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rats. While no teratogenic effects have been detected with ramipril in studies performed in mice, rats, rabbits, and cynomolgus mon-keys, fetal risk is increased in humans. If used in humans during the 2nd and 3rd trimesters increased rates o f fetal death, neonatal hypotension, skull hypoplasia, anuria, renal failure, oligohydramnios leading to fetal limb contractures, craniofacial deformation, and hypoplastic lung development were noted. In humans, ramipril has a “black box” warning regarding its use in pregnancy that states “When used in pregnancy during the second and third trimesters, angiotensin-converting enzyme (ACE) inhibitors can cause injury and even death to the developing fe-tus. When pregnancy is detected, ramipril should be discontinued as soon as possible. ” For humans, the FDA categorizes ramipril as category D for use during the 2nd and 3rd trimesters of 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) and as category C for use during the ﬁrst trimester of 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 whether ramipril (or ramiprilat) enters milk. Both the vet erinary label (UK) and human label recommended not using the drug during nursing. Overdosage/Acute Toxicity In dogs, ramipril appears quite safe; dosages as high as 1 gram/kg induced only mild GI distress. Lethal doses in rats and mice were noted at 10-11 g/kg. No information was located on overdoses in cats. In overdose situations, the primary concern is hypotension; supportive treatment with volume expansion with normal saline is recommended to correct blood pressure. Because of the drug's long duration of action, prolonged monitoring and treatment may be required. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ramipril and may be of signiﬁcance in veterinary patients: T ! ASPIRIN : Aspirin may potentially negate the decrease in systemic vascular resistance induced by ACE inhibitors. However, in one study in dogs using low-dose aspirin, hemodynamic effects of enalaprilat (active metabolite of enalapril, a related drug) were not affected. T ! ANTIDIABETIC AGENTS (insulin, oral agents ): Possible increased risk for hypoglycemia; enhanced monitoring recommended T ! DIURETICS (e. g., furosemide, hydrochlorothiazide ): Potential for in-creased hypotensive effects T ! DIURETICS, POTASSIUM SPARING (e. g., spironolactone, triamterene ): Increased hyperkalemic effects, enhanced monitoring of serum potassium T ! NSAIDS : Potential for increased risk of renal dysfunction or hy-perkalemia T ! POTASSIUM SUPPLEMENTS : Increased risk for hyperkalemia Laboratory Considerations T ! ACE inhibitors may cause a reversible decrease in localization and excretion of iodohippurate sodium I123/I134, or Technetium Tc99 pententate renal imaging in the affected kidney in patients with renal artery stenosis, which could lead to confusion in test inter-pretation Doses DOGS: a) For treatment of heart failure: Initially, 0. 125 mg/kg PO once daily; d epending on the severity of pulmonary congestion, dose may be increased to 0. 25 mg/kg PO once daily (Label information; Vasotop®—Intervet UK) CATS: a) For treatment of arterial hypertension: 0. 125 mg/kg PO once daily (Graff and Herve 2003) Monitoring T ! Clinical signs of CHF T ! Serum electrolytes, creatinine, BUN, urine protein T ! CBC with differential, periodic T ! Blood pressure (if treating hypertension or clinical signs associ-ated with hypotension arise) Client Information T ! For this drug to be maximally effective it must be given once daily at about the same time each day T ! Do not abruptly stop or reduce therapy without veterinarian's approval T ! Contact veterinarian if vomiting or diarrhea persist, are severe, or if animal's condition deteriorates Chemistry/Synonyms Ramipril occurs as a white to almost white, crystalline powder that is sparingly soluble in water and freely soluble in methyl alcohol. Ramipril may also be known as Hoe-498, ramiprilis, or ramipril-ium. There are many international trade names, including: Altace®, Car dase®, Delix®, Ramase®, Triatec®, and Tritace®. Storage/Stability Capsules should be stored at room temperature (15-30°C) pro-tected from light in tight containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None in the USA; in the UK and in other European countries: Ramipril Tablets: 0. 625 mg, 1. 25 mg, 2. 5 mg, & 5 mg; Vasotop® (In-tervet); (Rx). Approved for use in dogs. HUMAN-LABELED PRODUCTS: Ramipril Capsules: 1. 25 mg, 2. 5 mg, 5 mg, & 10 mg; Altace® (Mon-arch); (Rx) RANITIDINE HCL (rah-nit-a-deen) Zantac® H2 RECEPTOR ANTAGONIST; PROKINETIC Prescriber Highlights TT H2 receptor antagonist similar to cimetidine, but fewer drug interactions; used to reduce acid output in stomach; also has prokinetic activity TT Contraindications: Hypersensitivity. Caution: Geriatric pa-tients, hepatic or renal insufﬁciency TT Adverse Effects: Rare. IV boluses may cause vomiting. Potentially: Mental confusion, agranulocytosis, & tran-sient cardiac arrhythmias (too rapid IV injection). Pain at the injection site after IM administration.	pppbs.pdf
Uses/Indications In veterinary medicine, ranitidine has been used for the treatment and/or prophylaxis of gastric, abomasal, and duodenal ulcers, uremic gastritis, stress-related or drug-induced erosive gastritis, esophagitis, duodenal gastric reﬂux and esophageal reﬂux. It has also been employed to treat hypersecretory conditions associated with gastrinomas and systemic mastocytosis. Because of its effects on gastric motility, ranitidine may be useful in increasing gastric emptying, particularly when delayed gastric emptying is associated with gastric ulcer disease. Ranitidine may also be useful to stimulate colonic activity in cats via its prokinetic effects. Pharmacology/Actions At the H 2 receptors of the parietal cells, ranitidine competitively in-hibits histamine, thereby reducing gastric acid output both during basal c onditions and when stimulated by food, amino acids, penta-gastrin, histamine, or insulin. Ranitidine is between 3-13 times mor e potent (on a molar basis) as cimetidine. While ranitidine may cause gastric emptying times to be de-layed, it more likely will stimulate GI motility by inhibiting ace-tylcholinesterase (thereby increasing acetylcholine at muscarinic re ceptors). Lower esophageal sphincter pressures may be increased by ranitidine. By decreasing the amount of gastric juice produced, ranitidine decreases the amount of pepsin secreted. Ranitidine, unlike cimetidine, does not appear to have any ap-preciable effect on serum prolactin levels, although it may inhibit the re lease of vasopressin. Pharmacokinetics In dogs, the oral bioavailability is approximately 81%, serum half-life is 2. 2 hours and volume of distribution 2. 6 L/kg. In horses, oral ranitidine has a bioavailability of about 27% in ad ults and 38% in foals. Peak levels after oral dosing occur in about 100 minutes in adults and 60 minutes in foals. Apparent volume of distribution is approximately 1. 1 L/kg and 1. 5 L/kg in adults and foals, respectively. Clearance in adults is approximately 10 m L/min/ kg and 13. 3 m L/min/kg in foals. In humans, ranitidine is absorbed rapidly after oral adminis-tration, but undergoes extensive ﬁrst-pass metabolism with a net syst emic bioavailability of approximately 50%. Peak levels occur at about 2-3 hours after oral dosing. Food does not appreciably alter the extent of absorption or the peak serum levels attained. Ranitidine is distributed widely throughout the body and is only 10- 19% bound to plasma proteins. Ranitidine is distributed into human milk at levels 25-100% of those found in plasma. Ranitidine is both excreted in the urine by the kidneys (via glo merular ﬁltration and tubular secretion) and metabolized in the liver to inactive metabolites; accumulation of the drug can occur in patients with renal insufﬁciency. The serum half-life of ranitidine in humans averages 2-3 hours. The duration of action at usual doses is from 8-12 hours. Contraindications/Precautions/Warnings Ranitidine is contraindicated in patients who are hypersensitive to it. It should be used cautiously and possibly at reduced dosage in patients with diminished renal function. Ranitidine has caused increased serum ALT levels in humans receiving high, IV doses for longer than 5 days. The manufacturer recommends that with high dose, chronic therapy, serum ALT values be considered for monitoring. Adverse Effects Adverse effects appear to be very rare in animals at the dosages generally used. Potential adverse effects (documented in humans) that might be seen include mental confusion and headache. Rarely, agranulocytosis may develop and, if given rapidly IV, transient car-diac arrhythmias may be seen. Pain at the injection site may be not-ed after IM administration. IV boluses have been associated with vo miting in small animals. 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 fe tus, 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 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 thes e drugs are safe if they are not administered when the animal is near term. ) Ranitidine is excreted in human breast milk with milk:plasma rat ios of approximately 5:1 to 12:1. The drug is not recommended to be used in nursing humans; use with caution in nursing veteri-nary patients. Overdosage/Acute Toxicity Clinical experience with ranitidine overdosage is limited. In labo-ratory animals, very high dosages (225 mg/kg/day) have been as-sociated with muscular tremors, vomiting and rapid respirations. Sing le doses of 1 gram/kg in rodents did not cause death. Treatment of overdoses in animals should be handled us-ing standard protocols for oral ingestions of drugs; clinical signs may be treated symptomatically and supportively if necessary. Hemodialysis and peritoneal dialysis have been noted to remove ranitidine from the body. Drug Interactions Unlike cimetidine, ranitidine appears to have much less effect on the hepatic metabolism of drugs and is unlikely to cause clinically relevant drug interactions via this mechanism. The following drug interactions have either been reported or are theoretical in humans or animals receiving ranitidine and may be of signiﬁcance in vet-erinary patients: !TACETAMINOPHEN : Ranitidine (dose-dependent) may inhibit acet-aminophen metabolism !TANTACIDS (high doses): May decrease the absorption of ranitidine; give at separate times (2 hours apart) if used concurrently !TKETOCONAZOLE, ITRACONAZOLE : Absorption may be reduced sec-ondary to increased gastric p H !TMETOPROLOL : Ranitidine may increase metoprolol half-life, and peak levels !TNIFEDIPINE : Ranitidine may increase nifedipine AUC by 30% !TPROPANTHELINE : Delays the absorption but increases the peak se-rum level of ranitidine; relative bioavailability of ranitidine may be increased by 23% when propantheline is administered con-comitantly with ranitidine !TVITAMIN B-12 : Long-term ranitidine use may reduce oral absorp-tion of B-12 Laboratory Considerations !TRanitidine may cause a false-positive urine protein reading when using Multistix®. The sulfosalicylic acid reagent is recommended for determining urine protein when the patient is concomitantly receiving ranitidine.	pppbs.pdf
TDoses T ! DOGS: For esophagitis: a) 1-2 mg/kg PO twice daily (Watrous 1988) For chr onic gastritis: a) 0. 5 mg/kg PO twice daily (Hall and Twedt 1988) For ulce r disease: a) 0. 5-2 mg/kg PO, IV or IM q8-12h (Haskins 2000) b) 2 mg/kg PO, IV q8h (Matz 1995) c) 1-2 mg/kg PO, IV, SC q12h (also used for esophagitis) (Sell-on 2007b) d) 2 mg/kg PO, IV q12h (Waddell 2007a) For gast rinoma: a) 1-2 mg/kg PO, SC, IV q8-12h (Zerbe and Washabau 2000) b) 0. 5 mg/kg PO, IV or SC twice daily (Kay, Kruth, and Twedt 1988) T o treat h ypergastrinemia secondary to chronic renal failure: a) 1-2 mg/kg PO twice daily (Morgan 1988) T o treat hyperhistaminemia secondary to mast cell tumors: a) 2 mg/kg q12h (Fox 1995) A s a prokinetic agent to stimulate gastric contractions: a) 1-2 mg/kg PO q12h (Hall and Washabau 2000) T ! CATS: For ulcer disease/esophagitis:: a) 2. 5 mg/kg IV q12h or 3. 5 mg/kg PO q12h (Matz 1995), (Johnson 1996) b) 1 -2 mg/kg PO, IV, SC q12h (Sellon 2007b) c) 2 mg/kg PO, IV q12h (Waddell 2007a) As a prokine tic agent to stimulate colonic motility: a) 1-2 mg/kg PO q8-12h (Washabau and Holt 2000) b) 1-2 mg/kg PO q12h (Scherk 2003b) T ! HORSES: (Note : ARCI UCGFS Class 5 Drug) a) 6. 6 mg/kg PO q8h (Andrews and Nadeau 1999) b) Foals: 6. 6 mg/kg IV q4h or 0. 8-2. 2 mg/kg IV four times a day; 5-10 mg/kg PO two to four times a day. (Wilkins 2004b) c) 1. 5-2 mg/kg IV or IM q6-8h; 6. 6 mg/kg PO q8h (Sanchez 2004a) Monitoring T ! Clinical efﬁcacy (dependent on reason for use); monitored by de-crease in clinical signs, endoscopic examination, blood in feces, etc. Client Information T ! o maximize the beneﬁt of this medication, it must be adminis-tered as prescribed by the veterinarian; symptoms may reoccur if dosages ar e misse d. Chemistry/Synonyms An H 2 receptor antagonist, ranitidine HCl occurs as a white to pale-yellow granular substance with a bitter taste and a sulfur-like odor. The drug has p K as of 8. 2 and 2. 7. One gram is approximately soluble in 1. 5 m L of water or 6 m L of alcohol. The commercially available injection has a p H of 6. 7-7. 3. Ranitidine HCl may also be known as: AH-19065, ranitidini hy-drochloridum; many trade names are available. Storage/Stability Ranitidine tablets should be stored in tight, light-resistant contain-ers at room temperature. The injectable product should be stored prote cted from light and at a temperature less than 30°C. A slight darkening of the injectable solution does not affect the potency of the drug. Ranitidine injection is reportedly stable up to 48 hours when mixed w ith the commonly used IV solutions (including 5% sodium bicarbonate). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 5 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Ranitidine HCl Tablets: 75 mg, 150 mg & 300 mg (as base); Zan-tac® (Glaxo Smith Kline); (Rx); Zantac® 75 &-150 (Pﬁzer Consumer Healthcare); generic; (Rx or OTC) Ranitidine HCl Effervescent Tablets: 25 mg & 150 mg (as base); Zan-tac® EFFERdose (Glaxo Smith Kline); (Rx) Ranitidine HCl Syrup: 15 mg/m L (as base) in 480 m L; Zantac® (Glaxo S mith Kline); (Rx) Ranitidine HCl Injection: 1 mg/m L (premixed) & 25 mg/m L in 50 m L (prese rvative free) plastic containers, 2 m L single-dose and 6 m L multi-dose vials; Zantac® (Glaxo Smith Kline); generic (Bedford); (Rx) RIFAMPIN (rif-am-pin) Rifadin®, Rimactane® ANTIMICROBIAL Prescriber Highlights TT Antimicrobial with activity against a variety of microbes (Rhodococcus, mycobacteria, staphylococci); has some antifungal & antiviral activity as well. TT Contraindications: Hypersensitivity to it or other rifamycins TT Caution: Preexisting hepatic dysfunction (may need to reduce dosage) TT Adverse Effects: Uncommon; potentially rashes, GI dis-tress, & increases in liver enzymes. TT Should not be used alone as resistance develops rapidly TT Preferably, give on an empty stomach TT May cause red/orange urine, tears, & sweat (harmless) TT Drug Interactions, lab interactions Uses/Indications The principle use of rifampin in veterinary medicine is in the treat-ment of Rhodococcus equi (Cor ynebacterium equi) infections (usu-ally with erythromycin estolate) in young horses. It may also be useful to treat proliferative enteropathy caused by Lawsonia intra-cellularis in foals. In small animals, the drug is sometimes used in combination with othe r antifungal agents (amphotericin B and 5-FC) in the treatment of histoplasmosis or aspergillosis with CNS involvement.	pppbs.pdf
Pharmacology/Actions Rifampin may act as either a bactericidal or bacteriostatic anti-microbial dependent upon the susceptibility of the organism and the c oncentration of the drug. Rifampin acts by inhibiting DNA-dependent RNA polymerase in susceptible organisms, thereby sup-pressing the initiation of chain formation for RNA synthesis. It does not inhibit the mammalian e nzyme. Rifampin is active against a variety of mycobacterium species and Staph ylococcus aureus, Neisseria, Haemophilus, and Rhodococcus equi (C. equi). At very high levels, rifampin has activity against pox-viruses, adenoviruses, and Chlamydia trachomatis. Rifampin has antifungal activity when combined with other antifungal agents. Pharmacokinetics After oral administration, rifampin is relatively well absorbed from the GI tract. Oral bioavailability is reportedly about 40-70% in horses and 37% in adult sheep. If food is given concurrently, peak plasma levels may be delayed and slightly reduced. Rifampin is very lipophilic and readily penetrates most body tiss ues (including bone and prostate), cells and ﬂuids (including CSF). It also penetrates abscesses and caseous material. Rifampin is 70-90% bound to serum proteins, is distributed into milk and crosses the placenta. Mean volume of distribution is approximately 0. 9 L/kg in horses, and 1. 3 L/kg in sheep. Rifampin is metabolized in the liver to a deacetylated form that also has antibacterial activity. Both this metabolite and unchanged drug are excreted primarily in the bile, but up to 30% may be ex-creted in the urine. The parent drug is substantially reabsorbed in the gu t, but the metabolite is not. Reported elimination half-lives for various species are: 6-8 hours (horses), 8 hours (dogs), 3-5 hour's (sheep). Because rifampin can induce hepatic microsomal enzymes, elimination rates may increase with time. Contraindications/Precautions/Warnings Rifampin is contraindicated in patients hypersensitive to it or to other rifamycins. It should be used with caution in patients with preexisting hepatic dysfunction. Adverse Effects Rifampin can cause red-orange colored urine, tears, sweat, and sa-liva. There are no harmful consequences from this effect. In some spe cies (e. g., humans) rashes, GI distress, and increases in liver en-zymes may occur, particularly with long-term use. Because resistance develops rapidly when rifampin is used alone, it should be use d in combination with other effective antibiotics. Adverse effects in horses are apparently rare, but when com-bined with erythromycin, mild diarrhea (self-limiting) to severe ent erocolitis in foals and mares, hyperthermia, and acute respira-tory distress can occur. Although not commercially available, intra-venous rifampin has caused CNS depression, sweating, hemolysis, and anor exia in horses. Reproductive/Nursing Safety Rodents given high doses of rifampin 150-250 mg/kg/day resulted in some congenital malformations in offspring, but the drug has been used in pregnant women with no reported increases in terato-genicity. In humans, the FDA categorizes this drug as category C fo r 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. ) Rifampin is excreted in maternal milk; use with caution in nurs-ing veterinary patients. Overdosage/Acute Toxicity Clinical signs associated with overdosage of oral rifampin generally are extensions of the adverse effects outlined above (GI, orange-red coloring of ﬂuids, and skin), but massive overdoses may cause hepatotoxicity. There were 16 exposures to rifampin reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 6 were dogs with 1 showing clinical signs and 8 were cats with 1 showing clinical signs. The remaining 2 reported cases were both equine showing no clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included ataxia, and central nervous system depression. Common ﬁndings in cats recorded in decreasing frequency included edema of the face, ery-thema, injected mucous membranes, mydriasis and tachypnea. Should a massive oral overdosage occur, the gut should be emp-tied following standard protocols. Liver enzymes should be moni-tored and supportive treatment initiated if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving rifampin and may be of signiﬁcance in veterinary patients: !TFLUOROQUINOLONES : In vitro antagonism has been reported when rifampin is used concurrently with ﬂuoroquinolone antibiotics and concurrent use should be avoided Because rifampin has been documented to induce hepatic mi-crosomal enzymes, drugs that are metabolized by these enzymes may have their elimination half-lives shortened and serum levels de-creased; drugs/classes that may be affected by this process include: !!BARBITURATES !!BENZODIAZEPINES (e. g., diazepam ) !!CHLORAMPHENICOL !!CORTICOSTEROIDS ! !DAPSONE !!KETOCONAZOLE !!PROPRANOLOL !TQUINIDINE !!WARFARIN Laboratory Considerations !TMicrobiologic methods of assaying serum folate and vitamin B 12 are interfered with by rifampin. !TRifampin can cause false-positive BSP (bromosulfophthalein, sulfobromophthalein) test results by inhibiting the hepatic up-take of the drug Doses Note : Because resistance develops rapidly when rifampin is used alone, it should be used in combination with other effective antibiotics. !TDOGS: a) For combination therapy of atypical Mycobacteria infec-tions; treatment of resistant Staph endocarditis (in combi-nation with amoxicillin/clavulanate or trimethoprim/sulfa): 10- 20 mg/kg PO q8-12h (Trepanier 1999) b) For CNS fungal infections (aspergillosis/histoplasmosis): Ri-fampin 10-20 mg/kg PO three times daily with amphoteri-cin B and ﬂucytosine (Schunk 1988) c) For actinomycosis: 10-20 mg/kg PO q12h PO (Hardie 1984)	pppbs.pdf
T ! CATS: a) For CNS fungal infections (aspergillosis/histoplasmosis): Ri-fampin 10-20 mg/kg PO three times daily with amphoteri-cin B and ﬂucytosine (Schunk 1988) T ! HORSES: For treatment of Rhodococcus equi (C. equi) infections in foals: a) Rifampin 5 mg/kg PO two times daily with erythromycin 15-25 mg/kg, PO q12-24h. Conventional treatment, but erythromycin has numerous side effects including entero-colitis in foals and mares, hyperthermia, and acute respi-ratory distress. Clarithromycin may be superior. (Chafﬁn 2006b) b) Rifampin 5 mg/kg PO two times daily or 10 mg/kg PO once daily with erythromycin 25 mg/kg, PO q6-8h. Duration of therapy usually takes 4-9 weeks. (Giguere 2003b) For susceptible infections in foals: a) For treatment of proliferative enteropathy caused by Lawso-nia intracellularis in foals: Erythromycin estolate (25 mg/kg PO q6-8h) alone or in combination with rifampin: 10 mg/ kg PO once daily for a minimum of 21 days (Lavoie and Dro-let 2003) T ! BIRDS: For treatment of mycobacteriosis: a) Rifampin (45 mg/kg PO once daily) in combination with ethambut ol (30 mg/kg PO once daily) and one of the fol-lowing: clofazimine (6 mg/kg PO once daily) or isoniazid (30 mg/kg PO once daily). (Pollock 2007a) Monitoring T ! Clinical efﬁcacy T ! For monitoring C. equi infections in foals and response to ri-fampin/erythromycin: Chest radiographs and plasma ﬁbrinogen levels have been suggested as prognostic indicators when done after 1 week of therapy. (Hillidge and Zertuche 1987) T ! Adverse effects: may consider liver function monitoring with long-term therapy. Client Information T ! Rifampin may cause urine and other secretions (tears, saliva, etc. ) to turn red-orange in color; this is not abnormal T ! Preferably give on an empty stomach T ! May cause softening of stools in horses/foals Chemistry/Synonyms A semi-synthetic zwitterion derivative of rifamycin B, rifampin oc-curs as a red-brown, crystalline powder with a p K a of 7. 9. I t is very slightly soluble in water and slightly soluble in alcohol. Rifampin may also be known as: Ba-41166/E, L-5103, NSC-113926, rifaldazine, rifampicinum, rifamycin AMP; many trade names are availab le. Storage/Stability Rifampin capsules should be stored in tight, light-resistant contain-ers, preferably at room temperature (15-30°C). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Rifampin Capsules: 150 mg & 300 mg; Rifadin® (Aventis); Rimac-tane® (Novartis); generic; (Rx) Rifampin Powder for Injection: 600 mg; Rifadin® (Av entis); (Rx) ROMIFIDINE HCL (roe-mif-ih-deen) Sedivet® ALPHA-2 AGONIST SEDATIVE ANALGESIC Prescriber Highlights TT Alpha-2 agonist with sedative, muscle relaxant & analge-sic effects TT Indicated in USA for adult horses as a sedative & anal-gesic to facilitate handling, clinical examinations & pro-cedures, minor surgical procedures, & as preanesthetic prior to the induction of general anesthesia TT Labeled in some European countries for use in dogs & cats; has been used extra-label in foals & cattle TT Adverse effects in HORSES include bradycardia (pos-sibly profound), ﬁrst-& second-degree atrioventricular heart block, sinus ar rh ythmias (dose dependent), initial hypertension followed by hypotension, ataxia, sweating, piloerection, salivation, muscle tremors, penile-relaxation, urination, swelling of face, lips & upper airways, stridor, decreased GI motility, ﬂatulence & mild colic; anaphylaxis possible TT In DOGS & CATS, romiﬁdine may cause bradycardia, car-diac arrhythmias, hypotension, transient hyperglycemia, & alterations in thermoregulation. Dogs may pant, sali -vate, vomit (less likely than in cats), & develop muscle twitching. Vomiting in cats may be a problem TT Adjust dosage if used with other CNS depressant drugs Uses/Indications Romiﬁdine is an alpha-2 agonist with sedative, muscle relaxant and analgesic effects. It is indicated (in the USA) for use in adult horses as a sedative and analgesic to facilitate handling, clinical examina-tions and procedures, minor surgical procedures, and as a preanes-thetic prior to the induction of general anesthesia. In certain European countries, it is approved for use in dogs and cats as a sedativ e/preanesthetic. Although not approved, romiﬁdine has been used in cattle and foals. Pharmacology/Actions A potent alpha 2-adrenergic agonist, romiﬁdine is classiﬁed as a sed-ative/analgesic with muscle relaxant properties. Alpha-2 receptors are found in the CNS and several tissues peripherally; both presyn-aptically and postsynaptically. In the CNS, the primary action is a feedba ck inhibition of norepinephrine release. Opioids and alpha-2 agonists may have synergistic analgesic effects. Pharmacologic effects of romiﬁdine include sedation, an-algesia, and reduced catecholamine release from the CNS. Ther moregulatory mechanisms may be altered. Peripherally, an initial vasoconstrictive response occurs with increases in blood pressure. Within minutes a hypotensive phase occurs. Heart rate can signiﬁcantly decrease secondary to a vagal response to hyper-tension. A second-degree atrioventricular block may also occur. Anti muscarinic agents can prevent bradycardia, but their use is controversial as they can potentially cause hypertension, increased myocardial oxygen demand, and reduced GI motility. Alpha-2 ago-nists can transiently slow duodenal motility and increase mictura-tion in horses and can inhibit insulin release from pancreatic islet cells resulting in hyperglycemia. Other effects seen in horses in-	pppbs.pdf
clude sweating, mydriasis, decreases in hematocrit, and increased uterine pressure in non-pregnant mares. In horses, when compared with other alpha-2 agonists (xylazine, de tomidine, medetomidine), romiﬁdine does not appear to cause as much ataxia at sedative dosages and has the longest duration of sedation. Duration of analgesia is shorter than the duration of sedation. Pharmacokinetics Pharmacokinetic studies for romiﬁdine in horses were not located. In dogs and cats, bioavailability after IM administration is 86% and 95%, respectively. Bioavailability after subcutaneous injection in dogs is 92%. Peak levels after IM injection occur in approximate-ly 50 minutes in dogs and 25 minutes in cats. After IV injection, vol umes of distribution are about 3 L/kg in dogs, and 6 L/kg in cats. Romiﬁdine is biotransformed in the liver. In dogs, about 80% of an administered dose is eliminated in the urine; 20% in the feces. Elimination half-lives are approximately 2 hours for dogs, 6 hours for cats. Contraindications/Precautions/Warnings Romiﬁdine should not be used in animals hypersensitive to it or in combination with intravenous potentiated sulfonamides. The label states that this medication should not be used in horses with respiratory disease, hepatic or renal disease, or other systemic con-ditions of compromised health. It also states that the effects of this medicat ion have not been evaluated in horses with colic, or in foals. Because of its effects on heart rhythm and blood pressure, use very cautiously in horses with preexisting cardiac conditions. The manufacturer cautions that using with other sedatives, tran-quilizers, or opioids may potentiate the adverse effects of romiﬁ-dine and to avoid using epinephrine as it may potentiate the effects of alpha-2 agonists. Although animals may appear to be deeply sedated, some may resp ond (kick, etc. ) to external stimuli; use appropriate caution. When used in dogs and cats, the label for Rom ydis® (Virbac— Ireland) states: “Animals should be restrained to prevent injury, ensure that animals have sufﬁcient ﬂuid intake, and if undergoing prolonged sedation, animals should be prevented from becoming hypothermic. Additionally, care should be taken when used in ani-mals in poor health, suffering from respiratory distress, or in cases of cardiovascular, renal, hepatic or pancreatic disease. ” Cats with pancreatitis should be closely monitored. Because dogs and, partic-ularly, cats may vomit after receiving romiﬁdine, the manufacturer re commends not feeding for at least 12 hours prior to use. This medication can be absorbed through the skin and via oral rou tes. Persons administering the medication should handle it care-fully and avoid self-exposure. Adverse Effects In horses, romiﬁdine may cause bradycardia (possibly profound), ﬁrst-and second-degree atrioventricular heart block, and sinus arrhythmias (dose dependent). Initially, hypertension may occur followed by hypotension. Other adverse effects can include: ataxia, sweating,piloerection,salivation,muscle tremors,penile-relaxation, urination (occurs about one hour after dose), swelling of face, lips and upper airways, stridor, decreased GI motility, ﬂatulence and mild colic. There is a possibility that horses may react paradoxically (excitation) to romiﬁdine. Rarely, anaphylactic reactions to alpha-2 agonists have been reported in horses. In dogs and cats romiﬁdine may cause bradycardia, cardiac ar-rhythmias, hypotension, transient hyperglycemia, and alterations in ther moregulation (body temperature may increase or decrease de-pending on ambient temperature). Dogs may pant, salivate, vomit (less like ly than in cats), and develop muscle twitching. In cats, vomiting associated with romiﬁdine use can be seen and p ersist up to 24 hours after dosing. Pancreatitis has been noted in some cats receiving the drug repeatedly every 2 days for 6 days; dose related increases in BUN have been observed. Localized injec-tion site reactions have occurred in cats receiving the medication intr amuscularly. Reproductive/Nursing Safety The label for the US product states that the effects of this medica-tion have not been evaluated in pregnant mares, horses intended fo r breeding, or foals. The labeling for the equine and small animal products approved in E urope states that the drug is contraindicated in pregnant horses during the last month of pregnancy and during pregnancy in dogs and cats. Overdosage/Acute Toxicity Horses have received up to 600 mcg/kg (5X) in experimental stud-ies. Signs exhibited included sinus bradycardia, 2nd degree heart blo ck, occasional apnea and mild respiratory stridor, deep sedation, frequent urination, and sweating. No clinically signiﬁcant altera-tions in blood gases, acid-base, hematological or chemical param-eters were noted. If necessary, a reversal agent such as atipamezole (at a dose of 30-80 mcg/kg) or yohimbine may be used to reduce the duration and extent of adverse effects associated with acute toxicity. Dogs have been administered doses of up to 1 mg/kg (approx 8- 10X) IV daily for up to 4 weeks with no serious adverse effects reported. Drug Interactions !TINTRAVENOUS POTENTIATED SULFONAMIDES (e. g., trimethoprim/sulfa ): The manufacturer warns against using this agent with intrave-nous potentiated sulfonamides as fatal dysrhythmias may occur !TOTHER A LPHA-2 AGONISTS (e. g., xylazine, medetomidine, detomidine, clonidine and including epinephrine ): Not recommended to be used together with romiﬁdine as effects may be additive !TPHENOTHIAZINES (e. g., acepromazine ): Severe hypotension can result The following drug interactions have either been reported or are theoretical in humans receiving a similar alpha-2 agonist, dexmeto-midine and may be of signiﬁcance in veterinary patients: !TANESTHETICS, OPIATES, SEDATIVE/HYPNOTICS : Effects may be addi-tive; dosage reduction of one or both agents may be required; pot ential for increased risk for arrhythmias when used in combi-nation with thiopental, ketamine or halothane Laboratory Considerations !TADP-induced platelet aggregation : Can be inhibited in cats by me-detomidine (a related alpha-2 agonist); not known if romiﬁdine can hav e this effect Doses !THORSES (adults): a) For sedation and analgesia : 40-120 mcg/kg IV slowly one time. This dose is equivalent to 0. 4-1. 2 m L per 100 kg (220 lb) body weight using the 1% (10 mg/m L) injection. Degree of sedation and analgesia is dose and time dependent. Onset of action occurs between 30 seconds to 5 minutes and gradu-ally subsides during the next 2-4 hours. Duration of analge-sia is shorter than the duration of sedation. See the package inser t for expected onset and duration times for sedation and analgesia based upon dose.	pppbs.pdf
TAs a preanesthetic : 100 mcg/kg as slow, single IV injection. In-duce anesthesia after maximal sedation is achieved. Mild to moder ate sedation occurs in 2-4 minutes. Anesthetic doses may need to be decreased to prevent an overdose as romi-ﬁdine has anesthesia-sparing effects. (Label information; Sedave t®—B-I Vetmedica) T ! DOGS: a) For sedation : 40-120 mcg/kg IV, IM or SQ. IV administration causes sedation within approximately 5 minutes. With SC or IM injection sedation is delayed until about 30 minutes post-injection. Sedation depth is also lower than with IV injection. Atipamezole may be used to hasten recovery. A dose of 200 mcg/kg atipamezole IM will reverse a dose of 120 mcg/kg of romiﬁdine. As a preanesthetic : 40-120 mcg/kg IV, IM or SQ. Induce anesthesia (with propofol or thiopental) approximately 10 minutes after IV injection and 10-15 minutes after IM or SC injection. Label states to maintain anesthesia with halothane. (Label information; Romydis®—Virbac-Ireland) b) As an analgesic adjunct: 10-20 mcg/kg IM, SQ. May combine with an anticholinergic agent in exercise-tolerant patients free from heart disease. (Lamont and Tranquilli 2002) T ! CATS: a) For sedation : 200-400 mcg/kg IV or IM. An IM injection of 200 mcg/kg gives sedation in about 10 minutes and persists for about 60 minutes. IV administration gives a more rapid onset of action (5 minutes) and the duration is similar to IM. Atipamezole IM 30 minutes after IM romiﬁdine injection may be used to hasten recovery. A dose of 400 mcg/kg atipa-mezole IM will reverse a dose of 400 mcg/kg of romiﬁdine. As a preanesthetic : 200 mcg/kg IM 10-15 minutes prior to giving ketamine at 10 mg/kg IM will provide surgical anes-thesia for up to 30 minutes. Increasing the dose of romiﬁdine to 400 mcg/kg will extend period of surgical anesthesia. A ”top-up dose” of 50% of the initial doses of romiﬁdine and ketamine can be used to prolong anesthesia. (Label informa-tion; Romydis®—Virbac-Ireland) b) As an analgesic adjunct: 20-40 mcg/kg IM, IV. May combine with an anticholinergic agent in exercise-tolerant patients free from heart disease. (Lamont and Tranquilli 2002) T ! CATTLE: Note : Romiﬁdine is not approved for use in cattle or other food-producing animals in the USA. For guidance with determin-ing withdrawal times, contact FARAD (see Phone Numbers & Websites in the ap pendix for contact information). a) For epidural anesthesia for paralumbar analgesia or laparotomy : Romiﬁdine 50 mcg/kg plus morphine 0. 1 mg/kg. Duration of analgesia is 12 hours maximum. (Anderson 2006b) Monitoring T ! Level of sedation/analgesia T ! Respiratory rate T ! Heart rate/rhythm; blood pressure (during general anesthesia) T ! Body temperature for longer procedures using higher dosages Client Information T ! his medication should only be administered by veterinary pro-fessionals T ! If clients are involved with handling horses after they are dosed with romiﬁdine, they should be warned that although the horse looks fully sedated it may respond defensively (e. g., kick) when stimulated Chemistry/Synonyms Romiﬁdine HCl is an alpha-2 adrenoreceptor agonist that is struc-turally related to clonidine. It has a molecular weight of 258. 1 and occurs as a crystalline, white, odorless substance that is soluble in water. Its chemical name is 2-(2-Bromo-7-ﬂuoroanilino-)-2-imi-dazoline or 2-Bromo-6-ﬂuoro-N-(1-imidazolin-2yl)analine. Romiﬁdine may also be known as: STH-2130, romiﬁdiini, romi-ﬁdin, romiﬁdina, romiﬁdinum, Romidys ®, Sedivet®, and Sedivan®. Storage/Stability Romiﬁdine HCl injection should be stored at controlled room tem-perature (15-30°C). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Romiﬁdine HCl 1% (10 mg/m L) Injection; Sedivet® (B-IVetmedica); (Rx). In the USA: Approved for use in horses not intended for hu-man consumption. In the UK, slaughter withdrawal is 6 days for horses. A smal l animal product, Romidys ® (Virbac) containing 1 mg/m L is approved for use in dogs and cats in some European countries. HUMAN-LABELED PRODUCTS: None RONIDAZOLE (roe-nid-ah-zole) ANTIPROTOZOAL Prescriber Highlights TT Nitroimidazole antibiotic/antiparasitic drug that appears to be useful in treating Tritrichomonas foetus infections in cats; also used for treating trichomonas infections in non-food birds TT Potentially carcinogenic; avoid human exposure TT Neurotoxicity (reversible): more likely at higher doses (50 mg/kg twice daily), but can occur at lower dosages as well; GI effects possible TT Many potential drug interactions TT Must be compounded from bulk powder (100%) & ide-ally, put in gelatin capsules Uses/Indications Ronidazole is a nitroimidazole antibiotic/antiparasitic drug that appears to be useful in treating Tritrichomonas foetus infections in cats. The drug is not commercially available in the USA and must be compounded from bulk powder by a compounding pharmacy. The drug is also used for treating Trichomonas infections in non-food animal birds. Pharmacology/Actions Ronidazole, like other 5-nitroimidazoles such as metronidazole is convertedby hydrogenosomes (anorganellefound intrichomonads) into polar autotoxic anion radicals. T. foetus infections in cats have been resistant to treatment by metronidazole, but ronidazole ap-pears to have greater activity against the organism. Pharmacokinetics No information was located.	pppbs.pdf
TContraindications/Precautions/Warnings Ronidazole should not be used in patients hypersensitive to it or other 5-nitroimidazoles (e. g., metronidazole). The compound has been demonstrated to be carcinogenic in mice but not rats. While humans should avoid contact with this compound or with animal waste from treated patients, it can be safely compounded using a biological safety cabinet. The FDA prohibits this drug for use in food animals. Adverse Effects Reversible neurotoxicity similar to that reported with metronida-zole, has been reported in cats with ronidazole. Initial signs may in-clude ataxia, nystagmus, or behavior changes. Should neurotoxicity be diagnosed, discontinue ronidazole, treat supportively, and if nec-essary, consider administering a benzodiazepine such as diazepam to competitively inhibit GABA receptors in the CNS. Incidence of neurotoxicity appears to be higher when using the 50 mg/kg twice daily dosage, but may occur at lower dosages as well. Potentially, gastrointestinal effects can occur (anorexia, vomiting). Ronidazole is very bitter and should be administered to cats in capsule form. Ronidazole has been shown to increase the rate of benign mam-mary tumors in rats and increase the rates of benign and malignant pulmonar y tumors in mice at dosages at or above 20 mg/kg/day. Dogs given 30 mg/kg per day for two years (40 mg/kg/day the ﬁrst month) showed some testicular toxicity (type not speciﬁed), but no tumors. Reproductive/Nursing Safety Safety of this compound during pregnancy is not established. T eratology studies have been performed in mice, rats, and rabbits. In rabbits given 30 mg/kg/day, no embryotoxicity occurred, but fetal weights were signiﬁcantly decreased. Mice demonstrated no teratogenic effects at dosages of up to 200 mg/kg/day. Rats given up to 150 mg/kg/day demonstrated no embryotoxic effects, but at dosages of 200 mg/kg/day both maternal and fetal weights were decreased. If this compound is to be used in pregnant cats, weigh the po-tential beneﬁts of treating with the potential for adverse effects in the off spring and queen. It is not known if ronidazole is distributed into milk and safety cannot b e assured. Consider using milk replacer if treating nursing queens. Overdosage/Acute Toxicity No speciﬁc information was located. Cats receiving doses of 50 mg/ kg twice daily appear to have greater incidences of neurotoxicity (see Adverse Reactions). If overdoses cause neurotoxicity, discon-tinue further therapy and treat supportively. Consider administer-ing a GABA inhibitor such as diazepam, to competitively inhibit GABA r eceptors in the CNS. Drug Interactions In humans, the following drug interactions with metronidazole, a compound similar to ronidazole, have been reported or are theo-retical and may be of signiﬁcance in veterinary patients in patients re ceiving ronidazole: !TALCOHOL : May induce a disulﬁram-like (nausea, vomiting, cramps, etc. ) reaction !TCIMETIDINE, KETOCONAZOLE : May decrease the metabolism of ronidazole and increase the likelihood of dose-related side effects occurring !TCYCLOSPORINE, TACROLIMUS (systemic ): Ronidazole may increase the serum levels of cyclosporine or tacrolimus !TFLUOROURACIL (systemic ): Ronidazole may increase the serum lev-els of ﬂuorouracil and increase risk for toxicity !TLITHIUM : Ronidazole may increase lithium serum levels and in-crease risk for lithium toxicity !TOXYTETRACYCLINE : Reportedly may antagonize the therapeutic ef-fects of metronidazole (and presumably ronidazole) !TPHENOBARBITAL, RIFAMPIN or PHENYTOIN : May increase the metabo-lism of ronidazole thereby decreasing blood levels !TWARFARIN : Metronidazole (and potentially ronidazole), may pro-long INR/PT in patients taking coumarin anticoagulants; avoid co ncurrent use if possible; otherwise intensify monitoring Laboratory Considerations !TAST, ALT, LDH (lactic dehydrogenase ), Triglycerides, Hexokinase glucose : A related compound, metronidazole can cause falsely decreased readings when determined using methods measur-ing decreases in ultraviolet absorbance when NADH is reduced to NAD. It is not known if ronidazole can also cause falsely de-creased values. Doses !TCATS: a) For treatment of T. foetus infections: 30 mg/kg PO twice daily for 14 days. (Gookin 2007) Note : Based on results of a published study of experimental T. foetus infection (Gookin, Copple et al. 2006) the author suggested using 30-50 mg/kg twice daily for 14 days, but subsequent experience has dem-onstrated a higher incidence of neurotoxicity at the higher dose and she now recommends treating at 30 mg/kg PO twice daily. Monitoring !TClinical efﬁcacy (diarrhea improvement) !TAdverse effects (neurotoxicity, vomiting, anorexia) !TPCR testing (can be used to conﬁrm infection, but negative re-sults after treatment do not conclusively prove that infection has be en eradicated) Client Information !TRonidazole must be given by mouth twice daily (approximate-ly 12 hours apart) for 14 days for it to be effective. Do not skip doses. !TStore capsules in the freezer. !This drug is considered a carcinogen. Do not open or crush cap-sules; give whole. It is recommended to wear disposable gloves whe n administering this medication. !TWhen cleaning litter box, wear disposable gloves; double bag fe-ces and dispose in trash. !TContact veterinarian immediately if cat shows signs of behavior changes, eyes moving back and forth (nystagmus), or has difﬁ-culty walking, climbing stairs, etc. (ataxia). These could be signs that dr ug t oxicity is occurring. Chemistry/Synonyms Ronidazole is a 5-nitroimidazole compound that occurs as a white to yellowish-brown, odorless or almost odorless, bitter-tasting, powder. It is very slightly soluble in water or alcohol. Ro nidazole may also be known as ronidazol, ronidazolum, Belga®, Ridsol-S®, Ronida®, Ronivet®, Ronizol®, Turbosol®, Tricho Plus®, Trichocure®, or Trichorex®.	pppbs.pdf
Storage/Stability Compounded capsules should be stored in child-resistant, tight containers protected from light. Until further stability studies can be performed, capsules should be stored in the freezer. Aqueous solutions are reportedly not very stable. It is recom-mended that fresh solutions using the 10% powder for addition to drinking water (use d for pigeons) be freshly prepared every day. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None in the USA; a 10% ronidazole powder to be added to drink-ing water for treating Trichomonas infections in pigeons is available in some c ountries, but these products are unsuitable for use in cats due to the dosage required and the unpalatability (very bitter) of the powder and solution. Capsules prepared from 100% bulk powder for an individual feline patient should be obtained from a compounding pharmacy that can prepare the capsules in a bio-safety hood that will protect the compounder from drug exposure. The FDA prohibits this drug for use in food animals. HUMAN-LABELED PRODUCTS: None S-ADENOSYL-METHIONINE (SAMe) ADEMETIONINE (ess-ah-den-oh-seel meth-ie-oh-neen) HEP ATO PROTECTANT Prescriber Highlights TT “Nutraceutical” that can be used as an adjunctive treat-ment for liver disease (chronic hepatitis), osteoarthritis, or treatment of acetaminophen toxicity in small animals TT Well tolerated TT Not a regulated drug; choose products carefully Uses/Indications In small animal medicine, SAMe is most commonly used as an ad-junctive treatment for liver disease (chronic hepatitis, hepatic lipi-dosis, cholangiohepatitis, feline triad disease, etc. ). It may also be of beneﬁt in osteoarthritis, treatment of acute hepatotoxin-induced liver toxicity (e. g., acetaminophen toxicity), and at-risk patients on long-term therapy using drugs with hepatotoxic potential. In humans, SAMe is being used as a treatment for depression, osteoar thritis, AIDS-related myopathy, intrahepatic cholestasis, liver disease, alcoholic liver cirrhosis, ﬁbromyalgia, adult ADHD, Alzheimer's, migraines, etc. Pharmacology/Actions S-adenosyl-methionine (SAMe) is an endogenous molecule synthe-sized by cells throughout the body. SAMe is formed from the amino acid methio nine and ATP, in conjunction with SAMe synthetase enzyme (an enzyme manufactured in the liver, a rate-limiting step in the presence of liver compromise). SAMe is an essential part of three major biochemical pathways: transmethylation, transsulfura-tion, and aminopropylation. Normal function of these pathways is especial ly vital to the liver as many metabolic reactions occur there. In the transmethylation pathway, SAMe serves as a methyl donor (necessary for many substances and drugs to be activated and/or eliminated). Transmethylation is essential in phospholipid synthesis important to cell membrane structure, ﬂuidity, and func-tion. In aminopropylation, SAMe donates aminopropyl groups and is a sour ce of polyamines. Aminopropylation is important in producing substances that have antiinﬂammatory effects, protein and DNA synthesis, and promoting cell replication and liver mass regeneration. In transulfuration, SAMe generates sulfur contain-ing compounds important for conjugation reactions used in de-toxiﬁcation and as a precursor to glutathione (GSH). Glutathione is impor tant in many metabolic processes and cell detoxiﬁcation. The conversion of SAMe to glutathione requires the presence of folate, cyanocobalamin (B12), and pyridoxine (B6). Normally, the liver produces ample SAMe, but in liver disease or in the presence of hepatotoxic substances, endogenous conversion to glutathione may be deﬁcient. Exogenous SAMe has been shown to increase liver and red cell glutathione levels and/or prevent its depletion. SAMe inhib-its apoptosis secondary to alcohol or bile acids in hepatocytes. In humans, the mechanism for its antidepressant effects are not well understood, but it apparently increases serotonin turnover and increases dopamine and norepinephrine levels. Neuroimaging studies in humans show that SAMe affects the brain similarly to other antidepressant medications. Pharmacokinetics Oral bioavailability is dependent on the salt used to stabilize SAMe. Oral bioavailability of the tosylate salt is reportedly 1% whereas the 1,4-butanedisulfonate form has a bioavailability of 5%. The pres-ence of food in the gut can substantially reduce the amount of drug absorbe d. Peak levels occur in 1-6 hours after oral dosing. Once absorbed, SAMe enters the portal circulation and is primarily me-tabolized in the liver. In humans, 17% of a dose of radio-labeled SAMe was r ecovered in the urine within 48 hours of dosing; 27% in the feces. Contraindications/Precautions/Warnings There are no apparent contraindications to the use of SAMe. Adverse Effects Adverse effects appear to be minimal or non-existent in treated ani-mals. Most studies in humans have shown adverse effects similar to that of pla cebo. Oral SAMe in humans may cause anorexia, nausea, vomiting, diarrhea, ﬂatulence, constipation, dry mouth, insomnia/ nervousness, headache, sweating, and dizziness. Reproductive/Nursing Safety The safety of exogenous SAMe has not been proven in pregnan-cy; use with caution. Limited studies in laboratory animals and in preg nant women with liver disease have not demonstrated any ill effects to mother or fetus. It is unknown if SAMe enters maternal milk. Overdosage/Acute Toxicity SAMe appears to be quite safe. LD50 in rodents exceeds 4. 65 g/kg, and toxicit y studies in dogs and cats at the usual prescribed dos-ages demonstrated no deleterious effects. In the case of an overdose, gastro intestinal effects may be observed, but unlikely to require treatment. Drug Interactions No interactions have been documented, but theoretically, concur-rent use of SAMe with tramadol, meperidine, dextromethorphan, penta-zocine, monoamine oxidase inhibitors ( MAOIs ) including selegiline, selective serotonin reuptake inhibitors ( SSRIs ) such as ﬂuoxetine, or other antidepressants (e. g., amitriptyline, clomipramine ) could cause additive serotonergic effects.	pppbs.pdf
Laboratory Considerations No speciﬁc laboratory interactions or considerations noted. Doses T ! DOGS & CAT S: Daily dose for animals with body weights of: up to 12 pounds (5. 5 kg): one 90 mg tablet; 12-25 p ounds (5. 5-11 kg): two 90 mg tablets (or one 225 mg tablet, if more convenient); 25-35 pounds (11-16 kg): one 225 mg tablet; 35-65 pounds (16 -29. 5 kg): two 225 mg tablets; 65-90 pounds (29. 5 kg-41 kg): three 225 mg tablets; over 90 pounds (41 kg+): four 225 mg tablets. Daily dosage may also be calculated based on 18 mg/kg of body weight and rounded to the closest tablet size or combination of sizes. Product should be given on an empty stomach, at least one hour before feeding. If giving more than one tablet, may divide total daily dosage and give twice daily. The number of tablets can be gradually reduced or may be increased at any time de-pending on the pet's needs. (Package information; Denosyl ®— Nutramax) For Liver Disease: a) For adjunctive treatment of chronic hepatitis: Dogs: 17-20 mg/kg or hig he r per day given on an empty stomach Cats: 200 mg/day on an empty stomach. Reco mmend using a reliable product with proven research in dogs and cats such as Denosyl®. (Center 2002) b) 20 mg/kg once daily (Willard 2006b) Monitoring T ! Clinical signs (appetite, activity, attitude) T ! Liver enzymes, bilirubin, bile acids T ! Liver biopsies T ! Hepatic and erythrocyte glutathione levels (available at research institutions only at this time); may require 1-4 months before any chang es in lab v alues are noted Client Information T ! Administer tablets to animal with an empty stomach, preferably at least one hour before feeding T ! Keep tablets in original packaging until administration. Do not crush or split tablets Chemistry/Synonyms S-adenosyl-methionine (SAMe) is a naturally occurring molecule found throughout the body. Because pure SAMe is highly reactive and unstable, commercially available forms of SAMe are salt forms; sulfate, sulfate-p-toluenesulfonate (also known as tosylate), and butanedisulfonate salts can all be procured. SAMe may also be known as: S-adenosyl-L-methionine, S-adenosy lmethionine, SAM, SAM-e, adenosylmethionine, Sammy, methioninyl adenylate, Donamet®, Gumbaral®, Isimet®, Mood Lift®, S Amet®, Samyr®, Transmetil®, and Tunik®. Storage/Stability Unless otherwise labeled, SAMe tablets should be stored at room temperature. Avoid conditions of high temperature or humidity. SAMe is inherently unstable in acidic or aqueous environments; store in tightly sealed, moisture-resistant containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None as a pharmaceutical. SAMe is considered a nutritional supple-ment by the FDA. No standards have been accepted for potency, pu-rity, safety, or efﬁcacy by regulatory bodies. Supplements are available from a wide variety of sources and dosage forms include tablets in a variety of concentrations. There are speciﬁc products marketed for use in animals, including Denosyl® (Nutramax) in 90 mg, 225 mg, & 425 mg enteric-coated, blister-packed tablets and Zentonil® (Vetoqui-nol) in 100 mg, 200 mg and 400 mg tablets. Bioequivalence between SAMe pr oducts is not assured. A combination product Denamarin® (Nutramax), containing SAMe and silybin (silymarin) is also labeled for use in dogs and cats. HUMAN-LABELED PRODUCTS: None as a pharmaceutical. SALINE/HYPEROSMOTIC LAXATIVES MAGNESIUM SALTS PEG 3350 PRODUCTS Go LYTELY®, Epsom Salts LAXATIVES Prescriber Highlights TT Saline/hyperosmotic agents for constipation, bowel “cleansing”, & to increase elimination of GI toxins TT Contraindications: PEG 3350 solutions are contraindi-cated in patients with GI obstruction, gastric retention, bowel perforation, toxic colitis, or megacolon. Saline ca-thartics should be used with extreme caution in patients with renal insufﬁciency, pre-existing water-balance or electrolyte abnor malities, or cardiac disease. TT Adverse Effects: Cramping, nausea possible TT If magnesium salts used chronically: Hypermagnesemia (muscle weakness, ECG changes & CNS effects) TT Drug Interactions Uses/Indications The saline laxatives are used for their cathartic action to relieve con-stipation. They are also used to reduce intestinal transit time thereby reducing the absorption of orally ingested toxicants. Polyethylene glycol 3350 balanced electrolyte solutions are used to evacuate the colon prior to intestinal examination or surgery. Pharmacology/Actions Although unproven, it is commonly believed that the hyperosmotic effect of the poorly absorbed magnesium cation causes water re-tention, stimulates stretch receptors and enhances peristalsis in the small int estine and colon. Recent data, however, suggests that magnesium ions may directly decrease transit times and increase cholecystokinin release. Polyethylene glycol 3350 is a non-absorbable compound that acts as an osmotic agent. By adding sodium sulfate as the primary sodium source, sodium absorption is minimized. Other electrolytes (bicarbonate potassium and chloride) are also added so that no net	pppbs.pdf
change occurs with either absorption or secretion of electrolytes or water in the gut. Pharmacokinetics When magnesium salts are administered, up to 30% of the magne-sium dose of magnesium can be absorbed. Generally, the onset of action of saline cathartics (characterized by a loose, watery stool) occurs in 3-12 hours after dosing in mo-nogastric animals and within 18 hours in ruminants. Contraindications/Precautions/Warnings Saline cathartics are contraindicated for long-term or chronic use. Sodium containing laxatives are contraindicated in patients with congestive heart failure or congenital megacolon. PEG 3350 solu-tions are contraindicated in patients with GI obstruction, gastric re tention, bowel perforation, toxic colitis, or megacolon. Saline ca-thartics should be used with extreme caution in patients with renal insufﬁcie ncy, pre-existing water-balance or electrolyte abnormali-ties, or cardiac disease. Adverse Effects Except for possible cramping and nausea, adverse effects in other-wise healthy patients generally occur only with the saline cathartics with chronic use or overdoses. Hypermagnesemia manifested by muscle weakness, ECG changes and CNS effects can occur. Reproductive/Nursing Safety In humans, the FDA categorizes magnesium sulfate 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 demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Other saline or hyperosmolar cathartics should be safe to use in pregnancy when used infrequently. Magnesium emulsions administered orally did not affect the sto ols of nursing infants, although magnesium content in breast milk was slightly elevated compared with untreated patients. In veterinary patients, it should be safe to use during nursing when used infrequently. Overdosage/Acute Toxicity Clinical signs of overdosage of magnesium containing laxatives are described above. Treatment should consist of monitoring and cor-recting any ﬂuid imbalances that occur with parenteral ﬂuids. If hypermagnesemia occurs, furosemide may be used to enhance the r enal excretion of the excess magnesium. Calcium has been sug-gested to help antagonize the CNS effects of magnesium. Drug Interactions All orally administered saline laxatives may alter the rate and ex-tent of absorption of other orally administered drugs by decreasing intestinal transit times. The extent of these effects has not been well characterized for individual drugs, however. !TTETRACYCLINES : Magnesium laxatives should not be administered with tetracycline products Doses !TDOGS: Magnesium hydroxide (Milk of Magnesia) as a cathartic: a) 5-10 m L (Davis 1985a) b) 1-20 m L PO (Rossoff 1974) Mag nesium sulfate: a) 5-25 grams PO (Davis 1985a) b) 2-60 grams PO (Rossoff 1974) Polyethylene Glycol-Electrolyte Solution: a) For colonic cleansing prior to colonoscopy using Go-L yte-ly®: Keep animal from food for 24-36 hours. On the eve-ning prior to a morning colonoscopy (or the morning for an aft ernoon colonoscopy), give 60 m L/kg via orogastric tube. Repeat in 2 hours. A warm water enema should follow each dose and a third enema given prior to anesthesia. (Leib 2003), (Leib 2006) b) For colonic cleansing prior to colonoscopy using Go-L ytely®: 12-18 hours prior to colonoscopy give 25 m L/kg via oro-gastric tube three to ﬁve times, one hour apart. Give enema shor tly after last Go-Lytely® dose and one to two hours prior to endoscopy procedure. (Richter 2003) c) For colonic cleansing prior to colonoscopy using Go-L ytely®: Withhold food for 18-24 hours. Give two doses of 20 m L/ kg Go-Lytely® 4-6 hours apart the afternoon before an AM endoscopy. The morning of procedure, a warm-water enema is administered. (Jergens 2003) d) For mechanical bowel cleansing prior to (antibiotics and) colo nic surgery: Go-Lytely® (or similar osmotic cathartic): 50-75 m L/kg by stomach tube or NE tube the evening prior to surgery. (Trepanier 2003) !TCATS: Magnesium hydroxide (Milk of Magnesia) as a cathartic: a) 2-6 m L (Davis 1985a) b) 1-5 m L PO (Rossoff 1974) Mag nesium sulfate: a) 2-5 grams PO (Davis 1985a), (Rossoff 1974) Pol yethylene Glycol-Electrolyte Solution: a) For colonic cleansing prior to colonoscopy using Go-L ytely®: Keep animal from food for 24-36 hours. On the evening prior to a morning colonoscopy (or the morning for an af-ternoon colonoscopy), give 60 m L/kg via nasogastric tube. Re peat in 2 hours. A warm water enema should follow each dose and a third enema given prior to anesthesia. Metoclo-pramide (0. 2 mg/kg SC 15-20 minutes before the ﬁrst Go-Ly tely® dose is given to reduce vomiting. (Leib 2003), (Leib 2006) !TCATTLE: Magnesium sulfate (as a cathartic): a) 0. 5-1 kg/500 kg orally (Whitlock 1986b) b) 1-2 gm/kg PO (Howard 1986) Mag nesium oxide: a) 0. 5-1 kg/500 kg orally (Whitlock 1986b) !THORSES: Magnesium sulfate (Epsom salt): a) 0. 2 gm/kg diluted in 4 L of warm water administered via nasog astric tube. Administer only to well-hydrated animals (ideally in conjunction with IV ﬂuid therapy). Do not treat longer than 3 days or there is an increased risk of enteritis or magnesium toxicity occurring. (Clark and Becht 1987) b) As a laxative: 1 g/kg PO every 1-2 days; in colic delay treat-ment until rehydrated (Moore 1999) c) T o reduce absorption of toxicants and GI transit time: 500 gm (as a 20% solution) PO. If mineral oil has been used ini-tially, give saline cathartic 30-45 minutes after mineral oil. (Oehme 1987) d) F or cecal impactions: 1 g/kg dissolved in water dissolved in wate r and given via NG tube. Give with a balanced electro-lyte solution IV to stimulate secretion into the dehydrated ingesta. (White 2005a)	pppbs.pdf
T ! SWINE: Magnesium sulfate (as a cathartic): a) 1-2 gm/kg PO (Howard 1986) T ! BIRDS: Magnesium sulfate: a) T o act as a cathartic and reduce lead absorption: 0. 5-1 gm/ kg PO as a 5% solutio n in drinking water (Mc Donald 1986) Monitoring T ! Fluid and electrolyte status in susceptible patients, high doses, or chronic use T ! Clinical efﬁcacy Client Information T ! Do not give dosages greater than, or for periods longer than rec-ommended by veterinarian T ! Contact veterinarian if patient begins vomiting Chemistry/Synonyms Magnesium cation containing solutions of magnesium citrate, magnesium hydroxide, or magnesium sulfate act as saline laxatives. Magnesium citrate solutions contain 4. 71 m Eq of magnesium per 5 m L. Magnesium hydroxide contains 34. 3 m Eq of magnesium per gram and milk of magnesia contains 13. 66 m Eq per 5 m L. One gram of magnesium sulfate (Epsom salt) contains approximately 8. 1 m Eq of magnesium. Polyethylene glycol 3350 is a non-absorbable compound that acts as an osmotic ag ent. Storage/Stability Magnesium citrate solutions should be stored at 2-30°C. Store milk of magnesia at temperatures less than 35°C, but do not freeze. PEG 3350 reconstituted (from powder by the pharmacy, client, clinic, etc. ) solutions should be kept refrigerated and used within 24 hours. Dosage Forms/Regulatory Status Saline cathartic products have apparently not been formally approved for use in domestic animals. They are available without prescription (OTC). PEG 3350 products are available only by prescription and are approved for use in humans. VETERINARY-LABELED PRODUCTS: None located HUMAN-LABELED PRODUCTS: Saline Laxatives (not an inclusive list): Magnesium Hydroxide Suspension (Milk of Magnesia): equiv. to 30 m L milk of magnesia in 100 m L, 400 m L & UD 10 m L; magnesium hydroxide 160 mg/m L & 80 mg/m L in 180 m L, 240 m L, 360 m L, 400 m L, 480 m L, 780 m L, UD 30 m L; Milk of Magnesia Concentrated® (Roxane); Phillips'® Milk of Magnesia and Phillips'® Milk of Magnesia Concentrated (Bayer); generic; (OTC) Magnesium Sulfate (Epsom Salt) Granules: in 120 g, 1lb and 4lbs; gener ic; (OTC) Hyperosmotic Laxatives (not an inclusive list): Polyethylene Glycol-Electrolyte Solution: OCL® Solution (Abb ott); (Rx) Oral Solution in 1500 m L: 146 mg so-dium chloride, 168 mg sodium bicarbonate, 1. 29 g sodium sulfate decahy drate, 75 mg potassium chloride, 6 grams PEG-3350 and 30 mg polysorbate-80/100 m L Co Lyte® (Schwartz Pharma); (Rx); 1 gallon of Powder for Oral So-lution in bottles: 227. 1 g PEG 3350, 5. 53 gm sodium chloride, 6. 36 gm sodi um bicarbonate, 21. 5 gm sodium sulfate, 2. 82 gm potassium chloride; 4L of solution: 240 g PEG 3350, 22. 72 g sodium sulfate, 6. 72 g sodium bicar bonate, 5. 84 g Na Cl, 2. 98 g KCL Go LYTELY® (Braintree Labs); (Rx); Powder for Oral Solution in jugs: 5. 86 gm sodium chloride, 6. 74 gm sodium bicarbonate, 22. 74 gm so-dium sulfate, 2. 97 gm potassium chloride, 236 gm PEG 3350; Packets: 227. 1 g PEG 3350, 21. 5 g sodium sulfate, 6. 36 g sodium bicarbonate, 5. 53 g Na Cl, 2. 82 g KCl Nu Lytely® (Braintree Labs); Tri Ly te® (Schwarz Pharma); (Rx); Pow-der for Reconstitution in 4 L jugs: 420 g PEG 3350, 5. 72 g sodium bicarbo nate, 11. 2 g Na Cl, 1. 48 g KCL Movi Prep® (Salix); (Rx); Powder for Reconstitution in pouches: 100 g PEG 3350, 7. 5 g sodi um sulfate, 2. 691 g Na Cl, 1. 015 KCl. SELAMECTIN (sell-a-mek-tin) Revolution® A VERMECTIN (TOPICAL) ANTIPARASITIC Prescriber Highlights TT Topical avermectin antiparasiticide approved for multiple indications in dogs & cats TT Applied monthly (usually; some indications one time dosing) TT Adverse effect proﬁle appears minimal Uses/Indications T opical selamectin (Revolution®—Pﬁzer) is indicated for ﬂea in-festations (Ctenocephalides felis), prevention of heartworm disease (Diroﬁlar ia immitis), and for ear mites (Otodectes cynotis) in both dogs and cats. Additionally in dogs, it is indicated for sarcoptic mange (Sarcoptes scabeii), and tick infestations (Dermacentor vari-abilis). In cats: hookworm (Ancylostoma tubaeforme) and round-worm (Toxocara cati). The product (Revolution®) is labeled as not effective against ei-ther adult heartworms or clearing circulating microﬁlaria, but it possibly may have some efﬁcacy with prolonged, continuous ad-ministration (Atkins 2007b). Pharmacology/Actions Like other compounds in its class, selamectin is believed to act by enhancing chloride permeability or enhancing the release of gamma amino butyric acid (GABA) at presynaptic neurons. GABA acts as an inhibitory neurotransmitter and blocks the post-synaptic stimu-lation of the adjacent neuron in nematodes or the muscle ﬁber in arthrop ods. By stimulating the release of GABA, it causes paralysis of the parasite and eventual death. As liver ﬂukes and tapeworms do not use GABA as a peripheral nerve transmitter, selamectin would probably be ineffective against these parasites. Pharmacokinetics After topical administration to dogs, about 5% of the drug is bio-available and peak plasma levels occur about 3 days later. Elimination half-life after topical administration is about 11 days. After topical administration to cats, about 75% of the drug is bioav ailable and peak plasma levels occur about 15 hours later. Elimination half-life after topical administration is about 8 days. In cats, bioavailability is about 75% and peak levels may be 64 times those in dogs.	pppbs.pdf
The persistence of the drug in the body is believed to be due to the drug forming reservoirs in skin sebaceous glands. It is secreted into the intestine to kill susceptible endoparasites in cats. Contraindications/Precautions/Warnings The manufacturer recommends caution when using in sick, under-weight, or debilitated dogs or cats. It is not recommended for use in animals und er 6 weeks of age. At labeled doses of selamectin, dogs at risk for MDR1-allele mutation (Collies, Australian Shepherds, Shelties, Long-haired Whippet, etc “white feet”) should tolerate the medication, but use cautiously. Adverse Effects In ﬁeld trials (limited numbers of animals) adverse effects were rare. Approximately 1% of cats showed a transient, localized alopecia at the area of administration. Other effects reported (< or = 0. 5% incidence) include diarrhea, vomiting, muscle tremors, anorexia, pruritus/urticaria, erythema, lethargy, salivation and tachypnea. Very rarely, seizures and ataxia have been reported in dogs. Reproductive/Nursing Safety Selamectin appears to be safe to use in pregnant or lactating dogs or cats. Overdosage/Acute Toxicity Dogs: Oral overdoses of up to 15 mg/kg did not cause adverse ef-fects (except for ataxia in one avermectin sensitive collie). T opical ov erdoses (10x) to puppies caused no adverse effects; topical over-doses to avermectin-sensitive Collies caused salivation. Cats: Oral ingestion may cause salivation and vomiting. T opical ov erdoses of up to 10x caused no observable adverse effects. There were 218 exposures to selamectin reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 125 were dogs with 4 showing clini-cal signs and 86 cases were cats with 15 showing clinical signs. The re maining 7 cases consisted of 5 ferrets and 2 lagomorphs none of which had clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included hypersalivation, agitation, diar-rhea, edema of the face and hyperactivity. Common ﬁndings in cats re corded in decreasing frequency included vomiting, anorexia, hy-peresthesia, hyperthermia and mydriasis. Drug Interactions None documented, but caution is advised if using other drugs that can inhibit p-glycoprotein. Those dogs at risk for MDR1-allele muta-tion (Collies, Australian Shepherds, Shelties, Long-haired Whippet, et c “white feet”) should probably not receive selamectin with the following drugs, unless tested “normal”: Drugs and drug classes in-volved include: !!AMIODARONE !!CARV EDILOL ! !CLARITHROMYCIN !!CYCLOSPORINE !!DILTIAZEM ! !ERYTHROMYCIN ! !ITRACONAZOLE !!KETOCONAZOLE !!QUINIDINE !TSPIRONOLACTONE !!TAMOXIFEN ! !VERAPAMIL Laboratory Considerations None reported. Doses !TDOGS: For prophylaxis and treatment of diroﬁlariasis, it is suggested to re-view the guidelines published by the American Heartworm Society at www. heartwormsociety. org for more information a) The recommended topical dose is 6 mg/kg. Dosing frequen-cy: Heartworm prevention, ﬂea control = monthly; Ticks = monthl y (if heavy infestations, may repeat 2 weeks after the ﬁrst dose); Ear Mites, Sarcoptes = once, repeat in one month if necessary. See the package for speciﬁc instructions on ad-ministration technique. (Label information; Re volution®— Pﬁzer) !TCATS: a) The recommended topical dose is 6 mg/kg. Dosing fre-quency: Heartworm prevention, ﬂea control = monthly; Ear Mit es = once, repeat in one month if necessary. Hookworms, Roundworms = once. See the package for speciﬁc instruc-tions on administration technique. (Label information; Re volution®—Pﬁzer) !TFERRETS: a) For heartworm prevention: 18 mg/kg topically every 30 days. (J ohnson 2006c) !TRABBITS: a) For ear mites (P. Cunuculi): 6-18 mg/kg topically (Mc Tier, Hair e t al. 2003) Monitoring !TClinical efﬁcacy !TOwner compliance with treatment regimen Client Information !TFollow label directions for administration technique; do not massage into skin, and do not apply if hair coat is wet. Because the product contains alcohol, do not apply to broken skin. !TAvoid contact with animal while the application site is wet. !TWait two hours or more after applying to bathe the animal (or allow to go swimming). !TAvoid getting the product on human skin; if contact occurs, wash off immediately. Dispose of tubes in regular household refuse. !TDo not expose to ﬂame as the product is ﬂammable. Chemistry/Synonyms A semi-synthetic avermectin, selamectin is commercially available as a colorless to yellow solution (ﬂammable). Selamectin may also be known as UK-124114, or Revolution®. Storage/Stability The commercially available solution should be stored below 30°C (86°F). Keep away from ﬂame or other igniters. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Selamectin Topical Solution for Cats; Revolution® (Pﬁzer); (Rx): Up to 5 lbs in wt, Pkg. Color: mauve. 15 mg/tube. Tube volume: 0. 25 m L 5. 1-15 lbs in wt, Pkg. Color: blue. 45 mg/tube. Tube volume: 0. 75 m L	pppbs.pdf
Selamectin Topical Solution for Dogs; Revolution® (Pﬁzer); (Rx) Up to 5 lbs in wt, Pkg. Color: mauve. 15 mg/tube. Tube volume: 0. 25 m L 5. 1-10 lbs in wt, Pkg. Color: purple. 30 mg/tube. Tube volume: 0. 25 m L 10. 1-20 lbs in wt, Pkg. Color: brown. 60 mg/tube. Tube volume: 0. 5 m L 20. 1-40 lbs in wt, Pkg. Color: red. 120 mg/tube. Tube volume: 1 m L 40. 1-85 lbs in wt, Pkg. Color: teal. 240 mg/tube. Tube volume: 2 m L 85. 1-130 lbs in wt, Pkg. Color: plum. One 120 mg tube and one 240 mg tube. T otal volume: 3 m L HUMAN-LABELED PRODUCTS: None SELEGILINE HCL L-DEPRENYL (se-le-ji-leen) Anipryl®, Eldepryl® MONAMINE OXIDASE INHIBITOR Prescriber Highlights TT MAO-B inhibitor that may be useful for canine cognitive dysfunction syndrome or Cushing's (efﬁcacy in doubt for Cushing's) TT Contraindications: Hypersensitivity to it. May be contrain-dicated in patients receiving opiates TT Adverse Effects: Vomiting & diarrhea; CNS effects mani-fested by restlessness, repetitive movements, or lethargy; salivation & anorexia. Diminished hearing/deafness, pru-ritus, licking, shivers/trembles/shakes possible TT Drug Interactions Uses/Indications Selegiline is approved for use in dogs for the treatment of Cushing's disease and for Canine Cognitive Dysfunction (so-called “old dog dementia”). Its use for Cushing's disease is somewhat controversial as clinical studies evaluating its efﬁcacy have shown disappointing results. In humans, selegiline's primary indication is for the adjunc-tive treatment of Parkinson's disease. Pharmacology/Actions Selegiline's mechanism of action for treatment of Cushing's disease (pituitary dependent hyperadrenocorticism—PDH) is complex; a somewhat simpliﬁed explanation follows: In the hypothalamus, corticotropin-releasing hormone (CRH) acts to stimulate the pro-duction of ACTH in the pituitary and dopamine acts to inhibit the relea se of ACTH. As dogs age, there is a tendency for a decrease in do-pamine production that can contribute to the development of PDH. As dopamine is metabolized by monamine oxidase-B (MAO-B) and seleg iline inhibits MAO-B, dopamine levels can be increased at receptor sites after selegiline administration. In theory, this al-lows the levels of dopamine and CRH to be in balance in the hy-pothalamus, thereby reducing the amount of ACTH produced and ultimatel y, cortisol. While selegiline is labeled as a MAO-B inhibitor, at higher than labeled dosages, the drug loses its MAO-B speciﬁcity and also in-hibits MAO-A. Two of three metabolites of selegiline are amphet-amine and methamphetamine that may contribute to both the ef-ﬁcacy and the adverse effects of the drug. Pharmacokinetics There is only limited information on the pharmacokinetics of selegiline in dogs. A study done in 4 dogs showed that selegiline was absorbed rapidly and had an absolute bioavailability of about 10%. The volume of distribution of the central compartment was measured at approximately 7 L/kg. Terminal half-life was about one hour. In humans, selegiline pharmacokinetics have wide interpatient variabilit y. The drug has a high ﬁrst pass effect where extensive metabolism to L-desmethylselegiline, methylamphetamine, and L-amphetamine occur. Each of these metabolites is active. While L-desmethylselegiline does inhibit MAO-B, the others do not, but thye are CNS stimulants. The drug is excreted in the urine, primar-ily as conjugated and unconjugated metabolites. Contraindications/Precautions/Warnings Selegiline is contraindicated in patients known to be hypersensitive to it. In human patients, it is contraindicated in patients receiving meperidine and possibly with other opioids as well. The manufacturer cautions to perform appropriate diagnostic tests to conﬁrm the diagnosis before starting therapy and not to at-tempt to treat hyperadrenocorticism not of pituitary origin. Adverse Effects Adverse reports reported thus far in dogs include, vomiting, diar-rhea, CNS effects manifested by restlessness, repetitive movements or letharg y, salivation, and anorexia. Should GI effects be a prob-lem, discontinue the drug for a few days and restart at a lower dose. Diminished hear ing/deafness, pruritus, licking, shivers/trembles/ shakes have also been reported. The manufacturer advises to ob-serve animals carefully for atypical responses. Adverse effects that have been reported in human patients in-clude nausea (10%), hallucinations, confusion, depression, loss of balance, insomnia, and hypersexuality. These effects are noted be-cause of their “subjective” nature and they could help explain un-toward behavioral changes in canine patients should they occur. Because selegiline could potentially be abused by humans, veter-inarians should be alert for drug “shoppers. ” Selegiline is classiﬁed by the A ssociation of Racing Commissioners International (ARCI) as a class 2 agent (high abuse potential in racing horses). Reproductive/Nursing Safety Safety of selegiline in pregnant, breeding or lactating animals has not been established. Rat studies have not demonstrated overt teratogenicity. 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 selegiline is excreted in maternal milk. Overdosage/Acute Toxicity Oral LD 50 in laboratory animals was approximately 200-445 mg/ kg. In limited data, dogs receiving 3x dosages showed signs of de-creased weight, salivation, decreased pupillary response, panting, stere otypic behaviors and decreased skin elasticity (dehydration). Overdoses, if severe, should be treated with appropriate gut empty-ing and supportive treatments. Drug Interactions Evaluating the potential for drug interactions for selegiline in dogs is problematic. There are a plethora of signiﬁcant interactions with monamine oxidase inhibitors in humans for selegiline, but because there are signiﬁcant species differences in quantities and locations of MOA-A and B and selegiline's effects at various dosages on these	pppbs.pdf
enzymes, they may not apply to dogs. However, the following drug interactions are some of the more signiﬁcant interactions reported or are theoretical in humans or animals receiving selegiline and potentially could be of signiﬁcance in veterinary patients; cau-tion is advised particularly if using selegiline at higher than labeled dosages: T ! AMITRAZ : The manufacturer recommends not using selegiline concurrently with amitraz (Mitaban®) in dogs T ! BUPROPION : Potential for serotonin syndrome T ! EPHEDRINE : The manufacturer recommends not using selegiline concurrently with ephedrine in dogs T ! MEPERIDINE : In humans, severe agitation, hallucinations and death have occurred in some patients receiving meperidine and an MAO inhibitor. Until the data can be clariﬁed, it is recommended not to use selegiline and meperidine together. A separation of two weeks has been recommended. Other opioids (e. g., morphine) should be safer, but use with extreme caution, if at all. T ! PHENYLPROPANOLAMINE, PSEUDOEPHEDRINE : Increased risk for hy-pertension, hyperpyrexia T ! SSRI'S (e. g., ﬂuoxetine ): Potentially, the so-called serotonin syn-drome could occur if selegiline is used concurrently with selec-tive serotonin reuptake inhibitors (SSRIs); T ! TRAMADOL : Use contraindicated in humans; serotonin syndrome, nausea, vomiting, cardiovascular collapse T ! TRICYCLIC & TETRACYCLIC ANTIDEPRESSANTS (clomipramine, amitrip-tyline, etc. ): Potentially, the so-called serotonin syndrome could occur if selegiline is used concurrently with these agents and use together is not advised at this time; a 2-week separation between these compounds and selegiline is recommended. Doses T ! DOGS: For Cushing's disease: a) 1 mg/kg PO in the AM (with food as needed); Reevaluate clinically over next 2 mos. ; if no improvement, may increase to 2 mg/kg once daily; if no improvement or signs increase, reevaluate diagnosis or consider alternate treatment (Pack-age Insert; Anipryl®—Pﬁzer). For C anine Cognitive Dysfunction: a) 0. 5-1 mg/kg, PO once daily, preferably in the AM. Initially, dose to the nearest whole tablet; adjustments should then be made based upon response and tolerance to the drug (Pack-age Insert; Anipryl®—Pﬁzer). b) 0. 5-1 mg/kg PO once daily (give with food) (Hoskins 1999) Monitoring T ! Clinical efﬁcacy T ! Adverse effects. No correlation between low dose dexametha-sone suppression test results and clinical efﬁcacy of the drug. The manufac t urer recommends physical exam and history as the pri-mary methods to measure response to therapy. Client Information T ! Keep this and all medications out of reach of children T ! Have clients monitor closely for adverse effects T ! Clients should be advised on the importance of complying with the dosing recommendations to adequately evaluate therapeutic respo nse t o the drug Chemistry/Synonyms Selegiline HCl, also commonly called l-deprenyl, occurs as a white to off-white crystalline powder that is freely soluble in water. It has a p Ka of 7. 5. Selegiline HCl may also be known as: deprenyl, L-deprenyl, sele-gilini hydrochloridum; many trade names are available. Storage/Stability Commercially available veterinary tablets should be stored at con-trolled room temperature 20-25°C (68-77°F). The commercially available human-labeled tablets and capsules are recommended to be stored from 15-30°C. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Selegiline HCl Oral Tablets: 2 mg, 5 mg, 10 mg, 15 mg, 30 mg in blister-packs of 30 tablets; Anipryl® (Pﬁzer); (Rx). Approved for use in dogs. The ARCI (Racing Commissioners International) has designated this drug as a class 2 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: Selegiline HCl Tablets and Capsules: 1. 25 mg (orally disintegrating) & 5 mg; Eldepryl® (Somerset); Carbex® (Du Pont Pharma); Zelapar® (Valeant Pharmaceuticals); generic tablets; (Rx) Selegiline HCl Transdermal System: 6 mg/24 h (20 mg/20 cm2); 9 mg/24 h (30 mg/30 cm2) & 12 mg/25 h (40 mg/40cm2); Emsam® (Bristol-Myers Squibb); (Rx) SERTRALINE HCL (sir-trah-leen) Zoloft® SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI) Prescriber Highlights TT A selective serotonin reuptake inhibitor that may be use-ful in treating a variety of behavior-related diagnoses in dogs & cats, including aggression, anxiety-related beha v-iors & other obsessive-compulsive behaviors TT Caution: geriatric patients or those with severe hepatic disease; dosages may need to be adjusted 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. CATS: Seda-tion, decreased appetite/anorexia, vomiting, diarrhea, behavior changes (anxiety, ir ritability, sleep disturbances), & changes in elimination patterns TT Drug-drug interactions TT Relatively inexpensive generic forms now available Uses/Indications Sertraline may be considered for use in treating a variety of behav-ior-related diagnoses in dogs and cats, including aggression, and anxiety-re lated or other obsessive-compulsive behaviors. Pharmacology/Actions Sertraline is a highly selective inhibitor of the reuptake of sero-tonin (5-hydroxytryptamine) in the CNS thus potentiating its pharmac ologic activity. Sertraline apparently has little effect on dopamine or norepinephrine, and apparently no effect on other neurotransmitters.	pppbs.pdf
Pharmacokinetics In dogs, sertraline's volume of distribution is 25 L/kg and is 97% bound to plasma proteins. High ﬁrst-pass metabolism occurs; clearance is greater than 35 m L/min/kg. Bile is the major route of excretion in the dog. In humans, sertraline peak levels occur 30-45 minutes after oral dosing. It is 98% bound to plasma proteins. Sertraline appears to be highly metabolized primarily to N-desmethylsertraline, which is active. Elimination half-lives for sertraline and desmethylsertraline average 26 and 80 hours respectively. Contraindications/Precautions/Warnings Sertraline is contraindicated in patients hypersensitive to it or any SSRI, or receiving a monoamine oxidase inhibitor (MAOI) or cisap-ride. Use with caution in geriatric patients and those with hepatic impairme nt; dosages may need to be decreased or dosing interval increased. Adverse Effects Limited use of sertraline in dogs or cats makes it difﬁcult to com-pare its adverse effect proﬁle with other SSRIs (e. g., ﬂuoxetine, par-oxetine, ﬂuvoxamine). In dogs, SSRIs can cause lethargy, GI effects, anxiet y, 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 fe eding). Some dogs have persistent anorexia that precludes further treatment. Aggressive behavior in previously non-aggressive dogs has been reported. SSRI's in cats can cause sedation, decreased ap-petite/anorexia, vomiting, diarrhea, behavior changes (anxiety, ir-ritability, sleep disturbances), and changes in elimination patterns. Reproductive/Nursing Safety In humans, the FDA categorizes sertraline 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 and rabbits, sertraline was implicated in causing delayed ossiﬁcation. Sertraline decreased pup survival in rats exposed in utero. It is unknown if sertraline enters maternal milk. Overdosage/Acute Toxicity In overdoses, the SSRI's can cause vomiting, diarrhea, hypersaliva-tion, and lethargy. Serotonin syndrome may occur with signs that incl ude muscle tremors, rigidity, agitation, hyperthermia, vocaliza-tion, hypertension or hypotension, tachycardia, seizures, coma, and death. Human overdoses of as little of 2. 5 grams have caused death, but one patient survived after taking 13. 5 grams. There were 469 exposures to sertraline reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases 430 were dogs with 38 showing clinical signs and 37 were cats with 4 showing clinical signs. The remaining 2 cases were a bird and an unknown species that showed no clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included lethargy, hyperactivity, tachycardia, agitation and mydria-sis. Common ﬁndings in cats recorded in decreasing frequency in-cluded mydriasis, agitation, anorexia and hallucinating. Management of sertraline overdoses should be handled aggres-sively with supportive and symptomatic treatment. Veterinarians are encouraged to contact an animal poison control center for fur-ther guidance. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sertraline and may be of signiﬁcance in veterinary patients: !TBUSPIRONE : Increased risk for serotonin syndrome !TCIMETIDINE : May increase sertraline levels !TCYPROHEPTA DINE: May decrease or reverse the effects of SSRIs !TDIAZEPAM : Sertraline may decrease diazepam clearance !TISONIAZID : Increased risk for serotonin syndrome !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 ser traline and a 2 week washout period is required if ﬁrst discon-tinuing the MAO inhibitor !TPENTAZOCINE : Serotonin syndrome-like adverse effects possible !TTRICYCLIC ANTIDEPRESSANTS (e. g., clomipramine, amitriptyline ): Ser-traline may increase TCA blood levels and may increase the risk fo r serotonin syndrome !TWARFARIN : Sertraline may increase the risk for bleeding Laboratory Considerations No signiﬁcant laboratory interactions or considerations were located. Doses !TDOGS: a) For treatment of compulsive disorders: 2-4 mg/kg PO once daily o r divided twice daily (Landsberg 2004) b) 1-2 mg/kg PO q24h (once daily) (allow 6-8 weeks for initial tr ial) (Virga 2005b) c) 1-3 mg/kg PO once daily. Plan is to use the drug for a limited time (3-6 months) during which time behavioral modiﬁca-tion is also employed. The animal should learn appropriate be havior in previously problematic situations. Then the ani-mal should be weaned off the medication over a 2 to 4 week pe riod by halving the dose weekly (Neilson 2002) d) For treatment of behavioral diagnoses: 0. 25-0. 5 mg/kg PO q24h (o nce a day). Note : must treat for 3-5 weeks minimum to assess effects; then treat until “well” until either has no signs associated with diagnosis or some low, consistent level (a minimum of another 1-2 months). Then treat for anoth-er 1-2 months (minimum), so that reliability of assessment is r easonably 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) e) For compulsive disorder, anxiety: 1-4 mg/kg PO q24h (once daily) (S eibert 2003) !TCATS: a) For treatment of compulsive disorders: 0. 5 mg/kg PO once daily (Landsb erg 2004) b) For urine marking (spraying), aggression, anxiety—includ-ing anxiogenic house soiling, phobias, fears: 0. 5-1 mg/kg PO q24h (onc e daily) (Virga 2002) c) For treatment of behavioral diagnoses: 1 mg/kg PO q24h (onc e a day). Note : must treat for 3-5 weeks minimum to assess effects; then treat until “well” until either has no signs associated with diagnosis or some low, consistent level (a minimum of another 1-2 months). Then 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)	pppbs.pdf
d) For treatment of fear, affective or dominance aggression: 0. 5-1 mg/kg PO once daily (Crowell-Davis 2003b), (Crow-ell-Davis 2003a) e) For treatment of compulsive disorder, anxiety: 0. 5-1 mg/kg PO q24h (once daily) (S eibert 2003) Monitoring T ! Efﬁcacy T ! Adverse Effects; including appetite (weight) T ! Consider doing baseline liver function tests and ECG; re-test as needed Client Information T ! Because there has not as yet been widespread use of sertraline in dogs or cats, its adverse effect and efﬁcacy proﬁles have not been yet fully determined; clients should report any signiﬁcant abnor-mal ﬁndings to the veterinarian. T ! Clients should understand that this drug is unlikely to have an immediate effect (or even in the short-term) and must commit to using the drug for months to determine efﬁcacy Chemistry/Synonyms A selective serotonin reuptake inhibitor, sertraline hydrochloride is a white crystalline powder that is slightly soluble in water and isopropyl alcohol; sparingly soluble in ethanol. The commercially available oral solution contains 12% ethanol and has a menthol scent. Sertraline may also be known as: CP-51974-01; CP-51974-1; Altruline ®, Anilar®, Aremis®, Atenix®, Besitran®, Bicromil®, Gladem®, Insertec®, Irradial®, Lustral®, Novativ®, Sealdin®, Serad®, Sercerin®, Serlain®, Serta®, Tatig®, Tolrest®, Tresleen® or Zoloft®. Storage/Stability Store commercially available sertraline tablets and oral solution at controlled room temperature (25°C; 77°F); excursions permitted to 15-30°C (59-86°F). The manufacturer states to dilute the oral so-lution only in the following liquids: water, orange juice, ginger ale, lemonad e or lemon/lime soda; use immediately after dilution. 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: Sertraline HCl Tablets: 25 mg, 50 mg & 100 mg (as base); Zoloft® (Pﬁzer); generic; (Rx) Sertraline HCl Oral Concentrate: 20 mg/m L in 60 m L; Zoloft ® (Pﬁz-er); (Rx) SEVELAMER HCL (se-vel-a-mer) Renagel® PHOSPHORUS BINDING AGENT Prescriber Highlights TT Phosphorus binding agent (in the gut) for hyperphos-phatemia associated with chronic renal failure TT May be useful if patient cannot tolerate aluminum salts or aluminum salts are commercially unavailable TT Expensive when compared to aluminum hydroxide or cal-cium carbonate products TT Drug-drug interactions including nutrients Uses/Indications Sevalamer may be useful for treating hyperphosphatemia associ-ated with chronic renal failure, particularly when oral aluminum salts are not toler ated. Pharmacology/Actions Sevelamer binds phosphorus in the gut; when combined with de-creased phosphorus in the diet it can substantially reduce serum phosphor us levels. It also reduces serum low-density lipoproteins and total cholesterol. Pharmacokinetics Sevelamer is administered orally, but is not absorbed systemically. Contraindications/Precautions/Warnings Sevelamer is contraindicated in patients with hypophosphatemia, or bowel obstruction and in patients hypersensitive to it. Adverse Effects Adverse effects in humans are reported to be the same as placebo. Potentially some GI effects occur. As oral vitamin absorption may be reduced by sevalamer, con-sider the addition of vitamin supplementation during therapy. Reproductive/Nursing Safety Safety during pregnancy is not established; because of the potential for binding vitamins, additional vitamins (both fat and water sol-uble) may be necessary. In humans, the FDA categorizes this drug as categ ory 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. ) There are no adequate and well-controlled studies in nursing mothers. Overdosage/Acute Toxicity As sevalamer is not absorbed, acute toxicity potential appears to be negligible. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sevalamer and may be of signiﬁcance in veterinary patients: T ! ANTICONVU LSANTS (oral): Sevelamer may reduce oral absorption; give at least one hour before or three hours after sevalamer capsules	pppbs.pdf
T ! ANTIARRHYTHMICS (oral): Sevelamer may reduce oral absorp-tion; give at least one hour before or three hours after sevalamer capsules T ! CIPROFLOXACIN : Concurrent administration with sevelamer may decrease absorption by 50%; administer ciproﬂoxacin and other oral ﬂuoroquinolones at least one hour before or 3 hours after, sevelamer T ! ORAL MEDICATIONS : There are only a few medications having doc-umented reductions in oral administration when administered with sev elamer; consider dosing other oral drugs separately, par-ticularly for drugs with narrow therapeutic indexes T ! VITAMINS : Sevelamer may reduce vitamin absorption from food; consider administering vitamin supplements separately from sevelamer dose Doses T ! DOGS: a) For medium to large sized dog: 400 mg PO with meals (Vaden 2007) T ! CATS: a) Has been used at 200 mg 2-3 times daily. Anecdotally ap-pears to be safe and effective. (Sparkes 2006a) Monitoring T ! Serum phosphorus (and other electrolytes calcium, bicarbonate, chloride) T ! Consider a baseline coagulation screening test before and after sevalamer therapy implementation as vitamin K absorption may be impacted by the drug Chemistry/Synonyms A phosphorus binding agent, sevalamer HCl is a complex chemical that is hydrophilic, but insoluble in water. Sevelamer may also be known as GT16-026A and Renagel®. Storage/Stability Sevelamer capsules should be stored at room temperature and pro-tected from moisture. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Sevalamer HCl Tablets: 400 mg and 800 mg (on an anhydrous basis); Renagel® (Genzyme); (Rx) SEVOFLURANE (see-voe-ﬂoo-rane) Sevo Flo®, Ultane® INHALATIONAL ANESTHETIC Prescriber Highlights TT Inhalational anesthetic similar to isoﬂurane, but with more rapid induction & recovery TT Currently more expensive than isoﬂurane Uses/Indications Sevoﬂurane may be useful in a variety of species when rapid in-duction and/or rapid recoveries are desired with an inhalational anesthetic. 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. Sevoﬂurane has a very low blood:gas par-tition coefﬁcient (0. 6) allowing very rapid anesthesia induction and reco very. Rapid mask induction is possible. Pharmacologic effects of sevoﬂurane are similar to isoﬂurane and includ e: CNS depression, depression of body temperature reg-ulating centers, increased cerebral blood ﬂow, respiratory depres-sion, hypotension, vasodilatation, myocardial depression (less so than with halothane), and muscular r elaxation. Minimal Alveolar Concentration (MAC; %) in oxygen reported for se voﬂurane in various species: Dog = 2. 09-2. 4; Cat = 2. 58; Horse = 2. 31; Sheep = 3. 3; Swine = 1. 97-2. 66; Human (adult) = 1. 71-2. 05. Several factors may alter MAC (acid/base status, tem-perature, other CNS depressants on board, age, ongoing acute dis-ease, etc. ). Pharmacokinetics Because of its low solubility in blood, only small concentrations of sevoﬂurane in the blood are required to be dissolved in blood be-fore alveolar partial pressures are in equilibrium with arterial par-tial pressures. This low solubility means that sevoﬂurane is rapidly remov ed from the lungs. It is unknown what percent sevoﬂurane is bound to plasma proteins. The majority of sevoﬂurane is excreted via the lungs, but about 3% is metabolized in the liver via the cyto-chrome P450 2E1 isoenzyme system. Contraindications/Precautions/Warnings Sevoﬂurane 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 renal insufﬁciency. Because of its rapid action, use caution not to overdose during the induct ion phase. Because of the rapid recovery associated with sevoﬂurane use caution (and appropriate sedation during the re-covery phase), particularly with large animals. Geriatric animals may require less inhalation anesthetic. Sevoﬂurane does not appear to be a good inhalational anesthetic in rabbits (b reath holding, struggling). Adverse Effects Sevoﬂurane seems to be well tolerated. Hypotension may occur and is considered dose related. Dose-dependent respiratory depression and GI effects (nausea, vomiting, ileus) have been reported. While cardiodepression generally is minimal at doses causing surgical planes of anesthesia, it may occur; bradycardia is possible. Malignant hyperthermia may be triggered by this agent (like other inhalational anesthe tics). Sevoﬂurane can react with carbon dioxide absorbents to pro-duce “compound A ”, a nephrotoxin. After extensive clinical use in humans how ever, nephrotoxicity has not been demonstrated to be of clinical concern. Sevoﬂurane should be used in precision, agent-speciﬁc, out of circuit vapo rizers. Reproductive/Nursing Safety No overt fetotoxicity or teratogenicity has been demonstrated in lab animal studies, but deﬁnite safety has not been established for use during pregnancy.	pppbs.pdf
Overdosage/Acute Toxicity In the event of an overdosage, discontinue sevoﬂurane; maintain airway and support respiratory and cardiac function as necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sevoﬂurane and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES, LINCOSAMIDES : May enhance neuromuscular blockade !TBARBITURATES (phenobarbital, pentobarbital, etc. ): May increase concentrations of inorganic ﬂuoride !TISONIAZID : May increase concentrations of inorganic ﬂuoride !TMIDAZOLAM : May potentiate sevoﬂurane effects; decrease MAC !TNON-DEPOLARIZING NEUROMUSCULAR B LOCKING A GENTS (atracurium, pancuronium, vecuronium ): Additive neuromuscular blockade may occur !TOPIATES : May potentiate sevoﬂurane effects; decrease MAC !TST. JOHNS WORT : Increased risk for anesthetic complications; recommend discontinuing St. John's Wort 5 days in advance of surgery !TSUCCINYLCHOLINE : Sevoﬂurane may enhance effects !TSYMP ATHOMIMETICS (dopamine, epinephrine, norepinephrine, ephed-rine, metaraminol, etc. ): While sevoﬂurane sensitizes the myocar-dium to the effects of sympathomimetics less so than halothane, arr hythmias may still result; caution and monitoring is advised !TVERAPAMIL : May cause cardiodepression Laboratory Considerations !TInhalational anesthetics may cause transient increases in liver function tests, WBCs, and glucose Doses Minimal Alveolar Concentration (MAC; %) in oxygen reported for sevoﬂurane in various species: Dog = 2. 09-2. 4; Cat = 2. 58; Horse = 2. 31; Sheep = 3. 3; Swine = 1. 97-2. 66; Human (adult) = 1. 71-2. 05. Several factors may alter MAC (acid/base status, temperature, other CNS depressants on board, age, ongoing acute disease, etc. ) !TDOGS: Inspired Concentration: The delivered concentration of Sevo-Flo® (sevoﬂurane) should be known. Since the depth of an-esthesia may be altered easily and rapidly, only vaporizers pr oducing predictable percentage concentrations of sevoﬂu-rane should be used. Sevoﬂurane should be vaporized using a p recision vaporizer speciﬁcally calibrated for sevoﬂurane. Sevoﬂurane contains no stabilizer. Nothing in the drug prod-uct alters calibration or operation of these vaporizers. The administ ration of general anesthesia must be individualized based on the patient's response. When using sevoﬂurane, pa-tients should be continuously monitored and facilities for mainte-nance of patient airway, artiﬁcial ventilation, and oxygen supple-mentation must be immediately available. Replacement of Desiccated CO2 Absorbents: When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. An exothermic reaction occurs when sevoﬂu-rane is exposed to CO2 absorbents. This reaction is increased whe n the CO2 absorbent becomes desiccated. Premedication : No speciﬁc premedication is either indicated or contraindicated with sevoﬂurane. The necessity for and choice of premedication is left to the discretion of the veteri-narian. Preanesthetic doses for premedicants may be lower than the labe l directions for their use as a single medication. Induction : For mask induction using sevoﬂurane, inspired concentrations up to 7% sevoﬂurane with oxygen are em-ployed to induce surgical anesthesia in the healthy dog. These concentrations can be expected to produce surgical anesthesia in 3 to 14 minutes. Due to the rapid and dose depen-dent changes in anesthetic depth, care should be taken to prevent overdosing. Respiration must be monitored closely in the dog and supported when necessary with supplemental oxygen and/or as-sisted ventilation. Maintenance : Sevo Flo® may be used for maintenance anes-thesia following mask induction using sevoﬂurane or fol-lowing injectable induction agents. The concentration of vap or necessary to maintain anesthesia is much less than that required to induce it. Surgical levels of anesthesia in the healthy dog may be maintained with inhaled concentrations of 3. 7-4% sevoﬂurane in oxygen in the absence of premedi-cation and 3. 3-3. 6% in the presence of premedication. The use o f injectable induction agents without premedication has little effect on the concentrations of sevoﬂurane required for maintenance. Anesthetic regimens that include opioid, alpha2-agonist benzodiazepine or phenothiazine premedi-cation will allow the use of lower sevoﬂurane maintenance co ncentrations. (Label directions; Sevo Flo®—Abbott Animal Health) Monitoring !TRespiratory and ventilatory status !TCardiac rate/rhythm; blood pressure (particularly with “at risk” patients !TLevel of anesthesia Chemistry/Synonyms Sevoﬂurane is an isopropyl ether inhalational anesthetic with a mo-lecular wt. of 200, saturate vapor pressure at 20°C of 160 mm Hg and a boiling pt. of 58. 5°C. It is reported to have a pleasant odor and is not irritating to airways. It is non-ﬂammable and non-explosive. Sevoﬂurane is a clear, colorless liquid that is miscible with ethanol or ether and slightly soluble in water. Se voﬂurane may also be known as: BAX-3084, MR-654, Sevocris®, Sevo Flo®, Se vorane®, or Ultane®. Storage/Stability Sevoﬂurane should be stored at room temperature. Sevoﬂurane does not react with metal. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Sevoﬂurane in 250 m L btls; Sevo Flo® (Abbott); (Rx). Approved for use in dogs. HUMAN-LABELED PRODUCTS: Sevoﬂurane in 250 m L btls; Ultane® (Abbott); (Rx)	pppbs.pdf
SILDENAFIL CITRATE (sil-den-ah-ﬁl) Viagra®, Revatio® V ASODILATOR; PHOSPHODIESTERASE TYPE 5 INHIBITOR Prescriber Highlights TT Used in veterinary medicine for treating pulmonary hypertension TT Contraindicated if patients receiving organic nitrates TT Adverse effects not well-known; inguinal ﬂushing, pos-sible GI effects reported TT Treatment may be very expensive Uses/Indications Sildenaﬁl may be of beneﬁt in the adjunctive treatment of pulmo-nary hypertension in small animals. In humans, sildenaﬁl is indicated for erectile dysfunction or pul-monary hypertension. Pharmacology/Actions Sildenaﬁl inhibits cyclic guanosine monophosphate (c GMP) spe-ciﬁc phosphodiesterase type-5 (PDE5) found in the smooth muscle of the pulmo nary vasculature, corpus cavernosum and elsewhere, where PDE5 is responsible for degradation of c GMP. Sildenaﬁl in-creases c GMP thereby resulting in nitric oxide mediated vasodilata-tion within pulmonary vascular smooth muscle cells. Pharmacokinetics The pharmacokinetics of sildenaﬁl has been reported in dogs (Walker, Ackland et al. 1999). Oral bioavailability is approximately 50% (higher than humans); volume of distribution is about 5. 2 L/ kg (versus 1. 2 L/kg in humans); elimination half-life approximately 6 hours (signiﬁcant interpatient variability; average human half life is about 4 hours). Contraindications/Precautions/Warnings Sildenaﬁl should not be used concurrently with nitrates (see drug interactions) or in patients documented hypersensitive to it. Pulmonary vasodilators may signiﬁcantly worsen the cardio-vascular status of patients with pulmonary veno-occlusive disease (PVOD). Use w ith extreme caution in patients with resting hypotension, ﬂuid deple tion, severe left ventricular outﬂow obstruction, or auto-nomic dysfunction. Adverse Effects Because of limited use in dogs, the adverse effect proﬁle is not fully known. Cutaneous ﬂushing of the inguinal region has been report-ed and GI effects are possible. In humans, headache, visual distur-bances, dyspepsia, nasal congestion, myalgia, priapism, dizziness, and back pain hav e been reported. Reproductive/Nursing Safety No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in pregnant rats or rabbits, dosed at 200 mg/kg/day dur-ing organogenesis. In a rat pre-and postnatal development study, the no-obser ved-adverse-effect dose was 30 mg/kg/day. In humans, the FDA categorizes this drug as category B for use during preg-nancy (Animal studies have not yet demonstrated risk to the fetus, but there ar e no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have no t demonstrated a risk to the fetus in the ﬁrst trimester of preg-nancy, and there is no evidence of risk in later trimesters. ) It is not known if sildenaﬁl or its metabolites are excreted in milk. Overdosage/Acute Toxicity Little information is available. An adult women ingested 2000 mg and survived but developed tachycardia, nonspeciﬁc ST-T changes on ECG, headache, dizziness, and ﬂushing. It is expected that overdoses in animals would mirror the drugs adve rse effect proﬁle; treat supportively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sildenaﬁl and may be of signiﬁcance in veterinary patients: T ! ALPHA-ADRENERGIC BLOCKERS (e. g., phentolamine, phenothiazines, phenoxybenzamine ): May increase hypotensive effects T ! AMLODIPINE : Potential to increase hypotensive effects T ! ANTIHYPERTENSIVE, HYPOTENSIVE DRUGS : Potentially could increase hypotensive effects T ! AZOLE ANTIFUNGALS (ketoconazole, itraconazole ): May reduce sildenaﬁl metabolism and increase AUC T ! CIMETIDINE : May reduce sildenaﬁl metabolism and increase AUC T ! ERYTHROMYCIN, CLARITHROMYCIN : May reduce sildenaﬁl metabo-lism and increase AUC T ! HEPARIN : May increase bleeding risks T ! NITRATES (e. g., NTG, Isosorbide ): Signiﬁcant potentiation of vaso-dilatory effects; life-threatening hypotension possible T ! NITROPRUSSIDE SODIUM : Signiﬁcant potentiation of vasodilatory effects; life-threatening hypotension possible T ! PHENOBARBITAL : May decrease sildenaﬁl concentrations T ! RIFAMPIN : May decrease sildenaﬁl concentrations Laboratory Considerations None were noted. Doses T ! DOGS/CAT S: Dogs: From a retrospective study: median dose was 1. 9 mg/kg (range from 0. 5-2. 7 mg/kg) q8-24h. Dogs may have been also treated with oxygen, ACE inhibitors, furosemide, amlodipine, diltiazem, theophylline, phenobarbital and/or antibiotics. (Bach, Rozanski et al. 2006) For pulmonary hypertension documented by Doppler, chronic pulmonary disease, right-sided heart failure (HW disease; con-genital): 0. 5-1 mg/kg PO two times daily (higher dose of 2-3 mg/kg three times a day may be tolerated and needed) (Tilley 2007) Monitoring T ! Clinical efﬁcacy (improved syncope, cough, respiratory effort) T ! Pulmonary artery pressure, systemic blood pressure Client Information T ! Brief clients on the experimental nature of using this medication in small animals and the costs of therapy Chemistry/Synonyms Sildenaﬁl citrate occurs as a white to off-white crystalline powder with a solubility of 3. 5 mg/m L in water and a molecular weight of 666. 7.	pppbs.pdf
Sildenaﬁl may also be known as UK 92480, UK 92480-10, Aphrodil®, Revatio®, or Viagra®. Storage/Stability Sildenaﬁl tablets should be stored at room temperature (25°C; 77°F); excursions permitted to 15-30°C (59-86°F). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Sildenaﬁl Citrate Tablets: 20 mg (of sildenaﬁl); Revatio® (Pﬁzer); (Rx) Sildenaﬁl Citrate Tablets: 25 mg, 50 mg & 100 mg (of sildenaﬁl); Via-gra® (Pﬁz er); (Rx) SILYMARIN MILK THISTLE (sill-e-mar-in) Marin® NUTRACEUTICAL HEPATO-PROTECTANT Prescriber Highlights TT Nutraceutical that may be useful for treatment of chronic & acute liver disease, cirrhosis; as a hepato-protective agent when hepatotoxins (e. g., Aminita phalloide) in-gested TT Appears well-tolerated; potentially could cause GI effects TT Do not confuse Milk Thistle with Blessed Thistle TT Potential drug interactions Uses/Indications While controlled studies demonstrating efﬁcacy and a standardized form and concentration of silymarin are lacking, it is being used to treat a variety of liver diseases in humans and domestic companion animals (birds, dogs, cats, horses, rabbits). It is mostly of interest in treating chronic and acute liver disease, cirrhosis, and as a hepato-protective agent when hepatotoxic agents are ingested (e. g., Aminita phalloide; “Death Cap Mushrooms”). Pharmacology/Actions Silymarin has a variety of pharmacologic actions that may contrib-ute to its apparent effects in treating liver disease. It inhibits lipid pero xidase and beta-glucoronidase and acts as an anti-oxidant and free radical scavenger. Silymarin also inhibits the cytotoxic, inﬂam-matory, and apoptotic effects of tumor necrosis factor (TFN). It apparentl y can alter outer hepatocyte cell membranes that can pre-vent toxin penetration. Silymarin is thought to reduce hepatic col-lagen formation and increase hepatic glutathione content. Pharmacokinetics In humans, silymarin has an oral bioavailability of less than 50% and peak levels occur 2-4 hours post-dose. When silibinin (sily-bin, sylibin) is complexed with phosphatidylcholine, oral absorp-tion can be increased. The drug undergoes extensive enterohepatic circulation and has signiﬁcantly higher concentrations in liver cells and bile than in plasma. Elimination half-life in humans averages 6 hours. The majority of the drug is eliminated unchanged in the feces, but 20-40% is converted into glucuronide and sulfate con-jugates which are eliminated in the feces; only about 8% is excreted in the urine. Contraindications/Precautions/Warnings There are no reported absolute contraindications to silymarin in animals. Extracts from the plant parts of Milk Thistle (not the seeds which are used to make the extract silymarin), may possess estro-gen-like activity and should not be used in patients where exog-enous estrogens would be contraindicated. Adverse Effects Silymarin is apparently well tolerated when administered orally. In humans, GI disturbances have been reported on occasion (nausea to diarrhea). Patients who have allergies to other members of the Asteraceae/Compositae plant family (includes ragweed, marigolds, daisies, etc. ) may exhibit allergic reactions to Milk Thistle deriva-tives. Do not confuse Milk Thistle with Blessed Thistle. Reproductive/Nursing Safety Data on the safety of silymarin use during pregnancy or nursing is not available; its potential beneﬁt must be weighed against the uncertainty of its safety. Overdosage/Acute Toxicity Overdoses are unlikely to cause signiﬁcant morbidity. Gastrointestinal effects may be seen and treated in a supportive manner. Drug Interactions While no speciﬁc drug interactions have been reported, silymarin may inhibit cytochrome P450 isoenzyme 2C9 (CYP2C9). Drugs with narrow therapeutic indexes that are metabolized by this isoen-zyme should be used with caution when using silymarin. Drugs that could be affe cted include: warfarin, amitriptyline, verapamil, etc. Silymarin also may inhibit CYP3A4, but thus far this interaction does not appear to be clinically signiﬁcant. Silymarin may increase the clearance of drugs that undergo hepatic glucuronidation (not cats), including: acetaminophen, diazepam, morphine, and lamotrigine. Clinical signiﬁcance has not been determined for this interaction and the usefulness of silymarin for treating acetaminophen toxicity has not been determined. Laboratory Considerations No interactions with laboratory tests are reported. Doses T ! DOGS & CAT S: a) Therapeutic dosage is unknown, but suggested doses range from 50- 250 mg/day (Twedt 2004) b) For adjunctive therapy for chronic liver disease: 20-50 mg/ kg per day (extrapolated from human, monkey, rodent and dog research) (Center 2002) c) For chronic liver disease and ameliorating the effects of an-ticonvulsants: Dosages vary from 50-200 mg given every 12-24 hours ( Tams 2001) d) For hepatotoxicity, hepatic recovery/regeneration, hepatic ﬁ-brosis: 20-50 mg/kg/day. (Webb 2007b) e) Cats: 4-8 mg/kg/day (Zoran 2006b) Monitoring T ! Clinical efﬁcacy Client Information T ! Because silymarin experience in animals is limited, clients should understand the “investigational nature” of its use Chemistry/Synonyms Milk Thistle, the common name for Silybum marianum, has been used as a medicinal agent for at least two thousand years. The me-	pppbs.pdf
dicinal extract from the seeds of the plant is silymarin that contains the four ﬂavolignans: silichristin (sylichristin), isosilibinin, silydi-anin (silidianin), and the most biological active component, silibi-nin (sylibin, silybin, silibide). Milk Thistle extract contains approxi-mately 70% silymarin of which about 70% is silibinin. Silymarin is repo rtedly fairly insoluble in water. Silymarin or Milk thistle may also be known as Carduus mar i-anus, Holy Thistle, Legalon, or Marian Thistle. Blessed Thistle is a differe nt compound. Storage/Stability Unless otherwise labeled, commercially available products contain-ing silymarin should be stored at room temperature in tight con-tainers. Avoid storing the products in areas of high humidity. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Milk Thistle or silymarin is considered a nutritional supplement by the FDA. No standards have been accepted for potency, etc. by regula-tory bodies. Supplements are available from a wide variety of sources and dosage forms include tablets and capsules in a variety of concen-trations (150-1000 mg). When choosing a product it is recommend-ed to purchase ones that state the concentration (usually 70-80%) of silymarin c ontained in the product. Silybin A+B 9 mg (in a phosphatidylcholine complex) & Vitamin E 50 IU Tab lets: Marin® for Cats (Nutramax); Not considered a drug by the FDA. Silybin A+B 24 mg (in a phosphatidylcholine complex), Vitamin E 105 IU, & Zinc 17 mg Chewable Tablets: Marin® for Dogs (Nutra-max); Not considered a drug by the FDA. Labeled for use in small to medium dogs. Silybin A+B 70 mg (in a phosphatidylcholine complex), Vitamin E 300 IU, & Zinc 45 mg Chewable Tablets: Marin® for Dogs (Nutra-max); not considered a drug by the FDA. Labeled for use in large dogs. A combination product (Denamarin®, Nutramax) containing SAMe and silybin (sil ymarin) is also labeled for use in dogs and cats. HUMAN-LABELED PRODUCTS: None as pharmaceuticals SODIUM BICARBONATE (soe-dee-um bye-kar-boe-nate) Neut® ALKALINIZER Prescriber Highlights TT Alkalinizing agent used to treat metabolic acidosis & alkalinize urine; may be used adjunctively for hypercalce-mic or hyperkalemic crises TT Contraindications: Parenteral bicarbonate is generally contraindicated in patients with metabolic or respiratory alkalosis, excessive chloride loss secondary to vomiting or GI suction, at risk for development of diuretic-induced hypochloremic alkalosis, or with hypocalcemia where al-kalosis may induce tetany TT Extreme Caution: Hypocalcemia Caution: CHF, nephrotic syndrome, hypertension, oliguria or volume overload TT Adverse Effects: Especially with parenteral (high dose): metabolic alkalosis, hypokalemia, hypocalcemia, “over-shoot” alkalosis, hypernatremia, volume overload, con-gestive heart failure, shifts in the oxygen dissociation curve causing decreased tissue oxygenation, & paradoxi-cal CNS acidosis leading to respiratory arrest. If used dur-ing CPR: hypercapnia, if the patient is not well ventilated; patients may be predisposed to ventricular ﬁbrillation. TT Drug Interactions Uses/Indications Sodium bicarbonate is indicated to treat metabolic acidosis and al-kalinize the urine. It is also used as adjunctive therapy in treating hype rcalcemic or hyperkalemia crises. Pharmacology/Actions Bicarbonate ion is the conjugate base component of bicar-bonate:carbonic acid buffer, the principal extracellular buffer in the body. Contraindications/Precautions/Warnings Parenterally administered sodium bicarbonate is considered gener-ally contraindicated in patients with metabolic or respiratory alka-losis, excessive chloride loss secondary to vomiting or GI suction, at risk fo r development of diuretic-induced hypochloremic alkalosis, or with hypocalcemia where alkalosis may induce tetany. Use with extreme caution and give very slowly in patients with hypo calcemia. Because of the potential sodium load, use with cau-tion in patients with CHF, nephrotic syndrome, hypertension, olig-uria, or volume overload. Adverse Effects Sodium bicarbonate therapy (particularly high-dose parenteral use) can lead to metabolic alkalosis, hypokalemia, hypocalcemia, “overshoot” alkalosis, hypernatremia, volume overload, congestive heart failure, shifts in the oxygen dissociation curve causing de-creased tissue oxygenation, and paradoxical CNS acidosis leading to respirat ory arrest. When sodium bicarbonate is used during cardiopulmonary re-suscitation, hypercapnia may result if the patient is not well venti-lated; patients may be predisposed to ventricular ﬁbrillation. Oral and parenteral bicarbonate (especially at higher doses) may co ntribute signiﬁcant amounts of sodium and result in hyper-	pppbs.pdf
natremia and volume overload; use with caution in patients with CHF, or acute renal failure. Reproductive/Nursing Safety Reproductive safety studies have not been performed. Assess risk versus beneﬁt before using. Overdosage/Acute Toxicity Sodium bicarbonate can cause severe alkalosis, with irritability or tetany if overdosed or given too rapidly. Dosages should be thor-oughly checked and frequent monitoring of electrolyte and acid/ base status p erformed. Treatment may consist of simply discontinuing bicarbonate if alkalosis is mild or by using a rebreathing mask. Severe alkalosis may require intravenous calcium therapy. Sodium chloride or po-tassium chloride may be necessary if hypokalemia is present. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sodium bicarbonate and may be of signiﬁcance in veterinary patients: !TANTICHOLINERGIC AGENTS : Concomitant oral sodium bicarbonate may reduce absorption; administer separately !TAZOLE ANTIFUNGALS (ketoconazole, itraconazole ): Concomitant oral sodium bicarbonate may reduce absorption; administer separately !TCIPROFLOXACIN; ENROFLOXACIN : The solubility of ciproﬂoxacin and enroﬂoxacin is decreased in an alkaline environment; patients with alkaline urine should be monitored for signs of crystalluria !TCORTICOS TEROIDS: Patients receiving high dosages of sodium bicar-bonate and ACTH or glucocorticoids may develop hypernatremia !TDIURETICS (e. g., thiazides, furosemide ): Concurrent use of sodium bicarbonate in patients receiving potassium-wasting diuretics may cause hypochloremic alkalosis !TEPHEDRINE : When urine is alkalinized by sodium bicarbonate, ex-cretion may be decreased !THISTAMINE 2 BLOCKING A GENTS (e. g., cimetidine, ranitidine ): Con-comitant oral sodium bicarbonate may reduce absorption; ad-minister separately !TIRON PRODUCTS : Concomitant oral sodium bicarbonate may re-duce absorption; administer separately !TORAL MEDICATIONS : Because oral sodium bicarbonate can either increase or reduce the rate and/or extent of absorption of many orally administered drugs, it is recommended to avoid giving other drugs within 1-2 hours of sodium bicarbonate !TQUINIDINE : When urine is alkalinized by sodium bicarbonate, ex-cretion may be decreased !TSALICYLATES : When urine is alkalinized by sodium bicarbonate, excretion of weakly acidic drugs may be increased !TSUCRALFATE : Oral sodium bicarbonate may reduce the efﬁcacy of sucralfate if administered concurrently !TTETRACYCLINES : Concomitant oral sodium bicarbonate may re-duce absorption; administer separately Doses !TDOGS & CAT S: For severe metabolic acidosis: a) Main therapeutic goal should be to eliminate the underly-ing cause of acidosis. If causes are not readily reversible, arte-rial p H is <7. 2 (7. 1 if diabetic ketoacidosis), and ventilatory pr ocedures have not reduced acidemia, bicarbonate therapy should be considered. m Eq of bicarbonate required = 0. 5 x body weight in kgs. x (desired total CO 2 m Eq/L minus mea-sured total CO 2 m Eq/L). Give 1/2 of the calculated dose slowly over 3-4 hours IV. Recheck blood gases and assess the clinical status of the patient. Avoid over-alkalinization. (Schaer 1986) For adjunctive therapy of diabetic ketoacidosis: Note: Use of bicarb for this indication is somewhat controversial a) If plasma bicarbonate is ≤11 m Eq/L give bicarbonate thera-py. Dose (in m Eq) = body weight in kgs. x 0. 4 x (12-patient's bicar bonate) x 0. 5. Give above dose over 6 hours in IV ﬂuids and then recheck plasma bicarbonate or total venous CO2. If still ≤11 m Eq/L, recalculate dose and repeat therapy. (Nelson and Feldman 1988) For metabolic acidosis in acutely critical situations (cardiac ar-rest): a) 1 m Eq/kg IV initially, followed by 0. 5 m Eq/kg at 10-15 min-ute intervals during CPR (Moses 1988) b) Give none during the ﬁrst 5-10 minutes of arrest, then 0. 5 m Eq/kg every 5 minutes of cardiac arrest thereafter (Haskins 1989) For adjunctive treatment of hypercalcemic crisis: a) The m Eq of bicarbonate required = 0. 3 x body weight in kgs. x (d esired plasma bicarbonate m Eq/L-measured plasma bicarbonate m Eq/L); or 1 m Eq/kg IV every 10-15 minutes; maximum total dose: 4 m Eq/L (Kruger, Osborne, and Polzin 1986) For adjunctive therapy for hyperkalemic crises: a) If serum bicarbonate or total CO 2 is una vailable: 2-3 m Eq/ kg IV over 30 minutes if patient has decreased tissue perfu-sion or renal failure and does not have diabetic ketoacidosis. Must b e used judiciously. (Willard 1986) b) 1-2 m Eq/kg IV slowly (Macintire 2006a) Me tabolic acidosis secondary to renal failure: a) Dogs: Initial dose: 8-12 mg/kg PO q8h; adjust dosage to at-tain blood total CO 2 co ncentrations to 18-24 m Eq/L for re-nal failure. Although, inferior to monitoring total CO 2; ur ine p H may be used as a guideline for adjusting dosage. Urine p H should be between 6. 5-7. (Polzin and Osborne 1985) b) Initial dose: 8-12 mg/kg q8h; adjust dosage to attain blood total CO 2 c oncentrations to 18-24 m Eq/L (Allen 1989) c) 8-12 mg/kg PO q8-12h (Vaden 2007) T o alkaliniz e the urine: a) Dosage must be individualized to the patient. Initially give 10- 90 grains (650 mg-5. 85 grams) PO per day, depend-ing on the size of the patient and the pretreatment urine p H val ue. Goal of therapy is to maintain a urine p H of about 7; avoid p H >7. 5. (Osborne et al. 1989) b) For adjunctive therapy in dissolution and/or prevention of urat e urolithiasis in dogs: 0. 5-1 gram (1/8-1/4 tsp. ) per 5 kg of body weight three times daily PO. Goal of therapy is to attain a urine p H of from 7-7. 5. (Senior 1989) !THORSES: For metabolic acidosis: a) Associated with colic; if p H is <7. 3 and base deﬁcit is >10 m Eq/L estimate bicarbonate requirement using the formula: bicarbonate deﬁcit (HCO-3 m Eq) = base deﬁcit (m Eq/L) x 0. 4 x body weight (kg). May administer as a 5% sodium bi-carbonate solution. Each L of solution contains 600 m Eq of bicar bonate (hypertonic) and should not be administered any faster than 1-2 L/hr. Because acidotic horses with colic tend also to be dehydrated, may be preferable to give as iso-tonic sodium bicarbonate (150 m Eq/L). (Stover 1987)	pppbs.pdf
!TRUMINANTS: For acidosis: a) 2-5 m Eq/kg IV for a 4-8 hour period (Howard 1986) b) For severely dehydrated (10-16% dehydrated) acidotic calv es (usually comatose): Use isotonic sodium bicarbonate (156 m Eq/L). Most calves require about 2 liters of this so-lution given over 1-2 hours, then change to isotonic saline and so dium bicarbonate or a balanced electrolyte solution. Isotonic sodium bicarbonate may be made by dissolving 13 grams of sodium bicarbonate in 1 L of sterile water. Isotonic saline and sodium bicarbonate may be made by: mixing 1 L of isotonic saline with 1 L of isotonic sodium bicarbonate. (Radostits 1986) !TBIRDS: For metabolic acidosis: a) 1 m Eq/kg initially IV (then SC) for 15-30 minutes to a max-imum of 4 m Eq/kg (Clubb 1986) Monitoring !TAcid/base status !TSerum electrolytes !TUrine p H (if being used to alkalinize urine) Chemistry/Synonyms An alkalinizing agent, sodium bicarbonate occurs as a white, crys-talline powder having a slightly saline or alkaline taste. It is soluble in wat er and insoluble in alcohol. One gram of sodium bicarbonate contains about 12 m Eq each of sodium and bicarbonate; 84 mg of sodium bicarbonate contains 1 m Eq each of sodium and bicarbon-ate. A 1. 5% solution of sodium bicarbonate is approximately isoton-ic. An 8. 4% solution of sodium bicarbonate can be made isotonic by dil uting each m L with 4. 6 m L of sterile water for injection. Sodium Bicarbonate may also be known as: baking soda, E500, monoso dium carbonate, natrii bicarbonas, natrii hydrogenocarbo-nas, sal de vichy, sodium acid carbonate, Na HCO 3, so dium hydro-gen carbonate; many trade names are available. Storage/Stability/Compatibility Sodium bicarbonate tablets should be stored in tight containers, preferably at room temperature (15-30°C). Sodium bicarbonate injection should be stored at temperatures less than 40°C and pref-erably at room temperature; avoid freezing. Sodium bicarbonate powder is stable in dry air, but will slowly de compose upon exposure to moist air. Sodium bicarbonate is reportedly physically compatible with the following intravenous solutions and drugs: Dextrose in water, dextrose/saline combinations, dextrose-Ringer's combinations, sodium chloride injections, amikacin sulfate, aminophylline, amo-barbital sodium, amphotericin B, atropine sulfate, bretylium tosy-late, carbenicillin disodium, cefoxitin sodium, cephalothin sodium, ce phapirin sodium, chloramphenicol sodium succinate, chlorothi-azide sodium, cimetidine HCl, clindamycin phosphate, ergonovine maleate, erythromycin gluceptate/lactobionate, Innovar®, heparin sodium, hyaluronidase, hydrocortisone sodium succinate, kana-mycin sulfate, lidocaine HCl, metaraminol bitartrate, methotrex-ate sodium, methyldopate HCl, nafcillin sodium, netilmicin sulfate, oxa cillin sodium, oxytocin, phenobarbital sodium, phenyleph-rine HCl, phenytoin sodium, phytonadione, potassium chloride, pr ochlorperazine edisylate, and sodium iodide. Sodium bicarbonate compatibility information conﬂicts or is depen-dent on diluent or concentration factors with the following drugs or solutions: lactated Ringer's injection, Ringer's injection, sodium lactate 1/6 M, ampicillin sodium, calcium chloride/gluconate, me-thicillin sodium, penicillin G potassium, pentobarbital sodium, promazine HCl, thiopental sodium, vancomycin HCl, verapamil HCl, and vitamin B-complex with C. Consult specialized references or a hospital pharmacist for more speciﬁc information. Sodium bicarbonate is reportedly physically incompatible with the following solutions or drugs: alcohol 5%/dextrose 5%, D 5 lac-tated Ringer's, amrinone lactate, ascorbic acid injection, carmus-tine, cisplatin, codeine phosphate, corticotropin, dobutamine HCl, epine phrine HCl, glycopyrrolate, hydromorphone HCl, imipenem-cilastatin, regular insulin, isoproterenol HCl, labetolol HCl, levor-phanol bitartrate, magnesium sulfate, meperidine HCl, methadone HCl, metoclopramide HCl, norepinephrine bitartrate, oxytetracy-cline HCl, pentazocine lactate, procaine HCl, secobarbital sodium, str eptomycin sulfate, succinylcholine chloride, tetracycline HCl. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Sodium Bicarbonate Injection: 8. 4% (1 m Eq/m L) in 50 m L (50 m Eq/ vial), 100 m L (100 m Eq/vial) and 500 m L (500 m Eq/vial) vials; avail-able generically labeled; (Rx) HUMAN-LABELED PRODUCTS: Injectable Products: Sodium Bicarbonate Neutralizing Additive Solution: 4% (0. 48 m Eq/ m L) in 5 m L (2. 4 m Eq) vials; 4. 2% (0. 5 m Eq/m L) in 5 m L ﬁll in 6 m L vials (2. 5 m Eq); Neut® (Abbott); Sodium Bicarbonate (American Pharmaceutical Partners); (Rx) Sodium Bicarbonate Injection: 4. 2% (0. 5 m Eq/m L) in 10 m L (5 m Eq) syringes, 10 m L (5 m Eq) Bristoject syringes; generic, (Hospira, American Pharmaceutical Partners); (Rx) Sodium Bicarbonate Injection: 5% (0. 6 m Eq/m L) in 500 m L vials (297. 5 m Eq); generic, (Hospira, Baxter, Mc Gaw); (Rx) Sodium Bicarbonate Injection: 7. 5% (0. 9 m Eq/m L) in 50 m L (44. 6 m Eq) amps, syringes, vials, Bristoject syringes and 200 m L (179 m Eq) Maxi Vials; generic (Hospira, American Regent, American Pharma-ceutical Partners); (Rx) Sodium Bicarbonate Injection: 8. 4% (1 m Eq/m L) in 10 m L (10 m Eq) and 50 m L (50 m Eq) syringes and 50 m L vials (50 m Eq/vial); generic (Hospira, American Regent, American Pharmaceutical Partners); (Rx) Oral Products: Tablets: 325 mg & 650 mg; (1 g sodium bicarbonate provides 11. 9 m Mol sodium and 11. 9 m Mol bicarbonate); generic; (OTC) Powder: 120 g, 300 g & 1 lb; generic; (OTC) Omeprazole/Sodium Bicarbonate Capsules (immediate re-lease): 20 mg omeprazole/1,100 mg sodium bicarbonate) & 40 mg ome prazole/1,100 mg sodium bicarbonate; Zegerid® (Santarus); (Rx) Omeprazole/Sodium Bicarbonate Powder for Oral Suspension: 20 mg ome prazole/1,680 mg sodium bicarbonate & 40 mg omeprazole/1,680 mg sodium bicarbonate; Zegerid® (Santarus); (Rx) Sodium Bromide—see Bromides Sodium Chloride Injections—see the Intravenous Fluids section in the appendix Sodium Citrate— see Citrate Salts Sodium Hyaluronate—see Hyaluronate Sodium Sodium Iodide—see Iodide, Sodium Sodium Nitroprusside —See Nitroprusside Sodium Sodium Phosphate—see Phosphate, Parenteral	pppbs.pdf
SODIUM POLYSTYRENE SULFONATE (soe-dee-um pol-ee-stye-reen sulf-foe-nate) Kayexalate®, SPS CATIONIC EXCHANGE RESIN (HYPERKALEMIA) Prescriber Highlights TT Cation exchange resin used to treat hyperkalemia TT Contraindications: Patients who cannot tolerate a large sodium load TT Cause of hyperkalemia must be addressed TT Adverse Effects: Constipation, anorexia, vomiting, or nausea. Overdosage/overuse may lead to hypokalemia, hypocalcemia & hypomagnesemia. TT If given PO, often mixed with sorbitol to expedite removal of resin (& potassium) TT Drug Interactions Uses/Indications SPS is indicated as adjunctive treatment of hyperkalemia. The cause of the hyperkalemia should be elucidated and corrected if possible. Pharmacology/Actions SPS is a resin that exchanges sodium for other cations. After be-ing given orally, hydrogen ions will be exchanged for sodium (in an acidic e nvironment). As the resin travels through the intestinal tract, the hydrogen ions will be exchanged with other more concen-trated cations. Primary exchange with potassium occurs predomi-nantly in the large intestine. When given as a retention enema, SPS gener ally exchanges sodium for potassium directly in the colorec-tum. While theoretically, up to 3. 1 m Eq of potassium could be ex-changed per gram of SPS, it is unlikely that more than one m Eq will be exc hanged per gram of resin administered. Pharmacokinetics SPS is not absorbed from the GI tract. Its onset of action may be from hours to days; so severe hyperkalemia may require other treat-ments (e. g., dialysis) in the interim. Contraindications/Precautions/Warnings Because large quantities of sodium may be released and absorbed, patients on severely restricted sodium diets (severe CHF, hyperten-sion, oliguria) may beneﬁt from alternative methods of treatment. Over dosage/overuse may lead to hypokalemia, hypocalcemia and hypomagnesemia. Adverse Effects Large doses may cause constipation (fecal impactions have been re-ported rarely), anorexia, vomiting or nausea. Dose related hypocal-cemia, hypokalemia and sodium retention have also been noted. T o hasten the drug's action and prevent constipation, SPS is generally mixed with 70% sorbitol (3-4 m L per one gram of resin) when dosed orally. Reproductive/Nursing Safety While reproductive studies have apparently not been performed, it is unlikely the drug carries much teratogenic potential. 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 ther e are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) As SPS is not absorbed, it should be safe to use during nursing. Overdosage/Acute Toxicity Overdosage may cause the adverse effects noted (above); treat symptomatically. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving SPS and may be of sig-niﬁcance in veterinary patients: T ! ANTACIDS, LAXATIVES (calcium-or magnesium-containing ): SPS may bind with magnesium or calcium found in laxatives (milk of magnesia, magnesium sulfate, etc. ) or antacids which can prevent bicarbonate ion neutralization and lead to metabolic alkalosis. Concurrent use is not recommended during SPS therapy. Doses If dosed orally, to hasten the drug's action and to prevent constipa-tion SPS is generally mixed with 70% sorbitol (3-4 m L per one gram of resin); shake well before using. T ! DOGS: a) For hyperkalemia: 2 grams of resin/kg of body weight (each gram should be suspended in 3-4 m L of water; or use com-mercially prepared suspension products) divided into 3 daily doses. If given orally, give with a cathartic. Do not use a ca-thartic if using as a retention enema as it must be in the colon for at least 30 minutes. T o prepare a retention enema from the powder: add 15 grams per 100 m L of a 1% methylcel-lulose solution or 10% dextrose. If hyperkalemia is severe: 3-4 t imes the normal amount of resin may be given. (Wil-lard 1986) b) For mild hyperkalemia (<6 m Eq/L): 2 grams/kg PO in 3-4 divide d doses with 20% sorbitol; may also be give as an en-ema without sorbitol. (Cowgill and Francey 2005) T ! HORSES: a) For life-threatening hyperkalemia in neonatal foals: 15 grams of resin in 100 m L of 10% dextrose via enema. Monitor se-rum potassium and sodium closely. (Madigan 2002b) Monitoring T ! Serum electrolytes (sodium potassium (at least once a day), cal-cium, magnesium T ! Acid/base status, ECG, if warranted Chemistry/Synonyms A sulfonated cation exchange resin, sodium polystyrene sulfonate (SPS) occurs as a golden brown, ﬁne powder. It is odorless and tasteless. Each gram contains 4. 1 m Eq of sodium and has an in vitro exchange capacity of about 3. 1 m Eq of potassium (in actuality a maximum of 1 m Eq is usually exchanged). Sodium Polystyrene Sulfonate may also be known as: natrii poly-styrenesulfonas, sodium polystyrene sulphonate, Elutit-Natr ium®, K-Exit®, Kayexalate®, Kexelate®, Kionex®, Resinsodio®, Resonium®, Resonium A®, or SPS®. Storage/Stability Store products in well-closed containers at room temperature; do not heat. Suspensions made from powder should be freshly pre-pared and used within 24 hours.	pppbs.pdf
Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Sodium Polystyrene Sulfonate Powder: Sodium content is approxi-mately 100 mg (4. 1 m Eq) per g; in 1 lb. jars & 454 g; Kaye xalate® (Sanoﬁ Winthrop); Kionex® (Paddock); (Rx) Sodium Polystyrene Sulfonate Suspension: 15 g/60 m L (sodium 1. 5 g, 65 m Eq) in 60 m L, 120 m L, 200 m L, 480 m L, 500 m L and UD 60 m L; SPS® (Carolina Medical Products Co); generic; (Roxane); (Rx) SODIUM STIBOGLUCONATE SODIUM ANTIMONY GLUCONATE (sti-boe-gloo-koe-nate; an-ti-moe-nee gloo-koe-nate) Pentostam® ANTILEISHMANIAL Prescriber Highlights TT Antimony compound for treatment of leishmaniasis in humans & dogs TT Not commercially available in USA (CDC distributes) TT Contraindicated in renal failure, pre-existing arrhythmias TT Many potential adverse effects, including some very serious Uses/Indications Sodium stibogluconate is used for the treatment of leishmaniasis in dogs. Pharmacology/Actions Sodium stibogluconate's exact mode of action is unknown. It is believed that it may reduce ATP and GTP synthesis in susceptible amistigotes. Pharmacokinetics In dogs, stibogluconate's volume of distribution (steady-state) was 0. 25 L/kg, clearance 1. 71 L/kg/hr, and terminal half-life ranged from 0. 6 -1. 5 hours. The main route of excretion is via the kidneys; glomerular ﬁltration rate determines excretion rate. Contraindications/Precautions/Warnings Stibogluconate is contraindicated in patients with pre-existing car-diac arrhythmias, or signiﬁcantly impaired renal function. It should not be use d in those that have had a serious adverse reaction to a previous dose. Adverse Effects Dogs given 40 mg/kg of stibogluconate developed increased AST levels. Other reported adverse effects (incidence unknown) include pain on injection, musculoskeletal pain, hemolytic anemia, leuko-penia, vomiting, diarrhea, pancreatitis, myocardial injury and ar-rhythmias, renal toxicity, shock and sudden death. Intravenous ad-ministration can cause thrombophlebitis. Reportedly, the incidence of ad verse effects increases if the drug is administered for longer than 2 months. Reproductive/Nursing Safety Sodium stibogluconate has not been shown to cause fetal harm, but the manufacturer states that the drug should be withheld during pregnancy unless the beneﬁts outweigh the risks. The use of this drug during nursing is controversial. Some (e. g., The Ame rican Academy of Pediatrics) say that it is usually compat-ible with breast-feeding, but the manufacturer states that it should not be used in nur sing mothers. Overdosage/Acute Toxicity In the unlikely event of a parenterally administered overdose, it is suggested to contact an animal poison control center. Potentially, antimony can be chelated with dimercaptosuccinic acid (DMSA) or d-penicillamine. Drug Interactions No speciﬁc drug interactions were noted. Stibogluconate has re-portedly been used with allopurinol, paromomycin, or pentami-dine without problems. Laboratory Considerations No speciﬁc laboratory interactions or considerations noted. Doses T ! DOGS: a) For treatment of cutaneous leishmaniasis: 30-50 mg/kg IV or SC daily fo r 3-4 weeks (Anon 2004), (Brosey 2005) Monitoring T ! Laboratory and clinical signs associated with adverse effects (CBC, liver enzymes, renal function tests, ECG, etc. ) T ! Bone marrow cultures for Leishmania T ! Clinical efﬁcacy Client Information T ! Clients should understand the potential public health implica-tions of this disease (dependent on country) in dogs, the guarded prog nosis (even with treatment), risks of treatment and associ-ated expenses. Chemistry/Synonyms Sodium stibogluconate is a pentavalent antimony compound that contains between 30-34% antimony and is a colorless, odorless or almost odorless, amorphous powder. Sodium stibogluconate is very soluble in water and practically insoluble in alcohol or ether. The commercially available (not in the USA) injection has a p H between 5-5. 6. Sodium stibogluconate may also be known as: sodium anti-mony gluconate, stiboglucat-natr ium, natriumstibogluconat-9-wasser, solusurmin, stibogluconat, sodio st ibogluconato, and natrii stibogluconas. Storage/Stability The commercially available injection (Pentostam®) should be stored at temperatures below 25°C (76°F) and protected from freezing and exposure to light. After removing the ﬁrst dose, the vial should not be used after one month. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: None in the USA. Sodium Stibogluconate (sodium antimony gluconate) 100 mg (of antimony)/m L for injection in 6 m L and 100 m L (Pentostam®— Wellcome Foundation) is available from the Centers for Disease Con-trol (CDC). It may or may not be released for use in domestic ani-	pppbs.pdf
mals. Contact the CDC at 404-639-3670 from 8 AM-4:30 PM Eastern Time, Monday-Friday for more information or go to their website: www. cdc. gov/ncidod/srp/drugs/drug-service. html Pentostam® is available commercially in several countries. SODIUM SULFATE GLAUBER'S SALT (soe-dee-um sul-fayte; glow-bers salt) SALINE CATHARTIC Prescriber Highlights TT Used primarily in food animals TT Contraindications: Dehydration TT Caution in patients with severe CHF or in patients other-wise susceptible to sodium retention TT Adverse Effects: Diarrhea, cramping, & ﬂatulence may result; electrolyte abnormalities may occur with chronic use Uses/Indications Sodium sulfate is used as a saline cathartic, primarily in food animals. Pharmacology/Actions When given orally, sodium sulfate acts as a saline cathartic (draws water into small intestine). Sodium sulfate is considered the most effective saline cathartic on a molar basis. Sulfates also react with a variety of cations to form non-absorbable compounds, which may explain their efﬁcacy in reducing copper loads and reduce gut calcium. Pharmacokinetics Sodium sulfate is not appreciably absorbed from the GI tract and thereby acts a saline cathartic. Sodium may be absorbed however, after exchanging with other cations. Contraindications/Precautions/Warnings Saline cathartics should not be used in dehydrated animals. Because of the drug's high sodium content, it should be used with caution in patients with severe CHF or otherwise susceptible to sodium retention. Adverse Effects Diarrhea, cramping, and ﬂatulence may result. Electrolyte abnor-malities may occur with chronic use. Drug Interactions/Laboratory Considerations No speciﬁc drug or laboratory interactions or considerations were noted. Doses Note : When used in food animals, FARAD states that this salt is rapid-ly excreted and is not considered a residue concern in animal tissues; theref ore, a 24 hour preslaughter withdrawal interval (WDI) would be sufﬁcient. (Haskell, Payne et al. 2005) T ! CATTLE: a) As a cathartic: 500-750 g PO as a 6% solution via stomach tube (Dav is 1993) T ! SHEEP & GOATS: a) As a cathartic: 60 g PO as a 6% solution via stomach tube (Davis 1993) T ! SWINE: a) As a cathartic: 30-60 g PO as a 6% solution via stomach tube (Davis 1993) Chemistry/Synonyms Sodium sulfate (hexahydrate form) occurs as large, colorless, odor-less, crystals or white crystalline powder. It will efﬂoresce in dry air and partial ly dissolve in its own water of crystallization at about 33°C. 1 gram is soluble in about 2. 5 m L of water. Sodium sulfate may also be known as E514, Glauber's Salt, natrii sulphas, nat rio sulfata, or natrium sulfuricum. Storage/Stability Store in tight containers at temperatures not exceeding 30°C. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: None Sodium sulfate (hexahydrate) is available from chemical supply houses. SODIUM THIOSULFATE (soe-dee-um thye-oh-sul-fayte) Sodium Hyposulﬁte ANTIDOTE (ARSENIC, CYANIDE) Prescriber Highlights TT Used for cyanide or arsenic poisoning TT Contraindications: None TT Adverse Effects: Large doses by mouth may cause pro-fuse diarrhea TT Injectable forms should be given slowly IV Uses/Indications Sodium thiosulfate (alone or in combination with sodium nitrite) is useful in the treatment of cyanide toxicity. It has been touted for use in treating arsenic or other heavy metal poisonings, but its ef-ﬁcacy is in question for these purposes. However, because sodium thiosulfate is relatively non-toxic and inexpensive, it may be tried to treat arsenic poisoning. When used in combination with sodium molybdate, sodium thiosulfate may be useful for the treatment of copper poisoning. Sodium thiosulfate may be useful for the topical treatment for some fungal infections (Tinea). In humans, sodium thiosulfate has been used to reduce the nephrotoxicity of cisplatin therapy. A 3 or 4% solution has been used to inﬁltrate the site of extravasations of cisplatin, carboplatin, or dactinomycin. In combination with ste-roids, sodium thiosulfate may reduce the healing time associated with dox orubicin extravasation. Pharmacology/Actions By administering thiosulfate, an exogenous source of sulfur is avail-able to the body, thereby hastening the detoxiﬁcation of cyanide using the enzy me rhodanese. Rhodanese (thiosulfate cyanide sul-furtransferase) converts cyanide to the relatively nontoxic thiocya-nate ion; thiocyanate is then excreted in the urine.	pppbs.pdf
Sodium thiosulfate has been used in humans to treat extravasa-tion injuries secondary to carboplatin or cisplatin, for prophylaxis to pr event nephrotoxicity after cisplatin overdoses and ototoxicity with carboplatin overdoses. Sodium thiosulfate's topical antifungal activity is probably due to its slow re lease of colloidal sulfur. While sodium thiosulfate has been recommended for treating arsenic (and some other heavy metal) poisoning, the proposed mechanism of action is not known and its efﬁcacy is in question. Presumably, the sulfate moiety may react with and chelate the metal allowing its removal. Pharmacokinetics Sodium thiosulfate is relatively poorly absorbed from the GI tract. When substantial doses are given PO, it acts a saline cathartic. When administered intravenously, it is distributed in the extracel-lular ﬂuid and then rapidly excreted via the urine. Contraindications/Precautions/Warnings There are no absolute contraindications to the use of the drug. Adverse Effects The drug is relatively non-toxic. Large doses by mouth may cause profuse diarrhea. Injectable forms should be given slowly IV. Reproductive/Nursing Safety Safe use during pregnancy has not been established; use when ben-eﬁts outweigh the 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 reproduction studies and no adequate studies in humans. ) No lactation information was found. Drug Interactions/Laboratory Considerations No speciﬁc drug or laboratory interactions or considerations were noted. Doses T ! DOGS, CAT S: a) For cyanide toxicity: Contact an animal poison control cen-ter for guidance. b) For treating extravasation injuries secondary to doxorubicin, carboplat in, cisplatin infusions: Note : These are recommen-dations for human patients. Doxorubicin: Subcutaneous sodium thiosulfate 2% added to therapy with subcutaneous hydrocortisone and topical be-tamethasone decreased the healing time by half for cytotoxic drug ext ravasation (including doxorubicin and epirubicin) when compared to therapy without sodium thiosulfate. Carbo platin: Prepare a 0. 17 moles/L solution by mixing 4 m L sodium thiosulfate 10% w/v with 6 m L sterile water for injec-tion. Inject 5 m L into extravasation site. Cisplatin: F or extravasation of large amounts (greater than 20 m L) of highly concentrated (greater than 0. 5 mg/m L) solutio ns: Prepare a 0. 17 moles/L solution by mixing 4 m L sodium thiosulfate 10% w/v with 6 m L sterile water for in-jection. Inject into extravasation site. (DRUGDEX® Evalua-tions. Micromedex Healthcare Series; Thompson, 2007) T ! HORSES: a) For cyanide toxicity: First give sodium nitrite at a dose of 16 mg/kg IV fol lowed with a 20% solution of sodium thiosulfate given at a dose of 30-40 mg/kg IV. If repeating treatment, use sodium thiosulfate only. (Bailey and Garland 1992) b) For cyanide toxicity: First give sodium nitrite in a 20% solu-tion at a dose of 10-20 mg/kg IV followed with a 20% solu-tion of sodium thiosulfate given at a dose of 30-40 mg/kg IV (Osweiler 2003) c) F or arsenic toxicity: Sodium thiosulfate at 20-30 grams in 300 m L of water orally with dimercaprol (BAL) 3 mg/kg IM q4h (Jones 2004c) T ! RUMINANTS: Note : When used in food animals, FARAD states that this salt is rapidly excreted and is not considered a residue concern in animal tissues; therefore, a 24 hour preslaughter withdrawal in-terval (WDI) would be sufﬁcient. (Haskell, Payne et al. 2005) a) In combination with sodium molybdate for the treatment of co pper poisoning: In conjunction with ﬂuid replacement therapy, 500 mg sodium thiosulfate in combination with 200 mg ammonium or sodium molybdate PO daily for up to 3 weeks will help decrease total body burden of copper (Thompson and Buck 1993) b) For treatment of cyanide toxicity secondary to cyanogenic plants: 660 mg/kg IV sodium thiosulfate in a 30% solution given rapidly using a 12 or 14 gauge needle (Nicholson 1993), (Post and Keller 2000) c) For treatment of arsenic poisoning: 30-60 grams PO every 6 hours fo r 3-4 days and 30-60 grams as a 10-20% solution IV may be potentially useful in binding arsenic. Adjunctive ﬂuid and electrolyte replacement is necessary. (Galey 1993) Chemistry/Synonyms Sodium thiosulfate occurs as large, colorless crystals or coarse, crys-talline powder. It is very soluble in water, deliquescent in moist air and efﬂoresc es in dry air at temperatures >33°C. Sodium thiosulfate may also be known as: natrii thiosulfas, na-trium thiosulfuricum, sodium hyposulphite, sodium thiosulphate, Consep t Step 2®, Hiposul®, Hyposulfene®, or S-hydril®. Storage/Stability/Compatibility Unless otherwise stated by the manufacturer, store at room tem-perature. Crystals should be stored in tight containers. Sodium thios ulfate is not compatible mixed with cyanocobalamin. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Sodium Thiosulfate for Injection: 10% (100 mg/m L, as pentahydrate) & 25% (250 mg/m L) preservative-free in 10 m L & 50 m L single-use vials; generic, (American Regent); (Rx) SOMATOTROPIN (GROWTH HORMONE) (soe-ma-toe-troe-pin) HORMONE Prescriber Highlights TT Used for canine hypopituitary dwarﬁsm or growth hor-mone-responsive dermatosis (in adult dogs). TT May cause diabetes mellitus TT Availability & expense issues	pppbs.pdf
TUses/Indications Somatotropin may be useful in treating hypopituitary dwarﬁsm or growth hormone-responsive dermatosis (in adult dogs). Pharmacology/Actions Growth hormone (somatotropin) is responsible for, or contributes to, linear and skeletal growth, organ growth, and cell growth. It also is a factor in protein, carbohydrate, lipid, connective tissue, and mineral metabolism. Pharmacokinetics No canine information was located. Both the liver and kidney are major elimination organs for somatotropin. Contraindications/Precautions/Warnings Growth hormone derived from other species is contraindicated in patients hypersensitive to it. Adverse Effects Growth hormone may cause diabetes mellitus in dogs. This may be transient or permanent even after discontinuing treatment. Blood and urine glucose should be routinely monitored. If blood glucose exceeds 150 mg/dl, therapy should be stopped. Hypersensitivity reactions are possible, but less so if using porcine origin prod-uct. Long-term treatment at high doses may cause acromegaly. Acrome galy in dogs can cause increased size of paws and head, in-creased skin folds around head and neck area, prognathism, and inspirator y stridor. 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. ) Overdosage/Acute Toxicity Acute overdosage could cause hypoglycemia initially and then hy-perglycemia. Blood glucose should be monitored and supportive treatme nt (glucose/insulin) performed. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving somatotropin and may be of signiﬁcance in veterinary patients: T ! GLUCOCORTICOIDS : May inhibit the growth promoting effect of so-matotropin. When concurrent adrenal insufﬁciency is diagnosed, adjust glucocorticoid dose carefully to avoid negative effects on growth. Doses T ! DOGS: a) For treatment of hypopituitary dwarﬁsm: 0. 1 IU (0. 05 mg)/ kg SC thre e times per week for 4-6 weeks. Note : May also re-quire life-long thyroid hormone supplementation and if sec-ondary adrenal insufﬁciency present, glucocorticoid treat-ment. If after successful treatment, dermatologic signs recur, may dose as above (0. 1 IU/kg three times weekly for one week). Repeat these weekly regimens at intervals determined by the time lapse between treatments and relapse. (Feldman and Nelson 1996) b) For treatment of growth hormone-responsive dermatosis in adult d ogs: Dose as above (a), but thyroid and steroid supple-mentation not required (Feldman and Nelson 1996) c) For Alopecia X: 0. 15 IU/kg of porcine growth hormone SC 2 times weekl y for 6 weeks. (Hillier 2006a) Monitoring T ! Clinical efﬁcacy T ! Blood glucose (weekly) T ! Urine glucose (daily) T ! hyroid function, adrenal function initially and then periodically (pituitary dwarﬁsm pts. ) Client Information T ! Clients should be instructed on the methods for SC injection and testing urine glucose T ! May be expensive to treat and diabetes (permanent) can occur Synonyms Somatotropin may also be known as: CB-311, HGH, human growth hormone, LY-137998, somatropinum; many trade names are available. Dosage Forms/Regulatory Status There are several manufacturers of human recombinant DNA origin somatotr opin products, but these are expensive, can cause immuno-genicity reactions in dogs, and not sold for veterinary use. The bovine recombinant growth hormone product (Posilac®— Monsanto) is not suitable for canine use as it is a sustained release formulation and not easily diluted down to the smaller doses re-quired for dogs. Porcine growth hormone appears to have little immunogenicity in dogs and reportedly can be obtained via: Dr A. F. Partlow at: 310-222-3537 E-Mail: Partlow@HUMC. edu WEBSITE: www. humc. edu/ hormones T he ARCI (Racing Commissioners International) has designated this drug as a class 2 substanc e. See the appendix for more information. SOTALOL HCL (soh-ta-lole) Betapace® BETA-ADRENERGIC BLOCKER Prescriber Highlights TT Non-selective beta blocker/Class III antiarrhythmic for ventricular tachycardia TT Adverse Effects: Most serious: negative inotropism & pro-arrhythmic but dyspnea/bronchospasm, fatigue/dizzi-ness, & nausea/vomiting possible TT Treatment is relatively expensive Uses/Indications Sotalol may be useful in the treatment of ventricular tachycardias and, possibly, supraventricular tachycardias in dogs. Pharmacology/Actions Sotalol is a non-selective beta-blocker and Class III antiarrhythmic agent. The beta blocking activity of sotalol is about 30% that of propranolol. Its primary usage in veterinary medicine is associated with its antiarrhythmic activity. Like other Class III drugs, it pro-longs repolarization and refractoriness without affecting conduc-tion. The pharmacologic action is believed caused by selectively inhibiting potassi um channels.	pppbs.pdf
Pharmacokinetics Unlike propranolol, sotalol does not have any appreciable ﬁrst pass effect after oral administration. Food may reduce the bioavailability of sotalol by approximately 20% (human data) and, if given on an empty stomach, bioavailability is 90-100%. The drug has relatively low lipid solubility and virtually no protein binding. Elimination is almost all via the kidney and most of the drug is excreted un-changed. In dogs, sotalol's elimination half-life is 5 hours; in hu-mans about 12 hours. Contraindications/Precautions/Warnings Sotalol is considered contraindicated in patients with asthma, si-nus bradycardia, 2nd or 3rd degree heart block (unless artiﬁcially pac ed), long Q-T syndromes, cardiogenic shock or uncontrolled CHF. Because of the potential for negative inotropic effects, use with caution in CHF. Also, use with caution in patients with diabe-tes mellitus, or hyperthyroidism (may mask signs). Use with cau-tion in patients with renal dysfunction; dosage intervals may need to b e extended. Adverse Effects Primary concerns with sotalol in dogs are the potential for negative inotropic and proarrhythmic effects. These generally are not clini-cally important if dosage is not excessive. Other potential adverse eff ects include dyspnea/bronchospasm, fatigue/dizziness, and nau-sea/vomiting. Reproductive/Nursing Safety Sotalol did not cause any fetotoxicity or teratogenicity when given to pregnant lab animals at high dosages, but clear safety in preg-nancy has not been established. Sotalol enters maternal milk in co ncentrations up to 5X found in the serum; consider using milk replacer in nursing animals. In humans, the FDA categorizes this drug as category B fo r 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 demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Sotalol is excreted in milk; use with caution in nursing patients. It is not r ecommended for use in nursing humans. Overdosage/Acute Toxicity Overdoses may result in bradycardia, hypotension, CHF, broncho-spasm, and hypoglycemia. Use gut evacuation (if not contraindi-cated) when signiﬁcant risk of morbidity is possible. Treat adverse eff ects symptomatically and supportively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sotalol and may be of signiﬁcance in veterinary patients: !TAMIODARONE : May prolong refractory periods; concurrent use not recommended in human patients !TANESTHETICS, GENERAL : Additive myocardial depression may oc-cur with the concurrent use of sotalol and myocardial depressant anesthetic agents !TANTACIDS : May reduce oral sotalol absorption; separate doses by at least 2 hours !TANTIARRHYTHMICS, CLASS IA (quinidine, procainamide, disopyramide ): May prolong refractory periods; concurrent use not recommend-ed in human patients; may also prolong QT interval !TANTIARRHYTHMICS, CLASS IB, 1C (lidocaine, mexiletine, phenytoin, ﬂe-cainide etc. ): May prolong QT interval !TCALCIUM CHANNEL BLOCKERS (verapamil, diltiazem, etc. ): Potential to increase hypotensive effects; may have additive effects on A V conduction or ventricular function; use with caution, particu-larly in patients with preexisting cardiomyopathy or CHF !TCISAPRIDE : May prolong QT interval !TCLONIDINE : If clonidine is discontinued after concomitant therapy with sotalol, there is an increased risk for rebound hypertension !TDIGOXIN : Potential for increased risks for proarrhythmic events !TERYTHROMYCIN; CLARITHROMYCIN : May prolong QT interval !TLIDOCAINE : Clearance may be impaired by sotalol !TPHENOTHIAZINES : May prolong QT interval !TRESERPINE : May have additive effects (hypotension, bradycardia) with sotalol !TSYMP ATHOMIMETICS, BETA 2 AGONISTS (e. g., metaproterenol, terbuta-line, albuterol ): May have their actions blocked by sotalol !TTRICYCLIC ANTIDEPRESSANTS : May prolong QT interval Laboratory Considerations !TBeta-blockers may produce hypoglycemia and interfere with glu-cose or insulin tolerance tests !TSotalol may falsely elevate urine metanephrine levels (pheochro-mocytoma screen) if using a ﬂuorometric or photometric assay Doses !TDOGS: a) 1-2 mg/kg PO q12h (Fox 2003a), (Moise 2002) b) 2-3 mg/kg PO q12h (Meurs 2002) c) For ventricular tachycardia: 1-2 mg/kg PO twice daily (At-kins 2007a) d) For ventricular tachycardias, supraventricular tachycardias: 1- 2 mg/kg PO q12h (Smith 2007) e) For ventricular tachyarrhythmias in Boxers in combination with mexiletine: Sotalol 1. 5-3 mg/kg PO twice daily with mexiletine (5-7. 5 mg/kg PO three times daily). (Prosek, Es-trada et al. 2006) !TCATS: a) 2 mg/kg PO twice daily (Atkins 2003b) Monitoring !TEfﬁcacy (ECG) !TAdverse effects Client Information !TRelatively limited clinical experience; but appears safe !TMust be given as prescribed; do not stop drug suddenly or alter dosing without veterinarian guidance !TReport adverse effects to veterinarian immediately Chemistry/Synonyms A non-selective beta-blocker and Class III antiarrhythmic agent, so-talol HCl is a racemic mixture of the d-and l-forms. Both isomers exhib it antiarrhythmic (Class II) activity, but only the Levo-form has beta blocking activity. Sotalol HCl occurs as white, crystalline solid that is soluble in water. Sotalol may also be known as: MJ-1999, d,l-sotalol hydrochlo-ride, or sotaloli hydrochloridum; many trade names are available. Storage/Stability Store tablets at room temperature.	pppbs.pdf
Dosage Forms/Approval 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: Sotalol HCl Tablets: 80 mg, 120 mg, 160 mg & 240 mg; Betapace® & Betapace® AF (Berlex); generic; (Rx) SPECTINOMYCIN HCL SPECTINOMYCIN SULFATE (spek-ti-noe-mye-sin) Adspec®, Spectam® AMINOCYCLITOL ANTIBIOTIC Prescriber Highlights TT Aminocyclitol antibiotic used primarily in food producing animals; relatively broad spectrum but minimal activity against anaerobes & most strains of Pseudomonas TT Contraindications: Hypersensitive to it TT Adverse Effects: Appears to have minimal adverse ef-fects at labeled dosages; probably less nephrotoxicity/ ototoxicity than other aminocyclitols. Can cause neuro-muscular blockade. May cause swelling at SC injection sites. Uses/Indications Although occasionally used in dogs, cats, and horses for susceptible infections, Spectinomycin only has approved dosage forms for cat-tle, chickens, turkeys, and swine. Refer to the Dosage section below for mor e information on approved uses. Pharmacology/Actions Spectinomycin is primarily a bacteriostatic antibiotic that inhibits protein synthesis in susceptible bacteria by binding to the 30S ribo-somal subunit. Spectinomycin has activity against a wide variety of gram-positiv e and gram-negative bacteria, including E. coli, Klebsiella, Proteus, Enterobacter, Salmonella, Streptococci, Staphylococcus, and Mycoplasma. It has minimal activity against anaerobes, most strains of Pseudomonas, Chlamydia, or Treponema. In human medicine, spectinomycin is used principally for its ac-tivity against Neisseria gonorrhoeae. Pharmacokinetics After oral administration only about 7% of the dose is absorbed, but the drug that remains in the GI tract is active. When injected SC or IM, the drug is reportedly absorbed well with peak levels oc-curring in about 1 hour. Tissue levels of absorbed drug are lower than those found in the serum. Sp ectinomycin does not appreciably enter the CSF or the eye and is not bound signiﬁcantly to plasma proteins. It is unknown whether spectinomycin crosses the placenta or enters milk. Absorbed drug is excreted via glomerular ﬁltration into the urine mostly unchange d. In cattle, terminal half-life is about 2 hours. Contraindications/Precautions/Warnings Spectinomycin is contraindicated in patients hypersensitive to it. Adverse Effects When used as labeled, adverse effects are unlikely with this drug. It is reported that parenteral use of this drug is much safer than with other aminocyclitol antibiotics, but little is known regarding its prolonged use. It is probably safe to say that spectinomycin is signiﬁcantly less ototoxic and nephrotoxic than other commonly used aminocyclitol antibiotics, but can cause neuromuscular block-ade. Parenteral calcium administration will generally reverse the blocka de. Adverse effects that have been reported in human patients re-ceiving the drug in single or multidose studies include soreness at injectio n site, increases in BUN, alkaline phosphatase and SGPT, and decreases in hemoglobin, hematocrit, and creatinine clearance. Although increases in BUN and decreases in creatinine clearance and urine output have been noted, overt renal toxicity has not been demonstrated with this drug. Cattle receiving the sulfate form subcutaneously have developed swelling at the inje ction site. 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. ) It is not known whether spectinomycin is excreted in milk; use caution w hen administering to nursing patients. Overdosage/Acute Toxicity No speciﬁc information was located on oral overdoses, but because the drug is negligibly absorbed after oral administration, signiﬁcant toxicity is unlikely via this route. Injected doses of 90 mg produced transient ataxia in turkey poults. Drug Interactions T ! Antagonism has been reported when spectinomycin is used with chloramphenicol or tetracycline. Doses T ! DOGS: For susceptible infections: a) 5. 5-11 mg/kg q12h IM or 22 mg/kg PO q12h (for enteric infect ions; not absorbed) (Kirk 1989) b) 5-10 mg/kg IM q12h (Davis 1985) c) For acute infectious gastroenteritis: 5-12 mg/kg IM q12h (De Nov o 1986) T ! CATS: For susceptible infections: a) For acute infectious gastroenteritis: 5-12 mg/kg IM q12h (De Nov o 1986) T ! CATTLE: For susceptible infections: a) For bronchopneumonia and ﬁbrinous pneumonia: 33 mg/ kg SC q8h. S uggested withdrawal time is 60 days. (Hjerpe 1986) b) 22-39. 6 mg/kg/day IM divided three times daily (Upson 1988) c) For bovine respiratory disease: 10-15 mg/kg SC (in the neck; not more than 50 m L per site) once daily (q24h) for 3-5 consecutive days (Label directions; Adspec®)	pppbs.pdf
T ! HORSES: For susceptible infections: a) 20 mg/kg, IM three times daily (Robinson 1987) b) For pneumonia: 20 mg/kg IM q8h; may cause local myositis. Insufﬁcient data t o comment on use. (Beech 1987b) T ! SWINE: For susceptible enteric infections: a) 10 mg/kg, PO q12h (Howard 1986) b) For bacterial enteritis (white scours) in baby pigs associated with E. c oli susceptible to spectinomycin: 50 mg/10 lbs of body weight PO twice daily for 3-5 days (Label directions; Spectam Scour-Halt®—Ceva) c) 10 mg/kg, IM q12h (Baggot 1983) T ! BIRDS: a) For airsacculitis associated with M. meleagr idis or chronic re-spiratory disease associated with E. coli in turkey poults (1-3 days old): Inject 0. 1 m L (10 mg) SC in the base of the neck. For control and to lessen mortality due to infections from M. synoviae, S. typhimurium, S. infantis, and E. coli in newly hatched chicks: Dilute injection with normal saline to a con-centration of 2. 5-5 mg/0. 2 m L and inject SC. (Label direc-tions; Spectam® Injectable—Ceva) b) For prevention and control of chronic respiratory disease as-sociated with Myco plasma gallisepticum in broilers: Add suf-ﬁcient amount to drinking water to attain a ﬁnal concentra-tion of 2 g/gallon. For infectious synovitis associated with Myco plasma synoviae in broilers: Add sufﬁcient amount to drinking water to attain a ﬁnal concentration of 1 g/gallon. For improved weight gain/feed efﬁciency in ﬂoor-raised broile rs: Add sufﬁcient amount to drinking water to attain a ﬁnal concentration of 0. 5 g/gallon. (Label directions; Spec-tam® Water-Soluble—Ceva) Monitoring T ! Clinical efﬁcacy Chemistry/Synonyms An aminocyclitol antibiotic obtained from Streptomyces spectabilis, spectinomycin is available as the dihydrochloride pentahydrate and hexahydrate sulfate salts. It occurs as a white to pale buff, crystal-line powder with p K as of 7 and 8. 7. It is freely soluble in water and practically insoluble in alcohol. Spectinomycin may also be known as: M-141, actinospectacin, spect inomycini, U-18409AE, Adspec®, Amtech Spectam®, Kempi®, Kirin®, Spectoguard Scour-Chek®, Stanilo®, Togamycin®, Trobicin®, Trobicine®, or Vabicin®. Storage/Stability Unless otherwise instructed by the manufacturer, spectinomycin products should be stored at room temperature (15-30°C). Protect from freezing. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Spectinomycin Sulfate Injection: 100 mg/m L in 500 m L vials; Ad-spec®; (Pharmacia & Upjohn); (Rx). When used as labeled, slaughter withdrawal in cattle = 11 days; not to be used in veal calves or in dairy cattle 20 months of age or older. Spectinomycin Injection: 100 mg/m L in 500 m L vials; Amtech Spec-tam® Injectable (IVX); (OTC). Approved for use in 1-3 days old tur-key poults and newly hatched chicks. Spectinomycin Water Soluble Concentrate: 0. 5 g of spectinomycin per g ram Spectam® Water Soluble (Bimeda); (OTC). Approved for use in chickens (not layers). Slaughter withdrawal (at labeled doses) = 5 days. Spectinomycin Oral Solution: 50 mg/m L in 240 m L pump bottle and 500 and 1000 m L without pump; Amtech Spectam Scour-Halt®, (IVX), Spectoguard Scour-Chek® (Bimeda), Spectam Scour-Halt®, (Agri Pharm); (OTC). Approved for use in swine (Weighing less than 15 lbs and not older than 4 weeks of age). Slaughter withdrawal (at labeled doses) = 21 days. Spectinomycin/Lincomycin in a 2:1 ratio LS 50 Water Soluble Powder® (Pharmacia & Upjohn); Sepclinx-50® (Bimeda); generic (IVX, Agri Labs); in 2. 65 oz packets. Each packet contains lincomycin 16. 7 g and spectinomycin 33. 3 g. Approved for use in chickens up to 7 days of age. Lincomycin 50 mg/Spectinomycin 100 mg per m L in 20 m L vials; Linco-Sp ectin® Sterile Solution (Pharmacia & Upjohn); (OTC). Ap-proved for use in semen extenders only. HUMAN-LABELED PRODUCTS: Spectinomycin Powder for Injection: 400 mg (as the HCl) per m L after reconstitution in 2 g vial with 3. 2 m L diluent; Trobicin ® (Up-john); (Rx) SPIRONOLACTONE (speer-on-oh-lak-tone) Aldactone® ALDOSTERONE ANTAGONIST Prescriber Highlights TT Aldosterone antagonist used as a potassium sparing di-uretic or for adjunctive treatment for heart failure (use is somewhat controver sial f or CHF in dogs); should not be substituted for furosemide in CHF TT Contraindications: Hyperkalemia, Addison's disease, anu-ria, acute renal failure or signiﬁcant renal impairment TT Caution: Any renal impairment or hepatic disease TT Adverse Effects: Hyperkalemia, hyponatremia, & dehy-dration; increased BUN & mild acidosis in patients with renal impairment. GI distress (vomiting, anorexia, etc. ), CNS effects (lethargy, ataxia, headache, etc. ), & endo-crine changes possible Uses/Indications Spironolactone may be used in patients with congestive heart failure who do not adequately respond to furosemide and ACE inhibitors, who develop hypokalemia on other diuretics, and are unwilling or unable to supplement with exogenous potassium sources. It may also be effective in treating ascites as it has less potential to increase ammonia levels than other diuretics. Pharmacology/Actions Aldosterone is competitively inhibited by spironolactone in the dis-tal renal tubules with resultant increased excretion of sodium, chlo-ride, and water, and decreased excretion of potassium, ammonium, phosphate, and titratable acid. Spironolactone has no effect on car-bonic anhydrase or renal transport mechanisms and has its great-est effect in patients with hyperaldosteronism. When used alone in	pppbs.pdf
healthy dogs, spironolactone does not appear to cause signiﬁcant diuresis (Jeunesse, Wohrle et al. 2004). Spironolactone is not commonly used alone as most sodium is reabso rbed at the proximal tubules. Combining it with a thiazide or loop diuretic will yield maximum diuretic effect. After cats received 2. 7 mg/kg spironolactone twice daily for 7-9 day s, the following serum values increased (on average) signiﬁcant-ly: potassium 0. 39 m Eq/L, calcium 0. 48 mg/d L, creatinine 0. 22 mg/ d L, p hosphorus 0. 63 mg/d L and total protein 0. 51 mg/d L. (Abbott and Saker 2006) In humans, spironolactone can have antiﬁbrotic effects on car-diac muscle. Pharmacokinetics No information was found regarding the pharmacokinetics of spironolactone in veterinary species. In humans, spironolactone is >90% bioavailable and peak levels are reached within 1-2 hours. The diuretic action of spironolactone (when used alone) is gradu-ally attained and generally reaches its maximal effect on the third day o f therapy. Spironolactone and its active metabolite, canrenone, are both abou t 98% bound to plasma proteins. Both spironolactone and its metabolites may cross the placenta. Canrenone has been detected in breast milk. Spironolactone is rapidly metabolized (half-life of 1-2 hours) to several metabolites, including canrenone, which has diuretic activity. Canrenone is more slowly eliminated, with an av-erage half-life of around 20 hours. Contraindications/Precautions/Warnings Spironolactone is contraindicated in patients with hyperkalemia, Addison's disease, anuria, acute renal failure or signiﬁcant renal im-pairment. It should be used cautiously in patients with any renal impairme nt or hepatic disease. Adverse Effects Adverse effects are usually considered mild and reversible upon dis-continuation of the drug. Electrolyte (hyperkalemia, hyponatremia) and wat er balance (dehydration) abnormalities are the most likely effects with spironolactone therapy, but electrolytes in dogs do not appear to be signiﬁcantly affected. Transient increases in BUN and mild acidosis may occur in pa-tients with renal impairment. GI distress (vomiting, anorexia, etc. ), CNS e ffects (lethargy, ataxia, headache, etc. ), and endocrine chang-es (gynecomastia in human males) are all possible. Use of spironolactone in patients with renal impairment may lead to hyperkalemia. Spironolactone reportedly inhibits the syn-thesis of testosterone and may increase the peripheral conversion of testosterone to estradiol. Long-term toxicity studies in rats have demonstrated that spironolactone is tumorigenic in that species. Reproductive/Nursing Safety Spironolactone or its metabolites may cross the placental barrier. Feminization occurs in male rat fetuses. In humans, the FDA cat-egorizes this drug as category D fo r 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. ) Canrenone, a metabolite of spironolactone, appears in maternal milk. I n humans, the estimated maximum dose to the infant is ap-proximately 0. 2% of the mother's daily dose. Use with caution in nur sing patients, but it is unlikely of clinical signiﬁcance in veteri-nary patients. Overdosage/Acute Toxicity Information on overdosage of spironolactone is apparently un-available. Should an acute overdose occur, it is suggested to fol-low the guidelines outlined in the chlorothiazide and furosemide mono graphs. Contact an animal poison control center for further guidance. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving spironolactone and may be of signiﬁcance in veterinary patients: !TDIGOXIN : Spironolactone may increase the half-life of digoxin; en-hanced monitoring of digoxin serum levels and effects are war-ranted when spironolactone is used with these agents !TMITOTANE : Spironolactone may mute the effects of mitotane if given concurrently, but very limited information is available on this potential interaction; monitor carefully. !TNEUROMUSCULAR BLOCKERS, NON-DEPOLARIZING : Increase in neuro-muscular blockade effects possible !TPOTASSIUM-SPARING DIURETICS, OTHER (e. g., triamterene ): Hyper-kalemia possible !TPOTASSIUM SUPPLEMENTS : Hyperkalemia possible !TSALICYLATES : Spironolactone's diuretic effects may be decreased if aspirin or other salicylates are administered concomitantly Laboratory Considerations !TSpironolactone may give falsely elevated digoxin values, if using a radioimmune assay (RIA) method. !TFluorometric methods of determining plasma and urinary 17-hydroxycorticosteroids (cortisol) may be interfered with by spironolactone. Doses !TDOGS: As a diuretic in CHF: a) When furosemide and ACE inhibitors alone do not control ﬂuid a ccumulation in refractory CHF: 1-2 mg/kg PO q12h (Ware and Keene 2000) b) With other diuretics when hypokalemia is an issue: 2-4 mg/ kg PO onc e daily (Kittleson 2000) c) T o allow further reduction of furosemide dose (target dose fo r furosemide during maintenance phase: 1-2 mg/kg PO q24-48h): Spironolactone dose varies between 0. 5 mg/kg PO once daily (aldosterone blockage, weak diuretic effect) to 2 mg/kg twice daily (stronger diuretic effect). (de Madron 2004) For treating ascites: a) 1-2 mg/kg PO twice daily; if no response in 4-5 days, dou-ble dose for an additional 4-5 days; if no response, may dou-ble again (4-8 mg/kg twice daily). Monitor (weigh) patients daily and do not allow patient to become dehydrated or to lose more than 0. 25-0. 5 kg/day. (Hardy 1985) b) Attempt at treating underlying abnormality. When ascites is caused by right-sided heart failure: Be sure owner is admin-istering medication properly and the prescription is correct. Incr ease furosemide to 4-6 mg/kg PO q8h (generally speak-ing dose should be increased until all the abnormal accumu-lated ﬂuid is eliminated or unacceptable azotemia develops). Op timize ACE inhibitor dose. Restrict dietary sodium. Add spironolactone at 1-2 mg/kg PO q12h. Initially (3 times weekly) substitute one of the oral furosemide doses with a SC dose. Consider adding hydrochlorothiazide initially at 2 mg/kg PO every other day. (Connolly 2006)	pppbs.pdf
For adjunctive treatment of hypertension: a) 1-2 mg/kg PO q12h (Stepian 2006b) T ! CATS: As a diuretic in CHF: a) When furosemide and ACE inhibitors alone do not control ﬂuid accum ulation in refractory CHF: 1-2 mg/kg PO q12h (Ware and Keene 2000) b) 1 mg/kg q12h PO when serum potassium is low (Bonagura 1989) For adj unctive treatment of hypertension: a) 1-2 mg/kg PO q12h (Stepian 2006b) Monitoring T ! Serum electrolytes, BUN, creatinine T ! Hydration status T ! Blood pressure, if indicated T ! Clinical signs of edema/ascites; patient weight, if indicated Client Information T ! Notify veterinarian if GI symptoms ( e. g., vomiting, diarrhea, an-orexia), lethargy, or other CNS effects are severe or persist Chemistry/Synonyms A synthetically produced aldosterone antagonist, spironolactone occurs as a cream-colored to light tan, crystalline powder with a faint mercaptan-like odor. It has a melting range of 198°-207°, with decomposition. Spironolactone is practically insoluble in wa-ter and soluble in alcohol. Spironolactone may also be known as: espironolactona, SC-9420, spirolact one, spironolactonum; many trade names are available. Storage/Stability Spironolactone tablets should be stored at room temperature in tight, light-resistant containers. An extemporaneously prepared oral suspension can be prepared by pulverizing commercially avail-able tablets and adding cherry syrup. This preparation is reportedly stable for at least o ne month when refrigerated. 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: Spironolactone Tablets: 25 mg, 50 mg & 100 mg; Aldactone® (Searle); generic; (Rx) Also available in combination with hydrochlorothiazide. STANOZOLOL (stah-no-zo-lahl) Winstrol®-V ANABOLIC STEROID Prescriber Highlights TT Anabolic steroid; veterinary labeled products no longer marketed in USA TT Contraindications: Pregnant animals, breeding stallions, food animals. Extreme Caution: Cats, hepatic dysfunction, hypercalcemia, history of myocardial infarction, pituitary insufﬁciency, prostate carcinoma, mammary carcinoma, benign prostatic hypertrophy, & during the nephrotic stage of nephritis. Caution: Cardiac & renal dysfunction with enhanced ﬂuid & electrolyte monitoring. TT Adverse Effects: Potentially high incidence of hepatotox-icity in cats. Other possible effects: sodium, calcium, po-tassium, water, chloride, & phosphate retention; hepato-toxicity, behavioral (androgenic) changes, & reproductive abnormalities (oligospermia, estr us suppression) TT Category “ X” for pregnancy; teratogenicity outweighs any possible beneﬁt TT Controlled substance in the USA TT Drug Interactions; lab interactions Uses/Indications Labeled indications for the previously marketed veterinary sta-nozolol product Winstro l®-V (Winthrop/Upjohn) included “... to improve appetite, promote weight gain, and increase strength and vitality... ” in dogs, cats and horses. The manufacturer also stated that: “Anabolic therapy is intended primarily as an adjunct to other speciﬁc and supportive therapy, including nutritional therapy. ” Like nandrolone, stanozolol has been used to treat anemia of chronic disease. Because stanozolol has been demonstrated to en-hance ﬁbrinolysis after parenteral injection, it may be efﬁcacious in the tr eatment of feline aortic thromboembolism or thrombosis in nephrotic syndrome; however, clinical studies and/or experience are apparently lacking for this indication at present. Pharmacology/Actions Stanozolol possesses the actions of other anabolic agents but it may be less androgenic than other anabolics that are used in veterinary medicine. Refer to the discussion in the boldenone monograph for more information. Pharmacokinetics No speciﬁc information was located for this agent. It is generally recommended that the injectable suspension be dosed on a weekly basis in both small animals and horses. Contraindications/Precautions/Warnings Stanozolol is contraindicated in pregnant animals and in breeding stallions and should not be administered to horses intended for food purposes. Because of reported hepatotoxicity associated with this drug in cats, it should only be used in this species with extreme caution. The manufacturer recommends using stanozolol cautiously in patients w ith cardiac and renal dysfunction with enhanced ﬂuid and electrolyte monitoring.	pppbs.pdf
In humans, anabolic agents are contraindicated in patients with hepatic dysfunction, hypercalcemia, patients with a history of myo-cardial infarction (can cause hypercholesterolemia), pituitary in-sufﬁciency, prostate carcinoma, benign prostatic hypertrophy, dur-ing the nephrotic stage of nephritis, and in selected patients with br east carcinoma. Adverse Effects The manufacturer (Winthrop/Upjohn) lists as adverse effects in dogs, cats, and horses only “mild androgenic effects” and then only when used with excessively high doses for a prolonged period of time. One study in cats, demonstrated a very high incidence of hepa-totoxicity associated with stanozolol use and the authors recom-mended that this drug not be used in cats until further toxicological studies ar e performed. Potentially (from human data), adverse reactions of the ana-bolic agents in dogs and cats could include: sodium, calcium, po-tassium, water, chloride, and phosphate retention, hepatotoxicity, be havioral (androgenic) changes, and reproductive abnormalities (oligospermia, estrus suppression). Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category X for use during pregnancy (Studies in animals or humans demonstrate fetal abnormalities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any pos-sible beneﬁt. ) 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. ) It is not known whether anabolic steroids are excreted in mater-nal milk. Because of the potential for serious adverse reactions in nur sing offspring, use in nursing patients with extreme caution. Overdosage/Acute Toxicity No information was located for this speciﬁc agent. In humans, so-dium and water retention can occur after overdosage of anabolic ste roids. It is suggested to treat supportively and monitor liver func-tion should an inadvertent overdose be administered. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving stanozolol and may be of signiﬁcance in veterinary patients: !TANTICOAGULANTS (heparin, warfarin ): Anabolic agents as a class may potentiate the effects of anticoagulants; monitoring of INR/ PT's and dosage adjustment, if necessary, of the anticoagulant are recommended !TCORTICOSTEROIDS : Anabolics may enhance the edema that can be associated with ACTH or adrenal steroid therapy !TINSULIN : Diabetic patients receiving insulin may need dosage ad-justments if anabolic therapy is added or discontinued; anabolics may decrease blood glucose and decrease insulin requirements Laboratory Considerations !TConcentrations of protein bound iodine (PBI) can be decreased in patients receiving androgen/anabolic therapy, but the clinical signiﬁcance of this is probably not important. Androgen/ana-bolic agents can decrease amounts of thyroxine-binding globulin and decrease total T 4 concentrations and increase resin uptake of T3 and T 4. Free thyroid hormones are unaltered and there is no evidence of dysfunction. !TBoth creatinine and creatine excretion can be decreased by ana-bolic steroids. !TAnabolic steroids can increase the urinary excretion of 17-keto-steroids. !TAndrogenic/anabolic steroids may alter blood glucose levels. !TAndrogenic/anabolic steroids may suppress clotting factors II, V, VII, and X. !TAnabolic agents can affect liver function tests (BSP retention, SGOT, SGPT, bilirubin, and alkaline phosphatase). Doses !TDOGS: As an anabolic agent per labeled indications: a) Small Breeds: 1-2 mg PO twice daily; or 25 mg deep IM, may repeat weekly. Large Breeds: 2-4 mg PO twice daily; or 50 mg deep IM, may repeat weekly. Treatment should continue for several weeks, depend-ing on response and condition of animal. (Package Insert; Winst rol®-V —Winthrop/Upjohn) For anemia secondary to chronic renal failure: a) 1-4 mg PO once daily (Ross et al. 1988) b) For anemias secondary to uremia: 2-10 mg PO twice daily (Maggio-Price 1988) As an anab olic/appetite stimulant: a) 1-4 mg PO twice daily (Weller 1988) b) 1-2 mg PO twice daily or 25-50 mg IM weekly (Macy and Ralston 1989), (Bartges 2003b) Fo r canine cognitive dysfunction: a) 2 mg/kg IM for 4-6 weeks with 1-2 mg (total dose) PO once daily for dogs less than 23 kg and 4 mg (total dose) PO once daily for dogs greater than 23 kg. If drug has some positive effect, maintain oral dosing and gradually reduce injections to every 3-4 weeks. (Hoskins 1999) !TCATS: Note : See Warnings Above As an anabolic agent per labeled indications: a) 1-2 mg PO twice daily; or 25 mg deep IM, may repeat week-ly. Treatment should continue for several weeks, depend-ing on response and condition of animal. (Package Insert; Winst rol®-V —Winthrop/Upjohn) !TFERRETS: a) 0. 5 mg/kg PO or SC twice daily; use with caution in hepatic disease (W illiams 2000) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: As an appetite stimulant: 0. 5-2 mg PO once (Ivey and Mo rrisey 2000) !THORSES: (Note : ARCI UCGFS Class 4 Drug) As an anabolic agent per labeled indications: a) 0. 55 mg/kg (25 mg per 100 pounds of body weight) IM deep-ly. May repeat weekly for up to and including 4 weeks. (Pack-age Insert; Winst rol®-V—Winthrop/Upjohn) !TSHEEP & GOATS: For acute or subacute aﬂatoxicosis in ruminants: a) Stanozolol 2 mg/kg IM (plus activated charcoal 6. 7 mg/kg as a 30% w/v slurry in M/15, p H 7 phosphate buffer). Do not combine with oxytetracycline therapy. (Hatch 1988) !TBIRDS: As an anabolic agent to promote weight gain and recovery from disease: a) 0. 5-1 m L/kg (25-50 mg/kg) IM once or twice weekly. Use with cau tion in birds with renal disease. (Clubb 1986)	pppbs.pdf
TT ! REPTILES: For most species post-surgically and in very debilitated animals: a) 5 mg/kg IM once a week as needed (Gauvin 1993) Monitoring T ! Androgenic side effects T ! Fluid and electrolyte status, if indicated T ! Liver function tests if indicated T ! RBC count, indices, if indicated T ! Weight, appetite Client Information T ! ablets may be crushed and administered with food T ! Because of the potential for abuse of anabolic steroids this agent is a controlled drug; it should be kept in a secure area and out of the reach of children Chemistry/Synonyms An anabolic steroid, stanozolol occurs as an odorless, nearly color-less, crystalline powder that can exist in two forms: prisms that melt at appr oximately 235°C, and needles that melt at about 155°C. It is sparingly soluble in alcohol and insoluble in water. Stanozolol may also be known as: androstanazole, estanozolol, methylstanaz ole, NSC-43193, stanozololum, win-14833, Menabol®, Neurabol®, Stanol®, Stromba®, Strombaject® and Winstrol®. Storage/Stability Stanozolol tablets should be stored in tight, light-resistant packag-ing, preferably at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None Winstrol®-V (Pﬁzer) tablets and injection were previously available. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: Stanozolol Oral Tablets: 2 mg (scored); Winstrol® (Winthrop Pharm. ); (Rx, C-III) STAPHYLOCOCCAL PHAGE LYSATE (staf-loe-kok-al faje lye-sate) Staphage Lysate (SP)®, SPL IMMUNE STIMULANT Prescriber Highlights TT Injectable immune stimulant used to treat dogs with re-current, idiopathic, staphylococcal pyodermas TT May cause hypersensitivity (local or systemic) Uses/Indications Staphylococcal phage lysate (SPL) is labeled for treatment of ca-nine pyoderma and related staphylococcal hypersensitivity, or polymicr obial skin infections with a staphylococcal component. Veterinary dermatologists use SPL most commonly to treat recur-rent, idiopathic, staphylococcal pyodermas in combination (at least initially) w ith an appropriate antibiotic. Pharmacology/Actions SPL apparently enhances cell-mediated immunity. It stimulates the production of tumor necrosis factor, interleukin-6, interleukin-a, and a-interferon. Pharmacokinetics No information was located. Contraindications/Precautions/Warnings The label states that “there are no known contraindications to the use of SPL® except that in highly allergic patients, reduced desensi-tizing doses may be indicated. ” However, use with extreme caution, if at all, in patients with prior systemic hypersensitivity reactions to it or documented hypersensitivity reactions to beef products (con-tains unﬁltered beef heart infusion broth). Avoid administering subsequent doses at the same injection site. The p roduct contains no preservative so it must be handled aseptical ly. It is recommended to use the entire contents when the vial is opened. Adverse Effects Adverse effects reported for SPL include post vaccine-type reactions (fever, malaise, etc. ) and injection site reactions (redness, itching, swelling) that may occur in 2-3 hours after injection and persisting up to 3 days. If these effects are excessive, the manufacturer recom-mends dosage reduction. Systemic hypersensitivity reactions are thought to occur rarely. Signs c ould include weakness, vomiting, diarrhea, severe itching, rapid breathing, and/or fatigue/lassitude. Should an anaphylactic-type reaction occur, treat supportively; the manufacturer recom-mends epinephrine and atropine as antidotes. Reproductive/Nursing Safety Studies performed in rats and rabbits demonstrated no impaired fertility or fetal harm. No information was located on safety during nursing, but it is unlikely t o be of concern. Overdosage/Acute Toxicity No speciﬁc information was located. Other than an increased risk for local or systemic hypersensitivity reactions, signiﬁcant morbid-ity appears unlikely. Drug Interactions T ! CELL-MEDIATED IMMUNOSUPPRESSIVE DRUGS (e. g., corticosteroids, cyclosporine ): These drugs may reduce the efﬁcacy of SPL Laboratory Considerations No signiﬁcant concerns noted. Doses T ! DOGS: a) For labeled indications: Highly allergic patients: Skin test with 0. 05- 0. 1 m L intradermally. Therapy: Initially, 0. 2 m L SC, then incremental increases of 0. 2 m L once a week to 1 m L (a total of 5 injections). Then continue at 1 m L SC weekly for approximately 10-12 weeks. For non-allergic patients: 0. 5 m L SC twice weekly for 10-12 weeks, then 0. 5-1 m L every 1-2 weeks. Concomitant antibiotic therapy is recommended for an ini-tial 4-6 week period. Maximum dose should be decreased in small dogs and can be increase d cautiously, if necessary, in large dogs to 1. 5 m L. This dose is continued until improvement is demonstrated	pppbs.pdf
Tthen the interval may be lengthened gradually to the longest interval that maintains adequate clinical control. (Label in-formation; Staphage Ly sate (SPL)®—Delmont Labs) b) For idiopathic, recurrent pyoderma: Typically given 0. 5 m L SC twice weekly for 10-12 weeks, then tapered to effect. This agent is rarely needed, because in most cases, an underlying cause can be identiﬁed and treated. (Gram 2005) Monitoring T ! Clinical efﬁcacy T ! Local and systemic reactions (see adverse effects) Client Information T ! his medication should ideally be administered at a veterinary practice where suitable treatment can be instituted should a seri-ous adverse effect (e. g., anaphylaxis) occur T ! Report to veterinarian any adverse effects noted ( e. g., local effects at injection site, itching, change in behavior or activity level, dif-ﬁculty or unexplained rapid breathing, vomiting, diarrhea) Chemistry/Synonyms SPL is prepared by lysing cultures of Staphylococcal aureas (Cowan serologic types I & III; human strains) by a staphylococcal bacte-riophage. Pre-lysed cell counts (120-180 CFU/m L) are used to standardize the product; ultraﬁltration achieves bacteriologic ste-rility. The prepared solution contains Staphyloc occal aureas compo-nents (protein A extracts), bacteriophage, and unﬁltered beef heart infusion. Storage/Stability/Compatibility SPL should be stored in the refrigerator (2-7°C); do not freeze. Unopened, properly stored vials and ampules have an average expiratio n date of one year past the shipment date. The product contains no preservative and must be handled aseptically. It is rec-ommended using the entire contents of the vial after opening. Do not use if cont ents are cloudy. Do not mix with other drugs or solutions prior to admin istration. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Staphylococcal Phage Lysate (serotypes I & III): in 1 m L ampules (box of 10) and 10 m L multi-dose vials (no preservative added and manufacturer recommends using entire contents when opened); Staphage Lysate (SPL)® (Delmont Labs); (Biologic OTC) Note : This product is a USDA-licensed biologic and is not an FDA-approved product. HUMAN-LABELED PRODUCTS: None STREPTOKINASE (strep-toe-kin-ase) Streptase® THROMBOLYTIC Prescriber Highlights TT Used for serious thromboembolic disease in dogs TT May be contraindicated in cats; use is controversial in this species TT Adverse Effects (most frequent/serious): Hemorrhage, hyperkalemia, fever, & allergic reactions TT Expensive TT Patient must be intensively monitored Uses/Indications Streptokinase may be useful for the adjunctive treatment of serious thromboses. The use of thrombolytics (streptokinase, t-PA) in cats is controversial. Pharmacology/Actions Streptokinase promotes thrombolysis via a complex mechanism; put simply, streptokinase helps convert plasminogen into plasmin. Plasmin then degrades ﬁbrin and ﬁbrinogen to lyse thrombi. Pharmacokinetics After IV injection, streptokinase is cleared from the circula-tion rapidly via the reticuloendothelial system and by circulating antibodies. Contraindications/Precautions/Warnings Streptokinase is contraindicated in severe hypertension, internal bleeding, trauma within the past month, or when the risks of hem-orrhage outweigh the beneﬁts of therapy. Streptokinase use is controversial in cats and many clinicians be-lieve it is contraindicated in this species. While the drug has been used withou t mortality under research conditions, lack of efﬁcacy in the laboratory and high rates of death in clinical settings have occurred. Streptokinase therapy in veterinary medicine should be reserved for those hospitals where adequate monitoring is available (Heme/ coag lab) and having clinical experience in managing serious thrombotic and coagulation disorders. Adverse Effects The most severe and frequently reported adverse effects associated with streptokinase therapy in dogs are hemorrhage, fever, hyper-kalemia, and allergic reactions. Additionally, hypotension, arrhyth-mias, and phlebitis at the site of the injection have been noted. In cats, thrombolytic therapy has been associated with a high mortality and morbidity. Hyperkalemia, acidosis, mild hemor-rhage, and fever have been reported in cats. Streptokinase resistance has been reported in humans, particu-larly after a recent Streptococcal infection or if previous strepto-kinase therapy has been given. If thrombin time or other factors associated with lysis have not changed after 4 hours of therapy, it is recommended to discontinue therapy. Reproductive/Nursing Safety It is unknown if streptokinase can cause fetal harm. The drug may cause premature separation of the placenta if administered during the ﬁrst half of pregnancy. Streptokinase apparently does not cross	pppbs.pdf
the placenta, but antibodies to it do. In humans, the FDA categoriz-es 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. ) Overdosage/Acute Toxicity See Adverse Effects above. Treating severe spontaneous bleeding may include: discontinuing streptokinase infusions and giving plas-ma volume expanders (dextrans, hetastarch, and packed RBC's). In an emerg ency situation, aminocaproic acid may be considered to reduce the ﬁbrinolytic state. Doses for humans are: loading dose of 5 grams (IV or PO) followed by 1 gram per hour for 2-4 hours. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving streptokinase and may be of signiﬁcance in veterinary patients: T ! AMINOCAPROIC ACID : May reverse the ﬁbrinolytic effects of streptokinase T ! HEPARIN, WARFARIN : Other anticoagulants are often used in con-junction with streptokinase, but may increase the likelihood of bleeding; adequate monitoring is essential Laboratory Considerations T ! IV streptokinase will signiﬁcantly decrease plasminogen and ﬁbrin-ogen, and increase TT, a PTT and PT. Doses T ! DOGS: For the treatment of serious thrombosis: a) 90,000 IU IV over 1/2 hour followed by a constant rate infu-sion of 45,000 IU per hour for 7-12 hours. Must also speciﬁ-cally treat primary disease process and give supportive care to co rrect hypoxemia and loss of tissue perfusion. (Brooks 2000) b) 15,000-18,000 U/kg IV as a loading dose, followed by a maintenance dose of 45,000 U/hr for up to 12 hours. Use only if hemodynamically stable. (Kramer 2003b) c) For pulmonary thromboembolism: 90,000 IU IV over 30 minutes followed by a constant rate infusion of 45,000 IU per hour for 6-12 hours until respiration/hypoxemia improves. (Macintire 2006c) T ! CATS: Note : Thrombolytic therapy in cats is controversial. Use with ex-treme caution. For thro mbolytic treatment of serious thrombosis: a) 90,000 IU IV over 20 minutes followed by a constant rate infusion of 45,000 IU for 2-24 hours (Fox 2003b), (Fox 2007a) Monitoring Monitoring essential: T ! Coagulation status: hemorrhage, serial ﬁbrinogen, ﬁbrin degra-dation products T ! Blood pressure T ! Serum potassium T ! Clinical status (including temperature) Chemistry/Synonyms Produced by group C Beta-hemolytic streptococci, streptokinase is commercially available as a lyophilized white powder. It is freely soluble in water. Streptokinase may also be known as: estreptoquinasa, plasminoki-nase, streptokinasum, Kabikinase ®, Streptase®, Streptonase®, Uni-tinase®, or Zykinase®. Storage/Stability The powder should be stored at room temperature. Because they contain no preservatives, ideally, streptokinase solutions should be used immediately after reconstitution. If administration is delayed, refrigerate the solution and use within 24 hours. Do not mix with dextran solutions. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Streptokinase Powder for Injection lyophilized: 250,000 IU, 750,000 IU or 1. 5 million IU preservative-free in 6 m L vials and 50 m L infu-sion bottles; Stre ptase® (Aventis Behring); (Rx) STREPTOZOCIN (strep-toe-zoe-sin) Zanosar® ANTINEOPLA STIC Prescriber Highlights TT Antineoplastic used primarily for treating recurrent insuli-noma in dogs TT May be nephrotoxic, myelotoxic, hepatotoxic TT Vomiting after treatment may occur TT To reduce nephrotoxicity, must give saline diuresis during administration Uses/Indications At present the primary purpose for streptozocin use in veterinary medicine is as a treatment for insulinomas in dogs, particularly those with refractory hypoglycemia and when tumors are non-resectable or have metastasized. Streptozocin potentially could be used for othe r oncologic conditions as well. Pharmacology/Actions While streptozocin has activity against gram-positive and gram-negative bacteria, its cytotoxicity prevents it from clinical useful-ness for this purpose. While its antineoplastic activity is not well underst ood, streptozocin is considered an alkylating agent and it inhibits DNA synthesis, probably by inhibiting precursor incorpo-ration into DNA. Streptozocin also exhibits a species-speciﬁc (in dogs, not hu-mans) diabetogenic effect via reducing nicotinamide adenine di-nucleotide (NAD) concentration in pancreatic beta cells. This effect is usuall y irreversible in animals with preexisting normal beta cell function. Pharmacokinetics Streptozocin must be administered IV. Its distribution character-istics are not well known, but the drug does distribute to most tis-sues; concentrations in the pancreas are higher than those found in plasma. Str eptozocin is metabolized, probably in the liver. Both unchanged and metabolized drug are excreted in the urine.	pppbs.pdf
Contraindications/Precautions/Warnings Should be used for recurrent insulinoma only in dogs that have un-dergone previous surgery in which all of the tumor could not be resect ed. Conﬁrmed histologic diagnosis is mandatory. Streptozocin must be used with extreme caution in patients with decrease d renal, bone marrow, or hepatic function. Adverse Effects The primary concern when used for treating insulinomas in dogs is the potential for the development of serious, permanent renal tox-icity. Aggressive saline diuresis during drug administration appears to re duce this concern. Additionally, GI effects (vomiting/nausea) often occur and can be severe or protracted. Less commonly, hema-tologic changes (mild myelosuppression) and increases in liver en-zymes can occur. Injection site reactions (including severe necrosis) may occur if the drug extravasates. Reproductive/Nursing Safety Streptozocin has been shown to be teratogenic in rats; use during pregnancy 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 studies in humans; or there are no animal reproduc-tion studies and no adequate studies in humans. ) It is not known whether streptozocin is excreted in milk. Because of the p otential for serious adverse reactions in nursing offspring, consider using milk replacer if used in nursing patients. Overdosage/Acute Toxicity Severe toxicity may result if acutely overdosed (see Adverse Effects); calculate dosages carefully. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving streptozocin and may be of signiﬁcance in veterinary patients: T ! DOXORUBICIN : Streptozocin may prolong the half-life of doxorubi-cin; dosage adjustment may be required T ! MYELOSUPPRESSIVE DRUGS, OTHER : When streptozocin is used with other myelosuppressive drugs (e. g., carmustine ) additive or syner-gistic myelosuppression may occur T ! NEPHROTOXIC DRUGS, OTHER (aminoglycosides, amphotericin B, cis-platin, etc. ): May cause additive nephrotoxicity when used with streptozocin T ! NIACINAMIDE (nicotinamide ): Can block the diabetogenic effects of streptozocin without altering its antineoplastic activity; this may be beneﬁcial or detrimental depending on the reason for use Doses T ! DOGS: a) For “investigational” treatment of recurrent insulinoma after surger y: Begin saline diuresis: Give normal saline at 18-20 m L/kg/hour for 7-8 hours. Over the 4th-5th hour, give streptozocin in the saline solution at a dose of 500 mg/m2 IV. Give an antiemetic (e. g., buto rphanol) at the end of the 7-hour period. (Meleo and Caplan 2000) b) Normal saline is given IV at 18. 3 m L/kg/hr for 3 hours, then strep tozocin is administered at 500 mg/m2 over two hours with the saline diuresis continuing. After streptozocin infu-sion completed, continue saline diuresis for another 2 hours. Buto rphanol is administered as an antiemetic immediately after streptozocin. May repeat at 3 week intervals until evi-dence of tumor progression, recurrence of hypoglycemia, or drug to xicity. Monitor for myelosuppression and nephrotox-icity. (Moore, Nelson et al. 2002) Monitoring T ! Blood glucose (efﬁcacy) T ! Baseline renal function tests (including urinalyses) and after treatment T ! CBC T ! Baseline liver function tests and before retreatment T ! Hydration status (especially for the ﬁrst few days after treatment or if vomiting a problem). Client Information T ! Clients should understand the “experimental” nature of this treatment and the potential risks for serious adverse effects; fol-low-up monitoring is essential. Chemistry/Synonyms Streptozocin is an antineoplastic antibiotic produced by Streptomyces achromogenes, although the commercial product is prepared syn-thetically. It occurs as an ivory colored, crystalline powder. It is very soluble in wate r and has a p Ka of 1. 35. Streptozocin may also be known as: NSC-85998, streptozotocin, U-9889 and Zanosar®. Storage/Stability The lyophilized powder for injection should be stored in the refrig-erator and protected from light. It is stable for at least 3 years after manufact ure. If stored at room temperature, it is stable for at least one year after manufacture. After reconstitution, the lyophilized powder for injection has a p H of 3. 5 -4. 5. Dextrose 5% or 0. 9% sodium chloride are used to reconstitute the solution. Citric acid is added to buffer the solu-tion at a concentration of 22 mg/m L. The solution is stable for 48 hours at r oom temperature and 96 hours if refrigerated, but as no preservative is added the manufacturer recommends using the drug within 12 hours of mixing. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Streptozocin Powder for Injection: 1 gram (100 mg/m L) in vials; Zanosar® (Genesia Sicor); (Rx) SUCCIMER (sux-i-mer) Chemet®, DMSA, Dimercaptosuccinic acid ANTIDOTE; CHELATOR Prescriber Highlights TT Oral heavy metal chelator TT Appears to be safe & effective despite limited experience TT Most likely adverse effects noted are GI in nature; may also cause increased liver enzymes, rash TT High doses may be fatal in birds TT Unpleasant odor of capsules; may give feces, urine, sa-liva, etc. a very unpleasant smell TT Cost is an issue	pppbs.pdf
Uses/Indications In veterinary medicine, succimer may be useful for the oral treatment of lead poisoning in small animals (including birds). Potentially, it also may be of beneﬁt for the treatment of other toxic heavy metals such as arsenic or mercury, but more research must be done before this can be recommended. Pharmacology/Actions Succimer physically chelates heavy metals such as lead, mercury, and arsenic. These water-soluble chelates are then excreted via the kidneys. Pharmacokinetics No veterinary information was located. In humans, the drug is rap-idly absorbed after oral ingestion, but only incompletely. Absorbed drug is excreted primarily through the kidneys into the urine. Half-life in humans is about 2 days. Contraindications/Precautions/Warnings Succimer is contraindicated in patients hypersensitive to it. Chelation therapy should only be attempted if the source of lead is removed to prevent further exposure. Adverse Effects Most common adverse reactions reported in humans are GI relat-ed effects (vomiting, diarrhea, etc. ) or “ﬂu-like” symptoms (body ac hes, fatigue, etc. ). Increases in liver enzymes and rashes have also been reported. Reproductive/Nursing Safety It is unknown if succimer is safe to use during pregnancy. At high doses it was fetotoxic and teratogenic in mice. Mothers are discour-aged from nursing when taking succimer. In humans, the FDA cat-egorizes this drug as category C fo r 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 st udies in humans. ) It is not known whether this drug is excreted in breast milk. Disc ourage mothers requiring therapy from nursing their infants. Overdosage/Acute Toxicity In toxicology studies, doses of up to 200 mg/kg per day in dogs did not cause overt toxicity. Doses of 300 mg/day did cause fatalities in dogs; primarily kidney and GI tract lesions were seen. Doses of 80 mg/kg, PO q12h did cause a signiﬁcant number of fatalities in Cockatiels (but 40 mg/kg q12h did not). If an overdose situation is encountered, standardized gut evacuation with subsequent acti-vated charcoal protocols are recommended. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving succimer and may be of signiﬁcance in veterinary patients: !TCHELATING AGENTS, OTHER (Ca EDTA, dimercaprol, trientine, pen-icillamine, etc. ): Concomitant use with other chelating agents is not recommended in humans Laboratory Considerations !TFalse positive urine ketones can be reported when using nitrop-russide reagents (e. g., as in K etostix®) !TFalsely low measurements of CPK or serum uric acid can be caused by succimer Doses !TDOGS: For lead poisoning: a) 10 mg/kg, PO q8h for 10 days (Sisson 2000) b) 10 mg/kg PO three times daily for 5 days, followed by 10 mg/ kg PO twic e daily for 2 weeks (Poppenga 2002) !TCATS: For lead poisoning: a) 10 mg/kg PO three times daily for 5 days, followed by 10 mg/ kg PO twic e daily for 2 weeks (Poppenga 2002) !TBIRDS: For lead poisoning: a) 15-35 mg/kg PO twice daily for 5 days (Calvert and Mieurs 2000) b) 30 mg/kg PO twice daily for a minimum of 7 days. If severe neur ologic signs, may supplement with one dose of Ca EDTA (edetate calcium disodium; <50 mg/kg of body weight IM) (Hoogesteijn, Raphael et al. 2003) Monitoring !TBlood lead !TGI adverse effects !TLiver enzymes (AST, ALT) Client Information !TCapsules may have an unpleasant odor; this is no problem with the drug, but unpleasant odor may be transferred to saliva, urine, feces !TContents of capsules may be sprinkled on soft food !TAnimals must be adequately hydrated as the lead chelates are ex-creted in the urine Chemistry/Synonyms A heavy metal chelating agent also known as meso-2,3 dimercapto-succinic acid (DMSA), succimer is an analog of dimercaprol. It has an unpleasant od or. Succimer may also be known as: meso-2,3 dimercaptosuc-cinic acid, dimercaptosuccinic acid, DIM-SA, DMSA, Cheme t® or Succicaptal®. Storage/Stability Unless otherwise labeled, store succimer capsules in tight contain-ers at room temperature. Protect from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Succimer Capsules: 100 mg; Chemet® (Ovation); (Rx)	pppbs.pdf
SUCCINYLCHOLINE CHLORIDE (suks-sin-i-nil-koe-leen) Anectine® NEUROMUSCULAR BLOCKING AGENT Prescriber Highlights TT Depolarizing neuromuscular blocking agent TT Contraindications: Severe liver disease, chronic anemias, malnourishment, glaucoma or penetrating eye injuries, predisposition to malignant hyperthermia, & increased CPK values with resultant myopathies TT Extreme Caution: Traumatic wounds or burns, receiving quinidine or digoxin therapy, hyperkalemia or electrolyte imbalances TT Caution: Pulmonary, renal, cardiovascular, metabolic or hepatic dysfunction TT Adverse Effects: Muscle soreness, histamine release, ma-lignant hyperthermia, excessive salivation, hyperkalemia, rash, & myoglobinemia/m yoglobinuria. Cardio vascular effects, (bradycardia, tachycardia, hypertension, hypoten-sion, or arrhythmias) TT Speciﬁc recommendations for use in horses (see Con-traindications below) TT No analgesic or anesthetic effects Uses/Indications Succinylcholine chloride is indicated for short-term muscle relax-ation needed for surgical or diagnostic procedures, to facilitate en-dotracheal intubation in some species, and reducing the intensity of musc le contractions associated with electro-or pharmacolog-ical-induced convulsions. Dogs, cats, and horses are the primary vete rinary species where succinylcholine chloride has been used. Pharmacology/Actions An ultrashort-acting depolarizing skeletal muscle relaxant, suc-cinylcholine bonds with motor endplate cholinergic receptors to prod uce depolarization (perceived as fasciculations). The neuro-muscular block remains as long as sufﬁcient quantities of succinyl-choline remain, and is characterized by a ﬂaccid paralysis. Other pharmac ologic effects are discussed in the precautions and adverse effects sections. Pharmacokinetics The onset of action, with complete muscle relaxation, after IV ad-ministration is usually within 30-60 seconds. In humans, this ef-fect lasts for 2-3 minutes and then gradually diminishes within 10 minutes. The very short duration of action after a single IV dose is thought to occur because the drug diffuses away from the motor end plate. If multiple injections or a continuous infusion is per-formed, the brief activity is a result of rapid hydrolysis by pseudo-cholinesterases at the site of action. After IM injection, the onset of actio n is generally within 2-3 minutes and may persist for 10-30 minutes. Dogs exhibit a prolonged duration of action (≈ 20 min-utes); this species appears unique in this idiosyncratic response. Succinylcholine is metabolized by plasma pseudocholinesterases to suc cinylmonocholine and choline; 10% is excreted unchanged in the urine. Succinylmonocholine is partially excreted in the urine and may accumulate in patients with impaired renal function. Succinylmonocholine has approximately 1/20th the neuromuscu-lar blocking activity of succinylcholine, but if it accumulates, pro-longed periods of apnea may result. Contraindications/Precautions/Warnings Succinylcholine is contraindicated in patients with severe liver dis-ease, chronic anemias, malnourishment (chronic), glaucoma or penet rating eye injuries, predisposition to malignant hypertherm-ia, and increased CPK values with resultant myopathies. As suc-cinylcholine can exacerbate the effects of hyperkalemia, it should be used with extreme caution in patients who have suffered trau-matic wounds or burns, are receiving quinidine or digoxin therapy, or hav e preexisting hyperkalemia or electrolyte imbalances as ar-rhythmias or cardiac arrest may occur. It should be used with cau-tion in patients with pulmonary, renal, cardiovascular, metabolic, or hepatic d ysfunction. Succinylcholine should not be used if organophosphate agents have be en given or applied recently. Succinylcholine chloride does not have analgesic effects; and should be use d with appropriate analgesic, sedative, and anesthetic agents. In horses, The American Association of Equine Practitioners have mad e the following additional recommendations: 1) Inform the owner that succinylcholine chloride is to be used as a restraining ag ent, not as an anesthetic. 2) Obtain history before use; do not use in horses if within 30 days the y have received, an antibiotic ending in “mycin”, or-ganophosphate insecticides or anthelmintics, any other cho-linesterase inhibitor, or procaine. 3) Do not use in debilitated, excited, or exhausted horses. 4) If possible, withhold food for 4-6 hours before use. 5) Dosage of 0. 088 mg/kg IV may be used to paralyze skeletal muscles w ithout causing respiratory depression. Higher dos-es may cause apnea and death without respiratory support. Lowe r doses may be possible if used with a preanesthetic agent. 6) After administration, have someone hold the horse that is familiar with the actions of succinylcholine chloride so that the animal does not fall forward on its nose. Be prepared to administer oxygen and artiﬁcial respiration. 7) If death occurs, a necropsy should be performed. Adverse Effects Succinylcholine chloride can cause muscle soreness, histamine re-lease, malignant hyperthermia, excessive salivation, hyperkalemia, rash, and m yoglobinemia/myoglobinuria. Cardiovascular effects can include bradycardia, tachycardia, hypertension, hypotension, or arrhythmias. Reproductive/Nursing Safety It is unknown if succinylcholine can cause fetal harm. The drug does cross the placenta in low concentrations and a newly delivered neonate may show signs of neuromuscular blockade if the mother received high doses or prolonged administration of the drug prior to delivery. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse ef-fect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in hu-mans. ) 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 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. )	pppbs.pdf
TIt is not known whether this drug is excreted into milk; exercise caut ion when succinylcholine is administered to a nursing patient. Overdosage/Acute Toxicity Inadvertent overdoses, or standard doses in patients deﬁcient in pseudocholinesterase may result in prolonged apnea. Mechanical ventilation with O 2 should be used until recovery. Repeated or prolonged high dosages may cause patients to con-vert from a phase I to a phase II block. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving succinylcholine and may be of signiﬁcance in veterinary patients: !TAMPHOTERICIN B : May increase succinylcholine's effects by causing electrolyte imbalances !TDIGOXIN : Succinylcholine may cause a sudden outﬂux of potas-sium from muscle cells, thus causing arrhythmias in digitalized patie nts !TOPIATES : Potential for increased incidences of bradycardia and sinus arrest !TTHIAZIDE DIURETICS : May increase succinylcholine's effects by causing electrolyte imbalances The following drugs/drug classes may increase or prolong neuro-muscular blockade if used concurrently with succinylcholine: !!AMINOGLYCOSIDES !!ANESTHETICS, INHALATION (isoﬂurane, desﬂurane ) !!ANTIARRHYTHMICS (quinidine, lidocaine, procainamide ) !!BETA-ADRENERGIC BLOCKERS !!CHLOROQUINE !!CLINDAMYCIN !!CORTICOSTEROIDS !!CYCLOPHOSPHAMIDE !!MAGNESIUM SALTS !!MAO INHIBITORS !!METOCLOPRAMIDE !!NEOSTIGMINE !!ORGANOPHOSPHATES !!OXYTOCIN !!PANCURONIUM !!PHENOTHIAZINES !!PROCAINE (IV) !!TERBUTALINE !TTHIOTEPA Doses !TDOGS: a) 0. 07 mg/kg IV (Morgan 1988) b) 0. 22 mg/kg IV (Mandsager 1988) !TCATS: a) 0. 06 mg/kg IV (Morgan 1988) b) 0. 11 mg/kg IV (Mandsager 1988) !THORSES: See Precautions above. ( Note : ARCI UCGFS Class 2 Drug) a) 0. 088 mg/kg (Muir) b) 0. 088-0. 11 mg/kg IV, IM (Mandsager 1988) !TREPTILES: a) T o relax an animal to allow intubation: 0. 5-1 mg/kg IM. Espe cially helpful with turtles and crocodilians. (Lewbart 2001) Monitoring !TLevel of muscle relaxation !TCardiac rate/rhythm !TRespiratory depressant effect Client Information !This drug should only be used by professionals familiar with its use Chemistry/Synonyms A depolarizing neuromuscular blocking agent, succinylcholine chloride occurs as an odorless, white, crystalline powder. The di-hydrate form melts at 190°C and the anhydrous form at 160°C. Aq ueous solutions are acidic with a p H of approximately 4. One gram is soluble in about 1 m L of water and about 350 m L of alco-hol. Commercially available injections have a p H from 3-4. 5. Succinylcholine chloride may also be known as: choline chloride suc cinate, succicurarium chloride, succinylcholine chloride, sux-amethonii chloridum, suxametonklorid, suxamethonium chloride; many t rade names are available. Storage/Stability/Compatibility Commercial injectable solutions should be stored refrigerated (2°-8°C). One manufacturer (Anectine®—Glaxo Wellcome) states that multiple dose vials are stable up to 2 weeks at room tempera-ture with no signiﬁcant loss of potency. The powder forms of the drug are stable indeﬁnitely when stored unop ened at room temperature. After reconstitution with either D5W or normal saline, they are stable for 4 weeks at 5°C or 1 week at room temperature, but because they contain no preservative, it is recommended they be used within 24 hours. Succinylcholine chloride is physically compatible with all com-monly used IV solutions, amikacin sulfate, cephapirin sodium, iso-proterenol HCl, meperidine HCl, norepinephrine bitartrate, and sco polamine HBr. It may not be compatible with pentobarbital so-dium and is physically incompatible with sodium bicarbonate and thiopental sodium. 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: Succinylcholine Chloride Injection: 20 mg/m L & 50 mg/m L in 10 m L vials, amps and 5 m L Abboject syringes; Anectine® (Glaxo Wellcome); Quelicin® (Hospira); (Rx) Succinylcholine Chloride Powder for Infusion: 500 mg and 1 gram vials; A nectine® Flo-Pak (Glaxo Wellcome); (Rx)	pppbs.pdf
SUCRALFATE (soo-kral-fate) Carafate® GASTROPROTECTANT Prescriber Highlights TT Locally-acting treatment for GI ulcers; may also protect somewhat against GI ulceration. Potentially could be use-ful for lowering serum phosphorus in renal patients. TT Contraindications: None, use with caution where de-creased GI transit times may be harmful TT Adverse Effects: Unlikely; constipation possible TT Give on empty stomach if possible TT Drug Interactions Uses/Indications Sucralfate has been used in the treatment of oral, esophageal, gas-tric, and duodenal ulcers. It has also been employed to prevent drug-induce d (e. g., aspirin) gastric erosions, but efﬁcacy for this is somewhat sporadic. Sucralfate has been used in human patients with hyperphosphatemia secondary to renal failure and potentially could be useful for this in animals as well. Pharmacology/Actions While the exact mechanism of action of sucralfate as an antiulcer agent is not known, the drug has a local effect rather than a systemic one. After oral administration, sucralfate reacts with hydrochloric acid in the stomach to form a paste-like complex that will bind to the proteinaceous exudates that generally are found at ulcer sites. This insoluble complex forms a barrier at the site and protects the ulcer from further damage caused by pepsin, acid, or bile. Sucralfate may have some cytoprotective effects, possibly by stim-ulation of prostaglandin E 2 and I 2. Sucr alfate also has some antacid activity, but it is believed that this is not of clinical importance. Sucralfate does not signiﬁcantly affect gastric acid output, or trypsin or pancreatic amylase activity. It may decrease the rate of gastric emptying. As an aluminum salt, sucralfate can bind to gastrointestinal phosphor us. Pharmacokinetics Animal studies have indicated that only 3-5% of an oral dose is absorbed which is excreted in the urine unchanged within 48 hours. By reacting with hydrochloric acid in the gut, the remainder of the drug is converted to sucrose sulfate which is excreted in the feces within 48 hours. The duration of action (binding to ulcer site) may persist up to 6 hours after oral dosing. Contraindications/Precautions/Warnings There are no known contraindications to the use of sucralfate. Because it may cause constipation, it should be used with cau-tion in animals where decreased intestinal transit times might be delet erious. Adverse Effects Adverse effects are uncommon with sucralfate therapy. Constipation is the most prominent adverse effect reported in humans (2%) and dogs receiving the drug. Reproductive/Nursing Safety It is unknown if sucralfate crosses the placenta and whether it may deﬁnitively be used safely during pregnancy. In rats, dosages up to 38 times those used in humans caused no impaired fertility and doses up to 50 times normal caused no symptoms of teratogenicity. 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 fe-line pregnancy (Papich 1989), this drug is categorized as in class: A (Pro bably safe. Although speciﬁc studies may not have proved he safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) It is not known whether this drug is excreted in milk, but it is unlikely t o be of concern. Overdosage/Acute Toxicity Overdosage is unlikely to cause any signiﬁcant problems. Laboratory animals receiving up to 12 grams/kg orally demonstrated no inci-dence of mortality. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sucralfate and may be of signiﬁcance in veterinary patients: Sucralfate may impair the oral absorption of the following med-ications; separate dosing by at least 2 hours to minimize this effect: ! !CIPROFLOXACIN (assume other oral ﬂuoroquinolones as well) ! !DICLOFENAC ! !DIGOXIN ! !KETOCONAZOLE ! !LEVOTHYROXINE ! !PENICILLAMINE ! !TETRACYCLINES ! !VITAMINS (fat soluble ) T ! WARFARIN Doses T ! DOGS: a) For esophagitis: 0. 5-1 gram PO three times a day. Suspen-sions are more therapeutic than intact tablets. (Washabau 2000) b) For large dogs: 1 gram PO q8; for smaller dogs: 0. 5 gram PO q8h (Zerb e and Washabau 2000) c) 0. 5-1 gram PO 2-4 times a day; patients with severe GI blood loss give an initial loading dose of 3-6 grams and then resume lower dose. If also using an H2 blocker, administer sucralfate 30-60 minutes later. (Hall 2000) d) For eliminating Helicobacter gastritis infections: Using triple therapy : Metronidazole 33 mg/kg once daily, amoxicillin 11 mg/kg q12h and either sucralfate (0. 25-0. 5 grams q8h) or omeprazole 0. 66 mg/kg once daily (Hall 2000) e) In patients with severe hematemesis and anemia we some-times give a loading dose of 3-6 grams initially and then de-crease to 1 gram PO three to four times a day. May not always work in vomiting dogs. Suspensions may have less tendency to be vomited up in these patients. (Willard 2006d) f) For gastric ulcers, esophagitis: 0. 5-1 gram PO per dog q8-12h (Se llon 2007b)	pppbs.pdf
Tg) For GI ulcers/esophagitis associated with acute renal failure: 1 gram pe r 30 kg body weight PO q6h (Waddell 2007a) T ! CATS: a) 0. 25-0. 5 grams PO q8-12h (Zerbe and Washabau 2000) b) 0. 25 gram PO q8-12h (Matz 1995) c) For gastric ulcers, esophagitis: 0. 25-0. 5 grams PO per cat PO q8-12h (Se llon 2007b) T ! FERRETS: a) 75 mg/kg PO q4-6h; give 10 minutes prior to feeding (Wil-liams 2000) T ! HORSES: a) For adjunctive treatment for preventing stress-induced ul-cers in foals: 10-20 mg/kg PO q6-8h (Sanchez 2004b) b) For treating equine gastric ulcer syndrome: 20-40 mg/kg PO q8h (Sanchez 2004b), (N adeau and Andrews 2003) T ! REPTILES: a) For GI irritation in most species: 500-1,000 mg/kg PO q6-8h (Gauv in 1993) Monitoring T ! Clinical efﬁcacy (dependent on reason for use); monitored by decrease in symptomatology, endoscopic examination, blood in feces, etc. Client Information T ! o maximize the beneﬁt of this medication, it must be adminis-tered as prescribed by the veterinarian; clinical signs may reoccur if dosag es ar e missed T ! Unless otherwise instructed, give this medication to animal hav-ing an empty stomach (1 hour before feeding or 2 hours after) and at bedt ime Chemistry/Synonyms A basic, aluminum complex of sucrose sulfate, sucralfate occurs as a white, amorphous powder. It is practically insoluble in alcohol or water. Sucralfate is structurally related to heparin, but does not possess any app reciable anticoagulant activity. It is also structurally related to sucrose, but is not utilized as a sugar by the body. Sucralfate is also known as aluminum sucrose sulfate, basic and Carafate®. Storage/Stability Store sucralfate tablets in tight containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Sucralfate Tablets: 1 gram (scored); Carafate® (Axcan Sandipharm); generic; (Rx) Sucralfate Suspension: 1 g/10 m L in 10 m L unit dose cups & 415 m L; Carafate® (A xcan Scandipharm); generic (Precision Dose); (Rx) SUFENTANIL CITRATE (soo-fen-ta-nil) Sufenta® OPIATE AGONIST Prescriber Highlights TT Injectable, extremely potent opiate that may be useful for adjunctive anesthesia or epidural analgesia TT Marginal veterinary experience & little published data available to draw conclusions on appropriate usage in veterinary species TT Dose-related respiratory & CNS depression most likely adverse effects TT Class-II controlled substance; expensive when compared to fentanyl Uses/Indications An opioid analgesic, sufentanil may be useful as an anesthesia ad-junct or as an epidural analgesic. In humans, it has been used as the primary anesthetic in intubated patients with assisted ventilation, and as a post-operative analgesic. Pharmacology/Actions Sufentanil is a potent mu opioid with the expected sedative, an-algesic, and anesthetic properties. When comparing analgesic po-tencies, 0. 01-0. 04 mg of sufentanil is equivalent to 0. 4-0. 8 mg of alfe ntanil, 0. 1-0. 2 mg of fentanyl, and approximately 10 mg of morphine, when all are injected IM. Like fentanyl, sufentanil ap-pears to have less circulatory effects than does morphine. Sufentanil has a rapid onset of action (1-3 minutes) and a faster recovery time than fentanyl. Pharmacokinetics No information on the pharmacokinetics of sufentanil in domestic animals was located. In humans, the drug has rapid onset of ac-tion (1-3 minutes) after intravenous injection. The drug is highly lipid soluble and has volume of distribution in the central com-partment of 0. 1 L/kg. Approximately 93% is bound to plasma pro-teins; plasma concentrations rapidly decline due to redistribution. T erminal elimination half-life is about 2. 5 hours. Plasma clearance has been reported to be 11. 8 m L/min/kg. Sufentanil is metabolized primarily in the liver and small intestine via O-demethylation and N-dealkylation. The parent drug and these metabolites are excreted primarily in the urine. While the manufacturer states to use with caution in patients with impaired renal of hepatic function, limited pharmacokinetic studies in these patients, rarely showed any drug accumulation. Contraindications/Precautions/Warnings Sufentanil is contraindicated in patients hypersensitive to it or other opioids. It should be used with caution in debilitated or ge-riatric patients and those with severely diminished renal or hepatic function. B ecause of the drug's potency and potential for signiﬁcant ad-verse effects, it should only be used in situations where patient vital signs can b e continuously monitored. Initial dosage reduction may be required in geriatric or debilitated patients, particularly those with diminished cardiopulmonary function.	pppbs.pdf
Adverse Effects Adverse effects are generally dose related and consistent with other opiate agonists. Respiratory depression and/or CNS depression are most likely to be encountered. In humans, bradycardia that is usually responsive to anticho-linergic agents can occur. Dose-related skeletal muscle rigidity is not unc ommon, and neuromuscular blockers are routinely used. Sufentanil has rarely been associated with asystole, hypercarbia and hypersensitivity reactions. Respiratory or CNS depression may be exacerbated if sufentanil is gi ven with other drugs that can cause those effects. Reproductive/Nursing Safety In humans, the FDA categorizes sufentanil 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. ) While sufentanil is indicated for epidural use (mixed with bupi-vacaine ± epinephrine) in women for labor/delivery, it should not be administered systemically to a mother close to giving birth as offspring may show behavioral alterations (hypotonia, depression) associated with opioids. The effects of sufentanil on lactation or its safety for nursing off spring is not well-deﬁned, but sufentanil milk levels approximate those found in serum. This coupled with its low oral bioavailability, make it unlikely to cause signiﬁcant effects in nursing offspring. Overdosage/Acute Toxicity In dogs, the LD50 of intravenous sufentanil is 10. 1-19. 5 mg/kg. Int ravenous severe overdoses may cause apnea, circulatory collapse, pulmonary edema, seizures, cardiac arrest and death. Treatment is a combination of supportive therapy and administration of an opiate antagonist such as naloxone. Although sufentanil has a fairly rapid half-life, multiple doses of naloxone may be necessary. Because of the drug's potency, the use of a tuberculin syringe to measure dos-ages less than 1 m L, with a dosage calculation and measurement doub le-check system is recommended. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sufentanil and may be of signiﬁcance in veterinary patients: !TBETA-ADRENERGIC BLOCKERS : May increase bradycardia and hypotension !TCALCIUM-CHANNEL BLOCKERS : May increase bradycardia and hypotension !TCNS DEPRESSANTS, OTHER : Additive effects can occur if sufentanil is used concurrently with other drugs that can depress CNS or respiratory function (e. g., barbiturates, etc. ) !TNITROUS OXIDE : Can cause cardiovascular depression if used with high dose sufentanil Laboratory Considerations !TBecause opiates can increase biliary tract pressure and raise se-rum amylase and lipase values, these values may be unreliable for 24 hours after sufentanil is administered. Doses (NOTE : In very obese patients, ﬁgure dosages based upon lean body weight. ) !TDOGS: a) As a pre-med: 3 mcg/kg IV. As a combination for induction: Suf entanil 3 mcg/kg IV ﬁrst, then diazepam or midazolam 0. 2-0. 5 mg IV. (Banyard 2004) b) For epidural analgesia: 0. 7-1 mcg/kg diluted to a volume of 0. 26 m L/kg with sterile saline. Onset of action in 10-15 min-utes; duration 1-4 hours. (Otero 2006b) c) Acute pain relief in an emergency: 0. 75-2 mcg/kg IV; con-stant rate infusion of 1-2 mcg/kg/hour. (Otero 2006a) d) For surgical pain: 5 mcg/kg IV prior to a CRI. Duration of eff ect: 2-6 hours. CRI (post-operative) of 0. 1 mcg/kg/hour. (Ogilvie 2004) !TCATS: a) Acute pain relief in an emergency: 0. 1-0. 5 mcg/kg IV; con-stant rate infusion of 0. 5-1 mcg/kg/hour. (Otero 2006a) Monitoring !TAnesthetic and/or analgesic efﬁcacy !TCardiac and respiratory rate !TPulse oximetry or other methods to measure blood oxygenation when used for anesthesia Client Information !TSufentanil is a very potent opiate that should only be used by professionals in a setting where adequate patient monitoring is available. Chemistry/Synonyms A phenylpiperidine derivative opioid related to fentanyl, sufenta-nil citrate occurs as a white or almost white powder that is soluble in wat er, sparingly soluble in alcohol, acetone, or chloroform. The commercially available injection has a p H (adjusted with citric acid) of 3. 5-6. Sufentanil citrate may also be known as: R-33800, sufentanili citr as, fentathienel citrate, sufentanyl citrate, sulfentanil citrate, Fastfen®, Fentaientel® and Sufenta®. Storage/Stability/Compatibility Unless otherwise labeled, sufentanil injection should be stored pro-tected from light at room temperature. Sufentanil citrate is hydro-lyzed in acidic solutions. Sufentanil citrate is reportedly compatible with D5W and bupiva-caine. For Y-site injection it is compatible with solutions containing: atropine, dexamethasone sodium phosphate, diazepam, diphen-hydramine, etomidate, metoclopramide, midazolam, phenobarbi-tal, and propofol. It is incompatible with lorazepam, phenytoin and thiopental. 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: Sufentanil Citrate Injection: 50 mcg/m L (as base) in 1 m L, 2 m L and 5 m L amps; Sufenta® (preservative free) (Taylor); generic (with pre-servatives); (Rx, C-II).	pppbs.pdf
SULFACHLORPYRIDAZINE SODIUM (sul-fa-klor-pye-rid-a-zeen) Vetisulid® SULFONAMIDE ANTIBACTERIAL Prescriber Highlights TT Contraindications: Hypersensitivity to sulfas, thiazides, or sulfonylurea agents; severe renal or hepatic impairment TT Caution: Diminished renal or hepatic function, or urinary obstruction TT Adverse Effects: Can precipitate in the urine (especially with high dosages for prolonged periods, acidic urine or highly concentrated urine); DOGS: Keratoconjunctivitis sicca, bone marrow depression, hypersensitivity reactions (rashes, dermatitis), focal retinitis, fever, vomiting, & non-septic polyarthritis possible TT Potentially teratogenic; weigh risk vs. beneﬁt TT Too-rapid IV injection may cause muscle weakness, blind-ness, ataxia, & collapse; SC or IM injection may cause tissue irritation Uses/Indications Sulfachlorpyridazine is indicated for the treatment of diarrhea caused or complicated by E. coli in calves less than one month of age or colibacillosis in swine. It is also used parenterally as a general-purpose sulfonamide in adult cattle and other species. Pharmacology/Actions Sulfonamides are usually bacteriostatic agents when used alone. They are thought to prevent bacterial replication by competing with para-aminobenzoic acid (PABA) in the biosynthesis of tetra-hydrofolic acid in the pathway to form folic acid. Only microorgan-isms that synthesize their own folic acid are affected by sulfas. Microorganisms that are usually affected by sulfonamides in-clude some gram-positive bacteria, including some strains of strep-tococci, staphylococcus, Bacillus anthracis, Clostridium tetani, C. perfringens, and many strains of Nocardia. Sulfas have in vitro ac-tivity against some gram-negative species, including some strains of Shige lla, Salmonella, E. coli, Klebsiella, Enterobacter, Pasturella, and Proteus. Sulfas also have activity against some rickettsia and protozoa (T oxoplasma, Coccidia). Unfortunately, resistance to sul-fas is a progressing phenomenon and many strains of bacteria that were once susceptible to this class of antibacterial are now resistant. The sulfas are less efﬁcacious in pus, necrotic tissue, or in areas with extensive cellular debris. Pharmacokinetics Very limited information is available on the speciﬁc pharmacoki-netics for this agent. In general, sulfonamides are readily absorbed from the GI tract of non-ruminants, but absorption can vary de-pending on the drug, species, disease process, etc. Food delays the rate, b ut usually not the extent of absorption. Peak levels occur within 1-2 hours in non-ruminant (and young pre-ruminant) ani-mals. Adult ruminants may have signiﬁcant delays before the drug is absorbe d orally. Sulfas are well distributed throughout the body and some reach signiﬁcant lev els in the CSF. Levels of the drugs tend to be highest in liver, kidney, and lung, and lower in muscle and bone. The sulfas can be highly bound to serum proteins, but the extent of binding is species and drug dependent. When bound to proteins the sulfa is not acti ve. Sulfonamides are both renally excreted and metabolized. Renal excre tion of unchanged drug occurs via both tubular secretion and glomerular ﬁltration. Protein bound drug is not ﬁltered by the glomeruli. Metabolism is performed principally in the liver, but extra-hepatic metabolism is also involved. Mechanisms of metabo-lism are usually acetylation and glucuronidation. The acetylated metabolites may be less soluble and crystallization in the urine can occur with some sulfonamides, particularly at lower p H. The se-rum half-life of sulfachlorpyridazine is approximately 1. 2 hours in cattle. Contraindications/Precautions/Warnings Sulfonamides are contraindicated in patients hypersensitive to them, thiazides, or sulfonylurea agents. They are also considered contraindicated in patients with severe renal or hepatic impairment and should be used with caution in patients with diminished renal or hepatic function, or urinary obstruction. Oral sulfonamides can depress the normal cellulytic function of the ruminor eticulum, but this effect is generally temporary and the animal adapts. Adverse Effects Sulfonamides (or their metabolites) can precipitate in the urine, particularly when given at high dosages for prolonged periods. Acidic or highly concentrated urine may also contribute to in-creased risk of crystalluria, hematuria, and renal tubule obstruc-tion. Different sulfonamides have different solubilities at various p H's. Alkalinizat ion of the urine using sodium bicarbonate may prevent crystalluria, but it also decreases the amount available for tubular reabsorption. Crystalluria can usually be avoided with most of the commercially available sulfonamides by maintaining an ad-equate urine ﬂow. Normal urine p H in herbivores is usually 8 or more, so crystalluria is not frequently a problem. Sulfonamides can also cause various hypersensitivity reactions or diarrhea by altering the normal gut ﬂora. T oo rapid intravenous injection of the sulfas can cause muscle weakness, blindness, ataxia, and collapse. In dogs, keratoconjunctivitis sicca has been reported with sul-fonamide therapy. In addition, bone marrow depression, hypersen-sitivity reactions (rashes, dermatitis), focal retinitis, fever, vomiting and nonsept ic polyarthritis have been reported in dogs. Oral sulfonamides can depress the normal cellulytic function of the ruminor eticulum, but this effect is generally temporary and the animal adapts. Because solutions of sulfonamides are usually alkaline, they can cause tissue irritation and necrosis if injected intramuscularly or subcutaneously. Reproductive/Nursing Safety Sulfas cross the placenta and may reach fetal levels of 50% or great-er those found in maternal serum; teratogenicity has been reported in some lab oratory animals when given at very high doses. They should be used in pregnant animals only when the beneﬁts clearly outweigh the risks of therapy. Sulfonamides are distributed into milk. Safe use during lactation cannot be assumed; use with caution. Overdosage/Acute Toxicity Acute toxicity secondary to overdoses apparently occurs only rarely in veterinary species. In addition to the adverse effects listed above, CNS stimulation and myelin degeneration have been noted after very high dosages.	pppbs.pdf
TDrug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sulfachlorpyridazine and may be of signiﬁcance in veterinary patients: T ! ANTACIDS : May decrease the oral bioavailability of sulfonamides if administered concurrently Laboratory Considerations T ! Sulfonamides may give false-positive results for urine glucose de-terminations when using the Benedict's method. Doses T ! CATTLE: In calves for labeled indications: 33-49. 5 mg/kg PO, or IV twice daily for 1-5 days; suggest initiating therapy with intravenous preparation and then changing to oral if possible (Package in-sert; Vetisulid®—Fort Dodge) T ! SWINE: For labeled indications: 44-77 mg/kg PO per day (divide dose and give twice daily if treating individual animals) for 1-5 days (Package insert; Vetisulid®—Fort Dodge) T ! BIRDS: For enteric bacterial infections: a) Using the oral powder: Mix 1/4 teaspoonful per liter of water and use as o nly supply of drinking water for 5-10 days. May be effective for many E. coli enteric infections. (Clubb 1986) b) Using the oral powder: Mix 3/4 teaspoonsful per 2 quarts of water. Fairly effective for enteric infections, particularly E. coli. Reserved for clients who are unable to give other medi-cations by mouth or parenterally. (Mc Donald 1989) c) For pigeons: 1200 mg per gallon of drinking water. Very ef-fective for E. coli and it is a good coccidiostat. (Harlin 2006) Monitoring T ! Clinical efﬁcacy T ! Adverse effects Client Information T ! o help reduce the possibility of crystalluria occurring, animals should have free access to water; avoid dehydration. Chemistry/Synonyms Sulfachlorpyridazine sodium is listed as a short to intermediate-acting, low lipid soluble sulfonamide antibacterial. It is reportedly very soluble in urine at usual p H's. Sulfachlorpyridazine may also be known as cluricol, sulphachlo-rpyridazine, or Vetisulid®. Storage/Stability/Compatibility The injection should be stored at room temperature and protected from light; avoid freezing. The oral suspension should be stored at room temperature; avoid freezing. The oral boluses and powder should be stored at room temperature; avoid excessive heat (above 40°C/104°F). No information was located regarding the compatibility of sul-fachlorpyridazine with other ﬂuids or agents. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Sulfachlorpyridazine Sodium Oral powder: 54 grams per bottle; Vetisulid® Powder (Fort Dodge); (OTC) Indicated for use in calves under one month of age and swine. Slaughter withdrawal (at labeled doses) = 7 days for cattle and 4 days for swine. Sulfachlorpyridazine Sodium Oral Suspension: 50 mg/m L in 180 m L bottles; Vet isulid® Oral Suspension (Fort Dodge); (OTC). Approved for use in swine. Slaughter withdrawal (at labeled doses) = 4 days for swine. HUMAN-LABELED PRODUCTS: None Sulfadiazine/Pyrimethamine — See Pyrimethamine/ Sulfadiazine SULFADIAZINE/TRIMETHOPRIM SULFAMETHOXAZOLE/ TRIMETHOPRIM (sul-fa-dye-a-zeen; sul-fa-meth-ox-a-zole/trye-meth-ohe-prim) Co-trimoxazole, Tribrissen®, Bactrim®, Septra® POTENTIATED SULFONAMIDE ANTIMICROBIAL Note : In the practice of veterinary medicine in the USA, two sepa-rate combinations with trimethoprim are used clinically. There are trimetho prim/sulfadiazine products approved for use in dogs, cats, and horses in both parenteral and oral dosage forms. Many veterinarians also use the human approved, trimethoprim/sulfamethoxazole oral products. In Canada, sulfadoxine is available in combination with trimethoprim for veterinary use. Prescriber Highlights TT Potentiated sulfonamide antimicrobial agent TT Contraindications: Hypersensitivity to sulfas, thiazides, or sulfonylurea agents; severe renal or hepatic impairment TT Caution: Diminished renal or hepatic function, or urinary obstruction or urolithiasis TT Adverse Effects: DOGS: Keratoconjunctivitis sicca, hyper-sensitivity (type 1 or type 3), acute neutrophilic hepatitis with icterus, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, polydipsia, crystalluria, hematuria, polyuria, cholestasis, hypothy-roidism, anemias, agranulocytosis, idiosyncratic hepatic necrosis in dogs. CATS: Anorexia, crystalluria, hematuria, leukopenias & anemias. HORSES: Transient pruritic (after IV injection). Oral: diarrhea, hypersensitivity reactions & hematologic effects (anemias, thrombocytopenia, or leu-kopenias TT Local injection effects possible (check label for product recommendation for injection technique) TT Potentially teratogenic, weigh risk vs. beneﬁt Uses/Indications Although only approved for use in dogs and horses, trimethoprim/ sulfadiazine etc. is used in many species to treat infections caused by susceptible organisms. See Dosage section for more information. Pharmacology/Actions Alone, sulfonamides are bacteriostatic agents and trimethoprim is bactericidal, but when used in combination, the potentiated sul-fas are bactericidal. Potentiated sulfas sequentially inhibit enzymes in the folic acid pathway, inhibiting bacterial thymidine synthesis. The sulfonamide blocks the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid (DFA), and trimethoprim blocks the	pppbs.pdf
conversion of DFA to tetrahydrofolic acid by inhibiting dihydrofo-late reductase. The in vitro o ptimal ratio for most susceptible bacteria is ap-proximately 1:20 (trimethoprim:sulfa), but synergistic activity can re portedly occur with ratios of 1:1-1:40. The serum concentration of the trimethoprim component is considered more important than the sulfa concentration. For most susceptible bacteria, the MIC's for TMP are generally above 0. 5 mcg/m L. The potentiated sulfas have a fairly broad spectrum of activ-ity. Gram-positive bacteria that are generally susceptible include most st reptococci, many strains of staphylococcus, and Nocardia. In horses, approximately 30% of strains tested of Streptococcus zooepidemicus are resistant to TMP/Sulfa. Many gram-negative organisms of the family Enterobacteriaceae are susceptible to the potentiated sulfas, but not Pseudomonas aeruginosa. Some protozoa (Pneumocystis carinii, Coccidia, and T oxoplasma) are also inhibited by the combination. Potentiated sulfas reportedly have little activity against most anaerobes, but opinions on this vary. Resistance will develop more slowly to the combination of drugs than t o either one alone. In gram-negative organisms, resistance is usually plasmid-mediated. Pharmacokinetics Trimethoprim/sulfa is well absorbed after oral administration, with peak levels occurring about 1-4 hours after dosing; the drug is more slowly absorbed after subcutaneous absorption, however. In ruminants, trimethoprim is apparently trapped in the ruminoretic-ulum after oral administration and undergoes some degradation. Trimethoprim/sulfa is well distributed in the body. When me-ninges are inﬂamed, the drugs enter the CSF in levels of about 50% those f ound in the serum. Both drugs cross the placenta and are distributed into milk. The volume of distribution for trimethoprim in various species are: 1. 49 L/kg (dogs); 0. 59-1. 51 L/kg (horses). The volume of distribution for sulfadiazine in dogs is 1. 02 L/kg. Trimethoprim/sulfa is both renally excreted unchanged via glo merular ﬁltration and tubular secretion and metabolized by the liver. The sulfas are primarily acetylated and conjugated with glucuronic acid and trimethoprim is metabolized to oxide and hydroxylated metabolites. Trimethoprim may be more extensively metabolized in the liver in adult ruminants, than in other species. The serum elimination half-lives for trimethoprim in various spe-cies is: 2. 5 hours (dogs), 1. 91-3 hours (horses), 1. 5 hours (cattle). The se rum elimination half-lives for sulfadiazine in various species is: 9. 84 hours (dogs), 2. 71 hours (horses), and 2. 5 hours (cattle). While trimethoprim is rapidly eliminated from the serum, the drug may persist for a longer period of time in tissues. Because of the number of variables involved, it is extremely difﬁ-cult to apply pharmacokinetic values in making dosage recommen-dations with these combinations. Each drug (trimethoprim and the sulfa) has different pharmacokinetic parameters (absorption, distri-bution, elimination) in each species. Since different organisms have diffe rent MIC values and the optimal ratio of trimethoprim to sulfa differs from organism to organism, this problem is exacerbated. There is considerable controversy regarding the frequency of administ ration of these combinations. The veterinary product, trimethoprim/sulfadiazine is labeled for once daily administration in dogs and horses, but many clinicians believe that the drug is more efﬁcacious if given twice daily, regardless of which sulfa is used. Contraindications/Precautions/Warnings The manufacturer states that trimethoprim/sulfadiazine should not be used in dogs or horses showing marked liver parenchymal damage, blood dyscrasias, or those with a history of sulfonamide sensitivity. It is not for use in horses (or approved for other ani-mals) intended for food. This combination should be used with caution in patients with pr e-existing hepatic disease. Because of its potential for crystallization in the urine, it may be wise to avoid the use of sulfadiazine in dogs known to have uroliths, at increased risk for developing uroliths or known to have highly concentrated or acidic urine. Adverse Effects Adverse effects noted in dogs include: keratoconjunctivitis sicca (which may be irreversible), acute neutrophilic hepatitis with icter-us, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, pol yarthritis, facial swelling, polydipsia, polyuria and cholestasis. Potentiated sulfonamides may cause hypothyroidism in dogs, par-ticularly with extended therapy. Acute hypersensitivity reactions manifest ing as Type I (anaphylaxis) or Type III reaction (serum sickness) can be seen. Hypersensitivity reactions appear to be more common in large breed dogs; Doberman Pinschers may possibly be more susceptible to this effect than other breeds. Other hemato-logic effects (anemias, agranulocytosis) are possible, but fairly rare. TMP/Sulfa has rarely been noted to cause an idiosyncratic, moder-ate to massive hepatic necrosis. TMP/Sulfa may be a risk factor for de veloping acute pancreatitis, but cause and effect have not been deﬁnitively shown. Adverse effects noted in cats may include anorexia, leukopenias and anemias. I n horses, transient pruritus has been noted after intravenous injec tion. Oral therapy has resulted in diarrhea in some horses. Previous administration of potentiated sulfas has been implicated in increasing the mortality rate of associated with severe diarrhea. If the 48% injectable product is injected IM, SC, or extravasates af-ter IV administration, swelling, pain and minor tissue damage may res ult. Hypersensitivity reactions and hematologic effects (anemias, thrombocytopenia, or leukopenias) may also be seen; long-term therapy should include periodic hematologic monitoring. Sulfonamides (or their metabolites) can precipitate in the urine, particularly when given at high dosages for prolonged pe-riods. Acidic urine or highly concentrated urine may also contrib-ute to increased risk of crystalluria, hematuria, and renal tubule obst ruction. Reproductive/Nursing Safety Safety of trimethoprim/sulfa has not been clearly established in pregnant animals. Reports of teratogenicity (cleft palate) have been reported. Studies thus far in male animals have not dem-onstrated any decreases in reproductive performance. In humans, the FD A 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 ani-mal reproduction studies and no adequate studies in humans. ) In a se parate 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. )	pppbs.pdf
Use TMP/sulfa products in nursing animals with caution. TMP-SMZ is not recommended for human use in the nursing period as s ulfonamides are excreted in milk and may cause kernicterus. Premature infants and infants with hyperbilirubinemia or G-6-PD deﬁciency are also at risk for adverse effects. Overdosage/Acute Toxicity Manifestations of an acute overdosage can include clinical signs of GI distress (nausea, vomiting, diarrhea), CNS toxicity (depression, headache, and confusion), facial swelling, bone marrow depression and increases in serum aminotransferases. Oral overdoses can be treated by emptying the stomach, (following usual protocols), and initiating symptomatic and supportive therapy. Acidiﬁcation of the urine may increase the renal elimination of trimethoprim, but could also cause sulfonamide crystalluria, particularly with sulfadiazine containing products. Complete blood counts (and other labora-tory parameters) should be monitored as necessary. Bone marrow sup pression associated with chronic overdoses may be treated with folinic acid (leucovorin) if severe. Peritoneal dialysis is not effective in removing TMP or sulfas from the circulation. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving trimethoprim/sulfa and may be of signiﬁcance in veterinary patients: !TAMANTADINE : A human patient developed toxic delirium when re-ceiving amantadine with TMP/sulfa !TANTACIDS : May decrease the bioavailability of sulfonamides if ad-ministered concurrently !TCYCLO SPOR INE: TMP/sulfa may increase the risk of nephrotoxicity !TDIGOXIN : TMP/sulfa may increase digoxin levels !TDIURETICS, THIAZIDE : May increase risk for thrombocytopenia !THYPOGLYCEMIC AGENTS, ORAL : TMP/sulfa may potentiate effects !TMETHOTREXATE : TMP/sulfa may displace from plasma proteins and increase risk for toxic effects; it can also interfere with MTX assays (competitive protein binding technique) !TPHENYTOIN : TMP/sulfa may increase half-life !TTRICYCLIC ANTIDEPRESSANTS : TMP/sulfa may decrease efﬁcacy !TWARFARIN : TMP/sulfa may prolong INR/PT Laboratory Considerations !TWhen using the Jaffe alkaline picrate reaction assay for creatinine determination, trimethoprim/sulfa may cause an overestimation of approximately 10%. !TSulfonamides may give false-positive results for urine glucose de-terminations when using the Benedict's method. Doses Note : There is signiﬁcant controversy regarding the frequency of dos-ing these drugs. See the pharmacokinetic section above for more infor-mation. Unless otherwise noted, doses are for combined amounts of tr imethoprim/sulfa. !TDOGS: For susceptible infections: a) For UTI, pyoderma, soft tissue infections: 30 mg/kg PO q24h (not soft tissue infections) or 15 mg/kg PO q12h for 14 days. For chronic pyoderma, acanthamebiasis: 30 mg/kg PO q12h for 21-42 days. Fo r systemic infections; bacteremia: 30-45 mg/kg PO q12h for 3-5 days. (Greene, Hartmannn et al. 2006) b) For bacterial UTI: 30 mg/kg q12h PO (Bartges 2007) c) For protozoal diseases: Fo r toxoplasmosis: 15 mg/kg, PO q12h for 28 days. For Neospora: 15 mg/kg, PO q12h for 4 weeks. Used con-currently with clindamycin (10 mg/kg q12h for 4 weeks) or pyrimethamine (1 mg/kg PO once daily for 4 weeks). Fo r Hepatazoon canis: 15 mg/kg, PO q12h for 2-4 weeks. Used concurrently with clindamycin (10 mg/kg PO q8h for 2-4 weeks) and pyrimethamine (0. 25 mg/kg PO once daily for 2-4 weeks) (Lappin 2000) d) For coccidiosis: 30 mg/kg PO once daily for 10 days (Matz 1995) e) For pneumocystosis (Pneumocystis carinii): 15 mg/kg PO q8h or 30 mg/kg PO q12h, both for 3 weeks. May be given with cimetidine and levamisole as potential immune stimulants. (Hawkins 2000) f) For Hepatazoon americanum: TMP/sulfa (15 mg/kg PO q12h), pyrimethamine (0. 25 mg/kg PO q24h), and clin-damycin (10 mg/kg q8h). Once remission attained decoqui-nate (see monograph) can maintain. (Baneth 2007) g) For Hepatazoon americanum: TMP/sulfa (15 mg/kg PO q12h for 14 days), pyrimethamine (0. 25 mg/kg PO q24h for 14 days), and clindamycin (10 mg/kg q8h for 14 days). Once remission attained decoquinate (see monograph) can maintain. For neosporosis: pyrimethamine (1 mg/kg PO daily) with TMP/sulfa (15 -30 mg/kg PO twice daily. (Blagburn 2005a) !TCATS: For susceptible infections: a) For UTI: 30 mg/kg PO q24h for 7-14 days. For UTI, soft tissue infections: 15 mg/kg PO q12h for 7-14 day s. (Greene, Hartmannn et al. 2006) b) 30 mg/kg q12h (if treating Nocardia, double dose) (Ford and Ar onson 1985) c) For toxoplasmosis: 15 mg/kg PO q12h for 28 days (Lappin 2000) d) For bacterial UTI: 30 mg/kg q12h PO (Bartges 2007) !TFERRETS: For susceptible infections: a) 30 mg/kg PO twice daily (Williams 2000) b) For coccidiosis: 30 mg/kg PO once daily for 14 days. (John-son 2006c) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 15-30 mg/kg, PO q12-24h; 30-48 mg/kg SC q12h. Sulfa diazine has a very short half-life (approx. 1 hour) in rab-bits. (Ivey and Morrisey 2000) b) Chinchillas, Gerbils, Guinea Pigs, Hamsters, Mice, Rats: 15- 30 mg/kg PO q12h; or 30 mg/kg IM q12h (Adamcak and Otten 2000) c) Chinchillas: 30 mg/kg PO, SC or IM q12h (Hayes 2000) !TCATTLE: For susceptible infections: a) 44 mg/kg once daily IM or IV using 48% suspension (Upson 1988) b) 25 mg/kg, IV or IM q24h (Burrows 1980) c) Calves: 48 mg/kg IV or IM q24h (Baggot 1983) !THORSES: For susceptible infections: a) For respiratory tract infections: 15-30 mg/kg PO q12h. Give 30 min utes prior to feeding hay (grain is OK) (Foreman 1999)	pppbs.pdf
Tb) Foals: 15 mg/kg IV q12h; 30 mg/kg PO q12h (Brumbaugh 1999) c) 22 mg/kg IV q24h or 30 mg/kg, PO q24h (Upson 1988) d) 30 mg/kg PO once daily or 21. 3 mg/kg IV once daily (Pack-age inserts; Tr ibrissen®—Coopers) e) Foals: 15 mg/kg PO or IV twice daily (Furr 1999) f) For EPM: Sulfadiazine 20 mg/kg (either alone or as a poten-tiated sulfa) PO once or twice a day with Pyrimethamine (1 mg/kg PO once a day) for 90-120 days (or longer). Monitor: CBC's (Moore 1999) !TSWINE: For susceptible infections: a) 48 mg/kg, IM q24h (Baggot 1983) !TBIRDS: For susceptible infections: a) Using TMP/SMX oral suspension (240 mg/5 m L): 2 m L/kg PO tw ice daily. Good for many gram-positive and negative enteric and respiratory infections, particularly in hand-fed babies. May cause emesis in Macaws. (Mc Donald 1989) b) For respiratory and enteric infections in psittacines using the 24% injectable suspension: 0. 22 m L/kg IM once to twice daily. For coccidiosis in toucans and mynahs using TMP/SMX oral susp ension (240 mg/5 m L): 2. 2 m L/kg once daily for 5 days. May be added to feed. For respiratory and enteric infections in hand-fed baby psitt-acines using TMP/SMX oral suspension (240 mg/5 m L): 0. 22 m L/30 g rams twice daily to three times daily for 5-7 days. (Clubb 1986) c) Using oral suspension: 50-100 mg/kg (of combined prod-uct) PO q12h (Hoeffer 1995) d) Ratites: For T oxoplasma gondii: 30-50 mg/kg IM twice daily (J enson 1998) !TREPTILES: For susceptible infections: a) For most species: 30 mg/kg IM (upper part of body) once daily for 2 treatments, then every other day for 5-12 treat-ments. May be useful for enteric infections. (Gauvin 1993) b) For all species: 30 mg/kg IM, ﬁrst two doses 24 hours apart and then e very other day (Jacobson 1999) c) 15-25 mg/kg/day IM for 7-14 days (Lewbart 2001) Monitoring !TClinical efﬁcacy !TAdverse effects; with chronic therapy, periodic complete blood counts should be considered !Thyroid function tests should be considered (baseline and on-going) particularly in dogs receiving long-term treatment Client Information !TIf using oral suspension, shake well before using; does not need to be refrigerated !TAnimals must be allowed free access to water and must not be-come dehydrated while on therapy !TIf dogs eyes are dry or become irritated contact veterinarian Chemistry/Synonyms Trimethoprim occurs as odorless, bitter-tasting, white to cream-colored crystals or crystalline powder. It is very slightly soluble in water and slightly soluble in alcohol. Sulfadiazine occurs as an odorless or nearly odorless, white to slightl y yellow powder. It is practically insoluble in water and spar-ingly soluble in alcohol. Sulfamethoxazole occurs as a practically odorless, white to off-whit e, crystalline powder. Approximately 0. 29 mg are soluble in 1 m L of water and 20 mg are soluble in 1 m L of alcohol. In combination, these products may be known as: Co-trimoxazole, SMX-TMP, TMP-SMX, trimethoprim-sulfamethox-azole, sulfamethoxazole-trimethoprim, sulfadiazine-trimethoprim, tr imethoprim-sulfadiazine, TMP-SDZ, SDZ-TMP, Co-trimazine or by their various trade names. Storage/Stability Unless otherwise instructed by the manufacturer, trimethoprim/ sulfadiazine and co-trimoxazole products should be stored at room temperature (15-30°C) in tight containers. Dosage Forms/Regulatory Status/Withdrawal Times VETERINARY-LABELED PRODUCTS: Trimethoprim (TMP)/Sulfadiazine (SDZ) Oral Paste: Each gram con-tains 67 mg trimethoprim and 333 mg sulfadiazine. Available in 37. 5 gr am (total weight) syringes; Tribrissen® 400 Oral Paste (Schering-Plough); (Rx). Approved for use in horses not intended for food. Trimethoprim/Sulfadiazine Sterile Injection: 48% in 100 m L vials: Di-Bio tic® 48% (Phoenix Pharmaceutical), Tribrissen® 48% Injection (Schering-Plough); (Rx) Approved for use in horses not intended for food. Trimethoprim/Sulfadiazine Powder: 67 mg trimethoprim and 333 mg s ulfadiazine per gram: Tucoprim® Powder (Pharmacia & Upjohn) in 200 g & 400 g bottles and 2000 g pails, Uniprim® Powder (Macleod) in 37. 5 g and 1,125 g packets, 200 g jar, and 12 kg box; (Rx). Approved for use in horses not intended for food. In Canada, trimethoprim and sulfadoxine are available for use in cat-tle and swine (Trivetrin®—Wellcome; Bor gal®—Hoechst). Slaughter withdrawal = 10 days; milk withdrawal = 96 hours. HUMAN-LABELED PRODUCTS: Trimethoprim (alone) Tablets: 100 mg and 200 mg; Proloprim® (Glaxo Wellcome); Trimpex® (Roche); generic; (Rx) Trimethoprim 80 mg and Sulfamethoxazole 400 mg Tablets; Tr imethoprim 160 mg and Sulfamethoxazole 800 mg Tablets: Bactrim®, Bactrim-DS® (Roche); Septra®, Septra® DS, (Glaxo Well-come); generic; (Rx) Trimethoprim 8 mg/m L and Sulfamethoxazole 40 mg/m L oral sus-pension in 20 m L, 100 m L, 150 m L, 200 m L, 473 m L, and 480 m L; Sep tra® (Glaxo Wellcome); Cotrim® Pediatric (Lemmon), Sulfatrim®, (various); generic; (Rx) Trimethoprim 16 mg/5 m L (3. 2 mg/m L) and Sulfamethoxazole 80 mg/5 m L (16 mg/m L) for injection in 5 m L Carpuject; 80 mg/5 m L (16 mg/m L) trimethoprim and 400 mg/5 m L (80 mg/m L) sulfame-thoxazole in 10 m L, 20 m L, 30 m L multi-dose vials and 5 m L vials; Bac trim® IV (Roche); Septra® IV (Monarch); generic; (Rx)	pppbs.pdf
SULFADIMETHOXINE (sul-fa-dye-meth-ox-een) Albon® SULFONAMIDE ANTIMICROBIAL Prescriber Highlights TT Sulfonamide antimicrobial agent TT Contraindications: Hypersensitivity to sulfas, thiazides, or sulfonylurea agents; severe renal or hepatic impairment TT Caution: Diminished renal or hepatic function, or urinary obstruction. TT Adverse Effects: Can precipitate in the urine (esp. with high dosages for prolonged periods, acidic urine or highly concentrated urine). DOGS: Keratoconjunctivitis sicca, bone marrow depression, hypersensitivity reactions (rash-es, dermatitis), focal retinitis, fever, vomiting & nonseptic polyarthritis possible TT Potentially teratogenic; weigh risk vs. beneﬁt Uses/Indications Sulfadimethoxine injection and tablets are approved for use in dogs and cats for respiratory, genitourinary, enteric and soft tissue infec-tions caused by susceptible organisms. Sulfadimethoxine is used in the treat ment of coccidiosis in dogs although not approved for this indication. In horses, sulfadimethoxine injection is approved for the treat-ment of respiratory infections caused by Streptococcus equi. In cattle, the drug is approved for treating shipping fever com-plex, calf diphtheria, bacterial pneumonia and foot rot caused by suscep tible organisms. In poultry, sulfadimethoxine is added to drinking water to treat coccidiosis, fowl cholera, and infectious coryza. Pharmacology/Actions Sulfonamides are usually bacteriostatic agents when used alone. They are thought to prevent bacterial replication by competing with para-aminobenzoic acid (PABA) in the biosynthesis of tetra-hydrofolic acid in the pathway to form folic acid. Only microorgan-isms that synthesize their own folic acid are affected by sulfas. Microorganisms that are usually affected by sulfonamides in-clude some gram-positive bacteria, including some strains of strep-tococci, staphylococcus, Bacillus anthracis, Clostridium tetani, C. perfringens, and many strains of Nocardia. Sulfas also have in vitro activity against some gram-negative species, including some strains of Shigella, Salmonella, E. coli, Klebsiella, Enterobacter, Pasturella, and Proteus. Sulfas have activity against some rickettsia and proto-zoa (T oxoplasma, Coccidia). Unfortunately, resistance to sulfas is a prog ressing phenomenon and many strains of bacteria that were once susceptible to this class of antibacterial are now resistant. The sulfas are less efﬁcacious in pus, necrotic tissue, or in areas with extensive cellular debris. Pharmacokinetics In dogs, cats, swine, and sheep, sulfadimethoxine is reportedly read-ily absorbed and well distributed. Relative volumes of distribution range fr om 0. 17 L/kg in sheep to 0. 35 L/kg in cattle and horses. The drug is highly protein bound. In most species, sulfadimethoxine is acetylated in the liver to ac etylsulfadimethoxine and excreted unchanged in the liver. In dogs, the drug is not appreciably hepatically metabolized and renal excretion is the basis for the majority of elimination of the drug. Sulfadimethoxine's long elimination half-lives are a result of its appreciable reabsorption in the renal tubules. Serum half-lives reported in various species are: swine 14 hours; sheep 15 hours; horses 11. 3 hours. Contraindications/Precautions/Warnings Sulfonamides are contraindicated in patients hypersensitive to them, thiazides, or sulfonylurea agents. They are also considered contraindicated in patients with severe renal or hepatic impairment and should be used with caution in patients with diminished renal or hepatic function, or urinary obstruction. Oral sulfonamides can depress the normal cellulytic function of the ruminor eticulum, but this effect is generally temporary and the animal adapts. Adverse Effects Sulfonamides (or their metabolites) can precipitate in the urine, particularly when given at high dosages for prolonged periods. Acidic urine or highly concentrated urine may also contribute to increased risk of crystalluria, hematuria, and renal tubule obstruc-tion. Different sulfonamides have different solubilities at various p H's. Alkalinizat ion of the urine using sodium bicarbonate may prevent crystalluria, but it also decreases the amount available for tubular reabsorption. Crystalluria can usually be avoided with most of the commercially available sulfonamides by maintaining an ad-equate urine ﬂow. Normal urine p H in herbivores is usually 8 or more, so crystalluria is not frequently a problem. Sulfonamides can also cause various hypersensitivity reactions or diarrhea by altering the normal gut ﬂora. T oo rapid intravenous injection of the sulfas can cause muscle weakness, blindness, ataxia, and collapse. In dogs, keratoconjunctivitis sicca, bone marrow depression, hype rsensitivity reactions (rashes, dermatitis), focal retinitis, fever, vomiting and nonseptic polyarthritis have been reported with sul-fonamides. Oral sulfonamides can depress the normal cellulytic function of the ruminor eticulum, but this effect is generally temporary and the animal adapts. Because solutions of sulfonamides are usually alkaline, they can cause tissue irritation and necrosis if injected intramuscularly or subcutaneously. Reproductive/Nursing Safety Sulfas cross the placenta and may reach fetal levels of 50% or greater of those found in maternal serum; teratogenicity has been reported in some laboratory animals when given at very high doses. They should be used in pregnant animals only when the beneﬁts clearly outweigh the risks of therapy. Sulfonamides are distributed into milk.	pppbs.pdf
Overdosage/Acute Toxicity Acute toxicity secondary to overdoses apparently occurs only rarely in veterinary species. In addition to the adverse effects listed above, CNS stimulation and myelin degeneration have been noted after very high dosages. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sulfonamides and may be of signiﬁcance in veterinary patients: !TANTACIDS : May decrease the oral bioavailability of sulfonamides if administered concurrently Laboratory Considerations !TSulfonamides may give false-positive results for urine glucose de-terminations when using the Benedict's method. Doses !TDOGS: For susceptible infections: a) 25 mg/kg PO, IV, or IM once daily (Davis 1985), (Kirk 1989) b) 100 mg/kg PO, IV or IM once daily (Upson 1988) c) 55 mg/kg PO, or IV, or SC initially, then 27. 5 mg/kg once daily thereafter (Package insert; Albon ®—Roche) For coccidiosis: a) 55 mg/kg PO initially on the ﬁrst day of therapy, then 27. 5 mg/kg PO onc e daily for 9 days (Matz 1995) b) 50 mg/kg once daily for 10-14 days will eliminate oocyst ex-cretion in most dogs and cats. (Marks 2007c) c) During the infant period (2-6 weeks): 50 mg/kg PO on the ﬁrst day followed by a daily dose of 25 mg/kg PO until symp-toms regress (Macintire 2004) !TCATS: For susceptible infections: a) 25 mg/kg PO, IV, or IM once daily (Davis 1985), (Kirk 1989) b) 100 mg/kg PO, IV or IM once daily (Upson 1988) c) 55 mg/kg PO, or IV, or SC initially, then 27. 5 mg/kg once daily thereafter (Package insert; Albon ®—Roche) For coccidiosis: a) 50 mg/kg once daily for the ﬁrst day, then 25 mg/kg once daily for 14-20 days. Sulfas are coccidiostatic. It is important that supportive care, including ﬂuids and good nutrition be maintained during therapy. (Cornelius and Roberson 1986) b) 50 mg/kg once daily for 10-14 days will eliminate oocyst ex-cretion in most dogs and cats. (Marks 2007c) !TFERRETS: For susceptible infections: a) 25 mg/kg PO, SC or IM once daily (Williams 2000) b) For coccidiosis: 25 mg/kg PO once daily for 14 days. (John-son 2006c) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 10-15 mg/kg PO q12h (Ivey and Morrisey 2000) b) Rabbits: For coccidiosis: 25 mg/kg PO once daily (Burke 1999) c) Hedgehogs: 2-20 mg/kg/day IM, SC or PO (Smith 2000) d) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: As a c occidiostat: 50 mg/kg PO once, then 25 mg/kg PO once daily for 10-20 days or 75 mg/kg PO for 7-14 days (Adam-cak and Otten 2000) !TCATTLE: For susceptible infections: a) 110 mg/kg PO or IV once daily (Upson 1988) b) 55 mg/kg IV initially, then 27. 5 mg/kg IV once daily (Baggot 1983) c) 110 mg/kg, PO q24h (Burrows 1980) d) 55 mg/kg PO or IV initially, then 27. 5 mg/kg q24h (Jenkins 1986) e) 55 mg/kg IV or PO initially, then 27. 5 mg/kg q24h IV or PO fo r up to 5 days. If using sustained release boluses: 137. 5 mg/ kg PO every 4 days (Package insert; Albon®—Roche) !THORSES: For susceptible infections: a) 55 mg/kg, PO or IV q12h (Upson 1988) b) 55 mg/kg IV or PO initially, then 27. 5 mg/kg q24h IV (Pack-age insert; Albon®—Roche) !TREPTILES: For susceptible infections: a) For coccidia: 90 mg/kg PO on day one and then 45 mg/kg PO on 5 successive days; may also be given IM or IV. Maintain adequate hydration. (Lewbart 2001) Chemistry/Synonyms A long-acting sulfonamide, sulfadimethoxine occurs as an odorless or almost odorless, creamy white powder. It is very slightly soluble in water and slightly soluble in alcohol. Sulfadimethoxine may also be known as: solfadimetossina, solfadime tossipirimidina, sulphadimethoxine, Albon®, Amtech®, Chemiosalfa®, Deltin®, Di-Methox®, Risulpir®, Ritarsulfa®, SDM®, Sulfadren®, Sulfastop®, or Sulfasol®, and Sulfathox®. Storage/Stability Unless otherwise instructed by the manufacturer, store sulfadime-thoxine products at room temperature and protect from light. If cry stals form due to exposure to cold temperatures, either warm the vial or store at room temperature for several days to resolubolize the drug; efﬁcacy is not impaired by this process. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Sulfadimethoxine Injection: 400 mg/m L (40%) in 100 m L vials; Albon® Injection 40% (Pﬁzer Animal Health); Amtech® Sulfadime-thoxine Injection 40% (IV use only in cattle) (Phoenix Scientiﬁc), Di-Methox® Injection 40% (Agri Labs), generic; (Agripharm, Aspen, Butler, Durvet, Vedco), SDM® Injection (Phoenix Pharmaceutical); (Rx) Approved for use in dogs, cats, horses, swine and cattle. Not to be used in horses intended for food or calves to be processed for veal. Slaughter withdrawal (at labeled doses) = 5 days (cattle); milk with-drawal (at labeled doses) = 60 hours. Sulfadimethoxine Oral Tablets: 125 mg, 250 mg, and 500 mg; Albon ® Tablets (Pﬁzer Animal Health); (Rx). Approved for use in dogs and cats. Sulfadimethoxine Oral Suspension: 50 mg/m L in 2 oz. and 16 oz. Bottles; A lbon® (Pﬁzer); (Rx). Approved for use in dogs and cats. Sulfadimethoxine Oral Boluses: 5 g, and 15 g; Albon ® (Pﬁzer); (OTC). Approved for use in cattle. Not to be used in calves to be processed for veal. No withdrawal period has been established for this in pre-ruminating calves. Slaughter withdrawal (at labeled doses) = 7 days (cattle); milk w ithdrawal (at labeled doses) = 60 hours. Sulfadimethoxine Oral Boluses Sustained-Release: 12. 5 g; Albon ® SR (Pﬁzer); (Rx) Approved for use in non-lactating cattle. Slaughter	pppbs.pdf
withdrawal (at labeled doses) = 21 days (cattle), a withdrawal period has not been established for pre-ruminating calves. Not for use in calves intended to be processed for veal. Sulfadimethoxine Soluble Powder: 94. 6 g/packet (for addition to drinking wate r); Albon® (Pﬁzer), Di-Methox® Soluble Powder (Agri-Labs), generic; (Agri Pharm, Aspen, Durvet, Phoenix Scientiﬁc, Ve-dco), Sulfasol® (Med-Phar mex); (OTC) Approved for use in dairy calves, dairy heifers, beef cattle, broiler and replacement chickens only, and meat-producing turkeys. Slaughter withdrawal (at labeled doses) = 7 days (cattle); 5 days (poultry—do not use in chickens over 16 weeks old or in turkeys over 24 weeks old). Sulfadimethoxine 12. 5% Concentrated Solution (for addition to drinking wate r): Albon® (Pﬁzer), Amtech® generic; (Phoenix Scien-tiﬁc), Di-Methox® 12. 5% Oral Solution (Agri Labs), SDM® Solution (Phoenix Pharmaceutical), generic; (Agri Pharm, Aspen, Butler, Du-rvet, Vedco), Sulforal ® (Med-Pharmex); (OTC). Approved for use in chickens, turkeys and cattle. Slaughter withdrawal (at labeled doses) = 7 days (for dairy calves, dairy heifers and beef cattle only. With-drawal for pre-ruminating calves has not been established) Not to be used in cal ves to be processed for veal; 5 days (poultry—do not use in chickens over 16 weeks old or in turkeys over 24 weeks old). HUMAN-LABELED PRODUCTS: None SULFADIMETHOXINE/ ORMETOPRIM (or-me-toe-prim) Primor® POTENTIATED SULFONAMIDE ANTIMICROBIAL Prescriber Highlights TT Potentiated sulfa similar to trimethoprim/sulfa. The fol-lowing apply to TMP/Sulfa & may correlate to this agent as well: TT Contraindications: Hypersensitive to sulfas, thiazides, or sulfonylurea agents; severe renal or hepatic impairment TT Caution: Diminished renal or hepatic function, or urinary obstruction or urolithiasis TT Adverse Effects: DOGS: Keratoconjunctivitis sicca, hyper-sensitivity (type 1 or type 3) acute neutrophilic hepatitis with icterus, vomiting, anorexia, diarrhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swelling, polydipsia, crystalluria, hematuria, polyuria, cholestasis, hypothy-roidism, anemias, agranulocytosis, idiosyncratic hepatic necrosis in dogs. CATS: Anorexia, crystalluria, hematuria, leukopenias & anemias TT Potentially teratogenic, weigh risk vs. beneﬁt Uses/Indications Sulfadimethoxine/ormetoprim is approved for the treatment of skin and soft tissue infections in dogs caused by susceptible strains of Staphylococcus aureus and E. coli. Pharmacology/Actions Sulfadimethoxine/ormetoprim shares mechanisms of action and probably the bacterial spectrum of activity with trimethoprim/sulfa. Alone, sulfonamides are bacteriostatic agents, but in combination with either ormetoprim or trimethoprim, the potentiated sulfas are bactericidal. Potentiated sulfas sequentially inhibit enzymes in the folic acid pathway, thereby inhibiting bacterial thymidine synthe-sis. The sulfonamide blocks the conversion of para-aminobenzoic acid (PAB A) to dihydrofolic acid (DFA) and ormetoprim blocks the conversion of DFA to tetrahydrofolic acid by inhibiting dihydrofo-late reductase. The potentiated sulfas have a fairly broad spectrum of activ-ity. Gram-positive bacteria that are generally susceptible include most streptococci, many strains of staphylococcus, and Nocardia. Many gram-negative organisms of the family Enterobacteriaceae are susceptible to the potentiated sulfas, but not Pseudomonas aeruginosa. Some protozoa ( Pneumocystis carinii, Coccidia and Toxoplasma) are also inhibited by the combination. Potentiated sulfas reportedly have little activity against most anaerobes, but opinions on this vary. Resistance will develop more slowly to the combination of drugs, than to e ither one alone. In gram-negative organisms, resistance is usually plasmid-mediated. Pharmacokinetics The pharmacokinetics of sulfadimethoxine are outlined in the pre-vious monograph. Pharmacokinetic data for ormetoprim is not available at the time of this writing, but the manufacturer states that therapeutic levels are maintained over 24 hours at recommended doses. Contraindications/Precautions/Warnings The manufacturer states that ormetoprim/sulfadimethoxine should not be used in dogs showing marked liver parenchymal damage, blood dyscrasias, or in those with a history of sulfonamide sensitivity. This combination should be used with caution in patients with pre-exist ing hepatic or thyroid disease. Adverse Effects This combination would be expected to exhibit an adverse reac-tion proﬁle in dogs similar to that seen with trimethoprim/sulfa, including: k eratoconjunctivitis sicca (which may be irreversible), acute neutrophilic hepatitis with icterus, vomiting, anorexia, diar-rhea, fever, hemolytic anemia, urticaria, polyarthritis, facial swell-ing, polydipsia, polyuria, and cholestasis. Acute hypersensitivity react ions manifesting as Type I, (anaphylaxis) or Type III reaction (serum sickness) can also be seen. Hypersensitivity reactions ap-pear to be more common in large breed dogs; Doberman Pinschers may possib ly be more susceptible to this effect than other breeds. Other hematologic effects (anemias, agranulocytosis) are possible, but fairly rare. Long-term (8 weeks) therapy at recommended doses with orme-toprim/sulfadimethoxine (27. 5 mg/kg once daily) resulted in el-evated serum cholesterol, thyroid and liver weights, mild follicular thyro id hyperplasia, and enlarged basophilic cells in the pituitary. The manufacturer states that the principal treatment-related effect of extended or excessive usage is hypothyroidism. Reproductive/Nursing Safety Safety of ormetoprim/sulfadimethoxine has not been established in pregnant animals. Reports of teratogenicity (cleft palate) have been reported in some lab animals with trimethoprim/sulfa. Overdosage/Acute Toxicity In experimental studies in dogs, doses greater than 80 mg/kg re-sulted in slight tremors and increased motor activity in some dogs. Higher d oses may result in depression, anorexia, or seizures. It is suggested that very high oral overdoses be handled by emp-tying the gut using standard precautions and protocols and by treating c linical signs supportively and symptomatically.	pppbs.pdf
Drug Interactions; Laboratory Considerations None have been noted for this combination, but it would be expect-ed that the potential interactions outlined for the trimethoprim/ sulfa mono graph would also apply to this combination; refer to that monograph for more information. Doses T ! DOGS: For susceptible infections: a) Initially 55 mg/kg (combined drug) PO on the ﬁrst day of therapy, then 27. 5 mg/kg PO once daily for at least 2 days after remission of clinical signs. Not approved for treatment longer than 21 days. (Package insert; Primor®—Pﬁzer) Monitoring T ! Clinical efﬁcacy T ! Adverse effects Client Information T ! Animals must be allowed free access to water and must not be-come dehydrated while on therapy. Chemistry/Synonyms A diaminopyrimidine structurally related to trimethoprim, orme-toprim occurs as a white, almost tasteless powder. The chemistry of sulfadimetho xine is described in the previous monograph. Sulfadimethoxine may also be known as: solfadimetossina, sol-fadimetossipirimidina, sulphadimethoxine, Chemiosalfa®, Deltin®, Risulpir®, Ritarsulfa®, Sulfadren®, Sulfastop®, or Sulfathox®. Ormetoprim may also be known as NSC-95072, ormetoprima, orméto prime, ormetoprimum, or Ro-5-9754. Storage/Stability Unless otherwise instructed by the manufacturer, store tablets in tight, light resistant containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Sulfadimethoxine/Ormetoprim Tablets (scored) 120's: 100 mg Sulfadimethoxine, 20 mg Ormetoprim 240's: 200 mg Sulfadimethoxine, 40 mg Ormetoprim 600's: 500 mg Sulfadimethoxine, 100 mg Ormetoprim 1200's: 1000 mg Sulfadimethoxine, 200 mg Ormetoprim; Primor® (Pﬁz er); (Rx) Approved for use in dogs. Sulfadimethoxine/Ormetoprim medicated premix: 113. 5 g sulfadi-methoxine and 68. 1 g ormetoprim per pound in 50 lb bags. Approved for use in chickens [broilers, replacements (breeders and layers)], tur-keys, ducks, & Chukar partridges. Slaughter withdrawal (at labeled doses) = 5 days. Do not feed to chickens over 16 weeks or age, turkeys or ducks producing eggs for food. Rofenaid® 40 (Alpharma), Romet® 30 (Alpharma)—Approved for use in salmonids (trout and salmon) and catﬁsh. Slaughter or release as stocker ﬁsh = 42 days. (OTC) HUMAN-LABELED PRODUCTS: None SULFASALAZINE (sul-fa-sal-a-zeen) Azulﬁdine® SULFONAMIDE/SALICYLATE ANTIBACTERIAL/ IMMUNOSUPPRESSIVE Prescriber Highlights TT Sulfa-analog that has GI antibacterial & antiinﬂamma-tory activity used for inﬂammatory bowel disease; has also been used for vasculitis TT Contraindications: Hypersensitivity to it, sulfas or salicy-lates; intestinal or urinary obstructions TT Caution: Liver, renal or hematologic diseases; cats TT Adverse Effects: DOGS: Keratoconjunctivitis sicca, anorex-ia, vomiting, cholestatic jaundice, hemolytic anemia, leu-kopenia, vomiting, decreased sperm counts & an allergic dermatitis. CATS: Anorexia, vomiting, anemias Uses/Indications Sulfasalazine is used for the treatment of inﬂammatory bowel dis-ease in dogs and cats. It has also been suggested for adjunctive use in treating v asculitis in dogs. Pharmacology/Actions While the exact mechanism of action for its therapeutic effects in treating colitis in small animals has not been determined, it is believed that after sulfasalazine is cleaved into sulfapyridine and 5-aminosalicylic acid (5-ASA, mesalamine) by bacteria in the gut the antibacterial (sulfapyridine) and/or antiinﬂammatory (mesala-mine) activity alters the clinical signs/course of the disease. Levels of both drugs in the colon are higher then by giving them orally as separate agents. Pharmacokinetics Only about 10-33% of an orally administered dose of sulfasalazine is absorbed. Apparently, some of this absorbed drug is then excret-ed unchanged in the bile. Unabsorbed and biliary excreted drug is cleave d into 5-ASA and sulfapyridine in the colon by bacterial ﬂora. The sulfapyridine component is rapidly absorbed, but only a small percentage of the 5-ASA is absorbed. Absorbed sulfapyridine and 5-ASA are hepatically metabolized and then renal ly excreted. Contraindications/Precautions/Warnings Sulfasalazine is contraindicated in animals hypersensitive to it, sul-fonamides or salicylates. It is also contraindicated in patients with intestinal o r urinary obstructions. It should be used with caution in animals with preexisting liver, renal or hematologic diseases. Because cats can be sensitive to salicylates (see the aspirin mono-graph), use caution when using this drug in this species. Adverse Effects Although adverse effects do occur in dogs, with keratoconjunctivi-tis sicca (KCS) reported most frequently, they are considered to oc-cur relatively uncommonly. Other potential adverse effects include anorexia, vomiting, cholestatic jaundice, hemolytic anemia, leuko-penia, vomiting, decreased sperm counts and an allergic dermatitis. Should decr eased tear production be noted early, either reducing the dose or discontinuing the drug may prevent progression of KCS or increase tear production.	pppbs.pdf
Cats can occasionally develop anorexia and vomiting which may be alleviated by use of the enteric-coated tablets. Anemias second-ary to sulfasalazine are also potentially possible in cats. Reproductive/Nursing Safety Although sulfasalazine has not been proven harmful to use during pregnancy and incidences of neonatal kernicterus in infants born to women taking sulfasalazine are low, it should only be used when clearly indicated. In laboratory animal studies (rats, rabbits), doses of six times normal (human) caused impairment of fertility in male animals; this effect is thought to be caused by the sulfapyridine component and was reversible upon discontinuation of the drug. In humans, the FDA categorizes this drug as category B fo r 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 demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimes-ters. ) 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 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. ) Sulfonamides are excreted in milk. In human newborns, they co mpete with bilirubin for binding sites on plasma proteins and may cause kernicterus. Use with caution in nursing patients. Overdosage/Acute Toxicity Little speciﬁc information is available regarding overdoses with this agent, but because massive overdoses could cause signiﬁcant salicy-late and/or sulfonamide toxicity, standard protocols (empty stom-ach, cathartics, etc. ) should be considered. Urine alkalinization and fo rced diuresis may also be beneﬁcial in selected cases. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving sulfasalazine and may be of signiﬁcance in veterinary patients: !TCHLORPROPAMIDE : Hypoglycemic effects could be potentiated !TDIGOXIN : Sulfasalazine may reduce absorption !TFERROUS SULFATE or other iron salts : May decrease the blood levels of sulfasalazine if administered concurrently; clinical signiﬁcance is unknown !TFOLIC ACID : Oral absorption may be inhibited !TWARFARIN : Potentially sulfasalazine could potentiate warfarin Doses !TDOGS: For inﬂammatory large bowel disease: a) 20-30 mg/kg q8-12h PO. (Hall 2004) b) 10-15 mg/kg PO q8-12h for 2 weeks tapered to the lowest eff ective dose (Moore 2004) c) 20-48. 4 mg/kg (maximum total dose of one gram in refrac-tory patients) PO q8h. May consider an initial dose of 12. 5 mg/kg, q8h. Continue initial dose for a minimum of 4 weeks before modifying dosage. After signs of disease resolve, re-duce dosage by 25% at 2 week intervals and eventually dis-continue while maintaining dietary management. (Jergens and W illard 2000) d) For chronic colitis: If hypoallergenic diet does not control signs, sulfasalazine 20-50 mg/kg (up to a maximum of 1 gram) three times daily. Initial dosage usually 20-30 mg/ kg three times daily. Dose may be reduced at 2-4 week in-tervals if stool remains normal using the following protocol: Init ially same dose given twice daily, then 50% of initial dose twice daily, then 50% of that dose once daily, then discon-tinue. Some dogs may require chronic therapy. (Leib 2000) e) Usual initial dose is 20-40 mg/kg q8h for 3 weeks, followed by 20-40 mg/kg PO q12h for 3 weeks, then 10-20 mg/kg q12h for 3 weeks. (Marks 2007b) f) 10-25 mg/kg PO three times a day for 4-6 weeks. With resol ution of clinical signs, reduce dose by 25 percent at 2 week intervals and eventually discontinue while maintaining dietary management. (Washabau 2005) For adjunctive treatment of vasculitis: a) 20-40 mg/kg PO q8h (Hillier 2006d), (Grifﬁn 2006) b) 25 mg/kg PO three times a day. (Bloom 2006b) !TCATS: For inﬂammatory large bowel disease: a) 10-20 mg/kg PO once daily. Use cautiously in cats because of their sensitivity to salicylates (Jergens and Willard 2000) b) 10-20 mg/kg PO q24 hours (once daily) tapered to the low-est effective dose (Moore 2004), (Marks 2007b) c) 10-20 mg/kg PO q8-12h (maximum of 10 days) (Dimski 1995) d) 10-20 mg/kg PO q8-24h; up to a maximum of 10 days tr eatment (Krecic 2002) !TFERRETS: a) 10-20 mg/kg PO 2-3 times a day (Williams 2000) b) 25 mg (total dose) PO twice daily (Weiss 2002b) Monitoring !TEfﬁcacy !TAdverse effects, particularly KCS; Schirmer tear tests should be performed prior to therapy (and on rechecks), especially in mid-dle-aged to older dogs !TOccasional CBC, liver function tests are warranted with chronic therapy Client Information !TClients should monitor for clinical signs of KCS (dry cornea, blepharospasm, bilateral mucopurulent discharge) and report them to the veterinarian immediately. Chemistry/Synonyms Sulfasalazine is basically a molecule of sulfapyridine linked by a diazo bond to the diazonium salt of salicylic acid. It occurs as an odorless, bright yellow to brownish-yellow ﬁne powder. Less than 0. 1 mg is soluble in 1 m L of water and about 0. 34 mg is soluble in 1 m L of alcohol. Sulfasalazine may also be known as: salazosulfapyridine, sali-cylazosulfapyridine, sulfasalazinum, sulphasalazine, Azulﬁdine ®, Aculﬁn®, Azulﬁn®, Colo-Pleon®, Pleon RA®, Pyralin®, SAS®, Salazine®, Salazopirina®, Salazoprin®, Salazopyrin®, Salazopyrina®, Salazopyrine®, Salisulf Gastroprotetto®, Salopyrine®, Saridine®, Sazo®, Sulazine®, or Ulco®. Storage/Stability Sulfasalazine tablets (either plain or enteric-coated) should be stored at temperatures less than 40°C and preferably at room temperature (15-30°C, 59-86°F) in well-closed containers. The oral suspension should be stored at room temperature (15-30°C, 59-86°F); avoid freezing.	pppbs.pdf
TDosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Sulfasalazine Tablets: 500 mg; Azulﬁdine® (Pﬁzer); (Rx); generic; (Rx) Sulfasalazine Delayed-Release Tablets: 500 mg (enteric coated); Azul-ﬁdine® EN-tabs® (Pﬁzer); (Rx) Syrup of Ipecac-see Ipecac Syrup TAURINE (tor-een) AMINO ACID NUTRITIONAL Prescriber Highlights TT Amino acid used primarily for the treatment of taurine deﬁciency cardiomyopathies in cats & dogs TT May also be useful for many other conditions (e. g., sei-zures), but little supporting data available TT Very low toxic potential TT Laboratory considerations Uses/Indications Taurine has proven beneﬁcial in preventing retinal degeneration and the prevention and treatment of taurine-deﬁciency dilated cardiomyopathy in cats. Although modern commercial feline diets have added taurine, some cats still develop taurine-deﬁciency as-sociated dilated cardiomyopathy. It may also be of beneﬁt in tau-rine (±carnitine) deﬁcient cardiomyopathy in American Cocker Spaniels and c ertain other breeds such as, Golden Retrievers, Labrador Retrievers, Newfoundlands, Dalmations, Portuguese Water Dogs, and English Bulldogs. Preliminary studies have shown evidence that it may be useful as adjunctive treatment for cardiac disease in animals even if taurine deﬁciency is not present. Because of its low toxicity, some have suggested it be tried for a multitude of conditions in humans and animals; unfortunately, little scientiﬁc evidence exists for these uses. Pharmacology/Actions While classically considered a “non-essential” nutrient, taurine has been found to play several “essential” roles in various mammalian species. Taurine is important for bile acid conjugation, especially in cats and dogs. In vivo, taurine is synthesized from methionine. Cysteinesulﬁnic acid decarboxylase (CSAD) and vitamin B 6 are in-volved with this synthesis. Deﬁciencies of either will depress taurine synthesis. Cats ar e particularly susceptible to taurine deﬁciency as they have low CSAD activity and use taurine almost exclusively for bile acid conjugation. Additionally taurine is important in the modulation of calcium ﬂux, there by reducing platelet aggregation, stabilizing neuronal membranes, and affecting cardiac function. Taurine's effects on cardiac function include positive inotropic activity without affect-ing resting potential and modulating ionic currents across the cell membrane. Taurine is important for normal development of the CNS and it has a GABA-like effect that may make it useful for treat-ing some seizure disorders. Pharmacokinetics No speciﬁc information was located. Excess taurine is rapidly ex-creted in the kidneys, but if a deﬁciency exists, urinary excretion is reduc ed via reabsorption. Contraindications/Precautions/Warnings While taurine is safe, it should not be used as a substitute for ad-equate diagnosis. Adverse Effects Taurine appears to be very well tolerated. Minor GI distress poten-tially could occur after oral dosing. Overdosage/Acute Toxicity No speciﬁc information was located, but toxic potential appears to be very low. Drug Interactions None are reported. Laboratory Considerations T ! Because plasma levels may reﬂect the acute changes associated with dosing, whole blood levels are preferred to measure actual status of taurine in the body. Because intracellular levels of tau-rine are much higher than in plasma, hemolysis or collection of the buffy co at w ill negate the results. Doses T ! DOGS: a) For taurine-deﬁciency related cardiomyopathy: In American Cock er Spaniels: Give 500 mg taurine PO q12h (with 1 gram of carnitine PO q12h) (Kittleson 2000) b) Complementary therapy for seizures: 400 mg/40 lbs of body weight PO twice daily. “May” help decrease seizure activity (Neer 2000) T ! CATS: a) For taurine-deﬁciency related cardiomyopathy: 250 mg (per cat) PO q12- 24h. Because taurine is safe and inexpensive, recommend using for any case of myocardial failure. (Fox 2000) b) Complementary therapy for seizures: 500 mg Per cat PO twice daily. “May” help decrease seizure activity (Neer 2000) Monitoring T ! Clinical efﬁcacy T ! aurine levels (if possible and affordable; whole blood levels pref-erable to plasma/serum levels) Chemistry/Synonyms Taurine, an amino acid also known as 2-aminosulphonic acid, has a molecular wt. of 125. Solubility in 100 m L of water at 20°C is 8. 8 grams. Storage/Stability Unless otherwise labeled, store taurine tablets or capsules at room temperature. Protect from light and moisture. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: The following products are labeled for use in animals: Taurine Tablets: 250 mg: Formula V® Taurine Tablets (Pet Ag); La-beled for use in cats. Taurine Liquid: 375 mg/4 m L (one pump); Dyna-Taur ine® (Harl-men); Labeled for use in dogs and cats.	pppbs.pdf
HUMAN-LABELED PRODUCTS: There are several oral dosage form products available for taurine. T echnically considered a “nutrient” they are all OTC and may need to be obtained from health food stores. Most dosage forms available range from 125 mg to 500 mg. TEPOXALIN (te-pox-a-lin) Zubrin® NONSTEROIDAL ANTIINFLAMMATORY AGENT Prescriber Highlights TT NSAID dual inhibitor of COX & LOX indicated for the treatment of pain & inﬂammation associated with os-teoarthritis in dogs TT Adverse effect proﬁle still being determined, but may cause more vomiting & diarrhea than some other ap-proved NSAIDs TT Rapidly disintegrating tablet dosage form may be useful in difﬁcult to pill dogs Uses/Indications T epoxalin is indicated for the treatment of pain and inﬂammation associated with osteoarthritis in dogs. Because of the drug's inhibi-tory effects on leukotrienes, there is interest in seeing if it would be be neﬁcial in the adjunctive treatment of allergic conditions in dogs. Pharmacology/Actions T epoxalin is a dual inhibitor of both cyclooxygenase (COX) and 5-lipoxygenase (LOX). It inhibits both COX-1 and COX-2 enzymes, but it is not clear if it is COX-2 preferential in the dog (it is not COX-2 preferential in sheep uterine cells) or if its LOX inhibition reduces the adverse effects associated with COX-1 inhibition. By inhibiting COX-2 enzymes, tepoxalin reduces the production of prostaglandins associated with pain, hyperpyrexia and inﬂamma-tion. Its inhibition of LOX potentially reduces the production of leukotr ienes, including leukotriene B4. As leukotriene B4 may con-tribute to increased GI tract inﬂammation by increasing cytokine prod uction, neutrophil longevity and release of proteinases, inhibi-tion may reduce the GI effects routinely seen in dogs with COX-1 inhibitor s. Leukotrienes may also contribute to inﬂammatory re-sponses seen in osteoarthritic conditions and their inhibition could reduc e clinical signs seen with the condition. Pharmacokinetics After oral administration to dogs, tepoxalin is readily absorbed and peak levels occur between 2-3 hours post-dose. The presence of food in the gut increases bioavailability. T epoxalin is rapidly me-tabolized to several metabolites, including one that it active (tep-oxalin pyrazole acid). T epoxalin and tepoxalin pyrazole acid are highly b ound to plasma proteins (98-99%). Elimination half-lives for tepoxalin and tepoxalin pyrazole acid are about 2 hours and 13 hours, respectively. Metabolites are eliminated in the feces; only 1% of the drug is eliminated in the urine. Contraindications/Precautions/Warnings T epoxalin is contraindicated in dogs demonstrating prior hyper-sensitivity reactions to tepoxalin. It should be used with caution in patients w ith impaired hepatic, cardiovascular or renal function, or at risk for developing nephrotoxic affects associated with NSAIDs (i. e., dehydrated or on concomitant diuretic therapy). Patients with active gastrointestinal ulcers should probably not receive this drug. Dogs weighing less than 3 kg cannot be accurately dosed with avail-able dosage forms. Safety in dogs less than 6 months old has not been estab lished. Adverse Effects Adverse effects most likely seen in dogs include diarrhea, vomiting, anorexia/inappetence, enteritis, and lethargy. In one study where dogs received labeled doses for 4 weeks, 22% of dogs developed di-arrhea and 20% vomited. It is unknown if giving the drug with food will d ecrease vomiting incidence. Other adverse effects reported (incidences <1%) include incoordination, incontinence, increased appetite, eating grass, ﬂatulence, hair loss, and trembling. The manufacturer warns to discontinue the drug if signs such as inappe tence, vomiting, fecal abnormalities, anemia, icterus, or lethargy are observed. Safety studies in dogs less than 6 months of age have not been completed. Reproductive/Nursing Safety Safety of this drug has not been determined in pregnant, breeding, or lactating dogs; use with caution and with informed consent of client. Overdosage/Acute Toxicity Information on acute overdosage of tepoxalin was not located. Dogs receiving 300 mg/kg/day for 6 months showed decreases in total protein, albumin and calcium concentrations. At necropsy, all dogs showed gastric lesions. An acute overdose may cause signiﬁ-cant GI distress and ulceration with GI bleeding. It is suggested to treat s upportively and monitor CBC, hydration, renal function, and for evidence of GI bleeding. Contact an animal poison control cen-ter for more information. Drug Interactions A study in normal dogs showed no signiﬁcant changes in renal function when enalapril was used with tepoxalin. The following drug interactions have either been reported or are theoretical in humans or animals receiving tepoxalin and may be of signiﬁcance in veterinary patients: T ! ASPIRIN : May increase the risk of gastrointestinal toxicity (e. g., ul-ceration, bleeding, vomiting, diarrhea) T ! CORTICOSTEROIDS : As concomitant corticosteroid therapy may in-crease the occurrence of gastric ulceration, avoid the use of these drugs whe n also using tepoxalin T ! DIGOXIN : NSAIDS may increase serum levels T ! FLUCONAZOLE : Administration has increased plasma levels of cele-coxib in humans, it is unknown if ﬂuconazole affects tepoxalin levels in dogs T ! FUROSEMIDE : NSAIDs may reduce saluretic and diuretic effects T ! METHOTREXATE : Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate; use together with extre me caution T ! NEPHROTOXIC DRUGS (e. g., furosemide, aminoglycosides, amphotericin B, etc. ): May enhance the risk of nephrotoxicity T ! NSAIDS, OTHER : May increase the risk of gastrointestinal toxicity (e. g., ulceration, bleeding, vomiting, diarrhea) T ! WARFARIN : The manufacturer cautions to closely monitor pa-tients also receiving drugs that are highly bound to plasma pro-teins (e. g., warfarin), as tepoxalin and its active metabolite are 98-99% pr otein bound in the dog	pppbs.pdf
TLaboratory Considerations No speciﬁc laboratory interactions or considerations noted Doses T ! DOGS: For pain and inﬂammation associated with osteoarthritis: a) On ﬁrst day of treatment give 20 mg/kg PO (or 10 mg/kg PO); subseq uently give 10 mg/kg PO once daily. Duration of treatment should be based on clinical response and patient tolerance to therapy. (Package insert; Zubrin®—Schering-Plough) Monitoring T ! Clinical efﬁcacy T ! Baseline and periodic CBC, chemistry panel (including bilirubin and serum creatinine) T ! Signs associated with adverse effects (GI effects, appetite, vomit-ing, diarrhea, etc. ) Client Information T ! When dosing, the person administering the tablet should place it in dog's mouth and hold mouth closed for approximately 4 seconds t o assure tablet disintegration T ! Absorption may be enhanced (and vomiting reduced?) if given with food T ! Owners should be instructed to discontinue the drug and contact their veterinarian if diarrhea is severe or persists, or signs such as inappetence, vomiting, fecal abnormalities, anemia, icterus or lethargy are observed T ! Dogs should have access to water; dehydration should be avoided T ! he manufacturer provides a client information sheet and states to “Always provide client information sheet... ” Chemistry/Synonyms A non-steroidal antiinﬂammatory agent (NSAID), tepoxalin occurs as a white, tasteless, crystalline material that is insoluble in water and soluble in alcohol and most organic solvents. The commer-cially available tablets contain a micronized form of the drug in a highly p orous matrix that rapidly disintegrates in the mouth. Drug particles are released into the saliva and swallowed by the dog where it is absorbed in the intestines. T epoxalin may also be known as ORF-20485, RWJ-20485 and Zubrin®. Storage/Stability Tablets should be kept in their foil blister packs until used and stored at temperatures between 2-30°C (36-86°F). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: T epoxalin Oral (rapidly-disintegrating) Tablets: 30 mg, 50 mg, 100 mg, 200 mg in foil blisters containing 10 tablets in boxes of 10 foil blisters; Zubrin® (Schering-Plough); (Rx). Approved for use in dogs. HUMAN-LABELED PRODUCTS: None TERBINAFINE HCL (SYSTEMIC) (ter-bin-ah-ﬁn) Lamisil® ANTIFUNGAL Prescriber Highlights TT Oral & topical antifungal; used primarily for dermato-phytic infections, but may be useful for other fungi (e. g., aspergillus), especially in birds TT Comparatively (with azole antifungals) few drug interactions TT Appears to be very well tolerated, but limited experience; vomiting most likely adverse effect TT Caution if liver or renal disease TT Treatment is relatively expensive, but generics are now available Uses/Indications T erbinaﬁne may be useful for treating dermatophytic and other fungal infections in dogs and cats. T erbinaﬁne may also be useful for treating birds for systemic mycot ic (e. g., aspergillosis) infections. Pharmacology/Actions T erbinaﬁne is an inhibitor of the synthesis of ergosterol, a compo-nent of fungal cell membranes. By blocking the enzyme squalene monooxy genase (squalene 2,3-epoxidase), terbinaﬁne inhibits the conversion of squalene to sterols (especially ergosterol) and causes accumulation of squalene. Both these effects are thought to con-tribute to its antifungal action. T erbinaﬁne's mechanism for inhib-iting ergosterol is different from the azole antifungals. Unlike the azole agents, terbinaﬁne's actions are not mediated via the cy tochrome P-450 enzyme system, and, therefore, do not have the concerns of drug interactions or altering testosterone or cortisol. T erbinaﬁne primarily has clinical activity (fungicidal) against dermat ophytic organisms (Microsporum spp., Trichophyton spp., etc. ). It may only be fungistatic against the yeasts (Candida spp. ). T erbinaﬁne has activity against Aspergillus, Blastomyces, and Histoplasma but is usually not used clinically for infections caused by these organisms. Pharmacokinetics Little veterinary speciﬁc information is available. In cats dosed at 34-46 mg/kg PO once daily for 14 days terbinaﬁne persisted in hair above MIC for several weeks. (Foust, Marsella et al. 2007) In humans, terbinaﬁne given orally is greater than 70% ab-sorbed; after ﬁrst pass, metabolism bioavailability is about 40%. Food may enhance absorption somewhat. T erbinaﬁne is distributed to skin and into the sebum. Over 99% of drug in plasma is bound to plasma proteins. Drug in the circulation is metabolized in the liver and the effective elimination half-life is about 36 hours. The drug may persist in adipose tissue and skin for very long periods. Contraindications/Precautions/Warnings T erbinaﬁne is contraindicated in patients hypersensitive to it. The manufacturer does not recommend its use in patients with active or chronic liver disease or with signiﬁcantly impaired renal function. If terbinaﬁne is to be used in veterinary patents with markedly im-paired liver or renal function, do so with extreme caution; dosage adjustme nts should be considered.	pppbs.pdf
Adverse Effects Because of limited usage in veterinary patients the adverse effect proﬁle is not well deﬁned, but thus far, the drug appears to be well tolerated. GI effects (vomiting, inappetence, diarrhea) are possible. Very rarely in humans, liver failure, neutropenia or serious skin react ions (e. g., TEN, Stevens-Johnson syndrome) have occurred af-ter terbinaﬁne use. Reproductive/Nursing Safety High dose studies in pregnant rabbits and rats have not demon-strated overt fetotoxicity or teratogenicity, but deﬁnitive safety in preg nancy has not been determined. Use with caution (manufac-turer recommends NOT using in pregnant women). In humans, the FDA cate gorizes this drug 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 demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) The drug enters maternal milk at levels 7 times that found in plas-ma; the manufacturer recommends that mothers not nurse while taking this drug. U se with caution in nursing veterinary patients. Overdosage/Acute Toxicity Limited information; humans have taken doses of up to 5 grams without serious effects. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving terbinaﬁne and may be of signiﬁcance in veterinary patients: T ! CYCLOSPORINE : T erbinaﬁne may increase the elimination of cyclosporine T ! RIFAMPIN : May increase terbinaﬁne clearance As it shares the same metabolic pathway (CYP2D6), terbinaﬁne could affect the metabolism of: T ! BETA-BLOCKERS T ! MAO INHIBITORS (amitraz, selegiline ) T ! SSRI'S (ﬂuoxetine, etc. ) T ! TRICYCLIC ANTIDEPRESSANTS Laboratory Considerations No apparent issues Doses T ! DOGS & CAT S: For dermatophytic infections: a) 30-40 mg/kg PO once daily (Moriello 2004) b) 30 mg/kg PO once daily. Treatment should continue until two suc cessive brush cultures (separated by two weeks) are negative. First culture can be taken 3-4 weeks after starting therapy. (Foil 2003b) c) In cases where other drugs are not tolerated: 25 mg/kg PO q24h. (Rosenkrantz 2006a) For a djunctive treatment (with topical therapy) of nasal Asper-gillus infections if the cribriform pate is penetrated: a) 5-10 mg/kg PO q12h for 3-6 months (Kuehn 2007) For pythiosis where advanced disease precludes complete surgi-cal excision: a) 10 mg/kg PO q24h with itraconazole (10 mg/kg PO twice daily) (Marks 2007a) F or lagendiosis where disease precludes complete surgical excision: a) 5 -10 mg/kg PO q24h with itraconazole (10 mg/kg PO q24h) with re peated aggressive surgical resection was effective in one dog with multifocal cutaneous lesions, but no systemic lesions. (Grooters 2007) T ! BIRDS: For avian mycotic infections: a) 10-15 mg/kg PO q12-24h (Dalhausen, Lindstrom et al. 2000) b) 10-15 mg/kg PO q12-24h (suspend a 250 mg tablet in 25 m L water); Nebulization: 1 mg/m L (500 mg terbinaﬁne plus 1 m L Mucomyst® plus 500 m L of distilled water). T erbinaﬁne can be used in combination with itraconazole. (Flammer 2003a) Monitoring T ! Clinical efﬁcacy T ! Baseline liver enzymes and then as needed (especially if treating long-term) Client Information T ! Costs of treating can be considerable T ! Give with food, particularly if vomiting is a problem Chemistry/Synonyms A synthetic allylamine antifungal, terbinaﬁne HCl occurs as a white to off-white, ﬁne, crystalline powder. It is slightly soluble in water and soluble in ethanol. T erbinaﬁne HCl may also be known as: Alamil®, Daskil®, Daskyl®, Desenex Max®, Finex®, Lamisil®, Maditez®, Micosil®, or Terekol ®. Storage/Stability T erbinaﬁne tablets should be stored at room temperature, in tight containers; protect from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: T erbinaﬁne HCl Tablets: 250 mg; Lamisil® (Novartis), generic; (Rx) A topical cream and spray (1%) are also available (Rx). TERBUTALINE SULFATE (ter-byoo-ta-leen) Brethine® BETA-ADRENERGIC AGONIST Prescriber Highlights TT Beta agonist used as a bronchodilator & sometimes to treat bradyarrhythmias TT Contraindications: Hypersensitivity to terbutaline TT Caution: Diabetes, hyperthyroidism, hypertension, seizure disorders, or cardiac disease (especially with concurrent arrhythmias) TT Adverse Effects: Increased heart rate, tremors, CNS ex-citement (nervousness) & dizziness; after parenteral in-jection in horses, sweating & CNS excitation are possible	pppbs.pdf
Uses/Indications T erbutaline is used as a bronchodilating agent in the adjunctive treatment of cardiopulmonary diseases (including tracheobronchi-tis, collapsing trachea, pulmonary edema, and allergic bronchitis) in smal l animals. It may be of some beneﬁt in treating bradyar-rhythmias in dogs and cats. T erbutaline has been used occasionally in horses for its broncho-dilating effects, but adverse effects, short duration of activity after IV a dministration and poor oral absorption have limited its use. It has been shown to be useful as a diagnostic agent to diagnose anhidrosis in horses after intradermal injection. Oral and intravenous terbutaline has been used successfully in humans f or the inhibition of premature labor clinical signs. Pharmacology/Actions T erbutaline stimulates beta-adrenergic receptors found princi-pally in bronchial, vascular, and uterine smooth muscles (beta 2); br onchial and vascular smooth muscle relaxation occurs with re-sultant reduced airway resistance. At usual doses it has little effect on cardiac (beta 1) receptors and usually does not cause direct car-diostimulatory effects. Occasionally, a tachycardia develops which may be a result of either direct beta stimulation or a reﬂex response secondary to peripheral vasodilation. T erbutaline has virtually no alpha-adrenergic activity. Pharmacokinetics The pharmacokinetics of this agent have apparently not been thoroughly studied in domestic animals. In humans, only about 33-50% of an oral dose is absorbed; peak bronchial effects occur within 2-3 hours and activity persists up to 8 hours. T erbutaline is well-absorbed following SC administration with an onset of action occurring within 15 minutes, peak effects at 30-60 minutes, and duration of activity up to 4 hours. In horses, terbutaline is very poorly absorbed after oral adminis-tration with a bioavailability <1%. When given IV, mean residence time is about 30 minutes in horses and the drug probably needs to be given as a constant rate infusion if used therapeutically. T erbutaline is distributed into milk at levels approximately 1% of the oral dose given to the mother. T erbutaline is principally ex-creted unchanged in the urine (60%), but is also metabolized in the liv er to an inactive sulfate conjugate. Contraindications/Precautions/Warnings T erbutaline is contraindicated in patients hypersensitive to it. One veterinary school formulary (Schultz 1986) states that terbutaline is contraindicated in dogs and cats with heart disease, especially with CHF or cardiomyopathy. It should be used with caution in patients with diabetes, hyperthyroidism, hypertension, seizure disorders, or cardiac disease (especially with concurrent arrhythmias). Adverse Effects Most adverse effects are dose-related and those that would be ex-pected with sympathomimetic agents, including increased heart rat e, tremors, CNS excitement (nervousness) and dizziness. These effects are generally transient, mild and do not require discontinu-ation of therapy. After parenteral injection in horses, sweating and CNS ex citation have been reported. Transient hypokalemia has been reported in humans receiving be ta-adrenergic agents. If an animal is susceptible to developing hy-pokalemia, it is suggested that additional serum potassium moni-toring be done early in therapy. 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 fe tus, 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. ) T erbutaline is excreted in milk. In humans, nursing is not rec-ommended with systemic terbutaline therapy. Overdosage/Acute Toxicity Clinical signs of signiﬁcant overdose after systemic administration may include arrhythmias (bradycardia, tachycardia, heart block, extrasystoles), hypertension, fever, vomiting, mydriasis, and CNS stimulation. If a recent oral ingestion, it should be handled like oth-er overdoses (empty gut, give activated charcoal and a cathartic) if the animal does not have signiﬁcant cardiac or CNS effects. If cardi-ac arrhythmias require treatment, a beta-blocking agent (e. g., pro-pranolol) can be used, but may precipitate bronchoconstriction. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving terbutaline and may be of signiﬁcance in veterinary patients: !TANESTHETICS, INHALATION (e. g., halothane, isoﬂurane, methoxyﬂu-rane): Use with inhalation anesthetics may predispose the patient to ventricular arrhythmias, particularly in patients with preexist-ing cardiac disease—use cautiously !TBETA-ADRENERGIC BLOCKING A GENTS (e. g., propranolol ): May antago-nize the actions of terbutaline !TDIGOXIN : Use with digitalis glycosides may increase the risk of car-diac arrhythmias !TMONOAMINE OXIDASE INHIBITORS : May potentiate the vascular ef-fects of terbutaline !TSYMP ATHOMIMETICS, OTHER : Use of terbutaline with other sym-pathomimetic amines may increase the risk of developing ad-verse cardiovascular effects !TTRICYCLIC ANTIDEPRESSANTS : May potentiate the vascular effects of terbutaline Doses !TDOGS: a) For a trial to treat intrathoracic tracheal collapse, expira-tory cough or dyspnea and marked exercise intolerance: 1. 25-5 mg (total dose) PO two to three times daily (Johnson 2004c) b) As a bronchodilator in chronic bronchitis: Small dogs: 0. 625-1. 25 mg (total dose) PO q12h; medium-sized dogs: 1. 25-2. 5 mg (total dose) PO q12h; large dogs: 2. 5-5 mg PO q12h (J ohnson 2000) c) For bradyarrhythmias: 0. 2 mg/kg PO q8-12h; improvement usual ly partial and often temporary (Rishniw and Thomas 2000) d) For treatment of premature labor: 0. 03 mg/kg PO q8h or by co ntinuous IV infusion to effect (Davidson 2004c) e) For tracheal collapse: Small dogs: 0. 625-1. 25 mg (total dose) PO q12h; medium-sized dogs: 1. 25-2. 5 mg (total dose) PO q12h; large dogs: 2. 5-5 mg PO q12h; 0. 01 mg/kg IV, IM or SC (Ettinger and Kantrowitz 2005)	pppbs.pdf
T ! CATS: a) For acute exacerbations of feline asthma treated at home: 0. 01 mg/kg SC or IM; Beneﬁcial response (decrease of re-spiratory rate or effort by 50%) occurs in 15-30 minutes. A heart rat e that approaches 240 BPM indicates that the drug has been absorbed. (Padrid 2000) b) For feline asthma: 0. 312-0. 625 mg (total dose) per cat PO two to three times daily; may adjust dose up to 1. 25 mg in larger cats if needed (Noone 1999) c) For bradyarrhythmias: 0. 625 mg PO q8-12h; improvement usually partial and often temporary (Rishniw and Thomas 2000) d) For acute bronchoconstriction (initial crisis): 0. 01 mg/kg IV, SC, IM (Cohn 2007) T ! HORSES: (Note : ARCI UCGFS Class 3 Drug) a) 0. 0033 mg/kg IV (Robinson 1987) Monitoring T ! Clinical symptom improvement; auscultation T ! Cardiac rate, rhythm (if indicated) T ! Serum potassium, early in therapy if animal susceptible to hy-pokalemia Client Information T ! Contact veterinarian if animal's condition deteriorates or if it be-comes acutely ill Chemistry/Synonyms A synthetic sympathomimetic amine, terbutaline sulfate occurs as a slightly bitter-tasting, white to gray-white, crystalline powder that may have a faint odor of acetic acid. One gram is soluble in 1. 5 m L of water or 250 m L of alcohol. The commercially available injection has its p H adjusted to 3-5 with hydrochloric acid. T erbutaline Sulfate may also be known as: KWD-2019, terbuta-line sulphate, terbutalini sulfas; many trade names are available. Storage/Stability/Compatibility T erbutaline tablets should be stored in tight containers at room temperature (15-30°C). Tablets have an expiration date of 3 years beyond the date of manufacture. T erbutaline injection should be stored at room temperature (15-30°C) and protected from light. The injection has an expiration date of 2 years after the date of manufacture. T erbutaline injection is stable over a p H range of 1-7. Discolored solutio ns should not be used. It is physically compatible with D 5W and aminophylline. 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: T erbutaline Sulfate Tablets: 2. 5 mg & 5 mg; Brethine® (aai Pharma); generic; (Global) (Rx) T erbutaline Injection: 1 mg/m L in 1 m L vials & 2 m L amps with 1 m L ﬁll; Brethine ® (aai Pharma); generic; (Rx) TESTOSTERONE CYPIONATE TESTOSTERONE ENANTHATE TESTOSTERONE PROPIONATE (tess-toss-ter-ohn) ANDROGENIC HORMONE Prescriber Highlights TT Principle endogenous androgen used primarily for the treatment of testosterone-responsive urinary inconti-nence in neutered male dogs/cats; in bovine medicine to produce an estrus-detector animal TT Contraindications: Known hypersensitivity to the drug; prostate carcinoma. Caution: Renal, cardiac, or hepatic dysfunction TT Adverse Effects: Uncommon, but perianal adenomas, perineal hernias, prostatic disorders, & behavior changes possible TT Testosterone products are controlled substances (C-III) Uses/Indications The use of injectable esters of testosterone in veterinary medicine is limited primarily to its use in dogs (and perhaps cats) for the treat-ment of testosterone-responsive urinary incontinence in neutered males. T estost erone has been used to treat a rare form of dermatitis (exhibited by bilateral alopecia) in neutered male dogs. These drugs are also used in bovine medicine to produce an estrus-detector (teaser) animal in cull cows, heifers, and steers. The effectiveness of testosterone to increase libido, treat hypogo-nadism, aspermia, and infertility in domestic animals has been dis-appointing. Pharmacology/Actions The principle endogenous androgenic steroid, testosterone is re-sponsible for many secondary sex characteristic of the male as well as the matur ation and growth of the male reproductive organs and increasing libido. T estosterone has anabolic activity with resultant increased pro-tein anabolism and decreased protein catabolism. T estosterone causes nitro gen, sodium, potassium and phosphorus retention and decreases the urinary excretion of calcium. Nitrogen balance is im-proved only when an adequate intake of both calories and protein occurs. B y stimulating erythropoietic stimulating factor, testosterone can stimulat e the production of red blood cells. Large doses of ex-ogenous testosterone can inhibit spermatogenesis through a nega-tive feedback mechanism inhibiting luteinizing hormone (LH). T estosterone may help maintain the normal urethral muscle tone and integrity of the urethral mucosa in male dogs. It may also be necessary to prevent some types of dermatoses. Pharmacokinetics Orally administered testosterone is rapidly metabolized by the GI mucosa and the liver (ﬁrst-pass effect); very little reaches the sys-temic circulation. The esteriﬁed compounds, testosterone enanthate and cypionat e are less polar than testosterone and more slowly ab-sorbed from lipid tissue after IM injection. The duration of action of these c ompounds may persist for 2-4 weeks after IM injection. T estosterone propionate reportedly has a much shorter duration of	pppbs.pdf
action than the enanthate or cypionate esters. Because absorption is dependent upon several factors (volume injected, perfusion, etc. ), duration of action may be variable. T estosterone is highly bound to a speciﬁc testosterone-estradiol glo bulin (98% in humans). The quantity of this globulin determines the amount of drug that is in the free or bound form. The free form concentration determines the plasma half-life of the hormone. T estosterone is metabolized in the liver and is, with its metabo-lites, excreted in the urine (≈90%) and the feces (≈6%). The plasma half-life of testosterone has been reported to be between 10-100 minutes in humans. The plasma half-life of testosterone cypionate has been reported to be 8 days. Contraindications/Precautions/Warnings T estosterone therapy is contraindicated in patients with known hy-persensitivity to the drug or prostate carcinoma. It should be used with cau tion in patients with renal, cardiac or hepatic dysfunction. Adverse Effects Adverse effects are reportedly uncommon when injectable testos-terone products are used in male dogs to treat hormone-responsive inco ntinence. Perianal adenomas, perineal hernias, prostatic disor-ders, and behavior changes (aggression) are all possible, however. Be havioral changes have been reported in cats. Polycythemia has been reported in humans receiving high dosages of testosterone. High dosages or chronic usage may result in oligospermia or infer-tility in intact males. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category X for use during pregnancy (Studies in animals or humans demonstrate fetal abnormalities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any pos-sible beneﬁt. ) 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. ) It is not known whether androgens are excreted in milk; con-sider using milk replacer if using testosterone in nursing patients. Overdosage/Acute Toxicity No speciﬁc information was located; refer to the Adverse Effects section for further information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving testosterone and may be of signiﬁcance in veterinary patients: !TCORTICOSTEROIDS : Androgens may enhance the edema that can be associated with ACTH or adrenal steroid therapy !TINSULIN; ORAL ANTIDIABETIC AGENTS : T estosterone may decrease se-rum glucose levels !TPROPRANOLOL : T estosterone cypionate may increase propranolol clearance !TWARFARIN : T estosterone may increase anticoagulant effects Laboratory Considerations !TConcentrations of protein bound iodine (PBI) can be decreased in patients receiving testosterone therapy, but the clinical signiﬁ-cance of this is probably not important. Androgen agents can de-crease amounts of thyroxine-binding globulin and decrease total T4 concentrations and increase resin uptake of T 3 and T 4. Free thyroid hormones are unaltered and clinically, there is no evi-dence of dysfunction. !TBoth creatinine and creatine excretion can be decreased by testos-terone !TTe s to s te ro n e c a n i n c re a s e t h e u r i n a r y exc re t i o n o f 17-ketosteroids !TAndrogenic/anabolic steroids may alter blood glucose levels !TAndrogenic/anabolic steroids may suppress clotting factors II, V, VII, and X Doses !TDOGS: For testosterone-responsive urinary incontinence (may be used with phenylpropanolamine) in males: a) T estosterone propionate: approximately 2 mg/kg IM or SC 3 times per week. T estosterone cypionate: 200 mg IM once per month (La Bato 1988), (Polzin and Osborne 1985) b) T estosterone propionate: 2. 2 mg/kg IM q2-3 days. T estoster-one cypionate: 2. 2 mg/kg IM once per month (Moreau and Lappin 1989), (Chew, Di Bartola, and Fenner 1986) c) T estosterone cypionate: 2. 2 mg/kg IM q4-8 weeks (Lane 2002b) d) T estosterone propionate: 2. 2 mg/kg IM or SC every 2-3 day s. T estosterone cypionate: 2. 2 mg/kg every 30 days or 200 mg IM every 30 days. (Bartges 2006a) For estrus control: a) T estosterone enanthate or cypionate 0. 5 mg/kg IM once every 5 da ys or methyltestosterone tablets 25 mg PO twice a week; this dose is for Greyhound-sized dogs. (Purswell 1999) T o reduce mammary gland enlargement seen in pseud opregnancy: a) T estosterone enanthate or cypionate 0. 5-1 mg/kg IM once (Pur swell 1999) !TCATS: For infertility or reduced libido: Using either testosterone cypi-onate or propionate: a) 0. 1-1 mg every other day or every third day for 3-5 injec-tions IM or SC. Not indicated for testis descent. (Verstegen 2000) For testosterone-responsive urinary incontinence (may be used with p henylpropanolamine) in males: a) T estosterone propionate 5-10 mg IM as needed (Barsanti and Finc o 1986), (Osborne, Kruger et al. 2000), (Bartges 2006a) !TCATTLE: T o produce an estrus-detector (teaser) animal (cull cows, heifers, steers): a) T estosterone propionate 200 mg IM on day 1 and on days 4- 9. On day 10, give 1 gram IM and attach a chinball marker and put with the breeding herd. T o maintain the teaser give 1 gram booster every 10-14 days. Alternatively, initially give testosterone enanthate 0. 5 gram IM and 1. 5 gram SC (divided in two separate locations). Af-ter 4 days attach chinball marker and put in with breeding her d. T o maintain, give 0. 5-0. 75 gram SC every 10-14 days. (Wolfe 1986) Monitoring !TEfﬁcacy !TAdverse effects	pppbs.pdf
Chemistry/Synonyms The esteriﬁed compounds, testosterone cypionate, enanthate, and propionate are available commercially as injectable products. T estosterone cypionate occurs as an odorless to having a faint odor, creamy white or white, crystalline powder. It is insoluble in water, soluble in vegetable oils, and freely soluble in alcohol. T estosterone cypionate has a melting range of 98°-104°C. It may also be known as testosterone cyclopentylpropionate. T estosterone enanthate occurs as an odorless to having a faint odor, creamy white or white, crystalline powder. It is soluble in veg-etable oils, insoluble in water and melts between 34-39°C. T estosterone propionate occurs as odorless, creamy white to white, cr ystals or crystalline powder. It is insoluble in water, freely soluble in alcohol and soluble in vegetable oils. T estosterone propi-onate melts between 118-123°C. T estosterone Cypionate may also be known as: testosterone cyclop entylpropionate, testosterone cypionate, Deposteron®, Depotrone®, Depo-Testosterone®, Duratest®, Scheinpharm Testone-Cyp®, T-Cypionate®, Testex®, Testiormina®, Testred®, Virilon®, or dep Andro®. T estosterone Propionate may also be known as: NSC-9166, testoste roni propionas, Malogen in Oil®, Sostenon®, Sustanon®, Testanon 25®, Testex®, Testoviron®, Testoviron Depot®, Testovis®, Tesurene®, or Virormone®. Storage/Stability/Compatibility The commercially available injectable preparations of testosterone cypionate, enanthate and propionate should be stored at room tem-perature; avoid freezing or exposing to temperatures greater than 40°C. If e xposed to low temperature a precipitate may form, but should redissolve with shaking and rewarming. If a wet needle or syringe is used to draw up the parenteral solutions, cloudy solutions may result, but will not affect the drug's potency. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: No known testosterone products (with the exception of combinations with estradiol as growth promotant implants) approved for use in veterinary species were located. T estosterone propionate (200 mg) is available in combination with estradiol benzoate (20 mg) as a growth promotant. Trade names include Component E-H® (Vet Life); (OTC) and Synovex-H® (Fort Dodge); (OTC). For use in heifers weighing 400 or more pounds. T estosterone propionate (200 mg) with estradiol benzoate (28 mg); Synov ex-Plus® (Fort Dodge); (OTC); for steers. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: T estosterone Cypionate (in oil) Injection: 100 mg/m L, and 200 mg/ m L in 1 m L and 10 m L vials; Depo-Testosterone® (Pharmacia); ge-neric (Watson); (Rx, C-III) T estosterone Enanthate (in oil) Injection: 200 mg/m L in 5 m L multi-dose vials and 1 m L syr inges; Delatestyl® (Savient); (Rx, C-III) T estosterone Propionate Injection (in oil): 100 mg/m L in 10 m L vials; available g enerically; (Rx, C-III) T estosterone Pellets: 75 mg (0. 2 mg stearic acid, 2 mg polyvinylpyr-rolidone) in 1 pellet/vials; Testop el® (Bartor Pharmacal); (Rx, C-III) T estosterone Transdermal System: Release Rates: 5 and 2. 5 mg/24 hour, total testosterone contents: 24. 3 mg and 12. 2 mg (respectively): Androderm® (Watson Pharma); (Rx, C-III) T estosterone Gel: 1% testosterone in 2. 5 g or 5 g packets of gel to de-liver 25 mg or 50 mg testosterone and metered-dose pumps to deliver 75 g or 60 metered 1. 25 g doses; Andro Gel® 1% (Unimed Pharm. ); Testim® (Auxilium Pharm); (Rx, C-III) T estosterone, Buccal System: 30 mg testosterone in blister packs; Stri-ant® (C olumbia); (Rx, C-III) TETRACYCLINE HCL (tet-ra-sye-kleen) Aquadrops®, Panmycin® TETRACYCLINE ANTIBIOTIC Prescriber Highlights TT Prototype tetracycline antibiotic; many bacteria are now resistant, but still may be very useful to treat mycoplas-ma, rickettsia, spirochetes, & Chlamydia TT Dosing frequency may be an issue for small animals TT Contraindications: Hypersensitivity TT Extreme Caution: Pregnancy TT Caution: Liver or renal insufﬁciency TT Adverse Effects: GI distress, staining of developing teeth & bones, superinfections, photosensitivity; long-term use may cause uroliths. CATS: Do not tolerate very well. HORSES: If stressed may break with diarrheas (oral use). RUMINANTS: High oral doses can cause ruminal microﬂora depression & ruminoreticular stasis; rapid IV of undiluted propylene glycol-based products can cause intravascular hemolysis & cardiodepressant effects; IM: local reactions, yellow staining & necrosis may be seen at the injection site Uses/Indications While tetracycline still is used as an antimicrobial, most small ani-mal clinicians prefer doxycycline and large animal clinicians prefer oxyte tracycline when a tetracycline is indicated to treat susceptible infections. The most common use of tetracycline HCl today is in combination with niacinamide for the treatment of certain im-mune-mediated skin conditions in dogs, such as pemphigus. Pharmacology/Actions T etracyclines generally act as bacteriostatic antibiotics and inhibit protein synthesis by reversibly binding to 30S ribosomal subunits of susceptible organisms, thereby preventing binding to those ri-bosomes of aminoacyl transfer-RNA. T etracyclines are believed to reve rsibly bind to 50S ribosomes and additionally alter cytoplasmic membrane permeability in susceptible organisms. In high concen-trations, tetracyclines can inhibit protein synthesis by mammalian cells. A s a class, the tetracyclines have activity against most mycoplas-ma, spirochetes (including the Lyme disease organism), Chlamydia, and Rick ettsia. Against gram-positive bacteria, the tetracyclines have activity against some strains of staphylococcus and streptococci, but resistance of these organisms is increasing. Gram-positive bac-teria that are usually covered by tetracyclines include Actinom yces spp., Bacillus anthracis, Clostridium perfringens and tetani, Listeria monocytogenes, and Nocardia. Among gram-negative bacteria that tetracyclines usually have in vitro and in vivo activity include	pppbs.pdf
Bordetella spp., Brucella, Bartonella, Haemophilus spp., Pasturella multocida, Shigella, and Y ersinia pestis. Many or most strains of E. coli, Klebsiella, Bacteroides, Enterobacter, Proteus and Pseudomonas aeruginosa are resistant to the tetracyclines. While most strains of Pseudomonas aeruginosa show in vitro resistance to tetracyclines, those compounds attaining high urine levels (e. g., tetracycline, oxytetracycline) have been associated with clinical cures in dogs with UTI secondary to this organism. Oxytetracycline and tetracycline share nearly identical spec-trums of activity and patterns of cross-resistance and a tetracycline susc eptibility disk is usually used for in vitro testing for oxytetracy-cline susceptibility. T etracyclines have antiinﬂammatory and immunomodulating eff ects. They can suppress antibody production and chemotaxis of neutrophils; inhibit lipases, collagenases, prostaglandin synthesis, and activation of complement component 3. Pharmacokinetics Both oxytetracycline and tetracycline are readily absorbed after oral administration to fasting animals. Bioavailabilities are ap-proximately 60-80%. The presence of food or dairy products can signiﬁcantl y reduce the amount of tetracycline absorbed, with re-ductions of 50% or more possible. After IM administration, tetra-cycline is erratically and poorly absorbed with serum levels usually low er than those attainable with oral therapy. T etracyclines as a class, are widely distributed to heart, kidney, lung s, muscle, pleural ﬂuid, bronchial secretions, sputum, bile, sa-liva, urine, synovial ﬂuid, ascitic ﬂuid, and aqueous and vitreous humo r. Only small quantities of tetracycline and oxytetracycline are distributed to the CSF, and therapeutic levels may not be achiev-able. While all tetracyclines distribute to the prostate and eye, doxy-cycline or minocycline penetrate better into these and most other tiss ues. T etracyclines cross the placenta, enter fetal circulation and are distributed into milk. The volume of distribution of tetracycline is approximately 1. 2-1. 3 L/kg in small animals. The amount of plasma protein binding is about 20-67% for tetracycline. In cattle, the volume of distribution for oxytetracycline is between 1 and 2. 5 L/kg. Milk to plasma ratios for oxytetracycline and tetracycline are 0. 75 and 1. 2-1. 9, respectively. Both oxytetracycline and tetracycline are eliminated unchanged pr imarily via glomerular ﬁltration. Patients with impaired renal function can have prolonged elimination half-lives and accumu-late the drug with repeated dosing. These drugs apparently are not metab olized, but are excreted into the GI tract via both biliary and nonbiliary routes and may become inactive after chelation with fe-cal materials. The elimination half-life of tetracycline is approxi-mately 5-6 hours in dogs and cats. Contraindications/Precautions/Warnings T etracycline is contraindicated in patients hypersensitive to it or other tetracyclines. Because tetracyclines can retard fetal skeletal de-velopment and discolor deciduous teeth, they should only be used in the last half of pregnancy when the beneﬁts outweigh the fetal risks. Oxytetracycline and tetracycline are considered more likely to cause these abnormalities than either doxycycline or minocycline. In patients with renal insufﬁciency or hepatic impairment, tet-racycline must be used cautiously; lower than normal dosages are re commended with enhanced monitoring of renal and hepatic function. Avoid concurrent administration of other nephrotoxic or hepatotoxic drugs if tetracyclines are administered to these pa-tients. Monitoring of serum levels should be considered if long-term therapy is required. Adverse Effects Oxytetracycline and tetracycline given to young animals can cause discoloration of bones and teeth to a yellow, brown, or gray color. High dosages or chronic administration may delay bone growth and healing. T etracyclines in high levels can exert an antianabolic effect that can cause an increase in BUN and/or hepatotoxicity, particularly in patients with preexisting renal dysfunction. As renal function deteriorates secondary to drug accumulation, this effect may be exacerbated. In ruminants, high oral doses can cause ruminal microﬂora de-pression and ruminoreticular stasis. Rapid intravenous injection of undilu ted propylene glycol-based products can cause intravascular hemolysis with resultant hemoglobinuria. Propylene glycol based products have also caused cardiodepressant effects when admin-istered to calves. When administered IM, local reactions, yellow staining, and necrosis may be seen at the injection site. In small animals, tetracyclines can cause nausea, vomiting, an-orexia, and diarrhea. Cats do not tolerate oral tetracycline or oxytet-racycline very well, and may present with clinical signs of colic, fe ver, hair loss, and depression. There are reports that long-term tetracycline use may cause urolith formation in dogs. Horses that are stressed by surgery, anesthesia, trauma, etc., may br eak with severe diarrheas after receiving tetracyclines (especially with oral administration). T etracycline therapy (especially long-term) may result in over-growth of non-susceptible bacteria or fungi (superinfections). T etracyclines have also been associated with photosensitivity re-actions and, rarely, hepatotoxicity or blood dyscrasias. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category D for use dur-ing pregnancy (There is evidence of human fetal risk, but the potential be neﬁts 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 feline pregnancy (Papich 1989), this drug is categorized as in class: D (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) T etracyclines are excreted in milk, but because much of the drug wil l be bound to calcium in milk, it is unlikely to be of signiﬁcant risk to nursing animals. Overdosage/Acute Toxicity T etracyclines are generally well tolerated after acute overdoses. Dogs given more than 400 mg/kg/day orally or 100 mg/kg/day IM of oxytetracycline did not demonstrate any toxicity. Oral overdoses would most likely be associated with GI disturbances (vomiting, anorexia, and/or diarrhea). Should the patient develop severe em-esis or diarrhea, ﬂuids and electrolytes should be monitored and re placed if necessary. Chronic overdoses may lead to drug accumu-lation and nephrotoxicity. High oral doses given to ruminants, can cause ruminal micro-ﬂor a depression and ruminoreticular stasis. Rapid intravenous injection of undiluted propylene glycol-based products can cause intravascular hemolysis with resultant hemoglobinuria. Rapid intravenous injection of tetracyclines has induced tran-sient collapse and cardiac arrhythmias in several species, presum-ably due to chelation with intravascular calcium ions. Overdose quant ities of drug could exacerbate this effect if given too rapidly IV. If the drug must be given rapidly IV (less than 5 minutes), some clinicians recommend pre-treating the animal with intravenous calcium gluconate.	pppbs.pdf
T TDrug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving tetracyclines and may be of signiﬁcance in veterinary patients: !TATOVAQUONE : T etracyclines have caused decreased atovaquone levels !TBETA-LACTAM OR AMINOGLYCOSIDE ANTIBIOTICS : Bacteriostatic drugs, like the tetracyclines, may interfere with bactericidal activ-ity of the penicillins, cephalosporins, and aminoglycosides; there is so me controversy regarding the actual clinical signiﬁcance of this interaction, however. !TDIGOXIN : T etracyclines have increased the bioavailability of digox-in in a small percentage of human patients and caused digoxin to xicity. These effects may persist for months after discontinua-tion of the tetracycline. !TDIVALENT OR TRIVALENT CATIONS (oral antacids, saline cathartics or other GI products containing aluminum, calcium, iron, magnesium, zinc, or bismuth cations ): When orally administered, tetracyclines can chelate divalent or trivalent cations that can decrease the ab-sorption of the tetracycline or the other drug if it contains these catio ns; it is recommended that all oral tetracyclines be given at least 1-2 hours before or after the cation-containing products. !TMETHOXYFLURANE : Fatal nephrotoxicity has occurred in humans when used with tetracycline; concomitant use with oxytetracy-cline not recommended !TWARFARIN : T etracyclines may depress plasma prothrombin ac-tivity and patients on anticoagulant therapy may need dosage adj ustment Laboratory Considerations !Tetracyclines (not minocycline) may cause falsely elevated values of urine catecholamines when using ﬂuorometric methods of de-termination. !Tetracyclines reportedly can cause false-positive urine glucose re-sults if using the cupric sulfate method of determination (Bene-dict's reagent, Clinitest ®), but this may be the result of ascorbic acid that is found in some parenteral formulations of tetracy-clines. T etracyclines have also reportedly caused false-negative res ults in determining urine glucose when using the glucose oxi-dase method (Clinistix®, Tes-T ape®). Doses !TDOGS: For discoid lupus erythematosus: a) For dogs weighing 10 kg or more: 500 mg of niacinamide and 500 mg of tetracycline PO q8h. For dogs weighing from 5-10 kg: 250 mg of each PO q8h. For dogs weighing <5 kg: 100 mg of each PO q8h. Improvement is usually noted with-in 6 weeks. (White 2000) b) Dogs weighing more than 10 kg: 500 mg of niacinamide and 500 mg of tetracycline PO q8h. For dogs weighing less than 10 kg: 250 mg of each PO q8h. May use in combination with corticosteroids and Vitamin E. If adverse effects become a problem, reduce dose of niacinamide ﬁrst. May also try this regimen for pemphigus foliaceous or pemphigus erythema-tous. (Campbell 1999) c) For various immune-mediated diseases (discoid lupus ery-thematosus, pemphigus erythematosus, pemphigus folia-ceous, vasculitis, sterile pyelogranuloma, dermatomyositis and l upoid onychodystrophy: For dogs less than 10 kg: 250 mg each of niacinamide and tetracycline PO three times dai-ly. For dogs larger than 10 kg: 500 mg each of niacinamide and tetracycline PO three times daily. May substitute doxycy-cline for tetracycline at 5 mg/kg PO once a day. (Tapp 2002) Fo r susceptible infections: a) For UTI: 16 mg/kg PO q8h for 7-14 days; Fo r Rickettsiosis, Borreliosis: 22 mg/kg PO q8h for 14 days; For systemic bacteremia, brucellosis: 22-50 mg/kg PO q8h for 28 days. (Greene, Hartmannn et al. 2006) b) For Rocky Mountain Spotted Fever: 22 mg/kg q8h for 14-21 day s (Sellon and Breitschwerdt 1995) c) 20 mg/kg PO q8-12h; (may give with food if GI upset oc-curs; avoid or reduce dose in animals with renal or severe liv er failure; avoid in young, pregnant or breeding animals) (Vaden and Papich 1995) d) 22-33 mg/kg PO q8h (Aronson and Aucoin 1989) e) For Lyme disease: 22 mg/kg PO q8h for 14 days (Breitschw-erdt 2000) f) For small intestinal bacterial overgrowth: 5-10 mg/kg PO q8h f or 28 days; has been effective for uncomplicated cases (Ludlow and Davenport 2000) g) For rickettsial diseases: Ehrlichiosis: 22 mg/kg, PO three times daily for at least 14 day s Salmon poisoning: 22 mg/kg, PO three times daily for 10-14 days or 7 mg/kg IV three times daily Ro cky Mountain Spotted Fever: 22 mg/kg, PO three times daily for 10-14 days (Lissman 1988) For facial tear staining: a) 5-10 mg/kg/day or 50 mg per dog per day. Results are vari-able. (Kern 1986) Fo r pleurodesis: a) Using capsules or aqueous solution; mix 20 mg/kg in 4 m L pe r kg of saline and infuse into pleural space (Morgan 1988) !TCATS: For susceptible infections: a) For soft tissue infections: 20 mg/kg PO q8h for 21 days; For Hemotropic mycoplasmosis: 10-25 mg/kg PO q8-12h fo r 21 days; For bacteremia, systemic infections: 7 mg/kg IV, IM q12h as long as necessary. (Greene, Hartmannn et al. 2006) b) For rickettsial diseases: 16 mg/kg, PO three times daily for 21 day s (Morgan 1988) c) 20 mg/kg PO q8-12h; (may give with food if GI upset oc-curs; avoid or reduce dose in animals with renal or severe liv er failure; avoid in young, pregnant or breeding animals) (Vaden and Papich 1995) d) 22-33 mg/kg PO q8h (Aronson and Aucoin 1989) !TFERRETS: For susceptible infections: a) 25 mg/kg PO 2-3 times daily (Williams 2000) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 50-100 mg/kg PO q8-12h (Ivey and Morrisey 2000) b) Chinchillas: 50 mg/kg PO q8-12h (Hayes 2000) c) Chinchillas, Guinea Pigs, Rats: 20 mg/kg, PO q12h. Mice: 20 mg/kg, PO q12h or 50-60 mg/liter of drinking water Ham-sters: 30 mg/kg, PO q6h or 400 mg/liter, drinking water. Ger-bils: 20 mg/kg, PO or IM q24h (Adamcak and Otten 2000)	pppbs.pdf
!TCATTLE : For susceptible infections in calves: a) 11 mg/kg orally (Howard 1986) b) 11 mg/kg, PO twice daily for up to 5 days (Label directions; Po lyotic®—American Cyanamid) !TSHEEP: For susceptible infections: a) 11 mg/kg, PO twice daily for up to 5 days (Label directions; Po lyotic®—American Cyanamid) !THORSES: For susceptible infections: a) 5-7. 5 mg/kg IV q12h (Brumbaugh 1987) !TSWINE: For susceptible infections: a) 22 mg/kg, PO for 3 to 5 days in drinking water (Label direc-tions; Polyotic®—American Cyanamid) !TBIRDS: For susceptible infections: a) For treatment of psittacosis in conjunction with LA -200® (see oxytetracycline doses) and/or medicated pellets and/or Keet Life: Using 25 mg/m L oral suspension, mix 2 teaspoons-ful to 1 cup of soft food. For mild respiratory disease (especially ﬂock treatment): Mix 1 t easpoonful of 10 g/6. 4 oz. soluble powder per gallon of drinking water. Used as an adjunct for psittacosis with other tetracycline forms. Will not reach therapeutic levels by itself. Prepare fresh solution twice daily, as potency is rapidly lost. (Mc Donald 1989) b) Mix 1 teaspoonful of 10 g/6. 4 oz. soluble powder per gal-lon of drinking water and administer for 5-10 days. Prepare fresh sol ution 2-3 times daily, as potency is rapidly lost. For converting regimen to pelleted feeds administer oral susp ension by gavage at 200-250 mg/kg once or twice daily until feeds are accepted. Is not an adequate therapy for long-term treatment of chlamydiosis (psittacosis) (Clubb 1986) Monitoring !TAdverse effects !TClinical efﬁcacy !TLong-term use or in susceptible patients: periodic renal, hepatic, hematologic evaluations Client Information !TAvoid giving this drug orally within 1-2 hours of feeding, giving milk or other dairy products !TIf gastrointestinal upset occurs, giving with a small amount of food may help, but this may also reduce the amount of drug ab-sorbed Chemistry/Synonyms An antibiotic obtained from Streptomyces aureofaciens or derived semisynthetically from oxytetracycline, tetracycline HCl occurs as a moderately hygroscopic, yellow, crystalline powder. About 100 mg/m L is soluble in water and 10 mg/m L soluble in alcohol. T etracycline base has a solubility of about 0. 4 mg per m L of water and 20 mg per m L of alcohol. Commercially available tetracycline HCl for IM injection also contains magnesium chloride, procaine HCl and ascorbic acid. T etracycline may also be known as: tetracyclini hydrochloridum; many t rade names are available. Storage/Stability/Compatibility Unless otherwise instructed by the manufacturer, tetracycline oral tablets and capsules should be stored in tight, light resistant con-tainers at room temperature (15-30°C). The oral suspension and po wder for injection should be stored at room temperature; avoid freezing the oral suspension. After reconstituting the IM product, it may be stored at room te mperature but should be used within 24 hours. After reconstitut-ing the intravenous product with sterile water to a concentration of 50 mg/m L, the preparation is stable for 12 hours at room tempera-ture. If further diluted in an appropriate IV ﬂuid, use immediately. T etracycline HCl for intravenous injection is reportedly physi-cally compatible with the following IV ﬂuids and drugs: 0. 9% so-dium chloride, D 5W, D 5W in normal saline, Ringer's injection, lactated Ringer's injection, 10% invert sugar, dextrose-Ringer's and lactated Ringer's combinations, ascorbic acid, cimetidine HCl, colistimethate sodium, corticotropin, ephedrine sulfate, isoprotere-nol HCl, kanamycin sulfate, lidocaine HCl, metaraminol bitartrate, nor epinephrine bitartrate, oxytetracycline HCl, oxytocin, potassi-um chloride, prednisolone sodium phosphate, procaine HCl, pro-mazine HCl, and vitamin B complex with C. Drugs that are reportedly physically incompatible with tetracy-cline, data conﬂicts, or compatibility is concentration/time depen-dent, include: amikacin sulfate, aminophylline, ampicillin sodium, amobar bital sodium, amphotericin B, calcium chloride/gluconate, carbenicillin disodium, cephalothin sodium, cephapirin sodium, chloramphenicol sodium succinate, dimenhydrinate, erythromycin gluceptate/lactobionate, heparin sodium, hydrocortisone sodium succinate, meperidine HCl, morphine sulfate, methicillin sodium, methohexital sodium, methyldopate HCl, oxacillin sodium, peni-cillin G potassium/sodium, phenobarbital sodium, sodium bicar-bonate, thiopental sodium, and warfarin sodium. Compatibility is de pendent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references or a hospital phar-macist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: There are a variety of T etracycline HCl Soluble Powder (as a water additive) products that are available in various concentrations and sizes. Usual concentrations are either 25 grams/lb or 324 grams/lb and these products may be available in several sizes; may be approved for use in swine, cattle, or poultry. Withdrawal time may vary de-pending on age of animal and product. An oral combination product containing tetracycline, novobiocin and p rednisone (Delta Albaplex®) is also available; see the novobiocin monograph for more information. HUMAN-LABELED PRODUCTS: T etracycline HCl Capsules: 250 mg, and 500 mg; Sumycin®-250 & -500 (Par); generic; (Rx) T etracycline HCl Oral Suspension: 25 mg/m L in 473 m L; Sum ycin® Syrup (Par); (Rx) Theophylline—see Aminophylline	pppbs.pdf
THIABENDAZOLE (thye-a-ben-da-zole) ANTHELMINTIC; ANTIFUNGAL Prescriber Highlights TT Benzimidazole anthelmintic; has antifungal (dermato-phytes) activity TT Contraindications: None noted TT Adverse Effects: DOGS: Vomiting, diarrhea, hair loss, & lethargy. Dachshunds may be particularly sensitive to thiabendazole. Toxic epidermal necrolysis (TEN) is rarely seen. TT Parasitic-resistance is an issue TT Many veterinary products no longer available Uses/Indications Thiabendazole has been used for the removal of the following para-sites in dogs: ascarids (Toxocara canis, T. leonina), Strong yloides ster-coralis, and Filaroides. It has been used systemically as an anti-fun-gal agent in the treatment of nasal aspergillosis and penicillinosis. T opical and otic use of thiabendazole for the treatment of various fungi is also commonly employed. Thiabendazole is indicated (labeled) for the removal of the follow ing parasites in cattle: Haemonchus spp., Ostertagia spp., Trichostrongylus spp., Nematodirus spp., Cooperia spp. and Oesophagostomum radiatum. Thiabendazole is indicated (labeled) for the removal of the fol-lowing parasites in sheep and goats: Haemonchus spp., Ostertag ia spp., Trichostrongylus spp., Nematodirus spp., Cooperia spp., Chabertia spp., Bunostomum spp. and Oesophagostomum spp. Thiabendazole is indicated (labeled) for the removal of the follow ing parasites in horses: Strongylus spp., craterstomum spp., Oesphagodontus spp., Posteriostomum spp., Cyathostomum spp., Cylicocylus spp., Cylicostephanus spp., Oxyuris spp., and Parasacaris spp. Thiabendazole is indicated (labeled) for the removal or preven-tion of the following parasites in swine: large roundworms (Ascaris suum) (p revention), and in baby pigs infested with Strongyloides ransomi. Although not approved, thiabendazole has been used in pet birds and llamas. See the Dosage section for more information. In many geographic areas, signiﬁcant thiabendazole resistance prob lems have developed and, for many parasites, other anthelm-intics would be a better choice for treatment. When used topically, thiabendazole has antidermatophytic prop erties. Pharmacokinetics Thiabendazole is relatively well absorbed (for a benzimidazole) and is distributed throughout body tissues. Peak levels occur in ap-proximately 2-7 hours after dosing. Absorbed drug is rapidly me-tabolized in the liver by hydroxylation, glucuronidation and sulfate format ion. Within 48 hours of dosing, 90% of the drug is excreted in the urine (as metabolites) and 5% in the feces. Less than 1% of the drug is excreted in the urine unchanged. Five days after a dose, the drug is virtually eliminated from the body. Adverse Effects At recommended doses, thiabendazole is usually well tolerated in approved species. In dogs, vomiting, diarrhea, hair loss, and leth-argy are possible side effects, notably with high dose or long-term therapy. Dachshunds have been reported to be particularly sensi-tive to thiabendazole. T oxic epidermal necrolysis (TEN) has been repo rted in dogs receiving thiabendazole, but the incidence appears to be very rare. Reproductive/Nursing Safety Thiabendazole has not been demonstrated to be a teratogen and is considered generally safe to use during pregnancy. However, in high doses it has been implicated in causing toxemia in ewes. 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 dr ugs are safe if they are not administered when the animal is near term. ) It is not known whether this drug is excreted in milk, but it is unlikely t o be of clinical concern in nursing patients. Overdosage/Toxicity Thiabendazole has a safety margin of at least 20 times the recom-mended dose in horses. Doses of 800-1000 mg/kg are necessary to cause anore xia and depression in sheep. The minimum lethal dose is 700 mg/kg in cattle and 1200 mg/kg in sheep. It is unlikely that a modest overdose would cause signiﬁcant problems. If a massive overdose occurs,treat supportively and symp-tomatically. See 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 thiabendazole and may be of signiﬁcance in veterinary patients: T ! THEOPHYLLINE : Thiabendazole may compete with xanthines for metabolizing sites in the liver, thereby increasing xanthine blood levels Doses Note : There are no veterinary commercial products for systemic use currently being marketed in the USA. T ! DOGS: As an antiparasitic agent: a) For treatment of Strong yloides stercoralis: 50-60 mg/kg PO (T odd, Paul, and Di Pietro 1985) b) For treatment of Filaroides (now called Oslerus) infections: 35 mg/kg PO tw ice daily for 5 days, then 70 mg/kg PO twice daily for 21 days. Prednisone can also be given at 0. 55 mg/ kg, PO twice daily every other day (Ettinger, Kantrowitz et al. 2000) As an antifungal agent: a) For treatment of nasal aspergillosis/penicillinosis infec-tions: 30-70 mg/kg divided q12h PO in food for 20-45 days (Roudeb ush 1985) b) For the treatment of aspergillosis: 20 mg/kg PO, once a day or div ided twice daily; (with or without ketoconazole: 20 mg/kg PO, once a day or divided twice daily). Maintenance therapy: 10-20 mg/kg PO once a day (Greene, O'Neal, and Barsanti 1984)	pppbs.pdf
c) For penicillinosis: With appropriate adjunctive surgical cu-rettage and topical therapy, thiabendazole: 20 mg/kg/day PO for 4- 6 weeks (Barsanti 1984) d) For aspergillosis: Administer 10 mg/kg as nasal ﬂush. Dilute in 10-20 m L of water. Flush twice daily for 10 days. Orally : 20 mg/kg/day divided twice daily for 6 weeks (Mor-gan 1988) e) For treatment of nasal aspergillosis: 20 mg/kg divided q12h PO for 6-8 weeks. If anorexia or nausea develops, may with-draw drug and then gradually reintroduce to the full dosage. Administer with food to enhance absorption and reduce an-orexia. May be effective in 40-50% of dogs treated. (Sharp 1989) T ! RABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: For pinworms: 50-100 mg/kg PO for 5 days or 50 mg/kg PO, re peat in 3 weeks (Ivey and Morrisey 2000) b) Mice, Rats, Gerbils, Hamsters, Guinea pigs: 100 mg/kg, PO f or 5 days. Chinchil las: 50-100 mg/kg PO for 5 days (Adamcak and Ot-ten 2000) c) For pinworms in Mice, Rats, Hamsters, Gerbils and Rabbits: 50 mg/kg, PO onc e (Burke 1999) T ! CATTLE: For susceptible parasites: a) 66 mg/kg PO; 110 mg/kg PO for Cooperia and severe infec-tions of other susceptible nematodes. Retreat treatment in 2-3 we eks if indicated (Paul 1986), (Roberson 1988b) b) 50-100 mg/kg PO (Brander, Pugh, and Bywater 1982) T ! HORSES: For susceptible parasites: a) 44 mg/kg, PO (Robinson 1987) b) 44 mg/kg; 88 mg/kg for ascarids (Roberson 1988b) c) 50-100 mg/kg PO (Brander, Pugh, and Bywater 1982) T ! SWINE: For susceptible parasites: a) For baby pigs with Strong yloides ransomi: 62-83 mg/kg PO, retreat in 5-7 days if necessary. T o prevent Ascaris suum: Feed at 0. 05-0. 1% per ton of feed for 2 weeks, then 0. 005-0. 02% per to n for 8-14 weeks (Paul 1986) b) 75 mg/kg, PO (Roberson 1988b) c) 50 mg/kg, PO (Brander, Pugh, and Bywater 1982) T ! SHEEP & GOATS: For susceptible parasites: a) 44 mg/kg PO; 66 mg/kg PO for severe infections in goats (Paul 1986), (Ro berson 1988b) b) 50-100 mg/kg PO (sheep) (Brander, Pugh, and Bywater 1982) T ! LLAMAS: For susceptible parasites: a) 50-100 mg/kg PO for 1-3 days. Use higher dosage rate over sever al days when animal is severely parasitized. (Cheney and Allen 1989) b) 66 mg/kg PO (Fowler 1989) T ! BIRDS: For susceptible parasites: a) For ascarids: 250-500 mg/kg PO once. Repeat in 10-14 days. For S yngamus trachea: 100 mg/kg, PO once a day for 7-10 days (Clubb 1986) b) For ascarids, Capillaria, gapeworms: Chickens, pheasants, turkeys, and pigeons: Mix 0. 5% in feed for 10 day s or administer orally at 44 mg/kg as a single dose. Psittacines: 44 mg/kg PO; do not exceed this dose. Falcons: 100 mg/kg PO as a single dose (Stunkard 1984) c) For thorny headed worms in waterfowl and raptors: 250 mg/ lb (Stunkard 1984) Client Information T ! Shake suspension well before using. T ! Follow veterinarian's or label's directions carefully. Chemistry/Synonyms The prototypic benzimidazole, thiabendazole occurs as an odorless or nearly odorless, tasteless, white to practically white powder. It has a melting range of 296°-303°C and a p K a of 4. 7. Thiabendazole is practically insoluble in water and slightly soluble in alcohol. Thiabendazole may also be known as: E233, MK-360, tia-bendazolum, tiabendazole, Benzo l®, Eproﬁl®, Foldan®, Folderm®, Mintezol®, Thiaben®, Thianax®, Tiabenzol®, Tiabiose®, Tiaplex®, Triasox®, or Tutiverm®. Storage/Stability Thiabendazole tablets, boluses and oral suspension should be stored in tight containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None in the USA for systemic use. Thiabendazole is an active ingredi-ent in the topical/otic preparation Tresaderm®. Food residue tolerances: 0. 1 ppm in uncooked meat of cattle, pheas-ants, swine, sheep and goats; 0. 05 ppm in milk. HUMAN-LABELED PRODUCTS: Thiabendazole Chewable Scored Tablets: 500 mg; Mintezol® (Merck); (Rx) Thiabendazole Oral Suspension: 100 mg/m L in 120 m L; Mintezo l® (Merck); (Rx) Thiacetarsamide (no longer available)—See Melarsomine THIAMINE HCL VITAMIN B 1 (thye-a-min) NUTRITIONAL; B VITAMIN Prescriber Highlights TT A “B” vitamin used for treatment or prevention of thia-mine deﬁciency. May be useful for adjunctive treatment of lead poisoning & ethylene glycol toxicity TT Contraindications: hypersensitivity to it TT Adverse Effects: hypersensitivity reactions (rarely); ten-derness, or muscle soreness after IM injection TT Drug Interactions; lab interactions	pppbs.pdf
T TUses/Indications Thiamine is indicated in the treatment or prevention of thiamine deﬁciency states. Clinical signs of thiamine deﬁciency may be manifested as gastrointestinal (anorexia, salivation), neuromuscu-lar/CNS signs (ataxia, seizures, loss of reﬂexes), or cardiac effects (brady-or tachyarrhythmias). Deﬁciency states may be secondary to either a lack of thiamine in the diet or the presence of thiamine destroying compounds in the diet (e. g., bracken fern, raw ﬁsh, am-prolium, thiaminase-producing bacteria in ruminants). Thiamine has also been used in the adjunctive treatment of lead po isoning and ethylene glycol toxicity (to facilitate the conversion of glyoxylate to nontoxic metabolites). Pharmacology/Actions Thiamine combines with adenosine triphosphate (ATP) to form a compound (thiamine diphosphate/thiamine pyrophosphate) that is employed for carbohydrate metabolism, but does not effect blood glucose concentrations. Absence of thiamine results in decreased transketolase activity in r ed blood cells and increased pyruvic acid blood concentrations. Without thiamine triphosphate, pyruvic acid is not converted into acetyl-Co A; diminished NADH results with anaerobic glycolysis producing lactic acid. Lactic acid production is further increased secondary to pyruvic acid conversion; lactic acidosis may occur. Pharmacokinetics Thiamine is absorbed from the GI tract and is metabolized by the liver. Elimination is renal, the majority of the drug is eliminated as metabolites. Contraindications/Precautions/Warnings Thiamine injection is contraindicated in animals hypersensitive to it or to any component of it. Adverse Effects Hypersensitivity reactions have occurred after injecting this agent. Some tenderness or muscle soreness may result after IM injection. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category A for use dur-ing pregnancy (Adequate studies in pregnant women have not dem-onstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and ther e is no evidence of risk in later trimesters. ) If used in doses greater than the RDA, 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, but it should not be o f clinical concern. Overdosage/Acute Toxicity Very large doses of thiamine in laboratory animals have been asso-ciated with neuromuscular or ganglionic blockade, but the clinical signiﬁcanc e is unknown. Hypotension and respiratory depression may also occur with massive doses. A lethal dose of 350 mg/kg has been reported. Generally, no treatment should be required with most overdoses. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving thiamine and may be of signiﬁcance in veterinary patients: !TNEUROMUSCULAR BLOCKING AGENTS: Thiamine may enhance the activity of neuromuscular blocking agents; clinical signiﬁcance is unknown Laboratory Considerations !Thiamine may cause false-positive serum uric acid results when using the phosphotungstate method of determination or uro-bilinogen urine spot tests using Ehrlich's reagent !The Schack and Wexler method of determining theophylline con-centrations may be interfered with by large doses of thiamine Doses !TDOGS: For thiamine deﬁciency: a) 5-50 mg IM, SC, or IV (depending on formulation) (Phil-lips 1988b) b) 1-2 mg IM (Greene and Braund 1989) c) 2 mg/kg, PO once daily (Davis 1985) d) 100-250 mg SC twice daily for several days until regression of symptoms with complete recovery (Hoskins 1988) Fo r adjunctive treatment for ethylene glycol toxicity: a) 100 mg/day PO (Morgan 1988) !TCATS: For thiamine deﬁciency: a) 100-250 mg parenterally twice a day (experimentally, as little as 1 mg is eff ective) (Armstrong and Hand 1989) b) 1-2 mg IM (Greene and Braund 1989) c) 4 mg/kg, PO once daily (Davis 1985) d) 100-250 mg SC twice daily for several days until regression of symptoms with complete recovery (Hoskins 1988) e) 10-20 mg/kg IM or SC two to three times daily until signs abate, then 10 mg/kg PO once daily for 21 days (Morgan 1988) !TCATTLE: For thiamine deﬁciency: a) For polioencephalomalacia: Initially, 10 mg/kg IV; then, 10 mg/kg IM twice daily for 2-3 days. If no improvement with-in 4 days, may be advisable to recommend slaughter. (Dill 1986) b) 10-20 mg/kg IM or SC 3 times daily; if giving IV dilute in isoto nic saline or isotonic dextrose. (Walz 2006a) c) 10 mg/kg up to 4 times a day; ﬁrst dose may be given via slow IV and subsequent doses IM. Less severely affected animals may respond to lower or less frequent dosing. Severely af-fected animals may beneﬁt from corticosteroids (dexametha-sone 1-2 mg/kg) and mannitol (1 g/kg in a 20% solution IV throug h a ﬁltered IV set). (Cebra 2005) For adjunctive therapy of lead poisoning: a) 2 mg/kg IM (at same time as Ca EDTA therapy); total daily dose 8 mg/kg (B rattan and Kowalczyk 1989) !THORSES: For thiamine deﬁciency: a) 0. 5-5 mg/kg IV, IM or PO (Robinson 1987) b) 100-1000 mg IM, SC, or IV (depending on formulation) (Phillips 1988b) Fo r adjunctive treatment of perinatal asphyxia syndrome (hy-poxic ischemic encephalopathy): a) Foals: 1 gram in one liter of ﬂuids IV once a day (Slovis 2003b) !TSWINE: For thiamine deﬁciency: a) 5-100 mg IM, SC, or IV (depending on formulation) (Phil-lips 1988b)	pppbs.pdf
T ! SHEEP & GOATS: For thiamine deﬁciency: a) For polioencephalomalacia: Initially, 10 mg/kg IV; then, 10 mg/kg IM twic e daily for 2-3 days. If no improvement with-in 4 days, may be advisable to recommend slaughter. (Dill 1986) b) Sheep: 20-200 mg IM, SC, or IV (depending on formula-tion) (Phillips 1988b) Monitoring T ! Efﬁcacy Client Information T ! Epidemiologic investigation as to the cause of thiamine deﬁcien-cy (diet, plants, raw ﬁsh, etc. ) should be performed with neces-sary changes made to prevent recurrence Chemistry/Synonyms A water-soluble “B” vitamin, thiamine HCl occurs as bitter-tasting, white, small hygroscopic crystals, or crystalline powder that has a characteristic yeast-like odor. Thiamine HCl is freely soluble in wa-ter, slightly soluble in alcohol and has p K as of 4. 8 and 9. 0. The com-mercially available injection has a p H of 2. 5-4. 5. Thiamine HCl may also be known as: aneurine hydrochlo-ride, thiamin hydrochloride, thiamine chloride, thiamini hydro-chloridum, thiaminii chloridum, vitamin B-1; many trade names available. Storage/Stability/Compatibility Thiamine HCl for injection should be protected from light and stored at temperatures less than 40°C and preferably between 15-30°C; avoid freezing. Thiamine HCl is unstable in alkaline or neutral solutions or with oxidizing or re ducing agents. It is most stable at a p H of 2. Thiamine HCl is reportedly physically compatible with all com-monly used intravenous replacement ﬂuids. Compatibility is de-pendent upon factors such as p H, concentration, temperature, and diluent use d; consult specialized references or a hospital pharmacist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Thiamine HCl for Injection: 200 mg/m L in 100 m L and 250 m L vials; Amtech® Thiamine Hydrochloride Injection (Phoenix Scientiﬁc), Am-Vet® Thiamine Hydrochloride 200 Mg, (Neogen), generic, (Vet T ek, IVX, Vedco), Vita-Jec® Thiamine HCl (RXV); (Rx) Thiamine HCl for Injection: 500 mg/m L in 100 m L vials; Am-Vet ® Thiamine Hydrochloride 500 mg (Neogen), generic, (Butler, IVX, Ve-dco); (Rx). Labeled for use in horses, dogs and cats. Thiamine HCl Dietary Supplement: 8,200 mg/lb. ; Horse Care Durvit B-1 Crumbles® (Durvet); (OTC), Labeled for use in horses. Thiamine HCl Supplement: 500 mg/oz in 1. 5 lb, 4 lb and 20 lb con-tainers; Thia-Dex® (Neogen), Vitamin B-1 Powder® (AHC); (OTC). Labeled for use in dogs & horses. There are several B-complex vitamin preparations available that may also have thiamine incl uded. HUMAN-LABELED PRODUCTS: Thiamine Tablets: 50 mg, 100 mg, and 250 mg; generic; (OTC) Thiamine Enteric Coated Tablets: 20 mg; Thiamilate® ( Tyson); (OTC) Thiamine HCl Injection: 100 mg/m L in 1 m L, 2 m L multi-dose vials and 2 m L Tube x; generic; (Rx) THIOGUANINE (thye-oh-gwah-neen) ANTINEOPLA STIC Prescriber Highlights TT Oral purine analog antineoplastic that may be useful as adjunctive treatment for acute lymphocytic or granulo-cytic leukemia in dogs or cats TT Contraindications: Hypersensitivity to thioguanine TT Caution: Hepatic dysfunction, bone marrow depression, infection, renal function impairment (adjust dosage), or history of urate urinary stones TT Potentially mutagenic & teratogenic; use milk replacer if nursing TT Adverse Effects: GI effects, bone marrow suppression, hepatotoxicity, pancreatitis, GI (including oral) ulceration, & dermatologic reactions TT Cats may be more susceptible than dogs to adverse effects TT Low therapeutic index; monitoring mandatory Uses/Indications Thioguanine may be useful as adjunctive therapy for acute lympho-cytic or granulocytic leukemia in dogs or cats. Pharmacology/Actions Intracellularly, thioguanine is converted to ribonucleotides that cause the synthesis and utilization of purine nucleotides to be blocked. The drug's cytotoxic effects are believed to occur when these substitutednucleotidesareinsertedinto RNAand DNA. Thioguanine has limited immunosuppressive activity. Extensive cross-resistance usually occurs between thioguanine and mercaptopurine. Pharmacokinetics Thioguanine is administered orally, but absorption is variable. In humans, only about 30% of a dose is absorbed. Thioguanine is dis-tributed into the DNA and RNA of bone marrow, but several doses may be necessary for this to occur. It does not apparently enter the CNS, but does cross the placenta. It is unknown whether it enters maternal milk. Thioguanine is rapidly metabolized primarily in the liver to a methylat e derivative that is less active (and toxic) than the parent compound. This and other metabolites are eliminated in the urine. Contraindications/Precautions/Warnings Thioguanine is contraindicated in patients hypersensitive to it. The drug should be used cautiously (risk versus beneﬁt) in patients with hepatic dysfunction, bone marrow depression, infection, re-nal function impairment (adjust dosage) or with a history of urate urinary st ones. Thioguanine has a very low therapeutic index and should only be used by clinicians with experience in the use of cyto-toxic agents and able to monitor therapy appropriately. Adverse Effects At usual doses, GI effects (nausea, anorexia, vomiting, diarrhea) may occur in small animals. However, bone marrow suppression, hepatotoxicity, pancreatitis, GI (including oral) ulceration, and dermatologic reactions are potentially possible. Cats may be par-ticularly susceptible to the hematologic effects of thioguanine.	pppbs.pdf
TReproductive/Nursing Safety Thioguanine is potentially mutagenic and teratogenic and not rec-ommended for use during pregnancy. In humans, the FDA catego-rizes this drug as category D fo r 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 it is unknown whether thioguanine enters milk, use of milk re placer is recommended for nursing bitches or queens. Overdosage/Acute Toxicity T oxicity may be acute (GI effects) or delayed (bone marrow depres-sion, hepatotoxicity, gastroenteritis). It is suggested to use standard pr otocols to empty the GI tract if ingestion was recent and treat supportively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving thioguanine and may be of signiﬁcance in veterinary patients: !THEPATOTOXIC DRUGS (e. g., halothane, ketoconazole, valproic acid, phenobarbital, primidone, etc. ): Thioguanine should be used cau-tiously with other drugs that can cause hepatotoxicity !TIMMUNOSUPPRESSIVE DRUGS (e. g., azathioprine, cyclophosphamide, corticosteroids ): Use with other immunosuppressant drugs may increase the risk of infection !TMYELOSUPPRESSIVE DRUGS (e. g., chloramphenicol, ﬂucytosine, ampho-tericin B, or colchicine ): Use extreme caution when used concur-rently with other drugs that are also myelosuppressive, including many of the other antineoplastics and other bone marrow de-pressant drugs; bone marrow depression may be additive !TVACCINES, LIVE : Live virus vaccines should be used with caution during therapy, if at all Laboratory Considerations !Thioguanine may increase serum uric acid levels in some patients Doses !TDOGS: a) For acute lymphocytic and granulocytic leukemia: 40 mg/m2 PO o nce daily (q24 hours) for 4-5 days, then every 3rd day thereafter (Jacobs, Lumsden et al. 1992) b) As part of protocols for treatment of acute myelogenous leuk emias: Protocol 1: Cytarabine 100 mg/m2 SC daily for 2-6 days; Thioguanine 50 mg/m2 PO q24-48h. Protocol 2: Cytarabine 100 mg/m2 SC daily for 2-6 days; Thioguanine 50 mg/m2 PO q24-48h; Doxorubicin 10 mg/m2 IV once a week (Couto 2003) !TCATS: a) For acute lymphocytic and granulocytic leukemia: 25 mg/m2 PO o nce daily (q24 hours) for 1-5 days, then every 30 days thereafter as necessary (Jacobs, Lumsden et al. 1992) Monitoring !THemograms (including platelets) should be monitored closely; initially every 1-2 weeks and every 1-2 months once on mainte-nance therapy. It is recommended by some clinicians that if the WBC c ount drops to between 5,000-7,000 cells/mm3 the dose be reduced by 25%. If WBC count drops below 5,000 cells/mm3 treatment should be discontinued until leukopenia resolves !TLiver function tests; serum amylase, if indicated !TEfﬁcacy Client Information !TClients must be briefed on the possibilities of severe toxicity de-veloping from this drug, including drug-related neoplasms or mor tality. !TClients should contact veterinarian if the animal exhibits clinical signs of abnormal bleeding, bruising, anorexia, vomiting, jaun-dice, or infection. !TAlthough, no special precautions are necessary with handling in-tact tablets, it is recommended to wash hands after administering the dr ug. Chemistry/Synonyms A purine analog antineoplastic agent, thioguanine occurs as a pale yellow, odorless or practically odorless, crystalline powder. It is in-soluble in water or alcohol. Thioguanine may also be known as: NSC-752, 6-thiogua-nine, TG, 6-TG, 2-Amino-6-mercaptopurine, WR-1141, L anvis®, Tabloid®, or Tioguanina®. Storage/Stability Store tablets in tight containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Thioguanine Tablets: 40 mg; Tabloid® (Glaxo Smith Kline); (Rx)	pppbs.pdf
THIOPENTAL SODIUM (thye-oh-pen-tal) Pentothal® UL TRA-SHORT ACTING THIOBARBITURATE Prescriber Highlights TT Ultra-short acting thiobarbiturate used for anesthesia in-duction or anesthesia for very short procedures TT Contraindications: Absolute contraindications: absence of suitable veins for IV administration, history of hyper-sensitivity reactions to barbiturates, status asthmaticus. Relative contraindications: severe cardiovascular disease or preexisting ventricular ar rh ythmias, shock, increased intracranial pressure, myasthenia gravis, asthma, & con-ditions where hypnotic effects may be prolonged (e. g., severe hepatic disease, myxedema, severe anemia, ex-cessive premedication, etc. ). Greyhounds (& other sight hounds) metabolize thiobarbiturates much more slowly than other breeds; consider using methohexital instead. HORSES: preexisting leukopenia; thiopental alone may cause excessive ataxia & excitement TT Avoid: Extravasation, intra-carotid or intra-arterial injec-tions, & use of concentrations of less than 2% in sterile water. T oo rapid IV administration can cause signiﬁcant vascular dilatation & h ypoglycemia TT Adverse Effects: DOGS: Ventricular bigeminy CATS: Apnea after injection, mild arterial hypotension. HORSES: Excite-ment & severe ataxia (if used alone); transient leukope-nias, hyperglycemia, apnea, moderate tachycardia, mild respiratory acidosis TT Severe CNS toxicity & tissue damage has occurred in horses receiving intra-carotid injections of thiobarbiturates TT C-III controlled substance Uses/Indications Because of its rapid action and short duration, in young, healthy animals, thiopental is excellent induction agent (rapid IV bolus) for general anesthesia with other anesthetics or as the sole anesthet-ic agent for very short procedures. In sick or debilitated animals, thiopental may be used in a more cautious manner (IV, slowly to effect). Pharmacology/Actions Because of their high lipid solubility, thiobarbiturates rapidly enter the CNS and produce profound hypnosis and anesthesia. They are also known as ultrashort-acting barbiturates. See the monograph: Barbiturates, Pharmacology of, for additional information. Pharmacokinetics Following IV injection of therapeutic doses, hypnosis and anesthe-sia occur within one minute. The drug rapidly enters the CNS and then re distributes to muscle and adipose tissue in the body. The short duration of action (10-30 minutes) after intravenous dosing of thiopental is due less to rapid metabolism than to this redistribu-tion out of the CNS and into muscle and fat stores. Greyhounds and other sight hounds may exhibit longer recovery times than other breeds. This may be due to these breeds low body fat levels or differ-ences in the metabolic handling of the thiobarbiturates. Although anesthesia is short, r ecovery periods may require several hours. Thiopental is metabolized by the hepatic microsomal system and seve ral metabolites have been isolated. The elimination half-life in dogs has been reported as being approximately 7 hours and in sheep, 3-4 hours. Very little of the drug is excreted unchanged in the urine (0. 3% in humans), so dosage adjustments are not neces-sary in patients with chronic renal failure. Contraindications/Precautions/Warnings The following are considered absolute contraindications to the use of thiopental: absence of suitable veins for IV administration, his-tory of hypersensitivity reactions to the barbiturates, and status asthmaticus. Relative contraindications include: severe cardiovascu-lar disease or preexisting ventricular arrhythmias, shock, increased intracr anial pressure, myasthenia gravis, asthma, and conditions where hypnotic effects may be prolonged (e. g., severe hepatic dis-ease, myxedema, severe anemia, excessive premedication, etc. ). These re lative contraindications do not preclude the use of thio-pental, but dosage adjustments must be considered and the drug must be gi ven slowly and cautiously. Because greyhounds (and other sight hounds) metabolize thio-barbiturates much more slowly than methohexital, many clini-cians recommend using methohexital instead. In horses, thiopental should not be used if the patient has preexisting leukopenia. Some clinicians feel that thiopental should not be used alone in the horse as it may cause excessive ataxia and excitement. Concentrations of less than 2% in sterile water should not be used as the y may cause hemolysis. Extravasation and intra-arterial injections should be avoided because of the high alkalinity of the solution. Severe CNS toxicity and tissue damage has occurred in horses receiving intra-carotid injections of thiobarbiturates. Adverse Effects In dogs, thiopental has an approximate arrhythmogenic incidence of 40%. Ventricular bigeminy is the most common arrhythmia seen; it is usually transient and generally responds to additional oxygen. Administration of catecholamines may augment the ar-rhythmogenic effects of the thiobarbiturates, while lidocaine may inhibit it. C ardiac output may also be reduced, but is probably only clinically signiﬁcant in patients experiencing heart failure. Dose-related apnea and hypotension may be noted. Cats are susceptible to developing apnea after injection and may deve lop a mild arterial hypotension. Horses can exhibit clinical signs of excitement and severe ataxia during the recovery period if the drug is used alone. Horses can develop transient leukopenias and hyperglycemia after administra-tion. A period of apnea and moderate tachycardia and a mild respi-ratory acidosis may also develop after dosing. T oo rapid IV administration can cause signiﬁcant vascular dilatation and hypoglycemia. Repeated administration of thiopen-tal is not advised as recovery times can become signiﬁcantly pro-longed. Parasympathetic side effects (e. g., salivation, bradycardia) may be managed with the use of anticholinergic agents (atropine, glycopyrrolate). Prolonged recoveries may occur when repeated dosages of thio-pental are administered. Thiopental's high p H (10-11) can cause signiﬁcant tissue irri-tation and necrosis if administered perivascularly; administration through an IV cathet er is advised. Reproductive/Nursing Safety Thiopental readily crosses the placental barrier and should be used with caution 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	pppbs.pdf
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: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should be used cautiously as a last resort when the beneﬁt of therapy clearly outweighs the risks. ) Small amounts of thiopental may appear in milk following ad-ministration of large doses, but is unlikely to be of clinical signiﬁ-cance in nursing animals. Overdosage/Acute Toxicity Treatment of thiobarbiturate overdosage consists of supporting respirations (O 2, mechanical ventilation) and giving cardiovascular support (do not use catecholamines, e. g., epinephrine, etc. ). Drug Interactions A fatal interaction has been reported in a dog receiving the propri-etary product, Diathal ® (no longer marketed; contained procaine penicillin G, dihydrostreptomycin sulfate, diphemanil methylsul-fate, and chlorpheniramine) and the related compound thiamylal. The following drug interactions have either been reported or are theo retical in humans or animals receiving thiopental and may be of signiﬁcance in veterinary patients: !TCLONIDINE : IV clonidine prior to induction may reduce thiopen-tal dosage requirements by up to 37% !TCNS DEPRESSANTS, OTHER : May enhance respiratory and CNS depressant effects !TDIAZOXIDE : Potential for hypotension !TEPINEPHRINE, NOREPINEPHRINE : The ventricular ﬁbrillatory ef-fects of epinephrine and norepinephrine may be potentiated whe n used with thiobarbiturates and halothane !TMETOCLOPRAMIDE : Given prior to induction may reduce thio-pental dosage requirements !TMIDAZOLAM : May potentiate hypnotic effects !TOPIATES : Given prior to induction may reduce thiopental dosage requirements !TPHENOTHIAZINES : May potentiate thiopental effects; hypotension possible !TPROBENECID : May displace thiopental from plasma proteins !TSULFONAMIDES : Thiopental and sulfas may displace one another from plasma proteins Doses Note : Atropine sulfate (or glycopyrrolate) is often administered prior to thiobarbiturate anesthesia to prevent parasympathetic side effects; however, some clinicians question whether routine-administration of anticholinergic agents is necessary. Thiobarbiturates are administered strictly to effect; doses are guidelines only. !TDOGS: a) 13. 2-26. 4 mg/kg IV depending on duration of anesthesia re quired (Package insert; Pentothal®—Ceva Laboratories) b) 15-17 mg/kg IV for brief (7-10 minutes) anesthesia; 18-22 mg/kg IV for moderate (10-15 minutes) duration; 22-29 mg/kg IV for longer (15-25 minutes) duration (Booth 1988a) c) 22 mg/kg IV; or 15. 4 mg/kg IV after tranquilization; or 11 mg/kg IV afte r narcotic premedication (Mandsager 1988) d) Usually dosed at 12-15 mg/kg, with one-third of the drug administ ered rapidly and any additional amount adminis-tered to effect. Repeated doses will accumulate resulting in pr olonged recoveries; residual effect may last several hours. (Hellyer 2005a) !TCATS: a) 13. 2-26. 4 mg/kg IV depending on duration of anesthesia re quired (Package insert; Pentothal®—Ceva Laboratories) b) 22 mg/kg IV; or 15. 4 mg/kg IV after tranquilization; or 11 mg/kg IV afte r narcotic premedication (Mandsager 1988) c) Usually dosed at 12-15 mg/kg, with one-third of the drug administ ered rapidly and any additional amount adminis-tered to effect. Repeated doses will accumulate resulting in pr olonged recoveries; residual effect may last several hours. (Hellyer 2005a) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 15-30 mg/kg IV to effect (Ivey and Morrisey 2000) b) For chemical restraint: Mice: 50 mg/kg IP; Rats: 40 mg/kg IP; Hamst ers/Gerbils: 30-40 mg/kg IP; Guinea pig: 15-30 mg/ kg IV; Rabbits: 15-30 mg/kg IV (Burke 1999) !TCATTLE: a) 8. 14-15. 4 mg/kg IV; Fo r unweaned calves from which food has been withheld for 6-12 hours: no more than 6. 6 mg/kg IV for deep surgical anesthesia (P entothal® package insert; Ceva Laboratories) b) For calves under 2 weeks of age: 15-22 mg/kg IV slowly until co mplete muscular relaxation takes place, duration of anes-thesia usually lasts 10-12 minutes (Booth 1988a) c) 5. 5 mg/kg IV after sedation and administration with guaife-nesin; or 8. 8-11 mg/kg IV after tranquilization (Mandsager 1988) !THORSES: (Note : ARCI UCGFS Class 2 Drug) a) With preanesthetic tranquilization: 6-12 mg/kg IV (an aver-age of 8. 25 mg/kg is recommended); Without preanesthetic tr anquilization: 8. 8-15. 4 mg/kg IV (an average horse: 9. 9-11 mg/kg IV) (Package insert; Pentothal®—Ceva Laboratories) b) One gram of thiopental per 90 kg body weight as a 10% solu-tion given evenly over 20 seconds 15 minutes after premedi-cation with either 0. 22 mg/kg IV xylazine or 0. 05 mg/kg IV ac epromazine (Booth 1988a) c) 5. 5 mg/kg IV after sedation and administration with guaife-nesin; or 8. 8-11 mg/kg IV after tranquilization (Mandsager 1988) !TSWINE: a) 5. 5-11 mg/kg IV (Package insert; Pe ntothal®—Ceva Labora-tories) b) For swine weighing 5-50 kg: 10-11 mg/kg IV (Booth 1988a) !TSHEEP: 9. 9-15 mg/kg IV depending on depth of anesthesia required (Pa ckage insert; Pentothal®—Ceva Laboratories) !TGOATS: a) 20-22 mg/kg IV after atropine (0. 7 mg/kg) IM (Booth 1988a) Monitoring !TLevel of hypnosis/anesthesia !TRespiratory status; cardiac status (rate/rhythm/blood pressure) Client Information This drug should only be used by professionals familiar with its effects in a setting where adequate respiratory support can be performed.	pppbs.pdf
Chemistry/Synonyms A thiobarbiturate, thiopental occurs as a bitter tasting, white to off-white, crystalline powder or a yellow-white hygroscopic powder. It is soluble in water (1 gram in 1. 5 m L) and alcohol. Thiopental has a p K a of 7. 6 and is a weak organic acid. Thiopental sodium may also be known as: thiopentone sodium, natrium isopentylaethylthiobarbituricum, penthiobarbital sodique, thiomebumalnatrium cum natrii carbonate, thiopentalum natri-cum, thiopentobarbitalum solubile, tiopentol sodico, Anesthal®, B ensulf®, Farmotal®, Hipnopento®, Inductal®, Intraval®, Nesdonal®, Pensodital®, Pentothal®, Sandothal®, Sodipental®, Thionembutal®, Thiopentax®, Tiobarbital®, or Trapanal®. Storage/Stability/Compatibility When stored in the dry form, thiopental sodium is stable indeﬁ-nitely. Thiopental should be diluted with only sterile water for injectio n, sodium chloride injection, or D 5W. Concentrations of less than 2% in sterile water should not be used as they may cause hemolysis. After reconstitution, solutions are stable for 3 days at room temperature and 7 days if refrigerated; however, as no pre-servative is present, it is recommended it be used within 24 hours after r econstitution. After 48 hours, the solution has been reported to attack the glass bottle in which it is stored. Thiopental may also adsorb to plastic IV tubing and bags. Do not administer any solu-tion that has a visible precipitate. Preparation of Solution for Administration: Use only sterile water for injection, normal saline, or D 5W to dilute. A 5 gram vial di-luted with 100 m L will yield a 5% solution and diluted with 200 m L will yield a 2. 5% solution. Discard reconstituted solutions after 24 hours. The following agents have been reported to be physically compat-ible when mixed with thiopental: aminophylline, chloramphenicol sodium succinate, hyaluronidase, hydrocortisone sodium succinate, neostigmine methylsulfate, oxytocin, pentobarbital sodium, phe-nobarbital sodium, potassium chloride, scopolamine HBr, sodium iodide, and tubocurarine chloride (recommendations conﬂict with regard to tubocurarine; some clinicians recommend not mixing with thiopental). The following agents have been reported to be physically incom-patible when mixed with thiopental: Ringer's injection, Ringer's in-jection lactate, amikacin sulfate, atropine sulfate, benzquinamide, cephapir in sodium, chlorpromazine, codeine phosphate, dimen-hydrinate, diphenhydramine, ephedrine sulfate, glycopyrrolate, hydro morphone, insulin (regular), levorphanol bitartrate, mep-eridine, metaraminol, morphine sulfate, norepinephrine bitartrate, penicillin G potassium, prochlorperazine edisylate, promazine HCl, promethazine HCl, succinylcholine chloride, and tetracycline HCl. Compatibility is dependent upon factors such as p H, concentra-tion, temperature, and diluent used; consult specialized references or a hospital pharma cist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None presently being marketed in USA. The ARCI (Racing Commissioners International) has designated this drug as a class 2 substanc e. See the appendix for more information. HUMAN-LABELED PRODUCTS: Thiopental Sodium Powder for Injection: 2% (20 mg/m L) in 1 g, 2. 5 g and 5 g kits; 400 mg Min-I-Mix vials with Min-I-Mix injector; Ready-to-Mix and Ready-to-Mix Life Shield syringes; 2. 5% (25 mg/m L) in 250 mg and 500 mg Min-I-Mix vials; 500 mg, 1 g, 2. 5 g, 5 g and 10 g kits, 250 mg and 500 mg Ready-to-Mix syringes and Ready-to-Mix Life Shield syringes; Pentothal® (Abbott); generic; (Rx, C-III) THIOTEPA (thye-oh-tep-ah) ANTINEOPLA STIC Prescriber Highlights TT Antineoplastic used systemically for carcinomas, intrac-avitary for neoplastic effusions, & intravesical for transi-tional carcinomas; rarely used in small animal oncology TT Contraindications: Hypersensitivity to thiotepa; Caution: Hepatic dysfunction, bone marrow depression, infection, tumor cell inﬁltration of bone marrow, renal dysfunction, or history of urate urinary stones TT Adverse Effects: Leukopenia most likely adverse effect; other hematopoietic toxicity (thrombocytopenia, anemia, pancytopenia), GI toxicity possible. Intracavitary or intra-vesical instillation can also cause hematologic toxicity. TT Potentially teratogenic; use milk replacer if patient nursing TT Monitor diligently Uses/Indications Veterinary indications for thiotepa include: systemic use for adjunc-tive therapy against carcinomas, and intracavitary use for neoplastic effusions. I n dogs with transitional cell bladder carcinoma, intra-vesical instillation of thiotepa had signiﬁcantly less efﬁcacy (mean survi val time = 57 days) when compared to a systemic doxorubicin/ cyclophosphamide protocol (mean survival time = 259 days). Pharmacology/Actions Thiotepa is an alkylating agent, thereby interfering with DNA repli-cation and RNA transcription. It is cell cycle non-speciﬁc. Thiotepa has some imm unosuppressive activity. When given via the intrac-avitary route, thiotepa is thought to control malignant effusions by a direct ant ineoplastic effect. Pharmacokinetics Thiotepa is poorly absorbed from the GI tract. Systemic absorp-tion is variable from the pleural cavity, bladder, and after IM in-jection. Some studies in humans have shown that absorption from bladde r mucosa ranges from 10-100% of an administered dose. Distribution characteristics are not well described; it is unknown if the drug enters maternal milk. Thiotepa is extensively metabolized and then excreted in the urine. Contraindications/Precautions/Warnings Thiotepa is contraindicated in patients hypersensitive to it. The drug should be used cautiously (weigh risk versus beneﬁt) in pa-tients with hepatic dysfunction, bone marrow depression, infection, tumor c ell inﬁltration of bone marrow, renal function impairment (adjust dosage) or with a history of urate urinary stones. Thiotepa has a very low therapeutic index and should only be used by cli-nicians with experience in the use of cytotoxic agents and able to monitor the rapy appropriately. Adverse Effects When used systemically, leukopenia is the most likely adverse effect seen in small animals. Other hematopoietic toxicity (thrombocy-topenia, anemia, pancytopenia) may be noted. Intracavitary or in-travesical instillation of thiotepa may cause hematologic toxicity. GI toxicity (vomiting, diarrhea, stomatitis, intestinal ulceration) may	pppbs.pdf
Tbe noted and human patients have reported dizziness and headache as well. Reproductive/Nursing Safety Thiotepa is potentially mutagenic and teratogenic and is not recom-mended for use during pregnancy. 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 it is unknown whether thiotepa enters milk, use of milk replac er is recommended for nursing bitches or queens. Overdosage/Acute Toxicity There is no speciﬁc antidote for thiotepa overdose. Supportive ther-apy, including transfusions of appropriate blood products, may be beneﬁcial fo r treatment of hematologic toxicity. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving thiotepa and may be of signiﬁcance in veterinary patients: T ! IMMUNOSUPPRESSIVE DRUGS (e. g., azathioprine, cyclophosphamide, corticosteroids ): Use with other immunosuppressant drugs may increase the risk of infection T ! MYELOSUPPRESSIVE DRUGS (e. g., chloramphenicol, ﬂucytosine, ampho-tericin B, or colchicine ): Use extreme caution when used concur-rently with other drugs that are also myelosuppressive, including many of the other antineoplastics and other bone marrow de-pressant drugs; bone marrow depression may be additive T ! VACCINES, LIVE : Live virus vaccines should be used with caution during therapy, if at all Laboratory Considerations T ! hiotepa may increase serum uric acid levels in some patients Doses T ! DOGS: a) For intracavitary use neoplastic effusions or systemically for adjunct ive therapy of carcinomas: 0. 2-0. 5 mg/m2 intracavi-tary; IV. (Jacobs, Lumsden et al. 1992) Monitoring T ! Efﬁcacy T ! CBC with platelets Client Information T ! Clients must be briefed on the possibilities of severe toxicity de-veloping from this drug, including drug-related neoplasms or mortalit y T ! Clients should contact veterinarian should the animal exhibit clinical signs of abnormal bleeding, bruising, anorexia, vomiting, jaundice, or infection Chemistry/Synonyms An ethylene derivative alkylating agent antineoplastic, thiotepa oc-curs as ﬁne, white crystalline ﬂakes. The drug has a faint odor and is freel y soluble in water or alcohol. Thiotepa may also be known as: NSC-6396, TESPA, thio-phosphamide, triethylenethiophosphoramide, TSPA, WR-45312, Leder tepa®, Onco Tiotepa®, Tespamin®, or Thioplex®. Storage/Stability Store both the powder and the reconstituted solution refrigerat-ed (2-8°C) and protected from light. Do not use solution that is grossly opaque (slightly opaque is OK) or if a precipitate is present. If refrigerated, reconstituted solutions are stable for up to 5 days. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Thiotepa Lyophilized Powder for Injection: 15 mg & 30 mg in vials; Thioplex® (Amgen); generic, (Sicor); (Rx) THYROTROPIN THYROTROPIN ALFA (rh TSH) (thye-roe-troe-pin) Thyroid Stimulating Hormone, TSH HORMONE Prescriber Highlights TT Hormone used for thyroid stimulating hormone (TSH) test for thyroid function TT Contraindications: Adrenocortical insufﬁciency, hyperthy-roidism, coronary thrombosis, hypersensitivity to bovine thyrotropin TT Adverse Effects: Hypersensitivity (especially with repeat-ed injections) TT Availability (of bovine source TSH) and expense (human product) may be issues Uses/Indications The labeled indications for the formerly available veterinary prod-uct Dermathycin® (Mallinckrodt) was for “the treatment of acan-thosis nigr icans and for temporary supportive therapy in hypothy-roidism in dogs. ” In actuality however, TSH is used in veterinary medicine pr incipally as a diagnostic agent in the TSH stimulation test to diagnose primary hypothyroidism. Pharmacology/Actions Thyrotropin increases iodine uptake by the thyroid gland and in-creases the production and secretion of thyroid hormones. With prolong ed use, hyperplasia of thyroid cells may occur. Pharmacokinetics No speciﬁc information was located; exogenously administered TSH apparently exerts maximal increases in circulating T 4 approxi-mately 4-8 hours after IM or IV administration. Contraindications/Precautions/Warnings A previous veterinary manufacturer (Coopers), listed adrenocorti-cal insufﬁciency and hyperthyroidism as contraindications to TSH use for treatment purposes in dogs. In humans, TSH is contrain-dicated in patients with coronary thrombosis, untreated Addison's disease, or hy persensitive to bovine thyrotropin. Adverse Effects Because the product is derived from bovine sources, anaphylaxis may occur in patients sensitive to bovine proteins, particularly with repeated use.	pppbs.pdf
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 the drug is excreted in human milk, but is unlikely to be clinically signiﬁcant when used for diagnostic purposes. Overdosage/Acute Toxicity Chronic administration at high dosages can produce clinical signs of hyperthyroidism. Massive overdoses can cause clinical signs re-sembling thyroid storm. Refer to the levothyroxine monograph for more info rmation on treatment. Drug Interactions; Laboratory Considerations Refer to the information listed in the Levothyroxine monograph for more information. Doses T ! DOGS: For TSH stimulation test: a) Draw pre-dose baseline sample. Administer 0. 1 IU/kg IV (maximum of 5 IU). Collect sample for T 4 6 hours after dose. (Peterson and Ferguson 1989) b) 5 IU IV or 0. 1 IU/kg IV. Measure serum T 4 at 0 hours (pre-sample) and 4 or 6 hours after dose (Morgan 1988) c) Using the bovine product: Measure pre-dose (basal) T4; then 0. 1 Units/kg (maximum of 5 Units) IV. Measure post-dose T4 at 6 hours. Using the h uman recombinant product: 50-100 mcg (0. 05-0. 1 mg) IV; Measure serum T 4 at 0 hours (pre-sam-ple) and 4 hours post. Product may be frozen for at least 8 weeks with no loss o f potency. (Scott-Moncrieff 2006b) T ! CATS: For TSH stimulation test: a) Draw pre-dose baseline sample. Administer 1 IU/kg IV or 2. 5 IU IM. Col lect sample for T 4 6 hours after dose. (Peterson and Ferguson 1989) b) 2. 5 IU IV. Measure serum T 4 at 0 hours (pre-sample) and 4 or 6 hours after dose. (Morgan 1988) T ! HORSES: For TSH stimulation test: a) Draw pre-dose sample, then 5-10 IU of bovine TSH IV. Draw f ollow-up samples 4-8 hours after dosing. Normal thyroid gland should produce a 2-4 times increase in serum T3 and T 4 levels. (Chen and Li 1987) Client Information T ! Usually, TSH will be administered by professional staff Chemistry/Synonyms Commercially available thyrotropin (human; rh TSH) is now avail-able only as a lyophilized powder for reconstitution obtained via DNA re combinant technology. Originally obtained from bovine an-terior pituitary glands, thyrotropin is a highly puriﬁed preparation of thy roid-stimulating hormone (TSH). Thyrotropin is a glycopro-tein and has a molecular weight of approximately 28,000-30,000. Thyr otropin is measured in International Units (IU), with 7. 5 mi-crograms of thyrotropin approximately equivalent to 0. 037 units. Thyrotropin may also be known as: thyroid-stimulating hor-mone, thyrotrophic hormone, thyrotropin, TSH, Ambinon®, Thyreostimulin®, Thyrogen®, or Thytropar®. Storage/Stability Thyrotropin alfa (unreconstituted) should be stored between 2-8°C (36-46°F). If necessary, the reconstituted solution can be stored up to 24 hours between 2-8°C (36-46°F), while avoiding microbial contamination. However, it is reportedly stable if kept refrigerated (2-8°C) up to 4 weeks and up to 8 weeks if frozen (-20°C). After reconstitution visually inspect each vial for particulate matter o r discoloration before use. Do not use any vial exhibiting particulate matter or discoloration. Do not use after the expiration date on the vial. Protect from light. Thyrotropin lyophilized powder for injection (Bovine) is report-edly stable in the dry state. However, the veterinary manufacturer reco mmended storing the powder below 59°F, and after reconsti-tuting, storing in the refrigerator and discarding any unused drug after 48 hours. It has been suggested however, that reconstituted TSH (bovine) is stable for at least 3 weeks when refrigerated. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Thyrotropin (Thyroid Stimulating Hormone) Powder for Injection, Lyophilized: 1. 1 mg thyrotropin alfa (less than or equal to 4 IU)/vial in kits of two 1. 1 mg single-use vials of thyrotropin alfa and two 10 m L vials of diluent; Thyrogen® (Genzyme); (Rx) Thyroxine Sodium—See Levothyroxine Sodium TIAMULIN (tye-am-myoo-lin) Denagard® DITERPINE ANTIBIOTIC Prescriber Highlights TT Antibiotic used primarily in swine TT Contraindications: Access to feeds containing polyether ionophores (e. g., monensin, lasalocid, narasin, or salino-mycin); swine over 250 pounds TT Adverse Effects are unlikely TT Variable withdrawal times depending on dosage Uses/Indications Tiamulin is approved for use in swine to treat pneumonia caused by susceptible strains of Haemophilus pleuropneumoniae and swine dysentery caused by Treponema hyodysenteriae. As a feed additive, it is used to cause increased weight gain in swine. Pharmacology/Actions Tiamulin is usually a bacteriostatic antibiotic, but can be bacteri-cidal in very high concentrations against susceptible organisms. The drug acts by binding to the 50S ribosomal subunit, thereby in-hibiting bacterial protein synthesis. Tiamulin has good activity against many gram-positive cocci, in-cluding most Staphylococci and Streptococci (not group D streps). It also has good activity against Mycoplasma and spirochetes. With the exception of Haemophilus spp. and some E. coli and Klebsiella strains, the drug's activity is quite poor against gram-negative or-ganisms.	pppbs.pdf
Pharmacokinetics Tiamulin is well absorbed orally by swine. Approximately 85% of a dose is absorbed and peak levels occur between 2-4 hours after a single oral dose. Tiamulin is apparently well distributed, with high-est levels found in the lungs. Tiamulin is extensively metabolized to over 20 metabolites, some hav ing antibacterial activity. Approximately 30% of these metabolites are excreted in the urine with the remainder excreted in the feces. Contraindications/Precautions/Warnings Tiamulin should not be administered to animals having access to feeds containing polyether ionophores (e. g., monensin, lasalocid, narasin, or salinomycin) as adverse reactions may occur. Not for use in swine over 250 pounds. Reproductive/Nursing Safety T eratogenicity studies done in rodents demonstrated no terato-genic effects at doses up to 300 mg/kg. The manufacturer has con-cluded that the drug is not tumorigenic, carcinogenic, teratogenic, or mutag enic. Adverse Effects Adverse effects occurring with this drug at usual doses are consid-ered unlikely. Rarely, redness of the skin, primarily over the ham and under line, has been observed. It is recommended to discon-tinue the medication, provide clean drinking water, and hose down the area or mov e affected animals to clean pens. Overdosage/Acute Toxicity Oral overdoses in pigs may cause transient salivation, vomiting, and CNS depression (calming effect). Discontinue drug and treat symp-tomatically and supportively if necessary. Drug Interactions T ! POLYETHER IONOPHORES (e. g., monensin, lasalocid, narasin, or salino-mycin ): Tiamulin should not be administered to animals having access to feeds containing polyether ionophores as adverse reac-tions may occur T ! LINCOSAMIDES, MACROLIDES (e. g., clindamycin, lincomycin, erythromy-cin, tylosin ): Although not conﬁrmed with this drug, concomitant use with other antibiotics that bind to the 50S ribosome could lead to decreased efﬁcacy secondary to competition at the site of action Doses T ! SWINE: a) For swine dysentery: 7. 7 mg/kg PO daily in drinking water for 5 days. See package directions for dilution instructions. (Package insert; Denagard® Liquid Concentrate) b) For swine pneumonia: 23. 1 mg/kg PO daily in drinking wa-ter for 5 days. See package directions for dilution instruc-tions. (Package insert; Denagar d® Liquid Concentrate) c) For use as a medicated premix: See the label for the product. Monitoring T ! Clinical efﬁcacy Client Information T ! Prepare fresh medicated water daily T ! Avoid contact with skin or mucous membranes as irritation may occur Chemistry/Synonyms A semisynthetic diterpene-class antibiotic derived from pleuromu-lin, tiamulin is available commercially for oral use as the hydrogen fumarate salt. It occurs as white to yellow, crystalline powder with a faint but characteristic odor. Approximately 60 mg of the drug are soluble in 1 m L of water. Tiamulin may also be known as: 81723-hfu, SQ-14055, SQ-22947 (tiamulin fumarate), and Denagard®. Storage/Stability Protect from moisture; store in a dry place. In unopened packets, the powder is stable up to 5 years. Fresh solutions should be pre-pared daily when using clinically. Dosage Forms/Regulatory Status VETERINARY APPROVED PRODUCTS: Tiamulin Medicated Premix: 10 g/1 lb in 35 lb bags. Approved for use in swine not weighing over 250 lbs. Slaughter withdrawal period at the 35 g/ton use is 2 days and at the 200 g/ton dose is 7 days. Dena-gard® 10 (Novartis); (OTC) Tiamulin Solution: 12. 3% tiamulin hydrogen fumarate in an aqueous base in 32 o z bottles. Approved for use in swine. Slaughter withdraw-al: treatment at 3. 5 mg/lb = 3 days, at 10. 5 mg/lb = 7 days. Denagard® Liquid Conc entrate (Boehringer Ingelheim); Amtech® Tiamulin Liq-uid Concentrate (IVX); (OTC) Tiamulin Soluble Powder: 45% in 2. 28 oz packets (29. 1 g tiamulin per pa cket). Approved for use in swine. Slaughter withdrawal: treat-ment at 3. 5 mg/lb = 3 days, at 10. 5 mg/lb = 7 days. Denagard® Liquid Conce ntrate (Boehringer Ingelheim); Amtech® Tiamulin Soluble An-tibiotic (IVX); (OTC) HUMAN APPROVED PRODUCTS: None TICARCILLIN DISODIUM (tye-kar-sill-in) Ticar® PARENTERAL EXTENDED S PECTRUM PENICILLIN Prescriber Highlights TT Parenteral, anti-pseudomonal penicillin TT Contraindications: Known hypersensitivity (unless no other options) TT Adverse Effects: Hypersensitivity possible; very high doses may cause CNS effects. Potentially could cause bleeding TT Treatment is relatively expensive Uses/Indications A ticarcillin disodium product was approved for intrauterine use in horses in the treatment of endometritis in horses caused by beta hemolytic streptococci, but is apparently no longer marketed. Ticarcillin disodium injection is used in veterinary species in the treat ment of systemic Pseudomonas aeruginosa infections, often in combination with an appropriate aminoglycoside agent. When compared with carbenicillin, ticarcillin is about twice as potent (on a per weight basis) in the treatment against susceptible Pseudomonas. Synergy may occur against some Pseudomonas strains when used in combination with aminoglycosides, but in vitro inactivation of the aminoglycoside may also occur (see Drug Interactions) if the	pppbs.pdf
drugs are physically mixed together or in patients with severe renal failure. Ticarcillin (alone and with clavulanate) has been used in a vari-ety of compounded preparations for otic use. Pharmacology/Actions Penicillins are usually bactericidal against susceptible bacteria and act by inhibiting mucopeptide synthesis in the cell wall resulting in a defective barrier and an osmotically unstable spheroplast. The ex-act mechanism for this effect has not been deﬁnitively determined, bu t beta-lactam antibiotics have been shown to bind to several en-zymes (carboxypeptidases, transpeptidases, endopeptidases) within the ba cterial cytoplasmic membrane that are involved with cell wall synthesis. The different afﬁnities that various beta-lactam antibiot-ics have for these enzymes (also known as penicillin-binding pro-teins; PBPs) help explain the differences in spectrums of activity the dr ugs have that are not explained by the inﬂuence of beta-lacta-mases. Like other beta-lactam antibiotics, penicillins are generally co nsidered more effective against actively growing bacteria. The extended-spectrum penicillins, sometimes called anti-pseudomonal penicillins, include both alpha-carboxypenicillins (carb enicillin and ticarcillin) and acylaminopenicillins (piperacillin, azlocillin, and mezlocillin). These agents have similar spectrums of activity as the aminopenicillins but with additional activity against several gram-negative organisms of the family Enterobacteriaceae, including many strains of Pseudomonas aeruginosa. Like the amin-openicillins, these agents are susceptible to inactivation by beta-lactamases. Pharmacokinetics Ticarcillin is not appreciably absorbed after oral administration and must be given parenterally to achieve therapeutic serum levels. When given IM to humans, the drug is readily absorbed with peak levels occurring about 30-60 minutes after dosing. The reported bioavailability in the horse after IM administration is about 65%. After parenteral injection, ticarcillin is distributed into pleural ﬂuid, int erstitial ﬂuid, bile, sputum, and bone. Like other penicil-lins, CSF levels are low in patients with normal meninges (about 6% o f serum levels), but increased (39% of serum levels) if menin-ges are inﬂamed. The volume of distribution is reportedly 0. 34 L/ kg in dogs and 0. 22-0. 25 L/kg in the horse. The drug is 45-65% bound to serum proteins (human). Ticarcillin is thought to cross the placenta and found in small quantities in milk. In cattle, mas-titic milk levels of ticarcillin are approximately twice those found in nor mal milk, but are too low to treat most causal organisms. Ticarcillin is eliminated primarily by the kidneys, via both tu-bular secretion and glomerular ﬁltration. Concurrent probenecid administ ration can slow elimination and increase blood levels. In humans, about 10-15% of the drug is metabolized by hydrolysis to inactive compounds. The half-life in dogs and cats is reportedly 45-80 minutes; about 54 minutes in the horse. Clearance is 4. 3 m L/ kg/min in the dog and 2. 8-3. 2 m L/kg/min in the horse. Contraindications/Precautions/Warnings Penicillins are contraindicated in patients with a history of hyper-sensitivity to them. Because there may be cross-reactivity, use peni-cillins cautiously in patients who are documented hypersensitive to other beta-lactam antibiotics (e. g., cephalosporins, cefamycins, carbapenems). Ticarcillin has signiﬁcant quantities of sodium per gram and may cause electrolyte imbalances when used in large dosages in susceptible patients. Adverse Effects Adverse effects with the penicillins are usually not serious and have a relatively low frequency of occurrence. Hypersensitivity reactions unrelated to dose can occur with these ag ents and can manifest as rashes, fever, eosinophilia, neu-tropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, ly mphadenopathy, or full-blown anaphylaxis. In humans, it is esti-mated that up to 15% of patients hypersensitive to cephalosporins wil l also be hypersensitive to penicillins. The incidence of cross-reactivity in veterinary patients is unknown. Neurotoxicity (e. g., ataxia in dogs) has been associated with very high doses or very prolonged use. Although the penicillins are not considered hepatotoxic, elevated liver enzymes have been reported. Other effects reported in dogs include tachypnea, dyspnea, edema, and tachycardia. Ticarcillin has been implicated in causing bleeding problems in h umans; veterinary ramiﬁcations of this potential effect are unclear. Reproductive/Nursing Safety Penicillins have been shown to cross the placenta and safe use of them during pregnancy has not been ﬁrmly established, but neither have there been any documented teratogenic problems associated with these drugs; however, use only when the potential beneﬁts outweigh the risks. In humans, the FDA categorizes this drug 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 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: A (Probably safe. Although speciﬁc studies may not have proved he safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) Although penicillins can be distributed into milk, it is unlikely that t icarcillin would be of clinical concern in nursing veterinary patients. Overdosage/Acute Toxicity In humans, very high dosages of parenteral penicillins, especially in patients with renal disease, have induced CNS effects. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ticarcillin and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES (e. g., amikacin, gentamicin, tobramycin ): In vitro studies have demonstrated that penicillins can have synergistic or additive activity against certain bacteria when used with amino-glycosides; however, beta-lactam antibiotics can inactivate amin-oglycosides in v itro and in vivo in patients in renal failure or when penicillins are used in massive dosages. Amikacin is considered the most resistant aminoglycoside to this inactivation. !TPROBENECID : Can reduce the renal tubular secretion of ticarcillin, thereby maintaining higher systemic levels for a longer period of time !TWARFARIN; HEPARIN : As ticarcillin has been implicated in rarely causing bleeding, use with caution in patients receiving antico-agulant therapy	pppbs.pdf
Laboratory Considerations !TAminoglycoside serum quantitative analysis : As penicillins and oth-er beta-lactams can inactivate aminoglycosides in v itro (and in vivo in patients in renal failure or when penicillins are used in massive dosages), serum concentrations of aminoglycosides may be falsely decreased if the patient is also receiving beta-lactam antibiotics and the serum is stored prior to analysis. It is recom-mended that if the aminoglycoside assay is delayed, samples be fro zen and, if possible, drawn at times when the beta-lactam an-tibiotic is at a trough. !TDirect antiglobulin (Coombs' ) tests : False-positive results may occur !TUrine protein : May produce false-positive protein results with the sulfosalicylic acid and boiling test, nitric acid test, and the ace-tic acid test. Strips using bromophenol blue reagent (e. g., Mult i-Stix®) do not appear to be affected by high levels of penicillins in the urine Doses !TDOGS: For susceptible infections: a) For susceptible (to ticarcillin) infections demonstrated to be resistant to other less expensive and more convenient anti-biotics. Ticarcillin: 15-25 mg/kg as an IV infusion over 15 minu tes, followed by a constant rate IV infusion at 7. 5-15 mg/kg/hour (Trepanier 1999) b) For treatment of Ps eudomonas aeruginosa infections in con-junction with an aminoglycoside: 50-75 mg/kg IV or IM q8h (Auc oin 2002b) c) For soft tissue, systemic infections: 15-25 mg/kg IV, IM, SC q6-8h as long as necessary; Fo r septicemia: 40-50 mg/kg IV, IM q4-6h as long as necessary; For difﬁcult, severe systemic infections: 100 mg/kg IV q6-8h as long as ne cessary. (Greene, Hartmannn et al. 2006) d) As an otic solution for adjunctive treatment of Pseudomonas otit is using ticarcillin: Dilute according to manufacturer's directions to a concentration of 2 mg/m L and apply 5-10 drops per ear every 12 hours. (Kwochka 2003a) !TCATS: For susceptible infections: a) For susceptible (to ticarcillin) infections demonstrated to be resistant to other less expensive and more convenient anti-biotics. Ticarcillin: 15-25 mg/kg as an IV infusion over 15 minu tes, followed by a constant rate IV infusion at 7. 5-15 mg/kg/hour (Trepanier 1999) b) For treatment of Ps eudomonas aeruginosa infections in con-junction with an aminoglycoside: 50-75 mg/kg IV or IM q8h (Auc oin 2002b) c) For Pseudomonas soft tissue, systemic infections: 15-24 mg/ kg IV, IM, SC q8h as long as necessary; Fo r Pseudomonas systemic, bacteremia: 40-50 mg/kg IV q6h as long as necessary. (Greene, Hartmannn et al. 2006) !THORSES: For susceptible systemic infections: a) 22-44 mg/kg IV q6h. (Bertone 2003a) b) Foals: 40-60 mg/kg IV, IM q6-8h (Brumbaugh 1999) c) Foals: 50 mg/kg q6h IV or IM (Furr 1999) For treatment of endometritis secondary to susceptible bacteria: a) 6 grams intrauterine per day for 3 days during estrus. Re-constitute vial with 25 m L of Sterile Water for Injection, USP or Sodium Chloride Injection, USP. After dissolved, further dilute to a total volume of 100-500 m L with sterile water or sterile normal saline and aseptically instill into uterus. (Pack-age insert; Ticillin®—Beecham) !TBIRDS: For susceptible infections: a) 200 mg/kg IV or IM twice daily, three times daily or four times dail y (Clubb 1986) b) 200 mg/kg IM or IV q8h (Hoeffer 1995) Monitoring !TBecause penicillins usually have minimal toxicity associated with their use, monitoring for efﬁcacy is usually all that is required un-less toxic signs develop. Serum levels and therapeutic drug moni-toring are not routinely done with these agents. Chemistry/Synonyms An alpha-carboxypenicillin, ticarcillin disodium occurs as a white to pale yellow, hygroscopic powder or lyophilized cake with p K as of 2. 55 and 3. 42. More than 600 mg is soluble in 1 m L of water. Potency of ticarcillin disodium is expressed in terms of ticarcillin and one gram of the disodium contains not less than 800 mg of ti-carcillin anhydrous. One gram of the commercially available injec-tion contains 5. 2-6. 5 m Eq of sodium and after reconstituting the injec tion has a p H of 6-8. Ticarcillin Disodium may also be known as: BRL-2288, ticarcil-linum natricum, Ae rugipen®, Tarcil®, Ticar®, Ticarpen®, Ticillin®, or Triacilline®. Storage/Stability/Compatibility Ticarcillin injectable powder for injection should be stored at tem-peratures of less than 30°C (room temperature or colder). If stored at room temperature after reconstitution, polymer con-jugates can form that may increase the likelihood of hypersensi-tivity reactions occurring, therefore, many clinicians recommend eithe r refrigerating the solution or administering within 30 minutes of reconstitution. From a potency standpoint, the drug should be used generally within 24 hours if stored at room temperature and 72 hours if refrigerated, but the manufacturer has speciﬁc recom-mendations on stability depending on the concentration of the drug and the solution used; refer to the package insert. Frozen solutions are reportedly stable for at least 30 days when stored at-20°C. Ticarcillin disodium solutions are reportedly physically compati-ble with the following solutions and drugs: D 5W, Ringer's Injection, Lactated Ringer's Injection, sodium chloride 0. 9%, Sterile water for injection, acyclovir sodium, hydromorphone HCl, meperidine HCl, methylprednisolone sodium succinate, morphine sulfate, ranitidine HCl, perphenazine, and verapamil HCl. Ticarcillin disodium solutions are reportedly physically incom-patible with the aminoglycoside antibiotics; refer to the drug inter-action information in the Penicillins, General Information mono-graph for more information. Compatibility is dependent upon fac tors 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: Ticarcillin Disodium Powder for Injection: (contains 5. 2 m Eq sodium/g) 3 g in vials; Ticar® (Glaxo Smith Kline); (Rx)	pppbs.pdf
TICARCILLIN DISODIUM + CLAVULANATE POTASSIUM (tye-kar-sill-in; klav-yoo-lan-ate) Timentin® PARENTERAL EXTENDED SPECTRUM PENICILLIN + BETA-LACTAMASE INHIBITOR Prescriber Highlights TT Parenteral, extended action penicillin with a beta lacta-mase inhibitor; has increased spectrum of activity when compared with ticarcillin alone, but is more expensive TT Used for serious systemic infections & as a compounded otic prep for Pseudomonas otitis TT Limited experience or research in veterinary medicine, but appears quite safe TT Patients with signiﬁcantly impaired renal function or those receiving very high dosages may be more prone to develop platelet function abnormalities (bleeding) or CNS effects Uses/Indications Ticarcillin/clavulanate is used systemically to treat serious infections such as sepsis or nosocomial pneumonias in dogs, cats and horses. By adding clavulanate, enhanced spectrum of activity against beta-lactamase producing bacteria can be obtained. This drug combina-tion is sometimes used to treat Pseudomonas otitis in dogs. Pharmacology/Actions See the Ticarcillin monograph for information on ticarcillin. By adding clavulanate,ticarcillin's efﬁcacy can be extended against beta-lactamase-producing strains of otherwise resistant E. coli, Pasturella spp., Staphylococcus spp., Klebsiella, and Proteus. Clavulanic acid acts by competitively and irreversibly binding to beta-lactamases, including types II, III, IV, and V, and penicillinases produced by Staphylococcus. Type I beta-lactamases that are often associated with E. coli, Enterobacter, and Pseudomonas are not generally in-hibited by clavulanic acid. Clavulanic acid has only weak antibacterial activity when used alone and at present is only available in ﬁxed-dose combinations with either amoxicillin (oral) or ticarcillin (parenteral). Unlike sulbactam or tazobactam, clavulanic acid (clavulanate) can induce chromosomal beta-lactamases. Synergy against Pseudomonas aeruginosa can occur when used with an aminoglycoside, but the drugs cannot be mixed together (see Drug Interactions). Pharmacokinetics Ticarcillin pharmacokinetics are presented in the monograph pre-ceding this one. There is no evidence to suggest that the addition of clavulanic a cid alters ticarcillin pharmacokinetics. Clavulanic acid has an apparent volume of distribution of 0. 32 L/kg in do gs and is distributed (with ticarcillin) into the lungs, pleural ﬂuid and peritoneal ﬂuid. Low concentrations of both drugs are found in the saliva, sputum and CSF (uninﬂamed meninges). Higher concentrations in the CSF are expected when meninges are inﬂamed, but it is questionable whether therapeutic levels are attainable. Clavulanic acid is 13% bound to proteins in dog serum. Clavulanic acid is extensively metabolized in the dog (and rat) primarily to 1-amino-4-hydroxybutan-2-one. It is not known if this compound possesses any beta-lactamase inhibiting activity. Clavulanic acid is also excreted unchanged in the urine via glom-erular ﬁltration. In dogs, 34-52% of a dose is excreted in the urine as unchange d drug and metabolites, 25-27% in the feces, and 16-33% into respired air. The elimination half-life for clavulanic acid in dogs is faster than is ticarcillin. Contraindications/Precautions/Warnings Do not use this medication in patients with documented hypersen-sitivity reactions to penicillins or other beta-lactams. Dosage adjustments should be made in patients with signiﬁ-cantly impaired renal function. Adverse Effects Although clinical experience with this medication in veterinary patients is limited, it appears to be well tolerated' potentially, hy-persensitivity reactions can occur. In humans, high dosages (par-ticularly in patients with renal insufﬁciency) have caused platelet dysfunct ion and bleeding, and CNS effects (headache, giddiness, hallucinations, seizures). Intramuscular administration can cause pain, but reconstituting with 1% lidocaine (see Storage/Stability/ Compatibility) can alleviate this effect. Local irritation to veins after IV administration is possible and best avoided by using dilute con-centrations administered over not less than 30 minutes. Antibiotic-associated diarrhea or colitis may occur. Reproductive/Nursing Safety Penicillins have been shown to cross the placenta and safe use dur-ing pregnancy has not been ﬁrmly established, but neither have there b een any documented teratogenic problems associated with these drugs; however, use only when the potential beneﬁts outweigh the risks. In humans, the FDA categorizes ticarcillin/clavulanate 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 demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Although penicillins can be distributed into milk, it is unlikely that ticarcil lin/clavulanate would be of signiﬁcant clinical concern for nursing veterinary patients. Overdosage/Acute Toxicity A single inadvertent overdose is unlikely to cause signiﬁcant mor-bidity. In humans, very high dosages of parenteral penicillins such as ticarcil lin, especially in patients with renal disease, have induced CNS effects (hallucinations, headaches, seizures) and alterations in platelet function (bleeding). Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ticarcillin/clavulanate and may be of signiﬁcance in veterinary patients: T ! AMINOGLYCOSIDES (e. g., amikacin, gentamicin, tobramycin ): In vitro studies have demonstrated that penicillins can have synergistic or additive activity against certain bacteria when used with amino-glycosides. However, beta-lactam antibiotics can inactivate amin-oglycosides in vitr o and in vivo in patients in renal failure or when penicillins are used in massive dosages. Amikacin is considered the most resistant aminoglycoside to this inactivation. T ! PROBENECID : Can reduce the renal tubular secretion of ticarcillin, thereby maintaining higher systemic levels for a longer period of time; it does not affect the elimination of clavulanate	pppbs.pdf
!TWARFARIN; HEPARIN : As ticarcillin has been implicated in rarely causing bleeding, use with caution in patients receiving antico-agulant therapy Laboratory Considerations !TAminoglycoside serum quantitative analysis : As penicillins and oth-er beta-lactams can inactivate aminoglycosides in vitr o (and in vivo in patients in renal failure or when penicillins are used in massive dosages), serum concentrations of aminoglycosides may be falsely decreased if the patient is also receiving beta-lactam antibiotics and the serum is stored prior to analysis. It is recom-mended that if the aminoglycoside assay is delayed, samples be froze n and, if possible, drawn at times when the beta-lactam an-tibiotic is at a trough. !TDirect antiglobulin (Coombs' ) tests : False-positive results may occur !TUrine protein : May produce false-positive protein results with the sulfosalicylic acid and boiling test, nitric acid test, and the ace-tic acid test. Strips using bromophenol blue reagent (e. g., Multi-St ix®) do not appear to be affected by high levels of penicillins in the urine Doses Note : Unless otherwise indicated, this drug combination is dosed on the basis of ticarcillin content. !TDOGS: a) For sepsis: 40-50 mg/kg q6-8h IV (Hardie 2000) b) 15-50 mg/kg q6-8h IV, IM or SC (Lappin 2003c) For Pseudomonas sepsis/bac teremia: 20-50 mg/kg IV q6-8h (Greene, Hartmannn et al. 2006) c) As an otic solution for adjunctive treatment of Pseudomonas otitis using the ticarcillin/clavulanic acid product—Timen-tin®): Dilute according to manufacturer's directions, then draw int o 2 m L aliquots and freeze. Thaw and use each ali-quot as 0. 5 m L in each ear, twice daily. (White 2003c) !TCATS: a) For sepsis: 40-50 mg/kg q6-8h IV (Hardie 2000) b) For Pseudomonas sepsis/bac teremia: 40 mg/kg IV q6h (Greene, Hartmannn et al. 2006) c) 50 mg/kg IV or IM 4 times daily; may need more frequent dosing or constant rate infusion for resistant Pseudomonas infections (Trepanier 1999) d) 15-50 mg/kg q6-8h IV, IM or SC (Lappin 2003c) !THORSES: For susceptible infections: a) 50 mg/kg IV q6h (Bertone 2003a) b) Foals (neonatal septicemia): 40-60 mg/kg IV or IM q8h (Paradis 2003) c) F oals: 50 mg/kg IV or IM q6-8h (Brumbaugh 1999) Monitoring !TEfﬁcacy for the infection treated (WBC, clinical signs, etc. ) !TSerum levels and therapeutic drug monitoring are not routinely performed with this drug Client Information !TLimited experience in veterinary medicine when used systemically !TBest suited for inpatient use Chemistry/Synonyms An alpha-carboxypenicillin, ticarcillin disodium occurs as a white to pale yellow, hygroscopic powder or lyophilized cake with p K as of 2. 55 and 3. 42. More than 600 mg is soluble in 1 m L of water. Potency of ticarcillin disodium is expressed in terms of ticarcillin and one gram of the disodium contains not less than 800 mg of ticarcillin anhydrous. One gram of the commercially available in-jection contains 5. 2-6. 5 m Eq of sodium. A beta-lactamase inhibitor, clavulanate potassium occurs as an off-white, crystalline powder that has a p K a of 2. 7 (as the acid) and is very soluble in water and slightly soluble in alcohol at room tem-peratures. Although available commercially as the potassium salt, potency is e xpressed in terms of clavulanic acid. Ticarcillin Disodium may also be known as: BRL-2288, or ti-carcillinum natricum. Clavulanate potassium may also be known by the f ollowing synonyms: clavulanic acid, BRL-14151K, or kalii clavulanas. International trade names for ticarcillin/clavulanate in-clude Timentin® and Claventin®. Storage/Stability/Compatibility Unused vials should be stored at room temperature (below 24°C, 75°F). A darkening of the sterile powder or solution indicates degrada-tion and loss of potency of clavulanate. For IM use, reconstitute vial with 2 m L of sterile water for injec-tion, sodium chloride for injection, or 1% lidocaine (without epi-nephrine) per gram of ticarcillin. Each m L of the resulting solution will c ontain approximately 385 mg/m L (1 gram per 2. 6 m L) ticar-cillin. For humans, IM injections are recommended to be made into a relat ively large muscle and not to administer more than one gram (2. 6 m L) IM per injection site. For IV use, initially reconstitute 3. 1 gram vials with 13 m L of sodium c hloride injection, dextrose 5% or LRS. Resulting solution will contain approximately 200 mg of ticarcillin per m L. If admin-istered IV at this concentration, give as slowly as possible. Ideally, dilute further to a concentration of 10-100 mg (ticarcillin)/m L with a suitable diluent (e. g., NS, LRS, D5W). Concentrations of 50 mg/m L or less will cause less vein irritation; the solution should be administered as slowly as possible (over at least 30 minutes). When vials are reconstituted (as above) to 200 mg/m L, the re-sulting solution is stable for 6 hours at room temperature and 72 hours whe n refrigerated. Stability for solutions diluted for IV infu-sion (10-100 mg/m L): DILUENT ROOM TEMP REFRIGERATED FROZEN NS 24 hrs 7 days 30 days D5W 24 hrs 3 days 7 days LRS 24 hrs 7 days 30 days All thawed solutions should be used within 8 hours and not refro zen. Ticarcillin/clavulanate should not be mixed with aminoglyco-sides (e. g., gentamicin, amikacin) and may not be compatible when infused at a Y-site with solutions containing amphotericin B cho-lesteryl sulfate complex, azithromycin, or vancomycin. Y-site com-patible drugs include (partial listing): propofol, dexmetomidine, cefepime, diltiazem, doxorubicin HCl liposomes, etoposide, famo-tidine, ﬂuconazole, heparin sodium, hetastarch, regular insulin, meper idine, morphine sulfate, and ondansetron.	pppbs.pdf
Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Ticarcillin Disodium Powder for Injection (contains 4. 75 m Eq sodium/g) and Clavulanate Potassium (contains 0. 15 m Eq potassium/g): 3 g ticarcillin and 0. 1g clavulanic acid in 3. 1 g vials, piggyback bottles, ADD-Vantage vials and 31 g pharmacy bulk pack-ages; Timentin® (Glaxo Smith Kline); (Rx) Ticarcil lin Powder for Injection (contains 18. 7 m Eq sodium/100 m L) and Clav ulanate Potassium (contains 0. 5 m Eq potassium/100 m L): 3 g ticarcillin and 0. 1 g clavulanic acid/100 m L in 100 m L premixed, frozen Galaxy plastic containers; Timentin® (Glaxo Smith Kline); (Rx) TILETAMINE HCL/ZOLAZEPAM HCL (tye-let-a-meen and zoe-laze-a-pam) Telazol® INJECTABLE ANESTHETIC/TRANQUILIZER Prescriber Highlights TT Injectable anesthetic/tranquilizer combination similar to ketamine/diazepam TT Contraindications: Pancreatic disease, rabbits, severe cardiac disease, use in cesarean section, or pulmonary disease TT Caution: Renal disease, large exotic cats (use avoided) TT Protect patient's eyes after using TT Dosages may need to be reduced in geriatric, debilitated, or animals with renal dysfunction. TT Adverse Effects: Respiratory depression, pain after IM in-jection, athetoid movements, tachycardia (esp. dogs), em-esis during emergence, excessive salivation & bronchial/ trac heal secretions, transient apnea, vocalization, erratic &/or prolonged recovery, involuntary muscular twitching, hypertonia, cyanosis, cardiac arrest, pulmonary edema, muscle rigidity, & either hypertension or hypotension TT Monitor body temperature (may cause hypothermia) TT Class-III controlled substance Uses/Indications Telazol® is indicated for restraint or anesthesia combined with muscle relaxation in cats, and for restraint and minor procedures of short duration (≈30 minutes) which require mild to moderate analgesia in dogs. Although not ofﬁcially approved, it has been used also in horses and many exotic and wild species. Pharmacology/Actions In cats, tiletamine decreases cardiac rate and blood pressure after IM injections. Its effect on respiratory activity is controversial, and until these effects have been clariﬁed, respiratory function should be closely monitored. The pharmacology of this drug combination is similar to that of ketamine and diazepam; for more information, refer to their monographs. Pharmacokinetics Little pharmacokinetic information is available for these agents. The onset of action may be variable and be very rapid; animals should be observed carefully after injection. In cats, the onset of action is reported to be within 1-7 minutes after IM injection. Duration of anesthesia is dependent on dosage, but is usually about 0. 33-1 hour at peak effect. This is reported to be approximately 3 times the duration of ketamine anesthesia. The duration of effect of the zolazepam component is longer than that of the tiletamine, so there is a greater degree of tranquilization than anesthesia during the recovery period. The recovery times vary in length from approximately 1-5. 5 hours. In dogs, the onset of action following IM injection averages 7. 5 minutes. The mean duration of surgical anesthesia is about 27 minutes, with recovery times averaging approximately 4 hours. The duration of the tiletamine effect is longer than that of zolazepam, so there is a shorter duration of tranquilization than there is anes-thesia. Less than 4% of the drugs are reported excreted unchanged in the urine in the dog. Contraindications/Precautions/Warnings Telazol® is contraindicated in animals with pancreatic disease, or se-vere cardiac or pulmonary disease. Animals with renal disease may have pr olonged duration of anesthetic action or recovery times. Because Telazol® may cause hypothermia,susceptible animals (small bod y surface area, low ambient temperatures) should be monitored carefully and supplemental heat applied if needed. Like ketamine, Telazol® does not abolish pinnal, palpebral, pedal, laryngeal, and pharyngeal reﬂexes and its use (alone) may not be adequate if sur-gery is to be performed on these areas. It has been reported that this drug is contraindicated in rabbits due to re nal toxicity. Telazol® is generally avoided for use in large, exotic cats (con-traindicated in tigers) as it may cause seizures, permanent neuro-logic abnormalities, or death. Cats' eyes remain open after receiving Telazo l®, and they should be protected from injury and an ophthalmic lubricant (e. g., Lacrilube®) should be applied to prevent excessive drying of the cornea. Cats reportedly do not tolerate endotracheal tubes well with this agent. Dosages may need to be reduced in geriatric, debilitated, or ani-mals with renal dysfunction. Adverse Effects Respiratory depression is a deﬁnite possibility, especially with higher dosages of this product. Apnea may occur; observe animal carefully. Pain after IM injection (especially in cats) has been noted which may be a result of the low p H of the solution. Athetoid move-ments (constant succession of slow, writhing, involuntary move-ments of ﬂexion, extension, pronation, etc. ) may occur; do not give additional T elazol® in the attempt to diminish these actions. Large doses given SC or IM, versus small doses given IV, may result in longer, rougher recoveries. In dogs, tachycardia may be a common effect and last for 30 minutes. Insufﬁcient anesthesia after recommended doses has been reported in dogs. Telazol® has been implicated in causing nephrosis in lagamorphs (rabbits/har es) and is usually not recommended for use in these species.	pppbs.pdf
Other adverse effects listed by the manufacturer include: em-esis during emergence, excessive salivation and bronchial/tracheal secr etions (if atropine not administered beforehand), transient ap-nea, vocalization, erratic and/or prolonged recovery, involuntary muscular twitching, hypertonia, cyanosis, cardiac arrest, pulmonary edema, muscle rigidity, and either hypertension or hypotension. Reproductive/Nursing Safety Telazol® crosses the placenta and may cause respiratory depres-sion in newborns; the manufacturer lists its use in cesarean section as b eing contraindicated. The teratogenic potential of the drug is unknown, and it is not recommended for use during any stage of pregnancy. Overdosage/Acute Toxicity The manufacturer claims a 2X margin of safety in dogs, and a 4. 5 times margin of safety in cats. A preliminary study in dogs (Hatch et al. 1988) suggests that doxapram at 5. 5 mg/kg will enhance respira-tions and arousal after Te lazol®. In massive overdoses, it is suggested that mechanically assisted ventilation be performed if necessary and other clinical signs treated symptomatically and supportively. Drug Interactions Little speciﬁc information is available presently on drug interac-tions with this product. !TANESTHETICS, INHALATIONAL : Dosage may need to be reduced when used concomitantly with Telazol® !TBARBITURATES : Dosage may need to be reduced when used con-comitantly with Telazol® !TCHLORAMPHENICOL : In dogs, chloramphenicol apparently has no effect on recovery times with Telazol®, but in cats, anesthesia is prolonged on average of 30 minutes by chloramphenicol. !TPHENOTHIAZINES : Can cause increased respiratory and cardiac de-pression Fo r potential additional interactions from the related compounds, ketamine and midazolam: Ketamine: !TNEUROMUSCULAR B LOCKERS (e. g., succinylcholine and tubocurarine ): May cause enhanced or prolonged respiratory depression !TTHYROID HORMONES : When given concomitantly with ketamine, thyroid hormones have induced hypertension and tachycardia in humans; beta-blockers (e. g., propranolol ) may be of beneﬁt in treating these effects Midazolam: !TANESTHETICS, INHALATIONAL : Midazolam may decrease the dosages required !TAZOLE ANTIFUNGALS (ketoconazole, itraconazole ), ﬂuconazole ): May increase midazolam levels !TCALCIUM CHANNEL BLOCKERS (diltiazem, verapamil ): May increase midazolam levels !TCIMETIDINE : May increase midazolam levels !TCNS DEPRESSANTS, OTHER : May increase the risk of respiratory de-pression !TMACROLIDES (erythromycin, clarithromycin ): May increase midazo-lam levels !TOPIATES : May increase the hypnotic effects of midazolam and hy-potension has been reported when used with meperidine. !TPHENOBARBITAL : May decrease peak levels and AUC of midazolam !TRIFAMPIN : May decrease peak levels and AUC of midazolam !TTHIOPENTAL : Midazolam may decrease the dosages required Doses !TDOGS: a) For diagnostic purposes: 6. 6-9. 9 mg/kg IM For minor procedures of short duration: 9. 9-13. 2 mg/kg IM; If supplemental doses are necessary, give doses less than the initial dose and total dosage should not exceed 26. 4 mg/kg. At ropine 0. 04 mg/kg should be used concurrently to control hypersalivation. (Package Insert; Telazol®—Robins) b) Based upon the combination of drugs: 3-10 mg/kg IM or SC or 2 -5 mg/kg IV (Mama 2002a) !TCATS: a) 9. 7-11. 9 mg/kg IM for procedures such as dentistry, abscess tr eatment, foreign body removal, etc. For procedures that re-quire mild to moderate levels of analgesia (lacerations, cas-tration, etc. ) use 10. 6-12. 5 mg/kg IM. For ovariohysterectomy and onychectomy use 14. 3-15. 8 mg/kg IM. If supplemental doses are necessary, give doses less than the initial dose and the total dosage should not exceed 72 mg/kg. Atropine 0. 04 mg/kg should be used concurrently to control hypersalivation. (Package Insert; Telazol®—Robins) b) Based upon the combination of drugs: 3-10 mg/kg IM or SC or 2 -5 mg/kg IV (Mama 2002a) !TRUMINANTS: As an induction agent for cattle, llamas/alpacas, goats, sheep: a) Xylazine at 0. 05-0. 1 mg/kg IV, IM, then Te lazol® at 2-4 mg/ kg IV (IM). Caution: xylazine can cause severe hypoxemia and pulmonary edema in sheep. (Haskell 2005a) !TRABBITS, RODENTS, SMALL MAMMALS: For chemical restraint: a) Gerbils: 20 mg/kg IP (in combination with xylazine 10 mg/ kg) (Hue rkamp 1995) b) Mice: 80-100 mg/kg IM. Rats: 20-60 mg/kg IM. Hamsters/Gerbils: 20-80 mg/kg IM. Guinea pig: 10-80 mg/kg IM. Rabbits: Not recommended (Burke 1999) c) Chinchillas: 20-40 mg/kg IM. Hamst ers: 50-80 mg/kg IP for immobilization/anesthesia. Gerbils: 10-30 mg/kg IP. Mice: 80 mg/kg IP for immobilization Rats: 40 mg/kg IP for light anesthesia. Guinea pigs: 40-60 mg/kg IM for immobilization (Adamcak and Otten 2000) !TFERRETS: As a sedative/analgesic: a) 22 mg/kg IM combined with glycopyrrolate (0. 01 mg/kg IM). R apid onset, but slow and rough recovery (3-4 hours) (Finkler 1999) b) Telazol® alone: 22 mg/kg IM; Telazol® (1. 5 mg/kg) plus xylazine (1. 5 mg/kg) IM; may re-verse xylazine with yohimbine (0. 05 mg/kg IM) Te lazol® (1. 5 mg/kg) plus xylazine (1. 5 mg/kg) plus butorph-anol (0. 2 mg/kg) IM; may reverse xylazine with yohimbine (0. 05 mg/kg IM) (Williams 2000) !THORSES: (Note : ARCI UCGFS Class 2 Drug) a) Xylazine 1. 1 mg/kg IV, 5 minutes prior to Te lazol® at 1. 65-2. 2 mg/kg IV (Hubbell, Bednarski, and Muir 1989)	pppbs.pdf
T ! EXOTIC SPECIES: a) An extensive list of suggested Telazol® dosages may be found in the art icle by E. Schobert entitled, “Telazol® Use in Wild and Exotic Animals” in the October 1987 issue of Veterinary Medicine. b) For carnivorous mammals (not tigers): 2-4 mg/m L usually prov ides adequate restraint. (Suedmeyer 2003) T ! REPTILES: a) Large Snakes: 3 mg/kg IM to facilitate handling and anesthe-sia. Administer 30-45 minutes prior to handling. Sedation may pe rsist for up to 48 hours. May also be used in Crocodil-ians at 4-8 mg/kg. (Heard 1999) b) 3-10 mg/kg IM. Lizards and snakes can generally be treated with low er end of dosage range and chelonians may require high end. If sedation is inadequate, may give incrementally up to the maximum dose. Monitor closely for apnea and ven-tilate if required. (Innis 2003) c) Signiﬁcant interspecies and interpatient differences in ef-fectiveness. At lower doses of 4-10 mg/kg sedation may be sufﬁcie nt for some procedures (venipuncture, gastric la-vage, intubation for inhalation anesthesia). At higher doses (15-40 mg/kg), recovery may be greatly prolonged. Suggest starting out at 7-15 mg/kg the ﬁrst few times this is used on reptiles in your practice (and to use on your own “in house” pets ﬁrst!), and then use increasing dosages as needed. (Funk 2002) T ! BIRDS: a) Ratites: 5 mg/kg IM or IV (Jenson 1998) Monitoring T ! Level of anesthesia/analgesia T ! Respiratory function; cardiovascular status (rate, rhythm, BP if possible) T ! Monitor eyes to prevent drying or injury T ! Body temperature Client Information Should only be administered by individuals familiar with its use. Chemistry/Synonyms Tiletamine is an injectable anesthetic agent chemically related to ketamine. Zolazepam is a diazepinone minor tranquilizer. The p H of the injectable product, after reconstitution, is 2. 2-2. 8. Tiletamine HCl may also be known as: CI-634, CL-399, CN-54521-2, or Telazol®. Zolazepam HCl may also be known as: CI-716. Storage/Stability After reconstitution, solutions may be stored for 4 days at room temperature and 14 days if refrigerated. Do not use solutions that contain a precipitate or are discolored. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Tiletamine HCl (equivalent to 250 mg free base) and Zolazepam HCl (equivalent to 250 mg free base) as lyophilized powder/vial in 5 m L vials. When 5 m L of sterile diluent (sterile water) is added a concen-tration of 50 mg/m L of each drug (100 mg/m L combined) is pro-duced; Telazol® (Fort Dodge); (Rx, C-III). Approved for use in cats and dog s. Telazol® is a Class-III controlled substance. HUMAN-LABELED PRODUCTS: None TILMICOSIN (til-mi-coe-sin) Micotil®, Pulmotil® MACROLIDE ANTIBIOTIC Prescriber Highlights TT Macrolide antibiotic used in cattle, sheep, & sometimes rabbits; used in swine as a medicated feed article TT Contraindications: Not to be used in automatically pow-ered syringes or to be given IV TT May be fatal in swine (when injected) & non-human pri-mates; potentially in horses TT Adverse Effects: IM injections may cause a local tissue reaction resulting in trim loss; edema is possible at SC injection site TT Avoid contact with eyes TT In case of human injection, contact physician immediately Uses/Indications Tilmicosin is indicated for the treatment of bovine or ovine respi-ratory diseases (BRD) caused by Mannheimia (P asturella) haemo-lytica. Pharmacology/Actions Like other macrolides, tilmicosin has activity primarily against gram-positive bacteria, although some gram-negative bacteria are affected and the drug reportedly has some activity against myco-plasma. Preliminary studies have shown that 95% of studied iso-lates of Pasturella haemolytica are sensitive. Pharmacokinetics Tilmicosin apparently concentrates in lung tissue. At 3 days post injection, the lung:serum ratio is about 60:1. MIC 95 concentrations (3. 12 micrograms/m L) for P. Hae molytica persist for a minimum of 3 days after a single injection. Contraindications/Precautions/Warnings Not to be used in automatically powered syringes or to be given intravenously as fatalities may result. Tilmicosin has been shown to be fatal in swine (when injected), non-human primates and poten-tially, in horses. Avoid contact with eyes. Accidental self-injection can be fatal in humans. Do not use in automatically powered syringes. Emergency treatment includes applying ice to injection site and contacting a physician immediately. Emergency medical telephone numbers are 1-800-722-0987 or 1-317-276-2000. Adverse Effects If administered IM, a local tissue reaction may occur result-ing in trim loss. Edema may be noted at the site of subcutaneous injectio n. Reproductive/Nursing Safety Safe use in pregnant animals or animals to be used for breeding purposes has not been demonstrated.	pppbs.pdf
Overdosage/Acute Toxicity The cardiovascular system is apparently the target of toxicity in ani-mals. In cattle, doses up to 50 mg/kg IM did not cause death, but SC doses of 150 mg/kg did cause fatalities, as well as IV doses of 5 mg/ kg. Doses as low as 10 mg/kg in swine caused increased respiration, emesis and seizures; 20 mg/kg IM caused deaths in most animals tested. In monkeys, 10 mg/kg administered once caused no signs of toxicity, but 20 mg/kg caused vomiting; 30 mg/kg caused death. In cases of human injection, contact physician immediately. The manufact urer has emergency telephone numbers to assist in deal-ing with exposure: 1-800-722-0987 or 1-317-276-2000. Drug Interactions In swine, epinephrine increased the mortality associated with tilmi-cosin. No other speciﬁc information was noted; refer to the eryth-romycin monograph for potential interactions. Doses T ! CATTLE: For susceptible infections (subcutaneous injection under the skin in the neck, or if not accessible, behind the shoulders and over the ribs is suggested). a) For treatment of pneumonic pasteurellosis: 10 mg/kg SC ev-ery 72 hours (Shewen and Bateman 1993) b) Package insert (Micotil® 300—Elanco): 10 mg/kg SC (not more than 15 m L per injection site) T ! SHEEP: For susceptible infections: a) 10 mg/kg SC (not more than 15 m L per injection site). Sub-cutaneous injection under the skin in the neck, or if not ac-cessible, behind the shoulders and over the ribs is suggested. Do not use in lambs less than 15 kg of body weight. (Package insert; Micotil® 300—Elanco) T ! RABBITS, RODENTS, SMALL MAMMALS: Rabbits: Two regimens: 1) 25 mg/kg SC once; repeat in 3 days if necessary. 2) 5 mg/kg SC on day 0, if no reaction, give 10 mg/kg SC on days 7 and 14. C an cause weakness, pallor, tachypnea and sudden death. May cause acute death if given IV. SC injections can cause local swelling and necrosis. (Ivey and Morrisey 2000) Monitoring T ! Efﬁcacy T ! Withdrawal times Client Information T ! If clients are administering the drug, they should be warned about the potential toxicity to humans, swine, and horses if ac-cidentally injected T ! Carefully instruct in proper injection techniques T ! Avoid contact with eyes Chemistry/Synonyms A semi-synthetic macrolide antibiotic, tilmicosin phosphate is commercially available in a 300 mg/m L (of tilmicosin base) injec-tion with 25% propylene glycol. Tilmicosin may also be known as EL-870, LY-177370, Micot il® or Pulmotil®. Storage/Stability/Compatibility Store the injection at or below room temperature. Avoid exposure to direct sunlight. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Tilmicosin for Subcutaneous Injection: 300 mg/m L in 50 m L, 100 m L and 250 m L multi-dose vials; Micotil® 300 Injection (Elanco); (Rx). Approved for use in cattle and sheep. Not approved for use in female dairy cattle 20 months or older. Do not use in lactating ewes if milk is to be used for human consumption. Do not use in veal calves. Slaugh-ter withdrawal (at labeled doses) = 28 days. Tilmicosin Feed Medication: 90. 7 g/lb. Pulmotil ® 90 (Elanco); (OTC). Approved for veterinary use in swine only. Slaughter withdrawal (at labeled doses) = 7 days. HUMAN-LABELED PRODUCTS: None TILUDRONATE DISODIUM TILUDRONIC ACID (til-yoo-droe-nate) Tildren®, Skelid® BISPHOSPHONATE BONE RESORPTION INHIBITOR Prescriber Highlights TT Bisphosphonate bone resorption inhibitor available in some countries for the intravenous treatment of navicu-lar disease in horses TT Adverse effects: Signs of colic, muscle tremor (hypocal-cemia), fatigue/lassitude, sweating, injection site effects, salivation, tail hyper tonia TT Must be legally imported into the USA Uses/Indications Tiludronate disodium (tiludronic acid) is a bisphosphonate bone resorption inhibitor that is available in some countries for the in-travenous treatment of navicular disease in horses. Treatment earli-er in the course of the disease apparently results in greater efﬁcacy. For humans, there is an orally administered FDA-approved prod uct for treating Paget's disease (osteitis deformans). Pharmacology/Actions Tiludronate, like other bisphosphonates, inhibit osteoclastic bone resorption by inhibiting osteoclast function after binding to bone hydroxyapatite thereby helping to regulate bone remodeling. Pharmacokinetics After intravenous injection in horses the drug is rapidly distributed to bone. Binding is greater to cancellous bone than cortical bone. Plasma protein binding is reported to be approximately 85% and elimination half-life is approximately 4. 5 hours. Repeated daily doses do not result in accumulation in plasma. Unbound drug is eliminated unchanged in the urine. Approximately 25-50% of a single IV dose is eliminated in the urine over 96 hours. Contraindications/Precautions/Warnings The labeling for Tildren® states that the drug should not be used in horses with renal dysfunction or those producing milk for human consumption. Because there is an absence of data on the effects the drug may have on the skeleton of young animals, the manufacturer states to not administer to horses less than 3 years old.	pppbs.pdf
TSince the safety of tiludronate has not been studied in pregnant or lactating mares, the manufacturer recommends not using it dur-ing pregnancy or lactation. Use with caution in horses with hypocalcemia or cardiac dys-function. If used in these patients, slow the rate of injection and watc h these patients carefully for the ﬁrst few hours post-injection. Adverse Effects Acute adverse effects reported in horses include colic (reduced ap-petite, abdominal discomfort, pawing/scratching at ground, rest-lessness), muscle tremor, fatigue/lassitude and sweating. The inci-dences of these effects are reported at 5% or less and are postulated to be due to a mild hypoglycemic effect. The onset of colic signs appear within a few hours of treatment and generally resolve with-out treatment. Should they persist, conventional colic treatments are recommended. Muscle tremors may be treated with intravenous calcium if required. Up to 9% of patients develop local reactions at the injection site (e. g., phlebitis), particularly after the 4th injection. Other adverse effects reported include salivation and tail hy pertonia. Reproductive/Nursing Safety Studies performed in male and female rats at dosages as high as 75mg/kg/day demonstrated no effects on fertility. Studies in pregnant rabbits given 2X-5X human dosages showed no sk eletal abnormalities. Pregnant mice given 7X human dosages showed some adverse effects (decreased litter size, malformed paws in 6 fetuses from one litter). Rat studies have shown decreased litter sizes, but no teratogenic effects. In humans, the FDA categorizes tiludronate 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. ) As the safety of tiludronate has not been studied in pregnant or lac tating mares, the manufacturer recommends not using it during pregnancy or lactation. Overdosage/Acute Toxicity Limited information is available. The manufacturer reports that doses of 3X in horses caused an increased frequency of adverse ef-fects, particularly signs of colic and muscle tremor. Intravenous cal-cium administration may be considered for signs associated with hy pocalcemia. Drug Interactions !TCALCIUM-or MAGNESIUM-CONTAINING INTRAVENOUS FLUIDS : May complex with tiludronate and reduce its availability; do not mix with ﬂuids or administer with ﬂuids such as Lactated Ringer's, Ringer's, Plasma-Lyte®, Normasol®, etc. Laboratory Considerations No speciﬁc concerns were noted. Doses !THORSES: For navicular disease: a) 0. 1 mg/kg tiludronic acid slow IV (over 20-30 seconds per 10 m L given) once daily for 10 days. Alternate injection sites from day to day. (Label information; Tildren®—Ceva/ Sanoﬁ) Monitoring !TClinical Efﬁcacy !TSerum Calcium !TAdverse Effects (particularly within ﬁrst 4 hours after dosing) Client Information !This medication should be administered by a veterinary professional !TPatient should be observed for up to 4 hours post-administration for signs of hypocalcemia (muscle tremors, etc. ) or colic Chemistry/Synonyms Tiludronate disodium is a bisphosphonate that occurs as a white powder having a molecular weight of 380. 6. Commercially avail-able products contain the disodium salt of tiludronic acid. 120 mg of tiludronate disodium is equivalent to 100 mg of tiludronic acid. Tiludronate disodium or tiludronic acid may also be known as ME-3737, SR-41319, acidum tiludronicum, Tildren® or Skelid®. Storage/Stability/Compatibility Unless otherwise indicated, store the unreconstituted powder and diluent at room temperature (15-30°C) in the outer carton. Shelf life of properly stored unreconstituted product is generally 3 y ears. Reconstitute the powder by aseptically adding 10 m L of the provided diluent and mix gently. The resulting solution contains 5 mg/m L of tiludronic acid. After reconstitution, use immediately. Any remaining product should be discar ded. Do not mix or administer with intravenous ﬂuids containing calcium or magnesium (e. g., LRS, Ringer's, etc. ). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None in the USA; it is available in France, Spain, The Netherlands, and Italy as: Til udronic Acid: 50 mg (as tiludronate disodium) per vial, with one 10 m L vial of sterile water for reconstitution; Tildren® (Sanoﬁ/ Ceva). Labeled for use in horses. Not permitted for use in lactating animals producing milk for hu-man consumption. Labeled meat and offal withdrawal = 0 days. Re fer to individual product labels for more information. The FDA may allow legal importation of this medication for com-passionate use in animals; for more information, see the Inst ructions for Legally Importing Drugs for Compassionate Use in the USA found in the appendix. One source recommended for obtaining Tildr en® via this process is: manorveterinaryexports. com HUMAN-LABELED PRODUCTS: Tiludronate Disodium Tablets: 240 mg (equiv. to 200 mg tiludronic acid); Skelid® (Sanoﬁ-Synthelabo); (Rx) Note : The information presented in this monograph pertains to the veterinary-labeled intravenous product only.	pppbs.pdf
TINIDAZOLE (tye-ni-dah-zole) Tindamax® NITROIMIDAZOLE ANTIPROTOZOAL/ ANTIBIOTIC Prescriber Highlights TT Drug similar to metronidazole, potentially useful for treating anaerobic infections (especially in the mouth), trichomoniasis, amebiasis and balantidiasis TT Little experience in veterinary medicine TT Adverse effects most likely GI-related, like metronidazole and ronidazole could cause neurotoxicity TT Many potential drug interactions Uses/Indications Little information is presently available on the use of tinidazole in dogs, cats, or horses. It potentially could be useful for treating an-aerobic infections, particularly associated with dental infections in small animals. B ecause of its antiprotozoal effects, it has been used as an alternative for treating giardiasis in small animals, and it could have efﬁcacy against amebiasis, trichomoniasis or balantidiasis in veterinary species, but documentation of efﬁcacy is not available. Tinidazole has a longer duration of action in dogs and cats than does metronidazole. In humans, oral tinidazole is FDA-approved for treating extraint-estinal and intestinal amebiasis, (Entamoeba histolytica), giardiasis (Giardia duo denalis/lamblia), and trichomoniasis (T. vaginalis). Pharmacology/Actions Tinidazole is a 5-nitroimidazole similar to metronidazole. It is bac-tericidal against susceptible bacteria. Its exact mechanism of action is not co mpletely understood, but it is taken-up by anaerobic or-ganisms where it is reduced to an unidentiﬁed polar compound. It is belie ved that this compound is responsible for the drug's antimi-crobial activity by disrupting DNA and nucleic acid synthesis in the bacte ria. Tinidazole has activity against many obligate anaerobes and H. pylori. It has excellent activity against Porphyromonas spp. found in canine gingiva. Tinidazole is also trichomonacidal and amebicidal. Its mecha-nism of action for its antiprotozoal activity is not well under-stood. It has therapeutic activity against Entamoeb a histolytica, Trichomonas, and Giardia. Pharmacokinetics In dogs and cats, tinidazole is practically completely absorbed after oral administration. Apparent volumes of distribution are 0. 66 L/ kg in dogs and 0. 54 L/kg in cats. Dogs clear the drug about twice as fast as cats; elimination half-lives are about 4. 4 hours in dogs, 8. 4 hours in cats. In horses, tinidazole is practically completely absorbed after oral administrat ion. Apparent volume of distribution is 0. 66 L/kg an elimination half-life of about 5. 2 hours. Contraindications/Precautions/Warnings Tinidazole should not be used in patients documented to be hyper-sensitive to it or other 5-nitroimidazoles (e. g., metronidazole). Tinidazole is metabolized by the liver; use with caution in pa-tients with hepatic dysfunction. As other 5-nitroimidazoles (metronidazole, ronidazole) have been associated with neurotoxic signs in dogs and cats and seizures have been reported rarely with tinidazole use in humans, use with caution in animals susceptible to seizures. The human labeling for tinidazole carries a “black box warn-ing” stating: “Carcinogenicity has been seen in mice and rats treated chronical ly with another agent in the nitroimidazole class (metron-idazole). Although such data have not been reported for tinidazole, avoid unnecessary use of tinidazole. Reserve its use for the condi-tions for which it is indicated. ” Adverse Effects The adverse effect proﬁles for dogs, cats or horses are not well described since clinical use of this medication has been limited. Gastrointestinal effects including vomiting, inappetance, and diar-rhea are most likely. Giving the medication with food may help alle-viate these effects. Other 5-nitroimidazoles (metronidazole, ronida-zole) have been associated with neurotoxic signs in dogs and cats; seizures hav e been reported rarely with tinidazole use in humans. Tinidazole reportedly is very bitter tasting. If using compounded prod ucts, consider using capsules or having a ﬂavored suspension prepared. Reproductive/Nursing Safety In studies performed on male rats tinidazole decreased fertility and caused testicular histopathology. Tinidazole crosses the placenta. While studies in mice and rats have not demonstrated signiﬁcant fetal effects, because of its muta-genic potential, it is stated that it should not be used in women dur-ing the ﬁrst trimester of pregnancy. In humans, the FDA categorizes tinidazole 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. ) If considering use of this product in a pregnant animal, weigh the potential beneﬁts of treatment versus the risks. Tinidazole is distributed into maternal milk at levels approxi-mating those found in serum. It is suggested that milk replacer be used if tinidaz ole is necessary for treating a nursing dam. Overdosage/Acute Toxicity Very limited information is available. In studies done in rats and mice, the oral LD 50 was >3. 6 g/kg for mice and >2 g/kg for rats. Treatment of acute overdoses of tinidazole is symptomatic and supportive. Gastric lavage or induction of emesis may be helpful. Hemodialysis can remove approximately 43% of the amount in the body (human) in a 6 hour session. Drug Interactions In humans, the following drug interactions with metronidazole have been reported or are theoretical and may be of signiﬁcance in veterinary patients receiving tinidazole: T ! ALCOHOL : May induce a disulﬁram-like (nausea, vomiting, cramps, etc. ) reaction T ! CIMETIDINE, KETOCONAZOLE : May decrease the metabolism of ti-nidazole and increase the likelihood of dose-related side effects occurring T ! CYCLOSPORINE, TACROLIMUS (systemic ): Tinidazole may increase the serum levels of cyclosporine or tacrolimus T ! FLUOROURACIL (systemic ): Tinidazole may increase the serum lev-els of ﬂuorouracil and increase the risk of toxicity T ! LITHIUM : Tinidazole may increase lithium serum levels and in-crease the risk for lithium toxicity	pppbs.pdf
T ! OXYTETRACYCLINE : Reportedly, may antagonize the therapeutic ef-fects of metronidazole (and presumably tinidazole) T ! PHENOBARBITAL, RIFAMPIN or PHENYTOIN : May increase the metabo-lism of tinidazole thereby decreasing blood levels T ! WARFARIN : Metronidazole (and potentially tinidazole) may pro-long the prothrombin time (PT) in patients taking warfarin or other coumar in anticoagulants. Avoid concurrent use if possible; otherwise, intensify monitoring. Laboratory Considerations T ! AST, ALT, LDH, Triglycerides, Hexokinase glucose : Tinidazole, like metronidazole may interfere with enzymatic coupling of the as-say to oxidation-reduction of nicotinamide adenine. Falsely low values, inc luding zero, may result. Doses T ! DOGS: a) For stomatitis, anaerobic infections: 15-25 mg/kg PO q12h for 7 day s. (Greene, Hartmannn et al. 2006) b) For giardiasis: 44 mg/kg PO q24h for 6 days. Potentially may be useful for treating trichomoniasis, amebiasis and balan-tidiasis, but efﬁcacy data lacking for animals. (Barr 2006a) T ! CATS: a) For stomatitis, anaerobic infections: 15 mg/kg PO q24h for 7 days. (G reene, Hartmannn et al. 2006) T ! HORSES: a) For susceptible anaerobic infections: 10-15 mg/kg PO q12h (Pvorala, Kotilainen et al. 1990) Monitoring T ! Clinical efﬁcacy in treating the infection Client Information T ! Give this medication with food T ! Animals should not have access to alcohol when receiving this medication T ! If gastrointestinal signs (vomiting, lack of appetite, diarrhea) are severe or persist, contact veterinarian T ! Contact veterinarian immediately if animal shows signs of be-havior changes, eyes moving back and forth (nystagmus), con-vulsions, or if patient has difﬁculty walking, climbing stairs, etc. (ataxia); these could b e sig ns that drug toxicity is occurring Chemistry/Synonyms Tinidazole occurs as an almost white or pale yellow, crystalline powder. It is practically insoluble in water, soluble in acetone, and sparingly soluble in methyl alcohol. Tinidazole may also be known as CP-12574 or tinidazolum. Inter national trade names include: Estovyn-T®, Fasigyn®, Tindamax®, Tiniba®, Tiniameb®, or Tinidazol®. Storage/Stability Store tinidazole tablets at controlled room temperature (20-25°C) protected from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None As tinidazole is a nitroimidazole, its use is prohibited in animals to be used for food. HUMAN-LABELED PRODUCTS: Tinidazole Tablets (ﬁlm-coated): 250 mg, 500 mg; Tindamax® (Pre-sutti); (Rx) TIOPRONIN (tye-oh-proe-nin) Thiola®, 2-MPG ANTIUROLITHIC (CYSTINE) AGENT Prescriber Highlights TT Drug for prevention (& treatment) of cystine urolithiasis TT Cautions: Agranulocytosis, aplastic anemia, thrombo-cytopenia or other signiﬁcant hematologic abnormality, impaired renal or hepatic function, or sensitivity to either tiopronin or penicillamine TT Adverse Effects: Coombs'-positive regenerative sphero-cyte anemia, aggressiveness, proteinuria, thrombocytope-nia, elevations in liver enzymes, dermatologic effects, & myopathy Uses/Indications Tiopronin is indicated for the prevention of cystine urolithiasis in patients where dietary therapy combined with urinary alkaliniza-tion is not completely effective. It may also be useful in combina-tion with urine alkalinization to dissolve stones. Pharmacology/Actions Tiopronin is considered an antiurolithic agent. It undergoes thiol-disulﬁde exchange with cystine (cysteine-cysteine disulﬁde) to form tiopr onin-cystine disulﬁde. This complex is more water-soluble and is readily excreted thereby preventing cystine calculi from forming. Pharmacokinetics Tiopronin has a rapid onset of action and in humans, up to 48% of a dose is found in the urine within 4 hours of dosing. Tiopronin has a relatively short duration of action and its effect in humans disap-pears in about 10 hours. Elimination is primarily via renal routes. Contraindications/Precautions/Warnings Tiopronin's risks versus its beneﬁts should be considered before using in patients with agranulocytosis, aplastic anemia, thrombo-cytopenia or other signiﬁcant hematologic abnormality, impaired renal o r hepatic function, or sensitivity to either tiopronin or pen-icillamine. Adverse Effects There is limited information available on the adverse effect proﬁle of tiopronin in dogs. While tiopronin is thought to have fewer ad-verse effects than penicillamine in humans, it has been associated with Co ombs'-positive regenerative spherocyte anemia in dogs. Should this effect occur, the drug should be discontinued and ap-propriate treatment started (corticosteroids, blood component therapy as needed). Other adverse effects noted in dogs include aggressiveness, proteinuria, thrombocytopenia, elevations in liver enzymes, dermatologic effects, and myopathy. Adverse effects noted in humans that occur more frequently include dermatologic effects (ecchymosis, itching, rashes, mouth ulcers, jaundice) and GI distress; less frequently allergic reactions (speciﬁcally adenopathy), arthralgias, dyspnea, fever, hematologic abnormalities, edema, and nephrotic syndrome have been noted.	pppbs.pdf
Reproductive/Nursing Safety There is limited information on the reproductive safety of tiopronin. Skeletal defects, cleft palates and increased resorptions were noted when rats were given 10 times the human dose of penicillamine and, therefore, may also be of concern with tiopronin. Other animal studies have suggested that tiopronin may affect fetus viability at high doses. 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. ) Because tiopronin may be excreted in milk, at present it is not reco mmended for use in nursing animals. Overdosage/Acute Toxicity There is little information available. It is suggested to contact an animal poison control center for further information in the event of an overdose situation. Drug Interactions Potentially use of tiopronin with other drugs causing nephrotoxicity, hepatotoxicity, or bone marrow depression could cause additive toxic effects. Clinical signiﬁcance is not clear. TOBRAMYCIN SULFATE (toe-bra-mye-sin) Nebcin®, TOBI® AMINOGLYCOSIDE ANTIBIOTIC Prescriber Highlights TT Parenteral aminoglycoside antibiotic that has “good” ac-tivity against a variety of bacteria, predominantly gram-negative aerobic bacilli, also in ophthalmic preps TT Because of potential adverse effects usually reserved for serious infections when given systemically, may be less nephrotoxic than gentamicin TT Adverse Effects: Nephrotoxicity, ototoxicity, neuromuscu-lar blockade TT Cats may be more sensitive to toxic effects TT Risk factors for nephrotoxicity: Preexisting renal dis-ease, age (both neonatal & geriatric), fever, sepsis, & dehydration Doses T ! DOGS: For treatment or prevention of recurrence of cystine urinary calculi: a) In conjunction with an alkalinizing, protein and sodium re-stricted diet (e. g., u/d®), 30- 40 mg/kg PO divided into two daily doses. (Cowan 1994) b) Treatment: 20 mg/kg PO twice daily for 1-3 months; rela-tively high incidence of adverse effects; Prev ention: 15 mg/kg PO twice daily. (Adams and Syme 2005) Monitoring T ! Efﬁcacy (stone size) T ! CBC with platelets T ! Liver enzymes T ! Urinalyses including urine p H Client Information T ! Clients should be counseled on the importance of adequate com-pliance with this drug to maximize efﬁcacy and detailed on the clinical signs t o wat ch for regarding adverse effects. Chemistry/Synonyms A sulfhydryl compound related to penicillamine, tiopronin has a molecular weight of 163. 2. It occurs as a white crystalline powder which is freely soluble in water. Tiopronin may also be known as: SF 522, N-(2-Mercaptopropionyl)-glycine (MPG), 2-MPG, thiopronine, Acadione®, Captimer®, Epatiol®, Mucolysin®, Mucosyt®, Sutilan®, Thiola®, Thiosol®, or Tioglis®. Storage/Stability Store tablets at room temperature in tight containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Tiopronin Tablets: 100 mg; Thiola® (Mission); (Rx) Uses/Indications While most veterinarians use gentamicin or amikacin and there are no approved veterinary tobramycin products in the U. S., tobramy-cin can be useful clinically to treat serious gram-negative infections in most spe cies. It is often used in settings where gentamicin-re-sistant bacteria are a clinical problem. The inherent toxicity of the aminogly cosides limit their systemic use to serious infections when there is either a documented lack of susceptibility to other less toxic antibiotics or when the clinical situation dictates immediate treat-ment of a presumed gram-negative infection before culture and suscep tibility results are reported. Whether tobramycin is less nephrotoxic than either gentamicin or amikacin when used clinically is controversial. Laboratory stud-ies indicate that in a controlled setting in laboratory animals, it may indeed b e so. Pharmacology/Actions T obramycin, like the other aminoglycoside antibiotics, act on sus-ceptible bacteria presumably by irreversibly binding to the 30S ri-bosomal subunit thereby inhibiting protein synthesis. It is consid-ered a bactericidal antibiotic. T obramycin's spectrum of activity includes coverage against many aero bic gram-negative and some aerobic gram-positive bacteria, including most species of E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Enterobacter, Serratia, Shigella, Mycoplasma, and Staphylococcus. Antimicrobial activity of the aminoglycosides is enhanced in an alkaline envir onment. The aminoglycoside antibiotics are inactive against fungi, virus-es and most anaerobic bacteria. Pharmacokinetics T obramycin, like the other aminoglycosides, is not appreciably ab-sorbed after oral or intrauterine administration, but it is absorbed from t opical administration (not skin or urinary bladder) when used in irrigations during surgical procedures. Patients receiving oral aminoglycosides with hemorrhagic or necrotic enteritises may absorb appreciable quantities of the drug. Subcutaneous injection results in slightly delayed peak levels and more variability than af-ter IM injection. Bioavailability from extravascular injection (IM or SC) is greate r than 90%.	pppbs.pdf
TAfter absorption, aminoglycosides are distributed primarily in the e xtracellular 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 (other than streptomycin) are minimally protein bound (<20%) to plasma pro-teins. Aminoglycosides do not readily cross the blood-brain barrier nor penetrate ocular tissue. CSF levels are unpredictable and range from 0-50% 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. Aminoglycosides cross the placenta and fetal concentrations range from 15-50% those found in maternal serum. Elimination of aminoglycosides after parenteral administration oc curs almost entirely by glomerular ﬁltration. Patients with de-creased renal function can have signiﬁcantly prolonged half-lives. In humans with normal renal function, elimination rates can be highly variable with the aminoglycoside antibiotics. Contraindications/Precautions/Warnings Aminoglycosides are contraindicated in patients who are hyper-sensitive to them. Because these drugs are often the only effective age nts 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 b e 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 neur omuscular 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 ser um monitoring and dosage adjustment in neonatal or geriatric animals. Aminoglycosides are generally considered contraindicated in rab bits/hares as they adversely affect the GI ﬂora balance in these animals. Adverse Effects The aminoglycosides are infamous for their nephrotoxic and oto-toxic effects. The nephrotoxic (tubular necrosis) mechanisms of these dr ugs 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 normally manifests by increases in BUN, creatinine, nonprotein 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. Ne phrotoxicity 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 re quire equal caution and monitoring. Ototoxicity (8th cranial nerve toxicity) of the aminoglycosides can manif est with 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 either form 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 or inﬂammation at the injection site, peripheral neuropathy, and hypersensitivity reactions. Rarely, GI clinical signs, hematologic, and hepatic effects have been reported. Reproductive/Nursing Safety T obramycin can cross the placenta and concentrate in fetal kidneys and while rare, cause 8th cranial nerve toxicity or nephrotoxicity in fetuses. T otal irreversible deafness has been reported in some hu-man babies whose mothers received tobramycin during pregnancy. Be cause the drug should only be used in serious infections, the ben-eﬁts of therapy may exceed the potential risks. In humans, the FDA cate gorizes 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 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 uncovered risks, and these drugs should be used cautiously as a last resort when the beneﬁt of therapy clearly out-weighs the risks. ) Small amounts of aminoglycoside antibiotics are excreted in milk, b ut are unlikely to cause clinically signiﬁcant effects in nurs-ing offspring. Overdosage/Acute Toxicity Should an inadvertent overdosage be administered, three treat-ments have been recommended: 1) Hemodialysis is very effective in r educing 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 efﬁcacious; 3) Complexation of drug with either carbenicillin or ticarcillin (12-20 g/day in humans) is reportedly nearly as effective as hemodialysis. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving tobramycin 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 v itro (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 aminog lycosides, but this interaction has only been well docu-mented with cephaloridine and cephalothin (both no longer mark eted). !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 !Tobramycin 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 level.	pppbs.pdf
Doses Note : There is signiﬁcant inter-patient variability with amino-glycoside pharmacokinetic parameters. T o insure therapeutic lev els and to minimize the risks for toxicity development, con-sider monitoring serum levels for this drug. Like other amino-glycosides, most now recommend dosing mammals once daily; co nsider giving the total daily dose as a single dose (e. g., if dose listed is 2 mg/kg q8h, give 6 mg/kg once daily). !TDOGS & CAT S: For small animals, one pair of authors (Aronson and Aucoin 1989) make the following recommendations with regard to min-imizing risks of toxicity, yet maximizing efﬁcacy: 1) Dose according to animal size. The larger the animal, the smalle r the dose (on a mg/kg basis). 2) The more risk factors (age, fever, sepsis, renal disease, dehy-dration) the smaller the dose. 3) In old patients or those suspected of renal disease, increase dosing int erval from q8h to q16-24h. 4) Determine serum creatinine prior to therapy and adjust by chang es in level even if it remains in “normal range. ” 5) Monitor urine for changes in sediment (e. g., casts) or con-centrating ability. Not very useful in patients with UTI. 6) Therapeutic drug monitoring is recommended when possib le. a) 2 mg/kg IV, IM, or SC q8h (avoid use or reduce dosage in patie nts with renal failure; recommend therapeutic drug monitoring, particularly in young animals) (Vaden and Papich 1995) b) For susceptible UTI: 1-2 mg/kg SC q8h (Brovida 2003) c) For sepsis: 2-4 mg/kg IV three times daily (q8h) (T ello 2003b) d) Dogs: For soft tissue, systemic infections: 1-1. 7 mg/kg IV q8h or 3 -5. 1 mg/kg IV q24h for less than 7 days; For systemic infections: 2 mg/kg SC q8-12h or 4-6 mg/ kg SC q24h for less than 7 days; Fo r persistent bacteremia: 3-5 mg/kg IV, IM, SC q8h or 9-15 mg/kg IV, IM or SC q24h for 7 days or less. (Greene, Hartmannn et al. 2006) e) Cats: For soft tissue, systemic infections: 2 mg/kg IV, IM or SC q12h or 4 mg/kg IV, IM, SC q24h for 5 days or less; For persistent bacteremia: 2 mg/kg IV, IM, SC q8h or 6 mg/kg IV, IM or SC q24h for 5 days or less. (Gr eene, Hartmannn et al. 2006) !THORSES: For susceptible infections: a) 1-1. 7 mg/kg q8h IV (slowly) or IM ( Note : This is a human dose and should be used as a general guideline only) (Walker 1992) !TLLAMAS: For susceptible infections: a) 4 mg/kg IV q24h; 0. 75 mg/kg IV q8h (Baird 2003) !TBIRDS: For susceptible infections: a) 5 mg/kg IM every 12 hours (Bauck and Hoefer 1993) b) 2. 5-5 mg/kg/day; must be given parenterally (Flammer 2003b) !TREPTILES: For susceptible infections: a) 2. 5 mg/kg once daily IM (Gauvin 1993) Monitoring !TEfﬁcacy (cultures, clinical signs associated with infection) !TRenal toxicity; baseline urinalysis, and serum creatinine/BUN. Casts in the urine are often the initial sign of impending neph-rotoxicity. Frequency of monitoring during therapy is contro-versial, but daily urinalysis and serum creatinine may not be too fre quent. !TGross monitoring of vestibular or auditory toxicity is recommended !TSerum levels if possible Client Information !TWith appropriate training, owners may give subcutaneous injec-tions at home, but routine monitoring of therapy for efﬁcacy and to xicity must still be done !TClients should understand that the potential exists for severe toxicity (nephrotoxicity, ototoxicity) developing from this medication Chemistry/Synonyms An aminoglycoside derived from Streptomyces tenebrarius, to-bramycin occurs as a white to off-white, hygroscopic powder that is fr eely soluble in water and very slightly soluble in alcohol. The sulfate salt is formed during the manufacturing process. The com-mercial injection is a clear, colorless solution and the p H is adjusted to 6 -8 with sulfuric acid and/or sodium hydroxide. T obramycin Sulfate may also be known as: tobramycin sul-phate, Brulamycin®, Gernebcin®, Mytobrin®, Nebcina®, Nebcine®, N ebicina®, Obracin®, Tobra®, Tobra Gobens®, TOBI®, Tobra Laf®, Tobra-cell®, Tobracil®, Tobradistin®, Tobramina®, Tobraneg®, Tobrasix®, Tobrex ®, Tomycin®, or Trazil®. Storage/Stability/Compatibility T obramycin sulfate for injection should be stored at room tempera-ture (15-30°C); avoid freezing and temperatures above 40°C. Do not use the pr oduct if discolored. While the manufacturers state that tobramycin should not be mixe d with other drugs, it is reportedly physically compatible and stable in most commonly used intravenous solutions (not com-patible with dextrose and alcohol solutions, Polysal, Polysal M, or Isolyte E, M or P) and compatible with the following drugs: az-treonam, bleomycin sulfate, calcium gluconate, cefoxitin sodium, cipr oﬂoxacin lactate, clindamycin phosphate (not in syringes), ﬂoxacillin sodium, metronidazole (with or without sodium bicar-bonate), ranitidine HCl, and verapamil HCl. The following drugs or solutions are reportedly physically incompatible or only compatible in speciﬁc situations with to-bramycin: cefamandole naftate, furosemide and heparin sodium. Co mpatibility is dependent upon factors such as p H, concentra-tion, temperature, and diluent used; consult specialized references or a hospital p harmacist for more speciﬁc information. In vitro inactivation of aminoglycoside antibiotics by beta-la ctam antibiotics is well documented; see the information in the Drug I nteraction and Laboratory Consideration sections.	pppbs.pdf
Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: T obramycin Sulfate Injection: 0. 8 mg/m L and 1. 2 mg/m L (as sulfate) in 100 m L & 50 m L single-dose containers; 10 mg/m L in 2 m L vials; and 40 mg/m L in 1. 5 m L and 2 m L syringes, 2 m L and 30 m L vials; T obramycin in 0. 9% Sodium Chloride (Hospira); generic (various); (Rx) T obramycin Sulfate Powder for Injection: 1. 2 g vials (40 mg/m L after reco nstitution), preservative free in 50 m L bulk package vial; generic (American Pharmaceutical Partners); (Rx) T obramycin Nebulizer Solution: 60 mg/m L in 5 m L amps; TOBI® (Patho Ge nesis); (Rx) Also available in ophthalmic preparations. TOCAINIDE HCL (toe-kay-nide) Tonocard® ORAL ANTIARRHYTHMIC Prescriber Highlights TT Oral antiarrhythmic with similar activity as lidocaine; not commonly used in veterinary medicine TT Contraindications: Hypersensitivity reactions to it or amide-type local anesthetics, 2nd or 3rd degree AV block & not being artiﬁcially paced. Caution: Heart failure, hematologic abnormalities, or preexisting bone marrow failure. TT Adverse Effects: CNS effects (depression, ataxia, muscle tremors, etc. ), nausea & vomiting (usually transient), car-diovascular effects (hypotension, bradycardia, tachycar-dia, other arrhythmias, & exacerbation of CHF) TT Case reports of dogs on long-term therapy (>3 mos. ) de-veloping ocular & renal toxicity Uses/Indications Veterinary experience with tocainide is limited. At this time, dogs are the only veterinary species where enough clinical experience has been garnered to recommend its use. It is indicated for the oral ther-apy of ventricular arrhythmias, principally ventricular tachycardia and vent ricular premature complexes. In humans, response to lido-caine can usually predict whether tocainide might be effective. Pharmacology/Actions To c a i n i d e i s co n s i d e re d a cl a s s IB (membrane-stabilizing) antidys-rhythmic agent that demonstrates rapid rates of attachment and diss ociation to sodium channels. Like lidocaine, tocainide produces a dose-dependent decrease in potassium and sodium conductance that results in decreased excitability of myocardial cells. Automaticity, conduction velocity, and effective refractory periods are decreased at therapeutic levels. Little or no increases in PR intervals, QRS com-plexes, or QT intervals are seen at therapeutic levels. Like lidocaine, toca inide has little, if any effect, on autonomic tone. Pharmacokinetics Following oral administration, tocainide is rapidly and almost completely absorbed. The presence of food in the stomach may al-ter the rate, but not the extent, of absorption. Unlike lidocaine, the hepatic ﬁrst-pass effect is minimal with tocainide. In humans, peak plasma leve ls occur between 0. 5-2 hours when administered on an empty stomach. The distribution aspects of tocainide have not been fully de-scribed. In humans, the volume of distribution ranges from 1. 5-4 L/kg and has b een reported to be 1. 7 L/kg in dogs. T ocainide is minimally bound to plasma proteins. It is unknown if it crosses the placenta or enters into the milk. T ocainide is metabolized by the liver, but up to 50% of a dose is excre ted unchanged by the kidneys into the urine. Alkalinization of the urine may result in a substantial decrease in the amount of tocainide that is excreted unchanged into the urine, but acidiﬁca-tion of the urine reportedly does not enhance the excretion rate. Elimination half-lif e is dose-dependent and at the clinical doses used for dogs, not well-described. Contraindications/Precautions/Warnings T ocainide is contraindicated in patients who have demonstrated previous hypersensitivity reactions to it or amide-type local anes-thetics, or who have 2nd or 3rd degree A V block and are not being artiﬁciall y paced. Use tocainide cautiously in patients with heart failure as it has the pote ntial to aggravate the condition. Use with caution in pa-tients with hematologic abnormalities or preexisting bone marrow failure. Adverse Effects It is expected that tocainide would exhibit a similar adverse reaction proﬁle as lidocaine with anorexia, and vomiting being most likely. In dogs, tocainide serum concentrations of greater than 12 mcg/ m L have been associated with neurotoxicity (ataxia, head tremor). There are case reports of dogs receiving tocainide for more than 3 months developing ocular (corneal dystrophy) and renal toxicity. Although side effects are common in human patients, they are usually dose related, mild, and reversible upon discontinuation of the drug. CNS effects can include drowsiness, depression, ataxia, muscle tremors, etc. Nausea and vomiting may occur, but are usu-ally transient. Cardiovascular effects reported include hypotension, brad ycardia, tachycardia, other arrhythmias, and exacerbation of CHF. Rarely (<1% incidence), clinical signs of bone marrow de-pression or pulmonary effects (pulmonary ﬁbrosis, pneumonia, respirato ry arrest, pulmonary edema, etc. ) have been reported in humans. 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. ) T ocainide enters milk in signiﬁcant quantities and may poten-tially cause adverse effects in nursing offspring. Overdosage/Acute Toxicity Dogs tend to be rather resistant to the acute toxic effects of the drug. In one study, dogs were administered 750 mg/kg over 6 hours and emesis was the only frequent effect seen, but ECG changes were also seen in some animals. There is no speciﬁc antidote for tocainide overdose and treat-ment tends to be supportive and symptomatic. For more informa-tion, see the Lidocaine monograph. T ocainide can be removed with hemodialy sis.	pppbs.pdf
TDrug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving tocainide and may be of signiﬁcance in veterinary patients: T ! ANTIARRHYTHMICS, OTHER CLASS IB (e. g., lidocaine, phenytoin, mexi-letine ): T oxicities may be additive, with little or no therapeutic gain, if tocainide is used concurrently with other Class IB anti-dysrhythmics; use caution, when converting from one Class IB agent to anothe r T ! CIMETIDINE (and other H2 blockers ): May reduce tocainide bio-availability T ! METOPROLOL : T ocainide used concomitantly with metoprolol (a beta-adrenergic antagonist) can have additive effects on car-diac index and wedge pressure; may clinically signiﬁcant, par-ticularly in patients with sick sinus syndrome and impaired A V conduc tion T ! RIFAMPIN : May decrease tocainide effects by increasing metabolism Doses T ! DOGS: a) 10-20 mg/kg (up to 25 mg/kg) PO q8h (Ware 2000) b) 5-10 mg/kg PO three times daily (Atkins 2003a) c) 10-20 mg/kg PO q8h (Fox 2003a) d) 10-20 mg/kg PO two to three times a day (Tilley 2007) Monitoring T ! ECG T ! Clinical signs of toxicity (see Adverse Reactions); may wish to monitor CBC's if treating chronically ( Note: For human patients, the manufacturer recommends weekly CBC's with differential and platelets, be run at weekly intervals for the ﬁrst 3 months of therapy and periodically thereafter) T ! Serum levels (therapeutic levels in humans are usually 3-10 mi-crograms/m L), especially if clinical signs of toxicity or lack of ef-ﬁcacy are noted. Client Information T ! o be effective, the animal must receive all doses as prescribed T ! Notify veterinarian if the animal exhibits any abnormal bleeding or bruising, develops wheezing, shortness of breath, or a cough T ! If dog vomits or becomes anorexic after dosing, give with food; if vomiting persists or animal develops a change in behavior or attitud e, contact veterinarian Chemistry/Synonyms An amide-type local anesthetic, tocainide HCl occurs as a bit-ter tasting, white, crystalline powder with a p K a of 7. 8. I t is freely soluble in both water and alcohol. T ocainide is structurally related to lidocaine, but it is a primary amine where lidocaine is a tertiary amine. This modiﬁcation allows tocainide to be resistant to exten-sive ﬁrst-pass metabolism after oral administration. T ocainide HCl may also be known as W-36095, Tonocard® or Xylotocan®. Storage/Stability Protect tablets from light and store in well-closed containers. An expiration date of 4 years after manufacture is assigned to the com-mercially available tablets when packaged in high-density polyeth-ylene bottles. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: T ocainide HCl Oral Tablets: 400 mg, 600 mg; Tonocard® (Astra Mer-ck); (Rx) TOLAZOLINE HCL (toe-laz-oh-leen) Tolazine® ALPHA-ADRENERGIC BLOCKER Prescriber Highlights TT Alpha-adrenergic blocker used primarily as a reversal agent for xylazine TT Contraindications: Horses exhibiting signs of stress, de-bilitation, cardiac disease, sympathetic blockage, hypov-olemia or shock, hypersensitivity, or with coronary artery or cerebrovascular disease TT Adverse Effects: HORSES: Transient tachycardia; periph-eral vasodilatation presenting as sweating & injected mucous membranes of the gingiva & conjunctiva; hype-ralgesia of the lips (licking, ﬂipping of lips); piloerection; clear lacrimal & nasal discharge; muscle fasciculations; apprehensiveness Uses/Indications T olazoline is approved and indicated for the reversal of effects asso-ciated with xylazine in horses. It has also been used for this purpose in a var iety of other species as well, but less safety and efﬁcacy data is available. In humans, the primary uses for tolazoline are: treatment of per-sistent pulmonary hypertension in newborns, adjunctive treatment and diagnosis o f peripheral vasospastic disorders, and as a provoca-tive test for glaucoma after subconjunctival injection. Pharmacology/Actions By directly relaxing vascular smooth muscle, tolazoline has periph-eral vasodilating effects and decreases total peripheral resistance. T olazoline also is a competitive alpha 1 and alpha 2-adrenergic blocking agent, explaining its mechanism for reversing the effects of xylazine. T olazoline is rapid acting (usually within 5 minutes of IV administration), but has a short duration of action and repeat doses may be required. Pharmacokinetics After IV injection in horses, tolazoline is widely distributed. Animal studies have demonstrated that tolazoline is concentrated in the liver and kidneys. Half-life in horses at recommended doses is ap-proximately 1 hour. Contraindications/Precautions/Warnings The manufacturer does not recommend use in horses exhibiting signs of stress, debilitation, cardiac disease, sympathetic blockage, hypovolemia, or shock. Safe use for foals has not been established and some believe it should not be used in foals. as adverse reactions and fatalities have been reported. T olazoline should be considered contraindicated in patients known t o be hypersensitive to it, or with coronary artery or cerebro-vascular disease. Humans having any of the above-contraindicated conditio ns should use extra caution when handling the agent.	pppbs.pdf
Adverse Effects In horses adverse effects that may occur include: transient tachycar-dia; peripheral vasodilatation presenting as sweating and injected muc ous membranes of the gingiva and conjunctiva; hyperalgesia of the lips (licking, ﬂipping of lips); piloerection; clear lacrimal and nasal discharge; muscle fasciculations; apprehensiveness. Adverse effects should diminish with time and generally disappear within 2 hours of dosing. The potential for adverse effects increases if tola-zoline is given at higher than recommended dosages or if xylazine has not be p reviously administered. Reproductive/Nursing Safety Safety during pregnancy, in breeding or lactating animals has not been established. It is unknown if the drug enters maternal milk. Overdosage/Acute Toxicity In horses given tolazoline alone (no previous xylazine), doses of 5X recommended resulted in gastrointestinal hypermotility with resultant ﬂatulence and defecation or attempt to defecate. Some horses exhibited mild colic and transient diarrhea. Intraventricular conduction may be slowed when horses are overdosed, with a pro-longation of the QRS-complex noted. Ventricular arrhythmias may oc cur resulting in death with higher overdoses (5X). In humans, ephedrine (NOT epinephrine or norepinephrine) has been recom-mended to treat serious tolazoline-induced hypotension. A llama that received 4. 3 mg/kg IV and again 45 minutes later (app roximately a 5X overdose) developed signs of anxiety, hyperes-thesia, profuse salivation, GI tract hypermotility, diarrhea, convul-sions, hypotension, and tachypnea. Treatment including IV diaz-epam, phenylephrine, IV ﬂuids, and oxygen was successful. (Reed, Duk e et al. 2000). Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving tolazoline and may be of signiﬁcance in veterinary patients: !TALCOHOL : Accumulation of acetaldehyde can occur if tolazoline and alcohol are given simultaneously !TEPINEPHRINE, NOREPINEPHRINE : If large doses of tolazoline are given with either norepinephrine or epinephrine, a paradoxical drop in blood pressure can occur followed by a precipitous increase in blood pressure Doses !THORSES: For reversal of xylazine effects: a) 4 mg/kg slow IV (4 m L/220 lb. of body weight); administra-tion rate should approximate 1 m L/second (Package Insert; To lazine®—Lloyd Laboratories) !TDOGS & CAT S: For reversal of xylazine effects: a) 4 mg/kg slow IV (4 m L/220 lb. of body weight); administra-tion rate should approximate 1 m L/second (Package Insert; To lazine®—Lloyd Laboratories; New Zealand) Note : If reversal is warranted, the high concentration (100 mg/m L) of the veterinary drug may make accurate dosing difﬁcult; yohimbine or the human-labeled tolazoline prod-uct (25 mg/m L) may be safer alternatives than To lazine® (100 mg/m L). Note : T olazoline is not approved for use in dogs and cats in the USA and the US manufacturer does not recom-mend its use !TLLAMAS/ALPACAS: For reversal of xylazine/ketamine effects: a) 2 mg/kg IM (Du Bois, Prado et al. 2004) b) 1-2 mg/kg IV or IM; Caution: acute death has been reported afte r rapid IV administration of tolazoline at high dosages. (Anderson 2005) !TBIRDS: As a reversal agent for alpha2-adrenergic agonists (e. g., xylazine, detomidine, etc. ): a) 15 mg/kg IV (Clyde and Paul-Murphy 2000) !TDEER: Note : Not approved in the USA for use in food animals For reversal of xylazine effects: a) 2-4 mg/kg slow IV; titrate to effect; Slaughter withdrawal: 30 day s (Label Directions; Tolazine®—Lloyd Laboratories; New Zealand) !TCATTLE: Note : Not approved in the USA for use in food animals For reversal of xylazine effects: a) 2-4 mg/kg slow IV; titrate to effect; Slaughter withdrawal: 30 day s (Label Directions; Tolazine®—Lloyd Laboratories; New Zealand) !TSHEEP & GOATS: Note : Not approved in the USA for use in food animals For reversal of xylazine effects: a) 2-4 mg/kg slow IV; titrate to effect; Slaughter withdrawal: 30 day s (Label Directions; Tolazine®—Lloyd Laboratories; New Zealand) b) Goats: 1-2 mg/kg IV, inject slowly to effect (Hooper 2002) c) Sheep: 2. 2 mg/kg slowly IV. (Snyder 2006) Monitoring/Client Information !TReversal effects (efﬁcacy) !TAdverse effects (see above). Because of the risks associated with the use of xylazine and reversal by tolazoline, these drugs should be administered and monitored by veterinary professionals only. Chemistry/Synonyms An alpha-adrenergic blocking agent, tolazoline HCl is structurally related to phentolamine. It occurs as a white to off-white, crystal-line powder possessing a bitter taste and a slight aromatic odor. T olaz oline is freely soluble in ethanol or water. The commercially available (human) injection has p H between 3-4. T olazoline HCl may also be known as: benzazoline hydrochlo-ride, tolazolinium chloratum, Pr iscol®, Priscoline®, Tolazine® or Vaso-Dilatan®. Storage/Stability/Compatibility Commercially available injection products should be stored be-tween 15-30°C and protected from light. The drug is reportedly ph ysically compatible with the commonly used IV solutions. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: T olazoline HCl Injection: 100 mg/m L in 100 m L multi-dose vials; To-lazine® (Lloyd); (Rx). Approved for use in horses; not to be used in fo od-producing animals. HUMAN-LABELED PRODUCTS: None	pppbs.pdf
TTOLFENAMIC ACID (tole-fen-a-mik) Tolfedine® NONSTEROIDAL ANTIINFLAMMATORY AGENT Prescriber Highlights TT NSAID approved for dogs & cats in Canada, Europe TT Available (not in USA) in both oral & injectable dosage forms TT Relatively safe for short-term use Uses/Indications T olfenamic acid may be useful for the treatment of acute or chronic pain and/or inﬂammation in dogs and acute pain/inﬂammation in cats. In Europe, it is also approved for use in cattle. Pharmacology/Actions T olfenamic acid exhibits pharmacologic actions similar to those of aspirin. It is a potent inhibitor of cyclooxygenase, thereby inhibiting the release of prostaglandins. It also has direct inhibition of prosta-glandin receptors. T olfenamic acid has signiﬁcant anti-thrombox-ane activity and is not recommended for use pre-surgically because of its eff ects on platelet function. Pharmacokinetics T olfenamic acid is absorbed after oral administration. In dogs, peak levels occur from 2-4 hours after dosing. Enterohepatic recircula-tion is increased if given with food. This can increase the bioavail-ability, but also creates more variability in bioavailability than when give n to fasted dogs. The volume of distribution in dogs is reported to be 1. 2 L/kg and it has an elimination half-life of about 6. 5 hours. Duration of antiinﬂammatory effect is 24-36 hours. Contraindications/Precautions/Warnings T olfenamic acid is contraindicated in animals hypersensitive to it or to other drugs in its class (i. e., meclofenamic acid). Like other NSAIDs, it should not be used in animals with active GI bleeding or ulceration. Use with caution in patients with decreased renal or hepatic function. Adverse Effects T olfenamic acid is relatively safe when given as recommended in dogs and cats. Vomiting and diarrhea have been reported after oral use. Experimental studies did not demonstrate signiﬁcant renal or GI toxicity until doses were more than 10 times labeled. Because of its anti-thromboxane activity and resultant effects on plate let function, tolfenamic acid is not recommended for use pre-surgically. Reproductive/Nursing Safety No speciﬁc information was located; like other NSAIDs, tolfenamic acid should be used with caution in pregnancy. Overdosage/Acute Toxicity No speciﬁc information was located. It is suggested that if an acute, overdose occurs treatment follows standard overdose procedures (empty gut following oral ingestion, etc. ). Supportive treatment should be instituted as necessary and IV diazepam used to help control seizures. Monitor for GI bleeding. Because tolfenamic acid may cause renal effects, monitor electrolyte and ﬂuid balance care-fully and manage renal failure using established guidelines. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving tolfenamic acid or other NSAIDs and may be of signiﬁcance in veterinary patients: T ! ASPIRIN : May increase the risk of gastrointestinal toxicity (e. g., ul-ceration, bleeding, vomiting, diarrhea) T ! CORTICOSTEROIDS : As concomitant corticosteroid therapy may in-crease the occurrence of gastric ulceration, avoid the use of these drugs whe n also using tolfenamic acid T ! DIGOXIN : NSAIDS may increase serum levels T ! FLUCONAZOLE : Administration has increased plasma levels of cele-coxib in humans and potentially could also affect tolfenamic acid levels in d ogs T ! FUROSEMIDE : NSAIDs may reduce saluretic and diuretic effects T ! METHOTREXATE : Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate; use together with extreme caution T ! NEPHROTOXIC DRUGS (e. g., furosemide, aminoglycosides, amphotericin B, etc. ): May enhance the risk of nephrotoxicity T ! NSAIDS, OTHER : May increase the risk of gastrointestinal toxicity (e. g., ulceration, bleeding, vomiting, diarrhea) T ! WARFARIN : Closely monitor patients also receiving drugs that are highly bound to plasma proteins (e. g., warfarin), as tolfenamic acid and its active metabolite are 98-99% protein bound in the dog Doses T ! DOGS: a) For acute pain: 4 mg/kg once daily SC, IM or PO for 3-5 days. For c hronic pain: 4 mg/kg, PO once daily for 3-5 consecu-tive days per week. The injectable is suggested for the ﬁrst dose only. (Dowling 2000) b) First dose: 4 mg/kg SC or IM; follow with tablets at 4 mg/ kg PO onc e daily for 2-4 days. The treatment may be re-peated once a week as required, or as recommended by the vete rinarian, PO once daily for 3-5 days. (Label informa-tion; Tolfedine®—Vetoquinol Canada) T ! CATS: a) For acute pain: 4 mg/kg once daily SC, IM or PO for 3-5 days. The injec table is suggested for the ﬁrst dose only. (Dowling 2000) b) 4 mg/kg PO once daily for 3-5 days or as recommended by the vet erinarian. (Label information; Tolfedine®—Vetoquinol Canada) Monitoring T ! Clinical efﬁcacy T ! Adverse effects Client Information T ! he weekly dosing regimen (3-5 consecutive days per week for dogs) is important to follow to minimize risks of adverse effects T ! Report any changes in appetite, water consumption, or GI dis-tress to veterinarian Chemistry/Synonyms A non-steroidal antiinﬂammatory agent in the anthranilic acid (fe-namate) category, tolfenamic acid is related chemically to meclofe-namic acid.	pppbs.pdf
T olfenamic Acid may also be known as: acidum tolfenam-icum, Bifenac®, Clotam®, Clotan®, Fenamic®, Flocur®, Gantil®, Migea ®, Polmonin®, Purfalox®, Rociclyn®, Tolfamic®, Tolfedine® or Turbaund®. Storage/Stability Unless otherwise labeled, store tolfenamic acid tablets and solution at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None in the USA. In Canada and Europe: T olfenamic Acid Tablets: 6 mg, 30 mg, 60 mg and T olfenamic Acid Injection 40 mg/m L are available. Common trade name is Tolfedine® (Vetoquinol). HUMAN-LABELED PRODUCTS: None in the USA TOLTRAZURIL (tole-traz-yoo-ril) Baycox® ANTIPROTOZOAL/ANTICOCCIDIAL Prescriber Highlights TT Antiprotozoal labeled for treating coccidia in poultry (in Europe) TT May be considered as an alternative for treating coccidi-osis in dogs & cats, oocyst shedding stage of toxoplas-mosis in cats, etc. TT Not commercially available in the USA, must be legally imported TT Adverse effect proﬁle not well described Uses/Indications T oltrazuril is an antiprotozoal agent that may be considered as an alternative treatment for coccidiosis in dogs and cats, Hepatazoon infections, or for treating the oocyst shedding stage of toxoplasmo-sis in cats. It has also been used as a treatment for overwhelming parasitic loa ds in lizards (Bearded Dragons). T oltrazuril has activity against parasites of the genus Hepat ozoon, but other drugs (e. g., imidocarb, primaquine, doxycycline) are gen-erally used. While toltrazuril has been used to treat equine protozoal my-eloencephalitis (EPM) caused by Sarcocyst is neurona, use of ap-proved products now available (e. g., nitazoxanide, ponazuril, py-rimethamine/sulfadiazine) is preferred. T oltrazuril has been used in some countries to treat Isospor a suis in piglets. Pharmacology/Actions T oltrazuril is the parent compound to ponazuril (toltrazuril sul-fone). Its mechanism of action is not well understood, but it ap-pears to inhibit protozoal enzyme systems. T oltrazuril has activity against Hepat ozoon, Isospora, Sarcocystis, Toxoplasma, and all intracellular stages of coccidia. Pharmacokinetics Little information is available. T oltrazuril is about 50% absorbed after oral consumption in poultry. Highest concentrations are found in the liver; it is rapidly metabolized into the sulfone deriva-tive (ponazuril). Contraindications/Precautions/Warnings T oltrazuril should not be used in patients who have had prior hy-persensitivity reactions to it or other triazinone (triazine) antipro-tozoals (e. g., ponazuril, diclazuril). The principle metabolite of toltrazuril reportedly persists in the envir onment and can contaminate groundwater, however there ap-pears to be little risk for signiﬁcant environmental contamination when t oltrazuril is used in dogs, cats, horses, or other companion animals (pet birds, reptiles). Adverse Effects T oltrazuril appears to be well tolerated in birds. An adverse effect proﬁle in mammals is not well described. Potentially, GI signs could occur. Some horses receiving the related drug ponazuril, developed blisters on their nose and mouth, and some, a rash or hives during ﬁeld trials. Reproductive/Nursing Safety No reproductive or nursing safety information was located; weigh potential risks versus beneﬁts of use during pregnancy or lactation. Overdosage/Acute Toxicity Very limited information is available. Doses of up to 10x in horses were tolerated without signiﬁcant adverse effects. 5x overdoses in poultry have been tolerated without clinical signs noted. Decreased water intake has been seen if overdoses are greater than 5X. Drug Interactions None reported Laboratory Considerations No issues were noted. Doses T ! DOGS: a) For coccidiosis (Cystoisosporosis): 10-20 mg/kg PO one time to all puppies at 3-4 weeks of age will help prevent problems associated with intestinal coccidiosis (Daugschies, Mundt et al. 2000) b) For coccidiosis: 15 mg/kg PO once daily for 3-6 days (Dubey and Gree ne 2006) T ! CATS: a) For enteroepithelial cycle of toxoplasmosis (oocyst shed-ding): 5-10 mg/kg PO once daily for 2 days (Dubey and Lappin 2006) b) For coccidiosis: 30 mg/kg PO once daily for 2-3 days (Greene, Hartmannn et al. 2006) T ! BIRDS : a) For coccidiosis in raptors: 7 mg/kg PO once daily for 2-3 days (J ones 2004b) T ! REPTILES: a) For parasitism in Bearded Dragons: 5-15 mg/kg PO once daily for 3 da ys (Kramer 2006) Monitoring T ! Clinical efﬁcacy Client Information T ! Avoid direct contact with this medication; the manufacturer rec-ommends wearing synthetic rubber gloves when handling the 2. 5% solution. Wash exposed skin after use.	pppbs.pdf
Chemistry/Synonyms Related to other antiprotozoals such as ponazuril, toltrazuril is a triazinone (triazine) antiprotozoal (anticoccidial) agent. The com-mercially available (in Europe) 2. 5% oral solution is an alkaline, clear, c olorless to yellow brown solution which also contains tri-ethanolamine 30 mg/m L and polyethylene glycol 80. 7 mg/m L. T oltrazur il has a molecular weight of 425. 4 T oltrazuril may also be known as Bay-Vi-9142, toltrazurilo, tol-trazurilum and Baycox ®. Storage/Stability The 2. 5% solution should be stored at temperatures at 25°C or below. Dilutions in drinking water more concentrated than 1:1000 (1 m L of the 2. 5% solution to 1 liter of water) may precipitate. After dilution, the resulting solution is stable for 24 hours. It is recom-mended that medicated drinking water not consumed after 24 hours be discard ed. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None in the USA In some European countries: T oltrazuril 2. 5% (25 mg/m L) solu-tion for dilution in drinking water in 1 liter bottles; Bayco x® 2. 5% Solution (Bayer); (Rx). Approved for treatment of coccidiosis in poultry. In the UK, slaughter withdrawal is 18 days for poultry. Not for use in bir ds producing eggs for human consumption. The FDA may allow legal importation of this medication for com-passionate use in animals; for more information, see the Instruc tions for Legally Importing Drugs for Compassionate Use in the USA found in the appendix. HUMAN-LABELED PRODUCTS: None TOPIRAMATE (toe-pie-rah-mate) Topamax® ANTICONVULSANT Prescriber Highlights TT Antiseizure medication that may be useful for seizure disorders in dogs, particularly partial seizure activity; may be of beneﬁt in treating cats, but little information available TT Very short half-life in dogs (2-4 hours), but therapeutic activity may persist secondary to high afﬁnity for recep-tors in brain TT Adverse effect proﬁle may include GI distress, inap-petance, & irritability in dogs; in cats, sedation & inap-petance have been noted TT Expense may be an issue; generics now available Uses/Indications T opiramate may be useful for treating seizures in dogs, particularly partial seizure activity. It may also be of beneﬁt in treating cats, but little information is available. Pharmacology/Actions While the exact mechanism for its antiseizure action is not known, topiramate possesses three properties that probably play a role in its activity: T opiramate blocks in a time-dependent manner ac-tion potentials elicited repetitively by a sustained depolarization of neur ons; it increases the frequency that GABA activates GABAA receptors; and it antagonizes the kainite/AMPA receptors without affect ing the NMDA receptor subtype. T opiramate's actions are concentration-dependent; effects can ﬁrst be seen at 1micro Mole and maximize at 200 micro Moles. T opiramate is a weak inhibitor of carbonic anhydrase isoenzymes CA-II and CA-IV, but it is believed that this effect does not contribute signiﬁcantly to its antiepileptic actions. Pharmacokinetics In dogs, topiramate is rapidly absorbed after oral administration, but absolute bioavailability varies between 30-60%. Half-life rang-es from 2-4 hours after multiple doses. Comparatively, the half-life in humans is about 21 hours in adults, but shorter in children. In humans, the drug is not extensively metabolized and about 70% is excreted unchanged in the urine. Contraindications/Precautions/Warnings T opiramate is contraindicated in patients hypersensitive to it. It should be used with caution (in humans) with impaired hepatic or renal function. Adverse Effects Because this drug rarely has been used in veterinary patients, an ac-curate adverse effect proﬁle is not known. In dogs, most prevalent adve rse effects reported include GI distress, inappetance, and irrita-bility. In cats, sedation and inappetance have been noted. In humans, the most likely adverse effects include somnolence, dizziness, nerv ousness, confusion, and ataxia. Very rarely, acute myopia with secondary angle closure glaucoma has been reported. Incidence of kidney stones is about 2-4 times higher in patients taking topiramate than in the general population. Reproductive/Nursing Safety In humans, the FDA categorizes topiramate 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. ) T eratogenic effects were noted in mice and rats given topiramate at dosages equivalent to those used in humans. T opiramate enters maternal milk; use with caution in nursing patients. Overdosage/Acute Toxicity There were 132 exposures to topiramate reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 113 were dogs with 10 showing clini-cal signs and 19 were cats with 4 showing clinical signs. Common ﬁndings in d ogs recorded in decreasing frequency included ataxia, lethargy, anxiety, disorientation and head shaking. Common ﬁnd-ings in cats recorded in decreasing frequency included vomiting, ataxia and lethargy. O verdoses in humans have cause convulsions, drowsiness/leth-argy, slurred speech, blurred and double vision, impaired menta-tion/stupor, ataxia, metabolic acidosis, hypotension, agitation, and abdominal pain. Tr eatment consists of gut emptying protocols if the ingestion was rec ent, and supportive therapy. Hemodialysis is effective in en-hancing the elimination of topiramate from the body.	pppbs.pdf
Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving topiramate and may be of signiﬁcance in veterinary patients: T ! AMITRIPTYLINE : T opiramate may increase levels T ! CARBONIC ANHYDRASE INHIBITORS (acetazolamide, dichlorphenamide, etc. ): Used concomitantly with topiramate, may increase the risk of renal stone formation T ! CNS DEPRESSANT DRUGS, OTHER : Other CNS depressant drugs may exacerbate the adverse effects of topiramate T ! LAMOTRIGINE : May increase topiramate levels T ! PHENYTOIN : May decrease topiramate levels; phenytoin levels may increase T ! VALPROIC ACID : May decrease topiramate and VPA levels Laboratory Considerations No speciﬁc laboratory interactions or considerations were noted. Plasma concentrations of topiramate are usually not monitored in human patients, but therapeutic levels are thought to range from 2-25 mg/L. Doses T ! DOGS: a) As an alternative second line anticonvulsant: 5-10 mg/kg PO q12h (Shell 2003c) b) As an alternative treatment for refractory generalized and fo-cal seizures: 5-10 mg/kg PO twice daily (Smith 2002b) c) Initial dose of 2-10 mg/kg PO q12h. (Podell 2006a) d) 5-10 mg/kg PO twice daily; start at the lower dosage to re-duce adverse effects. (Kortz 2005) T ! CATS: a) 12. 5-25 mg PO (total dose) q8-12h. (Podell 2006a) Monitoring T ! Efﬁcacy T ! Adverse effects Client Information T ! Clients must understand that the clinical use of this agent is relatively “investigational” in veterinary patients, that it must be dosed often in dogs, and the potential costs T ! Caution clients not to stop therapy abruptly or “rebound” sei-zures may occur T ! Have clients maintain a seizure diary to help determine efﬁcacy Chemistry/Synonyms A sulfamate-substituted derivative of D-fructose antiepileptic, topi-ramate occurs as a white crystalline powder with a bitter taste. Its solubility in wat er is 9. 8 mg/m L; it is freely soluble in alcohol. T opiramate may also be known as: Mc N-4853, RWJ-17021, Epitomax®, Topamac®, Topamax®, or Topimax®. Storage/Stability T opiramate tablets should be stored in tight containers at room tem-perature (15-30°C; 59-86°F); protect from moisture. T opiramate sprinkle caps ules should be stored in tight containers at tempera-tures below 25°C (76°F); protect from moisture. 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: T opiramate Tablets: 25 mg, 50 mg and 100 mg; Sprinkle Capsules: 15 mg & 25 mg; Topamax® (Ortho-Mc Neil); generic; (Rx) TORSEMIDE (tor-she-myde) Demadex®, Torasemide LOO P DIURETIC Prescriber Highlights TT Potent loop diuretic potentially useful for adjunctive treatment of CHF in dogs & cats; very little information available on clinical use in veterinary medicine TT Approximately 10X more potent, longer diuretic action, & more potassium-sparing (in dogs) than furosemide TT May be more expensive than furosemide, but tablets are now available generically Uses/Indications T orsemide is a loop diuretic similar to furosemide, but it is more potent, its diuretic effects persist for a longer period, and it does not cause as much potassium excretion (in dogs). While clinical use in dogs and cats thus far has been minimal, it potentially may be a useful adjunctive treatment for congestive heart failure in dogs and cats, particularly in patients that have become refractory to furosemide. Pharmacology/Actions T orsemide, like furosemide inhibits sodium and chloride reabsorp-tion in the ascending loop of Henle via interference with the chlo-ride-binding site of the 1Na +, 1K+, 2Cl-c otransport system. T orsemide increases renal excretion of water, sodium, potassi-um, chloride, calcium, magnesium, hydrogen, ammonium, and bi-carbonate. In dogs, excretion of potassium is affected much less so than is sodi um (20:1); this is approximately twice the ratio of Na:K excreted than with furosemide. In cats, torsemide's effects on potas-sium excretion appear to be similar to that of furosemide. In dogs, torse mide appears to have differing effects on aldosterone than fu-rosemide. When compared to furosemide, torsemide increases plas-ma aldosterone levels and inhibits the amount of receptor-bound aldoster one, however, additional research must be performed to determine the clinical signiﬁcance of these effects. Pharmacokinetics/Pharmacodynamics Limited information is available. Oral bioavailability has been re-ported to be between 80-100% in dogs and cats. Elimination half-life in d ogs is about 8 hours which is longer than furosemide. In dogs, diuretic activity begins within one hour of dosing, peaks at about 2 hours and persists for approximately 12 hours. In cats, peak diuresis occurs about 4 hours post-dose and per-sists for 12 hours. Contraindications/Precautions/Warnings T orsemide should not be used in patients with known hypersensi-tivity to it or other sulfonylureas, or in anuric patients. Use torsemide cautiously in patients with signiﬁcant hepatic dysfunct ion, hyperuricemia (may increase serum uric acid), or dia-betes mellitus (may increase serum glucose). The ARCI (Racing Commissioners International) has designat-ed this drug as a class 3 substance when used in horses.	pppbs.pdf
TThe injection should be administered IV slowly over a period of 2 min utes. Ototoxicity has occurred in human patients receiving rapid IV administration of other loop diuretics. Adverse Effects Adverse effect proﬁles for dogs and cats have not been established due to the limited use of this drug in veterinary medicine. Furosemide, a related drug, can 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 with nor-mal food and water intake are much less likely to develop water and el ectrolyte imbalances than those that do not. Other potential adverse effects include gastrointestinal distur-bances, hematologic effects (anemia, leukopenia), weakness, and restlessness. T orsemide, unlike furosemide, apparently only rarely causes signiﬁcant ototoxic effects in humans; very high doses in laboratory animals have induced ototoxicity. Reproductive/Nursing Safety No effects on fertility were noted when female and male rats were administered up to 25 mg/kg/day. No adverse teratogenic effects were seen when pregnant rats and rab bits were administered up to 15X (human dose) and 5X (hu-man dose), respectively. Larger doses did increase fetal resorptions, de creased average body weight, and delayed fetal ossiﬁcation. In humans, the FDA categorizes torsemide as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fe tus, 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 unknown if torsemide enters milk, but furosemide is dis-tributed in milk. Clinical signiﬁcance for nursing offspring is unknow n. Overdosage/Acute Toxicity In dogs, the oral LD50 is >2 grams/kg. Fluid and electrolyte imbal-ance is the most likely risk associated with an overdose. Consider gut emptying protocols for very large or quantity unknown inges-tions. Acute overdoses should generally be managed by observation with ﬂuid, electrolyte and acid-base monitoring; supportive treat-ment should be initiated if required. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving torsemide 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. ): Other diuretics have been associated with increasing the ototoxic or nephrotoxic risks of aminoglycosides. It is unknown if torsemide can also have these effects and if so, what the clinical signiﬁcance may be. !TAMPHOTERICIN B : Loop diuretics may increase the risk for nephro-toxicity development !TDIGOXIN : Can increase the area under the curve of torsemide by 50%, but is unlikely to be of signiﬁcance clinically; torsemide-induced hypokalemia may increase the potential for digoxin toxicity !TLITHIUM : T orsemide may reduce lithium clearance !TNSAIDs : Some NSAIDs may reduce the natriuretic effects of torsemide !TPROBENECID : Can reduce the diuretic efﬁcacy of torsemide !TSALICYLATES : T orsemide can reduce the excretion of salicylates Laboratory Considerations !Torsemide can affect serum electrolytes, glucose, uric acid, and BUN concentrations. Doses !TDOGS/CAT S: While no referenced dosages were located, torsemide could be considered for use as an alternative to furosemide particularly in those patients that have become refractory to furosemide therapy. T orsemide is approximately 10 times more potent than furosemide, so a starting dose of 10% of furosemide could be considered. As torsemide has a more persistent diuretic ef-fect (approximately 12 hours), dosing frequency may also be re duced. Monitoring !TSerum electrolytes, BUN, creatinine, glucose (if diabetic) !THydration status !TBlood pressure, if indicated !TClinical signs of edema, patient weight, if indicated Client Information !TContact veterinarian if clinical signs of water or electrolyte imbal-ance occur. Signs such as excessive thirst, lethargy, restlessness, increase d urination, GI distress or rapid heart rate may indicate electrolyte or water balance problems. Chemistry/Synonyms T orsemide is a pyridyl sulfonylurea loop diuretic that occurs as white to off-white, crystalline powder. It is practically insoluble in water and slightly soluble in alcohol. The injection has a p H >8. 3. T orsemide may also be known as torasemide, AC-3525, AC 4464, BM-02. 015, JDL-464, and Demadex®. International trade names include Torem® and Unat®. Storage/Stability/Compatibility T orsemide tablets and injectable solution should be stored be-low 40°C; preferably between 15-30°C (59-86°F). Protect from fre ezing. T orsemide injection is stable in Na Cl 0. 9%, Na Cl 0. 45%, or D5W. Whe n given IV undiluted, the manufacturer recommends ﬂushing the line to avoid incompatibilities with other drugs secondary to torsemide's high p H. 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: T orsemide Tablets: 5 mg, 10 mg, 20 mg, & 100 mg; Demadex® (Roche), generic; (Rx) T o rsemide Injection: 10 mg/m L in 2 and 5 m L amps; Demadex® (Roche)	pppbs.pdf
TRAMADOL HCL (tram-ah-doll) Ultram® OPIATE (mu-RECEPTOR) AGONIST Prescriber Highlights TT Synthetic mu-receptor opiate agonist that also inhibits reuptake of serotonin & norepinephrine TT May be useful as an analgesic or antitussive TT Not a controlled drug in USA, but has some potential for human abuse TT Appears well tolerated in dogs; sedation most likely ad-verse effect TT Avoid use with SSRIs (e. g., ﬂuoxetine) or MAOIs (e. g., selegiline) TT Relatively inexpensive Uses/Indications Tramadol may be a useful alternative or adjunct for the treatment of pain or cough in dogs and, potentially, cats. When used in com-bination with NSAIDs, it may be particularly useful for chronic pain condit ions in dogs. Epidurally administered tramadol may also be useful as an analgesic in horses, but no appropriate com-mercial dosage forms are presently available in the USA. Pharmacology/Actions Tramadol is a centrally acting opiate agonist that has primarily mu-receptor activity, but also inhibits reuptake of serotonin and nor-epinephrine. These pharmacologic actions all contribute to its an-algesic properties. At least one metabolite (O-desmethyltramadol; ODT; M1) has activity. When compared to tramadol in lab animal studies, M1 is 6 times more potent an analgesic and has 20 times more potency in binding to mu-receptors. Naloxone only partially antagonizes the analgesic effects of tramadol. Pharmacokinetics In dogs after oral administration, bioavailability is about 65%, but there is signiﬁcant interpatient variability. Volume of distribution is approximately 3. 8 L/kg. T otal body clearance and half-life are about 55 m L/kg/min and 1. 7 hours, respectively. Tramadol is extensively metabolized via several metabolic pathways. At least one metabolite (M1) has agonist activity, but is a minor metabolite in dogs; M1 has a half-life of about 2 hours after oral tramadol administration in dogs. One study in 8 cats using the immediate release oral tablet, showed high interpatient variability in absorption (with two cats there was not enough data to analyze). The elimination half-life for the parent compound was about 2. 5 hours; for the M1 metabolite, 4. 5 hours. Neurologic effects (mydriasis, dysphoria) were seen in 25% of cats (2 of 4 females) in the study group and the drug was observed to be unpalatable to cats. (Papich and Bledsoe 2007) In neonatal and weaned foals, tramadol has different pharma-cokinetics. After oral administration, higher bioavailability (53% vs. 20%), sho rter time to peak concentration (1 hr. vs. 1. 25 hr. ), and peak levels occurred with neonatal (2 week old) versus weaned foals (4 months old). Elimination half-life did not signiﬁcantly differ (ap-prox. 2 hours). The active metabolite (M1; ODT) remained above the rep orted therapeutic concentration for humans for 3 hours in neonatal foals and 8 hours in weaned foals. (Stewart, Boothe et al. 2006) Contraindications/Precautions/Warnings Tramadol is contraindicated in patients hypersensitive to it or other opioids. The combination product containing acetaminophen is contraindicated in cats. Use with caution in conjunction with other drugs that can cause CNS or r espiratory depression. Because tramadol has caused sei-zures in humans, it should be used with caution in animals with pree xisting seizure disorders or receiving other drugs that may reduce the seizure threshold. Like other opiates, tramadol should be used with caution in geriatric or severely debilitated animals. Patients with impaired renal or hepatic function may need dosage adjustments. While the risk of physical dependence occurring is less than that of sev eral other opiates, it has been reported in humans. The drug should be withdrawn gradually in animals that have received it chronically. While not a controlled substance in the USA, humans can potentially abuse tramadol and signiﬁcant diversion of the drug reportedly occurs. Veterinarians should be alert to “clients” seeking tramadol for their animals. Adverse Effects Tramadol appears to be well tolerated in dogs. Potentially, it could cause a variety of adverse effects associated with its pharmacologic actions, including: CNS effects (excessive sedation, agitation, anxi-ety, tremor, dizziness), or GI (inappetence, vomiting, constipation to diarrhea). V ery limited information is available on the adverse effects in cats. Dysp horia, mydriasis, and dose avoidance (unpalatability) have been reported. Approximately 10% of humans receiving the drug develop prurit us. Injectable tramadol may cause respiratory and cardiac depression. Reproductive/Nursing Safety In humans, the FDA categorizes tramadol 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 dosages 3-15 times usual, tramadol was embryotoxic and fe-totoxic in laboratory animals. Tramadol and its active metabolite enter maternal milk in very low levels, but the drug's safety in neo-nates has not been established. Overdosage/Acute Toxicity Acute oral overdosage may cause respiratory depression, lethargy, coma, seizure, cardiac arrest and death. There were 11 exposures to tramadol reported to the ASPCA Animal Po ison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases all 11 were dogs with 1 showing clini-cal signs (subdued). Treatment is primarily supportive (maintaining respiration, treating seizures with benzodiazepines or barbiturates, etc. ). Naloxone may NOT be useful in tramadol overdoses as it may only partially reverse some of the effects of the drug and may, in fact, increase the risk of seizures. Naloxone did not decrease the drug's lethality in tramadol overdoses given to mice. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving tramadol and may be of signiﬁcance in veterinary patients: T ! DIGOXIN : In humans, tramadol has been rarely linked to digoxin toxicity T ! MAO INHIBITORS (including amitraz and possibly, selegiline ): Poten-tial for serotonin syndrome; use together should be avoided	pppbs.pdf