorption of glycopyrrolate is not available. In dogs, following IV administration, the onset of action is generally within one minute. After IM or SC administration, peak effects occur ap-proximately 30-45 minutes post injection. The vagolytic effects persist for 2-3 hours and the antisialagogue (reduced salivation) effects persist for up to 7 hours. After oral administration, the anti-cholinergic effects of glycopyrrolate may persist for 8-12 hours. Little information is available regarding the distributory aspects of glycopyrrolate. Being a quaternary ammonium compound, gly-copyrrolate is completely ionized; therefore, it has poor lipid solu-bility and does not readily penetrate into the CNS or eye. Glycopyrrolate crosses the placenta only marginally; it is un-known if it is excreted into milk. Glycopyrrolate is eliminated rapidly from the serum after IV administration and virtually no drug remains in the serum 30 min-utes to 3 hours after dosing. Only a small amount is metabolized and the majority is eliminated unchanged in the feces and urine. Contraindications/Precautions/Warnings One manufacturer (Fort Dodge) of the veterinary product lists contraindications to glycopyrrolate's use in dogs and cats hyper-sensitive to it and that it should not be used in pregnant animals.	pppbs.pdf
GLYCOPYRROLATE 435 However, it would be prudent to refer to the recommendations listed in the atropine monograph regarding contraindications and precautions. Adverse Effects With the exceptions of rare CNS adverse effects and being slightly less arrhythmogenic, glycopyrrolate can be expected to have a simi-lar adverse effect proﬁle as atropine. The manufacturer of the vet-erinary product (Fort Dodge) lists only mydriasis, tachycardia, and xerostomia as adverse effects in dogs and cats at the doses they rec-ommend. For more information, refer to the atropine monograph. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have un-covered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) No speciﬁc lactation safety information was found; however, it is unlikely to be excreted into milk in substantial quantities because of its quaternary structure. Overdosage/Acute Toxicity In dogs, the LD 50 for glycopyrrolate is reported to be 25 mg/kg IV. Doses of 2 mg/kg IV daily for 5 days per week for 4 weeks dem-onstrated no signs of toxicity. In the cat, the LD 50 after IM injec-tion is 283 mg/kg. Because of its quaternary structure, it would be expected that minimal CNS effects would occur after an overdose of glycopyrrolate when compared to atropine. See the information listed in the atropine monograph for more information. Drug Interactions Glycopyrrolate would be expected to have a similar drug interac-tion proﬁle as atropine. The following drug interactions have either been reported or are theoretical in humans or animals receiving atropine or glycopyrrolate and may be of signiﬁcance in veterinary patients: The following drugs may enhance the activity or toxicity of at-ropine and its derivatives: !!AMANTADINE !!ANTICHOLINERGIC AGENTS (other) !!ANTICHOLINERGIC MUSCLE RELAXANTS !!ANTIHISTAMINES (e. g., diphenhydramine ) !!DISOPYRAMIDE !!MEPERIDINE !!PHENOTHIAZINES !!PROCAINAMIDE !!PRIMIDONE !TTRICYCLIC ANTIDEPRESSANTS (e. g., amitriptyline, clomipramine ) !TAMITRAZ : Atropine may aggravate some signs seen with amitraz toxicity; leading to hypertension and further inhibition of peri-stalsis !TANTACIDS : May decrease PO atropine absorption; give oral atro-pine at least 1 hour prior to oral antacids !TCORTICOSTEROIDS (long-term use ): may increase intraocular pressure !TDIGOXIN (slow-dissolving ): Atropine may increase serum digoxin levels; use regular digoxin tablets or oral liquid !TKETOCONAZOLE : Increased gastric p H may decrease GI absorption; administer atropine 2 hours after ketoconazole !TMETOCLOPRAMIDE : Atropine and its derivatives may antagonize the actions of metoclopramide Doses !TDOGS: As an adjunct to anesthesia: a) 0. 011 mg/kg IV, IM, or SC (Package Insert; Robinul®-V —Fort Dodge) b) 0. 01-0. 02 mg/kg SC or IM (Bellah 1988) For adjunctive therapy of bradyarrhythmias: a) 0. 011 mg/kg IV or IM (Russell and Rush 1995) b) Associated with anesthesia: 0. 005-0. 01 mg/kg IV (Pablo 2003a) T o reduce hypersialism: a) 0. 01 mg/kg SC as needed (Krahwinkel 1988) !TCATS: As an adjunct to anesthesia: a) 0. 011 mg/kg IM, for maximum effect give 15 minutes prior to anesthetic administration (Package Insert; Robinul®-V— Fort Dodge) For bradyarrhythmias: a) 0. 005-0. 01 mg/kg IV or IM, 0. 01-0. 02 mg/kg SC (Tilley and Miller 1986) b) Associated with anesthesia: 0. 005-0. 01 mg/kg IV (Pablo 2003a) !TFERRETS: As a premed: a) 0. 01 mg/kg SC or IM (Williams 2000) !TRABBITS/RODENTS/SMALL MAMMALS: a) Rabbits: For prevention of bradycardia and to decrease air-way and salivary secretions: 0. 01-0. 1 mg/kg IM, SC; 0. 01 mg/kg IV (Ivey and Morrisey 2000) b) Rabbits: As adjunct to anesthesia: 0. 01-0. 02 mg/kg SC as need (Huerkamp 1995) !THORSES: (Note : ARCI UCGFS Class 3 Drug) For treatment of bradyarrhythmias: a) 0. 005-0. 01 (5-10 mcg/kg) mg/kg IV (Mogg 1999) As a bronchodilator: a) Initially, 2-3 mg IM two to three times daily for a 450 kg animal (Beech 1987) T o control muscarinic adverse effects associated with imidocarb therapy: a) 0. 0025 mg/kg IV (Donnellan, Page et al. 2003) Monitoring !TDependent on route of administration, dose, and reason for use. See the atropine monograph for more information. Client Information !TParenteral glycopyrrolate administration is best performed by professional staff and where adequate cardiac monitoring is available. !TIf animal is receiving glycopyrrolate tablets, allow animal free ac-cess to water and encourage drinking if dry mouth is a problem.	pppbs.pdf
436 GOLD SALTS, INJECTABLE Chemistry/Synonyms A synthetic quaternary ammonium antimuscarinic agent, glycopy-rrolate occurs as a bitter-tasting, practically odorless, white, crys-talline powder with a melting range of 193-198°C. One gram is soluble in 20 m L of water; 30 m L of alcohol. The commercially available injection is adjusted to a p H of 2-3 and contains 0. 9% benzyl alcohol as a preservative. Glycopyrrolate may also be known as: glycopyrronium bro-mide, AHR-504, Acpan®, Am Tech®, Gastrodyn®, Glycostigmin®, and Robinul®. Storage/Stability/Compatibility Glycopyrrolate tablets should be stored in tight containers and both the injection and tablets should be stored at room temperature (15-30°C). Glycopyrrolate is stable under ordinary conditions of light and temperature. It is most stable in solution at an acidic p H and un-dergoes ester hydrolysis at p H's above 6. Glycopyrrolate injection is physically stable in the following IV solutions: D 5W, D 5/half normal saline, Ringer's injection, and nor-mal saline. Glycopyrrolate may be administered via the tubing of an IV running lactated Ringer's, but rapid hydrolysis will occur if it is added to an IV bag of LRS. The following drugs are report-edly physically compatible with glycopyrrolate: atropine sulfate, benzquinamide, chlorpromazine HCl, codeine phosphate, diphen-hydramine HCl, droperidol, droperidol/fentanyl, hydromorphone, hydroxyzine HCl, lidocaine HCl, meperidine HCl, meperidine HCl/ promethazine HCl, morphine sulfate, neostigmine methylsulfate, oxymorphone HCl, procaine HCl, prochlorperazine HCl, promaz-ine HCl, promethazine HCl, pyridostigmine Br, scopolamine HBr, and trimethobenzamide HCl. The following drugs are reportedly physically incompatible with glycopyrrolate: chloramphenicol sodium succinate, dexametha-sone sodium phosphate, diazepam, dimenhydrinate, methohexital sodium, methylprednisolone sodium succinate, pentazocine lac-tate, pentobarbital sodium, secobarbital sodium, sodium bicarbon-ate, and thiopental sodium. Other alkaline drugs (e. g., thiamylal) would also be expected to be incompatible with glycopyrrolate. Compatibility is dependent upon factors such as p H, concentra-tion, temperature, and diluent used; consult specialized references for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Glycopyrrolate for Injection: 0. 2 mg/m L in 20 m L vials; Robinul®-V (Fort Dodge), Am Tech® Glycopyrrolate Injectable (IVX); (Rx). Ap-proved for use in dogs and cats. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Glycopyrrolate Tablets: 1 mg and 2 mg; Robinul® and Robinul Forte® (Horizon); generic (Rising); (Rx) Glycopyrrolate for Injection: 0. 2 mg/m L in 1 m L, 2 m L, 5 m L, and 20 m L vials; Robinul® (Robins); generic; (Rx) GOLD SALTS, INJECTABLE GOLD SODIUM THIOMALATE (gold soe-dee-um thye-oh-mal-ate) Aurothiomalate, Aurolate®, Myochrisine® AUROTHIOGLUCOSE (aur-oh-thye-oh-gloo-kose) Solganal® INJECTA BLE GOLD IMMUNOSUPPRESSIVES Prescriber Highlights TT Aurothioglucose may no longer be available com-mercially; potentially may substitute with gold sodium thiomalate (aurothiomalate) TT Injectable administered gold; for pemphigus complex in small animals or plasmacytic stomatitis/pyodermatitis in cats; may also be useful for pemphigus in goats or horses TT Can be quite toxic & expensive, intensive ongoing moni-toring required TT Considered contraindicated in SLE (exacerbates), renal or hepatic disease, preexisting hematologic abnormali-ties, severe debilitation, or uncontrolled diabetes TT Possible teratogen TT Litany of serious adverse effects possible; pain on injection Note : Aurothioglucose has traditionally been the injectable gold compound used in veterinary medicine, but it may no longer be commercially available. Some now use gold sodium thiomalate (aurothiomalate) in its place. The following monograph primarily applies to aurothioglucose, but the two drugs are thought to have similar actions, adverse effects, etc. Doses speciﬁc for gold sodium thiomalate are noted in the dosage section. Uses/Indications In human medicine, gold compounds are used primarily as a treat-ment for rheumatoid arthritis that has not adequately responded to less toxic treatment modalities. In veterinary medicine (primar-ily small animal medicine), its use has been generally for treating immune-mediated serious skin disorders such as pemphigus com-plex in dogs or cats and plasmacytic stomatitis/pyodermatitis in cats. Gold salts have also been used to treat goats and horses with pemphigus. Pharmacology/Actions Injectable gold compounds have antiinﬂammatory, antirheumatic, immunomodulating, and antimicrobial (in vitro) effects. The ex-act mechanisms for these actions are not well understood. Gold is taken up by macrophages where it inhibits phagocytosis and may inhibit lysosomal enzyme activity. Gold also inhibits the release of histamine, and production of prostaglandins. While gold does have antimicrobial effects in vitro, it is not clinically useful for this purpose.	pppbs.pdf
GOLD SALTS, INJECTABLE 437 Pharmacokinetics After IM injection, aurothioglucose is quite rapidly absorbed and peak serum concentrations are reached in 4-6 hours. It is distrib-uted to several tissues (liver, kidney, spleen, bone marrow, adrenals, and lymph nodes), but highest levels are found in the synovium. In plasma, 95% is bound to plasma proteins. Gold salts may be found in the epithelial cells in the renal tubules years after dosing has ended. Plasma half-lives increase in length after multiple doses have been given. These values have ranged from 21-168 hours in humans. Approximately 70% of a dose is excreted by the kidneys, while the remaining 30% is excreted in the feces. There appears to be no correlation with serum levels and efﬁ-cacy. It usually takes from 6-12 weeks for a beneﬁcial effect to be noted after beginning therapy. Contraindications/Precautions/Warnings Contraindications for chrysotherapy (gold therapy) include pa-tients with renal or hepatic disease, SLE (lupus erythematosus, dia-betes mellitus (uncontrolled), severe debilitation, and preexisting hematologic disorders. Do not administer these compounds intravenously. Adverse Effects Veterinary experience with these agents is limited. Pain at the in-jection site is common and some animals may develop thrombo-cytopenia with petechia and ecchymoses. One author (Kummel 1995), reports that four pemphigus canine cases treated with aurothioglucose given immediately after cessation of azathioprine, developed a fatal toxic epidermal necrolysis. Other adverse effects noted in cats or dogs include stomatitis, hepatic necrosis or renal dysfunction. Adverse reactions seen in people include: mucocutaneous reac-tions, which are fairly common (15-20%) and are characterized by rashes, (with or preceded by pruritus), and mucosal lesions (usu-ally seen as a stomatitis). Hematologic reactions (thrombocytope-nia, leukopenia, aplastic anemias), although rare in humans, can be life threatening. Renal effects are generally mild and if noted early, reversible with cessation of therapy. Proteinuria is an early sign associated with the proximal tubule damage that gold can cause. Reversible pulmonary inﬁltrates have been noted, but are reversible when therapy is discontinued. Enterocolitis, which may be fatal, has been reported in rare instances. Because of the serious nature of these adverse reactions, ade-quate patient monitoring is essential. Reproductive/Nursing Safety The safety of aurothioglucose or gold sodium thiomalate has not been established during pregnancy, and these drugs should only be used when the potential beneﬁts outweigh the risks involved. In humans, the FDA categorizes them as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Injectable gold is excreted in milk. Trace amounts appear in the serum and red blood cells of nursing offspring. As this may cause adverse effects in nursing offspring, switching to milk replacer is rec-ommended if gold therapy is to be continued in the dam. Because gold is slowly excreted, persistence in milk will occur even after the drug is discontinued. Overdosage/Acute Toxicity Overdosages resulting from a too rapid increase in dosage are ex-hibited by rapid development of toxic signs, primarily renal (hema-turia, proteinuria) and hematologic (thrombocytopenia, granulo-cytopenia) effects. Other clinical signs include: nausea, vomiting, diarrhea, skin lesions, and fever. Treat with dimercaprol (BAL) to chelate the gold and treat the hematologic and renal effects sup portively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving injectable gold com-pounds and may be of signiﬁcance in veterinary patients: !TCYTOTOXIC AGENTS (including high dose corticosteroids ): Aura-noﬁn's safety when used with these agents has not been estab-lished; use with caution !TPENICILLAMINE or ANTIMALARIAL DRUGS : Use with gold salts is not recommended due to the increased potential for hematologic or renal toxicity Doses Note : Dosages below are for the product aurothioglucose, un-less otherwise noted; however, dosing for both drugs appear to be equivalent. !TDOGS: For canine pemphigus foliaceus/vulgaris: a) Gold sodium thiomalate: 1-5 mg IM as a test dose then 1 mg/kg IM once weekly. Need to use initially with glucocor-ticoids as gold therapy may take 6-8 weeks to take effect. Side effects include skin lesions, thrombocytopenia and toxic epidermal necrolysis. (Logas 2005a) b) Gold sodium thiomalate: 1-5 mg (1 mg for small patients; 5 mg for large patients) IM as a test dose then 1 mg/kg IM once weekly until remission, then taper to monthly. (Morris 2004) c) For those cases where corticosteroids and/or azathioprine are ineffective or causing unacceptable adverse effects: Discon-tinue azathioprine for one month and then give 1 mg/5kg of body weight IM weekly for 10 weeks and then monthly thereafter. Note: Before treating, the reader is advised to re-fer to the full reference for additional information. (Kummel 1995) d) 1 mg/kg IM (the paraspinal muscles work best) weekly for 6-12 weeks; then decrease to every other week and if pos-sible, once monthly. Rarely, may be able to discontinue injec-tions if free from clinical signs for 6 months after switching to once monthly injections. Corticosteroids must usually be used with gold therapy. (White 2000) !TCATS: a) For pemphigus complex or plasmacytic/pododermatitis: Gold sodium thiomalate: 1-5 mg IM as a test dose then 1 mg/kg IM once weekly. Need to use initially with glucocor-ticoids as gold therapy may take 6-8 weeks to take effect. Side effects include skin lesions, thrombocytopenia and toxic epidermal necrolysis. (Logas 2005a) b) For pemphigus complex (rescue drug) or plasmacytic/podo-dermatitis: Gold sodium thiomalate: 1-5 mg (1 mg for small patients; 5 mg for large patients) IM as a test dose then 1 mg/ kg IM once weekly until remission, then taper to monthly. (Morris 2004) c) Give animal test dose of 1 mg IM the ﬁrst week and 2 mg the second week. If no adverse reactions seen (see adverse effects), give 1 mg/kg IM once weekly until either clinical im-	pppbs.pdf
438 GONADORELIN provement, toxic reactions occur, or weekly dosing has gone on for 20 weeks. Once remission is achieved, attempt to re-duce dose and/or increase dosing interval to denote animals that have gone into remission. (Long 1986) d) T est dose of 1-5 mg IM, then 1 mg/kg IM weekly until re-mission, then monthly (Morgan 1988) e) First week 1 mg IM, 2nd week 2 mg IM; then 1 mg/kg once weekly IM decreasing to once per month (Kirk 1986) f) 1 mg/kg IM per week. Clinical response may take 6-8 weeks and combination with glucocorticoids is recommended. May be associated with renal dysfunction, drug eruptions, hepatic necrosis and thrombocytopenia. (Shaw 2003) g) For idiopathic pruritus when nothing else works: 1 mg/kg IM every 7 days until remission (8-20 weeks), then 1 mg/kg IM every 4 weeks (Hnilica 2003c) T ! HORSES: a) 1 mg/kg IM once a week decreasing to once a month (Schultz 1986) b) Give 20 mg IM and then 40 mg IM one week apart. If no adverse effects (stomatitis, urticaria, sloughing, blood dys-crasias), give 1 mg/kg IM weekly until observing a response (6-12 weeks). Tailor maintenance therapy to the individual, which may involve biweekly or monthly therapy. Treatment can be very expensive. Perform weekly CBC/urinalysis for the ﬁrst month, then monthly if no abnormalities. (Rees 2004) Monitoring T ! Urinalysis—baseline, then weekly T ! CBC-baseline, then every 2 weeks; Note : eosinophilia may de-note impending reactions T ! Renal and hepatic function tests; baseline and periodic. After the patient is on maintenance therapy, hemograms and urinalyses may be done every month or two. Client Information T ! Clients should be instructed to notify the veterinarian if pruri-tus, rash, or diarrhea develops, or if the animal becomes ill or depressed Chemistry/Synonyms A water-soluble gold salt, aurothioglucose contains approximately 50% gold. It is practically insoluble in alcohol and insoluble in veg-etable oils. The commercial product is a 5% (50 mg/m L) suspen-sion in sesame oil, 2% aluminum monostearate, and propylparaben is added as a preservative. Gold sodium thiomalate occurs as an odorless, or practically odorless, yellow powder containing approximately 50% gold. It is very soluble in water. The injection is a light yellow to yellow solution with a p H of 5. 8-6. 5 and contains benzyl alcohol as a preservative. Aurothioglucose may also be known as: 1-aurothio-D-glu-copyranose, (D-glucosylthio)gold, gold thioglucose, Aureotan®, Auromyose®, Gold-50®and Solganal®. Gold sodium thiomalate may also be known as aurothiomalate, Aurolate®, and Myochrisine®. Storage/Stability/Compatibility Protect these products from light and store between 15-30° C; avoid freezing. A ﬁve-year expiration date is assigned after manu-facture. Do not mix with any other compound when injecting. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Gold Sodium Thiomalate Injection: 50 mg/m L in 2 m L and 10 m L vials; Aurolate® (Pasadena), Myochrisine® (Taylor), generic (Parenta); (Rx) Aurothioglucose Injection Suspension: 50 mg/m L in 10 m L vials & multidose vials; Aurothioglucose (Parenta); Solganal® (Schering); (Rx) Note : While the above products are still listed as being available in some current human drug references, they may be discontinued. GONADORELIN (goe-nad-oe-rell-in) Cystorelin®, Fertagyl®, Factrel® HORMONAL A GENT Prescriber Highlights TT Hypothalamic hormone used to treat ovarian cysts & other reproductive disorders in a variety of species TT Contraindications & adverse effects: None reported TT No slaughter or milk withdrawal when used as labeled Uses/Indications Gonadorelin is indicated (approved) for the treatment of ovarian follicular cysts in dairy cattle. Additionally, gonadorelin has been used in cattle to reduce the time interval from calving to ﬁrst ovu-lation and to increase the number of ovulations within the ﬁrst 3 months after calving. This may be particularly important in in-creasing fertility in cows with retained placenta. In dogs, gonadorelin has been used experimentally to help diag-nose reproductive disorders or to identify intact animals versus cas-trated ones by maximally stimulating FSH and LH production. It has also been used experimentally in dogs to induce estrus through pulsatile dosing. While apparently effective, specialized administra-tion equipment is required for this method. Gonadorelin has been used in cats as an alternate therapy to FSH or h CG to induce estrus in cats with prolonged anestrus. In Europe, a synthetic analogue buserelin has been used in hors-es to stimulate cyclic estrus. Its efﬁcacy rates poorly when compared to an artiﬁcial light program, however. In human medicine, gonadorelin has been used for the diagno-sis of hypothalamic-pituitary dysfunction, cryptorchidism, and de-pression secondary to prolonged severe stress. Pharmacology/Actions Gonadorelin stimulates the production and the release of FSH and LH from the anterior pituitary. Secretion of endogenous Gn RH from the hypothalamus is thought to be controlled by several fac-tors, including circulating sex hormones. Gonadorelin causes a surge-like release of FSH and LH after a single injection. In cows and ewes, this can induce ovulation, but not in estrus mares. A constant infusion of gonadorelin will initially stimulate LH and FSH release, but after a period of time, levels will return to baseline.	pppbs.pdf
GONADORELIN 439 Pharmacokinetics After intravenous injection in pigs, gonadorelin is rapidly distrib-uted to extracellular ﬂuid, with a distribution half-life of about 2 minutes. The elimination half-life of gonadorelin is approximately 13 minutes in the pig. After intravenous injection in humans, gonadorelin reportedly has a plasma half-life of only a few minutes. Within one hour, ap-proximately half the dose is excreted in the urine as metabolites. Contraindications/Precautions/Warnings None are noted on the label. Adverse Effects No reported adverse reactions were located for this agent. Syntheti-cally prepared gonadorelin should not cause any hypersensitivity reactions. This may not be the case with pituitary-obtained LH preparations or h CG. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) No speciﬁc lactation safety information was listed for this drug. Overdosage/Acute Toxicity In doses of up to 120 micrograms/kg, no untoward effects were noted in several species of test animals. Gonadorelin is unlikely to cause signiﬁcant adverse effects after inadvertent overdosage. Drug Interactions None were noted. Doses !TDOGS: a) Gn RH challenge to test pituitary sufﬁciency or testicular steroidogenesis: 125-250 ng/kg (refer to reference for more information) (Amann 1986) b) T o aid in the descent of cryptorchid testes: 50-100 micro-grams SC or IV; if no response give additional dose in 4-6 days (Cox 1986) c) T o increase libido in male dogs: Anecdotally, 50-100 mcg IM weekly for 4 to 6 weeks may improve libido. (Freshman 2002c) d) For cystic ovarian disease in bitches: 3. 3 mcg/kg IM once daily for 3 days. An elevated progesterone level (>2 ng/m L) measured 1-2 weeks post treatment veriﬁes success. (Pur-swell 1999) !TCATS: a) T o stimulate ovulation after mating: 25 micrograms IM after mating (Morgan 1988) b) For infertility, reduced libido, testis descent in male cats: 1 mcg/kg every 2-3 days (Verstegen 2000) c) T o detect ovarian remnants in queens after ovariohysterec-tomy: 25 mcg per cat. A progesterone level (>1 ng/m L) mea-sured 1-2 weeks post treatment veriﬁes presence of ovarian tissue in the abdomen. (Purswell 1999) !TFERRETS: a) 20 mcg IM; repeat in one week as necessary. Most effective 14 days after onset of estrus (Williams 2000) !TCATTLE: T o treat of ovarian cysts in cattle: a) 100 micrograms IM or IV (Package Insert; Cystorelin®— Ceva) b) 100 micrograms IM per cow (Package insert; Factrel®—Fort Dodge) !TSHEEP & GOATS: a) T o induce ovulation outside of the breeding season in the doe: 100 micrograms injected daily for 4-5 days (Smith 1986b) Chemistry/Synonyms A hormone produced by the hypothalamus, gonadorelin is obtained from natural sources or is synthetically produced. It is a decapeptide that occurs as white or faintly yellowish-white powder. One gram is soluble in 25 m L of water or in 50 m L of methyl alcohol. 50 mcg of gonadorelin acetate is approximately equivalent to 31 units. The commercially available products in the United States are the diac-etate decahydrate (Cystorelin®, others) and HCl (Factrel®) salts. Gonadorelin may also be known as: follicle stimulating hor-mone-releasing factor, Gn RH, gonadoliberin, gonadorelinum, gonadotrophin-releasing hormone, Hoe-471, LH/FSH-RF, LH/ FSH-RH, LH-RF, LH-RH, luliberin, luteinising hormone-releasing factor, Cryptocur®, Cystorelin®, Factrel®, Fertagyl®, Fertiral®, HRF®, Kryptocur®, LRH®, Luforan®, Luteoliberina®, Lutrefact®, Ovacyst®, Parlib®, Pulsti®, Relefact LH-RH®, and Stimu-LH®. Storage/Stability/Compatibility The manufacturers recommend storing gonadorelin in the re-frigerator (2-8°C). There is very little information available on the stability and compatibility of gonadorelin. Because bacterial con-tamination can inactivate the product, it has been recommended that multi-dose vials be used completely and as rapidly as possible. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Gonadorelin (diacetate tetrahydrate) for Injection: 50 micrograms/ m L, 2 m L single-use or 10 m L multi-dose vials; Cystorelin® (Meri-al); Fertagyl® (Intervet); Ovacyst®, (RXV); (Rx). Approved for use in dairy cattle. There are no withdrawal times required for either milk or slaughter. Gonadorelin HCl Solution for Injection: 50 mcg/m L in 2 m L single-use, and 20 m L multi-dose vials; Factrel® (Fort Dodge); (Rx). Ap-proved for use in cattle. No withdrawal period required. HUMAN-LABELED PRODUCTS: Gonadorelin HCl Powder for Injection (lyophilized): 100 mcg/vial, 500 mcg/vial (as hydrochloride) with 2 m L sterile diluent; Factrel® (Wyeth-Ayerst); (Rx) Gonadotropin, Chorionic — See Chorionic Gonadotropin	pppbs.pdf
440 GRANISETRON HCL TGRANISETRON HCL (gran-iss-eh-tron) Kytril® 5-HT3 ANTAGONIST ANTIEMETIC Prescriber Highlights TT 5-HT3 receptor antagonist for the treatment of severe vomiting or emesis prophylaxis before chemotherapy TT Appears to be safe TT Relatively expensive Uses/Indications Granisetron is an alternative to other 5-HT 3 receptor antagonists (e. g., ondansetron or dolasetron) for the treatment of severe vomit-ing or prophylaxis before administering antineoplastic drugs such as cisplatin that can cause severe vomiting. Pharmacology/Actions Granisetron, like ondansetron or dolasetron, exerts its anti-nausea and antiemetic actions by selectively antagonizing 5-hy-droxytryptamine 3 (5-HT 3; serotonin 3) receptors. These receptors are found primarily in the CNS chemoreceptor trigger zone,on vagal nerve terminals and enteric neurons in the GI tract. Chemotherapy associated vomiting in cats is believed primarily due to activation of 5-HT 3 receptors in the chemoreceptor trigger zone (CTZ), but in dogs, enteric and vagal receptors may be more important. Pharmacokinetics No pharmacokinetic data for dogs or cats was located. In humans, granisetron is rapidly absorbed after oral dosing and peak levels occur in about 2 hours. Oral bioavailability is only 60% due to ﬁrst-pass metabolism in the liver. The presence of food can decrease AUC by 5%, but increase peak levels by 30%. Granisetron has a vol-ume of distribution of about 3 L/kg and plasma protein binding is approximately 65%. The drug is metabolized in the liver, primarily via demethylation and oxidation and then conjugation. Less than 20% is excreted unchanged in the urine; the remainder is elimi-nated in the urine and feces as metabolites. Elimination half-life varies considerably, with reported values from about 1-30 hours. Cancer patients appear to have longer elimination half-lives than do healthy adults. Contraindications/Precautions/Warnings There are no known contraindications to using this medication in dogs or cats. In humans, granisetron is contraindicated in patients hypersensitive to it and it should not be used to treat vomiting as-sociated with apomorphine (see Drug Interactions). No dosage adjustments are required in elderly patients or those with impaired renal or hepatic function. Granisetron may mask the signs associated with progressive ileus and/or gastric distention; it should not replace required nasogastric suction. Adverse Effects Because of limited use in dogs and cats, a comprehensive adverse effect proﬁle for granisetron is not known, however, it appears to be tolerated well. In humans, the most common adverse effect reported is head-ache. Other adverse effects that may occur include abdominal pain, constipation or diarrhea, asthenia, or somnolence. Rarely, hyper-sensitivity reactions or cardiovascular effects (arrhythmias, chest pain, hypotension) have been reported. Reproductive/Nursing Safety Safety in pregnancy is not clearly established, but high dose studies in rodents and rabbits did not demonstrate overt fetal toxicity or teratogenicity. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demon-strated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) It is not known if granisetron enters milk, but it is probably safe to use during nursing. Overdosage/Acute Toxicity Limited information is available. An overdose of 38. 5 mg in a per-son caused only a slight headache. Observation and, if required, supportive treatment are suggested. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving granisetron and may be of signiﬁcance in veterinary patients: ! !APOMORPHINE : Profound hypotension can occur ! !KETOCONAZOLE : May inhibit the metabolism of granisetron ! !PHENOBARBITAL : Can induce the metabolism of granisetron Laboratory Considerations No speciﬁc laboratory concerns associated with granisetron Doses T ! DOGS/CAT S: a) Cats (with pancreatitis): 0. 1-0. 5 mg/kg PO or IV q12-24h. (Zoran 2006c), (Washabau 2006b) b) Dogs or Cats: 0. 1-0. 5 mg/kg PO or IV twice daily. (Washa-bau 2006a) Monitoring T ! Clinical efﬁcacy Client Information T ! his drug is usually used on an inpatient basis or during outpa-tient visits for chemotherapy T ! If used orally on an outpatient basis, have client contact veteri-narian for further instructions if vomiting is not controlled or if the dose is vomited up after administrating Chemistry/Synonyms Granisetron HCl occurs as a white or almost white powder that is freely soluble in water. Dosages are expressed in terms of the base; 1. 12 mg of granisetron HCl is equivalent to 1 mg of granisetron base. Granisetron may also be known as: granistroni, granisetrono, or BRL-43694A, Aludal®, Eumetic®, Granicip®, Granitron, Kytril®, Kevatril®, Rigmoz® or Setron®. Storage/Stability/Compatibility The commercially available tablets and oral solution should be stored at room temperature (15-30°C) in tight containers and protected from light. The oral solution should be stored in an up-right position. The injectable solution should be stored between 15-30°C; preferably at 25°C. Protect from light and do not freeze solution. Once the multi-dose vial is penetrated, it must be used within 30 days.	pppbs.pdf
GRISEOFULVIN 441 The injectable solution is compatible with sodium chloride 0. 9%, dextrose 5% in sodium chloride 0. 45% or 0. 9%, and dextrose 5% in water. It is compatible with many drugs at intravenous Y-sites, but is incompatible with amphotericin B. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Granisetron Oral Tablets: 1 mg (1. 12 mg as HCl); Kytril® (Roche); (Rx) Granisetron Oral Solution: 0. 2 mg/m L (0. 56 mg/m L as HCl, orange ﬂavor; contains sorbitol) in 30 m L bottles; Kytril® (Roche); (Rx) Granisetron Injection: 1 mg/m L (1. 12 mg/m L as HCl) in 1 m L single-dose and 4 m L multi-dose vials; Kytril® (Roche); (Rx) GRISEOFULVIN (MICROSIZE) GRISEOFULVIN (ULTRAMICROSIZE) (gri-see-oh-ful-vin) Fulvicin® ANTIFUNGAL AGENT Prescriber Highlights TT Fungistatic antibiotic used primarily for ringworm & other dermatophytic infections; no effect on other fungi TT Contraindications: Pregnancy, known hypersensitivity, or hepatocellular failure TT Caution: Kittens may be overly sensitive to the drug; cats with FIV TT Adverse Effects: Anorexia, vomiting, diarrhea, anemia, neutropenia, leukopenia, thrombocytopenia, depression, ataxia, hepatotoxicity, or dermatitis/photosensitivity TT Known teratogen in cats TT Only new hair & nail growth resistant to fungi after treating TT Dosing is different for microsize & ultramicrosize forms Uses/Indications In veterinary species, griseofulvin is approved for use in dogs and cats to treat dermatophytic fungal (see below) infections of the skin, hair and claws, and to treat ringworm (caused by T. equinum and M. gypseum) in horses. It has also been used in laboratory animals and ruminants for the same indications. The oral tablets approved for dogs and cats are no longer marketed in the USA, but human dosage forms are available. Pharmacology/Actions Griseofulvin acts on susceptible fungi by disrupting the structure of the cell's mitotic spindle, arresting the metaphase of cell divi-sion. Griseofulvin has activity against species of Trichophyton, Microsporum and Epidermophyton. Only new hair and nail growth is resistant to infection. It has no antibacterial activity and is not clini-cally useful against other pathogenic fungi, including Malessezia yeasts. Pharmacokinetics The microsized form of the drug is absorbed variably (25-70%); dietary fat will enhance absorption. The ultramicrosize form of the drug may be nearly 100% absorbed. Generally, the ultramicrosize form is absorbed 1. 5 times as well as the microsized form for a given patient. Griseofulvin is concentrated in skin, hair, nails, fat, skeletal mus-cle, and the liver, and can be found in the stratum corneum within 4 hours of dosing. Griseofulvin is metabolized by the liver via oxidative demethyla-tion and glucuronidation to 6-desmethylgriseofulvin, which is not active. In humans, the half-life is 9-24 hours. A serum half-life of 47 minutes has been reported for dogs. Less than 1% of the drug is excreted unchanged in the urine. Contraindications/Precautions/Warnings Griseofulvin is contraindicated in patients hypersensitive to it or with hepatocellular failure. It should not be used in pregnant animals. Because kittens may be overly sensitive to the adverse effects as-sociated with griseofulvin, they should be monitored carefully if treatment is instituted. Cats should be tested for FIV before using griseofulvin because of the possible neutropenic or panleukopenic effects of the drug. Adverse Effects Griseofulvin can cause anorexia, vomiting, diarrhea, anemia, neu-tropenia, leukopenia, thrombocytopenia, depression, ataxia, hepa-totoxicity, dermatitis/photosensitivity and toxic epidermal necrol-ysis. With the exception of GI clinical signs, adverse effects are uncommon at usual doses. Cats, particularly kittens, may be more susceptible to adverse effects (e. g., bone marrow depression) than other species. This could be due to this species' propensity to more slowly form glucuronide conjugates and thus metabolize the drug at a slower rate than either dogs or humans. Reproductive/Nursing Safety Griseofulvin is a known teratogen in cats and, probably, in dogs as well. Dosages of 35 mg/kg given to cats during the ﬁrst trimester caused cleft palate and other skeletal and brain malformations in kittens. Griseofulvin may also inhibit spermatogenesis. Because der-matophytic infections are not generally life-threatening and alter-native therapies are available, use of the drug should be considered contraindicated during pregnancy. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: D (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) No lactation safety information was found. Overdosage/Acute Toxicity No speciﬁcs regarding griseofulvin overdosage or acute toxicity were located. It is suggested that signiﬁcant overdoses be handled with gut emptying, charcoal and cathartic administration un-less contraindicated. Contact a poison control center for more information. Horses have received 100 mg/kg PO for 20 days without appar-ent ill effect.	pppbs.pdf
442 GRISEOFULVIN Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving griseofulvin and may be of signiﬁcance in veterinary patients: !!ALCOHOL : Griseofulvin may potentiate the effects of alcohol !!ASPIRIN : Griseofulvin may decrease salicylate levels !!CYCLOSPORINE : Griseofulvin may decrease cyclosporine levels !TPHENOBARBITAL : Phenobarbital and other barbiturates have been implicated in causing decreased griseofulvin blood concentra-tions, presumably by inducing hepatic microsomal enzymes and/or reducing absorption. If phenobarbital and griseofulvin are given concurrently, griseofulvin dosage adjustment may be necessary. !TTHEOPHYLLINE : In some patients, griseofulvin may decrease theo-phylline half-life and levels !TWARFARIN : Coumarin anticoagulants may have their anticoagu-lant activity reduced by griseofulvin; anticoagulant adjustment may be required Doses Note : all doses are for microsize preparations unless otherwise indicated. !TDOGS: For susceptible dermatophytic infections: a) Microsize: 25 mg/kg q12h PO for 42-56 days; Ultramicro-size: 5-10 mg/kg PO once daily for 42 days. May need to treat longer for Trichophyton than for Microsporum. Give following a fatty meal or administration of corn oil. Con-tinue for at least 2 weeks after resolution of signs and at least 5 months for onychomycosis. (Greene, Hartmannn et al. 2006) b) Microsize: 50 mg/kg PO once daily with fatty meal. Used with topical therapy (see references). May double dose in resistant cases. If GI distress occurs may divide dose and give twice daily with food. Prolonged course of therapy required. Begin taking cultures after 4 weeks of treatment. Continue therapy for 2 weeks beyond clinical cure and when 2-3 negative cul-tures are obtained at weekly intervals. (Frank 2000) !TCATS: For susceptible dermatophytic infections: a) Microsize: 50-120 mg/kg PO; divided daily. Give with a fatty meal. Ultramicrosize: 10-15 mg/kg PO twice daily. Give for 4-6 weeks or longer, until culture is negative. (Foil 2003b) b) Microsize: 50 mg/kg PO once daily or 25 mg/kg PO q12h for 42-70 days; Ultramicrosize: 5-10 mg/kg PO once daily for 42 days. Give following a fatty meal or administration of corn oil. Continue for at least 2 weeks after resolution of signs and at least 5 months for onychomycosis. (Greene, Hartmannn et al. 2006) c) For feline M. canis: After total body clip, griseofulvin 80-130 mg/kg PO once daily with a fatty meal or 2. 5-5 m L of corn oil. Re-clip after one month and continue treatment until signs of infection have disappeared and cultures are negative. (Thoday 1986) d) Microsize: 50 mg/kg PO once daily with fatty meal. Used with topical therapy (see references). May double dose in resistant cases. If GI distress occurs may divide dose and give twice daily with food. Prolonged course of therapy required. Begin taking cultures after 4 weeks of treatment. Continue therapy for 2 weeks beyond clinical cure and when 2-3 negative cul-tures are obtained at weekly intervals. (Frank 2000) e) For feline eosinophilic granuloma complex: Microsize: 25 mg/kg PO twice daily with food. Give at least for one month to judge efﬁcacy. (White 2003b) !TRABBITS/RODENTS/SMALL MAMMALS: a) Rabbits for advanced dermatophytosis: Ultramicrosize 6. 25 mg/kg PO q12h for 4-6 weeks. Microsize: 25 mg/kg PO q12-24h for one month (Ivey and Morrisey 2000) b) Chinchillas: 25 mg/kg PO once daily for 30-60 days (Hayes 2000) c) Gerbils, Guinea pigs, Hamsters, Rats: 25 mg/kg PO q24h for 14-28 days; Mice: 25 mg/kg PO q24h for 14 days; Chinchil-las: 25 mg/kg PO q24h for 28-40 days (Adamcak and Otten 2000) d) Guinea pigs for dermatophytosis: 25 mg/kg PO (as a suspen-sion) once daily for 28 days. (Johnson 2006d) e) Chinchillas: 25 mg/kg PO once daily (q24h) for 30 days (Johnson 2006a) !TCATTLE (and other ruminants): For susceptible dermatophytic infections: a) Ultramicrosize: 10-20 mg/kg PO once daily for 1-2 weeks. 100 mg/kg PO given twice (or more) 1 week apart may also be effective. Not approved for use in food animals and can be very expensive. (Pier 1986) b) 20 mg/kg PO once daily for 6 weeks (Howard 1986) !THORSES: For susceptible dermatophytic infections: a) 10 mg/kg PO once daily (Robinson 1987) b) 10 mg/kg PO (in feed) daily for 7 days (Brumbaugh 1987) !TSWINE: For susceptible dermatophytic infections: a) 20 mg/kg PO once daily for 6 weeks (Howard 1986) !TBIRDS: a) Ratites: 35-50 mg/kg PO once daily (Jenson 1998) Monitoring !TClinical efﬁcacy; culture !TAdverse effects !TCBC; before therapy and q1-3 weeks during therapy !TLiver enzymes (if indicated) Client Information !TClients should be instructed in procedures used to prevent rein-fection (destruction of old bedding, disinfection, periodic reex-aminations, hair clipping, etc. ), and the importance of compli-ance with the dosage regimen. !TShould animal develop adverse effects other than mild GI distur-bances, they should contact their veterinarian. Chemistry/Synonyms A fungistatic antibiotic produced by species of Penicillium (pri-marily P. griseofulvum), griseofulvin occurs as an odorless or nearly odorless, bitter tasting, white to creamy white powder. It is very slightly soluble in water and sparingly soluble in alcohol. Two forms of the drug are available commercially. Microsize griseofulvin contains particles with a predominant size of 4 mi-crometers in diameter, while the ultramicrosize form particle size averages less than 1 micron in diameter. Griseofulvin may also be known as: curling factor, griseofulvina, and griseofulvinum; many trade names are available.	pppbs.pdf
GUAIFENESIN 443 Storage/Stability/Compatibility Although griseofulvin is relatively thermostable, products should be stored at less than 40°C, preferably at 15-30°C. Griseofulvin suspension should be stored in tight, light-resistant containers. Microsize tablets and capsules should be stored in tight contain-ers; the ultramicrosize tablets should be stored in well-closed containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Griseofulvin (Microsize) Powder: 2. 5 g griseofulvin in 15 g sachets; Am Tech® Griseofulvin Powder (IVX); (Rx). Approved for use in hors-es not intended for food. HUMAN-LABELED PRODUCTS: Griseofulvin Microsize Tablets: 500 mg; Grifulvin V® (Ortho); (Rx) Griseofulvin Microsize Oral Suspension: 125 m L/5 m L in 120 m L; Grifulvin V® (Ortho); generic; (Rx) Griseofulvin Ultramicrosize Tablets: 125 mg & 250 mg; Gris-PEG® (Pedinol); (Rx) GUAIFENESIN (gwye-fen-e-sin) GG, Guailaxin® PARENTERAL MUSCLE RELAXANT/ORAL EXPECTORANT Prescriber Highlights TT An expectorant (oral) & muscle relaxant (parenteral) ad-junctive to anesthesia TT Contraindications: None noted except concurrent use with physostigmine TT Adverse Effects: Mild hypotensive effect & increase in cardiac rate, thrombophlebitis possible Uses/Indications In veterinary medicine, guaifenesin is used to induce muscle relax-ation and restraint as an adjunct to anesthesia for short procedures (30-60 minutes) in large and small animal species. There are com-bination oral products containing guaifenesin for treating respira-tory conditions in horses. In human medicine, guaifenesin has long been touted as an oral expectorant, but deﬁnitive proof of its efﬁcacy is lacking. Pharmacology/Actions While the exact mechanism of action for the muscle relaxant effect is not known, it is believed that guaifenesin acts centrally by de-pressing or blocking nerve impulse transmission at the internuncial neuron level of the subcortical areas of the brain, brainstem and spinal cord. It relaxes both the laryngeal and pharyngeal muscles, thus allowing easier intubation. Guaifenesin also has mild intrinsic analgesic and sedative qualities. Guaifenesin causes an excitement-free induction and recovery from anesthesia in horses. It produces relaxation of skeletal muscles but does not affect diaphragmatic function and has little, if any, ef-fect on respiratory function at usual doses. Possible effects on the cardiovascular system include transient mild decreases in blood pressure and increases in cardiac rate. Gastrointestinal motility may be increased, but generally no adversity is seen with this. Guaifenesin potentiates the activity of preanesthetic and anes-thetic agents. Pharmacokinetics The pharmacokinetics of guaifenesin have not been thoroughly studied in most species. When administered alone to horses IV, re-cumbency usually occurs within 2 minutes and light (not surgical level) restraint persists for about 6 minutes. Muscle relaxation re-portedly persists for 10-20 minutes after a single dose. Guaifenesin is conjugated in the liver and excreted into the urine. A gender difference in the elimination half-life of guaifene-sin in ponies has been demonstrated, with males having a t H o f approximately 85 minutes, and females a t H of about 60 minutes. Guaifenesin reportedly crosses the placenta, but adverse effects in newborns of mothers who received guaifenesin have not been described. Contraindications/Precautions/Warnings The manufacturer states that the use of physostigmine is con-traindicated with guaifenesin (see Drug Interactions). Adverse Effects At usual doses, side effects are transient and generally minor. A mild decrease in blood pressure and increase in cardiac rate can be seen. Thrombophlebitis has been reported after IV injection, and perivas-cular administration may cause some tissue reaction. Hemolysis may occur in solutions containing greater than a 5% concentration of guaifenesin, but some sources state this is insigniﬁcant at even a 15% concentration. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether guaifenesin is excreted in milk. Overdosage/Acute Toxicity The margin of safety is reportedly 3 times the usual dose. Clinical signs of apneustic breathing, nystagmus, hypotension, and contra-dictory muscle rigidity are associated with toxic levels of the drug. There were 69 exposures to guaifenesin reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org ) dur-ing 2000-2006. In these cases 59 were dogs with only 1 showing clinical signs and 8 cases were cats with only 1 showing clinical signs. The remaining 2 cases were birds which showed no clinical signs. The dog received a dosage estimated between 415 and 830 mg/kg and exhibited hypothermia, mild tremors, ataxia and vomit-ing. The cat received a dosage of 132 mg/kg and exhibited lethargy and anorexia. No speciﬁc antidote is available. It is suggested that treatment be supportive until the drug is cleared to sub-toxic levels. Drug Interactions Drug interactions with guaifenesin are not well studied. The fol-lowing drug interactions have either been reported or are theoreti-cal in animals receiving guaifenesin and may be of signiﬁcance in veterinary patients: T ! PHYSOSTIGMINE : The manufacturer (Robins) states that phys-ostigmine is contraindicated in horses receiving guaifenesin, but does not elucidate on the actual interaction. It may be logical to assume that other anticholinesterase agents ( neostigmine, pyri-dostigmine, edrophonium ) may also be contraindicated.	pppbs.pdf
444 GUAIFENESIN Doses !TDOGS: a) Guaifenesin only: 44-88 mg/kg IV; or guaifenesin 33-88 mg/kg IV with 2. 2-6. 6 mg/kg thiamylal or 1. 1 mg/kg ket-amine (Muir) b) 110 mg/kg IV for muscle relaxation during certain toxicoses (e. g., strychnine) or tetanus (Morgan 1988), (Bailey 1986a) c) For chemical restraint for ventilatory support: Combination of guaifenesin 50 mg/m L, ketamine 1 mg/m L, and xylazine 0. 25 mg/m L; give 0. 55 m L bolus initially followed by 2. 2 m L/ kg/hr thereafter (Pascoe 1986) !TCATTLE: a) Guaifenesin only: 66-132 mg/kg IV; or guaifenesin 44-88 mg/kg IV with 2. 2-6. 6 mg/kg thiamylal or 0. 66-1. 1 mg/kg ketamine (Muir) b) 55-110 mg/kg IV (Mandsager 1988) !THORSES: (Note : ARCI UCGFS Class 4 Drug) a) 110 mg/kg IV, give ﬁrst N-H of dose until horse falls gently, then give remainder unless respiratory or cardiovascular ef-fects are observed (Package Insert; Guailaxin®—Robins) b) Guaifenesin only: 66-132 mg/kg IV; or guaifenesin 44-88 mg/kg IV with 2. 2-6. 6 mg/kg thiamylal (Muir) c) 55-110 mg/kg IV (Mandsager 1988) d) For anesthesia: 100 mg/kg IV combined with barbiturate in 5% dextrose. As an expectorant: 3 mg/kg PO (Robinson 1987) e) For ﬁeld anesthesia: Sedate with xylazine (1 mg/kg IV; 2 mg/ kg IM) given 5-10 minutes (longer for IM route) before induction of anesthesia with ketamine (2 mg/kg IV). Horse must be adequately sedated (head to the knees) before giving the ketamine (ketamine can cause muscle rigidity and sei-zures). If adequate sedation does not occur, either 1) Redose xylazine: up to half the original dose; 2) Add butorphanol (0. 02-0. 04 mg/kg IV). Butorphanol can be given with the original xylazine if you suspect that the horse will be difﬁcult to tranquilize (e. g., high-strung Thoroughbreds) or added before the ketamine. This combination will improve induc-tion, increase analgesia and increase recumbency time by about 5-10 minutes; 3) Diazepam (0. 03 mg/kg IV). Mix the diazepam with the ketamine. This combination will improve induction when sedation is marginal, improve muscle re-laxation during anesthesia and prolong anesthesia by about 5-10 minutes; 4) Guaifenesin (5% solution administered IV to effect) can also be used to increase sedation and muscle relaxation. (Mathews 1999) f) For adjunctive symptomatic treatment of strychnine poison-ing: 110 mg/kg IV; repeated as necessary (Schmitz 2004) !TSWINE: a) Guaifenesin only: 44-88 mg/kg IV; or guaifenesin 33-88 mg/kg IV with 2. 2-6. 6 mg/kg thiamylal or 1. 1 mg/kg ket-amine (Muir) !TGOATS: a) Guaifenesin only: 66-132 mg/kg IV; or guaifenesin 44-88 mg/kg IV with 0. 66-1. 1 mg/kg ketamine (Muir) Monitoring !TLevel of muscle relaxation !TCardiac and respiratory rate Chemistry/Synonyms Formerly known as glyceryl guaiacolate, guaifenesin occurs as a white to slightly gray, crystalline powder that may have a character-istic odor. It is nonhygroscopic and melts between 78°-82°C. One gram is soluble in 15 m L of water and soluble in alcohol, propylene glycol and glycerin. Guaifenesin may also be known as: GG, glyceryl guaiacolate, glycerylguayacolum, guaiacol glycerol ether, guaiacyl glyceryl ether, guaifenesina, guaifenesinum, guaiphenesin, and guajacolum glyc-erolatum; many trade names are available. Storage/Stability/Compatibility Guaifenesin is stable in light and heat (less than melting point). It should be stored in well-closed containers. When dissolved into aqueous solutions, guaifenesin may slightly precipitate out of solution when the temperature is less than 22°C (72°F). Slight warming and agitation generally resolubilizes the drug. A microwave oven has been suggested for heating and dis-solving the drug. It is recommended that the solution be prepared freshly before use, but a 10% solution (in sterile water) may appar-ently be stored safely at room temperature for up to one week with only slight precipitation occurring. Guaifenesin is physically compatible with sterile water or D 5W. It is also reportedly compatible with ketamine, pentobarbital, thiamy-lal, thiopental, and xylazine. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Guaifenesin Injection 50 mg/m L in 1000 m L: Guaifenject® (Butler), generic, (IVX, RXV, Vedco, Phoenix Pharmaceutical); (Rx). Approved for use in horses not intended for food. There are several oral products containing guaifenesin in combina-tion with an antihistamine (pyrilamine) labeled for use in horses, in-cluding Anhist® (AHC), & Hist-EQ® Powder (Butler); (OTC) There are oral products containing guaifenesin and other expecto-rants (potassium iodide, ammonium chloride) labeled for use in horses, cattle, and sheep, including Spect-Aid® (AHC), and Spec-Tuss® (Neogen); (OTC) There may be veterinary oral cough syrups or tablets containing guaifenesin available labeled for use in small animals. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Guaifenesin (Glyceryl Guaiacolate) Tablets: 200 mg & 400 mg; 600 mg & 1200 mg (extended-release); Organidin NR® (Medpointe); All-fen Jr® (MCR American); Liquibid® (Capellon); (Rx); Guaifenesin (URL); Mucinex® (Adams); Humibid Maximum (Adams); generic; (OTC) Guaifenesin Granules: 50 mg or 100 mg/packet; Mucinex® Mini-Melts Children's & Junior Strength (Adams Laboratories); (OTC) Guaifenesin Syrup/Liquid: 100 mg/5m L in 118 m L, 237 m L & 473 m L; 200 mg/5 m L in 120 m L; Altarussin® (Altaire); Mucinex Chil-dren's® (Adams Laboratories); Diabetic Tussinv® (Health Care Prod-ucts); Robitussin® (Wyeth); Siltussin DAS® & SA® (Silarx); Scot-Tussin Expectorant® (Scot-Tussin); Naldecon Senior EX® (Sandoz); (OTC); Ganidin NR® (Cypress); Guaifenesin NR® (Silarx); Organidin NR® (Medpointe); (Rx) No parenteral preparations are approved. There are many OTC oral expectorant/cough preparations on the market.	pppbs.pdf
HALOTHANE 445 HALOTHANE (ha-loe-thane) Fluothane® GENERAL ANESTHETIC Prescriber Highlights TT Classic inhalant general anesthetic; still used but largely supplanted by newer agents TT Contraindications: History or predilection towards malig-nant hyperthermia; signiﬁcant hepatotoxicity after previ-ous exposure TT Caution in patients with hepatic function impairment, cardiac arrhythmias, increased CSF or head injury, myas-thenia gravis, or pheochromocytoma TT Adverse Effects: Dose related hypotension, malignant hyperthermia-stress syndrome, cardiac depression & dys-rhythmias, hepatotoxicity TT May be teratogenic; use with caution in pregnancy TT Drug interactions Uses/Indications Halothane remains a useful general anesthetic in veterinary medi-cine due to its relative safety, potency, controllability, non-ﬂamma-bility, and comparatively low cost. However, its use has been largely supplanted by newer agents such as isoﬂurane and sevoﬂurane that have less cardiodepressant effects. Pharmacology/Actions While the precise mechanism that inhalant anesthetics exert their general anesthetic effect is not precisely known, they may interfere with functioning of nerve cells in the brain by acting at the lipid matrix of the membrane. Some key pharmacologic effects noted with halothane include: CNS depression, depression of body tem-perature regulating centers, increased cerebral blood ﬂow, respira-tory depression (pronounced in ruminants), hypotension, vasodi-latation, and myocardial depression. Minimal Alveolar Concentration (MAC; %) in oxygen reported for halothane in various species: Dog = 0. 76; Cat = 0. 82; Horse = 0. 88; Human = 0. 76. Several factors may alter MAC (acid/base sta-tus, temperature, other CNS depressants on board, age, ongoing acute disease, etc. ). Pharmacokinetics Halothane is rapidly absorbed through the lungs. About 12% of ab-sorbed drug is metabolized by the liver to triﬂuoroacetic acid (only small amounts), chlorine, and bromine radicals that are excreted in the urine. The bulk of the absorbed drug is re-excreted by the lungs and eliminated with expired air. Halothane is distributed into milk. Contraindications/Precautions/Warnings Halothane is contraindicated in patients with a history or predilec-tion towards malignant hyperthermia or signiﬁcant hepatotoxic-ity after previous halothane exposure (see Adverse Effects below). It should be used with caution (beneﬁts vs. risks) in patients with hepatic function impairment, cardiac arrhythmias, increased CSF or head injury, myasthenia gravis, or pheochromocytoma (cardiac arrhythmias due to catecholamines). Adverse Effects Hypotension may occur and is considered dose-related. A ma-lignant hyperthermia-stress syndrome has been reported in pigs, horses, dogs, and cats. Halothane may cause cardiac depression and dysrhythmias. Halothane-induced hypotension may be treated by volume expansion and dobutamine. Lidocaine has been used to treat or prevent halothane-induced cardiac dysrhythmias. In hu-mans, jaundice and a postanesthetic fatal liver necrosis have been reported rarely. The incidence of this effect in veterinary species is not known, however, halothane should be considered contraindi-cated for future use if unexplained fever, jaundice, or other clinical signs associated with hepatotoxicity occur. Reproductive/Nursing Safety Some animal studies have shown that halothane may be teratogenic; use only when beneﬁts outweigh potential risks. In a system evalu-ating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncov-ered risks, and these drugs should be used cautiously as a last resort when the beneﬁt of therapy clearly outweighs the risks. ) Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving halothane and may be of signiﬁcance in veterinary patients: T ! ACETAMINOPHEN : Is not recommended for use for post-operative analgesia in patients that have received halothane anesthesia T ! ACEPROMAZINE : Can decrease requirements of halothane by up to 40% T ! AMINOGLYCOSIDES : Use with caution with halogenated anesthetic agents as additive neuromuscular blockade may occur T ! LINCOSAMIDES : Use with caution with halogenated anesthetic agents as additive neuromuscular blockade may occur T ! NON-DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS : Additive neuromuscular blockade may occur T ! SUCCINYLCHOLINE : With inhalation anesthetics, may induce in-creased incidences of cardiac effects (bradycardia, arrhythmias, sinus arrest and apnea) and, in susceptible patients, malignant hyperthermia T ! SYMPATHOMIMETICS (dopamine, epinephrine, norepinephrine, ephed-rine, metaraminol, etc. ): Because halothane sensitizes the myo-cardium to the effects of sympathomimetics, especially cate-cholamines, severe ventricular arrhythmias may result. If these drugs are needed, they should be used with caution and in sig-niﬁcantly reduced dosages with intensive monitoring T ! D-TUBOCURARINE : May cause signiﬁcant hypotension if used with halothane Laboratory Considerations T ! Halothane may transiently increase values of liver function tests. Doses T ! DOGS/CAT S: Note : Concentrations are dependent upon fresh gas ﬂow rate; the lower the ﬂow rate, the higher the concentration required. a) 3% (induction); 0. 5-1. 5% (maintenance) (Papich 1992) b) 0. 5-3. 5%, inhaled (Hubbell 1994) T ! RABBITS/RODENTS/SMALL MAMMALS: a) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: Using a non-rebreathing system: Induction: 2-4%, main-tenance: 0. 25-2% (Anderson 1994); (Adamcak and Otten 2000)	pppbs.pdf
446 HEMOGLOBIN GLUTAMER-200 T ! BIRDS: a) Using an anesthetic vaporizer, induction usually occurs in 2-4 minutes at a concentration of 2% for small birds and 2. 5-3% for large birds. Maintenance can generally be main-tained at concentrations of 0. 5-1. 5%. Recovery usually takes 3-5 minutes. Bradycardia, hypotension and hypothermia may occur, but rapidly resolve once halothane is discontin-ued. (Bennett 2002) T ! HORSES: a) For draft horses: Following induction, the largest ET tube that will comfortably ﬁt (20-40 mm) should be placed and cuff inﬂated. In an oxygen-enriched semi-closed large ani-mal circle system 4-5% of halothane is administered initially and is reduced as indicated by physical monitoring of neural reﬂexes and cardiopulmonary parameters. The goal should be the lowest concentration inhalant anesthetic that provides adequate surgical anesthesia and restraint. Most draft horses can be maintained on 2. 5-3% halothane. (See reference for more information on monitoring and use. ) (Geiser 1992) Monitoring T ! Respiratory and ventilatory status T ! Cardiac rate/rhythm; blood pressure (particularly with “at risk” patients) T ! Level of anesthesia Chemistry/Synonyms An inhalant general anesthetic agent, halothane occurs as a color-less, nonﬂammable, heavy liquid. It has a characteristic odor resem-bling chloroform and a sweet, burning taste. Halothane is slightly soluble in water and miscible with alcohol. At 20°C, halothane's speciﬁc gravity is 1. 872-1. 877 and vapor pressure is 243 mm Hg. Halothane may also be known as: phthorothanum, Fluothane®, and Ineltano®. Storage/Stability/Compatibility Store halothane below 40°C in a tight, light-resistant container. Halothane stability is maintained by the addition of thymol and ammonia. The thymol does not vaporize so it may accumulate in the vaporizer causing a yellow discoloration. Do not use discolored solutions. Discolored vaporizer and wick may be cleaned with di-ethyl ether (all ether must be removed before reuse). In the presence of moisture, halothane vapor can react with alu-minum, brass, and lead (not copper). Rubber and some plastics are soluble in halothane leading to their rapid deterioration. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Halothane in 250 m L bottles; (Abbott); (Rx) HCG-see Chorionic Gonadotropin HEMOGLOBIN GLUTAMER-200 (BOVINE) (hee-moe-gloe-bin gloo-ta-mer) Oxyglobin® SEMI-SYNTHETIC HEMOGLOBIN REPLACER; COLLOID Prescriber Highlights TT Bovine source polymerized hemoglobin product for the treatment of anemias TT Contraindications: Advanced cardiac disease, renal im-pairment with oliguria or anuria TT Many potential adverse effects; most are not serious (see below) TT Potential drug-lab interactions Uses/Indications Oxyglobin® is indicated for the treatment of dogs with anemia, re-gardless of the cause of anemia (hemolysis, blood loss, or ineffective erythropoiesis). From a prognostic standpoint, the drug should be more valuable in dogs with regenerative anemias (versus nonregen-erative anemias). It has also been used extra-label in other species as well, such as in foals for neonatal isoerythrolysis. Its primary beneﬁt is for the patient that is anemic and difﬁcult to transfuse due to unavailability of blood, or when no suitable do-nors are identiﬁed on crossmatch. (Jandrey 2007) Pharmacology/Actions The bovine hemoglobin in the product is polymerized into larger molecules to increase safety, efﬁcacy, and intravascular persistence, is shipped in a deoxygenated state and becomes oxygenated once circulated through the lungs. Oxyglobin® releases oxygen to tissue in a mechanism similar to endogenous hemoglobin; thereby in-creasing plasma and total hemoglobin concentrations, and systemic oxygen content. Because of its small size (in comparison to normal RBC's), it may better deliver oxygen to cells supplied by severely constricted arteries. Oxyglobin® also has colloidal properties similar to dextran 70 and hetastarch. Pharmacokinetics In dogs receiving 15 m L/kg: peak plasma hemoglobin concentra-tions increased approximately 2. 5 g/dl; at 30 m L/kg, approximately 4 mg/dl. Duration of effect continues for at least 24 hours. The plasma half-life in dogs at present labeled dosages is approximately 18-43 hours and Oxyglobin® can be detected in plasma for 5-7 days after a single dose. As with endogenous hemoglobin, Oxyglobin® is metabolized and eliminated by the reticuloendothelial system. Small amounts of unstabilized hemoglobin (<5%) may be excreted through the kidneys, causing discoloration (red) of the urine. Contraindications/Precautions/Warnings As safe use of Oxyglobin ® has not been tested for the follow-ing conditions and plasma expanders are generally contraindi-cated in them, the product is labeled as contraindicated in dogs with advanced cardiac disease ( i. e., congestive heart failure) or otherwise severely impaired cardiac function or renal impairment with oliguria or anuria. The safety and efﬁcacy of Oxyglobin ® has not been evaluated in dogs with DIC, thrombocytopenia	pppbs.pdf
HEMOGLOBIN GLUTAMER-200 447 T Twith active bleeding, hemoglobinemia and hemoglobinuria, or autoagglutination. Administration of any foreign protein has the potential to cause immunologic reactions. While low levels of Ig G antibodies have been detected after multiple dosages, no anaphylactic reactions have been reported thus far. If an immediate hypersensitivity reaction occurs, infusion should be immediately discontinued and appro-priate treatment administered. If a delayed type of hypersensitivity reaction occurs, immunosuppressant therapy is recommended. Adverse Effects The package insert lists the following frequency of adverse reactions that occurred in greater than 4% of dogs treated with Oxyglobin® ( Note : ﬁrst ﬁgure is % of dogs treated; in parentheses: % treated having hemolytic anemia): Discolored mucous membranes 69% (47%); discolored sclera (yellow, red, brown) 56% (48%); discol-ored urine (orange, red, brown) 52% (41%); discolored skin (yel-low) 12% (83%); increased central venous pressure (CVP) 33% (47%); ventricular arrhythmias (A V block, tachycardia, ventricu-lar premature contractions) 15% (78%); ecchymosis/petechiae 8% (50%); bradycardia 6% (67%); vomiting 35% (72%); diarrhea 15% (50%); anorexia 8% (25%); tachypnea 15% (50%); dyspnea 14% (71%); pulmonary edema 12% (67%); harsh lung sounds/crackles 8% (50%); pleural effusion 6% (67%); fever 17% (40%); death/eu-thanasia 15% (63%); peripheral edema 8% (25%); hemoglobinuria 6% (67%); dehydration 6% (33%). Adverse reactions occurring in 4% of the dogs treated with Oxyglobin® include: coughing, disseminated intravascular coagu-lopathy, melena, nasal discharge/crusts (red), peritoneal effusion, respiratory arrest, and weight loss (5-7% body weight). Adverse reactions occurring in less than 2% of the dogs treated with Oxyglobin® included: abdominal discomfort on palpation, acidosis, cardiac arrest, cardiovascular volume overload (by echocardiogra-phy), collapse, cystitis, dark stool, discolored soft stool (red-brown) and tongue (purple), focal hyperemic areas on gums, forelimb cel-lulitis/lameness, hematemesis or hemoptysis (unable to differenti-ate), hypernatremia, hypotension, hypoxemia, lack of neurologic responses, left forebrain signs, nystagmus, pancreatitis, pendulous abdomen, polyuria, pulmonary thromboembolism, ptosis, red-dened pinnae with papules/head shaking, reduction in heart rate, thrombocytopenia (worsening), and venous thrombosis. Small amounts of unstabilized hemoglobin (<5%) may be ex-creted through the kidneys, resulting in transient discoloration (red) of the urine following the infusion. This discoloration of the urine should not be interpreted as due to intravascular hemolysis and has no effect on renal function. In clinical use, Oxyglobin® has not been demonstrated to affect platelet function or impair coagulation. Increases in aspartate aminotransferase (AST) and alanine ami-notransferase (ALT) not associated with histopathologic changes in the liver, increase in serum total protein, and hemoglobinuria may also be seen. Reproductive/Nursing Safety Safe use in breeding dogs and pregnant or lactating bitches has not been determined. Overdosage/Acute Toxicity The clinical signs associated with Oxyglobin® administered at 1, 2, and 3 times the recommended dose twice, 3 days apart include yellow-orange discoloration of skin, ear canals, pinnae, mucous membranes (gums), and sclera, red-dark-green-black discoloration of feces, brown-black discoloration of urine, red spotting of skin and/or lips (less common), decreased appetite and thirst, vomiting, diarrhea, and decreased skin elasticity. The frequency and/or in-tensity of these signs increased with repeated and increasing doses. Healthy dogs administered 3X overdoses twice, all survived. Overdosage or an excessively rapid administration rate (i. e., >10 m L/kg/hr) may result in circulatory overload. Drug Interactions Other than concerns with compatibility, (no speciﬁc drug interac-tions have been noted. Laboratory Considerations !The presence of Oxyglobin® in serum may cause artifactual in-creases or decreases in the results of serum chemistry tests, de-pending on the type of analyzer and reagents used. May cause false increases in AST, or creatinine. May cause false decreases in LDH. May cause unacceptable interference with GGT, albumin, or bilirubin. !There is reportedly no interference with directly measured he-moglobin tests, but due to the dilutional effects of Oxyglobin®, PCV and RBC count are not accurate measures of the degree of anemia for 24 hours following administration. Prothrombin time (PT) and activated partial thromboplastin time (a PTT) determined using methods that are mechanical, magnetic and light scatter-ing are accurate, but optical methods are not reliable while Oxy-globin® is present. !TUrine dipstick measurements (i. e., p H, glucose, ketones, protein) are inaccurate while gross discoloration of the urine is present. Doses !TDOGS: a) For labeled indications: One-time dose of 10-30 m L/kg IV at a rate of up to 10 m L/kg/hr. May be warmed to 37°C prior to administration. Blood trans-fusions are not contraindicated in dogs which receive Oxy-globin® nor is Oxyglobin® contraindicated in dogs which have previously received a blood transfusion. There is no need for typing or crossmatching before use. Should be administered using aseptic technique via a standard intravenous infusion set and catheter through a central or peripheral vein at a rate of 10 m L/kg/hr. Do not administer with other ﬂuids or drugs via the same infusion set. Do not add medications or other solutions to the bag. Do not combine the contents of more than one bag. (Package Insert; Oxyglobin®—Biopure) b) For resuscitation of trauma patients in shock with or without hemorrhage: Empirically, 3-5 m L/kg with concurrent crys-talloid at H to 2 times maintenance. (Gfeller 2002) c) T o provide a “bridge” until immunosuppressive drugs take effect in dogs with IMHA with a transfusion reaction: 7-10 m L/kg q12h can maintain hemoglobin levels above 3. 5 g/dl; higher doses 30 m L/kg may provide oxygen carrying support for 48-72 hours. (Macintire 2006c) Monitoring !THgb; clinical signs of adequate tissue oxygenation !TSigns of circulatory overload (CVP) !TOther adverse effects (see above) Client Information !TClients should be informed of the cost/risk/beneﬁt proﬁle for this agent before use. Chemistry/Synonyms Oxyglobin® is a sterile, clear, dark purple solution containing 13 g/ dl puriﬁed, polymerized hemoglobin of bovine origin in a modiﬁed lactated Ringer's solution. It has an osmolality of 300 m Osm/kg and	pppbs.pdf
448 HEPARIN a p H of 7. 8. Less than 5% of the hemoglobin are as unstabilized te-tramers, and approximately 50% have a molecular weight between 65 and 130 k D, with no more than 10% having a molecular weight >500 k D. The product contains less than the detectable level of 3. 5 mcg/m L free-glutaraldehyde and 0. 05 EU/m L, endotoxin. Storage/Stability/Compatibility The product remains stable at room temperature or refrigerated (2°-30°C) for up to 3 years; expiration date is printed on the bag. Outdated product is not returnable. Do not freeze. It must remain in its over wrap during storage; once removed, it should be used within 24 hours. The foil over wrap serves as an oxygen barrier, protecting the hemoglobin from conversion to methemoglobin. The manufacturer states that Oxyglobin® is physically compat-ible with any other IV ﬂuid, but should not be mixed with other solutions or medications in the bag; other intravenous solutions and medications may be administered via a separate site and line, however. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Hemoglobin Glutamer-200 (bovine) in 60 m L and 125 m L ready to use infusion bags; Oxyglobin® (Biopure); (Rx). Approved for use in dogs. The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. It is prohibited to be at racing premises. See the appendix for more information. HUMAN-LABELED PRODUCTS: None in USA at present HEPARIN SODIUM HEPARIN CALCIUM (hep-ah-rin) ANTIC OAG ULANT Prescriber Highlights TT Parenteral anticoagulant used primarily for treatment of DIC (use controversial) & thromboembolic disease TT Contraindications: Known hypersensitivity, severe throm-bocytopenia, or uncontrollable bleeding (caused by some-thing other than DIC) TT Adverse Effects: Most common are bleeding & thrombocytopenia TT Protamine may reverse effects TT Intensive monitoring required Uses/Indications Heparin's primary uses in small animal medicine has included treatment of Disseminated Intravascular Coagulation (DIC) and prophylaxis of thromboembolic disease. In horses, it has been used in the treatment of DIC and as prophylactic therapy for laminitis (unproven efﬁcacy). Use for treating DIC has become increasingly controversial. The most recent evidence suggests that heparin not be used during DIC in patients with concurrent inﬂammatory processes. Pharmacology/Actions Heparin acts on coagulation factors in both the intrinsic and ex-trinsic coagulation pathways. Low concentrations of heparin when combined with antithrombin III inactivate factor X a and prevent the conversion of prothrombin to thrombin. In higher doses, hep-arin inactivates thrombin, blocks the conversion of ﬁbrinogen to ﬁbrin and when combined with antithrombin III inactivates fac-tors IX, X, XI, XII. By inhibiting the activation of factor XIII (ﬁbrin stabilizing factor), heparin prevents the formation of stable ﬁbrin clots. While heparin will inhibit the reactions that lead to clotting, it does not signiﬁcantly change the concentrations of clotting fac-tors. Heparin does not lyse clots, but it can prevent the growth of existing clots. Heparin causes increased release of lipoprotein lipase, thereby increasing the clearance of circulating lipids and boosting plasma levels of free fatty acids. Pharmacokinetics Heparin is not absorbed by the gut if administered orally; it must be given parenterally to be effective. Anticoagulant activity begins immediately after direct IV bolus injection, but may take up to one hour after deep SC injection. When heparin is given by continuous IV infusion, an initial bolus must be administered for full antico-agulant activity to begin. Heparin is extensively protein bound, primarily to ﬁbrinogen, low-density lipoproteins and globulins. It does not appreciably cross the placenta or enter milk. Heparin's metabolic fate is not completely understood. The drug is apparently partially metabolized by the liver and also inactivated by the reticuloendothelial system. Serum half-lives in humans aver-ages 1-2 hours. In healthy dogs, bioavailability after subcutaneous injection is about 50%. When 200 units/kg were administered to healthy dogs SC, plasma heparin concentrations were in the therapeutic range between 1 and 6 hours after administration. (Diquelou, Barbaste et al. 2005) Contraindications/Precautions/Warnings Heparin is contraindicated in patients hypersensitive to it, having severe thrombocytopenia or uncontrollable bleeding (caused by something other than DIC). One author (Green 1989) states that with DIC “heparin should not be given to actively bleeding patients that have severe factor depletion and thrombocytopenia, as fatal hemorrhage may result. ” Use for treating DIC has become increasingly controversial. The most recent evidence suggests that heparin should not be used dur-ing DIC in patients with concurrent inﬂammatory processes. Until further evidence suggests practices to the contrary, heparin should be used with extreme caution in both human and veterinary pa-tients with dysfunctional interactions between inﬂammatory and hemostatic systems and the endothelium. (Bateman 2005a) Do not administer IM as heparin may cause hematoma forma-tion. Hematomas, pain, and irritation may occur after deep SC dosing. Dogs with renal insufﬁciency may have lower plasma levels and faster elimination rates of heparin; dosage adjustment may be required. Adverse Effects Bleeding and thrombocytopenia are the most common adverse ef-fects associated with heparin therapy. Because heparin is derived from bovine or porcine tissues, hypersensitivity reactions may be possible. Less commonly encountered adverse effects that have been reported in animals and/or humans include vasospastic reactions	pppbs.pdf
HEPARIN 449 T(after several days of therapy), osteoporosis and diminished renal function (after long-term, high-dose therapy), rebound hyperlipi-demia, hyperkalemia, alopecia, suppressed aldosterone synthesis and priapism. In horses, high IV dosages of heparin may cause ag-glutination of red cells and a decrease in hematocrits. Reproductive/Nursing Safety While heparin does not cross the placenta and is generally felt to be the anticoagulant of choice during pregnancy, its safe use in preg-nancy has not been ﬁrmly established and pregnancy outcomes may be unfavorable. It should be used cautiously and only when clearly necessary. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Heparin is not excreted into milk. Overdosage/Acute Toxicity Overdosage of heparin is associated with bleeding. Clinical signs that could be seen before frank bleeding occurs include hematuria, tarry stools, petechiae, bruising, etc. Protamine can reverse hepa-rin's effects; see the Protamine monograph for more information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving heparin and may be of signiﬁcance in veterinary patients: !!ASPIRIN : May increase the risk for hemorrhage !!DEXTRAN : May increase the risk for hemorrhage !!NSAIDS : May increase the risk for hemorrhage !!WARFARIN : May increase the risk for hemorrhage !The following drugs may partially counteract heparin's antico-agulant effects: ANTIHISTAMINES, NITROGLYCERIN (IV), PROPYLENE GLYCOL, DIGOXIN, and TETRACYCLINES. Laboratory Considerations !TUnless heparin is administered by continuous infusion, it can al-ter prothrombin time, ( PT), which can be misleading in patients also receiving a coumarin or an indanedione anticoagulant. !THeparin can interfere with the results of the BSP (sulfobro-mophthalein, bromosulfophthalein) test by changing the color intensity of the dye and shifting the absorption peak from 580 nm to 595 nm. !THeparin can cause falsely elevated values of serum t hyroxine if us-ing competitive protein binding methods of determination. Ra-dioimmunoassay (RIA) and protein bound iodine methods are apparently unaffected by heparin. !TWhen heparin is used as an anticoagulant in vitro (e. g., in blood collection containers ), white cell counts should be performed within 2 hours of collection. Do not use heparinized blood for platelet counts, erythrocyte sedimentation rates, erythrocyte fragmentation tests, or for any tests involving complement or isoagglutinins. Errors in blood gas determinations for CO 2 pres-sure, bicarbonate concentration, or base excess may occur if hep-arin encompasses 10% or more of the blood sample. Doses !TDOGS & CAT S: For adjunctive treatment of DIC (See Contraindications/Warn-ings above): Note : Heparin therapy may be only one aspect of suc-cessful treatment of DIC. Alleviation of the precipitating causes, administration of ﬂuids, blood, aspirin, and diligent monitoring of coagulation tests (a PTT, PT), ﬁbrin degradation products, and ﬁbrinogen may all be important factors in the treatment of DIC. Doses of heparin are controversial; dosage ranges and methods may vary widely depending on the clinician/author. a) 75 Units/kg SC three times daily (Wingﬁeld and Van Pelt 1989) b) Add 5,000 U of heparin/500 m L warmed whole blood 30 minutes before transfusion. Alternatively, give 10-150 U/kg SC q12h. Heparin must be tapered over 48 hours or a “re-bound effect” may occur. (Feldman 1985) c) After p H has been corrected and perfusion maximized, transfuse heparinized whole fresh blood or plasma (75 U/kg heparin) one time. Then begin mini-dose heparin therapy at 5-10 U/kg/hour by continuous IV infusion or 75 U/kg SC q8h. Continue without interruption until DIC has complete-ly disappeared. With these doses, bleeding risk is negligible and a PTT monitoring not necessary, although thrombocy-topenia may develop. (Slappendel 1989) d) Before administering heparin, provide sufﬁcient fresh whole blood to maintain platelet counts above 30,000/microliter and ﬁbrinogen levels over 50 mg/dl. Then give heparin at 50-100 U/kg SC q6h. Alternatively, dose heparin sufﬁciently to increase a PTT to 1. 5-2 times normal (may be more effec-tive in patients susceptible to thromboembolization). (Green 1989) For adjunctive treatment of thromboembolic disease: a) For feline arterial thromboembolism: 250-300 U/kg SC q8h. First dose is administered IV to cats showing signs of shock. Monitoring a PTT (1. 5-2. 5 fold) and ACT (15-20 sec) should be regarded as rough guidelines only, as these may still result in heparin levels below the recommended thera-peutic range. (Smith 2004) b) Dogs: 200-500 U/kg subcutaneously every 8 hours; target a PTT to 1. 5-2 times pretreatment value (Brooks 2000) c) For maintenance therapy for arterial thromboembolic dis-ease in cats: 250-300 Units/kg SC every 8 hours for the ini-tial in-hospital therapy. (Lunsford and Mackin 2007) d) For maintenance therapy for pulmonary thromboembo-lism in small animals: 200-500 Units/kg SC every 8 hours and then adjusted to reach a target a PTT of 1. 5-2 times the (pre)treatment values or an anti-factor Xa activity be-tween 0. 35-0. 7 U/m L. Warfarin is also given concurrently. (Lunsford and Mackin 2007) e) For canine arterial thrombosis and thromboembolism: Keep dog in a quiet and warm place; give analgesics if necessary. Give heparin initially at 220 U/kg IV. Correct dehydration and dilute blood by administering electrolyte solutions. Dex-tran products may be helpful. Follow-up doses of heparin should be started low and increased until a PTT is 2-2. 5 times normal. After 3-5 days of therapy, gradually reduce heparin over 48-72 hours while dog is put on oral antico-agulant therapy (see warfarin monograph). (Suter 1989) T o prevent clots forming when performing closed chest lavage with pyothorax: a) Add 1000 U of heparin per liter of lavage ﬂuid (warm normal saline). This ﬂuid is instilled at 20 m L/kg twice daily for 5-7 days. Antibiotics (often penicillin) or enzymes (e. g., strep-tokinase) may also be added to ﬂuid. (Berkwitt and Berzon 1988)	pppbs.pdf
450 HEPARIN For adjunctive therapy of acute complicated or severe pancrea-titis in dogs: a) 50-75 U/kg SC twice a day to three times a day; may reduce thromboembolic tendencies, but efﬁcacy is unknown and heparin is not indicated in all cases (Bunch 1988) For detection of lipoprotein lipase activity (heparin stimulation test): a) Measure serum lipids just before and 15 minutes after hepa-rin at 100 U/kg IV. Lack of increase in lipolytic activity is suggestive of lipoprotein lipase deﬁciency. (Kay, Kruth, and Twedt 1988) !THORSES: For adjunctive treatment of DIC: Note : Heparin therapy may be only one aspect of successful treatment of DIC. Alleviation of the precipitating causes, ad-ministration of ﬂuids, blood, aspirin, and diligent monitoring of coagulation tests (APTT, PT), ﬁbrin degradation products, and ﬁbrinogen may all be important factors in the treatment of DIC. a) 80-100 U/kg IV q4-6h (may be added to ﬂuids and given as a slow drip). Low grade DIC may be treated with 25-40 U/ kg SC 2-3 times a day. (Byars 1987) As adjunctive therapy in endotoxic shock: a) 40 Units/kg IV or SC 2-3 times a day may prevent the devel-opment of microthrombi; additional studies are required to conﬁrm positive beneﬁts (Semrad and Moore 1987) As adjunctive therapy in the prevention of laminitis: a) 25-100 Units/kg subcutaneously 3 times daily. Higher doses used when a thrombotic event is underway, lower dosages should have fewer adverse effects and still have antithrombotic activity. Ideally, APTT and ACT should be monitored. Tar-gets are 1. 5-2. 5 times baseline for APTT and 1. 2-1. 4 times baseline for ACT. (Brumbaugh, Lopez et al. 1999) Monitoring Note : The frequency of monitoring is controversial and is depen-dent on several factors, including heparin dose, patient's condition, concomitant problems, etc. Because of the high incidence of hem-orrhage associated with heparin use, frequent monitoring of a PTT is essential early in therapy (particularly using higher dosages) and in critically ill animals. !TWhile whole blood clotting time (WBCT), partial thrombo-plastin time (PTT), and activated partial thromboplastin times (a PTT) may all be used to monitor therapy, APTT is most often recommended; !TPlatelet counts and hematocrit (PCV) should be done periodically; !TOccult blood in stool and urine; other observations for bleeding; !TClinical efﬁcacy Client Information !TBecause of the intense monitoring necessary with heparin's use and the serious nature of the disease states in which it is used, this drug should be utilized only by professionals familiar with it, preferably in an inpatient setting. Chemistry/Synonyms Heparin is an anionic, heterogeneous sulfated glycosaminoglycan molecule with an average molecular weight of 12,000 that is found naturally in mast cells. It is available commercially as either sodium or calcium salts and is obtained from either porcine intestinal mu-cosa (both calcium and sodium salts) or from bovine lung tissue (sodium salt only). Heparin sodium and calcium occur as white or pale-colored, amorphous, hygroscopic powders having a faint odor. Both are soluble in water and practically insoluble in alcohol; the commercial injections have a p H of 5-7. 5. Heparin potency is expressed in terms of USP Heparin units and values are obtained by comparing against a standard reference from the USP. The USP requires that potencies be not less than 120 units/mg on a dried basis for heparin derived from lung tissue, and 140 units/mg when derived from all other tissue sources. Heparin sodium may also be as: heparinum natricum, sodium heparin, and soluble heparin; many trade names are available. Storage/Stability/Compatibility Heparin solutions should be stored at room temperature (15-30°C) and not frozen. Avoid excessive exposure to heat. Heparin sodium is reportedly physically compatible with the following intravenous solutions and drugs: amino acids 4. 25%-dextrose 25%, dextrose-Ringer's combinations, dextrose-lactated Ringer's solutions, fat emulsion 10%, Ringer's injection, Normosol R, aminophylline, amphotericin B with or without hydrocortisone sodium phosphate, ascorbic acid injection, bleomycin sulfate, cal-cium gluconate, cephapirin sodium, chloramphenicol sodium succinate, clindamycin phosphate, dimenhydrinate, dopamine HCl, erythromycin gluceptate, isoproterenol HCl, lidocaine HCl, methylprednisolone sodium succinate, metronidazole with sodium succinate, nafcillin sodium, norepinephrine bitartrate, potassium chloride, prednisolone sodium succinate, promazine HCl, sodium bicarbonate, verapamil HCl, and vitamin B-complex with or with-out vitamin C. Heparin compatibility information conﬂicts or is dependent on diluent or concentration factors with the following drugs or so-lutions: dextrose-saline combinations, dextrose in water, lactated Ringer's injection, saline solutions, ampicillin sodium, cephalothin sodium, dobutamine HCl, hydrocortisone sodium succinate, me-thicillin sodium, oxytetracycline HCl, penicillin G sodium/potassi-um, and tetracycline HCl. Compatibility is dependent upon factors such as p H, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more speciﬁc information. Heparin sodium is reported physically incompatible when mixed with the following solutions or drugs: sodium lactate 1/6 M, ami-kacin sulfate, chlorpromazine HCl, codeine phosphate, cytara-bine, daunorubicin HCl, diazepam, doxorubicin HCl, droperidol HCl with and without fentanyl citrate, erythromycin lactobionate, gentamicin sulfate, hyaluronidase, kanamycin sulfate, levorphanol bitartrate, meperidine HCl, methadone HCl, morphine sulfate, pentazocine lactate, phenytoin sodium, polymyxin B sulfate, strep-tomycin sulfate, and vancomycin HCl. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Heparin Sodium Injection: 1000 U/m L, 2000 U/m L, 2500 U/m L, 5000 U/m L, 10,000 U/m L, 20,000 U/m L, & 40,000 U/m L in 0. 5, 1, 2, 4, 5, 10, and 30 m L amps, vials and multi-dose vials (depending on concentration and manufacturer); generic; (Rx). Heparin Unit-Dose Sodium Injection: 1000 U/dose, 2500 U/dose, 5000 U/dose, 7500 U/dose, 10,000 U/dose and 20,000 U/dose in 1, 10, and 30 m L Dosette vials, 0. 5 m L & 1 m L Tubex, 0. 5, 1, 4 and 10 m L vials, and 1 m L ﬁll in 2 m L Carpuject (depending on concentration and manufacturer); generic; (Rx) Heparin Sodium and 0. 9% Sodium Chloride Injection: 1000 and 2000 units in 500 m L and 1000 m L, respectively; in Viaﬂex (Baxter Healthcare); (Rx)	pppbs.pdf
HETASTA RCH 451 Heparin Sodium and 0. 45% Sodium Chloride Injection: 12,500 and 25,000 units in 250 m L (12,500 only) and 500 m L; (Abbott); (Rx) Heparin Sodium Lock Flush Solution— (IV use) Injection: 1 unit/ m L in 1, 2, 2. 5, 5 & 10 m L syringes; 10 U/m L and 100 U/m L in 1, 2, 5, 10 m L (regular and preservative free), 30 m L and 50 m L vials; 1 (reg-ular and preservative free) and 2 m L Dosette vials; 1, 2. 5 m L Dosette cartridge needle units; 1 m L amps; 1, 2, 2. 5, 3, and 5 m L disposable syringes; Hep-Lock® and Hep-Loc® U/P (Elkins-Sinn); Hepﬂush-10® (American Pharmaceutical Partners); Heparin I. V. Flush (Medeﬁl); generic; (Rx) HETASTARCH (het-a-starch) COLLOID VOLUME EXPANDER Prescriber Highlights TT Volume expander used to treat hypovolemia where colloidal therapy required TT Contraindications: Severe heart failure, severe bleeding disorders, & patients in oliguric or anuric renal failure TT Caution: Thrombocytopenia, patients undergoing CNS surgery; liver disease TT May cause volume overload: Use with caution in patients with renal dysfunction, congestive heart failure, or pulmo-nary edema TT Adverse Effects: Coagulopathies possible; too rapid administration to small animals (especially cats) may cause nausea/vomiting; hypersensitivity reactions pos-sible but very rare Uses/Indications In hypovolemic patients where total protein is less than 3. 5 g/dl and crystalloid therapy is likely to reduce this level further, colloid ther-apy (plasma, dextran or hetastarch) should be considered as part of intravascular volume restoration. It is often used when colloid therapy is required and blood products are unavailable, or time is of the essence and the wait for crossmatching is unacceptable. Because of the expense, hetastarch is generally used only in small animals. Pharmacology/Actions Hetastarch acts as a plasma volume expander by increasing the on-cotic pressure within the intravascular space similarly to either dex-tran or albumin. Maximum volume expansion occurs within a few minutes of the completion of infusion. Duration of effect is vari-able, but may persist for 24 hours or more. When added to whole blood in humans, hetastarch causes an increase in erythrocyte sedi-mentation rate. Pharmacokinetics Lower molecular weight molecules, (less than 50,000) are rapidly excreted by the kidneys; larger molecules are slowly degraded enzy-matically to a size where they then can be excreted. About 40% of a dose is excreted in the ﬁrst 24 hours after infusion. After about 2 weeks, practically all of the drug is excreted. Contraindications/Precautions/Warnings In humans, hetastarch is contraindicated in patients with severe heart failure, severe bleeding disorders and patients in oliguric or anuric renal failure. It is believed that signiﬁcant bleeding can occur if hetastarch is used in animals with compromised coagulation systems. For exam-ple, use in patients with von Willebrand's disease could signiﬁcantly increase the risk for bleeding. Because of the danger of volume overload, use of hetastarch for the treatment of shock not accompanied by hypovolemia may be hazardous. As it has no oxygen carrying capacity, hetastarch is not a replacement for whole blood or red blood cells. Because of its effect on platelets, hetastarch should be used with caution in patients with thrombocytopenia and with extreme cau-tion in patients undergoing CNS surgery. Because of its effects on indirect serum bilirubin levels, hetastarch should be used with cau-tion in patients with liver disease. Because of the threat of volume overload, hetastarch should be used in caution in patients with renal dysfunction, congestive heart failure or pulmonary edema. Adverse Effects Hetastarch can affect platelet function and clotting tests can be transiently prolonged. It is less antigenic than dextran, but can cause sensitivity reactions and interfere with antigen-antibody test-ing. Anaphylactic reactions and coagulopathies are considered to occur rarely, however. When given via rapid infusion to cats, hetastarch may cause signs of nausea and vomiting; if administered over 15-30 minutes, these signs are eliminated. At recommended dosages, hetastarch may cause minor changes in clotting times and platelet counts due to direct (precipitation of factor VIII) and dilutional causes. Clinically these effects are usually insigniﬁcant, but patients with preexisting coagulopathies may be predisposed to further bleeding. In humans, increases in serum indirect bilirubin have occurred occasionally. No effect on other liver function tests were noted and the increases subsided over several days. Serum amylase levels may be falsely elevated for several days after hetastarch is administered. While clinically insigniﬁcant, the changes may preclude using serum amylase to diagnosis or monitor patients with acute pancreatitis. Circulatory overload leading to pulmonary edema is possible, particularly when large dosages are administered to patients with diminished renal function. Do not give intramuscularly as bleed-ing, bruising, or hematomas may occur. Reproductive/Nursing Safety Hetastarch's safety during pregnancy has not been established, but no untoward effects have apparently been reported. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduc-tion studies and no adequate studies in humans. ) It is not known whether hetastarch is excreted in milk, but it is unlikely to pose much risk to offspring. Overdosage/Acute Toxicity Overdosage could result in volume overload in susceptible patients. Dose and monitor ﬂuid status carefully. Drug Interactions Hetastarch apparently has no drug interactions that are clinically signiﬁcant.	pppbs.pdf
452 HYALURONATE Doses T ! DOGS/CAT S: For use as a plasma volume expander in shock: Note : Rate of ad-ministration is determined by individual patient requirements (i. e., blood volume, indication, and patient response); adequate monitoring for successful treatment of shock is mandatory. The following dosages are NOT “Give and forget”; they should be used as general guidelines for treatment. a) Shock bolus (resuscitation): 10-20 m L/kg in dogs and 5-10 m L/kg in cats. (Petrollini 2003) b) Shock bolus (resuscitation): 10-20 m L/kg in dogs and 5-10 m L/kg in cats. As an infusion: Dogs: 1-2 m L/kg/hr; not to exceed 20 m L/ kg in a 24 hour period; Cats: 1-2 m L/kg/hr; not to exceed 10 m L/kg in a 24 hour period (Hopper 2006c) c) Dogs: 20 m L/kg /day; cats: 10/m L/kg/day. Rate of adminis-tration depends on the condition treated. For emergent situ-ations, it can be given as a slow bolus over 15-30 minutes. For supporting colloid oncotic pressure in hypoalbuminemic patients, it can be given as a 24-hour infusion with low-rate crystalloid infusion. (Martin 2004) d) For shock resuscitation, standard dose is 20 m L/kg. The dose is given as an IV bolus (slower in the cat). When used for col-loid oncotic support the dose is given over 24 hours. Rapid administration to cats can cause nausea and vomiting. Pa-tients may have elevations in prothrombin time and activat-ed partial thromboplastin time without evidence of bleeding. (Barton 2002a) T ! HORSES: a) Adult horses: 8-10 m L/kg/day. Foals who require rapid vol-ume support: 3-5 m L/kg in addition to crystalloids. May also be used in horses that are hypo-oncotic, but well hydrated at: 0. 5-1 m L/kg per hour, up to 10 m L/kg/day. (Magdesian 2004) Monitoring T ! Other than the regular monitoring performed in patients that would require volume expansion therapy, there is no inordinate monitoring required speciﬁc to hetastarch therapy, but consider monitoring coagulation parameters particularly in high risk pa-tients or when using high dosages of hetastarch Client Information T ! As hetastarch is used in an in-patient setting only, the two factors to consider when communicating with clients are the drug's cost and the reasons for using colloid therapy. Chemistry/Synonyms A synthetic polymer derived from a waxy starch, hetastarch is com-posed primarily of amylopectin. T o avoid degradation by serum amylase, hydroxyethyl ether groups are added to the glucose units. It has an average molecular weight of 450,000, but ranges in size from about MW 10,000-1,000,000. Hetastarch occurs as a white powder. It is very soluble in water and insoluble in alcohol. The commercially available colloidal solution appears as a clear, pale yellow to amber solution. In 500 m L of the commercial prepa-ration containing hetastarch 6% and 0. 9% sodium chloride, there are 77 m Eq of sodium and chloride. It has an osmolality of 310 m Osm/L and a p H of about 5. 5. The product in lactated electrolyte solution (Hextend ®) contains 143 m Eq/L of sodium, 124 m Eq/L of chloride, 28 m Eq/L of lactate, 5 m Eq/L of calcium, 3 m Eq/L of potassium, 0. 9 m Eq/L of magne-sium, and 0. 99 grams/L of dextrose. These values approximate what is found in human plasma. Hetastarch may also be known by the following synonyms: etheriﬁed starches, HES, and hydroxyethyl starch; many trade names are available. Storage/Stability/Compatibility Hetastarch 6% in 0. 9% Na Cl or lactated electrolyte should be stored at temperatures less than 40°C; freezing should be avoided. Exposure to temperature extremes may result in formation of a crystalline precipitate or a color change to a turbid deep brown. Do not use should this occur. The following drugs are reported compatible at Y-sites with het-astarch: cimetidine, diltiazem, enalaprilat. For Hextend®: Do not administer simultaneously with blood through the same adminis-tration set as there is a risk of coagulation. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Hetastarch Injection: 6% (6 g/100 m L) in 0. 9% sodium chloride in 500 m L IV infusion bottles & single-dose containers; Hespan® (B. Braun Medical); 6% Hetastarch (Hospira); (Rx) Hetastarch Injection: 6% (6 g/100 m L) in lactated electrolyte in 500 m L IV infusion single-dose containers; Hextend® (Hospira), generic; (Rx) HYALURONATE SODIUM SODIUM HYALURONATE (hy-al-yoo-ron-nate) Hyalovet®, Hyvisc®, Legend® MUCOPOLYSACCHARIDE Prescriber Highlights TT Parenteral, high viscosity mucopolysaccharide used for synovitis TT Contraindications: None on label TT Adverse Effects: Local reactions possible TT Different products have different dosages, etc; check la-bel before using Uses/Indications Hyaluronate sodium (HS) is useful in the treatment of synovitis not associated with severe degenerative joint disease. It may be helpful to treat secondary synovitis in conditions where full thickness carti-lage loss exists. The choice of a high molecular weight product (MW >1x106) versus a low molecular weight one is quite controversial. One au-thor (Nixon 1992) states that “... low molecular weight products (which tend to be less expensive) can be equally efﬁcacious in ame-liorating signs of joint disease. When synovial adhesions and pan-nus are to be avoided (as in most surgeries for carpal and fetlock fracture fragment removal), higher molecular weight preparations are recommended because they inhibit proliferation of synovial ﬁbroblasts. ”	pppbs.pdf
HYDRALAZINE HCL 453 Pharmacology/Actions Hyaluronate sodium (HS) is found naturally in the connective tis-sue of both man and animals and is identical chemically regardless of species. Highest concentrations found naturally are in the syn-ovial ﬂuid, vitreous of the eye and umbilical cord. Surfaces of artic-ular cartilage are covered with a thin layer of a protein-hyaluronate complex; hyaluronate is also found in synovial ﬂuid and the car-tilage matrix. The net effects in joints include a cushioning effect, reduction of protein and cellular inﬂux into the joint, and a lubri-cating effect. Hyaluronate has a direct antiinﬂammatory effect in joints by scavenging free radicals and suppressing prostaglandins. Pharmacokinetics No speciﬁc information located. Contraindications/Precautions/Warnings No contraindications to HS's use are noted on the label. HS should not be used as a substitute for adequate diagnosis; radiographic examinations should be performed to rule out serious fractures. Do not perform intra-articular injections through skin that has been recently ﬁred or blistered, or that has excessive scurf and counterir-ritants on it. Adverse Effects Some patients may develop local reactions manifested by heat, swelling, and/or effusion. Effects generally subside within 24-48 hours; some animals may require up to 96 hours for resolution. No treatment for this effect is recommended. When used in combina-tion with other drugs, incidence of ﬂares may actually be higher. No systemic adverse effects have been noted. Reproductive/Nursing Safety While HS is unlikely to cause problems, safe use in breeding animals has not been established and most manufacturers caution against its use in these animals. Overdosage/Acute Toxicity Acute toxicology studies performed in horses have demonstrated no systemic toxicity associated with overdoses. Drug Interactions/Laboratory Considerations None were noted. Doses T ! HORSES: a) Because of the differences in the commercially available products, see each individual product's label for speciﬁc dos-ing information. T ! DOGS: a) For the adjunctive treatment of synovitis (rather than the presence of a damaged articular cartilage): Using a high mo-lecular weight compound: 3-5 mg intra-articularly using sterile technique at weekly intervals. Long-term effects are not achieved. (Bloomberg 1992) Client Information T ! HS should be administered by a veterinarian only, using aseptic technique. Chemistry/Synonyms Hyaluronate sodium (HS) is the sodium salt of hyaluronic acid which is a naturally occurring high-viscosity mucopolysaccharide. Hyaluronate sodium may also be known as: hyaluronic acid, and natrii hyaluronas; many trade names are available. Storage/Stability Store at room temperature or refrigerate depending on the product used—check label; do not freeze. Protect from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Hyaluronate Sodium: (average MW of 500,000-730,000) 20 mg/m L in 2 m L disposable syringes; Hyalovet® (Fort Dodge); (Rx). Approved for use in horses not intended for food. Hyaluronate Sodium Injection: 2 m L vial for IA administration; 4 m L, & 20 m L vials for IV administration; Legend ® (Bayer); (Rx); Ap-proved for use in horses not intended for food. Hyaluronate Sodium Injection: 11 mg/m L in 2 m L syringes; Hyvisc® (Boehringer Ingelheim); (Rx). Approved for use in horses not in-tended for food. Hyaluronate Sodium: 10 mg/m L (MW 3. 5 * 106) in 2 m L disposable syringes; Hylartin®V (Pﬁzer); (Rx). Approved for use in horses not intended for food. Hyaluronate Sodium: 10 mg/m L (Avg. MW >1 mm Daltons) 2 m L, 6 m L, 10 m L in 2 m L vials; Hycoat® (Neogen); (Rx). Approved for use in horses, dogs, cats in surgical procedures. There may also be hyaluronate products in oral supplements. HUMAN-LABELED PRODUCTS: None HYDRALAZINE HCL (hye-dral-a-zeen) Apresoline® V ASODILATOR Prescriber Highlights TT Vasodilator drug used primarily for hypertension or ad-junctive treatment of heart failure TT Contraindications: Known hypersensitivity, coronary ar-tery disease, hypovolemia or preexisting hypotension TT Caution: Severe renal disease, intracerebral bleeding, preexisting autoimmune diseases TT Adverse Effects: Hypotension, reﬂex tachycardia, sodium/ water retention (if not given concurrently with a diuretic), or GI distress (vomiting, diarrhea) TT Drug interactions Uses/Indications Primary use of hydralazine in veterinary medicine is as an afterload reducer for the adjunctive treatment in CHF in small animals, par-ticularly if mitral valve insufﬁciency is the primary cause. It is also useful in dogs and cats with large septal defects or severe aortic re-gurgitation. Hydralazine is usually used in cases where enalapril is not effective in clinical improving dogs with mitral insufﬁciency. It is used to treat systemic hypertension, particularly in combination with other drugs (e. g., beta-blockers) to offset hydralazine's tenden-cy to cause reﬂex tachycardia and ﬂuid retention. Pharmacology/Actions Hydralazine acts upon vascular smooth muscle and reduces pe-ripheral resistance and blood pressure. It is believed that hydrala-zine alters cellular calcium metabolism in smooth muscle, thereby interfering with calcium movements and preventing the initiation	pppbs.pdf
454 HYDRALAZINE HCL and maintenance of the contractile state. Hydralazine has more ef-fect on arterioles than on veins. In patients with CHF, hydralazine signiﬁcantly increases cardiac output, and decreases systemic vascular resistance. Cardiac rate may be slightly increased or unchanged, while blood pressure, pul-monary venous pressure, and right atrial pressure may be decreased or unchanged. When used to treat hypertensive patients (without CHF), in-creased heart rate, cardiac output and stroke volume can be noted. The renin-angiotensin system can be activated with a resultant in-crease in sodium and water retention if not given with diuretics or sympathetic blocking drugs. Parenteral hydralazine administration can cause respiratory stimulation. Pharmacokinetics In dogs, hydralazine is rapidly absorbed after oral administration with an onset of action within one hour and peak effects at 3-5 hours. There is a high ﬁrst-pass effect after oral administration. The presence of food may enhance the bioavailability of hydralazine tablets. Hydralazine is widely distributed in body tissues. In humans, approximately 85% of the drug in the blood is bound to plasma proteins. Hydralazine crosses the placenta and very small amounts are excreted into the milk. Hydralazine is extensively metabolized in the liver and approxi-mately 15% is excreted unchanged in the urine. The half-life in hu-mans is usually 2-4 hours, but may be as long as 8 hours. Speciﬁc pharmacokinetic parameters for this drug in veteri-nary species are limited, but the duration of action of hydrala-zine in dogs after oral administration is reportedly 11-13 hours. Vasodilating effects occur within one hour and peak within 3 hours of dosing. Food decreases oral bioavailability in dogs by about 63%. At lower doses there is relatively high ﬁrst pass effect, but this is ap-parently a saturable process as bioavailability increases with dose. N-acetylation is a primary enzymatic pathway for hydralazine me-tabolism and this pathway is mostly absent in dogs leading to con-cerns for increased risks for toxicity. Contraindications/Precautions/Warnings Hydralazine is contraindicated in patients hypersensitive to it and those with coronary artery disease. The drug is listed as contrain-dicated in human patients with mitral valvular rheumatic disease, but it has been recommended for use in small animal patients with mitral valve insufﬁciency. It is recommended not to use the drug in patients with hypovolemia or preexisting hypotension. Hydralazine should be used with caution in patients with se-vere renal disease or intracerebral bleeding. In humans, a syndrome resembling systemic lupus erythematosus (SLE) has been docu-mented after hydralazine use. While this syndrome has not been documented in veterinary patients, the drug should be used with caution in patients with preexisting autoimmune diseases. Adverse Effects The most prevalent adverse effects seen in small animals include: hypotension, reﬂex tachycardia, sodium/water retention (if not given concurrently with a diuretic), and GI distress (vomiting, di-arrhea). Initially, transient weakness and lethargy can occur, but usually resolve in 3-4 days. Other adverse effects documented in humans that could occur include: an SLE-like syndrome, lacrima-tion, conjunctivitis, peripheral neuritis, blood dyscrasias, urinary retention, constipation, and hypersensitivity reactions. Tachycardias may be treated with concomitant digitalis treat-ment or a beta-blocker (Caution: beta-blockers may reduce cardiac performance). Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have un-covered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) Hydralazine is excreted in milk. According to the American Academy of Pediatrics, hydralazine is compatible with breastfeed-ing, but exercise caution. Overdosage /Acute Toxicity Overdoses may be characterized by severe hypotension, tachycar-dia or other arrhythmias, skin ﬂushing, and myocardial ischemia. Cardiovascular system support is the primary treatment modality. Evacuate gastric contents and administer activated charcoal using standard precautionary measures if the ingestion was recent and cardiovascular status has been stabilized. Treat shock using volume expanders without using pressor agents if possible. If a pressor agent is required to maintain blood pressure, the use of a mini-mally arrhythmogenic agent (e. g., phenylephrine or methoxamine) is recommended. Digitalis agents may be required. Monitor blood pressure and renal function diligently. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving hydralazine and may be of signiﬁcance in veterinary patients: !TACE-INHIBITORS : May cause additive hypotensive effect; usually used for therapeutic advantage !TBETA-BLOCKERS : May cause additive hypotensive effect; usually used for therapeutic advantage !TDIAZOXIDE : Potentially could cause profound hypotension !TDIURETICS : May cause additive hypotensive effect; usually used for therapeutic advantage !TFUROSEMIDE : Hydralazine may increase furosemide's renal effects !TMAO INHIBITORS : May cause additive hypotensive effect !TSYMPATHOMIMETICS (e. g., epinephrine ): Hydralazine may cause de-creased pressor effect and may cause additive tachycardia Doses Because of the sodium/water retention associated with this drug it should be given concurrently with a diuretic. Many clinicians rec-ommend adding a venous dilating agent (e. g., nitroglycerin oint-ment) to reduce preload. !TDOGS: For adjunctive therapy in treatment of heart failure: a) Effective dose is 0. 5-3 mg/kg PO q12h. Dose must be titrat-ed, starting with a low dose and titrating upwards. In dogs not receiving ACE inhibitors: Get initial baseline as-sessment (mucous membrane color, capillary reﬁll time, murmur intensity, cardiac size on radiographs, and severity of pulmonary edema). Starting dose is 1 mg/kg PO q12h and repeat assessments made in 12-48 hours. If no response iden-tiﬁed, increase dosage to 2 mg/kg q12h. Repeat assessments as above and increase to 3 mg/kg PO q12h If no response. Can be titrated with or without blood pressure monitoring. If BP cannot be monitored titration is performed more slowly and clinical and radiographic signs are monitored.	pppbs.pdf
HYDROCHLOROTHIAZIDE 455 If blood pressure measurement available, dosage titration can be made more rapidly than above: Measure baseline blood pressure. Administer 1 mg/kg PO. Repeat BP in 1-2 hours and if it has decreased by at least 15 mm Hg, administer q12h from then on. If response inadequate, give another 1 mg/kg and repeat BP measurement in 1-2 hours. This may be re-peated until a cumulative dose of 3 mg/kg has been given within a 12 hour period. The resulting cumulative dose be-comes the dosage to be given q12h. For dogs with acute, fulminant heart failure due to severe mi-tral regurgitation and not receiving ACE inhibitors: 2 mg/kg along with IV furosemide. May cause hypotension, but the risks of not effectively treating fulminant pulmonary edema outweigh the risks of treatment. For dogs receiving ACE inhibitors: Give hydralazine with cau-tion as severe hypotension may occur if dosage not titrated carefully. Begin dosing at 0. 5 mg/kg with blood pressure moni-toring and increase in 0. 5 mg/kg increments until a response is identiﬁed to a maximum of 3 mg/kg. Consider referral. (Kittleson 2000), (Kittleson 2007) b) When an ACEI is not well tolerated or affordable: hydrala-zine at 0. 5-2 mg/kg PO q12h with either nitroglycerin oint-ment (H to 1. 5 inches q8-12h cutaneously), or isosorbide dinitrate (0. 5-2 mg/kg PO q8h) (Ware and Keene 2000) For treatment of systemic hypertension: a) 0. 5-2 mg/kg PO two to three times daily (Morgan 1988) b) 0. 5-2 mg/kg PO q12h (Stepian 2006a) T ! CATS: For adjunctive therapy in treatment of heart failure: a) See (a) above “For adjunctive therapy in treatment of heart failure in dogs:”, but start titration at 2. 5 mg (total dose) and if necessary, increase up to 10 mg. (Kittleson 1985b) For treatment of systemic hypertension: a) 2. 5 mg PO twice daily (Morgan 1988) b) 2. 5 mg (total dose) PO q12-24h (Stepian 2006a) T ! HORSES: (Note : ARCI UCGFS Class 3 Drug) For adjunctive therapy in treatment of heart failure (afterload reducer): a) 0. 5 mg/kg IV; for long-term therapy use 0. 5-1. 5 mg/kg PO q12h (Mogg 1999) Monitoring T ! Baseline thoracic radiographs T ! Mucous membrane color T ! Serum electrolytes T ! If possible, arterial blood pressure and venous PO 2 T ! Because blood dyscrasias are a possibility, an occasional CBC should be considered. Client Information T ! Compliance with directions is necessary to maximize the beneﬁts from this drug. T ! Notify veterinarian if the animal's condition deteriorates or if it becomes lethargic, weak or depressed, (signs of hypotension). Chemistry/Synonyms A phthalazine-derivative antihypertensive and vasodilating agent, hydralazine HCl occurs as an odorless, white to off-white crystal-line powder with a melting point between 270-280°C and a p K a of 7. 3. One gram is soluble in approximately 25 m L of water or 500 m L of alcohol. The commercially available injection has a p H of 3. 4-4. Hydralazine may also be known as: apressinum, hydralazini, hydrallazine, idralazina, Alphapress®, Apresolin®, Apresolina®, Bionobal®, Cesoline®, Hidral®, Hydrapres®, Hyperex ®, Hyperphen®, Ipolina®, Nepresol®, Novo-Hylazin®, Nu-Hydral®, Rolazine®, Slow-Apresoline®, and Supres®. Storage/Stability/Compatibility Hydralazine tablets should be stored in tight, light resistant contain-ers at room temperature. The injectable product should be stored at room temperature; avoid refrigeration or freezing. When mixed with most infusion solutions a color change can occur which does not necessarily indicate a loss in potency (if oc-curred over 8-12 hours). Hydralazine is reported to be physically compatible with the fol-lowing infusion solutions/drugs: dextrose-Ringer's combinations, dextrose-saline combinations, Ringer's injection, lactated Ringer's injection, sodium chloride solutions, and dobutamine HCl. Hydralazine is reported to be physically incompatible when mixed with 10% dextrose or fructose and is reported to be physically in-compatible when mixed with the following drugs: aminophylline, ampicillin sodium, chlorothiazide sodium, edetate calcium diso-dium, hydrocortisone sodium succinate, mephentermine sulfate, methohexital sodium, phenobarbital sodium, and verapamil HCl. Compatibility is dependent upon factors such as p H, concentra-tion, temperature, and diluent used; consult specialized references for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Hydralazine HCl Tablets: 10 mg, 25 mg, 50 mg and 100 mg; Apreso-line® (Novartis); generic; (Rx) Hydralazine Injection: 20 mg/m L in 1 m L vials; generic; (Solopak); (Rx) HYDROCHLOROTHIAZIDE (hye-droe-klor-oh-thye-a-zide) Hydro DIURIL® THIAZIDE DIURETIC Prescriber Highlights TT Thiazide diuretic used for nephrogenic diabetes insipidus, hypertension, calcium oxalate uroliths, hypoglycemia, & diuretic for heart failure TT Contraindications: Hypersensitivity; pregnancy (relative contraindication) TT Extreme Caution/Avoid: Severe renal disease, preexisting electrolyte/water balance abnormalities, impaired he-patic function, hyperuricemia, SLE, diabetes mellitus TT Adverse Effects: Hypokalemia, hypochloremic alkalosis, other electrolyte imbalances, hyperuricemia, GI effects TT Many possible drug interactions; lab test interactions	pppbs.pdf
456 HYDROCHLOROTHIAZIDE Uses/Indications In veterinary medicine, furosemide has largely supplanted the use of thiazides as a general diuretic (edema treatment). Thiazides are still used for the treatment of systemic hypertension, nephrogenic diabetes insipidus, and to help prevent the recurrence of calcium oxalate uroliths in dogs. Pharmacology/Actions Thiazide diuretics act by interfering with the transport of sodium ions across renal tubular epithelium possibly by altering the me-tabolism of tubular cells. The principle site of action is at the cor-tical diluting segment of the nephron. Enhanced excretion of so-dium, chloride, and water results. Thiazides increase the excretion of potassium, magnesium, phosphate, iodide, and bromide and decrease the glomerular ﬁltration rate (GFR). Plasma renin and resulting aldosterone levels are increased which contribute to the hypokalemic effects of the thiazides. Bicarbonate excretion is in-creased, but effects on urine p H are usually minimal. Thiazides ini-tially have a hypercalciuric effect, although with continued therapy calcium excretion this is signiﬁcantly decreased. Uric acid excre-tion is decreased by the thiazides. Thiazides can cause or exacerbate hyperglycemia in diabetic patients or induce diabetes mellitus in prediabetic patients. The antihypertensive effects of thiazides are well known and these agents are used extensively in human medicine for treating essential hypertension. The exact mechanism for this effect has not been established. Thiazides paradoxically reduce urine output in patients with diabetes insipidus (DI). They have been used as adjunctive therapy in patients with neurogenic DI and are the only drug therapy for nephrogenic DI. Pharmacokinetics The pharmacokinetics of the thiazides have apparently not been studied in domestic animals. In humans, hydrochlorothiazide is about 65-75% absorbed after oral administration. The onset of diuretic activity occurs in 2 hours; peaks at 4-6 hours. The serum half-life is approximately 5. 6-14. 8 hours and the duration of activ-ity is 6-12 hours. The drug is apparently not metabolized and is excreted unchanged into the urine. Like all thiazides, the antihy-pertensive effects of hydrochlorothiazide may take several days to occur. Contraindications/Precautions/Warnings Thiazides are contraindicated in patients hypersensitive to any one of these agents or to sulfonamides, and in patients with anuria. In humans, their use is inappropriate during pregnancy in women who are otherwise healthy and have only mild edema. Thiazides should be used with extreme caution, if at all, in pa-tients with severe renal disease or with preexisting electrolyte or water balance abnormalities, impaired hepatic function (may pre-cipitate hepatic coma), hyperuricemia, lupus (SLE), or diabetes mellitus. Patients with conditions that may lead to electrolyte or water balance abnormalities (e. g., vomiting, diarrhea, etc. ) should be monitored carefully. Adverse Effects Hypokalemia is one of the most common adverse effects associ-ated with the thiazides but rarely causes clinical signs or progresses, however, monitoring of potassium is recommended with chronic therapy. Hypochloremic alkalosis (with hypokalemia) may develop, es-pecially if there are other causes of potassium and chloride loss (e. g., vomiting, diarrhea, potassium-losing nephropathies, etc. ) or the patient has cirrhotic liver disease. Dilutional hyponatremia and hypomagnesemia may occur. Hyperparathyroid-like effects of hy-percalcemia and hypophosphatemia have been reported in humans, but have not led to effects such as nephrolithiasis, bone resorption, or peptic ulceration. Hyperuricemia can occur, but is usually asymptomatic. Other possible adverse effects include: GI reactions (vomiting, diarrhea, etc. ), hypersensitivity/dermatologic reactions, GU reac-tions (polyuria), hematologic toxicity, hyperglycemia, hyperlipi-demias, and orthostatic hypotension. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), thaizides are categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should be used cau-tiously as a last resort when the beneﬁt of therapy clearly outweighs the risks. ) Thiazides may appear in milk and there have been case reports of newborn human infants developing thrombocytopenia when their mothers received thiazides. Overdosage/Acute Toxicity Acute overdosage may cause electrolyte and water balance prob-lems, CNS effects (lethargy to coma and seizures), and GI effects (hypermotility, GI distress). Transient increases in BUN have been reported. Treatment consists of emptying the gut after recent oral inges-tion using standard protocols. Avoid giving concomitant cathartics as they may exacerbate the ﬂuid and electrolyte imbalances that may ensue. Monitor and treat electrolyte and water balance abnor-malities supportively. Additionally, monitor respiratory, CNS, and cardiovascular status; treat supportively and symptomatically if re-quired. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving hydrochlorothiazide and may be of signiﬁcance in veterinary patients: !TAMPHOTERICIN B : Use with thiazides can lead to an increased risk for severe hypokalemia !TCORTICOSTEROIDS, CORTICOTROPIN : Use with thiazides can lead to an increased risk for severe hypokalemia !TDIAZOXIDE : Increased risk for hyperglycemia, hyperuricemia, and hypotension !TDIGOXIN : Thiazide-induced hypokalemia, hypo-magnesemia, and/ or hypercalcemia may increase the likelihood of digitalis toxicity !TINSULIN : Thiazides may increase insulin requirements !TLITHIUM : Thiazides can increase serum lithium concentrations !TMETHENAMINE : Thiazides can alkalinize urine and reduce meth-enamine effectiveness !TNSAIDS : Thiazides may increase risk for renal toxicity and NSAIDs may reduce diuretic actions of thiazides !TNEUROMUSCULAR BLOCKING AGENTS : Tubocurarine or other non-depolarizing neuromuscular blocking agents response or dura-tion of effect may be increased !TPROBENECID : Blocks thiazide-induced uric acid retention (used to therapeutic advantage)	pppbs.pdf
HYDROCHLOROTHIAZIDE 457 !TQUINIDINE : Half-life may be prolonged by thiazides (thiazides can alkalinize the urine) !TVITAMIN D or CALCIUM SALTS : Hypercalcemia may be exacerbated if thiazides are concurrently administered Laboratory Considerations !TAMYLASE : Thiazides can increase serum amylase values in asymp-tomatic patients and those in the developmental stages of acute pancreatitis (humans) !TCORTISOL : Thiazides can decrease the renal excretion of cortisol !TESTROGEN, URINARY : Hydrochlorothiazide may falsely decrease to-tal urinary estrogen when using a spectrophotometric assay !THISTAMINE : Thiazides may cause false-negative results when test-ing for pheochromocytoma !TPARAT HYROID-FUNCTION TESTS : Thiazides may elevate serum cal-cium; recommend to discontinue thiazides prior to testing !TPHENOLSULFONPHTHALEIN (PSP): Thiazides can compete for secre-tion at proximal renal tubules !TPHENTOLAMINE TEST : Thiazides may give false-negative results !TPROTEIN-BOUND IODINE : Thiazides may decrease values !TTRIIODOTHYRONINE RESIN UPTAKE TEST : Thiazides may slightly re-duce uptake !TTYRAMINE : Thaizides can cause false-negative results Doses !TDOGS: For treatment of nephrogenic diabetes insipidus: a) 0. 5-1 mg/kg PO twice daily (Morgan 1988) b) 2. 5-5 mg/kg PO twice daily (Nichols 1989) For treatment of systemic hypertension: a) 1 mg/kg PO q12-24h; may combine with spironolactone (1-2 mg/kg PO q12 hours) to reduce potassium loss (Brown and Henik 2000) For treatment of recurrent calcium oxalate uroliths with renal hypercalcuria: a) 2 mg/kg q12h PO Note: Do not use in patients with absorp-tive (intestinal) hypercalcuria as hypercalcemia may result (Polzin and Osborne 1985) b) 2. 2 mg/kg PO q12h; repeat urinalysis q2-4 weeks and moni-tor serum electrolytes within several weeks of initial dose and within 2 weeks of dosage adjustment (Lulich, Osborne et al. 2000) c) 2-4 mg/kg PO q12h (Bartges 2006b) As a diuretic: a) For heart failure In combination with furosemide in patients who have become refractory to furosemide alone: 2-4 mg/ kg PO q12h (Kittleson 2000), (Kittleson 2006a) b) For ascites secondary to right-sided heart failure; In addition to furosemide (4-6 mg/kg PO q8h), spironolactone (1-2 mg/kg PO q12h), ACE inhibitors, dietary sodium restriction, etc consider: hydrochlorothiazide at 2 mg/kg initially on an every other day bases; monitor electrolytes and renal func-tion. (Connolly 2006) For treatment of hypoglycemia (with diazoxide): a) 2-4 mg/kg PO twice daily (Morgan 1988) !TCATS: For treatment of systemic hypertension: a) 1 mg/kg PO q12-24h; may combine with spironolactone (1-2 mg/kg PO q12 hours) to reduce potassium loss (Brown and Henik 2000) b) 2-4 mg/kg PO q12h. Not effective as a single agent in cats, and may be contraindicated (e. g., chronic renal failure). Possibly helpful acutely with retinal detachment. (Sparkes 2003b) As a diuretic for heart failure: a) In combination with furosemide in patients who have be-come refractory to furosemide alone: 1-2 mg/kg PO q12h (Kittleson 2000), (Kittleson 2006a) Client Information !TClients should contact veterinarian if clinical signs of water or electrolyte imbalance occur. Clinical signs such as excessive thirst, lethargy, lassitude, restlessness, oliguria, GI distress, or tachycar-dia may indicate electrolyte or water balance problem. Chemistry/Synonyms Hydrochlorothiazide occurs as a practically odorless, slightly bitter-tasting, white, or practically white, crystalline powder with p K as of 7. 9 and 9. 2. It is slightly soluble in water and soluble in alcohol. Hydrochlorothiazide may also be known as: hidroclorotiazida, and hydrochlorothiazidum; many trade names are available. Storage/Stability Hydrochlorothiazide capsules and tablets should be stored at room temperature in well-closed containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None. An oral bolus product containing trichlormethiazide and dex-amethasone (Naquasone®—Schering-Plough) is available for treat-ing udder edema in dairy cattle. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Hydrochlorothiazide Tablets: 25 mg, 50 mg, 100 mg; Hydro DIURIL® (Merck); Hydro-Par® (Parmed); Ezide® (Econo Med); generic; (Rx) Hydrochlorothiazide Capsules: 12. 5 mg; Microzide® Capsules (Wat-son); generic; (Rx) Fixed dose combinations of hydrochlorothiazide with: hydralazine, amiloride, propranolol, triamterene, captopril, reserpine, enalapril, guanethidine, metoprolol, spironolactone, timolol, methyldopa or labetolol are also available.	pppbs.pdf
458 HYDROCODONE BITARTRATE HYDROCODONE BITARTRATE (hye-droe-koe-done) Tussigon®, Hycodan® OPIATE Prescriber Highlights TT Opiate agonist used primarily as an antitussive in dogs TT Contraindications: Hypersensitivity to narcotic analgesic, patients receiving monoamine oxidase inhibitors (MAOIs; Selegiline?), diarrhea caused by a toxic ingestion TT Caution: Patients with hypothyroidism, severe renal insuf-ﬁciency, adrenocortical insufﬁciency (Addison's), head injuries or increased intracranial pressure, acute abdomi-nal conditions, & geriatric or severely debilitated patients TT Use extreme caution in patients suffering from respira-tory diseases when respiratory secretions are increased or when liquids are nebulized into the respiratory tract TT Adverse Effects: Sedation, constipation (with chronic therapy), vomiting, or other GI disturbances TT May mask the clinical signs (cough) of respiratory disease TT Combination product is a C-III controlled substance Uses/Indications Used principally in canine medicine as an antitussive for cough sec-ondary to conditions such as collapsing trachea, bronchitis, or ca-nine upper respiratory infection complex (C-URI, “kennel cough”, canine infectious tracheobronchitis). Its use is generally reserved for harsh, dry, non-productive coughs. Hydrocodone may be useful in treating opioid-related behavior problems in dogs and cats (lick granuloma, stereotypies) by providing an exogenous source of opi-oid, thereby reducing the need for the self-stimulating behavior. Pharmacology/Actions While hydrocodone exhibits the characteristics of other opiate ago-nists, it tends to have a slightly greater antitussive effect than codeine (on a weight basis). The mechanism of this effect is thought to be as a result of direct suppression of the cough reﬂex on the cough center in the medulla. Hydrocodone tends to have a drying effect on respiratory mucosa and the viscosity of respiratory secretions may be increased; the addition of homatropine MBr (in Hycodan® and others) may enhance this effect. Hydrocodone may also be more sedating than codeine, but it is not more constipating. Pharmacokinetics In humans, hydrocodone is well absorbed after oral administration and has a serum half-life of about 3. 8 hours; antitussive effect usu-ally lasts 4-6 hours in adults. There does not appear to be any pharmacokinetic data published in dogs. The antitussive action generally persists for 6-12 hours. Contraindications/Precautions/Warnings Hydrocodone is contraindicated in cases where the patient is hy-persensitive to narcotic analgesics, and those with diarrhea caused by a toxic ingestion (until the toxin is eliminated from the GI tract). All opiates should be used with caution in patients with hypothy-roidism, severe renal insufﬁciency, adrenocortical insufﬁciency (Addison's), and geriatric or severely debilitated patients. Hydrocodone should be used with caution in patients with head injuries or increased intracranial pressure and acute abdomi-nal conditions as it may obscure the diagnosis or clinical course of these conditions. It should be used with extreme caution in patients suffering from respiratory diseases when respiratory secretions are increased or when liquids are nebulized into the respiratory tract. Adverse Effects Side effects that may be encountered with hydrocodone therapy in dogs include sedation, constipation (with chronic therapy), vomit-ing or other GI disturbances. Hydrocodone may mask the clinical signs (cough) of respiratory disease and should not take the place of appropriate speciﬁc treat-ments for the underlying cause of coughs. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). It is unknown if hydrocodone enters milk; use with caution. Overdosage/Acute Toxicity The initial concern with a very large overdose of Hycodan® (or equivalent) would be the CNS, cardiovascular and respiratory de-pression secondary to the opiate effects. There were 21 exposures to hydrocodone bitartrate reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. as-pca. org) during 2001-2006. In these cases 18 were dogs and 3 were cats. No clinical signs were reported in these cases. If the ingestion was recent, emptying the gut using standard protocols should be performed and treatment with naloxone in-stituted as necessary. The homatropine ingredient may give rise to anticholinergic effects that may complicate the clinical picture, but its relatively low toxicity may not require any treatment. For further information on handling opiate or anticholinergic overdoses, refer to the meperidine and atropine monographs, respectively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving hydrocodone and may be of signiﬁcance in veterinary patients: T ! ACEPROMAZINE : Acepromazine and hydrocodone may cause addi-tive hypotension in dogs with collapsing trachea T ! ANTICHOLINERGIC DRUGS : May cause additive anticholinergic effects T ! ANTIDEPRESSANTS, TRICYCLIC & MOA INHIBITORS : Use with hy-drocodone may potentiate the adverse effects associated with the antidepressant T ! CNS DEPRESSANTS, OTHER : Other CNS depressants (e. g., anes-thetic agents, antihistamines, phenothiazines, barbiturates, tran-quilizers, alcohol, etc. ) may cause increased CNS or respiratory depression when used with hydrocodone. Doses T ! DOGS: a) 0. 22 mg/kg PO q6-12h; goal is to suppress coughing with-out causing excessive sedation (Johnson 2000) b) For collapsing trachea: 0. 25 mg/kg PO two to four times a day (Prueter 1988b) c) For cough: G to 1 tablet (5 mg) once to 4 times daily in small and medium sized dogs. For lick granulomas: 5-10 mg (1-2 tablets) per 20 kg of body weight PO three times daily (Trepanier 1999) d) For adjunctive treatment of opioid-related stereotypies, lick granuloma: 0. 22-0. 25 mg/kg PO q8-12h. Supplies exog-enous opioids to decrease the need for self-stimulation. (Sie-bert 2003c)	pppbs.pdf
HYDROCORTISONE 459 T ! CATS: a) For adjunctive treatment of opioid-related stereotypies: 1. 25-5 mg per cat PO q12h. Supplies exogenous opioids to decrease the need for self-stimulation. (Siebert 2003c) Monitoring T ! Clinical efﬁcacy T ! Adverse effects Chemistry/Synonyms A phenanthrene-derivative opiate agonist, hydrocodone bitartrate occurs as ﬁne, white crystals or crystalline powder. One gram is soluble in about 16 m L of water; it is slightly soluble in alcohol. Hydrocodone bitartrate may also be as: hydrocodone tartrate, dihydrocodeinone acid tartrate, hydrocodone acid tartrate, hy-drocodoni bitartras, hydrocone bitartrate, Biocodone®, Dicodid®, Hydrokon®, and Robidone®. Storage/Stability/Compatibility Products should be protected from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 1 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Hydrocodone Bitartrate 5 mg, Homatropine MBr 1. 5 mg Tablets: Tussigon® (Daniels); Hycodan® (Endo); (Rx, C-III) Hydrocodone Bitartrate Syrup: 5 mg, Homatropine MBr 1. 5 mg (per 5 m L) in 473 m L and 3. 8 L; Hycodan® Syrup (Endo); Hydromet® Syrup (Alpharma); Hydromide® Syrup (Major); Hydropane® Syrup (Watson); (Rx, C-III) The products listed above are the ones most commonly used in small animal medicine. Other oral tablets and liquids with hydrocodone are available in combination with decongestants (pseudoephedrine, phenylephrine, or phenylpropanolamine), antihistamines (chlorphe-niramine), analgesics (acetaminophen. ibuprofen or aspirin) or ex-pectorants (guaifenesin). In the USA, there are no hydrocodone prod-ucts available as a sole ingredient. All commercially available products containing hydrocodone are Class-III controlled substances. HYDROCORTISONE HYDROCORTISONE SODIUM SUCCINATE (hye-droe-kor-ti-zone) Cortef®, Solu-Cortef® GLUCOCORTICOID Prescriber Highlights TT “Benchmark” injectable, oral, & topical glucocorticoid (depending on salt) TT Has both mineralocorticoid & glucocorticoid activity TT If using for therapy, goal is to use as much as is required & as little as possible, for as short an amount of time as possible TT Primary adverse effects are “Cushingoid” in nature with sustained use TT Many potential drug & lab interactions Uses/Indications Because of its rapid effect and relatively high mineralocorticoid ef-fect, hydrocortisone sodium succinate (Solu-Cortef®) is the most commonly used form of this medication when an acute glucocorti-coid/mineralocorticoid effect is desired (e. g., acute adrenal insufﬁ-ciency). Corticosteroids have not been shown beneﬁcial in treating hypovolemic shock, but low dose glucocorticoids probably reduce mortality associated with septic shock. Glucocorticoids have been used in an attempt to treat practically every malady that afﬂicts man or animal, but there are three broad uses and dosage ranges for use of these agents. 1) Replacement of glucocorticoid activity in patients with adrenal insufﬁciency, 2) as an antiinﬂammatory agent, and 3) as an immunosuppressive. Among some of the uses for glucocorticoids include treatment of: endocrine conditions (e. g., adrenal insufﬁciency), rheumatic dis-eases (e. g., rheumatoid arthritis), collagen diseases (e. g., systemic lupus), allergic states, respiratory diseases (e. g., asthma), dermato-logic diseases (e. g., pemphigus, allergic dermatoses), hematologic disorders (e. g., thrombocytopenias, autoimmune hemolytic ane-mias), neoplasias, nervous system disorders (increased CSF pres-sure), GI diseases (e. g., ulcerative colitis exacerbations), and renal diseases (e. g., nephrotic syndrome). Some glucocorticoids are used topically in the eye and skin for various conditions or are injected intra-articularly or intra-lesionally. The above listing is certainly not complete. Pharmacology/Actions Glucocorticoids have effects on virtually every cell type and system in mammals. An overview of the effects of these agents follows: Cardiovascular System : Glucocorticoids can reduce capillary per-meability and enhance vasoconstriction. A relatively clinically in-signiﬁcant positive inotropic effect can occur after glucocorticoid administration. Increased blood pressure can result from both the drugs' vasoconstrictive properties and increased blood volume that may be produced. Cells : Glucocorticoids inhibit ﬁbroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lympho-cytes, and the cellular response to mediators of inﬂammation. Glucocorticoids stabilize lysosomal membranes. CNS/Autonomic Nervous System : Glucocorticoids can lower seizure threshold, alter mood and behavior, diminish the response to py-rogens, stimulate appetite, and maintain alpha rhythm. Glucocor-ticoids are necessary for normal adrenergic receptor sensitivity. Endocrine System : When animals are not stressed, glucocorticoids will suppress the release of ACTH from the anterior pituitary, thereby reducing or preventing the release of endogenous corticos-teroids. Stress factors (e. g., renal disease, liver disease, diabetes) may sometimes nullify the suppressing aspects of exogenously admin-istered steroids. Release of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), prolactin, and luteinizing hormone (LH) may all be reduced when glucocorticoids are ad-ministered at pharmacological doses. Conversion of thyroxine (T 4) to triiodothyronine (T 3) may be reduced by glucocorticoids; and plasma levels of parathyroid hormone increased. Glucocorticoids may inhibit osteoblast function. Vasopressin (ADH) activity is re-duced at the renal tubules and diuresis may occur. Glucocorticoids inhibit insulin binding to insulin-receptors and the post-receptor effects of insulin. Hematopoietic System : Glucocorticoids can increase the numbers of circulating platelets, neutrophils, and red blood cells, but platelet aggregation is inhibited. Decreased amounts of lymphocytes (pe-ripheral), monocytes, and eosinophils are seen as glucocorticoids can sequester these cells into the lungs and spleen and prompt de-	pppbs.pdf
460 HYDROCORTISONE creased release from the bone marrow. Removal of old red blood cells is diminished. Glucocorticoids can cause involution of lym-phoid tissue. GI Tract and Hepatic System : Glucocorticoids increase the secretion of gastric acid, pepsin, and trypsin. They alter the structure of mu-cin and decrease mucosal cell proliferation. Iron salts and calcium absorption are decreased while fat absorption is increased. Hepatic changes can include increased fat and glycogen deposits within he-patocytes,increased serum levels of alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT). Signiﬁcant increases can be seen in serum alkaline phosphatase levels. Glucocorticoids can cause minor increases in BSP (bromosulfophthalein) retention time. Immune System (also see Cells and Hematopoietic System): Glucocorticoids can decrease circulating levels of T-lymphocytes; inhibit lymphokines; inhibit neutrophil, macrophage, and mono-cyte migration; reduce production of interferon; inhibit phagocyto-sis and chemotaxis; antigen processing; and diminish intracellular killing. Speciﬁc acquired immunity is affected less than nonspeciﬁc immune responses. Glucocorticoids can antagonize the comple-ment cascade and mask the clinical signs of infection. Mast cells are decreased in number and histamine synthesis is suppressed. Many of these effects only occur at high or very high doses and there are species differences in response. Metabolic effects : Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body (e. g., abdomen) and adipose tissue can be redistributed away from the extremities to the trunk. Fatty acids are mobilized from tissues and their oxi-dation is increased. Plasma levels of triglycerides, cholesterol, and glycerol are increased. Protein is mobilized from most areas of the body (not the liver). Musculoskeletal : Glucocorticoids may cause muscular weakness (also caused if there is a lack of glucocorticoids), atrophy, and os-teoporosis. Bone growth can be inhibited via growth hormone and somatomedin inhibition, increased calcium excretion, and inhibi-tion of vitamin D activation. Resorption of bone can be enhanced. Fibrocartilage growth is also inhibited. Ophthalmic : Prolonged corticosteroid use (both systemic or topically to the eye) can cause increased intraocular pressure and glaucoma, cataracts, and exophthalmos. Renal, Fluid, & Electrolytes : Glucocorticoids can increase potassium and calcium excretion; sodium and chloride reabsorption and ex-tracellular ﬂuid volume. Hypokalemia and/or hypocalcemia occur rarely. Diuresis may occur following glucocorticoid administration. Skin: Thinning of dermal tissue and skin atrophy can be seen with glucocorticoid therapy. Hair follicles can become distended and alopecia may occur. Pharmacokinetics In humans, hydrocortisone is readily absorbed after oral adminis-tration. Hydrocortisone sodium succinate is administered paren-terally, and absorption is rapid after IM administration. Contraindications/Precautions/Warnings Systemic use of glucocorticoids are generally considered contrain-dicated in systemic fungal infections (unless used for replacement therapy in Addison's), when administered IM in patients with id-iopathic thrombocytopenia, and in patients hypersensitive to a particular compound. Use of sustained-release injectable gluco-corticoids is considered contraindicated for chronic corticosteroid therapy of systemic diseases. Animals that have received glucocorticoids systemically other than with “burst” therapy, should be tapered off the drugs. Patients who have received the drugs chronically should be tapered off slowly as endogenous ACTH and corticosteroid function may re-turn slowly. Should the animal undergo a “stressor” (e. g., surgery, trauma, illness, etc. ) during the tapering process or until normal adrenal and pituitary function resume, additional glucocorticoids should be administered. Adverse Effects Adverse effects are generally associated with long-term administra-tion of these drugs, especially if given at high dosages or not on an alternate day regimen. Effects generally manifest as clinical signs of hyperadrenocorticism. When administered to young, grow-ing animals, glucocorticoids can retard growth. Many of the po-tential effects, adverse and otherwise, are outlined above in the Pharmacology section. In dogs, polydipsia (PD), polyphagia (PP), and polyuria (PU), may all be seen with short-term “burst” therapy as well as with alternate-day maintenance therapy on days when drug is given. Ad-verse effects in dogs can include: dull, dry haircoat, weight gain, panting, vomiting, diarrhea, elevated liver enzymes, pancreatitis, GI ulceration, lipidemias, activation or worsening of diabetes mel-litus, muscle wasting and behavioral changes (depression, lethargy, viciousness). Discontinuation of the drug may be necessary; chang-ing to an alternate steroid may also alleviate the problem. With the exception of PU/PD/PP, adverse effects associated with antiinﬂam-matory therapy are relatively uncommon. Adverse effects associated with immunosuppressive doses are more common and potentially more severe. Cats generally require higher dosages than dogs for clinical effect, but tend to develop fewer adverse effects. Occasionally, polydipsia, polyuria, polyphagia with weight gain, diarrhea, or depression can be seen. Long-term, high dose therapy can lead to “Cushingoid” effects. Reproductive/Nursing Safety Glucocorticoids are probably necessary for normal fetal develop-ment. They may be required for adequate surfactant production, myelin, retinal, pancreatic, and mammary development. Excessive dosages early in pregnancy may lead to teratogenic effects. In horses and ruminants, exogenous steroid administration may induce par-turition when administered in the latter stages of pregnancy. In hu-mans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Glucocorticoids unbound to plasma proteins will enter milk. High dosages or prolonged administration to mothers may poten-tially inhibit the growth of nursing newborns. Overdosage/Acute Toxicity Glucocorticoids when given short-term are unlikely to cause harm-ful effects, even in massive dosages. One incidence of a dog develop-ing acute CNS effects after accidental ingestion of glucocorticoids has been reported. Should clinical signs occur, use supportive treat-ment if required. Chronic usage of glucocorticoids can lead to serious adverse ef-fects. Refer to Adverse Effects above for more information.	pppbs.pdf
HYDROCORTISONE 461 Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving hydrocortisone and may be of signiﬁcance in veterinary patients: !TAMPHOTERICIN B : Administered concomitantly with glucocorti-coids may cause hypokalemia; in humans, there have been cases of CHF and cardiac enlargement reported after using hydrocor-tisone to treat Amphotericin B adverse effects !TANTICHOLINESTERASE AGENTS (e. g., pyridostigmine, neostigmine, etc. ): In patients with myasthenia gravis, concomitant gluco-corticoid and anticholinesterase agent administration may lead to profound muscle weakness. If possible, discontinue anticho-linesterase medication at least 24 hours prior to corticosteroid administration !TASPIRIN : Glucocorticoids may reduce salicylate blood levels !TBARBITURATES : May increase the metabolism of glucocorticoids and decrease ﬂumethasone blood levels !TCYCLOPHOSPHAMIDE : Glucocorticoids may inhibit the hepatic metabolism of cyclophosphamide; dosage adjustments may be required !TCYCLOSPORINE : Concomitant administration of glucocorticoids and cyclosporine may increase the blood levels of each by mutu-ally inhibiting the hepatic metabolism of each other; the clinical signiﬁcance of this interaction is not clear !TDIURETICS, POTASSIUM-DEPLETING (e. g., spironolactone, triamterene ): Administered concomitantly with glucocorticoids may cause hypokalemia !TEPHEDRINE : May reduce hydrocortisone blood levels !TESTROGENS : The effects of hydrocortisone and, possibly, other glucocorticoids, may be potentiated by concomitant administra-tion with estrogens !TINSULIN : Insulin requirements may increase in patients receiving glucocorticoids !TKETOCONAZOLE and other AZOLE ANTIFUNGALS : May decrease the me-tabolism of glucocorticoids and increase hydrocortisone blood levels; ketoconazole may induce adrenal insufﬁciency when glu-cocorticoids are withdrawn by inhibiting adrenal corticosteroid synthesis !TMACROLIDE ANTIBIOTICS (erythromycin, clarithromycin ): May de-crease the metabolism of glucocorticoids and increase hydrocor-tisone blood levels !TMITOTANE : May alter the metabolism of steroids; higher than usu-al doses of steroids may be necessary to treat mitotane-induced adrenal insufﬁciency !TNSAID s: Administration of ulcerogenic drugs with glucocorticoids may increase the risk of gastrointestinal ulceration !TPHENOBARBITAL : May increase the metabolism of glucocorticoids and decrease hydrocortisone blood levels !TRIFAMPIN : May increase the metabolism of glucocorticoids and decrease hydrocortisone blood levels !TVACCINES : Patients receiving corticosteroids at immunosuppres-sive dosages should generally not receive live attenuated-virus vaccines as virus replication may be augmented; a diminished immune response may occur after vaccine, toxoid, or bacterin administration in patients receiving glucocorticoids !!WARFARIN : Hydrocortisone may affect INR's; monitor Laboratory Considerations !TGlucocorticoids may increase serum cholesterol !TGlucocorticoids may increase urine glucose levels !TGlucocorticoids may decrease serum potassium !TGlucocorticoids can suppress the release of thyroid stimulat-ing hormone (TSH) and reduce T3 & T4 values. Thyroid gland atrophy has been reported after chronic glucocorticoid ad-ministration. Uptake of I131 by the thyroid may be decreased by glucocorticoids. !TReactions to skin tests may be suppressed by glucocorticoids !TFalse-negative results of the nitroblue tetrazolium test for systemic bacterial infections may be induced by glucocorticoids !TGlucocorticoids may cause neutrophilia within 4-8 hours after dosing and return to baseline within 24-48 hours after drug dis-continuation !TGlucocorticoids can cause lymphopenia which can persist for weeks after drug discontinuation in dogs Doses !TDOGS: For adjunctive therapy for adrenocortical insufﬁciency: a) For acute hypoadrenocortical crisis: Hydrocortisone sodium succinate/phosphate 0. 5-0. 625 mg/kg/hr as an IV infusion. (Mooney 2003) b) For glucocorticoid “coverage” in animals that have iatrogenic secondary adrenocortical insufﬁciency and/or HPA suppres-sion: Animals exhibiting mild to moderate signs of glucocor-ticoid deﬁciency: 0. 2-0. 5 mg/kg PO every day. For animals with HPA suppression undergoing a “stress” fac-tor: Hydrocortisone sodium succinate 4-5 mg/kg just before and after stressful events (e. g., major surgery). Continue with lower dosages until at least 3rd post-operative day. Access to a water-soluble form of glucocorticoid should be available should animal “collapse. ” (Kemppainen 1986) c) For adrenalectomy in patients with hyperadrenocorticism: Soluble salt of hydrocortisone 4-5 mg/kg IV either 1 hour prior to surgery or at the time of anesthesia induction. May also be added to IV ﬂuids and infused during surgery. Re-peat dosage at end of procedure; may give IM or IV. Glu-cocorticoid supplementation must be maintained using an oral product (initially predniso(lo)ne 0. 5 mg/kg twice daily, cortisone acetate 2. 5 mg/kg twice daily, or dexamethasone 0. 1 mg/kg once daily). Slowly taper to maintenance levels (predniso(lo)ne 0. 2 mg/kg once a day, or cortisone acetate 0. 5 mg/kg twice daily) over 7-10 days. Should complica-tions develop during the taper, reinitiate doses at 5 times the maintenance dose. Most dogs can stop exogenous steroid therapy in about 2 months (based on an ACTH stimulation test). (Peterson 1986) For adjunctive therapy of septic shock: a) 0. 08 mg/kg/hr IV. Low-dose hydrocortisone infusions can re-duce the time that vasopressors are required and lead to ear-lier resolution of sepsis-induced organ dysfunction. (Crowe 2002) For glucocorticoid (antiinﬂammatory) activity: a) 5 mg/kg PO every 12 hours; 5 mg/kg (salt not speciﬁed) IV or IM once daily (Jenkins 1985) b) 4. 4 mg/kg PO q12h (Kirk 1989) !TCATS: For glucocorticoid (antiinﬂammatory) activity: a) 5 mg/kg PO, IV or IM every 12 hours (Davis 1985) b) 4. 4 mg/kg PO q12h (Kirk 1989)	pppbs.pdf
462 HYDROGEN PEROXIDE 3% (ORAL) TFor adjunctive therapy of septic shock: a) 0. 08 mg/kg/hr IV. Low-dose hydrocortisone infusions can re-duce the time that vasopressors are required and lead to ear-lier resolution of sepsis-induced organ dysfunction. (Crowe 2002) T ! CATTLE: For adjunctive treatment of photosensitization reactions: a) 100-600 mg (salt not speciﬁed) in 1000 m L of 10% dextrose saline IV or SC. (Black 1986) T ! HORSES: (Note : ARCI UCGFS Class 4 Drug) As a glucocorticoid: a) Hydrocortisone sodium succinate: 1-4 mg/kg as an IV infu-sion (Robinson 1987) Monitoring Monitoring of glucocorticoid therapy is dependent on its reason for use, dosage, agent used (amount of mineralocorticoid activity), dosage schedule (daily versus alternate day therapy), duration of therapy, and the animal's age and condition. The following list may not be appropriate or complete for all animals; use clinical assess-ment and judgment should adverse effects be noted: T ! Weight, appetite, signs of edema T ! Serum and/or urine electrolytes T ! otal plasma proteins, albumin T ! Blood glucose T ! Growth and development in young animals T ! ACTH stimulation test if necessary Client Information T ! Clients should carefully follow the dosage instructions and should not discontinue the drug abruptly without consulting with the veterinarian beforehand. T ! Clients should be briefed on the potential adverse effects that can be seen with these drugs and instructed to contact the veterinar-ian should these effects become severe or progress. Chemistry/Synonyms Also known as compound F or cortisol, hydrocortisone is secreted by the adrenal gland. Hydrocortisone occurs as an odorless, white to practically white, crystalline powder. It is very slightly soluble in water and sparingly soluble in alcohol. Hydrocortisone is adminis-tered orally. Hydrocortisone sodium succinate occurs as an odorless, white to nearly white, hygroscopic, amorphous solid. It is very soluble in both water and alcohol. Hydrocortisone sodium succinate injection is administered via IM or IV routes. Hydrocortisone may also be known as: antiinﬂammatory hor-mone, compound F, cortisol, hydrocortisonum, 17-hydroxycorti-costerone, and NSC-10483; many trade names are available. Storage/Stability/Compatibility Hydrocortisone tablets should be stored in well-closed containers. The cypionate oral suspension should be stored in tight, light re-sistant containers. All products should be stored at room tempera-ture (15-30°C); avoid freezing the suspensions or solutions. After reconstituting solutions, only use products that are clear. Discard unused solutions after 3 days. Hydrocortisone sodium succinate is reportedly physically com-patible with the following solutions and drugs: dextrose-Ringer's injection combinations, dextrose-Ringer's lactate injection combi-nations, dextrose-saline combinations, dextrose injections, Ringer's injection, lactated Ringer's injection, sodium chloride injections, amikacin sulfate, aminophylline, amphotericin B (limited quan-tities), calcium chloride/gluconate, cephalothin sodium (not in combination with aminophylline), cephapirin sodium, chloram-phenicol sodium succinate, clindamycin phosphate, corticotropin, daunorubicin HCl, dopamine HCl, erythromycin gluceptate, eryth-romycin lactobionate, lidocaine HCl, mephentermine sulfate, met-ronidazole with sodium bicarbonate, netilmicin sodium, penicillin G potassium/sodium, piperacillin sodium, polymyxin B sulfate, po-tassium chloride, prochlorperazine edisylate, sodium bicarbonate, thiopental sodium, vancomycin HCl, verapamil HCl, and vitamin B-complex with C. Hydrocortisone sodium succinate is reportedly physically in-compatible when mixed with the following solutions and drugs: ampicillin sodium, bleomycin sulfate, colistimethate sodium, di-menhydrinate, diphenhydramine HCl, doxorubicin HCl, ephedrine sulfate, heparin sodium, hydralazine HCl, metaraminol bitartrate, methicillin sodium, nafcillin sodium, oxytetracycline HCl, pento-barbital sodium, phenobarbital sodium, promethazine HCl, seco-barbital sodium, and tetracycline HCl. Compatibility is dependent upon factors such as p H, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: There are no products containing hydrocortisone (or its salts) known for systemic use. There are a variety of hydrocortisone veterinary products for topical use. A 10 ppb tolerance has been established for hydrocortisone (as the succinate or acetate) in milk. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Hydrocortisone Tablets: 5 mg, 10 mg, 20 mg; Cortef® (Upjohn); ge-neric; (Rx) Hydrocortisone Sodium Succinate Injection: 100 mg/vial, 250 mg/ vial, 500 mg/vial, 1000 mg/vial (as sodium succinate) in 2 m L, 4 m L and 8 m L Univials, ﬂiptop vials, Act-O-Vials and vials; Solu-Cortef® (Upjohn); A-Hydrocort® (Abbott); (Rx) There are many OTC and Rx topical and anorectal products available in a variety of dosage forms. HYDROGEN PEROXIDE 3% (ORAL) (hye-droe-jen per-oks-ide) ORAL EMETIC, TOPICAL ANTISEPTIC Also see the Decontamination information in the appendix Prescriber Highlights TT Topical antiseptic that is used orally as an emetic in dogs & sometimes cats particularly when clients cannot transport the patient to a veterinary hospital in a timely manner TT Many contraindications to use (for emesis)	pppbs.pdf
HYDROGEN PEROXIDE 3% (ORAL) 463 Uses/Indications Hydrogen peroxide 3% solution can be used as an orally adminis-tered emetic in dogs and cats. It is best reserved for those cases when animals cannot be transported to a veterinary hospital in a timely way and immediate emesis is required. Apomorphine for dogs and cats (apomorphine is somewhat controversial for cats), or xylazine for cats are generally preferred emetic agents to be administered in a veterinary practice. Pharmacology/Actions Orally administered hydrogen peroxide solution (3%) induces a vomiting reﬂex via direct irritant effects of the oropharynx and gas-tric lining. After administering PO to dogs or cats, emesis usually ensues within 10 minutes. Pharmacokinetics No pharmacokinetic information located. Contraindications/Precautions/Warnings Do not induce emesis in those dogs or cats that are already vomiting, severely lethargic, comatose, debilitated (e. g., respiratory distress, decreased swallowing reﬂex, bradycardia, etc. ), seizuring or hyper-active, have had recent abdominal surgery or with megaesophagus. Emesis is generally contraindicated after ingestions of corrosives/ caustics (e. g., acids, alkalis), sharp objects, or bagged illicit drugs. Emesis is usually contraindicated after ingestion of a hydrocarbon or petroleum distillate. Use caution when attempting to induce emesis in a dog that has ingested a compound that can cause seizures or CNS depression as CNS status may rapidly deteriorate. Before inducing emesis, obtain a complete history of the inges-tion and ensure that vital signs are stable. Administration and emesis generally must occur within 4 hours (some say 2 hours or 6 hours maximum) of the toxic ingestion. Do not use emetics in rodents or rabbits. If home administration of hydrogen peroxide is necessary, be sure that clients use only the 3% medical grade solution and not another more concentrated hydrogen peroxide product. Because aspiration and/or bradycardia are possible, animals should be closely observed after administration. Suctioning, respi-ratory and cardiovascular support (e. g., atropine) should be avail-able. Do not allow animal to re-ingest vomitus. Successful induction of emesis does not ensure that stomach contents have been emptied and signiﬁcant quantities of the in-gested drug/toxin may remain or already been absorbed. Adverse Effects Aspiration of hydrogen peroxide solution during administration or stomach contents after inducing emesis is possible. Inducing emesis in animals with cardiovascular compromise may cause a vasovagal (bradycardic) response. Gastric ulceration in cats and gastric-dila-tation-volvulus in dogs have been reported. Reproductive/Nursing Safety No speciﬁc information was located. While orally administered 3% hydrogen peroxide is unlikely to cause reproductive harm, weigh the risks to the dam and offspring of the ingested toxin versus the risks associated with inducing emesis. Overdosage/Acute Toxicity Hydrogen peroxide 3% solution is relatively non-toxic (see Adverse Effects) after oral ingestion. Hydrogen peroxide in concentrations of 10% or greater can be very corrosive (severe burns to oral/gastric mucosa) and induce oxygen emboli after oral ingestion. Drug Interactions !TACETYLCYSTEINE (oral): Hydrogen peroxide can oxidize acetyl-cysteine in the gut and although clinical signiﬁcance is unclear, alternative emetics (e. g., apomorphine, xylazine) are preferred for acetaminophen overdoses !TANTIEMETICS (e. g., ondansetron, maropitant, etc. ): Preadministra-tion or ingestion of these products may negate the emetic effects of hydrogen peroxide Laboratory Considerations No speciﬁc concerns were noted. Doses !TDOGS/CAT S: As an emetic: a) 1-2 m L/kg PO up to 2-3 times (Rudloff 2006b) b) 1-5 m L/kg PO; generally not to exceed 50 m L for dogs and 10 m L for cats; may repeat one time if after 10 minutes em-esis does not occur. Inducing emesis is most effective if ad-ministered after a small meal. (Peterson 2006c) c) 0. 25-0. 5 m L/kg PO; may repeat once after 5-15 minutes if vomiting has not occurred. (Cote 2005) Monitoring !TEfﬁcacy (emesis, signs associated with toxicity of the substance ingested, blood levels of toxicants if applicable) !THeart rate/respiration rate & auscultation after emesis Client Information !TUse only under the direct instructions of a veterinarian or a poi-son control center !TOnly use hydrogen peroxide 3%; stronger concentrations can be very toxic !TCarefully administer; do not allow patient to “inhale” the liquid !TObserve animal after administration, do not allow them to re-ingest the vomited material (vomitus) !TSave all vomitus for the veterinarian to examine Chemistry/Synonyms Hydrogen peroxide 3% solution is a clear, colorless liquid contain-ing 2. 5-3. 5% w/v hydrogen peroxide. Up to 0. 05% of the liquid may contain preservatives. Hydrogen peroxide 3% solution may also be known as dilute hy-drogen peroxide solution, hydrogen peroxide solution 10-volume ( Note : NOT 10%), or hydrogen peroxide topical solution. Storage/Stability Store 3% solutions in airtight containers at room temperature and protected from light. Hydrogen peroxide 3% can deteriorate with time; outdated or improperly stored products may not be effective as an emetic. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None as an oral emetic HUMAN-LABELED PRODUCTS: None as an oral emetic. Hydrogen Peroxide 3% Solution is readily available over-the-counter from a variety of manufacturers. It is usu-ally sold in pint bottles.	pppbs.pdf
464 HYDROMORPHONE HYDROMORPHONE (hye-droe-mor-fone) Dilaudid® OPIATE AGONIST Prescriber Highlights TT Injectable opiate sedative/restraining agent, analgesic, & preanesthetic similar to oxymorphone TT Less expensive than oxymorphone on a per m L basis, but has shorter duration of action TT Contraindications: Hypersensitivity to it, diarrhea caused by a toxic ingestion, prior to GI obstructive surgery (may cause vomiting) TT Extreme caution: Respiratory disease or acute respira-tory dysfunction TT Caution: Hypothyroidism, severe renal insufﬁciency (acute uremia), adrenocortical insufﬁciency, geriatric or severely debilitated patients, head injuries or increased intracra-nial pressure & acute abdominal conditions (e. g., colic) TT Adverse Effects: CNS depression, respiratory depression, & bradycardia; decreased GI motility with resultant con-stipation possible TT CATS: Ataxia, hyperesthesia, hyperthermia, & behavioral changes (without concomitant tranquilization) TT Drug-drug; drug-lab interactions TT C-II controlled substance Uses/Indications Like oxymorphone, hydromorphone is used in dogs and cats as a sedative/restraining agent, analgesic and preanesthetic. It may also be useful in other species, but little data or experience is available. Because of expense and availability issues with oxymorphone, hydromorphone is rapidly replacing it in veterinary medicine. In dogs and cats, hydromorphone is generally less sedating that mor-phine, usually causes minimal histamine release after IV adminis-tration, and rarely causes vasodilation and hypotension. Pharmacology/Actions Receptors for opiate analgesics are found in high concentrations in the limbic system, spinal cord, thalamus, hypothalamus, striatum, and midbrain. They are also found in tissues such as the gastroin-testinal tract, urinary tract, and in other smooth muscle. The morphine-like agonists (morphine, meperidine, oxymor-phone, hydromorphone) have primary activity at the mu recep-tors, with some activity possible at the delta receptor. The primary pharmaco logic effects of these agents include: analgesia, antitus-sive activity, respiratory depression, sedation, emesis, physical dependence, and intestinal effects (constipation/defecation). Secondary pharmaco logic effects include: CNS: euphoria, seda-tion, and confusion. Cardiovascular: bradycardia due to central vagal stimulation, alpha-adrenergic receptors may be depressed resulting in peripheral vasodilation, decreased peripheral resis-tance, and baroreceptor inhibition. Orthostatic hypotension and syncope may occur. Urinary: Increased bladder sphincter tone can induce urinary retention. Various species may exhibit contradictory effects from these agents. For example, horses, cattle, swine, and cats may develop ex-citement and dogs may defecate after morphine injections. These effects are in contrast to the expected effects of sedation and consti-pation. Dogs and humans may develop miosis, while other species (especially cats) may develop mydriasis. Hydromorphone is approximately 5 times more potent an an-algesic on a per weight basis when compared to morphine and ap-proximately equal in potency to oxymorphone. At the usual doses employed, hydromorphone alone has good sedative qualities in the dog. Respiratory depression can occur especially in debilitated, neo-natal, or geriatric patients. Bradycardia, as well as a slight decrease in cardiac contractility and blood pressure, may be seen. Like oxy-morphone, hydromorphone does initially increase the respiratory rate (panting in dogs) while actual oxygenation may be decreased and blood CO 2 levels may increase by 10 mm Hg or more. Gut motility is decreased with resultant increases in stomach emptying times. Unlike either morphine or meperidine, hydromorphone may only infrequently cause mild histamine release in dogs or cats after IV injection. Pharmacokinetics Hydromorphone is absorbed when given by IV, IM, SC, and rectal routes. The onset of analgesic efﬁcacy occurs within 15-30 min-utes, depending on route of administration. The drug is metabolized in the liver, primarily by glucuronida-tion. Because cats are deﬁcient in this metabolic pathway, half-lives in cats are probably prolonged. The glucuronidated metabolite is excreted by the kidney. Contraindications/Precautions/Warnings All opiates should be used with caution in patients with hypo-thyroidism, severe renal insufﬁciency, adrenocortical insufﬁ-ciency (Addison's), and geriatric or severely debilitated patients. Hydromorphone is contraindicated in patients hypersensitive to narcotic analgesics, and those with diarrhea caused by a toxic in-gestion (until the toxin is eliminated from the GI tract). All opi-ates should be used with caution in patients with hypothyroidism, severe renal insufﬁciency, adrenocortical insufﬁciency (Addison's), and geriatric or severely debilitated patients. Because it may cause vomiting, hydromorphone use should be considered contraindicated as a preanesthetic med in animals with suspected gastric dilation, volvulus, or intestinal obstruction. Hydromorphone should be used with extreme caution in pa-tients with head injuries, increased intracranial pressure, and acute abdominal conditions (e. g., colic) as it may obscure the diagnosis or clinical course of these conditions. It should be used with extreme caution in patients suffering from respiratory disease or acute re-spiratory dysfunction (e. g., pulmonary edema secondary to smoke inhalation). Hydromorphone can cause bradycardia and therefore should be used cautiously in patients with preexisting bradyarrhythmias. Neonatal, debilitated, or geriatric patients may be more sus-ceptible to the effects of hydromorphone and may require lower dosages. Patients with severe hepatic disease may have prolonged duration of action of the drug. If used in cats at high dosages, the drug has been recommended to be given along with a tranquilizing agent, as hydromorphone can produce bizarre behavioral changes in this species. This also is true in cats for the other opiate agents, such as morphine. Opiate analgesics are contraindicated in patients who have been stung by the scorpion species Centruroides sculpturatus Ewing and C. gertschi Stahnke as it may potentiate these venoms. Adverse Effects Hydromorphone has a similar adverse effect proﬁle to oxymor-phone or morphine in dogs and cats. CNS depression may be greater than desired, particularly when treating moderate to severe pain. Dose related respiratory depression is possible, and more	pppbs.pdf
HYDROMORPHONE 465 likely during general anesthesia. Panting (may occur more often than with oxymorphone) and cough suppression (may be of ben-eﬁt) may occur. Cats may be prone to developing hyperthermia. Secondary to enhanced vagal tone, hydromorphone can cause bra-dycardia. This apparently occurs on par with morphine or oxymor-phone. Hydromorphone may cause histamine release which, while generally clinically insigniﬁcant, may be signiﬁcant in critically ill animals. Vomiting and defecation can occur after dosing; use cau-tion when using as a preanesthetic. Constipation is possible with chronic dosing. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Most opiates are excreted into milk, but effects on nursing off-spring may not be signiﬁcant. Overdosage/Acute Toxicity Massive overdoses may produce profound respiratory and/or CNS depression in most species. Other effects may include cardiovascu-lar collapse, hypothermia, and skeletal muscle hypotonia. Naloxone is the agent of choice in treating respiratory depression. In mas-sive overdoses, naloxone doses may need to be repeated, and ani-mals should be closely observed as naloxone's effects may diminish before sub-toxic levels of oxymorphone are attained. Mechanical respiratory support should be considered in cases of severe respira-tory depression. In susceptible patients, moderate overdoses may require nalox-one and supportive treatment as well. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving hydromorphone and may be of signiﬁcance in veterinary patients: !TBUTORPHANOL, NALBUPHINE : Potentially could antagonize opiate effects !TCNS DEPRESSANTS, OTHER : Additive CNS effects possible !TDIURETICS : Opiates may decrease efﬁcacy in CHF patients !TMONOAMINE OXIDASE INHIBITORS (e. g., amitraz and potentially, sele-giline ): Severe and unpredictable opiate potentiation may be seen; not recommended (in humans) if MAO inhibitor has been used within 14 days !TMUSCLE RELAXANTS, SKELETAL : Hydromorphone may enhance effects !TPHENOTHIAZINES : Some phenothiazines may antagonize analgesic effects and increase risk for hypotension !TTRICYCLIC ANTIDEPRESSANTS (clomipramine, amitriptyline, etc. ): Hydromorphone may exacerbate the effects of tricyclic antidepressants !TWARFARIN : Opiates may potentiate anticoagulant activity Laboratory Considerations !TAs they may increase biliary tract pressure, opiates can increase plasma amylase and lipase values up to 24 hours following their administration. Doses !TDOGS: a) As an analgesic: 0. 05-0. 2 mg/kg IM, IV or SC q2-6 hours (Wagner 2002) b) For cancer pain: 0. 08-0. 2 mg/kg IV, IM, or SC (Lester and Gaynor 2000) c) For moderate to severe pain: 0. 08-0. 3+ mg/kg IV, IM or SC q2-6 hours (Mathews 2000) d) As an analgesic: 0. 05-0. 2 mg/kg IV, IM, SC q2-4h (Hansen 2003b), (Hardie 2006) e) As an analgesic: 0. 2-0. 6 mg/kg PO q6-8h; For periopera-tive pain: 0. 1-0. 2 mg/kg IV, IM, SC q2-4h (Pascoe 2006) f) As a premed prior to moderately painful procedures: 0. 1 mg/kg; may be combined with acepromazine (0. 02-0. 05 mg/kg) in young, healthy patients. As a sedative/restraint agent for fractious or aggressive dogs: 0. 1-0. 2 mg/kg mixed with acepromazine (0. 05 mg/kg) IM. Maximal effect usually reached in about 15 minutes, but an additional wait of an-other 15 minutes may be necessary in some dogs. As an alternate induction method (especially in critical pa-tients): hydromorphone 0. 05-0. 2 mg/kg IV, slowly to effect followed by diazepam 0. 02 mg/kg IV (do not mix two drugs together). Endotracheal intubation may be possible after ad-ministration, if not, delivery of an inhalant by facemask will give a greater depth of anesthesia. Positive pressure ventila-tion likely will be necessary. If bradycardia requires treatment, use either glycopyrrolate (0. 01-0. 02 mg/kg IV) or atropine (0. 02-0. 04 mg/kg IV). (Pettifer and Dyson 2000) !TCATS: a) As an analgesic: 0. 05-0. 1 mg/kg IM, IV or SC q2-6 hours (Wagner 2002) b) For cancer pain: 0. 08-0. 2 mg/kg IV, IM, or SC (Lester and Gaynor 2000) c) As an analgesic: 0. 02-0. 05 mg/kg IV, IM, SC q2-4h (Hansen 2003b), (Hardie 2006) d) For moderate to severe pain: 0. 08-0. 3+ mg/kg IV, IM or SC q2-6 hours (Mathews 2000) e) As a premed prior to moderately painful procedures: 0. 1 mg/ kg; may be combined with acepromazine (0. 05-0. 2 mg/kg) in young, healthy patients. As an alternate induction method (especially in critical pa-tients): hydromorphone 0. 05-0. 2 mg/kg IV, slowly to effect followed by diazepam 0. 02 mg/kg IV (do not mix two drugs together). Endotracheal intubation may be possible after ad-ministration, if not, delivery of an inhalant by facemask will give a greater depth of anesthesia. Positive pressure ventila-tion likely will be necessary. If bradycardia requires treatment, use either glycopyrrolate (0. 01-0. 02 mg/kg IV) or atropine (0. 02-0. 04 mg/kg IV). (Pettifer and Dyson 2000) !TFERRETS: a) As a pre-op: 0. 05-0. 1 mg/kg IV; as a CRI post-op: 0. 05 mg/ kg IV loading dose, then 0. 05-0. 1 mg/kg/hr (Lichtenberger 2006a) !TSMALL MAMMALS: a) Rabbits: 0. 05-0. 1 mg/kg IV; as a CRI post-op: 0. 05 mg/kg IV loading dose, then 0. 05-0. 1 mg/kg/hr (Lichtenberger 2006a) Monitoring !TRespiratory rate/depth (pulse oximetry highly recommended) !TCNS level of depression/excitation !TBlood pressure (especially with IV use) !TCardiac rate !TAnalgesic efﬁcacy	pppbs.pdf
466 HYDROXYUREA Client Information T ! When given parenterally, this agent should be used in an inpa-tient setting or with direct professional supervision Chemistry/Synonyms A semi-synthetic phenanthrene-derivative opiate related to mor-phine, hydromorphone HCl occurs as white, ﬁne, crystalline pow-der. It is freely soluble in water. The commercial injection has a p H of 4-5. 5. Hydromorphone may also be known as: dihydromorphinone hydrochloride, Dolonovag®, Hydal®, Hydro Stat IR®, Hydromorph®, Opidol®, Palladon®, Palladone®, and Sophidone®. Storage/Stability/Compatibility The injection should be stored at room temperature and protected from light. A slight yellowish tint to the solution may occur, but does not indicate loss of potency. The injection remains stable for at least 24 hours when mixed with commonly used IV ﬂuids if pro-tected from light. Hydromorphone tablets should be stored at room temperature in tight, light resistant containers. The suppositories should be kept in the refrigerator. Hydromorphone injection is compatible in commonly used IV ﬂuids (for 24 hours when protected from light at 25°C) and with midazolam, ondansetron, potassium chloride, and heparin so-dium. Hydromorphone injection mixed in the same syringe with atropine and medetomidine (Domitor®) for use as a preop in dogs prior to sevoﬂurane or propofol anesthesia has been described (Ko 2005). Hydromorphone is incompatible with sodium bicarbonate, or thiopental. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Hydromorphone HCl Injection: 1 mg/m L in 1 m L amps & syringes, 2 mg/m L in 1 m L amps, 1 m L syringes, 1 m L amps and 20 m L vials & multidose vials; 4 mg/m L in1 m L amps & syringes; and 10 mg/m L in 1 m L, 5 m L, single-dose vials & amps and 50 m L single-dose vials; Dilaudid® and Dilandid-HP® (Abbott); generic; (Rx, C-II) Hydromorphone HCl Powder for Injection, lyophilized: 250 mg (10 mg/m L after reconstitution) in single-dose vials; Dilaudid-HP ® (Ab-bott); (Rx, C-II) Hydromorphone HCl Tablets: 2 mg, 4 mg, and 8 mg; Dilaudid® (Ab-bott); generic, (Rx, C-II) Hydromorphone HCl Capsules (extended-release): 12 mg, 16 mg, 24 mg, & 32 mg; Palladone® (Purdue Pharma); (Rx, C-II) Hydromorphone HCL Oral Solution: 1 mg/1 m L in 4 m L UD and 8 m L UD patient cups; 250 m L & 473 m L; Dilaudid-5® (Abbott); generic; (Rx, C-II) Hydromorphone Suppositories: 3 mg; Hydromorphone HCl (Pad-dock); Dilaudid® (Abbott); (Rx, C-II) Hydroxyethyl Starch — See Hetastarch HYDROXYUREA (hye-drox-ee-yor-ee-a) Hydrea®, Droxia®, Mylocel® ANTINEOPLASTIC Prescriber Highlights TT Antineoplastic used for treatment of polycythemia vera, mastocytomas, & leukemias in dogs & cats TT Caution: Anemia, bone marrow depression, history of urate stones, infection, impaired renal function, or in patients who have received previous chemotherapy or radiotherapy TT Adverse Effects: GI effects, stomatitis, sloughing of nails, alopecia, & dysuria; most serious are bone marrow de-pression & pulmonary ﬁbrosis TT Proven teratogen Uses/Indications Hydroxyurea may be useful in the treatment of polycythemia vera, mastocytomas, and leukemias in dogs and cats. It is often used to treat dogs with chronic myelogenous leukemia no longer respon-sive to busulfan. Hydroxyurea, potentially, may be of beneﬁt in the treatment of feline hypereosinophilic syndrome and in the adjunc-tive treatment of canine meningiomas. It can also be used in dogs for the adjunctive medical treatment (to reduce hematocrit) of right to left shunting patent ductus arteriosis or tetralogy of Fallot. Pharmacology/Actions While the exact mechanism of action for hydroxyurea has not been determined, it appears to interfere with DNA synthesis without in-terfering with RNA or protein synthesis. Hydroxyurea apparently inhibits thymidine incorporation into DNS and may directly dam-age DNA. It is an S-phase inhibitor, but may also arrest cells at the G1-S border. Hydroxyurea inhibits urease, but is less potent than acetohy-droxamic acid. Hydroxyurea can stimulate production of fetal he-moglobin. Pharmacokinetics Hydroxyurea is well absorbed after oral administration and crosses the blood-brain barrier. Approximately 50% of an absorbed dose is excreted unchanged in the urine and about 50% is metabolized in the liver and then excreted in the urine. Contraindications/Precautions/Warnings Risk versus beneﬁt should be considered before using hydroxyurea in patients with the following conditions: anemia, bone marrow de-pression, history of urate stones, current infection, impaired renal function, or in patients who have received previous chemotherapy or radiotherapy. Adverse Effects Potential adverse effects include GI effects (anorexia, vomiting, diarrhea), stomatitis, sloughing of nails, alopecia, and dysuria. The most serious adverse effects associated with hydroxyurea are bone marrow depression (anemia, thrombocytopenia, leukopenia) and pulmonary ﬁbrosis. If myelotoxicity occurs, it is recommended to halt therapy until values return to normal. Methemoglobinemia has been reported in cats given high dosages (>500 mg).	pppbs.pdf
HYDROXYZINE 467 Reproductive/Nursing Safety Hydroxyurea is a teratogen. Use only during pregnancy when the beneﬁts to the mother outweigh the risks to the offspring. Hydroxyurea can suppress gonadal function; arrest of spermato-genesis has been noted in dogs. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Although hydroxyurea distribution into milk has not been doc-umented, nursing puppies or kittens should receive milk replacer when the dam is receiving hydroxyurea. Overdosage/Acute Toxicity Cats given hydroxyurea in doses greater than 500 mg (total) may develop methemoglobinemia. Because of the potential toxicity of the drug, overdoses should be treated aggressively with gut emp-tying protocols employed when possible. For further information, refer to an animal poison control center. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving hydroxyurea and may be of signiﬁcance in veterinary patients: T ! BONE MARROW DEPRESSANT DRUGS, OTHER (e. g., other antineoplas-tics, chloramphenicol, ﬂucytosine, amphotericin B, or colchicine ): Other bone marrow depressant drugs may cause additive myelo-suppression when used with hydroxyurea Laboratory Considerations T ! Hydroxyurea may raise serum uric acid levels; drugs such as al-lopurinol may be required to control hyperuricemia Doses For more information on using hydroxyurea as part of chemo-therapy protocols, refer to the protocols found in the appendix or other dosages/protocols found in numerous references, including: Withrow and Mac Ewen's Small Animal Clinical Oncology, 4th Ed. (Withrow and Vail 2007); Canine and Feline Geriatric Oncology (Villalobos 2007); Small Animal Internal Medicine, 3rd Edition (Nelson and Couto 2003); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edition (Ettinger and Feldman 2005); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. (Tilley and Smith 2004). T ! DOGS: For polycythemia vera; chronic myelogenous leukemia: a) 50 mg/kg 3 times per week (Jacobs, Lumsden et al. 1992) For polycythemia vera: a) Initially at 20-25 mg/kg PO twice daily; once the hematocrit is below 60% give every other day. (Vail and Thamm 2005) b) 30 mg/kg once daily for one week, then 15 mg/kg once daily until remission; then taper to lowest effective frequency by monitoring hematocrit (Raskin 1994) c) 50-80 mg/kg PO every 3 days (Kitchell and Dhaliwal 2000) For chronic myelogenous leukemia: a) 50 mg/kg PO q24h for 1-2 weeks, then every other day (Couto 2003) T ! CATS: For polycythemia vera; chronic myelogenous leukemia: a) 25 mg/kg 3 times per week (Jacobs, Lumsden et al. 1992) For polycythemia vera: a) Initially at 10-15 mg/kg PO twice daily; once the hematocrit is below 60% give every other day. (Vail and Thamm 2005) b) 30 mg/kg once daily for one week, then 15 mg/kg once daily until remission; then taper to lowest effective frequency by monitoring hematocrit. Cats must be monitored more fre-quently than dogs as they have a greater risk of developing bone marrow toxicity. (Raskin 1994) Monitoring T ! CBC with platelets at least every 1-2 weeks until stable; then ev-ery 3 months T ! BUN/Serum Creatinine; initially before starting treatment and then every 3-4 months Chemistry/Synonyms Structurally similar to urea and acetohydroxamic acid, hydroxyurea occurs as white, crystalline powder that is freely soluble in water. It is moisture labile. Hydroxyurea may also be known as: hydroxycarbamide, hy-droxycarbamidum, NSC-32065, SQ-1089, WR-83799, Dacrodil®, Droxiurea®, Hydrea®, Droxia®, Hydrine®, Litalir®, Medroxyurea®, Neodrea®, Onco-Carbide®, Oxeron®, and Syrea®. Storage/Stability Capsules should be stored in tight containers at room temperature. Avoid excessive heat. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Hydroxyurea Capsules: 200 mg, 300 mg, 400 mg and 500 mg; Hy-drea® (Bristol-Myers Squibb); Droxia® (Bristol-Myers Squibb Oncol-ogy); generic; (Rx) HYDROXYZINE HCL HYDROXYZINE PAMOATE (hye-drox-i-zeen) Atarax®, Vistaril® ANTIHISTAMINE Prescriber Highlights TT Used principally for antihistaminic, antipruritic, & seda-tive/tranquilization qualities, often in atopic patients TT Contraindications: Hypersensitivity to the drug TT Caution in patients with prostatic hypertrophy, bladder neck obstruction, severe cardiac failure, angle-closure glaucoma, or pyeloduodenal obstruction TT Adverse Effects: Sedation most likely; DOGS (rarely): Tremors, seizures; CAT S: Polydipsia, depression, or behav-ioral changes. Uses/Indications Hydroxyzine is used principally for its antihistaminic, antipruritic, and sedative/tranquilization qualities, often in atopic patients. Pharmacology/Actions Like other H 1-receptor antihistamines, hydroxyzine acts by com-peting with histamine for sites on H 1-receptor sites on effector cells. Antihistamines do not block histamine release, but can antagonize its effects. In addition to its antihistaminic effects, hydroxyzine pos-	pppbs.pdf
468 HYDROXYZINE sesses anticholinergic, sedative, tranquilizing, antispasmodic, local anesthetic, mild bronchodilative, and antiemetic activities. Pharmacokinetics Hydroxyzine is rapidly and well absorbed after oral administration. Effects generally persist for 6-8 hours in dogs and up to 12 hours in cats. Hydroxyzine is apparently metabolized in liver. Contraindications/Precautions/Warnings Hydroxyzine is contraindicated in patients hypersensitive to it. It should be used with caution in patients with prostatic hypertrophy, bladder neck obstruction, severe cardiac failure, angle-closure glau-coma, or pyeloduodenal obstruction. Adverse Effects The most likely adverse effect associated with hydroxyzine is seda-tion. In dogs, this is usually mild and transient. Occasionally an-tihistamines can cause a hyperexcitability reaction. Dogs have re-portedly developed ﬁne rapid tremors, whole body tremors and, rarely, seizures while receiving this drug. Cats may develop polydip-sia, depression, or behavioral changes while on this medication. Reproductive/Nursing Safety At doses substantially greater than those used therapeutically, hy-droxyzine has been shown to be teratogenic in lab animals. Use dur-ing pregnancy (particularly during the ﬁrst trimester) only when the beneﬁts outweigh the risks. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate stud-ies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is unknown if hydroxyzine enters maternal milk; cetirizine a metabolite of hydroxyzine, has been detected in milk. Overdosage/Acute Toxicity There is limited information available. There are no speciﬁc anti-dotes available. Overdoses would be expected to cause increased se-dation and perhaps, hypotension. Gut emptying protocols should be considered with large or unknown quantity overdoses. Supportive and symptomatic treatment is recommended if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving hydroxyzine and may be of signiﬁcance in veterinary patients: !TANTICHOLINERGIC AGENTS : Additive anticholinergic effects may oc-cur when hydroxyzine is used concomitantly with other anticho-linergic agents !TCNS DEPRESSANT DRUGS, OTHER : Additive CNS depression may be seen if combining hydroxyzine with other CNS depressant medi-cations, such as barbiturates, tranquilizers, etc !TEPINEPHRINE : Hydroxyzine may inhibit or reverse the vasopres-sor effects of epinephrine; use norepinephrine or metaraminol instead Laboratory Considerations !TFalse increases have been reported in 17-hydroxycorticosteroid urine values after hydroxyzine use !TBecause antihistamines can decrease the wheal and ﬂair response to skin allergen testing, antihistamines should be discontinued from 3-7 days (depending on the antihistamine used and the reference) before intradermal skin tests Doses !TDOGS: As an antipruritic/antihistamine: a) 2. 2 mg/kg PO three times daily (q8h) (Gershwin 1992), (Par-adis and Scott 1992), (White 2007) b) For ﬂea allergy dermatitis: 2 mg/kg q8h PO (Griffen 1994) !TCATS: As an antipruritic/antihistamine: a) For pruritus: 1-2 mg/kg or 5-10 mg/cat PO q8-12h (Messinger 2000) b) For pruritus: 5-10 mg (total dose) or 2. 2 mg/kg PO q8-12h (Hnilica 2003c) For frequently recurrent idiopathic lower urinary tract disease: a) 5-10 mg (total dose) per cat PO q12h (Lane 2002a) !TFERRETS: a) 2 mg/kg PO 3 times daily (Williams 2000) !THORSES: (Note : ARCI UCGFS Class 2 Drug) a) 0. 5-1 mg/kg IM or PO twice daily (Robinson 1992) b) Using the pamoate salt: 0. 67 mg/kg PO twice daily (Duran 1992) !TBIRDS: For pruritus associated with allergies, feather picking, or self-mutilation: a) 2 mg/kg q8h PO or 1. 5-2 mg per 4 oz of drinking water daily; adjust dose to minimize drowsiness and maximize ef-fect (Hillyer 1994) b) 2 mg/kg PO q12h (Siebert 2003b) Monitoring !TEfﬁcacy !TAdverse effects Client Information !TMay cause drowsiness and impede working dogs' abilities Chemistry/Synonyms A piperazine-derivative antihistamine, hydroxyzine HCl occurs as a white, odorless powder. It is very soluble in water and freely soluble in alcohol. Hydroxyzine pamoate occurs as a light yellow, practical-ly odorless powder. It is practically insoluble in water or alcohol. Hydroxyzine may also be known as: hydroxyzine embonate, hy-droxyzine pamoate, hydroxyzine HCl, hydroxyzini HCl, Vistaril®, Atarax® or Masmoran®. Storage/Stability/Compatibility Hydroxyzine oral products should be stored at room temperature in tight, light-resistant containers. Avoid freezing all liquid products. The HCl injection has been reported to be physically compatible with the following drugs when mixed in syringes: atropine sulfate, benzquinamide HCl, butorphanol tartrate, chlorpromazine HCl, cimetidine HCl, codeine phosphate, diphenhydramine HCl, dox-apram HCl, droperidol, fentanyl citrate, glycopyrrolate, hydromor-phone HCl, lidocaine HCl, meperidine HCl, methotrimeprazine, metoclopramide HCl, midazolam HCl, morphine sulfate, oxymor-phone HCl, pentazocine lactate, procaine HCl, prochlorperazine edisylate, promazine HCl, promethazine HCl, and scopolamine HBr. Compatibility is dependent upon factors such as p H, concen-tration, temperature and diluent used; consult specialized referenc-es or a hospital pharmacist for more speciﬁc information.	pppbs.pdf
HYOSCYAMINE SULFATE 469 Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Hydroxyzine HCl Oral Tablets: 10 mg, 25 mg, & 50 mg; generic; (Rx) Hydroxyzine HCl Oral Solution: 10 mg/5 m L in 16 m L, 118 m L, 120 m L and 473 m L, gal and UD 5, 12. 5 and 25 m L; Atarax® (Roerig); (Rx); generic; (Rx) Hydroxyzine HCl Injection: 25 mg/m L in 1 m L and 2 m L vials; 50 mg/m L in 1 m L, 2 m L and 10 m L vials; generic; (Rx) Hydroxyzine Pamoate Capsules (equivalent to hydroxyzine HCl): 50 mg, & 100 mg; Vistaril® (Pﬁzer); generic; (Rx) Hydroxyzine Pamoate Suspension (equivalent to hydroxyzine HCl): 25 mg/5 m L (as pamoate) in 120 m L & 473 m L; Vistaril® (Pﬁzer); (Rx) HYOSCYAMINE SULFATE (hye-oh-sye-ah-meen or hye-ah-ska-meen) Levsin® ORAL AND INJECTA BLE ANTICHOLINERGIC Prescriber Highlights TT Anticholinergic that may be useful for treating hypermo-tile GI conditions such as irritable bowel syndrome or bradycardia in dogs TT Limited use in veterinary medicine TT Adverse effects can include mydriasis, xerostomia, consti-pation, urinary retention, & xerophthalmia Uses/Indications Although not commonly used in veterinary medicine, hyoscyamine may be useful as an alternative to other anticholinergic drugs such as glycopyrrolate for treating bradycardia or hypermotile GI condi-tions such as irritable bowel syndrome in dogs. It, potentially, could be useful for treating hypersalivation, urinary spasms, vomiting, or reducing secretions peri-operatively, but little is known regarding safety and efﬁcacy in animals when used for these conditions. In humans, hyoscyamine is used primarily for its effects in re-ducing GI tract motility or to decrease pharyngeal, bronchial and tracheal secretions. Pharmacology/Actions Hyoscyamine is an anticholinergic agent similar to atropine, but more potent both in central and peripheral effects. It inhibits acetylcholine at tissues innervated by postganglionic nerves and smooth muscles that respond to acetylcholine but do not have cho-linergic innervation. It does not have action on autonomic ganglia. Pharmacologic effects include dose-related reductions in secretions, gastrointestinal and urinary tract motility, mydriasis, and increased heart rate. Pharmacokinetics No pharmacokinetic data was located for veterinary species. In humans, hyoscyamine is rapidly and nearly completely absorbed after oral or sublingual administration. Extended release oral dos-age forms may have somewhat reduced oral bioavailability. It is distributed throughout the body, enters the CNS and crosses the placenta. Hyoscyamine is partially hydrolyzed in the liver to tropic acid and tropine. The majority of the drug is excreted unchanged in the urine. Elimination half-life is about 3. 5 hours; about 7 hours for the sustained-release product, Levsinex®. Average duration of action in humans is approximately 4-6 hours. Contraindications/Precautions/Warnings Hyoscyamine is contraindicated in patients hypersensitive to it. Patients sensitive to one belladonna alkaloid or derivative may be sensitive to another. Use with caution in patients with renal dysfunction as hyoscy-amine elimination may be reduced. Use of anticholinergics should be carefully considered in patients with tachyarrhythmias, cardiac valve disease or congestive heart failure. Patients with myasthenia gravis may have their condition aggravated with concurrent use of hyoscyamine. Other contraindications for using hyoscyamine in humans include: glaucoma (narrow or wide angle), intestinal ob-struction, toxic megacolon, intestinal atony, severe ulcerative colitis, obstructive uropathy, or acute hemorrhage. Adverse Effects Adverse effects can include mydriasis, xerostomia, constipation, urinary retention, and xerophthalmia. Higher dosages may cause CNS effects (somnolence or excitement) or tachycardia. Reproductive/Nursing Safety There is limited information available on the drug's use during pregnancy. While hyoscyamine crosses the placenta, reproductive studies in animals have not been performed. Two limited studies (322 & 281 pregnancies) in humans have been published evaluat-ing hyoscyamine safety during pregnancy. One study showed no increase in congenital malformations, but the other showed a slight increase above normally expected malformations in infants. In hu-mans, the FDA categorizes hyoscyamine as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Only traces of hyoscyamine are detected in milk. While no prob-lems have been reported and risk to offspring cannot be ruled out, it is probably safe to use in nursing patients. Overdosage/Acute Toxicity The LD 50 for hyoscyamine in rats is 375 mg/kg. Signiﬁcant over-dosage in animals may be serious and contacting an animal poison control center is advised. T oxicity is exhibited by intensiﬁed and prolonged anticholinergic effects; signs include: increased heart rate, CNS effects (behavior changes, depression, seizures), urinary retention, decreased gut sounds/motility, and mydriasis. Protocols to decrease oral absorption should be considered if overdose was recent. Severe anticholinergic effects can be treated with physostig-mine or neostigmine, but it is suggested to do so only under the guidance of an animal poison control center. In humans, delirium or excitement has been treated with small doses of short-acting barbiturates or benzodiazepines. Hyoscyamine can be removed by hemodialysis. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving hyoscyamine and may be of signiﬁcance in veterinary patients: T ! ANTACIDS containing magnesium, aluminum or calcium salts : May in-terfere with hyoscyamine absorption	pppbs.pdf
470 IBAFLOXACIN T ! ANTICHOLINERGICS, OTHER (atropine, glycopyrrolate, etc. ): Additive actions and adverse effects can occur T ! ANTIHISTAMINES, FIRST GENERATION (e. g., diphenhydramine ): Addi-tive actions and adverse effects can occur T ! PROKINETIC AGENTS (e. g., cisapride, metoclopramide ): Hyoscyamine may counteract their effects Laboratory Considerations No speciﬁc concerns noted with hyoscyamine Doses T ! DOGS: Note : The following dosages are assumed to be for the immediate release oral dosage forms. Potentially, the extended release tablets or capsules could be effective and reduce dosing frequency, par-ticularly in larger dogs, but no data is available for using them. a) For irritable bowel syndrome: 0. 003-0. 006 mg/kg PO two to three times a day (Leib 2005) b) For long-term management of symptomatic patients with si-nus node disease: 0. 003-0. 006 mg/kg PO q8h (Smith 2005) Monitoring T ! Clinical efﬁcacy T ! Adverse effects (e. g., heart rate, bowel or urinary elimination difﬁculties) Client Information T ! Contact the veterinarian if patient has difﬁculty urinating or def-ecating, dry eyes, difﬁculty swallowing, or demonstrates changes in behavior or activity Chemistry/Synonyms Hyoscyamine sulfate is a tertiary amine that occurs as white, odor-less, crystals or crystalline powder. One gram is soluble in 0. 5 m L of water or in 1 m L of alcohol. It is practically insoluble in ether. Hyoscyamine may also be known as: daturin, duboisine, tro-pine-L-tropate. International trade names include: Egazil Duretter® and Neo-Allospasmin®. Storage/Stability/Compatibility Unless otherwise advised by the manufacturer, hyoscyamine sulfate oral products should be stored at room temperature, in tight con-tainers, and protected from light. The injectable product should be stored at room temperature and protected from freezing. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None as single ingredient products. HUMAN-LABELED PRODUCTS: Hyoscyamine Tablets: 0. 125 mg, & 0. 15 mg; Anaspaz® (Ascher), ED-SPAZ® (Edwards), Levsin® (Schwarz), Cystospaz® (Poly Medica), generic; (Rx) Hyoscyamine Orally Disintegrating Tablets: 0. 125 mg, & 0. 25 mg; Neosol® (Breckenridge), Nu Lev® (Schwarz), Symax Fas Tab® (Capellon), Mar-Spas® (Marnel); (Rx) Hyoscyamine Sublingual Tablets: 0. 125 mg; Levsin-SL® (Schwarz), Symax-SL® (Capellon); (Rx) Hyoscyamine Extended/Sustained-Release Tablets: 0. 375 mg; Levbid® (Schwarz), Symax-SR®, generic; (Rx) Hyoscyamine Extended/Timed-Release Capsules: 0. 375 mg; Levsinex® (Schwarz), generic; (Rx) Hyoscyamine Oral Solution: 0. 125 mg/m L in 15 m L btls; Levsin Drops® (Schwarz), generic; (Rx) Hyoscyamine Oral Elixir: 0. 025 mg/m L (0. 125mg/5m L) in pint bottles; Levsin® (Schwarz), generic; (Rx) Hyoscyamine Oral Spray: 0. 125 mg/spray in 30 m L btls; IB-Stat® (In Kline); (Rx) Hyoscyamine Injection: 0. 05 mg/m L in 1 m L ampules and 10 m L multi-dose vials; Levsin® (Schwarz); (Rx) IBAFLOXACIN (ih-bah-ﬂoks-ah-sin) Ibaﬂin® ORAL FLUORO QUINOLONE ANTIBIOTIC Prescriber Highlights TT Oral ﬂuoroquinolone used in dogs & cats primarily in Eu-rope (not available in USA); oral dosage form is a gel in a “dial” syringe TT Similar to other veterinary ﬂuoroquinolones, but may not be as effective against Pseudomonas TT Adverse effects can include diarrhea/soft feces, vomit-ing, dullness, anorexia & salivation TT No indication of causing ocular toxicity in cats Uses/Indications Ibaﬂoxacin is used in dogs and cats to treat infections susceptible to it. It is labeled (in the UK) for treating dogs with dermal infec-tions (superﬁcial and deep pyoderma, wounds, abscesses) and in cats for treating dermal infections (soft tissue infections—wounds, abscesses) and upper respiratory tract infections caused by suscep-tible bacteria. Ibaﬂoxacin may also be useful in treating urinary tract infections in dogs. Pharmacology/Actions Ibaﬂoxacin is a bactericidal ﬂuoroquinolone antibiotic and acts by inhibiting bacterial DNA-gyrase (a type-II topoisomerase), preventing DNA supercoiling and synthesis. It has a similar spec-trum of activity as other veterinary commercially available agents (Enterobacteriaceae, Staphylococcus spp), but is not very effective against Pseudomonas spp, Streptococcus spp. or Proteus mirabilis. Ibaﬂoxacin's primary metabolites, 8-hydroxy-ibaﬂoxacin and 7-hydroxy-ibaﬂoxacin, are also active (but less so than ibaﬂoxacin) and contribute to the drug's overall efﬁcacy. Pharmacokinetics In dogs, oral bioavailability is about 70-80% with peak levels oc-curring around 1. 5 hours after dosing. At 15 mg/kg, Cmax was 6 mcg/m L; volume of distribution at steady state was 1. 1 L/kg. Ibaﬂoxacin is presumably metabolized in the liver to at least two metabolites, 8-hydroxy-ibaﬂoxacin and 7-hydroxy-ibaﬂoxacin. Both metabolites have been shown to be active, but less so than the parent compound. Elimination occurs in both the urine and feces as unchanged drug and glucuronidated metabolites. T otal clearance is 8. 7 m L/min/kg and elimination half-life, 5. 2 hours. In cats, ibaﬂoxacin is rapidly absorbed after oral dosing. After dosing with food, peak levels occur in about 2-3 hours. Food slightly delays absorption, but peak levels are doubled and AUC in-creased when compared to fasted administration. Cats appear to metabolize and eliminate ibaﬂoxacin in a similar manner as dogs; with repeated dosing, cats, unlike dogs, apparently show signiﬁcant	pppbs.pdf
IFOSFAMIDE 471 increases over time in both AUC and Cmax of the parent drug and active metabolites. Contraindications/Precautions/Warnings The label (UK) states that for the majority of breeds, use is con-traindicated in dogs less than 8 months of age and in giant breeds less than 18 months old. It is contraindicated in cats less than 8 months old. It is also contraindicated in dogs or cats with known quinolone hypersensitivity. It is stated that the product should only be used based upon susceptibility testing. Adverse Effects Adverse effects reported in dogs and cats include diarrhea, soft fe-ces, vomiting, dullness, anorexia and salivation. These reportedly are mild and transient and occur with low frequency. No reports of ibaﬂoxacin-associated ocular toxicity in cats were found. In dogs, other ﬂuoroquinolones have, in rare incidences, caused elevated hepatic enzymes, ataxia, seizures, depression, lethargy, or nervousness; these could potentially also occur with ibaﬂoxacin. Reproductive/Nursing Safety The label (UK) states that ibaﬂoxacin can be used during pregnancy in dogs, but that safety has not been established in pregnant cats or in lactating dogs and cats. After dosing to goats, ibaﬂoxacin was detected in milk only in scant quantities. Overdosage/Acute Toxicity Speciﬁc information not located for ibaﬂoxacin. It is unlikely an acute overdose of ibaﬂoxacin would result in signs more serious than anorexia or vomiting, but the adverse effects noted above could occur. If the overdose occurs in cats, ophthalmic monitoring is recommended. In dogs doses of 75 mg/kg/day (5X) were appar-ently well tolerated; cats receiving up to 75 mg/kg/day demonstrat-ed salivation and vomiting. Drug Interactions Drug interactions associated with other ﬂuoroquinolones would also be expected with ibaﬂoxacin. The label states that ibaﬂoxacin should not be used with NSAIDs in dogs with a history of seizures. Other drug interactions with oral ﬂuoroquinolones include: T ! ANTACIDS or SUPPLEMENTS CONTAINING CATIONS (iron, zinc, magne-sium, aluminum, calcium ): May bind to ibaﬂoxacin and prevent its absorption T ! CYCLOSPORINE : Fluoroquinolones may exacerbate the nephrotox-icity of cyclosporine (used systemically) T ! NITROFURANTOIN : May antagonize the antimicrobial activity of the ﬂuoroquinolones; concomitant use is not recommended T ! SUCRALFATE : May inhibit absorption of ibaﬂoxacin, separate dos-es of these drugs by at least 2 hours T ! THEOPHYLLINE : Ibaﬂoxacin may increase theophylline blood levels Laboratory Considerations No speciﬁc laboratory concerns noted Doses T ! DOGS/CAT S: For susceptible infections: a) Using the 3% oral gel for labeled indications (dogs: dermal infections; cats: dermal or respiratory tract infections): 15 mg/kg PO once daily. The syringe should be adjusted to the calculated dosage by setting the syringe ring (steps of 0. 5 m L for the 15 m L syringe). Give at time of feeding. Duration treatment depends upon infection nature and severity; usu-ally a 10-day course is sufﬁcient, but can be extended until response is considered adequate. Reconsider treatment if no improvement in clinical response is seen after 5 days of ther-apy. In cases of deep pyoderma, reconsider treatment if suf-ﬁcient improvement not seen in 21 days of treatment. (Label Information; Ibaﬂin®—Intervet UK) Monitoring T ! Clinical efﬁcacy T ! Adverse effects—GI (vomiting, hypersalivation, diarrhea, an-orexia) Client Information T ! Give at the time of feeding T ! Contact veterinarian if vomiting, diarrhea or lack of appetite per-sist or are severe T ! Give as directed for the period the veterinarian speciﬁes, even if the patient seems well Chemistry/Synonyms Ibaﬂoxacin is a ﬂuoroquinolone with a molecular weight of 275. 28 and is available commercially as the racemate. Ibaﬂoxacin may also be known as S-25030 or Ibaﬂin®. Storage/Stability The oral gel should not be stored at temperatures more than 25°C. Once opened, it is recommended that the syringe be used within 8 weeks. Once a course of treatment is completed, dispose of unused product. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None in the USA A 3% Oral Gel (30 mg ibaﬂoxacin per gram of gel; 30. 9 mg per m L of gel) in 15 m L syringes with 0. 5 m L steps is available and labeled for use in dogs and cats in the UK, and in several other EU coun-tries; Ibaﬂin® (Intervet); (Rx). Depending on the market, 7. 5% oral gel, 30 mg, 150 mg, 300 mg, and 900 mg tablets may be available for use in dogs. HUMAN-LABELED PRODUCTS: None IFOSFAMIDE (eye-foss-fa-mide) Ifex® ANTINEOPLASTIC Prescriber Highlights TT Alkylating agent that may be useful in treating lympho-mas & sarcomas in dogs & cats TT Very limited veterinary clinical experience to date TT May be very toxic (myelosuppression, nephrotoxic, blad-der toxicity, neurotoxicity, GI, etc. ) TT Must be given with saline diuresis & bladder-protective agent (mesna) Uses/Indications In small animals, ifosfamide may be of beneﬁt as part of treatment protocols for a variety of neoplasms. Treatment of lymphomas and soft tissue sarcomas with ifosfamide in dogs and cats has been in-vestigated to some extent; some efﬁcacy has been demonstrated.	pppbs.pdf
472 IFOSFAMIDE In humans, ifosfamide is used in various treatment protocols for testicular neoplasms, bone and soft tissue sarcomas, bladder can-cer, lung cancer, cervical cancer, ovarian cancer, and some types of lymphomas. Pharmacology/Actions Ifosfamide appears to act similarly to other alkylating agents. Its active metabolites interfere with DNA replication and transcription of RNA, thereby disrupting nucleic acid function. It is cycle-phase nonspeciﬁc. Pharmacokinetics As ifosfamide is a prodrug and does not have pharmacologic activ-ity, it must be biotransformed into active metabolites. Ifosfamide's pharmacokinetics are very complex and are not well understood. While normally given IV, it is well absorbed after SC injection or oral administration; bioavailabilities via these routes are 90% or greater. Ifosfamide and its metabolites are widely distributed and enter into both bone and CNS. Ifosfamide is converted into its me-tabolites primarily via oxidative pathways found in the liver and, to a smaller extent, in the lungs. It then is catalyzed (primarily in cells) into the primary active alkylating agent, ifosfamide mustard. Ifosfamide and its metabolites are primarily excreted via the kidney into urine. Contraindications/Precautions/Warnings Because of its toxicity, ifosfamide should only be used by clinicians experienced with the use of cytotoxic agents and able to adequately monitor the effects of therapy. Ifosfamide is contraindicated in pa-tients hypersensitive to it or with severely depressed bone marrow function or active hemorrhagic cystitis. Ifosfamide should be used with extreme caution in patients with impaired renal function. Ifosfamide must be used in conjunction with mesna to reduce the risk for hemorrhagic cystitis. Adverse Effects Dose related myelosuppression occurs with ifosfamide use; neu-tropenia generally occurs at 5-7 days post treatment, but may be delayed (14-21 days) with repeated dosing. Nadirs in cats are seen typically at day 7 or 8. Platelets can also be signiﬁcantly impacted. Ifosfamide can damage bladder epithelium, and cause nephrotox-icity with resultant electrolyte abnormalities. Renal toxicity is pri-marily focused on proximal and distal tubular damage, but glom-erular effects may occur. T o reduce the incidence of nephrotoxicity and bladder toxicity, saline diuresis is performed (see dosages) and mesna given concomitantly to reduce bladder epithelial toxicity (see below). Volume overload with pulmonary edema may result however, particularly in patients with preexisting cardiac disease. Other adverse effects that may occur include: hypersensitivity reac-tions, nausea, particularly during infusion, vomiting, neurotoxicity (somnolence to confusion, coma, encephalopathy), alopecia, and abnormal liver function tests. Administering mesna with ifosfamide signiﬁcantly reduces the incidence and severity of ifosfamide-induced hemorrhagic cystitis and hematuria. Mesna interacts with metabolites of ifosfamide that cause the toxicity. Because mesna is hydrophilic, it does not enter most cells and, therefore, does not appear to signiﬁcantly reduce the anti-tumor efﬁcacy of ifosfamide. Mesna does not prevent or reduce the incidence of other adverse effects associated with ifosfamide (e. g., myelosuppression, GI effects, neurotoxicity, renal toxicity). Like other cytotoxic drugs, ifosfamide should be handled and disposed of appropriately. Reproductive/Nursing Safety In pregnant humans, ifosfamide is designated by the FDA as a cat-egory D drug (There is evidence of human fetal risk, but the poten-tial beneﬁts from the use of the drug in pregnant women may be ac-ceptable despite its potential risks. ) T eratogenic and fetotoxic effects have been demonstrated at usual doses in humans and laboratory animals. Ifosfamide is excreted in maternal milk. If this drug is being used in lactating mothers, consider using milk replacer. Overdosage/Acute Toxicity There is limited information available on acute overdoses. It would be expected that toxicity would be exacerbations of the adverse ef-fects seen at usual doses. No speciﬁc antidote (including mesna) is known; treatment is supportive. Methylene blue (50 mg in a 1-2% aqueous solution IV over 5 minutes) has been suggested to treat ifosfamide-induced encephalopathy in humans. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ifosfamide and may be of signiﬁcance in veterinary patients: !TBENZODIAZEPINES : A study where mice received benzodiazepines (diazepam, chlordiazepoxide, oxazepam ) prior to receiving ifosf-amide had increased concentrations of active ifosfamide and showed increased toxicity to the drug; clinical signiﬁcance has not been determined for human (or dog or cat) patients !TCISPLATIN : Ifosfamide may enhance cisplatin-induced ototoxicity and nephrotoxicity !TMYELOSUPPRESSIVE DRUGS, OTHER (e. g., other antineoplastics, chloramphenicol, ﬂucytosine, amphotericin B, or colchicine ): Oth-er bone marrow depressant drugs may cause additive myelo-suppression when used with ifosfamide Laboratory Considerations No speciﬁc laboratory interactions or considerations were noted. Doses !TDOGS: a) For treating lymphomas and soft tissue sarcomas: Give IV sa-line at 18. 3 m L/kg/hr for 6 hours. Give ifosfamide at 350 mg/ m2 (if patient weighs less than 10 kg), 375 mg/m2 (if greater than 10 kg) IV during the second 30 minutes of the 6-hour infusion. Mesna at a dose of 20% of the ifosfamide dose is given as an IV bolus at the start of the IV infusion and again 2 and 5 hours after the ifosfamide infusion. Repeat every 3 weeks. (Brewer 2003) !TCATS: a) For treating lymphomas and soft tissue sarcomas: Give IV sa-line at 18. 3 m L/kg/hr for 6 hours. Give ifosfamide at 350-500 mg/m2 IV during the second 30 minutes of the 6-hour infu-sion. Mesna at a dose of 20% of the ifosfamide dose is given as an IV bolus at the start of the IV infusion and again 2 and 5 hours after the ifosfamide infusion. Repeat every 3 weeks. (Brewer 2003) b) For sarcomas: 900 mg/m2 (with mesna and saline diuresis) IV q3 weeks. (Smith 2003a)	pppbs.pdf
IMIDOCARB DIPROPINATE 473 Monitoring T ! CBC with platelets (baseline and before re-dosing) T ! Renal function with electrolytes (baseline and before re-dosing) T ! Urinalysis baseline and periodic) T ! Liver function (baseline and periodic) T ! Other adverse effects (volume overload/pulmonary edema, neu-rotoxicity, GI toxicity) T ! Efﬁcacy Client Information T ! Clients should understand the relative investigational nature of using ifosfamide in dogs or cats and accept the possibility of se-vere adverse effects due to its use. T ! Owners should be instructed to avoid contact with animal's sa-liva or urine for at least 24 hours after dosing. Chemistry/Synonyms An alkylating agent structurally related to cyclophosphamide, ifosf-amide occurs as a white, crystalline powder with a melting point of 40°C. It is freely soluble in water and very soluble in alcohol. A 10% solution in water has a p H between 4 and 7. Ifosfamide may also be known as: MJF-9325, NSC-109724, Z-4942, Ifex®, Asoifos®, Cuantil®, Duvaxan®, Fentul®, Holoxan®, Holaxane®, Ifex ®, IFO-cell®, IFX®, Ifocris®, Ifolem ®, Ifomida®, Ifos®, Ifosmixan®, Ifoxan®, Mitoxana®, Seromida®, or Troxanol®. Storage/Stability/Compatibility Ifosfamide powder for injection should be stored at 20-25°C (68-77°F). It should be protected from temperatures greater than 30°C (86°F) as the drug may liquefy at temperatures greater than 35°C (95°F). Once reconstituted with sterile water for injection or bacteriostatic water for injection the solution is stable for 24 hours when refrigerated. ( Note : one reference states that bacteriostatic wa-ter for injection containing benzyl alcohol caused the solution to become turbid at concentrations of ifosfamide greater than 60 mg/ m L. No such incompatibility occurred when using bacteriostatic water for injection containing parabens. ) The reconstituted drug is compatible with D5W, normal saline, or lactated Ringer's and is sta-ble for up to 24 hours when refrigerated. Ifosfamide is compatible and stable when mixed with mesna in D 5W or lactated Ringer's. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Ifosfamide Powder: for IV infusion 1 g with 200 mg amps of Mesnex (mesna) in single dose vials; 3 g with 400 mg amps of Mesnex (mes-na) in single dose vials; Ifex® (Mead Johnson Oncology); Ifosfamide (American Pharmaceutical Partners); (Rx) Imidacloprid — See the listing in the Topical Dermatologic section in the appendix IMIDOCARB DIPROPINATE (i-mid-oh-karb) Imizol® ANTIPROTOZOAL Prescriber Highlights TT Antiprotozoal useful against Babesia & related parasites TT Contraindications: Patients exposed to cholinesterase-inhibiting drugs (e. g., pyridostigmine), pesticides, or chemicals TT Caution: Impaired lung, hepatic or renal function; safety in puppies, pregnant, lactating, or breeding animals has not been established TT Adverse Effects: Most common are pain during injec-tion & mild cholinergic signs (salivation, nasal drip, & brief episodes of vomiting); less common: panting, diar-rhea, injection site inﬂammation (rarely ulceration), & restlessness TT Not for intravenous administration Uses/Indications Imidocarb is approved for use to treat Babesia canis infections (babesiosis) in dogs, but the drug may also be efﬁcacious against Ehrlichia canis in this species. Imidocarb may be of beneﬁt in treat-ing Babesia and related parasitic diseases in a variety of domestic and exotic animals. Imidocarb appears to be more effective against B. canis than B. gibsoni. Pharmacology/Actions Imidocarb is thought to act by combining with nucleic acids of DNA in susceptible organisms, causing the DNA to unwind and denature. This damage to DNA is believed to inhibit cellular repair and replication. Pharmacokinetics No speciﬁc information was located for this drug. Contraindications/Precautions/Warnings Do not use imidocarb in patients exposed to cholinesterase-inhib-iting drugs, pesticides, or chemicals. The manufacturer states to consider risks versus beneﬁts before treating dogs with impaired lung, hepatic, or renal function. Donkeys appear to be sensitive to the toxic effects of the drug. Adverse Effects Most commonly reported adverse effects in dogs include pain dur-ing injection and mild cholinergic signs (salivation, nasal drip and brief episodes of vomiting). Less commonly reported effects in-clude panting, diarrhea, injection site inﬂammation (rarely ulcer-ation), and restlessness. Rarely, severe renal tubular or hepatic ne-crosis have occurred. Imidocarb has reportedly caused an increase incidence of tumor formation in rats. Horses given high therapeutic dosages (4 mg/kg) develop lacri-mation, sweating, and serous nasal discharge for 30 minutes after treatment. Do not administer intravenously. Reproductive/Nursing Safety Safety in puppies, pregnant, lactating, or breeding animals has not been established.	pppbs.pdf
474 IMIPENEM-CILASTATIN SODIUM Overdosage/Acute Toxicity Dogs receiving a dosage of 9. 9 mg/kg (1. 5X labeled dose) showed signs of liver injury (slightly increased liver enzymes), pain and swelling at the injection site, and vomiting. Overdoses or chronic toxicity may present with cholinergic signs (vomiting, weakness, lethargy, salivation) or adverse changes in liver, kidney, lung, or in-testinal function. Treatment with atropine may be useful to treat cholinergic signs associated with imidocarb. The LD-50 in horses is reportedly 16 mg/kg. Drug Interactions The manufacturer warns not use imidocarb in patients exposed to cholinesterase-inhibiting drugs, pesticides, or chemicals. Laboratory Considerations T ! Imidocarb IM injections may cause signiﬁcant increases in cre-atine kinase (CK). Doses T ! DOGS: For treatment of babesiosis: a) 6. 6 mg/kg IM or SC; repeat dose in 2 weeks (Package Insert; Imizol®—Schering) b) 5-6. 6 mg/kg IM or SC; repeat in 14 days or 7. 5 mg/kg IM or SC once. A single dose of 6 mg/kg the day following a dose of diminazene at 3. 5 mg/kg has also been shown to clear the infection. (Taboada and Lobetti 2006) For treatment of Ehrlichiosis: Note : A study (Eddlestone, Neer et al. 2005) demonstrated that imidocarb was not effective (alone) in clearing Ehrlichia canis from the blood of experimentally infected dogs. a) 5 mg/kg IM or SC; repeat in 14-21 days or 5 mg/kg IM re-peat in 84 days (Greene and Watson 1998) b) In particularly severe cases, imidocarb at 5 mg/kg SC (in a single injection or two injections 15 days apart) with doxycy-cline at 10 mg/kg/day for 28 days (Sainz 2002) For treatment of hepatozoonosis (H. canis): a) 5 mg/kg IM or SC; every 14 days until parasitemia clears. Usually 1-2 injections are sufﬁcient. (Macintire 1999) T ! CATS: For treatment of Cytauxzoon felis: a) 5 mg/kg IM every 2 weeks (Lappin 2000) b) 2-5 mg/kg IM; generally repeated 7 days after initial dose. Efﬁcacy not proven. Cholinergic effects can be mitigated by pre-treating with atropine. Must also give supportive therapy (IV ﬂuids, prophylactic heparin, nutritional/nursing care, analgesia, and potentially transfusion) (Cohn 2006) c) 5 mg/kg IM once and then 14 days later. (Greene, Meinkoth et al. 2006) For treatment of recurrent Haemobartonellosis (Mycoplasma haemofelis, Mycoplasma Haemominutum): a) Doxycycline is preferred, but in cats intolerant of doxycycline the following alternatives may be effective: imidocarb can be used at 5 mg/kg IM, SC every 14 days until able to maintain a normal PCV. Other optional treatment includes enroﬂoxa-cin at 5 mg/kg PO daily or marboﬂoxacin at 2. 75 mg/kg PO daily. (Lappin 2002b), (Lappin 2006c) T ! HORSES: For treatment of equine piroplasmosis (Babesia caballi; Babesia equi): a) 2. 2 mg/kg IM will generally allow clinical signs to subside. T o eliminate B. caballi inject 2 mg/kg IM once a day for 2 days. B. equi more difﬁcult to eliminate; there has been some suc-cess reported when imidocarb is given at 4 mg/kg IM at 72 hour intervals for 4 doses. (Sellon 2004) T ! SHEEP: For treatment of babesiosis: a) 1. 2 mg/kg IM; repeat in 10-14 days (Mc Hardy, Woolon et al. 1986) Monitoring T ! Efﬁcacy T ! Adverse effect proﬁle Chemistry/Synonyms Imidocarb dipropinate is a diamidine of the carbanalide series of antiprotozoal compounds. Imidocarb may also be known as 4A65 (imidocarb hydrochlo-ride) and Imizol®. Storage/Stability The injection should be stored between 2°-25°C (36°-77°F) and protected from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Imidocarb Dipropinate for IM or SC Injection: 120 mg/m L in 10 m L multi-dose vials; Imizol® (Schering-Plough); (Rx). Approved for use in dogs. HUMAN-LABELED PRODUCTS: None IMIPENEM-CILASTATIN SODIUM (ih-me-peh-nem sye-la-sta-tin) Primaxin® CARBAPENEM ANTIBIOTIC Prescriber Highlights TT Broad spectrum antibiotic/deactivating enzyme inhibitor combination used for serious infections where a single agent is desired TT Contraindications/Cautions: Patients hypersensitive to it or other beta-lactams, patients with renal impairment (dosages adjustment may be required), CNS disorders (e. g., seizures, head trauma) TT Adverse Effects: GI effects, CNS toxicity (seizures, tremors), hypersensitivity, & infusion reactions (thrombophlebitis) TT Too rapid IV infusions may cause GI toxicity or other untoward effects); Rarely: increases in renal or hepatic function tests; hypotension or tachycardia TT Separate dosage forms for IM or IV use TT Can be expensive Uses/Indications Imipenem may be useful in equine or small animal medicine to treat serious infections when other less expensive antibiotics are in-effective or have unacceptable adverse effect proﬁles. Pharmacology/Actions This ﬁxed combination of a carbapenem antibiotic (imipenem) and an inhibitor (cilastatin) of dehydropeptidase I (DHP I) has a very broad spectrum of activity. Imipenem is generally considered to be a bactericidal agent, but may be static against some bacteria.	pppbs.pdf
IMIPENEM-CILASTATIN SODIUM 475 It has an afﬁnity for and binds to most penicillin-binding protein sites, thereby inhibiting bacterial cell wall synthesis. Imipenem has activity against a wide variety of bacteria, in-cluding gram-positive aerobic cocci (including some bacterio-static activity against some enterococci), gram-positive aerobic bacilli (including static activity against Listeria), gram-negative aerobic bacteria (Haemophilus, Enterobacteriaceae, many strains of Pseudomonas aeruginosa), and anaerobes (including some strains of Bacteroides). Imipenem is not efﬁcacious for treating infections caused by me-thicillin-resistant staphylococci or resistant strains of Enterococcus faecium. Cilastatin inhibits the metabolism of imipenem by DHP 1 on the brush borders of renal tubular cells. This serves two functions: it allows higher urine levels and may protect against proximal renal tubular necrosis that can occur when imipenem is used alone. Pharmacokinetics Neither drug is absorbed appreciably from the GI tract and, there-fore, they are given parenterally. Bioavailability after IM injection is approximately 95% for imipenem and 75% for cilastatin. In dogs, bioavailability of imipenem after SC injection is complete. Imipenem is distributed widely throughout the body, with the ex-ception of the CSF. Imipenem crosses the placenta and is distrib-uted into milk. When given with cilastatin, imipenem is eliminated by both renal and non-renal mechanisms. Approximately 75% of a dose is excreted in the urine and about 25% is excreted by un-known non-renal mechanisms. Half-lives in patients with normal renal function range from 1-3 hours on average. In horses average elimination time is 70 minutes; 60 minutes in dogs. Contraindications/Precautions/Warnings The potential risks versus beneﬁts should be carefully weighed be-fore using imipenem/cilastatin in patients hypersensitive to it or other beta-lactam antibiotics (e. g., penicillins, cephalosporins as partial cross-reactivity may occur), with renal function impairment (dosages may need to be reduced or time between doses length-ened), or with CNS disorders (e. g., seizures, head trauma) as CNS adverse effects may be more likely to occur. Adverse Effects Potential adverse effects include: GI effects (vomiting, anorexia, di-arrhea), CNS toxicity (seizures, tremors), hypersensitivity (pruri-tus, fever to anaphylaxis) and infusion reactions (thrombophlebitis; too rapid IV infusions may cause GI toxicity or other untoward effects). Rarely, transient increases in renal (BUN or serum creatinine values) or hepatic (AST/ALT/Alk Phosphatase) function tests may be noted, as well as, hypotension or tachycardias. Reproductive/Nursing Safety While no teratogenic effects have been noted in animal studies, safe use during pregnancy has not been ﬁrmly established. In humans, the FDA categorizes this drug as category C for use during preg-nancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal re-production studies and no adequate studies in humans. ) While imipenem enters milk, no adverse effects attributable to it have been noted in nursing offspring. Overdosage/Acute Toxicity Little information is available. The LD 50 of imipenem:cilastatin in a 1:1 ratio in mice and rats is approximately 1 g/kg/day. Acute overdoses should be handled by halting therapy then treating sup-portively and symptomatically. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving imipenem-cilastatin and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES : Additive effects or synergy may result when aminoglycosides are added to imipenem/cilastatin therapy, par-ticularly against Enterococcus, Staph. aureus, and Listeria mono-cytogenes. There is apparently neither synergy nor antagonism when used in combination against Enterobacteriaceae, including Pseudomonas aeruginosa. !TBETA-LACTAM ANTIBIOTICS : Antagonism may occur when used in combination with other beta lactam antibiotics against several Enterobacteriaceae (including many strains of Pseudomonas aeruginosa and some strains of Klebsiella, Enterobacter, Serratia, Enterobacter, Citrobacter, and Morganella); clinical importance of this interaction is unclear, but at present it is not recommend-ed to use imipenem in conjunction with other beta-lactam anti-biotics. !TCHLORAMPHENICOL : May antagonize the antibacterial effects of imipenem (in vitro evidence) !TPROBENECID : May increase concentrations and elimination half-life of cilastatin, but not imipenem; concurrent use not recommended !TTRIMETHOPRIM/SULFA : Synergy may occur against Nocardia as-teroides when imipenem is used in combination with trimetho-prim/sulfa Laboratory Considerations !TImipenem may cause a false-positive urine glucose determination when using the cupric sulfate solution test (e. g., Clinitest®), Bene-dict' solution or Fehling's solution. Enzymatic glucose oxidase based tests are not affected (e. g., Tes-Tape®, Clinistix®). Doses Note : When giving IM, the manufacturer recommends a 21g nee-dle (deep IM) with aspiration, to avoid IV administration. !TDOGS & CAT S: For susceptible infections: a) 5-10 mg/kg IV, SC or IM (IM form is different) q8h (Aucoin 2002b) b) 2-5 mg/kg every 8 hours (Lappin 1997) c) 5-10 mg/kg IV (given over 30 minutes) q6h or IM q6h (mixed with 1% lidocaine to reduce pain). Note : Cannot in-terchange IV and IM dosage forms. (Trepanier 1999) d) For tissue infections: 3-7. 5 mg/kg IV, SC or IM q4-6h for 3-5 days; for sepsis, more resistant organisms give 5 mg/kg IV q4h (multi-drug resistant bacteria may require q2h dos-ing) for 3-5 days (Greene, Hartmannn et al. 2006) e) For treatment of Nocardiosis: 2-5 mg/kg IV q8h (Lemarie 2003a) !THORSES: For susceptible infections: a) Adult horses: 10-20 mg/kg via slow IV (over a 10 minute period) q6h; alternatively a CRI of 16 mcg/kg/minute should maintain synovial concentrations greater than 1 mcg/m L. (Orsini, Moate et al. 2005) b) Foals: 20 mg/kg IV q6-8h (Brumbaugh 1999) c) Foals: 10-20 mg/kg IV q6h; seizures have been reported (Wilkins 2004b) d) Foals: 5-10 mg/kg IM q12h. (Mc Kenzie 2005)	pppbs.pdf
476 IMIPRAMINE Monitoring T ! Efﬁcacy T ! Adverse effects (including renal and hepatic function tests if treatment is prolonged or patient's renal or hepatic functions are in question) Client Information T ! Imipenem/cilastatin should be administered in an inpatient setting. T ! Clients should be informed of the cost of using this medication. Chemistry/Synonyms Imipenem monohydrate is a carbapenem antibiotic that occurs as white or off-white, non-hygroscopic, crystalline compound. At room temperature, 11 mg are soluble in 1 m L of water. Cilastatin sodium, an inhibitor of dehydropeptidase I (DHP I), occurs as an off-white to yellowish, hygroscopic, amorphous compound. More than 2 grams are soluble in 1 m L of water. The commercially available injections are available in a 1:1 ﬁxed dose ratio. The solutions are clear to yellowish in color. p H after reconstitution ranges from 6. 5 to 7. 5. These products have sodium bicarbonate added as a buffer. The suspensions for IM use are white to light tan in color. Imipenem may also be known as: N-formimidoyl thienamycin, imipemide, MK-787, and MK-0787; multi-ingredient preparations: Imipem®, Klonam®, Primaxin®, Tenacid®, Tienam®, Tracix®, and Zienam®. Storage/Stability/Compatibility Commercially available sterile powders for injection should be stored at room temperature (<25°C). After reconstitution, the solu-tion is stable for 4 hours at room temperature; 10 hours when re-frigerated. If other diluents are used, stability times may be reduced (see package insert). Do not freeze solutions. The manufacturer does not recommend admixing with other drugs. After reconstitution the sterile powder for suspension with 1% lidocaine HCl injection, the suspension should be used within one hour. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Imipenem Cilastatin Powder for Injection: 250 mg and 250 mg cilas-tatin (0. 8 m Eq sodium); 500 mg and 500 mg cilastatin (1. 6 m Eq so-dium) in vials, infusion bottles and ADD-Vantage vials; Primaxin® I. V. (Merck); (Rx) Imipenem Cilastatin Powder for Injection: 500 mg and 500 mg cilas-tatin (1. 4 m Eq sodium); 750 mg and 750 mg cilastatin (2. 1 m Eq so-dium) in vials; Primaxin® I. M. (Merck); (Rx) IMIPRAMINE HCL IMIPRAMINE PAMOATE (im-ip-ra-meen) Tofranil® TRICYCLIC ANTIDEPRESSANT Prescriber Highlights TT Tricyclic “antidepressant” used primarily for cataplexy & urinary incontinence (dogs/cats) narcolepsy & ejacula-tory dysfunction (horses) TT May reduce seizure thresholds in epileptic animals TT Very toxic in overdoses to both animals & humans TT May be teratogenic TT Adverse Effects: Sedation & anticholinergic effects (tachycardia, hyperexcitability, tremors) most likely Uses/Indications In dogs and cats, imipramine has been used to treat cataplexy and urinary incontinence. In horses, imipramine has been used to treat narcolepsy and ejaculatory dysfunction (no parenteral dosage forms available). Pharmacology/Actions Imipramine and its active metabolite, desipramine, have a com-plicated pharmacologic proﬁle. From a slightly oversimpliﬁed viewpoint, they have 3 main characteristics: blockage of the amine pump, thereby increasing neurotransmitter levels (principally se-rotonin, but also norepinephrine), sedation, and central and pe-ripheral anticholinergic activity. While not completely understood, the antienuretic activity of imipramine is thought to be related to its anticholinergic effects. In animals, tricyclic antidepressants are similar to the actions of phenothiazines in altering avoidance behaviors. Pharmacokinetics Imipramine is rapidly absorbed from both the GI tract and from parenteral injection sites. Peak levels occur within 1-2 hours af-ter oral dosing. Imipramine and desipramine enter the CNS and maternal milk in levels equal to that found in maternal serum. The drug is metabolized in the liver to several metabolites, including desipramine, which is active. In humans the terminal half-life is ap-proximately 8-16 hours. Contraindications/Precautions/Warnings These agents are contraindicated if prior sensitivity has been noted with any other tricyclic. Concomitant use with monoamine oxidase inhibitors is generally contraindicated. Adverse Effects While there is little experience with this drug in domestic animals, the most predominant adverse effects seen with the tricyclics are related to their sedating and anticholinergic (dry mouth, constipa-tion, tachycardia, hyperexcitability, tremors) properties. They can cause CNS stimulation (seizures) however, and adverse effects can run the entire gamut of systems including hematologic (bone mar-row suppression), GI (diarrhea, vomiting), endocrine, etc. Reproductive/Nursing Safety Isolated reports of limb reduction abnormalities have been noted; restrict use to pregnant animals when the beneﬁts clearly outweigh	pppbs.pdf
IMIPRAMINE 477 the risks. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Imipramine is excreted into milk in low concentrations (ap-proximate milk:plasma ratio of 0. 4 to 1. 5). Overdosage/Acute Toxicity Overdosage with tricyclics can be life-threatening (arrhythmias, cardiorespiratory collapse). Because the toxicities and therapies for treatment are complicated and controversial, it is recommended to contact a poison control center for further information in any po-tential overdose situation. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving imipramine and may be of signiﬁcance in veterinary patients: !TANTICHOLINERGIC AGENTS : Because of additive effects, use with imipramine cautiously !TCIMETIDINE : May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity !TCISAPRIDE : Increased risk for prolonged QT interval !TCLONIDINE : Tricyclics may increase blood pressure !TCNS DEPRESSANTS : Because of additive effects, use with imip-ramine cautiously !TLEVODOPA : Imipramine may decrease levodopa oral absorption !TPHENOBARBITAL : May decrease tricyclic levels !TQUINIDINE : Increased risk for imipramine toxicity !TRIFAMPIN : May decrease tricyclic blood levels !TSSRIs (e. g., ﬂuoxetine, paroxetine, sertraline, etc. ): Increased risk for serotonin syndrome !TSYMPATHOMIMETIC AGENTS : Use in combination with sympath-omimetic agents may increase the risk of cardiac effects (arrhyth-mias, hypertension, hyperpyrexia) !TMONOAMINE OXIDASE INHIBITORS (including amitraz, and possibly selegiline ): Concomitant use (within 14 days) with monoam-ine oxidase inhibitors is generally contraindicated (serotonin syndrome) !TTHYROID AGENTS : May increase risk for cardiac arrhythmias Laboratory Considerations !TECG: Tricyclics can widen QRS complexes, prolong PR intervals and invert or ﬂatten T-waves on ECG !TGLUCOSE, BLOOD : Tricyclics may alter (increase or decrease) blood glucose levels Doses !TDOGS: For urethral incompetence: a) 5-15 mg (total dose) PO q12h (Labato 1994), (Bartges 2006a) b) For urinary incontinence when other agents fail: 5-20 mg (total dose) PO q12h (Lane 2000) For cataplexy: a) 0. 5-1 mg/kg PO q8h; titrate dose based on clinical effect (Fenner 1994); (Coleman 1999) For behavior-related conditions: a) For adjunctive treatment of separation anxiety or other tri-cyclic antidepressant-responsive behavior disorders: 2. 2-4. 4 mg/kg PO once to twice daily (Marder 1991) For adjunctive treatment of pain: a) For adjunctive cancer pain treatment: 0. 5-1 mg/kg PO q8h (Lester and Gaynor 2000) !TCATS: For urethral incompetence: a) 2. 5-5 mg (total dose) PO q12h (Labato 1994); (Bartges 2006a) For adjunctive cancer pain treatment: a) 2. 5-5 mg (total dose) PO q12h (Lester and Gaynor 2000) !THORSES: (Note : ARCI UCGFS Class 2 Drug) Note : The injectable product is no longer marketed in the USA. a) For pharmacologic induced ejaculation: 2 mg/kg IV. If imi-pramine alone does not induce erection and ejaculation in 10-15 minutes, give xylazine 0. 2-0. 3 mg/kg IV. (Samper 2004) b) For narcolepsy/cataplexy: 0. 55 mg/kg IV or 250-750 mg (total dose) orally. PO administration produces inconsistent results. (Andrews and Matthews 2004) Monitoring !TEfﬁcacy !TAdverse effects Client Information !TAll tricyclics should be dispensed in child-resistant packaging and kept well away from children or pets. !TInform clients that several weeks may be required before efﬁcacy is noted and to continue dosing as prescribed. Chemistry/Synonyms A tricyclic antidepressant agent, imipramine is available commer-cially in either the hydrochloride or pamoate salts. Imipramine HCl occurs as an odorless or practically odorless, white to off-white crystalline powder that is freely soluble in water or alcohol. Imipramine pamoate occurs as a ﬁne yellow powder that is practi-cally insoluble in water, but soluble in alcohol. The HCl injection has a p H of 4-5. Imipramine HCl may also be known as: imipramini chloridum, imipramini hydrochloridum, imizine, Antidep®, Celamine®, Depramina®, Depsonil®, Elepsin®, Ethipramine®, Imipra ®, Imiprex®, Imiprin®, Imp-Tab®, Impril®, Janimine®, Melipramine®, Mipralin®, Novo-Pramine®, Praminan®, Primonil®, Pryleugan®, Sermonil®, Surplix®, Talpramin®, and Tofranil®. Storage/Stability Imipramine HCl tablets and the pamoate capsules should be stored in tight, light resistant containers, preferably at room temperature. The HCl injection should be stored at temperatures less than 40°C and freezing should be avoided. Expiration dates for oral HCL products are from 3-5 years after manufacture; for the pamoate, 3 years. Imipramine HCl will turn yellow to reddish on exposure. Slight discoloration will not affect potency, but marked changes in color are associated with a loss of potency. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Imipramine HCl Tablets: 10 mg, 25 mg & 50 mg; Tofranil® (Norvar-tis), generic; (Rx)	pppbs.pdf
478 INAMRINONE LACTATE Imipramine Pamoate Capsules: 75 mg, 100 mg, 125 mg & 150 mg; Tofranil®-PM (Norvartis), generic; (Rx) Imiquimod—see the Topical Dermatologic section in the appendix INAMRINONE LACTATE (in-am-ri-none) Amrinone, Inocor® INOTROPIC AGENT Prescriber Highlights TT Second-line agent for short-term management of CHF TT Contraindicated with severe aortic or pulmonic valve disease; use extreme caution with hypertrophic cardiomyopathy TT Monitoring of cardiac effects & adverse effects mandatory Uses/Indications Inamrinone is considered a second line agent for the short-term management of CHF. It was originally called amrinone, but was changed to inamrinone presumably to avoid confusion with amiodarone. Pharmacology/Actions The exact mechanisms of amrinone's cardiac effects are not well un-derstood. It is thought the primary effects are due to its vasodilatory effects, thereby reducing both preload and after load. Because it inhib-its phosphodiesterase, it may directly stimulate cardiac contractility. Pharmacokinetics Although no oral commercial dosage forms are available, inamri-none is rapidly absorbed after oral administration. After initial intravenous injection, effects begin within 2-3 minutes and peak effects occur within 10 minutes. Cardiac effects generally correlate with the drug's serum level. Amrinone's distribution characteristics are not well described. In humans, it has an apparent volume of distribution of 1. 2 L/kg. It exhibits low to moderate protein bind-ing (10-49%). It is unknown if it crosses the placenta, blood-brain barrier, or enters into maternal milk. Inamrinone is eliminated pri-marily via the kidneys. About 63% of a dose is excreted (10-40% unchanged) into the urine. The duration of effect (in humans) is dose related with a single dose lasting from 30 minutes after a 0. 75 mg/kg IV dose to 2 hours after a 3 mg/kg dose. Plasma half-lives may be prolonged in patients with CHF. Contraindications/Precautions/Warnings Inamrinone is considered contraindicated when severe aortic or pulmonic valve disease is present or in patients hypersensitive to it or bisulﬁtes. The potential risks versus beneﬁts of therapy with inamrinone should be carefully considered in patients with hyper-trophic cardiomyopathy. Adverse Effects Use in domestic animals is very limited. Adverse effects that po-tentially could be seen include arrhythmias (drug is not inherently arrhythmogenic, but CHF patients are more susceptible to arrhyth-mias secondary to any drug), hypotension, GI effects (vomiting, di-arrhea), thrombocytopenia (particularly with prolonged therapy), hepatotoxicity, and hypersensitivity reactions (variable symptoma-tology: pericarditis to myositis, etc. ). Inamrinone should only be used in settings where appropriate monitoring may be employed. Reproductive/Nursing Safety Reproductive safety data are conﬂicting; use only when beneﬁts outweigh risks. In humans, the FDA categorizes this drug as cat-egory C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in hu-mans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether inamrinone is secreted in milk; exercise caution. Overdosage/Acute Toxicity Only one case (human) of accidental massive overdose resulting in death has been reported (causal relationship not unequivocally es-tablished). Because hypotension is the primary problem that would generally be seen, circulatory support should be instituted. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving inamrinone lactate and may be of signiﬁcance in veterinary patients: T ! DIGOXIN : Digoxin and other inotropic cardiac glycosides have an additive effect with inamrinone; this is generally considered a positive drug interaction. T ! DISOPYRAMIDE : May cause excessive hypotension when used with inamrinone Doses T ! DOGS: As a positive inotropic agent: a) 1-3 mg/kg IV as a slow IV bolus followed by a 10-100 mcg/ kg/min IV CRI; H the initial bolus may be administered 20-30 minutes after the ﬁrst bolus. (Kittleson 2006a) b) 1-3 mg/kg IV followed by a 30-100 mcg/kg/min IV CRI (Muir and Bonagura 1994) c) 2 mg/kg bolus IV, followed by 30-300 mcg/kg/min IV infu-sion (Fox 2003a) d) For patients coming off cardiopulmonary bypass with poor cardiac contractility: 0. 25-0. 6 mg/kg loading, then 5-45 mcg/kg/min CRI (Nelson 2003a) T ! CATS: a) 1-3 mg/kg IV followed by 30-100 mcg/kg/min IV infusion (Muir and Bonagura 1994) b) 1-3 mg/kg IV as a slow IV bolus followed by a 10-100 mcg/ kg/min IV CRI; H the initial bolus may be administered 20-30 minutes after the ﬁrst bolus. (Kittleson 2006a) Monitoring T ! Blood pressure T ! Heart rate/rhythm; continuous ECG recommended T ! Body weight T ! Platelet counts Client Information T ! Clients should be made aware of the “investigational nature” of the use of this drug in dogs or cats Chemistry/Synonyms Formerly known as amrinone lactate, inamrinone is unrelated structurally to cardiac glycosides or catecholamines, and is a bipyr-dine cardiac inotropic agent. It occurs as a pale yellow, crystalline powder and is insoluble in water and slightly soluble in alcohol. The	pppbs.pdf
INSULIN 479 commercially available injection has a p H adjusted to 3. 2-4 and an osmolality of 101 m Osm/L. Inamrinone may also be known as: amrinone, Win-40680, Amcoral®, Inocor®, Vesistol®, and Wincoram®. Storage/Stability/Compatibility The commercially available injection should be stored at room temperature and protected from light. It is stable for 2 years after manufacture. Inamrinone lactate for injection is reportedly compatible with 0. 45% or 0. 9% sodium chloride injection, propranolol HCl, vera-pamil HCl. It is reportedly incompatible with solutions containing dextrose or sodium bicarbonate. Compatibility is dependent upon factors such as p H, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Inamrinone Lactate for Injection: 5 mg/m L (as lactate) in 20 m L amps; generic (Abbott Hospital); (Rx) INSULIN INJECTION, REGULAR (CRYSTALLINE ZINC) INSULIN, ISOPHANE SUSPENSION (NPH) INSULIN, PROTAMINE ZINC SUSPENSION (PZI) INSULIN, PORCINE ZINC SUSPENSION (LENTE) INSULIN, GLARGINE (in-su-lin) HORMONE Note : Insulin preparations available to the practitioner are in a constant state of change. It is highly recommended to review current references or sources of information pertaining to insulin therapy for dogs and cats to maximize efﬁcacy of therapy and reduce the chance for errors. Prescriber Highlights TT Pancreatic hormone used to treat diabetic ketoacidosis, uncomplicated diabetes mellitus, & as adjunctive therapy in treating hyperkalemia TT Contraindications: No absolute contraindications TT Adverse Effects: Hypoglycemia, insulin-induced hypergly-cemia (“Somogyi effect”), insulin antagonism/resistance, rapid insulin metabolism, & local reactions to the “for-eign” proteins TT Do not confuse insulin types, strengths, syringes TT Drug Interactions Monograph by Dinah Jordan, Pharm D, DICVP Uses/Indications Insulin preparations have been used for the adjunctive treatment of diabetic ketoacidosis, uncomplicated diabetes mellitus, and as adjunctive therapy in treating hyperkalemia. Insulin treatment in veterinary species has been primarily in dogs and cats. Experience using insulin in other veterinary species is limited. Regular insulin is commonly used for stabilization of the dia-betic patient and is the only formulation appropriate for intrave-nous administration (IV); it is also administered by intramuscular (IM) and subcutaneous (SC) injection. Only regular insulin should be used in patients with diabetic ketoacidosis or diabetic coma. Regular insulin is preferred in patients with poor tissue perfusion, shock, or cardiovascular collapse, or in patients requiring insulin for the treatment of severe, life-threatening hyperkalemia causing cardiotoxicity (i. e., >8 m Eq/L). Pharmacology Eliciting multiple biological responses, insulin initiates its actions by binding to cell-surface receptors, present in varying numbers in virtually all mammalian cells. This binding results in a cascade of intracellular events which can be studied in detail by consulting a physiology text. Insulin is the primary hormone responsible for controlling the uptake, utilization, and storage of cellular nutrients. Insulin affects primarily liver, muscle, and adipose tissues, but also exerts potent regulatory effects on other cell types as well. Insulin stimulates car-bohydrate metabolism in cardiac, skeletal, and adipose tissue by facilitating the uptake of glucose by these cells. Other tissues, such as brain, nerve, intestinal, liver, and kidney tubules, do not require insulin for glucose transport. Liver cells do need insulin to convert glucose to glycogen (for storage), and the hypothalamus requires insulin for glucose entry into the satiety center. Insulin has a direct effect on fat and protein metabolism. The hormone stimulates lipo-genesis, increases protein synthesis, and inhibits lipolysis and free fatty acid release from adipose tissues. Insulin promotes an intrac-ellular shift of potassium and magnesium. Exogenous insulin elicits all the pharmacologic responses usually produced by endogenous insulin. Pharmacokinetics Insulin is metabolized mainly by the liver and kidneys (also muscle and fat to a lesser degree) by enzymatic reduction to form peptides and amino acids. About 50% of the insulin that reaches the liver via the portal vein is destroyed and never reaches the general cir-culation. Insulin is ﬁltered by the renal glomeruli and is reabsorbed by the tubules, which also degrade it. Severe impairment of renal function appears to affect the rate of clearance of circulating insu-lin to a greater extent than hepatic disease. Hepatic degradation of insulin operates near its maximal capacity and cannot compensate for diminished renal breakdown of the hormone. The half-life of endogenous insulin is less than ten minutes in normal subjects and in patients with uncomplicated diabetes. Note : The pharmacokinetics of various insulin formulations can vary widely from published values between species, among individ-uals within a species, and within the same individual patient from day to day. Therefore, the values should only be used as a general reference guide. Regular insulin injection: When the recombinant human insulin product is given IV to dogs and cats, it has an immediate onset of action, with maximum effects occurring at 0. 5-2 hours; dura-tion of action is 1-4 hours. Following IM administration, onset is 10-30 minutes; peak 1-4 hours; and duration 3-8 hours. After subcutaneous administration, onset is generally 10-30 minutes; peak from 1-5 hours; duration 4-10 hours.	pppbs.pdf
480 INSULIN Although the kinetics of all insulin products vary markedly for the individual product between species, regular insulin appears to ex-hibit the most similar properties. Isophane insulin suspension (NPH): NPH is administered by the sub-cutaneous route only. Following SC administration of the recombi-nant human insulin product, onset is 0. 5-2 hours in dogs and cats; peak is 2-10 hours in dogs and 2-8 hours in cats; and duration is 6-18 hours in dogs and 4-12 hours in cats. Porcine insulin zinc suspension (Lente ): Lente is classiﬁed as inter-mediate-acting; it has two peaks of activity following subcutane-ous administration (the ﬁrst at around 4 hours and the second at around 11 hours). The duration of activity varies between 14 and 24 hours. The peak(s), duration of activity, and dose required to adequately control diabetic signs will vary between dogs. Following SC administration of the recombinant human insulin lente prod-uct, onset is 0. 5-2 hours in dogs and cats. Pharmacokinetics of the puriﬁed pork product are similar to the human product. Protamine zinc suspension (PZI): Following SC administration, onset is 1-4 hours in dogs and cats; peak is 4-8 hours; duration is 6-28 hours in dogs; 6-24 hours in cats. Insulin glargine injection : Following SC injection, the acidic solution is neutralized, and microprecipitates are formed which slowly re-lease small amounts of insulin glargine. This action results in a rela-tively constant concentration/time proﬁle over 24 hours with no pronounced peak in humans. A small Australian study compared equal doses of insulin glargine, PZI (mixed beef/pork), and puriﬁed pork lente insulin in 9 healthy cats. Results showed no signiﬁcant difference in onset of action or nadir glucose concentrations among the insulins; time to reach nadir glucose concentration was longer for glargine (~16 hours) vs. PZI (~6 hours) and lente (~4. 5 hours). Duration was signiﬁcantly shorter for lente than for glargine or PZI, with glargine and PZI not signiﬁcantly different. The study in healthy cats also showed there were deﬁnite peaks in insulin con-centration and glucose lowering effects of glargine. (Marshall and Rand 2004) Contraindications/Precautions/Warnings Because there are no alternatives for insulin when it is used for dia-betic indications, there are no absolute contraindications to its use. If animals develop hypersensitivity (local or otherwise) or should insulin resistance develop, a change in type or species of insulin should be tried. Pork insulin is identical to canine insulin and is considered the insulin source of choice for diabetic dogs. Human insulin has a low potential for producing insulin antibodies in dogs (~5%), while beef/pork insulin produces antibody formation in a higher percentage of dogs (~45%) and is associated with insulin re-sistance and poor or erratic glycemic control. Dogs known to have a systemic allergy to pork or pork products should not be treated with Vetsulin®. Beef/pork insulin is considered the source of choice in cats, although the incidence of insulin antibody production is low and approximately the same in cats treated with either beef/ pork or human insulin. Overt insulin resistance caused by insulin antibodies occurs in less than 5% of cats treated with recombinant human insulin. Do not inject insulin at the same site day after day or lipodystro-phic reactions can occur. Adverse Effects Adverse effects of insulin therapy may include hypoglycemia (see overdosage below), insulin-induced hyperglycemia (“Somogyi ef-fect”), insulin antagonism/resistance, rapid insulin metabolism, and local reactions to the “foreign” proteins. Reproductive/Nursing Safety In humans, the FDA categorizes all human insulin and puriﬁed pork insulin as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrat-ed a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In humans, the FDA categorizes insulin glargine as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no ad-equate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Insulin is compatible with nursing. Overdosage/Acute Toxicity Overdosage of insulin can lead to various degrees of hypoglycemia. Signs may include weakness, shaking, head tilting, lethargy, ataxia, seizures, blindness, bizarre behavior, and coma. Other signs may include restlessness, hunger, and muscle fasciculations. Prolonged hypoglycemia can result in permanent brain damage or death. Mild hypoglycemia may be treated by offering the animal its usu-al food. More serious symptoms (such as seizure) should be treated with oral dextrose solutions (e. g., Karo® syrup) rubbed on the oral mucosa (not poured down the throat) or by intravenous injections of 50% dextrose solutions (small amounts, slowly administered— usually 2-15 m L). If the animal is seizuring, ﬁngers should not be placed in the animal's mouth. Once the animal's hypoglycemia is alleviated (response usually occurs within 1-2 minutes), it should be closely monitored (both by physical observation and serial blood glucose levels) to prevent a recurrence of hypoglycemia (especially with the slower absorbed products) and to prevent hyperglycemia from developing. Future insulin dosages or feeding habits should be adjusted to prevent further occurrences of hypoglycemia. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving insulin and may be of signiﬁcance in veterinary patients: !TBETA-ADRENERGIC BLOCKERS (e. g., propranolol ): Can have variable effects on glycemic control and can mask the signs associated with hypoglycemia !TCLONIDINE; RESERPINE : Can mask the signs associated with hypo-glycemia !TDIGOXIN : Because insulin can alter serum potassium levels, pa-tients receiving concomitant cardiac glycoside (e. g., digoxin) therapy should be closely monitored; especially true in patients receiving concurrent diuretic therapy The following drugs or drug classes may potentiate the hypoglycemic activity of insulin : !!ALCO H OL !!ANABOLIC STEROIDS (e. g., stanozolol, boldenone ) !!ANGIOTENSIN CONVERTING ENZYME INHIBITORS (e. g., captopril, enalapril ) !!ASPIRIN or other salicylates !!DISOPYRAMIDE !!FLUOXETINE !!MONOAMINE OXIDASE INHIBITORS !!SOMATOSTATIN DERIVATIVES (e. g., octreotide ) !TSULFONAMIDES	pppbs.pdf
INSULIN 481 The following drugs or drug classes may decrease the hypoglycemic activity of insulin : !!CALCIUM CHANNEL BLOCKERS (e. g., diltiazem ) !!CORTICOSTEROIDS !!DANAZOL !!DIURETICS !!ISONIAZID !!NIACIN !!PHENOTHIAZINES !TTHYROID HORMONES (can elevate blood glucose levels in diabetic patients when thyroid hormone therapy is ﬁrst initiated) Doses Note : Treatment of diabetes mellitus and in particular, diabetic ke-toacidosis is complex. Insulin is only one component of therapy; ﬂuid and electrolytes, acid/base, and if necessary, antimicrobial therapy must also be employed. Adequate patient monitoring is mandatory. The reader is strongly encouraged to refer to more thorough discussions of treatment in veterinary endocrinology or internal medicine references for additional information. !TDOGS: For adjunctive therapy of diabetic ketoacidosis: a) Using Regular insulin, choose either the intermittent IM technique or low-dose IV infusion technique. Intermittent IM technique : Initial Dose: 0. 2 U/kg IM into mus-cles of the rear legs; repeat IM doses of 0. 1 U/kg hourly. Initial doses may be reduced by 25-50% in animals with severe hy-pokalemia. Goal is to slowly lower blood glucose to 200-250 mg/d L over a 6-10 hour period. As blood glucose approach-es 250 mg/dl, switch to IM regular insulin at 0. 1-0. 4 U/kg q4-6h or subcutaneous (if hydration status is good) q6-8h. Goal is to keep blood glucose in the 150-300 mg/d L range. Giving 5% dextrose IV is necessary during this stage. Constant Low-Dose Infusion Technique : Initially give regular insulin at a rate of 0. 05-0. 1 U/kg/hr in an IV line separate from that for ﬂuid therapy. Initial doses may be reduced by 25-50% in animals with severe hypokalemia. Adjust infu-sion rate based upon hourly blood glucose determinations. An hourly reduction in blood glucose by 50-100 mg/d L is ideal. Once blood glucose approaches 250 mg/d L switch to IM regular insulin every 4-6 hours or to subcutaneous regu-lar insulin at 0. 1-0. 4 U/kg q6-8h if hydration status is good. Goal is to keep blood glucose in the 150-300 mg/d L range. Giving 5% dextrose IV is necessary during this stage. Alter-natively, may continue IV infusion at a decreased rate until exchanged for a longer-acting product. (Nelson and Elliott 2003a) For adjunctive treatment of severe hyperkalemia (>8 m Eq/L): a) Give regular insulin 0. 25-0. 5 U/kg slow IV bolus followed by 50% dextrose (4 m L/U of administered insulin); or give regular 0. 5-1 U/kg in parenteral ﬂuids plus 2 grams dextrose per unit insulin administered (Nelson and Elliott 2003b) Insulin treatment of uncomplicated diabetes mellitus: a) Vetsulin®: The initial recommended dose is 1 U insulin/kg body weight plus a body weight-dependent dose supplement (as shown in the table below) given SC once daily concur-rently with, or right after a meal. Re-evaluation of the patient should be performed at appropriate intervals and insulin doses adjusted as needed. (Vetsulin® package insert) DOSE DOSE PLUS DOSE INITIAL DOSE SUPPLEMENT <10 kg (Weight in 1 Unit 1 U/kg + 1 kg) x 1 U/kg Unit 10-11 kg (Weight in 2 Units 1 U/kg + 2 kg) x 1 U/kg Units 12-20 kg (Weight in 3 Units 1 U/kg + 3 kg) x 1 U/kg Units >20 kg (Weight in 4 Units 1 U/kg + 4 kg) x 1 U/kg Units Twice daily dosing may be required if the duration of action is insufﬁcient. T o calculate the twice daily dose, decrease the total once daily dose by 25% and give that calculated dose twice daily. For example, the new dose for a dog previously receiving 20 Units once daily would be 15 Units twice daily. (Intervet; T echnical Services) b) NPH insulin of recombinant human origin: give 0. 25 U/kg SC every 12 hours. (Nelson 2007) Note : More than 90% of dogs will require twice daily doses of intermediate acting insulin; therefore, initiating therapy with this regimen may result in better and easier glycemic control and fewer problems with hypoglycemia and the So-mogyi effect). Dietary therapy is used concurrently. Follow-ing stabilization, diabetic dogs are typically evaluated every 7 days until an effective insulin protocol is established. (Nelson and Elliott 2003a) c) Insulin glargine: Initiate dose of insulin glargine at 0. 25 U/ kg SC q12 hours in dogs with poor response to porcine zinc insulin or NPH. (Nelson 2007) !TCATS: For adjunctive therapy of diabetic ketoacidosis: a) Use the same protocol as described above in “a” for dogs (Nelson and Elliott 2003a) Insulin treatment of uncomplicated diabetes mellitus: Note : Cats are very unpredictable in their response to insulin therapy, and no single type of insulin is routinely effective in maintaining glycemic control, even with twice daily dosing. Cats should be closely monitored during the ﬁrst month of insulin therapy. a) Using PZI: Starting dose: 0. 1-0. 3 Units per pound body weight (0. 22-0. 6 Units/kg) SC every 12 to 24 hours (maxi-mum starting dose should not exceed 3 total Units per cat every 12 hours); reevaluate every 7-14 days and adjust insu-lin dose as necessary to achieve regulation (PZI-VET product information) b) Using PZI: Starting dose: 1 Unit per cat SC every 12 hours (Nelson 2007) c) Using Porcine insulin zinc (lente): Starting dose: 1-2 Units per cat SC every 12 hours. Half of the cat's total daily caloric intake should be offered at the time of each insulin injection, and the cat should have access to any uneaten food until time for the next injection. Patients should be evaluated at appro-priate intervals and insulin dose adjustments made accord-ingly. (Nelson and Elliott 2003a) d) Using Porcine insulin zinc (lente): Starting dose: 0. 25 U/kg twice daily if the blood glucose concentration is between 216-342 mg/d L and 0. 5 U/kg twice daily if the blood glucose concentration is >360 mg/d L. (Rand 1997, Behrend 2007)	pppbs.pdf
482 INSULIN Te) Using Porcine insulin zinc (lente): Starting dose: 1 Unit/cat twice daily for cats weighing less than 4 kg and 1. 5-2 Unit/ cat twice daily for cats weighing >4 kg can be used to initiate therapy (Reusch 2005, Behrend 2007) f) Using NPH: Starting dose: 0. 5 U/kg SC every 12 hours. (Boothe 2001) g) Using NPH: Starting dose: 1-2 Units per cat SC every 12 hours (Cohn, Graves 2007) h) Using Insulin glargine (Lantus): 1 Unit per cat SC every 24 hours; increase to twice daily injections if subsequent blood glucose evaluations indicate less than 12 hours duration. (Nelson 2007) i) Using Insulin glargine (Lantus): 0. 25-0. 5 U/kg SC every 12 hours, not to exceed 3 Units per cat q12 hours starting dose (Peterson, Kintzer 2007) Note : insulin glargine may have little or no effect on blood glucose in cats for the ﬁrst 3 days after initiation of therapy. Dose increases are not recommended for the ﬁrst week of therapy to avoid possible hypoglycemia. Some cats may re-quire a decrease in dose, and some may achieve diabetic re-mission after one month of glargine therapy. !TBIRDS: Diabetes mellitus is most common in budgies,cockatiels,and tou-cans. Blood glucose levels in diabetic birds range from 600-2000 mg/d L (Deﬁnitive diagnosis requires persistently elevated blood glucose levels >800 mg/d L). Insulin therapy is sometimes hin-dered by the highly variable dose needed for individual birds, the development of insulin resistance, and the development of pancreatic atrophy and pancreatic insufﬁciency. a) Insulin dose: Initially,0. 1-0. 2 U/kg regular insulin. When sta-bilized, NPH insulin can be started. Dose range is 0. 067-3. 3 U/kg IM every 12-24 hours. (Oglesbee 2003) A blood glu-cose curve should be obtained. Determine blood glucose lev-els initially, then every 2-3 hours for 12-24 hours. The dose is adjusted based on blood glucose levels. Frequency varies from twice daily to once every several days. Bird should be placed on a low-carbohydrate diet. Clinical sign of success-ful treatment is weight gain. Monitor for hypoglycemia. Treat hypoglycemia with oral or injectable dextrose or oral corn syrup. (Rupley 1997) !TFERRETS: Treatment of diabetes mellitus: a) NPH 0. 5-1 Unit per ferret SC twice daily. Goal of therapy is negative ketones and a small amount of glucose in the urine. (Quesenberry and Carpenter 2003) b) NPH 0. 1-0. 5 IU/kg IM or SC twice daily to start; adjust to optimal dose. May require insulin to be diluted; monitor urine for glucose/ketones. (Williams 2000) !TCATTLE: For adjunctive treatment of ketosis: a) PZI insulin 200 Units (total dose) SC once every 48 hours (Smith 2002a) !THORSES: For diabetes mellitus: a) True diabetes mellitus rarely occurs in horses. Most cases are a result of pituitary tumors that cause hyperglycemia secondary to excessive ACTH or growth hormone. A case is cited where an animal received 0. 5-1 Unit/kg of PZI insulin and the hyperglycemia was controlled. Patients with hyper-glycemia secondary to a pituitary tumor are apparently in-sulin-resistant (Merritt 1987). b) PZI insulin 0. 15 U/kg IM or SC twice daily (Robinson 1987) For treatment of hyperlipemia in ponies: a) For a 200 kg pony: PZI 30 U (total dose) IM every 12 hours on odd days (given with 100 grams glucose orally once dai-ly); PZI 15 U (total dose) IM every 12 hours on even days (given with 100 grams galactose orally once daily) until hy-perlipemia resolves. (Smith 2002a) Monitoring Parameters !TBlood glucose !TPatient weight, appetite, ﬂuid intake/output !TBlood, urine ketones (if warranted) !TGlycosylated hemoglobin and fructosamine [goal = fructosamine <450 micromol/L] (if available and warranted) Client Information !TKeep insulin products away from temperature extremes. If stored in the refrigerator, allow to come to room temperature in syringe before injecting. !TClients must be instructed in proper techniques for withdrawing insulin into the syringe, including rolling the vial, not shaking before withdrawing into syringe, and using the proper syringe size with insulin concentration (e. g., not confusing U-40 insulin/ syringes with U-100 insulin/syringes). !TProper injection techniques should be taught and practiced with the client before the animal's discharge. !The symptoms of hypoglycemia should be thoroughly reviewed with the owner. !TA written protocol outlining monitoring pro cedures and treatment steps for hypoglycemia should be sent home with the owner. !TWhen traveling, insulin should not be left in carry-on luggage that will pass through airport surveillance equipment. Generally, insulin stability is not affected by a single pass through surveil-lance equipment; however, longer than normal exposure or re-peated passes through surveillance equipment may alter insulin potency. Chemistry and Biosynthesis The endocrine component of the pancreas is organized as discrete islets (islets of Langerhans) that contain four cell types, each of which produces a different hormone. Insulin is produced in the beta cells, which comprise 60-80% of the islet. Insulin is a protein consisting of two chains, designated A and B, with 21 and 30 amino acids respectively that are connected by two disulﬁde bonds. The amino acid composition of insulin has been determined in various species of animals. The insulin of dogs, pigs, and certain whales (sperm and ﬁn) is identical in structure; sheep insulin is identical to goat. Cattle, sheep, horses, and dogs differ only in positions 8, 9, and 10 of the A chain. Porcine insulin differs from human insu-lin by one amino acid [alanine instead of threonine at the carboxy terminal of the B chain (i. e., in position B 30)], and bovine insulin differs by two additional alterations in the A chain (threonine and isoleucine in positions A8 and A10 are replaced by alanine and va-line, respectively). Of the domestic species, feline insulin is most similar to bovine insulin, differing by only 1 amino acid (at position 18 of the A chain). Human insulin differs from rabbit insulin by a single amino acid. There is a single insulin gene and a single protein product in most mammalian species (multiple insulins appear to occur frequently among ﬁshes). For therapeutic purposes, doses and concentrations of insu-lin are expressed in Units (U). One unit of insulin is equal to the amount required to reduce the concentration of blood glucose in a fasting rabbit to 45 mg/dl (2. 5 m M). All commercial preparations	pppbs.pdf
INSULIN 483 of human insulin currently manufactured in the U. S. are supplied in solution or suspension at a concentration of 100 U/m L, which is approximately 3. 6 mg of insulin per milliliter; likewise, one unit of insulin equals about 36 micrograms of insulin. Insulin is a small protein; human insulin has a molecular weight of 5808. Insulin secretion is a tightly regulated process designed to provide stable concentrations of glucose in blood during fasting and feeding. This regulation is achieved by the coordinated interplay of various nutrients, gastrointestinal and pancreatic hormones, and autonomic neurotransmitters. The primary stimulus for secretion of endogenous insulin is glucose. Regular insulin is a rapid-acting sterile solution prepared by precipitating insulin in the presence of zinc chloride to form zinc insulin crystals. Regular insulin 100 U/m L is a clear and colorless or almost colorless solution. Discoloration, turbidity, or unusual viscosity indicates deterioration or contamination. Isophane insulin, more commonly known as NPH, is an in-termediate-acting, sterile suspension of zinc insulin crystals and protamine sulfate in buffered water for injection. Porcine Lente insulin is a sterile aqueous suspension of puriﬁed pork Lente insulin consisting of 30% amorphous zinc insulin and 70% crystalline zinc insulin. It is available only as a U-40 insulin concentration and is a cloudy or milky suspension of a mixture of characteristic crystals and particles with no uniform shape. Protamine zinc suspension (PZI) is composed of 90% beef/10% pork insulin combined with zinc and protamine (a protein extract-ed from salmon testes), which slow the release of the insulin into tissues. PZI is clear (not cloudy) with white sediment (no clumps), that when mixed gently, looks like watery milk. It is available only as a U-40 insulin concentration. Insulin glargine is a long-acting human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic labo-ratory strain of E. coli. It differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine, and two arginines are added to the C-terminus of the B chain. The injec-tion consists of insulin glargine dissolved in a clear aqueous ﬂuid. It is available only as a U-100 insulin concentration. All human, puriﬁed pork, and beef/pork insulin products have a neutral p H of approximately 7-7. 8, while insulin glargine has an acidic p H of approximately 4. Stability/Storage/Compatibility Manufacturers of insulin recommend that all insulin products be stored in the refrigerator but protected from freezing temperatures (do not store at temperatures <36$F or <2$C). Freezing may al-ter the protein structure, decreasing potency. Particle aggregation and crystal damage may be visible to the naked eye or may require microscopic examination. Higher temperature (>86$F or >30$C) extremes and direct exposure to sunlight should be avoided (such as might occur when insulin is stored in a car glove compartment or on a window sill), since insulin transformation products and ﬁ-bril formation may occur. Although the manufacturers recommend a maximum of 30 days storage at room temperature, studies have actually shown that regular insulin maintains stability of 24-30 months at 25°C. One study showed a 5% loss of biological potency after about 36 months at 25°C. According to the manufacturer's label, insulin glargine has a dis-card date of 28 days after the initial puncture of the vial (consistent with all human-labeled insulin products) and stored at room tem-perature, although clinical reports indicate that opened vials stored in the refrigerator can be used for up to 6 months; discard vial im-mediately if there is any discoloration. Bacterial contamination and precipitation associated with p H change can cause cloudiness (Marshall and Rand 2006). For animals requiring small doses of glargine, the 3 m L cartridge may be preferable to the 10 m L vial to prevent the need for extend-ed use beyond the recommended discard date. Flocculation of NPH human insulin may appear 3-6 weeks after opening the vial. Deterioration in glycemic control may appear be-fore frosting of the vial. If unexplained hyperglycemia is observed, a new vial of insulin should be used. Regular and NPH insulin may be stored in plastic or glass sy-ringes under refrigeration for 5-7 days without loss of potency. One study found no degradation after 14 days storage under refrig-eration. Other sources state that preﬁlled insulin syringes are stable for 30 days when stored in the refrigerator. It is generally accepted that syringes of insulin can be stored for 28 days under refrigeration without fear of potency loss. Regular insulin is reportedly physically compatible with follow-ing drugs/solutions: normal saline, TPN solutions (4% amino ac-ids, 25% dextrose with electrolytes and vitamins; must occasionally shake bag to prevent separation), bretylium tosylate, cimetidine HCl, lidocaine HCl, oxytetracycline HCl, and verapamil HCl. Regular insulin may be mixed with other insulin products (except for glargine) used in veterinary medicine (e. g., NPH, PZI, etc. ). Regular insulin is reportedly physically incompatible when mixed with the following drugs/solutions: aminophylline, amobarbital sodium, chlorothiazide sodium, cytarabine, dobutamine HCl, ni-trofurantoin sodium, pentobarbital sodium, phenobarbital sodi-um, phenytoin sodium, secobarbital sodium, sodium bicarbonate, sulﬁsoxazole sodium, and thiopental sodium. Compatibility is dependent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references for more speciﬁc information. Diluting insulin : Other than for immediate use, insulin should only be diluted using product-speciﬁc sterile diluents supplied by the manu-facturer. Diluents for Regular insulin ( Humulin R) and NPH insulin (Humulin N) and sterile vials can be obtained by telephoning the manufacturer. Diluted insulin is stable for 4 (preferred) to 6 weeks and should be stored in the refrigerator. For immediate use, insulin products (except glargine) can be diluted with normal saline for in-jection, but the potency cannot be predicted after 24 hours. Insulin glargine must not be diluted or mixed with any other insulin or solution because the prolonged action is dependent on its p H. Adsorption : The adsorption of regular insulin to the surfaces of IV infusion solution containers, glass and plastic (including PVC, eth-ylene vinyl acetate, polyethylene, and other polyoleﬁns), tubing, and ﬁlters has been demonstrated. Estimates of loss of potency range from 20-80%, although reports of 20-30% are more common. The percent adsorbed is inversely proportional to the concentration of the insulin, and may include other factors such as the amount of container surface area, the ﬁll volume of the solution, the type of solution, type and length of administration set, temperature, previ-ous exposure of tubing to insulin, and the presence of other drugs, blood, etc. The adsorption process is instantaneous, with the bulk of insulin adsorption occurring within the ﬁrst 30-60 minutes. T o saturate binding sites and deliver a more predictable dose to the patient through an IV infusion, it is recommended that the ﬁrst 50 m L be run through the IV tubing and discarded. Insulin Syringes : Syringes are designed for use with a speciﬁc strength of insulin, with the needle covers color-coded according to strength. U-40 syringes have a red top, while U-100 syringes have an orange top. U-40 syringes contain H cc (equivalent to 0. 5 m L) and have 20 unit marks. Measuring U-40 insulin to the one unit mark in a U-40 syringe will contain 1U of insulin. U-100 syringes are available in 3/10cc, Hcc, and 1cc size. Measuring U-100 insulin to one mark in a U-100 syringe will contain 1U of insulin.	pppbs.pdf
484 INTERFERON—ALFA Tuberculin syringes can also be used, but are not generally recom-mended because the potential for confusion is substantial. If using 100U/m L or TB syringes to measure 40U/m L insulin doses: T ! Determine the required dose in units. T ! If using U-100 insulin syringes (orange top), multiply the re-quired Units of U-40 insulin by 2. 5 (e. g. If required dose is 10 units, 10 x 2. 5=25 units). T ! If using TB syringes, multiply the required Units of U-40 insulin x 0. 025 (e. g., If the required dose is 10 Units, 10 x 0. 025= 0. 25 m L). Reuse of Insulin Syringes : Reuse of disposable insulin syringes has been suggested to reduce client costs. However, disposable insulin syringes are usually siliconized, and reuse can result in contamina-tion of vials of insulin with silicone oil, causing a white precipitate and impairment of biological effects. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Porcine insulin zinc suspension 40 U/m L in 10 m L vials, interme-diate-acting; Vetsulinº (Intervet) in U. S. ; Caninsulin® (Intervet) in Canada & Europe; (Rx). FDA approved for use in dogs. Protamine zinc insulin (beef 90%/pork 10%) 40 U/m L in 10 m L vi-als; long-acting; PZI VETº (IDEXX); (Rx). Not fully FDA approved, but distribution is allowed under the Medically Necessary Veterinary Products Policy for use in cats. HUMAN-LABELED PRODUCTS: Note : partial listing; includes only those products generally used in veterinary medicine. Insulin Injection, Regular — (short-acting): Human (r DNA): 100 U/m L in 10 m L vials; Humulin· R (Eli Lilly); Novolin·R & Novolin R· Preﬁlled (Novo Nordisk); (OTC) Isophane (Neutral Protamine Hagedorn; NPH) — (intermediate-acting): Human (r DNA) 100 U/m L in 10 m L vials, 5 x 1. 5 m L preﬁlled sy-ringes & 5 x 3 m L pen insulin delivery devices; Humulin·N (Lilly); Novolin·N & Preﬁlled (Novo Nordisk); (OTC) Human (r DNA) Cartridges (suspension) 100 U/m L in 5 x1. 5 m L & 5 x 3 m L; Novolin N · Pen Fill (Novo Nordisk); (OTC) Combination: Insulin Isophane & Regular Injection (suspension): Human (r DNA) 100 U/m L 70% isophane insulin (NPH) & 30 % in-sulin injection (regular) in 5 x 3 m L disposable pen insulin delivery devices, 10 m L vials & 5 x 1. 5 m L preﬁlled syringes; Humulin · 70/30 (Lilly); Novolin· 70/30 & Preﬁlled (Novo Nordisk); (OTC) Human (r DNA) Cartridges (suspension): 100 U/m L; 70% isophane insulin (NPH) & 30% insulin injection (regular) in 5 x 1. 5 & 5 x 3 m L; Novolin® 70/30 Pen Fill (Novo Nordisk); (OTC) Human (r DNA) Injection (suspension): 100 U/m L; 50% isophane insulin (NPH) & 50% insulin injection (regular) in 10 m L vials; Humulin · 50/50 (Lilly); (OTC) Insulin Glargine Injection—(long-acting): Human (r DNA) 100 U/m L in 10 m L vials & 3 m L cartridge system for use with Opti Clik; Lantus º (Aventis); (Rx) INTERFERON ALFA, HUMAN RECOMBINANT (in-ter-feer-on) Roferon-A®, Intron-A® IMMUNOMODULATOR Prescriber Highlights TT Cytokine used to alleviate clinical effects of certain viral diseases; little scientiﬁc info available to document safe-ty/efﬁcacy in small animals TT Cautions: Preexisting autoimmune disease, severe cardi-ac disease, pulmonary disease, “brittle” diabetes, Herpes infections, hypersensitivity to the drug, or CNS disorders TT Adverse Effects: In cats, adverse effects are apparently uncommon with PO; higher dosages given parenterally may cause malaise; fever, allergic reactions, myelotoxic-ity & myalgia are possible Uses/Indications Interferon alfa use in veterinary medicine in the past has primar-ily been centered on its oral/buccal administration in cats to treat non-neoplastic Fe LV disease. Oral interferon may also be of beneﬁt in the treatment of ocular herpes infection. Feline interferon-omega has recently become available in several countries and it may be found signiﬁcantly useful in treating viral diseases in both cats and dogs. A separate monograph for this agent, follows this one. Pharmacology/Actions The pharmacologic effects of the interferons are widespread and complex. Sufﬁce it to say, that interferon alfa has antiviral, antipro-liferative, and immunomodulating effects. Its antiproliferative and antiviral activities are thought to be due to its effects on the syn-thesis of RNA, DNA, and cellular proteins (oncogenes included). The mechanisms for its antineoplastic activities are not well un-derstood, but are probably related these effects as well. Pharmacokinetics Interferon alfa is poorly absorbed after oral administration due to its degradation by proteolytic enzymes and studies have not detect-ed measurable levels in the systemic circulation, however, there may be some absorption via upper GI mucosa. Interferon alfa is widely distributed throughout the body, al-though it does not penetrate into the CNS well. It is unknown if it crosses the placenta. Interferon alfa is freely ﬁltered by the glom-eruli, but is absorbed by the renal tubules where it is metabolized by brush border or lysosomes. Hepatic metabolism is of minor impor-tance. The plasma half-life in cats has been reported as 2. 9 hours. Contraindications/Precautions/Warnings When used parenterally, consider the risks versus beneﬁts in pa-tients with preexisting autoimmune disease, severe cardiac disease, pulmonary disease, “brittle” diabetes, Herpes infections, hypersen-sitivity to the drug, or CNS disorders. Adverse Effects When used orally in cats, adverse effects are apparently uncommon. Higher dosages given parenterally to cats may cause malaise; fever, allergic reactions, myelotoxicity, and myalgia are possible. Cats given human interferon-alfa parenterally may develop signiﬁcant antibodies to it after 7-8 weeks of treatment. When used systemi-	pppbs.pdf
INTERFERON—ALFA 485 cally in humans, adverse effects have included anemia, leukopenias, thrombocytopenia, hepatotoxicity, neurotoxicity, taste sensation changes, anorexia, nausea, vomiting, diarrhea, dizziness, “ﬂu-like” syndrome, transient hypotension, skin rashes, and dry mouth. Except for the “ﬂu-like “syndrome, most adverse effects are dose-related and may vary depending on the condition treated. Reproductive/Nursing Safety Safety during pregnancy has not been established; high parenteral doses in monkeys did not cause teratogenic effects, but did increase abortifacient activity. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether this drug is excreted in milk. Overdosage/Acute Toxicity No information was located. Determine dosages carefully. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving interferon and may be of signiﬁcance in veterinary patients: !TACYCLOVIR, ZIDOVUDINE, VIDARABINE : Additive or synergistic antivi-ral effects may occur when interferon alfa is used in conjunction with zidovudine (AZT) or acyclovir. This effect does not appear to occur with vidarabine, although increased toxicities may oc-cur. The veterinary signiﬁcance of these potential interactions is unclear. Doses !TDOGS: For cutaneus T-cell lymphoma and severe cases of oral/cutaneus papillomas: a) 1. 5-2 million units/m2 SC 3 times weekly (White 2000) For immunosuppression: a) 1 Unit/5 kg PO once daily for 7 days. Treat alternate weeks or continuously. (Greene and Watson 1998) !TCATS: For indolent lip ulcers: a) 60-120 Units PO or SC daily (White 2000) For treatment of Fe LV-infected cats: a) Low dose: 30 U cat PO daily; 7 days on, 7 days off); Hi dose: 10,000-1,000,000 U/kg SC once daily. Little in the way of large, controlled trials to determine which, if any, immuno-modulating therapies (interferon or other agents) are likely to beneﬁt Fe LV-infected cats. (Levy 2004) For treatment of FIV-infected cats: a) 30 U cat PO daily; 7 days on, 7 days off (Barr and Phillips 2000) For adjunctive treatment of FHV-1-infected cats: a) For chronic infections: 30 U cat PO daily; 7 days on, 7 days off; repeat cycle. May also use topical ophthalmic therapy: one drop of 25-50 IU/m L of saline in affected eye(s) q4-6 hours. (Powell 2002) b) For acute life-threatening infections in kittens: 10,000 IU/kg SC daily for up to 3 weeks (Lappin 2003b) For treatment of FIP-infected cats: a) For exudative form (wet): 20,000 U/cat IM once daily for 14-21 days. For nonexudative form (dry): 30 U/cat PO once daily for 7 days. Treat alternate weeks. (Greene and Watson 1998) T o prepare a 3 U/m L solution for oral administration: Using the 3 million IU vial (see below), dilute the entire contents into 100 m L of sterile water; mix well. Resulting solution contains approximately 30,000 IU/m L. Take 0. 1 m L of this solution and add to one liter of sterile saline that has 4 m L of 25% albumin added to it. Albumin is optional but adds stability. Solution is now 3 U/m L. Divide into aliquots of 15 m L and freeze, preferably at-70°C. Thaw as needed and keep refrigerated. Discard unused portion after 60 days. Discard unused 30,000 U/m L solution within 2-3 hours of making initial dilutions. Preparation of solution for 30 U/m L oral administration: Us-ing the 3 million IU vial (see below), dilute the entire con-tents into a 1 L bag of sterile normal saline; mix well. Re-sulting solution contains approximately 3,000 IU/m L. Divide into aliquots of either 1 or 10 m L and freeze. By diluting fur-ther 100 fold (1 m L of 3000 IU/m L solution with 100 m L of sterile saline, or 10 m L with 1000 m L of sterile saline) a 30 IU/m L solution will result. Some have advised aliquoting the diluted solution into 1 m L volumes for freezing up to a year; defrost as necessary. Once defrosted, the drug can be refriger-ated up to one week. Freezing the most dilute solutions is as-sociated with loss in activity unless protein such as albumin (see above) is added during dilution. (Greene, Hartmannn et al. 2006) Client Information !TOwners should be made aware of the “investigational” nature of this compound and understand that efﬁcacy and safety have not necessarily been established. Chemistry/Synonyms Prepared from genetically engineered cultures of E. coli with genes from human leukocytes, interferon alfa-2a is commercially avail-able as a sterile solution or sterile powder. Human interferon alfa is a complex protein that contains 165 or 166 amino acids. Interferon may also be known as: IFN-alpha, interferon-alpha, Ro-22-8181 (interferon alfa-2a), Sch-30500 (interferon alfa-2b); there are many internationally registered trade names available. Storage/Stability/Compatibility Commercially available products should be stored in the refrig-erator; do not freeze the accompanying diluent. Do not expose solutions to room temperature for longer than 24 hours. Do not vigorously shake solutions. An article proposing using this product in cats for the treatment of Fe LV states that after dilution of 3 million IU in one liter of ster-ile saline the resultant solution remains active for years if frozen or for months if refrigerated. However, data corroborating this is apparently not available. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Interferon Alfa-2a (recombinant r IFN-A; IFLr A) Injection: Preﬁlled syringes: 3 million I. U. /syringe (0. 5 m L single-use syringes); 6 mil-lion I. U. /syringe (0. 5 m L single-use syringes); 9 million I. U. /syringe (0. 5 m L single-use syringes); Roferon-A® (Hoffman La-Roche); (Rx) Interferon Alfa-2b (recombinant (IFN-alpha2; r IFN-a2; a-2-interfer-on) Powder for Injection: 5 million IU/vial; 10 million IU/vial; 18 million IU/vial; 25 million IU/vial & 50 million IU/vial in vials with a m L, 2 m L or 5 m L diluent/vial; Intron A® (Schering); (Rx)	pppbs.pdf
486 INTERFERON—OMEGA TInterferon Alfa-2b (recombinant (IFN-alpha2; r IFN-a2; a-2-interfer-on) Injection: 3 million IU/dose; 5 million IU/dose, & 10 million IU/ dose in multidose pens; Intron A® (Schering); (Rx) Interferon Alfa-2b (recombinant (IFN-alpha2; r IFN-a2; a-2-interfer-on) Solution for Injection: 3 million IU/vial, 5 million IU/vial; 10 mil-lion IU/vial; 18 million IU/vial & 25 million IU/vial in vials, Pak-3,-5,-10 (vials & syringes); & in multidose vials (22. 8 million IU/3. 8 m L/ vial or 32 million IU/3. 2 m L/vial); Intron A® (Schering); (Rx) Interferon Alfa-N3 (human leukocyte derived) Injection: 5 million IU/m L (8 mg Na Cl, 1. 74 mg Na phosphate dibasic, 0. 2 mg K phos-phate monobasic, 0. 2 mg KCl) in 1 m L vials; Alferon N ® (Interferon Sciences Inc. ); (Rx) INTERFERON-1 (OMEGA) (in-ter-feer-on oh-may-ga) Virbagen Omega®, Recombinant Omega Interferon of Feline Origin, r Fel FN-Omega IMMUNOMODULATOR Prescriber Highlights TT Immunomodulating cytokine labeled for treating Fe LV & FIV in cats & Parvo in dogs; not commercially available in USA TT Appears to be well tolerated; adverse effects include: hyperthermia, vomiting, diarrhea (cats), fatigue (cats) TT Increases in ALT & decreases in RBC, WBC, & platelet counts have been seen TT Treatment may be very expensive Uses/Indications Omega interferon (feline) is labeled (in the EU) for dogs 1 month of age or older for the reduction in mortality and clinical signs of parvovirus (enteric form). In cats 9 weeks of age or older, it is la-beled for treating Fe LV and/or FIV, in non-terminal clinical stages. It may be of beneﬁt in treating canine distemper, acute feline cali-civirus infections, FIP, or topically for feline herpetic keratitis, but data is still being gathered to document efﬁcacy. Pharmacology/Actions Omega interferon is a type 1 interferon related to alpha interfer-on. Its principle action is not as a direct anti-viral, but by acting on virus-infected cells inhibiting m RNA and translation proteins thereby inhibiting viral replication. It may also nonspeciﬁcally en-hance immune defense mechanisms. Pharmacokinetics It has been stated that omega interferon pharmacokinetics in dogs and cats is similar to that of human interferons. After intravenous injection, omega interferon is rapidly bound to speciﬁc receptor sites on a variety of cells. Highest tissue levels are found in the liver and kidneys. Interferon is ﬁltered in the renal glomeruli and catab-olized in the kidneys. In dogs, volume of distribution at steady state is about 0. 1L/kg. Biphasic elimination occurs with an alpha half-life of 3. 14 hours and a beta half-life of 0. 24 hours. T otal body clearance is 6. 9 m L/min/kg. Contraindications/Precautions/Warnings The manufacturer cautions against vaccinating dogs currently be-ing treated with omega interferon and not to vaccinate until the patient appears to have recovered. As both Fe LV and FIV infections are known to be immunosuppressive, the manufacturer states that cat vaccinations are contraindicated during and after omega inter-feron treatment. There are several different interferons available for use in hu-mans (several sub-types of alpha, beta, or gamma interferon); one cannot be substituted for another. Adverse Effects In cats and dogs, hyperthermia (3-6 hours post-dose) and vom-iting have been reported. Slight decreases in RBCs, platelets and WBCs, and increased ALT have been observed but, reportedly, these indices return to normal within a week of the last injection. Additionally, soft feces/mild diarrhea and transient fatigue may be noted in cats. Intravenous administration to cats may cause in-creased incidence and severity of adverse effects. Dogs may develop antibodies to interferon omega if treatment is prolonged (beyond labeled dosage period) or repeated. Reproductive/Nursing Safety Safety during pregnancy or lactation has not been established. Overdosage/Acute Toxicity 10X overdoses in dogs and cats caused mild lethargy/somnolence, slight hyperthermia, slight increases in respiratory and heart rates. In animals tested, signs resolved within 7 days and no treatment was required. Drug Interactions No reported drug interactions at the time of writing, but use caution when using other drugs that can be hepatotoxic or myelosuppressive. Laboratory Considerations No speciﬁc concerns were noted Doses T ! DOGS: a) For treatment of parvovirus as labeled: 2. 5 million Units/ kg IV once daily for 3 days. The earlier the dog is treated, the more likely of success. (Label information; Virbagen Omega®—Virbac UK) T ! CATS: a) For treatment of Fe LV or FV as labeled: 1 million Units/kg SC once daily for 5 days. Three separate 5-day treatments performed at day 0, day 14, and day 60. (Label information; Virbagen Omega®—Virbac UK) Monitoring T ! Monitor for efﬁcacy for infection treated T ! CBC and hepatic function tests suggested Client Information T ! his drug is best administered on an inpatient basis where the patient may be observed and supported Chemistry/Synonyms Interferon omega of feline origin is a type 1 recombinant interfer-on obtained from silkworms after inoculation with a recombinant baculovirus. It is provided commercially as a lyophilisate powder with a separate solvent. Recombinant omega interferon of feline origin may also be known as: Interferon omega, omega interferon, interferon-t, IFN-t, IFN-t (feline recombinant), r Fel FN-t, and Virbagen Omega ®.	pppbs.pdf
IODIDE 487 Storage/Stability/Compatibility The commercial veterinary product should be stored in its original carton refrigerated (4°C ± 2°C) and protected from freezing. It has a designated shelf life of 2 years when properly stored. Once re-constituted with the supplied isotonic sodium chloride solution, it should be used immediately as it contains no preservative, however, the solution is reported to be stable for at least 3 weeks when refrig-erated. No data was located on the stability of the reconstituted so-lution when frozen. The manufacturer states: Do not mix with any other vaccine/immunological product, except the solvent supplied for use with the product. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None in the USA In the EU: Recombinant Omega Interferon of Feline Origin 10 million Units/ vial; Virbagen Omega® (Virbac); (Rx). Approved for dogs and cats. A 5 million Unit vial may be available in some countries. The FDA may allow legal importation into the USA of this medica-tion for compassionate use in animals; for more information, see the Instructions for Legally Importing Drugs for Compassionate Use in the USA found in the appendix. HUMAN-LABELED PRODUCTS: None IODIDE, SODIUM IODIDE, POTASSIUM (eye-oh-dide) SSKI, Iodoject® ANTIFUNGAL, NUTRITIONAL Prescriber Highlights TT Iodides used for actinobacillosis in ruminants, sporo-trichosis in horses, dogs, & cats TT Contraindications: Iodide hypersensitivity, lactating ani-mals, hyperthyroidism, renal failure, or dehydration TT Do not inject IM; give IV slowly & with caution to horses as severe generalized reactions have been reported TT May cause abortion in cattle TT Adverse Effects: Iodism: Excessive tearing, vomiting, anorexia nasal discharge, muscle twitching, cardiomyo-pathy, scaly haircoats/dandruff, hyperthermia, decreased milk production & weight gain, coughing, inappetence, & diarrhea TT Cats more prone to developing toxicity Uses/Indications The primary use for sodium iodide is in the treatment of actinoba-cillosis and actinomycosis in cattle. It has been used as an expec-torant with little success in a variety of species and occasionally as a supplement for iodine deﬁciency disorders. In horses, dogs and cats, oral sodium or potassium iodide has been used in the treat-ment of sporotrichosis. Use in cats is controversial as they may be prone to developing adverse effects; cats may require other antifun-gal (e. g., itraconazole) therapy. Potassium iodide has also been used as an expectorant, but documentation of efﬁcacy is lacking. Pharmacology/Actions While the exact mode of action for its efﬁcacy in treating actinoba-cillosis is unknown, iodides probably have some effect on the gran-ulomatous inﬂammatory process. Iodides have little, if any, in vitro antibiotic activity. Pharmacokinetics Little published information appears to be available. Therapeutic efﬁcacy of intravenous sodium iodide for actinobacillosis is rapid, with beneﬁcial effects usually seen within 48 hours of therapy. Contraindications/Precautions/Warnings Sodium iodide injection labels state that it should not be given to lactating animals or to animals with hyperthyroidism. Do not inject intramuscularly (IM). Iodides given parenterally should be administered slowly intra-venously and with caution to horses; severe generalized reactions have been reported. Should not be used in animals in renal failure or that are severely dehydrated. Adverse Effects In ruminants, the adverse effect proﬁle is related to excessive iodine (see Overdosage below). Y oung animals may be more susceptible to iodism than adults. Foals have developed goiter when mares have been excessively supplemented. Chronic use or overdoses may cause iodism. Cats are apparently more prone to developing this than other species. Signs can include vomiting, inappetance, depression, twitching, hypothermia, and cardiovascular failure. Reproductive/Nursing Safety Anecdotal reports that iodides can cause abortion in cattle persist and label information of some veterinary products state not to use in pregnant animals. Clearly, potential risks versus beneﬁts of ther-apy must be weighed. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fe-tal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Iodides are excreted in milk. If iodides are required in the nurs-ing dam, switch to milk replacer. Overdosage/Acute Toxicity Excessive iodine in animals can cause excessive tearing, vomiting, anorexia, nasal discharge, muscle twitching, cardiomyopathy, scaly haircoats/dandruff, hyperthermia, decreased milk production and weight gain, coughing, inappetence, and diarrhea. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving iodide and may be of signiﬁcance in veterinary patients: T ! ANTITHYROID MEDICATIONS : Iodides may decrease the efﬁcacy of antithyroid medications T ! THYROID SUPPLEMENTS : Iodides may enhance the efﬁcacy of thy-roid medications Doses T ! DOGS: For Sporotrichosis: a) Using SSKI: 40 mg/kg PO q8h for at least 60 days (Greene and Watson 1998) b) Using SSKI: 40 mg/kg PO q12h with food; itraconazole less likely to have adverse effects (Grooters 2005)	pppbs.pdf
488 IPECAC T ! CATS: For Sporotrichosis: a) 20 mg/kg PO q12-24h for at least 60 days (Greene and Wat-son 1998) b) Using SSKI: 20 mg/kg PO q12-24h with food; itraconazole less likely to cause adverse effects (Grooters 2005) T ! CATTLE, SHEEP & GOATS: a) For treatment of actinobacillosis (woody tongue): 70 mg/kg IV given as a 10% or 20% solution; repeat at least one more time at a 7-10 day interval. Refractory cases may require more frequent (2-3 day intervals) treatment. Severe, gener-alized, or refractory cases may require adjunctive treatment with antibiotics (sulfas, aminoglycoside or tetracyclines). (Smith 1996) b) For treatment of actinomycosis (lumpy jaw): 70 mg/kg IV given as a 10% or 20% solution at 7-10 day intervals or more frequently until signs of iodism occur (see Overdose above). Also requires adjunctive treatment with antibiotics: isoniazid (10 mg/kg/day PO for one month), penicillin (10, 000 U/kg twice daily) and an aminoglycoside when treating a valuable animal or twice daily dosing for 7-14 days is pos-sible. (Smith 1996) c) For treatment of actinobacillosis or actinomycosis in sheep: 20 m L of a 10% solution SC; repeated weekly for 4-5 weeks (Howard 1986) T ! HORSES: a) For treatment of sporotrichosis: Sodium iodide 20-40 mg/ kg orally daily for several weeks (Fadok 1992) b) Loading dose of sodium iodide at 20-40 mg/kg IV for 2-5 days, then 20-40 mg/kg PO once daily for at least 3 weeks after all clinical lesions disappear. May administer via oral syringe or mixed in sweet feed. T opical hot packs of 20% so-dium iodide may be used on open wounds. (Rees 2004) c) For Conidiobolomycosis: A mare with C. coronatus granu-lomatous tracheitis was successfully treated with 20% sodi-um iodide at 44 mg/kg IV for 7 days, then ethylenediamine dihydroiodide (iodide powder, granules) at 1. 3 mg/kg PO q12h for 4 months, then q24h for 1 year, then once per week. Excessive lacrimation was occasionally noted, but resolved if the drug was held for one day. (Stewart and Salazar 2005) Monitoring T ! Clinical efﬁcacy T ! Signs of iodism (excessive tearing, nasal discharge, scaly hair-coats/dandruff, hyperthermia, decreased milk production and weight gain, coughing, inappetence, and diarrhea Client Information T ! Although formal withholding times were not located, there is concern about using this product in food animals about to be slaughtered. In the interest of public health, contact FARAD (see appendix) for guidance. T ! When giving orally in small animals, give with food or a fatty liquid (whole milk, cream) as the taste is extremely unpleasant and nausea or vomiting may otherwise occur. Chemistry/Synonyms Sodium iodide occurs as colorless, odorless crystals or white crystalline powder. It develops a brown tint upon degradation. Approximately 1 gram is soluble in 0. 6 m L of water and 2 m L of alcohol. Potassium iodide occurs as a clear to white granular powder. Approximately 1 gram is soluble in 0. 7 m L of water. One gram (one m L) of SSKI contains 6 m Eq of potassium. Potassium iodide oral solution may also be known as SSKI (su-per saturated potassium iodide), or Pima®. Storage/Stability/Compatibility Commercially available veterinary injectable products should gen-erally be stored at room temperature (15-30° C). Sodium iodide injection is reportedly physically incompatible with vitamins B and C injection. Supersaturated potassium iodide (SSKI) solution should be stored below 40°C (104°F) and preferably between 15-30°C (59-86°F) in a tight, light-resistant container; protect from freez-ing. Crystallization can occur, particularly if stored at low tempera-tures; re-warming the contents and shaking will usually redissolve the crystals. If oxidation occurs, the solution will turn brownish yel-low in color; discard should this occur. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Sodium Iodide Injection: 20 g/100 m L (20%; 200 mg/m L) in 250 m L vials—available as multi-or single use vials; generic, (Agri Labs, RXV, Vedco, Butler); (Rx) Approved for use in non-lactating cattle. Oral iodide powders/granules for addition to feeds are available. Ac-tive ingredient is ethylenediamine dihydroiodide. HUMAN-LABELED PRODUCTS: Potassium Iodide Solution: 1 g potassium iodide/m L; 325 mg potas-sium iodide/5 m L in 30 m L, 24 m L, pt & gal; SSKI® (Upsher-Smith); generic; (Rx) Potassium Iodide Oral Syrup: 62. 5 mg potassium iodide/m L in pints and gallons; Pima® (Fleming); (Rx) There are radioactive iodine compounds available for thyroid diag-nostic and treatment. IPECAC SYRUP (ip-e-kak) Also see the Decontamination information in the appendix EMETIC Prescriber Highlights TT Oral emetic agent for dogs & cats TT Contraindications: Rodents or rabbits; patients that are hypoxic, dyspneic, in shock, lack normal pharyngeal re-ﬂexes, seizuring, comatose, severely CNS depressed or where CNS function is deteriorating, previously vomited repeatedly, ingested strong acids, alkalies, other caustic agents, or extremely physically weak TT Usually contraindicated after petroleum distillate ingestion TT Caution after ingestion of strychnine or other CNS stimu-lants (may precipitate seizures), preexisting severe car-diac dysfunction, esophageal or gastric abnormalities TT Adverse Effects: Rare at usual doses, but can induce lacrimation, salivation, & an increase in bronchial secre-tions; may cause repeated vomiting TT Food interactions	pppbs.pdf
IPECAC 489 Uses/Indications Ipecac can be used to induce vomiting in dogs and cats after inges-tions of certain toxic compounds or drugs in overdose quantities. Pharmacology/Actions The major alkaloids of ipecac, emetine and cephaeline, are believed to cause the major pharmacologic actions of the drug. Ipecac acts both locally by irritating the gastric mucosa and centrally by stimu-lating the chemoreceptor trigger zone. The medullary centers must be responsive for emesis to occur, however. Contents of both the stomach and upper intestinal tract may be evacuated by ipecac. Pharmacokinetics Little is known regarding the pharmacokinetics of ipecac or its al-kaloids. The amount absorbed tends to be highly interpatient vari-able. When administered to dogs or cats, vomiting usually occurs within 10-30 minutes (average = 23 minutes). Contraindications/Precautions/Warnings Emetics can be an important aspect in the treatment of orally in-gested toxins, but must not be used injudiciously. Emetics should not be used in rodents or rabbits, because they are either unable to vomit or do not have stomach walls strong enough to tolerate the act of emesis. Emetics are also contraindicated in patients that are: hypoxic, dyspneic, in shock, lack normal pharyngeal reﬂexes, seizuring, comatose, severely CNS depressed or when CNS func-tion is deteriorating, or extremely physically weak. Emetics should be withheld in patients who have previously vomited repeatedly. Emetics are contraindicated in patients who have ingested strong acids, alkalies, or other caustic agents because of the risks of addi-tional esophageal or gastric injury with emesis. Because of the risks of aspiration, emetics are usually contraindicated after petroleum distillate ingestion, but may be employed when the risks of toxicity of the compound are greater than the risks of aspiration. Use of emetics after ingestion of strychnine or other CNS stimulants may precipitate seizures. Emetics generally do not remove more than 80% of the material in the stomach (usually 40-60%) and successful induction of em-esis does not signal the end of appropriate monitoring or therapy. Because of the drug's potential cardiotoxic effects, use with caution in animals with preexisting severe cardiac dysfunction. Because of its unpleasant taste, owners may have a difﬁcult time administering to cats. Warning : Do not confuse ipecac syrup with ipecac ﬂuidextract, which is about 14 times more potent than ipecac syrup and could cause cardiotoxicity and death if used at ipecac syrup dosages. Ipecac ﬂu-idextract is no longer commercially available in the United States. Adverse Effects At recommended doses, ipecac rarely exhibits toxic effects, but can induce lacrimation, salivation, and an increase in bronchial secre-tions. In humans, ipecac has rarely caused protracted vomiting, di-arrhea and lethargy. If, after a second ipecac dose, emesis does not occur, many clini-cians recommend performing gastric lavage to remove the ingested toxicant because of the potential for ipecac-induced cardiotoxicity or prolonged vomiting. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether ipecac alkaloids are excreted in milk; exercise caution. Overdosage/Acute Toxicity Overdoses of ipecac may result in serious cardiotoxicity with result-ing arrhythmias, hypotension, or fatal myocarditis. No speciﬁc an-tidotal therapy is available, but activated charcoal may be given to help adsorb any unabsorbed ipecac; supportive therapy may also be employed. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ipecac and may be of signiﬁcance in veterinary patients: !TCHARCOAL, ACTIVATED : While activated charcoal will adsorb ipecac syrup and several veterinary references state that ipecac should not be used when charcoal therapy is contemplated, ipecac may be given initially followed by activated charcoal after vomiting has occurred !TMILK, DAIRY PRODUCTS, CARBONATED BEVERAGES : Do not adminis-ter with milk, dairy products, or carbonated beverages as ipecac efﬁcacy may be diminished Doses !TDOGS: T o induce emesis: a) 1-2. 5 m L/kg PO; if animal has a nearly empty stomach, give 5 m L/kg of water immediately after ipecac (Beasley and Dor-man 1990) b) 2-6 m L PO (Rumbeiha 2000) c) 1-2 m L/kg PO; do not exceed 15 m L total per dog; repeat in 20 minutes if emesis does not occur. If emesis does not occur after second dose, perform gastric lavage to recover ipecac. (Bailey 1989) !TCATS: T o induce emesis: a) 3. 3 m L/kg PO; because cats ﬁnd ipecac syrup objectionable, a diluted 50:50 solution in water (total volume 6. 6 m L/kg) via stomach or nasogastric tube may be preferable (Beasley and Dorman 1990) b) 1-2 teaspoonsful (5-10 m L) PO; may require second dose, but if not effective, institute gastric lavage (Reid and Oehme 1989) c) 1-2 m L/kg PO; repeat in 20 minutes if emesis does not oc-cur. If emesis does not occur after second dose, perform gas-tric lavage to recover ipecac. (Bailey 1989) Monitoring !TCardiac function (rate/rhythm, blood pressure) should be moni-tored in susceptible animals and if animal does not vomit after ipecac !TVomitus should be quantitated, examined for contents, and saved for possible later analysis Client Information !TIf clients are instructed to use this agent at home or in transit to professional help, they should save any vomitus for analysis Chemistry/Synonym Ipecac syrup is prepared from powdered ipecac, which is derived from the roots and rhizomes of certain plants. Ipecac has two active alkaloids, emetine and cephaeline. Each m L of Ipecac syrup con-tains 70 mg of powdered ipecac (1. 23-1. 57 mg of the ether soluble alkaloids). Ipecac syrup has a characteristic odor and occurs as a clear, to amber colored hydroalcoholic syrup.	pppbs.pdf
490 IPODATE SODIUM Ipecac syrup may also be known as syrup of ipecac, ipecacuanha, ipecac, ipecacuanha syrup, ipecacuanha root, ipecacuanhae radix, Ipeca®, Ipecacuanha Tincture®, Ipecavom®, Ipetitrin®, or Orpec®. Storage/Stability Store ipecac syrup in tight containers at temperatures less than 25°C. Although ipecac syrup may be effective for several years after the labeled expiration date, delayed emetic action or lack of efﬁcacy has been reported with the use of expired product; expired prod-ucts cannot be recommended for use if alternatives exist. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Ipecac Oral Syrup: 1. 5% to 1. 75% alcohol in 15 m L & 30 m L; (OTC); 2% alcohol in 15 and 30 m L; generic (Rx) IPODATE SODIUM (eye-poe-date) ANTITHYROID A GENT Prescriber Highlights TT Organic iodine compound that may be useful in some cats for medical treatment of hyperthyroidism TT Very limited experience TT Less effective for cats with severe hyperthyroidism TT Efﬁcacy may be transient TT Dosage forms must be compounded Uses/Indications Ipodate may be useful in some cats for the medical treatment of hyperthyroidism when methimazole (or carbimazole) cannot be tolerated. Because it uses a different mechanism of action than me-thimazole, ipodate may, potentially, be useful in reducing methima-zole dosages (and hence toxicity). Pharmacology/Actions Ipodate's efﬁcacy in treating hyperthyroidism is thought to be pri-marily due to inhibition of the conversion of T 4 to T3. Ipodate may also block T 3 receptors and thereby protecting the heart from the hypertrophic effects of hyperthyroidism. It may block the actions of TSH. Pharmacokinetics The drug is well absorbed after oral administration. Other perti-nent pharmacokinetic data for cats is unavailable. Contraindications/Precautions/Warnings Ipodate is contraindicated in patients with known hypersensitiv-ity to it. It should be used with caution in patients who have had previous reactions to iodine compounds. Humans with hepatic dysfunction should not receive multiple doses of the drug as renal toxicity has resulted in a few patients. It is recommended for use with caution in human patients with hyperuricemia (possible uric acid nephropathy). Adverse Effects Cats reportedly tolerate ipodate well, but may become refractory to treatment after a relatively short time. Oral iodine containing products can cause GI distress (nausea, vomiting, diarrhea, cramp-ing, inappetence). Skin rashes, itching, dizziness and headache have been reported by human patients. Reproductive/Nursing Safety If administered to pregnant cats, congenital hypothyroidism is a possibility. Overdosage/Acute Toxicity No speciﬁc information located. Cats have reportedly tolerated daily doses up to 400 mg. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ipodate and may be of signiﬁcance in veterinary patients: T ! IODINE, RADIOACTIVE : Ipodate may interfere with radioactive io-dine therapy. It is suggested to treat no sooner than 2 weeks after discontinuing ipodate (3-4 weeks or more if possible). Laboratory Considerations T ! Ipodate may increase BSP retention times and serum bilirubin levels T ! False positive urine protein determinations may occur Doses T ! CATS: For medical treatment of hyperthyroidism in patients who can-not tolerate methimazole and whose owners will not permit sur-gery or radioiodine therapy: a) 100-200 mg (total dose) PO once daily (Lorenz and Me-lendez 2002a) b) 50 mg per cat PO twice daily, if “good' clinical response not obtained, at 2 week intervals may increase dose to 150 mg/ day (100 mg AM, 50 mg PM) and then to 200 mg/day (100 mg twice daily). Cats with severe hyperthyroidism are less likely to respond. (Murray and Peterson 1997) c) For use before surgery: 15 mg/kg PO q12h. (Jones 2006) Monitoring T ! Clinical efﬁcacy (heart rate, body weight, etc. ) T ! Serum T 3 (Note : T4 did not change—remained high in study group) Client Information T ! It must be stressed to owners that this drug will decrease exces-sive thyroid hormones, but does not cure the condition and that compliance with the treatment regimen is necessary for success. T ! Long-term efﬁcacy is questionable. Chemistry/Synonyms An orally administered radiopaque organic iodine compound, ipo-date sodium occurs as a white to off-white, ﬁne crystalline powder. It is freely soluble in alcohol and water. Each 500 mg capsule con-tains 61. 4% (or 333. 4 mg) of iodine. Ipodate calcium may also be known as: calcium iopodate, cal-cium ipodate, ipodate calcium, Solu-Biloptin®, and Solubiloptine®. Ipodate sodium may also be known as: sodium iopodate, sodi-um ipodate, NSC-106962, Bilivist®, Biloptin®, and Oragraﬁn®. Storage/Stability Store capsules in tight containers and protect from light.	pppbs.pdf
IPRAT ROPIUM BROMIDE 491 TDosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: None; must obtained via a compounding pharmacy. Note : Most of the studies using ipodate in cats have been done with calcium ipodate. It is likely that sodium ipodate would be fairly equivalent. If the compounding pharmacy has access to calcium ipo-date, it is suggested to use that form. IPRATROPIUM BROMIDE (eye-prah-troh-pee-um) Atrovent® INHALED ANTIMUSCARINIC Prescriber Highlights TT Inhaled antimuscarinic agent for adjunctive treatment of bronchoconstrictive conditions TT Very little information available for use in small animals TT Likely safe TT May need to be administered quite often, duration of ac-tivity is relatively short Uses/Indications Locally administered (inhaled) ipratropium bromide can be used for the adjunctive treatment of bronchospastic conditions. Pharmacology/Actions Ipratropium inhibits vagally mediated reﬂexes by antagonizing acetylcholine. Increases in intracellular concentrations of cyclic guanosine monophosphate (cyclic GMP) secondary to acetylcho-line are prevented, thereby reducing bronchial smooth muscle constriction. Pharmacokinetics Because the medication is inhaled, minimal drug is absorbed in the systemic circulation. In humans, elimination half-life is about 2 hours. In healthy cats with experimentally induced bronchospasm, inhaled (neb) ipratropium gave maximal efﬁcacy for about 4 hours. When combined with albuterol (salbutamol), increased efﬁcacy re-sulted. (Leemans, Kischvink et al. 2006) In horses, duration of effect is approximately 4-6 hours. Contraindications/Precautions/Warnings Ipratropium is contraindicated in patients hypersensitive to it or other atropine derivatives. It should be used with caution in other conditions where an-timuscarinics may be harmful, including narrow-angle glaucoma, bladder-neck obstruction, or prostatic hypertrophy. Adverse Effects Adverse effects are unlikely to be signiﬁcant. Tracheal or bronchi-al irritation (coughing) have been reported on occasion. Allergic responses are possible and some patients develop anticholinergic effects. Reproductive/Nursing Safety Large oral dosages in laboratory animals did not cause teratogenic effects. In humans, the FDA categorizes ipratropium as category B for use during the ﬁrst two trimesters of pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrat-ed a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Ipratropium is likely to be safe to use during nursing. Overdosage/Acute Toxicity Overdosage is unlikely to be a cause for concern. The drug is not well absorbed orally or after inhalation and oral LD50 values for laboratory animals were greater than 1 gram/kg. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ipratropium and may be of signiﬁcance in veterinary patients: T ! ANTICHOLINERGIC DRUGS : May cause additive antimuscarinic effects T ! BETA-ADRENERGIC AGONISTS (e. g., albuterol ): May have additive therapeutic effects Laboratory Considerations No speciﬁc concerns were noted Doses T ! HORSES: For RAO, heaves: a) 90-180 mcg inhaled aerosol q12h (Rush 2006a) Monitoring T ! Clinical efﬁcacy Client Information T ! If using the aerosol metered dose inhalers, do not use after 200 inhalations (puffs) even if there appears to be medication re-maining; active ingredient cannot be assured; do not shake the HFA canister before using T ! his medication is not for treating an acute asthma attack, it is for maintenance treatment Chemistry/Synonyms Ipratropium bromide occurs as a white or almost white crystalline powder. It is soluble in water and slightly soluble in alcohol The p H of a 1% solution is between 5 and 7. 5. Ipratropium bromide may also be known as Sch-1000; many trade names are available including Atrovent. ® Storage/Stability/Compatibility The solution for inhalation should be stored at room temperature and protected from light. Keep in foil pouch until time of use. The metered dose inhalers should be stored at room temperature. The solution for nebulization may be mixed with albuterol or metaproterenol if used within one hour. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Ipratropium Bromide Solution for Inhalation: 0. 02% (500 mcg) in 2. 5 m L UD “nebs”; generic (Dey); (Rx) Ipratropium Bromide Aerosol for Inhalation: each actuation de-livers 17 mcg in 12. 9 g metered dose inhaler; Atrovent® HFA (BI); (Rx) Ipratropium Bromide Aerosol for Inhalation: each actuation deliv-ers 18 mcg in 14. 7 g metered dose inhaler; Atrovent® (BI); (Rx)	pppbs.pdf
492 IRBESARTAN Nasal sprays are available, and in combination with albuterol as nebs: Duo Neb® (Dey) and as a metered dose inhaler, Combivent® (BI). IRBESARTAN (ihr-beh-sar-tan) Avapro® ANGIOTENSIN-II RECEPTOR BLOCKER (ARB) Prescriber Highlights TT ARB that may be useful in treating dogs with hyperten-sion secondary to renal insufﬁciency TT Very limited experience in veterinary medicine TT Not safe during pregnancy Uses/Indications Although experience in veterinary medicine is minimal irbesartan may be useful in treating canine hypertension associated with renal insufﬁciency. It may be effective in treating heart failure when dogs are unable to tolerate ACE inhibitors, but documentation for this use is lacking. One study, using very high irbesartan dosages (60 mg/kg PO twice daily) in dogs with subacute mitral regurgitation, demonstrated no improvement in left ventricular function or pre-vention of left ventricular remodeling (Perry, Wei et al. 2002). Pharmacology/Actions Irbesartan is an angiotensin-II receptor blocker (ARB). By selec-tively blocking the AT 1receptor, aldosterone synthesis and secre-tion is reduced causing vasodilation and decreased potassium and increased sodium excretion. While plasma concentrations of renin and angiotensin-II are increased, this does not counteract the blood pressure lowering effects of irbesartan. Irbesartan does not interfere with substance P or bradykinin responses. Irbesartan does not need to be converted to an active metabolite as does the ARB, losartan (Cozaar®). Dogs, unlike humans, report-edly do not covert losartan to the active metabolite. Pharmacokinetics After single 30 mg/kg oral doses in dogs with experimentally in-duced renal hypertension, irbesartan peak levels occurred between 3-4 hours later and elimination half-life was approximately 9 hours. After 30 mg/kg doses PO once daily for 8 days, the elimina-tion half-life was approximately 21 hours (Huang, Qiu et al. 2005). In humans, absorption is rapid and bioavailability ranges from 60-80%. Peak levels occur in about 1. 5-2 hours. Bioavailability is not altered by the presence of food. The drug is 90% bound to plasma proteins and crosses the blood-brain barrier and placenta in small quantities. Irbesartan is metabolized in the liver via glucuroni-dation and oxidation; metabolites are not active. Both metabolites and unchanged drug are eliminated primarily in the feces and to a lesser extent, in urine. T erminal elimination half-life ranges from 11-15 hours. Dosages do not need to be adjusted in patients with renal dysfunction. Contraindications/Precautions/Warnings Patients who are volume or sodium depleted should have these cor-rected before starting therapy. Do not use in hypotensive patients. In humans, the drug is contraindicated in patients hypersensitive to it. It should not be used during pregnancy (see Reproductive Safety). Adverse Effects An adverse effect proﬁle for dogs is not known due to limited use of this medication. In humans, the most commonly reported adverse effects include diarrhea, dyspepsia, fatigue, and orthostatic dizzi-ness/hypotension. Reproductive/Nursing Safety Irbesartan is not safe to use during pregnancy. Studies in pregnant rats given high doses demonstrated a variety of fetal abnormali-ties (renal pelvic cavitation, hydroureter, absence of renal papilla). Smaller doses in rabbits caused increased maternal death and spon-taneous abortion. In humans, the drug is considered teratogenic, particularly during the 2nd and 3rd trimesters. During this time, the FDA categorizes irbesartan as category D for use during preg-nancy (There is evidence of human fetal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) If pregnancy is detected in patients receiving irbesartan, the drug should be discontinued as soon as possible. Because small amounts of irbesartan have been detected in rat milk, and there is signiﬁcant concern about the safety of the drug in neonates, the manufacturer recommends that it not be used in nursing women. Overdosage/Acute Toxicity Rats and mice survived acute oral overdoses in excess of 2000mg/kg. Likely effects seen in an overdose situation include hypotension and either bradycardia or tachycardia; treatment is supportive. Contact an animal poison control center for further information. Drug Interactions In humans or veterinary patients, no clinically signiﬁcant drug interactions have been reported. Because of the drug's pharmaco-logic actions, use caution with other drugs that can reduce blood pressure. Laboratory Considerations No speciﬁc concerns were noted Doses T ! DOGS: a) As an alternative to ACE inhibitors for treatment of hy-pertension associated with renal insufﬁciency: 5 mg/kg PO q12-24 hours. (Brown 2004) Monitoring T ! Blood pressure, heart rate T ! Serum electrolytes, BUN, creatinine T ! Adverse Effects: possibly GI (diarrhea), somnolence/activity changes Client Information T ! Clients should understand that veterinary experience with this medication is limited and that the adverse effect proﬁle is not well known; anything unusual should be reported to the veteri-narian T ! May be given with food or on an empty stomach Chemistry/Synonyms Irbesartan is a nonpeptide angiotensin-II antagonist and occurs as white to off-white, crystalline powder. It is practically insoluble in water and slightly soluble in alcohol. Irbesartan may also be known as: BMS 186295, SR 47436, Irbesartanum, Aprovel ®, Arbit®, Avalide®, Avapro®, Cavapro®, Coaproval®, Ecard®, Ibsan®, Irban®, Irbes ®, Iretensa®, Irovel ®, Irvell ®, Isart®, and Karvea®.	pppbs.pdf
IRON DEXTRAN 493 Storage/Stability Irbesartan tablets should be stored at room temperature (15-30°C). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. HUMAN-LABELED PRODUCTS: Irbesartan Tablets: 75 mg, 150 mg, & 300 mg; Avapro® (Bristol-Myers Squibb); (Rx) Irbesartan 150 mg with Hydrochlorothiazide 12. 5 mg Tablets, Irbesartan 300 mg with Hydrochlorothiazide 12. 5 mg or 25 mg Tablets; Avalide®; (Bristol-Myers Squibb); (Rx) IRON DEXTRAN (eye-urn dex-tran) INJECTA BLE HEMATINIC Prescriber Highlights TT Injectable hematinic TT Contraindications: Known hypersensitivity to iron dextran, or with any anemia other than iron deﬁciency anemia; acute renal infections, in conjunction with oral iron sup-plements TT Adverse Effects: Prostration & muscular weakness, ana-phylactoid reactions TT High dosages may cause increased incidences of terato-genicity & embryotoxicity TT Pigs born of vitamin E/selenium-deﬁcient sows may demonstrate nausea, vomiting, & sudden death within 1 hour of injection TT IM use in pigs after 4 weeks of age may cause muscle tissue staining Uses/Indications Iron dextran is used in the treatment and prophylaxis of iron deﬁ-ciency anemias, primarily in neonatal food-producing animals. Pharmacology/Actions Iron is necessary for myoglobin and hemoglobin in the transport and utilization of oxygen. While neither stimulating erythropoiesis nor correcting hemoglobin abnormalities not caused by iron de-ﬁciency, iron administration does correct both physical signs and decreased hemoglobin levels secondary to iron deﬁciency. Ionized iron is a component in the enzymes cytochrome oxi-dase, succinic dehydrogenase, and xanthine oxidase. Pharmacokinetics After IM injection, iron dextran is slowly absorbed primarily via the lymphatic system. About 60% of the drug is absorbed within 3 days of injection and up to 90% of the dose is absorbed after 1-3 weeks. The remaining drug may be absorbed slowly over several months. After absorption, the reticuloendothelial cells of the liver, spleen, and bone marrow gradually clear the drug from plasma. The iron is cleaved from the dextran component and the dextran is then metabolized or excreted. The iron is immediately bound to protein elements to form hemosiderin, ferritin or transferrin. Iron crosses the placenta, but in what form is unknown. Only traces of iron are excreted in milk. Iron is not readily eliminated from the body. Iron liberated by the destruction of hemoglobin is reused by the body and only small amounts are lost by the body via hair and nail growth, normal skin desquamation, and GI tract sloughing. Accumulation can result with repeated dosing as only trace amounts of iron are eliminated in the feces, bile, or urine. Contraindications/Precautions/Warnings Iron dextran is contraindicated in patients with known hypersensi-tivity to it or with any anemia other than iron deﬁciency anemia. It is not to be used in patients with acute renal infections, and should not be used in conjunction with oral iron supplements. Adverse Effects The manufacturers of iron dextran injection for use in pigs state that occasionally pigs may react after injection with iron dextran, characterized by prostration and muscular weakness. Rarely, death may result from an anaphylactoid reaction. Iron dextran used in pigs born of vitamin E/selenium-deﬁcient sows may demonstrate nausea, vomiting, and sudden death within 1 hour of injection. Iron dextran injected IM in pigs after 4 weeks of age may cause muscle tissue staining. Large SC doses have been associated with the development of sarcomas in laboratory animals (rabbits, mice, rats, and hamsters). Reproductive/Nursing Safety High dosages may cause increased incidences of teratogenicity and embryotoxicity. Use only when clearly necessary at recommended doses in pregnant animals. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate stud-ies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Traces of unmetabolized iron dextran are excreted in milk. Overdosage/Acute Toxicity Depending on the size of the dose, inadvertent overdose injections may require chelation therapy. For more information, refer to the Ferrous Sulfate monograph for information on using deferoxamine and other treatments for iron toxicity. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving iron and may be of sig-niﬁcance in veterinary patients: T ! CHLORAMPHENICOL : Because chloramphenicol may delay the re-sponse to iron administration, avoid using chloramphenicol in patients with iron deﬁciency anemia Laboratory Considerations T ! Large doses of injectable iron may discolor the serum brown which can cause falsely elevated serum bilirubin values and falsely decreased serum calcium values. T ! After large doses of iron dextran, serum iron values may not be meaningful for up to 3 weeks. Doses T ! DOGS: For iron deﬁciency anemia: a) Iron dextran 10-20 mg/kg once, followed by oral therapy with ferrous sulfate (see ferrous sulfate monograph) (Weiser 1989b)	pppbs.pdf
494 ISOFLUPREDONE ACETATE T ! CATS: For iron deﬁciency anemia: a) For prevention of transient neonatal iron deﬁciency ane-mia: 50 mg iron dextran injection at 18 days of age (Weiser 1989a) b) For adjunctive therapy with erythropoietin treatment: 50 mg IM q3-4 weeks (Cowgill 2002) c) For adjunctive therapy with erythropoietin treatment in cats who cannot tolerate oral iron therapy: 50 mg IM q3-4 weeks (Hoskins 2005b) T ! FERRETS: a) 10 mg/kg IM once weekly (Williams 2000) T ! SWINE: For prevention of iron deﬁciency anemia in baby pigs (1-3 days of age): a) 100-150 mg of elemental iron IM per pig. (Label directions; Ferrextran-100®—Fort Dodge) For treatment of iron deﬁciency anemia in baby pigs: a) 100-200 mg of elemental iron IM per pig. May repeat in 10-14 days. Label directions; Ferrextran-100®—Fort Dodge) T ! BIRDS: For iron deﬁciency anemia or following hemorrhage: a) 10 mg/kg IM; repeat in 7-10 days if PCV fails to return to normal (Clubb 1986) b) 10 mg/kg IM; repeat weekly (Mc Donald 1989) Monitoring T ! If indicated: CBC, RBC indices T ! Adverse reactions Client Information T ! In pigs, inject IM in the back of the ham Chemistry/Synonyms Iron dextran is a complex of ferric oxyhydroxide and low molecular weight partially hydrolyzed dextran derivative. The commercially available injection occurs as a dark brown, slightly viscous liquid that is completely miscible with water or normal saline and has a p H of 5. 2-6. 5. Iron dextran may also be known as: iron-dextran complex, Cosmofer®, Dex Ferrum®, Dexiron®, Driken ®, Fercayl®, Ferrocel®, Ferroin®, Ferrum Hausmann®, Fexiron®, Imferdex®, Imferon®, In Fe D®, and Infufer®. Storage/Stability/Compatibility Iron dextran injection should be stored at room temperature (15-30°C); avoid freezing. Iron dextran injection is reportedly physically incompatible when mixed with oxytetracycline HCl and sulfadiazine sodium. Dosage Forms/Regulatory Status/Withdrawal Times VETERINARY-LABELED PRODUCTS: Iron Dextran Injection: 100 mg of elemental iron/m L and 200 mg of elemental iron/m L in 100 m L vials; various manufacturers and trade names; (OTC). Approved for use in swine. No slaughter withdrawal time required. HUMAN-LABELED PRODUCTS: Iron Dextran Injection: 50 mg of elemental iron/m L (as dextran) in 1 m L & 2 m L single-dose vials; In Fe D® (Schein); Dex Ferrum® (Ameri-can Regent); (Rx) ISOFLUPREDONE ACETATE (eye-so-ﬂoo-preh-dohn) Predef 2X® INJECTA BLE GLUCOCORTICOID For topical or otic use of isoﬂupredone, see the T opical Dermatological Agents, and Otic Appendixes Prescriber Highlights TT Injectable glucocorticoid labeled for use in cattle, horses & swine for antiinﬂammatory & immunosuppressive effects TT Less likely to cause early parturition than dexametha-sone or betamethasone, but avoid use in pregnancy TT May have mineralocorticoid effects in horses & cattle; hypokalemia has been noted Uses/Indications Isoﬂupredone acetate is a potent glucocorticoid and like other glu-cocorticoids can be used for its antiinﬂammatory or immunosup-pressive effects. Labeled indications for isoﬂupredone include: ad-junctive treatment of bovine ketosis, alleviating pain and lameness associated with musculoskeletal conditions, acute hypersensitivity reactions, adjunctive treatment of overwhelming infections with severe toxicity, shock, supportive therapy in the treatment of stress conditions (e. g., surgery), dystocia, retained placenta, inﬂammatory ocular conditions, snakebite and parturient paresis. In horses, isoﬂupredone has been used parenterally to reduce inﬂammation associated with recurrent airway obstruction (RAO, “heaves”, COPD). While the drug could be used in small animals, it is recommend-ed to use other glucocorticoid agents instead, where there has been more experience and other approved products for dogs and cats are available. Pharmacology/Actions Isoﬂupredone's antiinﬂammatory potency is approximately 17 times that of hydrocortisone (cortisol). The label states that the glucocorticoid activity of isoﬂupredone is 50 times that of hydro-cortisone and 10 times that of prednisolone as measured by liver glycogen deposition in rats. Isoﬂupredone reportedly has minimal mineralocorticoid effects, but recent work has demonstrated that it can cause hypokalemia. For more information on the pharmacologic actions associ-ated with glucocorticoids, see the Glucocorticoid Agents, General Information monograph. Pharmacokinetics No speciﬁc pharmacokinetic values were located. The manufac-turer states that gluconeogenic activity persists for 48 hours after dosing in cattle. Contraindications/Precautions/Warnings Systemic use of glucocorticoids is generally considered contrain-dicated in systemic fungal infections (unless used for replacement therapy in Addison's), when administered IM in patients with idio-pathic thrombocytopenia, and in patients hypersensitive to a par-ticular compound. Because of their ulcerogenic potential, glucocor-ticoids should be used with extreme caution in patients with active GI ulcers or those susceptible to them. Use cautiously in patients with diabetes mellitus.	pppbs.pdf
ISOFLUPREDONE ACETATE 495 Chronic use in young, growing animals must be undertaken cautiously, as decreased growth may occur. Not to be used in calves to be processed into veal. See Reproductive Safety for information on use during pregnancy. Adverse Effects Adverse effects are generally associated with long-term administra-tion of glucocorticoids, particularly if given at higher dosages; these effects generally are manifested as signs of hyperadrenocorticism. Recent research has indicated, however, that even single doses ad-ministered to dairy cattle can cause hypokalemia. Potential adverse effects include: reduced milk production, hypokalemia, delayed wound healing, GI ulceration, increased infection rates, diabetes mellitus exacerbation/hyperglycemia, pancreatitis, hepatopathy, re-nal dysfunction, osteoporosis, laminitis (horses), hypothyroidism, and hyperlipidemia. When administered to young, growing animals, glucocorticoids can retard growth. Reproductive/Nursing Safety Avoid using isoﬂupredone during pregnancy. Glucocorticoids can induce abortion or early parturition in the later stages of pregnancy; most commonly seen in ruminants. Isoﬂupredone appears to have a lower abortifacient potential (like hydrocortisone, prednisolone, triamcinolone) than steroids such as dexamethasone, betametha-sone or ﬂumethasone; it may induce premature parturition with retained placenta and its use should be avoided during the later stages of pregnancy. Glucocorticoids used during the ﬁrst trimester have been linked to a variety of teratogenic effects in dogs and laboratory animals. Glucocorticoid administration may reduce milk production. Glucocorticoids unbound to plasma proteins will enter milk. High dosages or prolonged administration to mothers may potentially inhibit the growth of nursing newborns. Overdosage/Acute Toxicity A single overdose of isoﬂupredone is unlikely to cause harmful effects. Should clinical signs require intervention, use supportive treatment. Chronic usage of glucocorticoids can lead to serious adverse ef-fects. Refer to the Adverse Effects section for more information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving isoﬂupredone or other glucocorticoids and may be of signiﬁcance in veterinary patients: !TDIGITALIS GLYCOSIDES (digoxin ): Increased chance of digitalis toxic-ity may occur should hypokalemia develop; diligent monitoring of potassium and digitalis glycoside levels is recommended !TPOTASSIUM-DEPLETING DIURETICS (furosemide, thiazides ): Ad-ministered concomitantly with glucocorticoids may cause hy-pokalemia !TSALICYLATES : Glucocorticoids may reduce salicylate blood levels !TULCEROGENIC DRUGS (e. g., NSAIDs ): With glucocorticoids may in-crease the risk of gastrointestinal ulceration !TVACCINES, TOXOIDS, BACTERINS : A diminished immune response may occur after vaccine, toxoid, or bacterin administration; pa-tients receiving corticosteroids at immunosuppressive dosages should generally not receive live attenuated-virus vaccines as vi-rus replication may be augmented Laboratory Considerations !TGlucocorticoids may increase serum cholesterol and serum and urine glucose levels !TGlucocorticoids may decrease serum potassium !TGlucocorticoids can suppress the release of thyroid stimulating hormone (TSH) and reduce T3 & T4 values; thyroid gland atro-phy has been reported after chronic glucocorticoid administra-tion !TReactions to skin tests may be suppressed by glucocorticoids. !TGlucocorticoids may cause false-negative results of the nitroblue tetrazolium test for systemic bacterial infections. Doses !TCATTLE: a) For labeled systemic indications: 10-20 mg (total dose) IM, according to the size of the animal and severity of the condi-tion. The dose may be repeated in 12 to 24 hours if indicated. (Label information; Predef 2X®—Pharmacia & Upjohn) !THORSES: (Note : RCI: Class 4) a) For labeled systemic indications: 5-20 mg (total dose) IM re-peated as necessary. For intrasynovial administration: 5-20 mg or more depending on the size of the joint cavity. (Label information; Predef 2X®—Pharmacia & Upjohn) b) For intraarticular administration: 4-20 mg; has a short to medium duration of action. (Goodrich 2006) c) For treatment of “heaves” (RAO): 10-14 mg (total dose) IM once daily for a horse weighing between 450-500 kg. (Lavoie 2003) d) For treatment of recurrent airway obstruction (RAO): 0. 03 mg/kg IM once daily. Patients were treated for 14 days and developed signiﬁcant decreases in serum potassium. (Pican-det, Leguillette et al. 2003) !TSWINE: a) For labeled systemic indications: 5 mg (total dose) IM for a 300 lb. animal. Adjust dose proportionally for a smaller or larger animal. (Label information; Predef 2X®—Pharmacia & Upjohn) Monitoring !TSingle injections may not require monitoring beyond observa-tion of the patient for efﬁcacy and adverse effects, but consider evaluating serum potassium !TOngoing usage requires enhanced monitoring including: renal and liver function, CBC, blood glucose and serum electrolytes !TACTH stimulation tests may be indicated to determine extent of HPA axis suppression !TConsider thyroid hormone monitoring if use is prolonged or pa-tient exhibits signs associated with thyroid hormone deﬁciency Client Information !TIf used in dairy cattle, warn producer that milk production may be affected !TIf owners are to administer the medication, caution them to only administer as the veterinarian directs Chemistry/Synonyms Isoﬂupredone acetate is a ﬂuorinated synthetic corticosteroid with a molecular weight of 420. 5. The commercial injection is in an aqueous suspension that also contains sodium citrate, polyethylene glycol 3350, and povidone. Isoﬂupredone acetate may also be known as: U-6013, 9alpha-ﬂuoroprednisolone acetate, and Predef 2x®.	pppbs.pdf
496 ISOFLURANE Storage/Stability The injection should be stored at controlled room temperature 20°-25°C. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Isoﬂupredone acetate 2 mg/m L aqueous suspension for injection in 10 m L and 100 m L vials; Predef 2x® (Pharmacia & Upjohn); (Rx). In the USA, Predef 2x® is approved for use in cattle, horses and swine. Meat withdrawal time is 7 days; it is not to be used in calves to be processed for veal. There is no milk withdrawal time for isoﬂu-predone in the USA, but in Canada a 72-hour withdrawal time is speciﬁed. Isoﬂupredone is also found in some topical and otic products. For more information see the Dermatological Agents, Topical and Otic Appendixes. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. HUMAN-LABELED PRODUCTS: None ISOFLURANE (eye-soe-ﬂure-ane) Isoﬂo®, Iso-Thesia® GENERAL ANESTHETIC, INHALANT Prescriber Highlights TT Inhalant general anesthetic TT Contraindications: History or predilection towards malig-nant hyperthermia TT Caution with increased CSF or head injury, or myasthenia gravis TT Adverse Effects: Dose related hypotension, respiratory depression, & GI effects (nausea, vomiting, ileus); car-diodepression generally is minimal at doses causing sur-gical planes of anesthesia. Arrhythmias are rare. TT May be fetotoxic TT Drug interactions Uses/Indications Isoﬂurane is an inhalant anesthetic that has some distinct advan-tages over either halothane or methoxyﬂurane due to its lessened myocardial depressant and catecholamine sensitizing effects, and the ability to use it safely in patients with either hepatic or renal disease. Isoﬂurane's higher cost than either methoxyﬂurane or ha-lothane is a disadvantage. Horses may recover more rapidly than with halothane, but be more susceptible to anesthetic associated-myopathy. Pharmacology/Actions While the precise mechanism that inhalant anesthetics exert their general anesthetic effects is not precisely known, they may interfere with functioning of nerve cells in the brain by acting at the lipid matrix of the membrane. Some key pharmacologic effects noted with isoﬂurane include: CNS depression, depression of body tem-perature regulating centers, increased cerebral blood ﬂow, respira-tory depression, hypotension, vasodilatation, myocardial depres-sion (less so than with halothane), and muscular relaxation. Minimal Alveolar Concentration (MAC; %) in oxygen reported for isoﬂurane in various species: Dog = 1. 5; Cat = 1. 2; Horse = 1. 31; Human = 1. 2. Several factors may alter MAC (acid/base status, tem-perature, other CNS depressants on board, age, ongoing acute dis-ease, etc. ). Pharmacokinetics Isoﬂurane is rapidly absorbed from the alveoli. It is rapidly distrib-uted into the CNS and crosses the placenta. The vast majority of the drug is eliminated via the lungs; only about 0. 17% is metabolized in liver and only very small amounts of inorganic ﬂuoride is formed. Contraindications/Precautions/Warnings Isoﬂurane is contraindicated in patients with a history or predi-lection towards malignant hyperthermia. It should be used with caution (beneﬁts vs. risks) in patients with increased CSF or head injury, or myasthenia gravis. Adverse Effects Hypotension (secondary to vasodilation, not cardiodepression) may occur and is considered to be dose related. Dose-dependent respiratory depression, and GI effects (nausea, vomiting, ileus) have been reported. While cardiodepression generally is minimal at dos-es causing surgical planes of anesthesia, it may occur. Arrhythmias have rarely been reported. Reproductive/Nursing Safety Some animal studies have indicated that isoﬂurane may be feto-toxic. Use during pregnancy with caution. In a system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving isoﬂurane and may be of signiﬁcance in veterinary patients: T ! AMINOGLYCOSIDES : Use with caution with halogenated anesthetic agents as additive neuromuscular blockade may occur T ! LINCOSAMIDES : Use with caution with halogenated anesthetic agents as additive neuromuscular blockade may occur T ! NON-DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS : Additive neuromuscular blockade may occur T ! SUCCINYLCHOLINE : With inhalation anesthetics, may induce in-creased incidences of cardiac effects (bradycardia, arrhythmias, sinus arrest and apnea) and, in susceptible patients, malignant hyperthermia T ! SYMPATHOMIMETICS (dopamine, epinephrine, norepinephrine, ephed-rine, metaraminol, etc. ): While isoﬂurane sensitizes the myocar-dium to the effects of sympathomimetics less so than halothane, arrhythmias may still result. If these drugs are needed, they should be used with caution and in signiﬁcantly reduced dosages with intensive monitoring Doses T ! DOGS & CAT S: (Note : Concentrations are dependent upon fresh gas ﬂow rate; the lower the ﬂow rate, the higher the concentration required. ) a) 5% induction; 1. 5-2. 5% maintenance (Papich 1992) b) 0. 5-3 %, inhaled (Hubbell 1994) T ! FERRETS/SMALL MAMMALS: a) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: Using a non-rebreathing system: Induction: 2-3%, maintenance: 0. 25-2% (Anderson 1994); (Adamcak and Otten 2000)	pppbs.pdf
ISONIAZID (INH) 497 b) Ferrets: After premed with medetomidine at 50-100 mcg/ kg. Atropine at 0. 05 mg/kg SC is used to counteract hypersal-ivation and bradycardia. Starting isoﬂurane at 1-2% will be less irritating to the ferret and cause less of a struggle. Use a non-rebreathing system. Consider intubation in procedures lasting longer than 30 minutes. For post-op pain either bu-torphanol at 0. 1 mg/kg SC or buprenorphine at 0. 02 mg/kg SC. (Johnson 2006c) T ! REPTILES: a) Give 5% isoﬂurane and oxygen in a clear plastic bag or in-duction chamber. Fill chamber with gas and seal. Induc-tion time may take 30-60 minutes, but can be shortened to 15-30 minutes with increased depth of anesthesia if animal is injected with 10-20 mg/kg of ketamine (SC or IM). Pa-tient should be kept warm by placing on a water blanket. Surgical anesthesia can be determined by the loss of righting reﬂex. After induction, use either a mask, ET tube, or leave head in chamber. Maintenance levels are 3-5% (if isoﬂurane used alone). If apnea occurs during or after anesthesia, dis-continue gas anesthetic and apply gentle manual ventilation 2-4 times per minute with small doses of doxapram IV. Nor-mal respiration generally resumes in 3-5 minutes. Righting reﬂex generally recovers in an hour, but animal may be tran-quilized for up to 24 hours. (Gillespie 1994) b) Anesthetic gas of choice for reptiles. Induction can be with a face mask, or with a “cat box. ” Animal may be intubated, especially if has been preanesthetized with ketamine or Te-lazol, and “bag” it down with positive pressure ventilation. Maintenance is usually 1. 5-3%. (Funk 2002) T ! BIRDS: a) Small birds can be anesthetized safely in 15-30 seconds at 4% (Ludders 1992) b) Induction occurs within 1-2 minutes at a concentration of 3-5%. Maintenance at 1. 5-2% is adequate for most birds. Anesthetic of choice for birds; heart rate may decrease, but not to the same degree as halothane. Recovery very rapid; most patients are standing and cage safe within 5 min. after anesthesia discontinued, but there seems to be a direct rela-tionship between anesthesia time and recovery time. (Ben-nett 2002) Monitoring T ! Respiratory and ventilatory status T ! Cardiac rate/rhythm; blood pressure (particularly with “at risk” patients T ! Level of anesthesia Chemistry/Synonyms An inhalant general anesthetic agent, isoﬂurane occurs as a color-less, nonﬂammable, stable liquid. It has a characteristic mildly pun-gent musty, ethereal odor. At 20°C, isoﬂurane's speciﬁc gravity is 1. 496 and vapor pressure is 238 mm Hg. Isoﬂurane may also be known as: compound 469, isoﬂura-num, AErrane®, Forene®, Forenium®, Forthane®, Isoﬂo®, Isofor®, Isoforine®, Isosol®, Isothane®, Iso-Thesia®, Lisorane®, Soﬂoran®, Tensocold®, Terrell ® and Zuﬂax®. Storage/Stability/Compatibility Isoﬂurane should be stored at room temperature; it is relatively un-affected by exposure to light, but should be stored in a tight, light-resistant container. Isoﬂurane does not attack aluminum, brass, tin, iron, or copper. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Isoﬂurane Inhalation Anesthetic: 99. 9%/m L in 100 m L and 250 m L bottles; Isoﬂo® (Abbott), Isosol® (Vedco), Iso-Thesia® (Butler), gener-ic, (Halocarbon, Vet One, Phoenix Pharmaceutical); (Rx). Approved for use in horses (those not intended for food) and dogs. HUMAN-LABELED PRODUCTS: Isoﬂurane in 100 m L bottles; Forane® (Anaquest); Terrell ® (Minrad); generic (Abbott); (Rx) ISONIAZID (INH) (eye-so-nye-ah-zid) Isonicotinic acid hydrazide ANTIMYCOBACTERIAL Prescriber Highlights TT Antimycobacterial that may be used for chemoprophy-laxis of M. bovis or M. tuberculosis in small animals TT Treating active infections is controversial because of po-tential public health risks associated with the infections TT Hepatotoxicity & neurotoxicity possible; narrow therapeu-tic index Uses/Indications Isoniazid (INH) is sometimes used for chemoprophylaxis in small animals in households having a human with tuberculosis. It po-tentially can be used in combination with other antimycobacterial drugs to treat infections of M. bovis or M. tuberculosis in dogs or cats. But because of the public health risks, particularly in the face of increased populations of immunocompromised people, treatment of mycobacterial (M. bovis, M. tuberculosis) infections in domestic or captive animals is controversial. In addition, INH has a narrow therapeutic index and toxicity is a concern (see Adverse Effects). In humans, isoniazid (INH) is routinely used alone to treat la-tent tuberculosis infections (positive tuberculin skin test) and in combination with other antimycobacterial agents to treat active disease. Pharmacology/Actions Isoniazid inhibits the synthesis of mycoloic acids, a component of mycobacterial cell walls; its exact mechanism is not well understood. It is most active against mycobacteria that are actively dividing and affects both extracellular and intracellular mycobacteria. Isoniazid is only active against M. tuberculosis, M. bovis and some strains of M. kansasii. In humans, resistance develops rapidly if used alone against active clinical disease, but not when used for prophylactic treatment. Pharmacokinetics No information was located on the pharmacokinetics of INH in dogs or cats. In humans, isoniazid is rapidly absorbed after oral administra-tion; food can decrease absorption somewhat and INH may un-dergo signiﬁcant ﬁrst pass metabolism. The drug is highly distrib-uted in the body and crosses into the CSF and caseous material. It is distributed into milk and crosses the placenta. It is only slightly (10%) bound to plasma proteins. In humans, the drug is initially primarily acetylated in the liver. The N-acetylated form is then fur-ther biotransformed to isonicotinic acid and monoacetylhydrazine.	pppbs.pdf
498 ISONIAZID (INH) Monoacetylhydrazine is thought to play a role in the drug's he-patic toxicity. As dogs, like some humans, lack N-acetyltransferase, increased potential for INH toxicity may occur in this species. Elimination half-life in fast acetylators (humans) is 0. 5-1. 6 hours and 2-5 hours in slow acetylators. Patients with acute or chronic liver disease may have substantially longer half-lives (2X). The drug is mostly eliminated in the urine as inactive metabolites. Contraindications/Precautions/Warnings Isoniazid is contraindicated in patients with acute liver disease or those that developed hepatopathy while taking the medication in the past. It should be used with caution in patients with decreased hepatic function or severe renal disease. Adverse Effects The primary adverse effects associated with INH is hepatotoxic-ity with increased serum liver enzymes. Additional adverse effects reported in dogs include CNS stimulation, peripheral neuropathy and thrombocytopenia. Ataxia, seizures, salivation, diarrhea, vom-iting and arrhythmias have been reported after overdoses in dogs. No adverse effect proﬁle for isoniazid was located for cats. In hu-mans, urticaria, hepatotoxicity and peripheral neuropathy are com-monly reported; rarely, blood dyscrasias, SLE, and seizures have been reported. Reproductive/Nursing Safety Isoniazid crosses the placenta and has been found to be embryocid-al in some laboratory species, but teratogenic effects have not been detected in mice, rabbits, or rats. In humans, the FDA categorizes isoniazid as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Isoniazid is excreted in milk in low concentrations (approx. 1-2% of maternal serum concentrations in humans) and it is thought to be safe to use during nursing. Ingested levels via milk are not high enough to serve as prophylaxis for tuberculosis in nursing infants. Overdosage/Acute Toxicity Overdosage of INH can be very serious. In dogs, the reported LD50 is 50 mg/kg; serious toxicity can occur with as little as one 300 mg tablet ingested. Ataxia, seizures, salivation, diarrhea, vom-iting, acidosis, and arrhythmias have been reported after overdoses in dogs; it is strongly recommended to contact an animal poison control center in the event of any inadvertent ingestion. Treatment may include activated charcoal and drugs such as diazepam or phenobarbital to control seizures. Fluids and acidemia may need correction. Pyridoxine (Vitamin B-6) has been suggested to be administered intravenously (preferably over 30-60 minutes) on a mg per mg of INH-ingested basis. It is commercially available as a 100 mg/m L 1 m L vial, but it may be difﬁcult to obtain in an emergency situation. A local human hospital may stock it. Drug Interactions Drug interactions have not been reported with isoniazid in animals. The following drug interactions have either been reported or are theoretical in humans receiving INH and may be of signiﬁcance in veterinary patients: !TALFENTANIL : Prolonged alfentanil duration of action !TANTACIDS (especially those containing aluminum ): Decreased INH absorption !TBENZODIAZEPINES : INH may reduce benzodiazepine metabolism !TCORTICOSTEROIDS : May reduce INH efﬁcacy !TKETOCONAZOLE : INH may reduce ketoconazole serum concentrations !TOTHER HEPATOTOXIC DRUGS (e. g., acetaminophen, itraconazole, ﬂu-conazole, methimazole, ketoconazole, phenothiazines, sulfonamides, estrogens, etc. ): increased risk of hepatotoxicity !TOTHER NEUROTOXIC DRUGS : Increased risk of neurotoxicity !TPYRIDOXINE : INH may antagonize or increase the excretion of pyridoxine, increased pyridoxine may be required; increased peripheral neuritis may occur secondary to pyridoxine/INH interaction !TPHENYTOIN : INH may inhibit metabolism and increase risks for phenytoin toxicity !TRIFAMPIN : Increased risk for hepatotoxicity !TTHEOPHYLLINE : Increased risk of theophylline toxicity FOOD INTERACTIONS in humans: cheese (Swiss, Cheshire, etc. ) or ﬁsh (Tuna, Skipjack, Sardinella): INH may interfere with metabolism of tyramine and histamine found in ﬁsh and cheese Laboratory Considerations !TINH may cause false-positive urine glucose determinations when using cupric sulfate solution (Benedict's Solution, Clinitest®); tests utilizing glucose oxidase (Tes-Tape®, Clinistix®) are not affected Doses !TDOGS: a) For M. tuberculosis chemoprophylaxis: 10 mg/kg PO once daily. Drug can be hepatotoxic and dose is extrapolated from human data. Treatment of M. tuberculosis or M. bovis infec-tions in dogs and cats is not recommended. (Greene and Gunn-Moore 2006) Monitoring !TBaseline and periodic physical exam, including clinical efﬁcacy and adverse effect queries !TBaseline and periodic: CBC, liver function, renal function Client Information !TBest to administer on an empty stomach !TIf this medication is to be effective, it must be given regularly as directed !TIf a dose is missed, do not double the next dose !TStore well out of reach of children or pets; overdoses can be very serious !TContact veterinarian if any of the following occur: vomiting, de-creased appetite/weight loss, diarrhea or loose stools, changes in behavior or activity, yellowing of whites of eyes or mucous mem-branes, or difﬁculty running or going up/down stairs Chemistry/Synonyms Isoniazid occurs as colorless, or white, odorless crystals. It is freely soluble in water and sparingly soluble in alcohol. It is recommend-ed not to use sugars such as glucose, fructose or sucrose in com-pounded oral solutions, as a condensation product can be formed that can impair absorption. Isoniazid may also be known as: INH, INAH, isonicotinic acid hydrazide, isonicotinylhydrazide, isonicotinylhydrazine, or tubazid. INH is available throughout the world in many trade names, some of the more commonly used names include Isotamine®, Laniazid®, or Nydrazid®. Caution : Isopyrin® is one isoniazid trade name that in some countries contains ramifenazone and not isoniazid.	pppbs.pdf
ISOPROTERENOL HCL 499 Storage/Stability Isoniazid tablets should be stored at temperatures below 40°C, pref-erably between 15-30°C, in well-closed, light-resistant contain-ers. The oral syrup should be stored at temperatures below 40°C, preferably between 15-30°C, in well-closed, light-resistant con-tainers protected from freezing. The injection should be stored at temperatures below 40°C, preferably between 15-30°C; protected from light and freezing. At low temperatures, crystals may form in the injectable solution; crystals should redissolve upon warming to room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Isoniazid Tablets: 150 mg, 300 mg; generic; (Rx) Isoniazid Oral Syrup: 10 mg/m L in pints; generic; (Rx) Isoniazid Injection: 100 mg/m L in 10 m L multidose vials; Nydrazid® (Apothecon); (Rx) Combination Products: Rifampin 120 mg, Isoniazid 50 mg, Pyrazinamide 300 mg Tablets; Rifater® (Aventis); (Rx) Rifampin 300 mg, Isoniazid 150 mg Capsules; Isona Rif® (Versa Pharm), Rifamate® (Aventis); (Rx) ISOPROTERENOL HCL (eye-soe-proe-ter-e-nole) Isuprel® BETA-ADRENERGIC AGONIST Prescriber Highlights TT Non-speciﬁc beta agonist rarely used for acute bronchial constriction, cardiac arrhythmias (complete AV block), & as adjunctive therapy in shock or heart failure TT Contraindications: Tachycardias or AV block caused by cardiac glycoside intoxication, ventricular arrhythmias that do not require increased inotropic activity TT Caution: Coronary insufﬁciency, hyperthyroidism, renal disease, hypertension, or diabetes; not a substitute for adequate ﬂuid replacement in shock TT Adverse Effects: Tachycardia, anxiety, tremors, excitability, headache, weakness, & vomiting; more arrhythmogenic than dopamine or dobutamine TT Short duration of activity (including adverse effects) Uses/Indications Isoproterenol is primarily used in veterinary medicine in the treat-ment of acute bronchial constriction, cardiac arrhythmias (com-plete A V block) and, occasionally, as adjunctive therapy in shock or heart failure (limited use because of increases in heart rate and ventricular arrhythmogenicity). Pharmacology/Actions Isoproterenol is a synthetic beta1-and beta2-adrenergic agonist that has no appreciable alpha activity at therapeutic doses. It is thought that isoproterenol's adrenergic activity is a result of stimulating cyclic-AMP production. Its primary actions are increased inotro-pism and chronotropism, relaxation of bronchial smooth muscle, and peripheral vasodilatation. Isoproterenol may increase perfu-sion to skeletal muscle (at the expense of vital organs in shock). Isoproterenol will inhibit the antigen-mediated release of histamine and slow releasing substance of anaphylaxis (SRS-A). Hemodynamic effects noted include decreased total peripheral resistance, increased cardiac output, increased venous return to the heart, and increased rate of discharge by cardiac pacemakers. Pharmacokinetics Isoproterenol is rapidly inactivated by the GI tract and metabolized by the liver after oral administration. Sublingual administration is not reliably absorbed and effects may take up to 30 minutes to be seen. Intravenous administration results in immediate effects, but only persists for a few minutes after discontinuation. It is unknown if isoproterenol is distributed into milk. The phar-macologic actions of isoproterenol are ended primarily through tis-sue uptake. Isoproterenol is metabolized in the liver and other tis-sues by catechol-O-methyltransferase (COMT) to a weakly active metabolite. Contraindications/Precautions/Warnings Isoproterenol is contraindicated in patients that have tachycar-dias or A V block caused by cardiac glycoside intoxication. It is also contraindicated in ventricular arrhythmias that do not require in-creased inotropic activity. Use isoproterenol with caution in patients with coronary insuf-ﬁciency, hyperthyroidism, renal disease, hypertension or diabetes. Isoproterenol is not a substitute for adequate ﬂuid replacement in shock. Adverse Effects Isoproterenol can cause tachycardia, anxiety, tremors, excitability, headache, weakness, and vomiting. Because of isoproterenol's short duration of action, adverse effects are usually transient and do not require cessation of therapy, but may require lowering the dose or infusion rate. Isoproterenol is considered more arrhythmogenic than either dopamine or dobutamine, so it is rarely used in the treatment of heart failure. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and fe-line pregnancy (Papich 1989), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should be used cau-tiously as a last resort when the beneﬁt of therapy clearly outweighs the risks. ) No speciﬁc lactation safety information was found, however, as isoproterenol is rapidly deactivated in the gut, it is unlikely to pose much risk to nursing offspring. Overdosage/Acute Toxicity In addition to the signs listed in the Adverse Effects section, high doses may cause an initial hypertension, followed by hypotension as well as tachycardias and other arrhythmias. Besides halting or reducing the drug, treatment is considered to be supportive. Should tachycardias persist, a beta-blocker could be considered for treat-ment (if patient does not have a bronchospastic disease).	pppbs.pdf
500 ISOSORBIDE Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving isoproterenol and may be of signiﬁcance in veterinary patients: T ! ANESTHETICS, GENERAL : An increased risk of arrhythmias develop-ing can occur if isoproterenol is administered to patients who have received cyclopropane or a halogenated hydrocarbon an-esthetic agent. Propranolol may be administered should these occur. T ! BETA-BLOCKERS : May antagonize isoproterenol's cardiac, bron-chodilating, and vasodilating effects by blocking the beta effects of isoproterenol. Beta-blockers may be administered to treat the tachycardia associated with isoproterenol use, but use with cau-tion in patient's with bronchospastic disease. T ! DIGOXIN : An increased risk of arrhythmias may occur if isoprot-erenol is used concurrently with digitalis glycosides. T ! OXYTOCIC AGENTS : Hypertension may result if isoproterenol is used with oxytocic agents. T ! SYMPATHOMIMETIC AGENTS, OTHER : Isoproterenol should not be administered with other sympathomimetic agents (e. g., phenyl-propanolamine ) as increased toxicity may result. T ! THEOPHYLLINE : Isoproterenol may increase the risk for theophyl-line toxicity. Doses Note : Because of the cardiostimulatory properties of isoproterenol, its parenteral use in human medicine for the treatment of bron-chospasm has been largely supplanted by other more beta 2 speciﬁc drugs (e. g., terbutaline) and administration methods (nebuliza-tion). Use with care. T ! DOGS: For sinoatrial arrest, sinus bradycardia, complete A V block: a) 0. 4 mg in 250 m L D 5W drip slowly to effect; or Isuprel® Glossets 5-10 mg sublingually or rectally q 4-6h (Tilley and Miller 1986) b) 0. 04-0. 08 micrograms/kg/min IV infusion; or 0. 1-0. 2 mg IM, SC q4h; or 0. 4 mg in 250 m L D 5W IV slowly (Morgan 1988) For bronchodilatation: a) 0. 1-0. 2 mg q6h IM or SC (Papich 1986) T ! CATS: For sinoatrial arrest, sinus bradycardia, complete A V block: a) 0. 4 mg in 250 m L D 5W drip slowly to effect (Tilley and Mill-er 1986) For feline asthma: a) 0. 2 mg in 100 m L of D 5W and give IV to effect three times daily; or 0. 004-0. 006 mg IM q30 minutes as needed (Mor-gan 1988) T ! HORSES: (Note : ARCI UCGFS Class 2 Drug) For short-term bronchodilatation: a) Dilute 0. 2 mg in 50 m L of saline and administer 0. 4 micro-grams/kg as an IV infusion, monitor heart rate continuously and discontinue when heart rate doubles. Effects may only last for an hour. (Derksen 1987) Monitoring T ! Cardiac rate/rhythm T ! Respiratory rate/auscultation during anaphylaxis T ! Urine ﬂow if possible T ! Blood pressure, and blood gases if indicated and possible Client Information T ! Isoproterenol for injection should be used only by trained person-nel in a setting where adequate monitoring can be performed. Chemistry/Synonyms Isoproterenol HCl is a synthetic beta-adrenergic agent that occurs as a white to practically white, crystalline powder that is freely sol-uble in water and sparingly soluble in alcohol. The p H of the com-mercially available injection is 3. 5-4. 5. Isoproterenol HCl may also be known as: isoprenaline hydro-chloride, isopropylarterenol hydrochloride, isopropylnoradrenaline hydrochloride, Imuprel®, Isolin®, Isuprel®, Lenoprel®, Norisodrine Aerotrol ®, Proterenal, Saventrine®, and Vapo-iso®. Storage/Stability/Compatibility Store isoproterenol preparations in tight, light-resistant contain-ers. It is stable indeﬁnitely at room temperature. Isoproterenol salts will darken with time upon exposure to air, light, or heat. Sulﬁtes or sulfur dioxide may be added to preparations as an antioxidant. Solutions may become pink or brownish-pink if exposed to air, al-kalies, or metals. Do not use solutions that are discolored or contain a precipitate. If isoproterenol is mixed with other drugs or ﬂuids that result in a solution with a p H greater than 6, it is recommended that it be used immediately. Isoproterenol for injection is reported to be physically compat-ible with all commonly used IV solutions (except 5% sodium bi-carbonate), and the following drugs: calcium chloride/gluceptate, cephalothin sodium, cimetidine HCl, dobutamine HCl, heparin so-dium, magnesium sulfate, multivitamin infusion, netilmicin sulfate, oxytetracycline HCl, potassium chloride, succinylcholine chloride, tetracycline HCl, verapamil HCl, and vitamin B complex with C. It is reported to be physically incompatible when mixed with: aminophylline or sodium bicarbonate. Compatibility is dependent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Isoproterenol HCl for Injection: 1:5000 solution (0. 2 mg/m L) in 1 m L & 5 m L amps; 5 m L & 10 m L vials; Isuprel® (Sanoﬁ Winthrop); generic; (Rx) Isoproterenol HCl for Injection: 1:50,000 (0. 02 mg/m L) in 10 m L with needle; Isuprel® (Sanoﬁ Winthrop); (Rx) ISOSORBIDE DINITRATE ISOSORBIDE MONONITRATE (eye-soe-sor-bide) Isordil®, Ismo®, Imdur® V ASODILATOR Prescriber Highlights TT Limited clinical experience; but may have some utility in small animal medicine for adjunctive treatment of heart failure	pppbs.pdf