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CHl ORPHENIRAm INE m Al EATE 185 also reportedly compatible with the following drugs: cime tidine HCl, lidocaine HCl, nafcillin sodium, and sodium bicarbonate. Chlorothiazide sodium is reportedly incompatible with the fol-lowing drugs: amikacin sulfate, chlorpromazine HCl, codeine phosphate, hydralazine HCl, insulin (regular), morphine sulfate, nore pinephrine bitartrate, polymyxin B sulfate, procaine HCl, prochlorperazine edisylate and mesylate, promazine HCl, promet-hazine HCl, streptomycin sulfate, tetracycline HCl, trifluopromaz-ine HCl, and vancomycin HCl. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Chlorothiazide Tablets: 250 mg & 500 mg; Diuril® (Merck); Diuri-gen® (Goldline); generic; (Rx) Chlorothiazide Oral Suspension: 50 mg/m L in 237 m L; Diuril® (Merck); (Rx) Chlorothiazide Sodium Powder for Injection (lyophilized): 500 mg (0. 25 g mannitol) in 20 m L vials; Diuril® (Merck); (Rx) chlorphenir Amine m Ale A te (klor-fen-ir-a-meen) Chlor-Trimetron® antihistamine Prescriber Highlights An alkylamine antihistamine used primarily for its anti-T T histamine/antipruritic effects; oc casionally used for CNS depressant (sedative) effects Contraindications: Hypersensitivity. Caution: narrow angle T T glaucoma, hypertension, GI or urinary obstruction, hyper-tension, hyperthyroidism, cardiovascular disease Adverse Effects: Sedation, anticholinergic effects, GI T T effects Uses/Indications Antihistamines are used in veterinary medicine to reduce or help prevent his tamine mediated adverse effects. Chlorpheniramine is one the more commonly used antihistamines in the cat for the treatment of pruritus. It may also be of benefit as a mild sedative in small animals due to its CNS depressant effects. Pharmacology/Actions Antihistamines (H 1-receptor antagonists) competitively inhibit histamine at H 1 re ceptor sites. They do not inactivate or prevent the release of histamine, but can prevent histamine's action on the cell. Besides their antihistaminic activity, these agents all have vary-ing degrees of anti cholinergic and CNS activity (sedation). Some antihistamines have antiemetic activity (e. g., diphen hydramine) or antiserotonin activity (e. g., cyproheptadine, azatadine). Pharmacokinetics Chlorpheniramine pharmacokinetics have not been described in domestic species. In humans, the drug is well absorbed after oral administration, but because of a relatively high degree of metabo-lism in the GI mucosa and the liver, only about 25-60% of the drug is avail able to the systemic circulation. Chlorpheniramine is well distributed after IV injection; the highest distribution of the drug (in rabbits) occurs in the lungs, heart, kidneys, brain, small intestine, and spleen. In humans, the apparent steady-state volume of distribution is 2. 5-3. 2 L/kg and about 70% is bound to plasma proteins. It is unknown if chlorphe-niramine is excreted into the milk. Chlorpheniramine is metabolized in the liver and practically all the drug (as metabolites and un changed drug) is excreted in the urine. In human patients with normal renal and hepatic function, the terminal serum half-life the drug ranges from 13. 2-43 hours. Contraindications/Precautions/Warnings Chlorpheniramine is contraindicated in patients who are hyper-sensitive to it or other antihistamines in its class. Because of their anticholinergic activity, antihis tamines should be used with caution in patients with angle closure glaucoma, prostatic hypertrophy, py-loroduodenal or bladder neck obstruction, and COPD if mucosal secretions are a problem. Addi tionally, they should be cautiously used in patients with hyperthyroidism, cardiovascular disease or hypertension. Adverse Effects Most commonly seen adverse effects are CNS depression (lethargy, somnolence) and GI effects (diarrhea, vomiting, anorexia). The seda-tive effects of antihistamines may diminish with time. Anticholinergic effects (dry mouth, urinary retention) are a possibility. The sedative effects of antihistamines may adversely affect the performance of working dogs. Chlorpheniramine may cause paradoxical excitement in cats. Palatability is also an issue with this drug and felines. 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 unknown if chlorpheniramine is excreted into milk; use with caution in dams nursing neonates. Overdosage/Acute Toxicity Overdosage may cause CNS stimulation (excitement to seizures) or depression (lethargy to coma), anticholinergic effects, respiratory depression, and death. Treatment consists of emptying the gut (if the ingestion was oral) using standard protocols. Induce emesis if the patient is alert and CNS status is stable. Administration of a saline cathartic and/or activated charcoal may be given after emesis or gastric lavage. Treatment of other clinical signs should be performed using symp-tomatic and supportive therapies. Phenytoin (IV) is recommended in the treatment of seizures caused by antihistamine overdoses in humans; barbiturates and diazepam should be avoided. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving chlorpheniramine and may be of significance in veterinary patients: ANTICOAg Ul ANTST! (heparin, warfarin ): Antihistamines may partially counteract the anticoagulation effects of heparin or warfarin m AO INHIb ITORST! (including amitraz, and possibly selegiline ): May prolong and exacerbate anticholinergic effects OTHER CNS DEPRESSANT DRUg ST! : Increased sedation can occur | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
186 CHl ORPROm Az INE HCl laboratory Considerations Antihistamines can decrease the wheal and flare response to T! anti gen skin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days before testing. Doses Note : Contents of sustained-release capsules may be placed on food, but should not be al lowed to dissolve before ingestion. DOg S:T! a) 4-8 mg (maximum of 0. 5 mg/kg) PO q8-12h PO; many cli-nicians use as adjunctive treatment of chemotherapy of mast cell tumors (Papich 2000) b) 4-12 mg (total dose) two to three times daily (Mac Donald 2002a) c) 2-8 mg (total dose) per dog PO every 12 hours, not to exceed 0. 5 mg/kg every 12 hours (Cote 2005) As a trial for pruritus in atopic dogs: a) 0. 4-0. 8 mg/kg two to three times daily (Rosychuk 2002) As a mild sedative: a) 0. 22 mg/kg PO q8h; 4-20 mg (total dose per day) divided q8-12h (Overall 2000) CATS:T! a) 2 mg (total dose) per cat PO every 12 hours (Cote 2005) b) 2-4 mg per cat q12-24h PO (Hnilica 2003c), (Rosychuk 2002) c) Most common dosage in cats is: 2 mg per cat two to three times daily (Mac Donald 2002a) For pruritus: a) 2-4 mg/cat twice daily; rarely may be maintained on once daily dosing. Palatability may be enhanced by dipping the split tablet into tuna fish “juice”, butter or petrolatum; placing split tablets into empty gelatin capsules or sprinkling or mix-ing timed release beads (partial contents of an 8 mg capsule) with food. (Messinger 2000) As a mild sedative: a) 1-2 mg per cat q12-24h (low dose), 2-4 mg/cat PO q12-24h (high dose) (Overall 2000) FERRETS:T! a) 1-2 mg/kg PO 2-3 times a day (Williams 2000) monitoring Clinical efficacy T! Adverse effects T! Client Information Chlorpheniramine is approved for use in humans; the oral dosage T! forms are either prescription or non-prescription agents, depend-ing on the product's labeling Most common adverse effects are drowsiness/sleepiness; cats may T! become excited Do not crush or allow animal to chew sustained-release products T! Chemistry/Synonyms A propylamine (alkylamine) antihistaminic agent, chlorphenira-mine maleate occurs as an odorless, white, crystalline powder with a melting point between 130-135° C and a p K a of 9. 2. One gram is soluble in about 4 m L of water or 10 m L of alcohol. Chlorpheniramine maleate may also be known as chlorphe-namini maleas; many trade names are available. Storage/Stability Chlorpheniramine tablets and sustained-release tablets should be stored in tight containers. The sustained-release capsules should be stored in well-closed containers. The oral solution should be stored in light-resistant containers; avoid freez ing. All chlorpheniramine products should be stored at room temperature (15-30°C). Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Chlorpheniramine Maleate Tablets: 2 mg (chewable), Chlo-Amine® (Hollister-Stier); (OTC); 4 mg tablets, Aller-Chlor® (Rugby); Aller-Chlor® (Rugby); Allergy ® (Major); Allergy Relief® (Zee Medical); ge-neric; (OTC); Chlorpheniramine Maleate Sustained-release Tablets & Capsules: 8 mg, 12 mg & 16 mg; Chlor-Trimeton® Allergy 8 or 12 Hour (Schering-Plough Healthcare); Efidac® 24 (Hogil); QDALL AR® (Atley); generic; (Rx & OTC) Chlorpheniramine Caplets: 8 mg (as tannate); ED-CHLOR-TAN® (Edwards Pharmaceuticals); (Rx)Chlorpheniramine Maleate Syrup: 2 mg/5 m L in 118 m L; Aller-Chlor® (Rugby); (OTC); Oral Suspension: 8 mg (as tannate) in 473 m L; Pediatan® (Pro Ethic); (Rx) Many combination products are available that combine chlorphe-niramine with decongestants, anal gesics, and/or antitussives. chlorprom Azine hcl (klor-proe-ma-zeen) Thorazine® phen O thiazine sedative/antiemetic Prescriber Highlights Prototype phenothiazine used primarily as an antiemetic, T T occasionally as a pre-med sedative Generally contraindicated in horses T T Negligible analgesic effects T T Dosage may need to be reduced in debilitated/geriatric T T animals, those with hepatic or cardiac disease or when combined with other agents Use with caution in dehydrated patients because phe-T T nothiazines can cause vasodilation & reduce perfusion; rehydrate before use Inject diluted solution IV slowly; do not inject into arter-T T ies; do not inject IM in rabbits May cause significant hypotension, cardiac rate abnor-T T malities, hypo-or hyperthermia; may cause extrapyrami-dal effects at high doses in cats Uses/Indications The clinical use of chlorpromazine as a neuroleptic agent has di-minished, but the drug is still used for its antiemetic effects in small animals and occasionally as a preoperative medi cation and tranquil-izer. As an antiemetic, chlorpromazine will inhibit apomorphine-induced emesis in the dog but not the cat. It will also inhibit the emetic effects of morphine in the dog. It does not inhibit emesis caused by copper sulfate, or digitalis glycosides. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CHl ORPROm Az INE HCl 187 Once the principle phenothiazine used in veterinary medicine, chlorpromazine has been largely supplanted by acepromazine. It has similar pharmacologic activities as acepromazine, but is less po-tent and has a longer duration of action. For further information, refer to the acepro mazine monograph. Pharmacokinetics Chlorpromazine is absorbed rapidly after oral administration, but undergoes extensive first pass metabolism in the liver. The drug is also well absorbed after IM injection, but onsets of action are slow-er than after IV administration. Chlorpromazine is distributed throughout the body and brain concentrations are higher than those in plasma. Approximately 95% of chlorpromazine in plasma is bound to plasma proteins (primarily albumin). The drug is extensively metabolized principally in the liver and kidneys, but little specific informa tion is available regarding its ex-cretion in dogs and cats. Contraindications/Precautions/Warnings Chlorpromazine causes severe muscle discomfort and swelling when injected IM into rabbits; use IV only in this species. Animals may require lower dosages of general anesthetics follow ing phenothiazines. Use cautiously and in smaller doses in animals with hepatic dysfunction, cardiac disease, or general debili-tation. Because of its hypotensive effects, phenothiazines are rela-tively contraindicated in patients with hypovolemia or shock, and in patients with tetanus or strychnine intoxication due to effects on the ex trapyramidal system. Intravenous injections must be diluted with saline to con-centrations of no more than 1 mg/m L and administered slowly. Chlorpromazine has no analgesic effects; treat animals with appro-priate analgesics to control pain. Dogs with MDR1 mutations (many Collies, Australian shep-herds, etc. ) may develop a more pronounced sedation that persists longer than normal with this agent. It may be prudent to reduce initial doses by 25% to determine the reaction of a patient identi-fied or suspect of having this mutation. Phenothiazines should be used very cautiously as restraining agents in aggressive dogs: it may make the animal more prone to startle and react to noises or other sensory inputs. Adverse Effects In addition to the possible effects listed in the acepromazine mono-graph (e. g., hypotension, contradictory effects such as CNS stimula-tion, bradycardia), chlorpromazine may cause extrapyramidal signs in the cat when used at high dosages. These can include tremors, shivering, rigidity and loss of the righting reflexes. Lethargy, diar-rhea, and loss of anal sphincter tone may also be seen. Horses may develop an ataxic reaction with resultant excitation and violent consequences. These ataxic periods may cycle with pe-riods of sedation. Because of this effect, chlorpromazine is rarely used in equine medicine today. 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. ) Chlorpromazine is thought to be excreted into maternal milk and safety to nursing offspring cannot be assured. Overdosage/Acute Toxicity Most small overdoses cause only somnolence; larger overdoses can cause serious effects including coma, agitation/seizures, ECG changes/arrhythmias, hypotension and extrapyramidal effects. Contact an animal poison control center in the event of a suspected large overdose or if multiple drugs are involved. Most overdoses can be handled by monitoring the patient and treating signs as they occur; massive oral overdoses should definite-ly be treated by emptying the gut if possible. Hypotension should not be treated with epinephrine; use either phenylephrine or nor-epinephrine (levarterenol). Seizures may be controlled with barbi-turates or diazepam. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving chlorpromazine or other phenothiazines and may be of significance in veterinary patients: ACETAm INOPHENT! : Possible increased risk for hypothermia ANTACIDST! : May cause reduced GI absorption of oral phenothiazines ANTIDIARRHEAl m Ix TUREST! (e. g., kaolin/pectin, bismuth subsali cylate mixtures ): May cause reduced GI absorption of oral phenothiazines CNS DEPRESSANT Ag ENTST! (barbiturates, narcotics, anesthetics, etc. ): May cause additive CNS depression if used with phenothiazines DIPy RONET! : May cause serious hypothermia EPINEPHRINET! : Phenothiazines block alpha-adrenergic receptors and concomitant epinephrine can lead to unop posed beta-activ-ity causing vasodilation and increased cardiac rate OPIATEST! : May enhance the hypotensive effects of the phenothiaz-ines; dosages of chlorpromazine may need to be reduced when used with an opiate ORg ANOPHOSPHATE Ag ENTS T! : Phenothiazines should not be given within one month of worming with these agents as their effects may be potentiated PARAQUATT! : T oxicity may be increased by chlorpromazine PHENy TOINT! : Metabolism may be decreased if given concurrently with phenothiazines PHy SOSTIgm INET! : T oxicity may be en hanced by chlorpromazine PROCAINET! : Activity may be enhanced by phenothiazines PROPRANOl Ol T! : Increased blood levels of both drugs may result if administered with phenothiazines QUINIDINET! : With phenothiazines may cause additive cardiac depression Doses DOg S:T! As an antiemetic: a) 0. 5 mg/kg IV, IM or SC three to four times daily (Dowling 2003a) b) 0. 5 mg/kg q6-8h IM or SC (Papich 2000) c) 0. 2-0. 4 mg/kg SC, IM q8h (Washabau 2006a) d) 0. 11-0. 44 mg/kg IM 3-4 times a day (Hall 2000) As a sedative/restraining agent: a) 3 mg/kg PO q12h; 0. 5 mg/kg IM or IV q12h (Davis 1985b) As a preanesthetic: a) up to 1. 1 mg/kg IM 1-1. 5 hours prior to surgery (Booth 1988a) As a muscle relaxant during tetanus: a) 2 mg/kg IM twice daily (Morgan 1988) As an adjunctive treatment for amphetamine toxicosis: a) 10-18 mg/kg IV (Dumonceaux 1995) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
188 CHl ORPROPAm IDE CATS:T! As an antiemetic: a) 0. 5 mg/kg IV, IM or SC three to four times daily (Dowling 2003a) b) 0. 5 mg/kg q6-8h IM or SC (Papich 2000) c) 0. 22-0. 44 mg/kg IM 3-4 times a day (Hall 2000) As a sedative/restraining agent: a) 3 mg/kg PO once daily; 0. 5 mg/kg IM or IV once daily (Davis 1985b) As a preanesthetic: a) up to 1. 1 mg/kg IM 1-1. 5 hours prior to surgery (Booth 1988a) CATTl E:T! a) Premedication for cattle undergoing standing procedures: Up to 1 mg/kg IM (may cause regurgitation if animal undergoes general anesthesia) (Hall and Clarke 1983) b) 0. 22-1 mg/kg IV; 1-4. 4 mg/kg IM (Howard 1986) HORSES: T! (Note : ARCI UCGFS Class 2 Drug) Note : Because of side effects (ataxia, panic reaction) this drug is not recommended for use in horses; use acepromazine or promazine if phenothiazine therapy is desired. SWINE:T! a) Premedication: 1 mg/kg IM (Hall and Clarke 1983) b) 0. 55-3. 3 mg/kg IV; 2-4 mg/kg IM (Howard 1986) c) Restraint: 1. 1 mg/kg IM (effects are at peak in 45-60 min-utes); Prior to barbiturate anesthesia: 2-4 mg/kg IM (Booth 1988a) SHEEP & g OATS:T! a) 0. 55-4. 4 mg/kg IV, 2. 2-6. 6 mg/kg IM (Lumb and Jones 1984) b) Goats: 2-3. 5 mg/kg IV q5-6h (Booth 1988a) monitoring Cardiac rate/rhythm/blood pressure if indicated and possible to T! measure Degree of tranquilization/anti-emetic activity if indicated T! Body temperature (especially if ambient temperature is very hot T! or cold) Client Information Avoid getting solutions on hands or clothing; contact dermatitis T! may de velop. May discolor the urine to a pink or red-brown color; this is not T! abnormal. Chemistry/Synonyms A propylamino-phenothiazine derivative, chlorpromazine is the prototypic phenoth iazine agent. It occurs as a white to slightly creamy white, odorless, bitter tasting, crystalline powder. One gram is soluble in 1 m L of water and 1. 5 m L of alcohol. The commercially available injection is a solution of chlorpromazine HCl in sterile wa-ter at a p H of 3-5. Chlorpromazine HCl may also be known as aminazine, or chlo-rpromazini hydrochloridum; many trade names are available. Storage/Stability/Compatibility Protect from light and store at room temperature; avoid freezing the oral solution and injection. Dispense oral solution in amber bottles. Store oral tablets in tight containers. Do not store in plastic syringes or IV bags for prolonged periods as the drug may adsorb to plastic. Chlorpromazine will darken upon prolonged exposure to light; do not use solutions that are darkly colored or if precipitates have formed. A slight yellowish color will not affect potency or efficacy. Alkaline solutions will cause the drug to oxidize. The following products have been reported to be compatible when mixed with chlorpromazine HCl injection: all usual intravenous fluids, ascorbic acid, atropine sulfate, butorphanol tartrate, diphen-hydramine, droperidol, fentanyl citrate, glycopyrrolate, heparin so-dium, hydromorphone HCl, hydroxyzine HCl, lidocaine HCl, mep-eridine, metoclopramide, metaraminol bitartrate, morphine sul fate, pentazocine lactate, promazine HCl, promethazine, scopolamine HBr, and tetracycline HCl. The following products have been reported as being incompatible when mixed with chlorpro mazine: aminophylline, amphotericin B, chloramphenicol sodium succinate, chlorothiazide sodium, dimen-hydrinate, methicillin sodium, methohexital sodium, nafcillin so-dium, penicillin g potassium, pentobarbital sodium, phenobarbital sodium, and thiopental sodium. Compatibility is dependent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references or a hospital pharmacist for more spe-cific in formation. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Chlorpromazine Tablets: 10 mg, 25 mg, 50 mg, 100 mg & 200 mg; Thorazine® (Glaxo Smith Kline); generic; (Rx) Rectal suppositories: 100 mg (as base); Thorazine® (Glaxo Smith-Kline); (Rx)Injection: 25 mg/m L in 1 m L and 2 m L amps; Thorazine® (Glaxo S-mith Kline); generic; (Rx) chlorprop Amide (klor-proe-pa-mide) Diabenese® sulf Onylurea antidiabetic Prescriber Highlights Oral sulfonylurea antidiabetic agent sometimes used in T T dogs or cats for diabetes in sipidus; potentially for diabe-tes mellitus Many contraindications/cautions T T Most likely adverse effects are hypoglycemia or GI T T distress Uses/Indications While chlorpropamide could potentially be of benefit in the adjunc-tive treatment of diabetes mellitus in small animals, its use has been primarily for adjunctive therapy in diabetes insipidus in dogs and cats. Pharmacology/Actions Sulfonylureas lower blood glucose concentrations in both diabetic and non-diabet ic patients. The exact mechanism of action is not known, but these agents are thought to exert the effect primarily by stimulating the beta cells in the pancreas to secrete additional endogenous insulin. On going use of the sulfonylureas appears to en- | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CHl ORPROPAm IDE 189 hance peripheral sensitivity to insulin and reduce the production of hepatic basal glucose. The mechanisms causing these effects are yet to be fully ex plained. Chlorpropamide has antidiuretic activity, pre-sumably by potentiating vasopressin's ef fects on the renal tubules. It may also stimulate secretion of vasopressin. Pharmacokinetics Chlorpropamide is absorbed well from the GI tract. Its distribution characteris tics have not been well described, but it is highly bound to plasma proteins and is excreted into milk. Elimination half-lives have not been described in domestic animals, but in humans the elimination half-life is about 36 hours. The drug is both metabo-lized in the liver and excreted unchanged. Elimi nation of chlorpro-pamide is enhanced in alkaline urine; decreased in acidic urine. Contraindications/Precautions/Warnings Oral antidiabetic agents are considered con traindicated with the following conditions: severe burns, severe trauma, severe infec-tion, diabetic coma or other hypoglycemic conditions, major sur-gery, ketosis, ketoacidosis, or other significant aci dotic conditions. Chlorpropamide should only be used when its potential benefits outweigh its risks during untreated adrenal or pituitary insuffi-ciency, thyroid, cardiac, renal or hepatic function im pairment, pro-longed vomiting, high fever, malnourishment or debilitated condi-tion, or when fluid retention is present. Adverse Effects Hypoglycemia and GI disturbances are the most common adverse effects noted with this agent. Syndrome of inappropriate antidi-uretic hormone (SIADH), anorexia, diarrhea, hepatotoxicity, skin eruptions, lassitude or other CNS effects, and hematologic toxicity are all potentially possible. Reproductive/Nursing Safety Safe use during pregnancy has not been established. 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. ) Chlorpropamide enters maternal milk; in humans it is not rec-ommended for use during nursing. Overdosage/Acute Toxicity Profound hypoglycemia is the greatest concern after an overdose. Gut emptying protocols should be employed when warranted. Because of its long half-life, blood glucose monitoring and treat-ment with parenteral glucose may be required for several days. Overdoses may require additional monitoring (blood gases, serum electrolytes) and supportive therapy. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving chlorpropamide and may be of significance in veterinary patients: Al COHOl T! : A disulfiram-like reaction (anorexia, nausea, vomiting) has been reported in humans who have ingested alcohol within 48-72 hours of receiving chlorpropamide b ARb ITURATES!! : Barbiturate duration of action may be prolonged The following drugs may potentiate hypoglycemia if administered with chlorpropamide, or be displaced by chlorpropamide from plasma proteins thereby causing enhanced pharmacologic effects of the two drugs involved: CHl ORAm PHENICOl!! b ETAbl OCKERS!!m AOI'S !! (including amitraz and possibly, selegiline) NSAIDS !! PROb ENECID!! SAl ICyl ATES!! SUl FONAm IDES !! WAR FARINT! The following drugs may potentiate hyperglycemia if administered with chlorpropamide: CAl CIUm CHANNEl bl OCKERS!! (e. g., diltiazem, amlodipine ) CORTICOSTEROIDS!! ESTROg ENS!! ISONIAz ID!! PHENOTHIAz INES!! PHENy TOIN!! THIAz IDES!! THy ROID m EDICATIONST! laboratory Considerations Chlorpropamide may mildly increase values of T! liver enzymes, b UN, or serum creatinine. Doses For adjunctive therapy in diabetes insipidus in dogs and cats. Beneficial effects may be seen in less than 50% of animals treated. A trial period of at least one week of therapy should be given be fore assessing effect. DOg S & CATS:T! For adjunctive treatment of diabetes insipidus in animals with partial ADH deficiency: a) 10-40 mg/kg PO daily (Randolph and Peterson 1994), (Beh-rend 2003b) b) Dogs: 50-250 mg (total dose) PO daily; Cats: 50 mg (total dose) PO daily (Hoskins 2005b) monitoring Serum electrolytes, plasma and urine osmolarity, urine output; T! if used for DI Blood Glucose T! Chemistry/Synonyms An oral sulfonylurea antidiabetic agent, chlorpropamide occurs as a white, crystalline powder having a slight odor. It is practically in-soluble in water. Chlorpropamide may also be known as: chlorpropamidum, Anti-D®, Chlomide®, Clordiabet®, Copamide®, Deavynfar®, Diabecontrol®, Diabeedol®, Diabemide®, Diabenese®, Diabet®, Diabexan®, Diabiclor®, Diabines®, Diabitex®, Dibecon®, Glicoben ®, Gliconorm®, Glicorp®, Glycemin®, Glymese®, Hypomide®, Idle ®, Insogen®, Normoglic®, Novo-Propamide®, Propamide®, or Trane®. Storage/Stability Chlorpropamide tablets should be stored in well-closed contain ers at room temperature. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Chlorpropamide Tablets: 100 mg & 250 mg; Diabenese® (Pfizer); generic; (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
190 CHl ORTETRACy Cl INE chlortetr Acycline (klor-te-tra-sye-kleen) Aureomycin®, Pennchlor® tetracycline antibi O tic Prescriber Highlights Tetracycline antibiotic used primarily in water or feed T T treatments or topically for oph thalmic use Many bacteria are now resistant; may still be very useful T T to treat mycoplasma, rickettsia, spirochetes, & Chlamydia Contraindications: Hypersensitivity. Extreme caution: T T Pregnancy. Caution: liver, renal in sufficiency Adverse Effects: GI distress, staining of developing teeth T T & bones, superinfections, photosensitivity Drug-drug; drug-lab interactions T T Uses/Indications There are a variety of approved chlortetracycline products for use in food ani mals. It may also be useful in treating susceptible infections in dogs, cats, birds and small mammals (not Guinea pigs). For more information, refer to the Doses section below. Pharmacology/Actions T etracyclines generally act as bacteriostatic antibiotics inhibiting pro-tein synthesis by reversibly binding to 30S ribosomal subunits of sus-ceptible organisms thereby preventing bind ing to those ribosomes of aminoacyl transfer-RNA. T etracyclines are believed to reversibly bind to 50S ribosomes and additionally alter cytoplasmic membrane per-meability in susceptible organ isms. In high concentrations, tetracy-clines can inhibit protein synthesis by mammalian cells. As a class, the tetracyclines have activity against most mycoplas-ma, spirochetes (including the Lyme disease organism), Chlamydia, and Rickettsia. Against gram-positive bacteria, the tetracy clines 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: Actinomyces spp., Bacillus anthracis, Clostridium perfringens and tetani, Listeria monocytogenes, and Nocardia. Among gram-negative bacteria that tetracyclines usually have in vitro and in vivo ac tivity include Bordetella spp., Brucella, Bartonella, Haemophilus spp., Pasturella multocida, Shigella, and Yersinia pestis. Many or most strains of E. coli, Klebsiella, Bacteroides, Enterobacter, Proteus and Pseudomonas aeruginosa are resistant to the tetracyclines. While most strains of Pseu domonas 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, chlortetracycline, and tetracycline share nearly identical spectrums of activity and patterns of cross-resistance and a tetracycline susceptibility disk is usually used for in vitro testing for chlortetracycline susceptibility. Pharmacokinetics Refer to the oxytetracycline monograph for general information on the pharma cokinetics of tetracyclines. Contraindications/Precautions/Warnings Chlortetracycline is contraindicated in pa tients hypersensitive to it or other tetracyclines. Because tetracyclines can retard fetal skeletal devel opment and discolor deciduous teeth, they should only be used in the last half of pregnancy when the benefits outweigh the fetal risks. Oxytetracycline, chlortetracycline and tetracycline are consid-ered more likely to cause these abnormalities than either doxycy-cline or minocycline. In patients with renal insufficiency or hepatic impairment, chlo-rtetracycline must be used cau tiously. Lower than normal dosages are recommended with enhanced monitoring of renal and hep atic function. Avoid concurrent administration of other nephrotoxic or hepatotoxic drugs. Because it may cause clostridial enterotoxemia in guinea pigs, chlortetracycline should not be used this species. Adverse Effects Chlortetracycline 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 dete-riorates secondary to drug accumulation, this effect may be exacer-bated. In ruminants, high oral doses can cause ruminal microflora de-pression and ruminoreticular stasis. Rapid intravenous injection of undiluted propylene glycol-based products can cause intravascular hemolysis with resultant hemoglobinuria. Propylene glycol based products have also caused car diodepressant effects when adminis-tered to calves. In small animals, tetracyclines can cause nausea, vomiting, an-orexia, and diarrhea. Cats do not tol erate oral tetracycline or oxytet-racycline very well; signs of colic, fever, hair loss, and depression may be seen. There are reports that long-term tetracycline use may cause urolith formation in dogs. Horses that are stressed by surgery, anesthesia, trauma, etc., may break with severe diarrheas after receiving tetracyclines (especially with oral administration). T etracycline therapy (especially long-term) may result in over-growth (superinfections) of non-sus ceptible bacteria or fungi. T etracyclines have been associated with photosensitivity reac-tions and, rarely, hepatotoxicity or blood dyscrasias. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category D (tetracy-clines-general) 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. ) T etracyclines are excreted in milk, but because much of the drug will 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, an-orexia, and/or diarrhea). Should the patient develop severe emesis or diarrhea, fluids and elec trolytes should be monitored and replaced if necessary. Chronic overdoses may lead to drug accumu lation and nephrotoxicity. High oral doses given to ruminants, can cause ruminal microflora depression and ruminoreticular stasis. Rapid intravenous injection of undiluted propylene glycol-based products can cause intravas-cular 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 quantities of drug could exacerbate this effect if given too rapidly | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CHORIONIC g ONADOTROPIN (HCg) 191 IV. If the drug must be given rapidly IV (less than 5 minutes), some clinicians recommend pre-treating the animal with intravenous calcium glu conate. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving chlortetracycline and may be of significance in veterinary patients: b ETAl ACTAm OR Am INOgly COSIDE ANTIb IOTICS T! : Bacteriostatic drugs, like the tetracyclines, may interfere with bactericidal activ-ity of the penicillins, cephalosporins, and aminoglycosides; there is some controversy regarding the actual clinical significance of this interaction, however DIg Ox INT! : T etracyclines may increase the bioavailability of digoxin in a small percentage of patients (human) and lead to digoxin toxicity. These effects may persist for months after discontinua-tion of the tetra cycline. DIVAl ENT OR TRIVAl ENT CATIONS T! (oral antacids, saline cathartics or other g I products containing aluminum, calcium, iron, magne sium, 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 cations; it is recommended that all oral tetracyclines be given at least 1-2 hours before or after the cation-containing products WARFARINT! : T etracyclines may depress plasma prothrombin activ-ity and patients on anticoagulant (e. g., war farin) therapy may need dosage adjustment. laboratory Considerations T etracyclines (not minocycline) may cause falsely elevated values T! of urine catecholamines when using fluorometric methods of de-termination. T etracyclines reportedly can cause false-positive T! 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 results in determining urine glucose when using the glucose oxi-dase method (Clinistix®, Tes-Tape®). Doses DOg S/CATS:T! For susceptible infections: a) 25 mg/kg PO q6-8h (Papich 1992) b) T o prevent recurrence of mycoplasma or chlamydial con-junctivitis in large catteries where topical therapy is imprac-tical: soluble chlortetracycline powder in food at a dose of 50 mg per day per cat for 1 month (Carro 1994) RAbb ITS/RODENTS/Sm All m Amm Al S:T! Note : Not recommended for use in guinea pigs a) Rabbits: 50 mg/kg PO q12-24h (Ivey and Morrisey 2000) b) Chinchillas: 50 mg/kg PO q12h (Hayes 2000) c) Hamsters: 20 mg/kg IM or SC q12h; Mice: 25 mg/kg SC or IM q12h; Rats: 6-10 mg/kg SC or IM q12h (Adamcak and Otten 2000) b IRDS:T! a) For the treatment of chlamydiosis: In small birds add chlo-rtetracycline to food in a con centration of 0. 05%; larger psit-tacines require 1% CTC. (Flammer 1992) b) Ratites: 15-20 mg/kg PO three times daily (Jenson 1998) c) Pigeons: 50 mg/kg PO q6- 8h; or 1000-1500 mg/gallon drinking water; in warm weather mix fresh every 12 hours. Best used in combination with tylosin for ornithosis com-plex; calcium inhibits absorption therefore grit and layer pel-lets should be withheld during treatment. (Harlin 2006) CATTl E AND SWINE:T! For susceptible infections: a) 6-10 mg/kg IV or IM; 10-20 mg/kg PO ( Note : Although not specified in this reference, chlortetracycline is generally ad-ministered once daily. ) (Howard 1993) Chemistry/Synonyms A tetracycline antibiotic, chlortetracycline occurs as yellow, odor-less crystals. It is slightly soluble in water. Chlortetracycline may also be known as clortetraciclina, A-377, NRRL-2209, SF-66, Aureomycin or CLTC® 100 MR. Storage/Stability Chlortetracycline should be stored in tight containers and pro-tected from light. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: There are several feed additive/water mix preparations available containing chlortetracycline. Trade names include Aureomycin®; (Fort Dodge), CTC ® (Agri Labs) CLTC ® 100 MR (Philbro); (AL Labs); CLTC ® 100 MR (Pennfield/Durvet). There are also combi-nation products containing chlortetracycline and sulfamethazine (Aureomycin Sulmet®, Aureo S 700®), chlortetracycline, sulfamet-hazine and penicillin (Aureomix 500®, Pennclor SP 250 & 500®), chlortetracycline, sulfathiazole, and penicillin (Aureozol 500®) See individual labels for more information. HUm ANl Ab El ED PRODUCTS: None Chondroitin Sulfate — See Glucosamine/Chondroitin chorionic gon Adotropin (hcg) (kor-ee-on-ic goe-nad-oh-troe-pin) Chorulon® repr Oductive h Orm One Prescriber Highlights Human hormone that mimics luteinizing hormone & T T some FSH activity; used for a va riety of theriogenology conditions in many species Only administered parenterally T T Contraindications: Androgen responsive neoplasias, T T hypersensitivity Adverse Effects: Antibodies/hypersensitivity, pain on T T injection Uses/Indications The veterinary product's labeled indication is for “parenteral use in cows for the treatment of nymphomania (frequent or constant heat) due to cystic ovaries. ” It has been used for other purposes in several species; refer to the Dosage section for more information. Pharmacology/Actions HCG mimics quite closely the effects of luteinizing hormone (LH) but also has some FSH-like activity. In males, HCG can stimulate the differentiation of, and androgen production by, testicular inter- | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
192 CHORIONIC g ONADOTROPIN (HCg) stitial (Leydig) cells. It may also stimulate testicular descent when no anatomical abnormality is present. In females, HCG will stimulate the corpus luteum to produce pro-gesterone and can induce ovula tion (possibly also in patients with cystic ovaries). In the bitch HCG will induce estrogen secretion. Pharmacokinetics HCG is destroyed in the GI tract after oral administration, so it must be given parenterally. After IM injection, peak plasma levels occur in about 6 hours. HCG is distributed primarily to the ovaries in females and to the testes in males, but some may also be distributed to the proximal tubules in the renal cortex. HCG is eliminated from the blood in biphasic manner. The ini-tial elimination half-life is about 11 hours and the terminal half-life is approximately 23 hours. Contraindications/Precautions/Warnings In humans, HCG is contraindicated in patients with prostatic car-cinoma or other androgen-dependent neoplasias, precocious puber-ty or having a previous hypersen sitivity reaction to HCG. No labeled contraindications for veterinary patients were noted, but the above human contraindications should be used as guidelines. Antibody production to this hormone has been reported after repetitive use, resulting in diminished effect. Adverse Effects Potentially, hypersensitivity reactions are possible with this agent. HCG may cause abortion in mares prior to the 35th day of preg-nancy, perhaps due to increased es trogen levels. No other reported adverse reactions were noted for veterinary patients. In humans, HCG has caused pain at the injection site, gyneco-mastia, headache, depression, irritabil ity, and edema. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category X for use dur-ing pregnancy (Studies in animals or humans demonstrate fetal ab-normalities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any possible ben-efit. ) It is unknown if HCG enters maternal milk. Overdosage/Acute Toxicity No overdosage cases have been reported with HCG. Drug/lab Interactions No interactions have apparently been reported with HCG. Doses DOg S:T! For cryptorchidism: a) 500 Units injected twice weekly for 4-6 weeks (Mc Donald 1988) For HCG Challenge test (to determine if testicular tissue remains in castrated male dogs; in fe males to diagnose sexual differentia-tion disorders or if functional ovarian tissue remains after ovari-ohysterectomy):a) Male dogs or females with suspected sexual differentiation disorder: Take sample for resting testosterone level. Admin-ister 44 micrograms/kg HCG IM and take a 4 hour post sample. Female dogs: 100-1000 IU IM during apparent estrous epi-sode. Measure progesterone level in 5-7 days. If above 1 ng/ m L, this indicates functional ovarian tissue. (Shille and Olson 1989)T o produce luteinization of a persistent follicular cyst: a) 500 IU IM; repeat in 48 hours. If effective, will convert from proestrus to estrus in 1-2 days and sexual behavior should stop within 2 weeks. (Barton 1988) For infertile bitches cycling normally with low progesterone due to lack of corpus luteum for mation: a) Next cycle, give 500 IU HCG SC on days 10-11 of heat cycle or when vaginal smear in dicates breeding readiness. Breed 2 days after HCG administration. (Barton and Wolf 1988) For male infertility secondary to low testosterone, LH and FSH: a) HCG 500 IU SC twice weekly for 4 weeks. Add PMSG (Preg-nant Mare Serum Go nadotropin) 20 IU/kg SC 3 times weekly. If PMSG is unavailable, use FSH-P at same dose (1 mg FSH = ≈10-14 IU). Continue for 3 months. Once spermatogen-esis ensues, may continue with HCG only. (Barton and Wolf 1988) CATS:T! For HCG Challenge test (to determine if testicular tissue remains in castrated male cats; in fe males to diagnose sexual differentia-tion disorders or if functional ovarian tissue remains after ovari-ohysterectomy):a) Male cats or females with suspected sexual differentiation dis-order: Take sample for resting testosterone level. Administer 250 micrograms HCG IM and take a 4 hour post sample. Queens: 50-100 IU IM during apparent estrous episode. Measure progesterone level in 5-7 days. If above 1 ng/m L, this indicates functional ovarian tissue. (Shille and Olson 1989) For infertility, reduced libido, testis descent in male cats:a) 50-100 IU repeated if necessary (Verstegen 2000) For infertility in queens due to confirmed ovulation failure:a) 100-500 IU IM (Barton and Wolf 1988) T o induce ovulation in anestrus queens:a) Give FSH-P 2 mg IM daily (for up to 5 days) until estrus is observed. Give 250 micro grams HCG on first and second day of estrus (Kraemer and Bowen 1986) After artificial insemination: a) 50-75 IU IM immediately after insemination; repeat insemi-nation and injection in 24 hours (Sojka 1986) FERRETS:T! a) 100 IU IM; repeat in 1 week as necessary. Most effective 14 days after onset of estrus. (Williams 2000) RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Guinea pigs: For cystic ovaries: 1000 Units/animal IM, repeat in 7-10 days (Adamcak and Otten 2000) b IRDS:T! T o reduce feather plucking (especially in female birds): a) Dosage is empirical; 500-1,000 units/kg IM. If no response in 3 days, repeat. If no response after second injection, unlikely to be of benefit at any dose. If reduces feather plucking, will need to repeat after 4-6 weeks. Major drawback is that with repeated usage, time between treatments is reduced. (Light-foot 2001) CATTl E:T! For treatment of ovarian cysts:a) 10,000 Units deep IM or 2500-5000 Units IV, may repeat in 14 days if animal's behav ior or physical exam indicates a need for retreatment. Alternatively, 500-2500 Units in jected di-rectly into the follicle. (Package Insert; Follutein®—Solvay) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CHROm IUm 193 HORSES:T! For cryptorchidism: a) Foals: 1000 Units injected twice weekly for 4-6 weeks (Mc-Donald 1988) ( Note : Many clinicians believe that medical treatment is unwarranted and that surgery should be per-formed. ) T o induce ovulation in early estrus when one, large, dominant follicle that is palpable with a di ameter >35 mm is present: a) HCG: 2000-3000 IU IV (preferable to treat mare 6 hours before mating) (Hopkins 1987) For treatment of persistent follicles during the early transition period:a) 1000-5000 IU (results are variable) (Van Camp 1986) T o hasten ovulation and reduce variability of estrus after prostaglandin synchronization: a) HCG: 1500-3300 IU 5-6 days after the second prostaglan-din treatment or on the first or second day of estrus (Bristol 1986) Chemistry/Synonyms A gonad-stimulating polypeptide secreted by the placenta, chori-onic gonadotropin is obtained from the urine of pregnant women. It occurs as a white or practically white, amorphous, lyophilized powder. It is soluble in water and practically insoluble in alcohol. One International Unit of HCG is equal to one USP unit. There are at least 1500 USP Units per mg. Chorionic gonadotropin may also be known as: human chori-onic gonadotropin, HCG, h CG, LH 500, CG, chorionic gonadotro-phin, dynatropin, gonadotropine chorionique, gonadotrophinum chorionicum, choriogonadotrophin, chorionogonadotropin, preg-nancy-urine hormone, or PU; there are many trade names inter-nationally. Storage/Stability Chorionic gonadotropin powder for injection should be stored at room temperature (15-30°C) and protected from light. After re-constitution, the resultant solution is stable for 30-90 days (de-pending on the product) when stored at 2-15°C. The labels for the veterinary products, Chorulon® and P. G. 600® state to use the vial immediately after reconstituting with the supplied diluent. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Chorionic Gonadotropin (HCG) Injection: 10,000 Units per 10 m L double vial packs containing 10,000 USP units per vial with bacte-riostatic water for injection; single dose 10 m L vials of freeze-dried powder and five 10 m L vials of sterile diluent; Chorulon ® (Intervet); (Rx). Approved for use in cows and finfish. No withdrawal time is required when used as labeled. Chorionic Gonadotropin freeze-dried powder: Single dose 5 m L vi-als when reconstituted contains pregnant mare serum gonadotro-pin (PMSG) 400 IU and human chorionic gonadotropin (h CG) 200 IU; five dose 25 m L vials that when reconstituted contains pregnant mare serum gonadotropin (PMSG) 2,000 IU and human chorionic gonadotropin (h CG) 1,000 IU; P. G. 600 ® (Intervet); (OTC). Ap-proved for use in swine (prepuberal gilts and sows at weaning); no meat withdrawal time is required when used as labeled. HUm ANl Ab El ED PRODUCTS: Chorionic Gonadotropin Powder for Injection: 5,000 units/vial with 10 m L diluent (to make 500 units/m L; 10,000 units/vial with 10 m L diluent (to make 1,000 units/m L); 20,000 units/vial with 10 m L diluent (to make 2,000 units/m L) in 10 m L vials; Profasi® (Se-rono); Choron 10® (Forest); Gonic® (Hauck); Novarel® (Ferring); Pregnyl ® (Organon); generic; (Rx) chromium chromium picolin A te (kroe-mee-um pik-oh-lin-ate) transiti On trace metal Prescriber Highlights Trace metal “nutraceutical” that may be useful as an ad-T T junctive treatment for diabetes mellitus & obesity in cats Efficacy in question, but probably safe T T Uses/Indications Chromium supplementation may be useful in the adjunctive treat-ment of diabetes mellitus or obesity, particularly in cats; there is controversy whether this treatment is beneficial. It does not appear to be useful in dogs with diabetes mellitus. Pharmacology/Actions Metallic chromium has no pharmacologic activity, but other va-lence states have activity. Chromium VI (hexavalent form) is used in the welding and chemical industries and is considered a carcino-gen. Chromium III (trivalent) is the form used in supplements and found naturally in foods. Chromium is thought to play a role in insulin function. It is an active component of so-called glucose tol-erance factor (GTF). GTF is a complex of molecules that includes glycine, glutamic acid, cystiene and nicotinic acid. Chromium's ex-act role in carbohydrate and nitrogen metabolism is not clear. It does not lower blood glucose levels in normal patients. In humans, chromium deficiency can cause impaired tolerance to glucose and insulin function, increased serum cholesterol and triglyceride lev-els, neuropathy, weight loss, impaired nitrogen metabolism, and decreased respiratory function. Pharmacokinetics Chromium is not absorbed very well from the GI tract and most of a dose is excreted in the feces. When given as a salt (picolinate, chloride, nicotinate), lipophilicity and solubility are increased and absorption is enhanced. Absorbed chromium is eliminated via the kidneys. Contraindications/Precautions/Warnings Chromium supplements could, potentially, exacerbate renal insuf-ficiency; use with caution in these patients. Because the picolinate salt can potentially alter behavior, consider using chromium chlo-ride, or chromium nicotinate in patients receiving SSRI's or other behavioral therapies. Adverse Effects Chromium supplements (Cr III) at usual dosages appear to be well tolerated. Some human patients have complained of cognitive, per-ceptual, and motor dysfunction after receiving the picolinate salt. Reproductive/Nursing Safety In humans, chromium (up to 8 mcg/kg) is probably safe to use in pregnancy but information remains sketchy. Because cats may receive much higher dosages than the human dosages for treating diabetes, use cautiously in pregnant animals. Chromium supplements are likely to be safe to use in lactating animals. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
194 CIm ETIDINE Overdosage/Acute Toxicity Little information on acute overdoses was located. There are at least two case reports of women developing renal failure after taking ex-cessive doses of chromium picolinate. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving chromium and may be of significance in veterinary patients: CORTICOSTEROIDST! : May increase the urinary excretion of chromium HT!2 bl OCKERS (cimetidine, ranitidine, famotidine, etc. ) or PROTON PUm P INHIb ITORS (PPI's, omeprazole, etc. ): May decrease chromium levels by inhibiting their absorption; clinical significance is unclear NSAIDs T! : May increase the absorption and retention of chromium; clinical significance is unlikely z INCT! : Theoretically, co-administration of zinc with chromium could decrease the oral absorption of both laboratory Considerations No specific laboratory interactions or considerations noted Doses CATS:T! For use as an oral hypoglycemic agent: a) Chromium picolinate 200 mcg PO once a day. (Dowling 2000); (Greco 2002b) For adjunctive treatment of feline obesity: a) Chromium picolinate 20 mcg/kg PO every other a day (Flores 2004) monitoring As there is no reliable way to measure chromium in the body, a T! clinical trial is the only way to determine whether chromium is effective in helping to control blood glucose. Standard methods of monitoring diabetes treatment efficacy should be followed (e. g., fasting blood glucose, appetite, attitude, body condition/weight, PU/PD resolution and, perhaps, serum fructosamine and/or gly-cosylated hemoglobin levels). Client Information Clients should give the medication only as prescribed and not T! change brands without their veterinarian's approval. Chemistry/Synonyms A trace element (Cr; atomic number 24), oral chromium supple-ments are usually given as the picolinate salt (also known as chro-mium tripicolinate). Storage/Stability Chromium picolinate should be stored in tight containers. For stor-age recommendations, refer to the label for each product used. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: No oral products approved as pharmaceuticals. Injectable chromium: (as chromic chloride hexahydrate): 4 mcg/ m L (as 20. 5 mcg chromic chloride hexahydrate) and 20 mcg/m L (as 102. 5 mcg chromic chloride hexahydrate) in 5 m L (20 mcg/m L only), 10 m L & 30 m L; Chromic Chloride (various); Chroma-Pak® (Smith & Nephew Solo Pak); generic; (Rx) Oral chromium products are considered to be nutritional supplements by the FDA. No stan-dards have been accepted for potency, purity, safety or efficacy by regulatory bodies. Supplements are available from a wide variety of sources. Most vet-erinary use in small animals is with chromium picolinate dosage forms. Common tablet sizes include 200 mcg, 400 mcg, 500 mcg and 800 mcg. Bioequivalence between products cannot be assumed. cimetidine cimetidine hcl (sye-met-i-deen) Tagamet® histamine 2 bl Ocker Prescriber Highlights Prototype histamine-2 blocker used to reduce GI acid T T production Newer HT T2 blockers (e. g., ranitidine, famotidine) & other agents (e. g., omeprazole) may be more effective, have longer duration of activity, & fewer drug interactions Contraindications: Hypersensitivity. Caution: Geriatric T T patients, hepatic or renal insufficiency Comparatively (with newer HT T2 blockers), many drug interactions Uses/Indications In veterinary medicine, cimetidine has been used for the treatment and/or prophy laxis of gastric, abomasal and duodenal ulcers, uremic gastritis, stress-related or drug-induced ero sive gastritis, esophagi-tis, duodenal gastric reflux, and esophageal reflux. It has also been employed to treat hypersecretory conditions associated with gastri-nomas and systemic mastocytosis. Cimeti dine has also been used investigationally as a immunomodulating agent (see doses) in dogs. Cimetidine has been used for the treatment of melanomas in horses, but the drug's poor bioavailability and subsequent high doses (48 mg/kg/day) in adult horses makes it a very expensive, unproven treatment. Pharmacology/Actions At the H 2 receptors of the parietal cells, cimetidine competitively inhibits his tamine thereby reducing gastric acid output both during basal conditions and when stimulated by food, pentagastrin, hista-mine, or insulin. Gastric emptying time, pancreatic or biliary secre-tion, and lower esophageal pressures are not altered by cimetidine. By decreasing the amount of gastric juice produced, cimetidine also decreases the amount of pepsin secreted. Cimetidine has an apparent immunomodulating effect as it has been demonstrated to reverse sup pressor T-cell-mediated immune suppression. It also possesses weak anti-androgenic activity. Pharmacokinetics In dogs, the oral bioavailability is reported to be approximately 95%, serum half-life is 1. 3 hours and volume of distribution is 1. 2 L/kg. In horses, after intragastric administration oral bioavailability is only about 14%, steady-state volume of distribution 0. 77 L/kg, median plasma clearance 8. 2 m L/min/kg, and terminal elimination half-life is approximately 90 minutes. In humans, cimetidine is rapidly and well absorbed after oral administration, but a small amount is metabolized in the liver be- | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CIm ETIDINE 195 fore entering the systemic circulation (first-pass effect). The oral bioavail ability is 70-80%. Food may delay absorption and slightly decrease the amount absorbed, but when given with food, peak lev-els occur when the stomach is not protected by the buffering capa-bilities of the ingesta. Cimetidine is well distributed in body tissues and only 15-20% is bound to plasma proteins. The drug enters milk and crosses the placenta. Cimetidine is both metabolized in the liver and excreted un-changed by the kidneys. More of the drug is excreted by the kid-neys when administered parenterally (75%) than when given orally (48%). The average serum half-life is 2 hours in humans, but can be prolonged in elderly patients and those with renal or hepatic dis-ease. Peritoneal dialysis does not appreciably enhance the removal of cime tidine from the body. Contraindications/Precautions/Warnings Cimetidine is contraindicated in patients with known hypersensi-tivity to the drug. Cimetidine should be used cautiously in geriatric patients and in patients with significantly im paired hepatic or renal function. In humans meeting these criteria, increased risk of CNS effects (con-fusion) may occur; dosage reductions may be necessary. Adverse Effects Adverse effects appear to be very rare in animals at the dosages gener ally used. Potential adverse effects (documented in humans) that could be seen include mental con fusion, headache (upon dis-continuation of the drug), gynecomastia, and decreased libido. Rarely, agranulocytosis may develop and, if given rapidly IV, tran-sient cardiac arrhythmias may be seen. Pain at the injection site may occur after IM administration. Cimetidine does inhibit microsomal enzymes in the liver and may alter the metabolic rates of other drugs (see Drug Interactions below). Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: B (Safe for use if used cautiously. Studies in laboratory animals may have un-covered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) Cimetidine is distributed into milk; while safety during nursing is not assured, it is usually considered compatible with nursing in humans. Overdosage/Acute Toxicity Clinical experience with cimetidine overdosage is limited. In labora-tory animals, very high dosages have been associated with tachycar-dia and respiratory failure; respiratory support and beta-adrenergic blockers have been suggested for use should these signs occur. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving cimetidine and may be of significance in veterinary patients: Cimetidine may inhibit the hepatic microsomal enzyme system and thereby re duce the metabolism, prolong serum half-lives, and increase the serum levels of several drugs and/or reduce the hepatic blood flow and reduce the amount of hepatic extraction of drugs that have a high first-pass effect, including: b ENz ODIAz EPINES!! (e. g., diazepam ) b ETAbl OCKERS!! (e. g., propranolol ) CAl CIUm CHANNEl bl OCKERS!! (e. g., verapamil ) CHl ORAm PHENICOl !! l IDO CAINE!! m ETRONIDAz Ol E !! PHENy TOIN!! PROCAINAm IDE!! THEOPHyll INE !! TRIAm TERENE!! TRICy Cl IC ANTIDEPRESSANTS!! WARFARINT! ANTACIDST! : May decrease the absorption of cimetidine; stagger doses (separate by 2 hours if possible) KETOCONAz Ol E, ITRACONAz Ol ET!, etc: Cimetidine may decrease the absorption of these drugs; give these medications at least two hours before cimetidine my El OSUPPRESSIVE DRUg ST! : Cimetidine may exacerbate leukope-nias when used with myelosuppressive agents laboratory Considerations Creatinine T! : Cimetidine may cause small increases in plasma crea-tinine con centrations early in therapy; these increases are gener-ally mild, non-progressive, and have disap peared when therapy is discontinued gastric Acid Secretion Tests T! : Histamine 2 blockers may antagonize the effects of histamine and pentagastrin in the evaluation of gas-tric acid secretion; it is recommended that histamine 2 blockers be discontinued at least 24 hours before performing this test Allergen Extract Skin Tests T! : Histamine 2 antagonists may inhibit histamine responses; it is recommended that histamine 2 blockers be discontinued at least 24 hours before performing this test Doses DOg S:T! For esophagitis:a) 5-10 mg/kg PO q6h (do not give with antacids) (Jones 1985) b) 4 mg/kg PO four times daily (Watrous 1988) For prevention of drug-induced gastric erosion/ulceration:a) 5 mg/kg PO, SC, three times daily (Schunk 1988) For chronic gastritis:a) 5-10 mg/kg PO, IM or IV three to four times daily (Hall and Twedt 1988) For ulcer disease:a) 5-10 mg/kg PO, IM or IV three to four times daily (Hall and Twedt 1988) b) 4-5 mg/kg PO, IV, or SC three to four times daily (Chiapella 1988) c) 5 mg/kg IV or PO four times daily (Moreland 1988) d) 5-10 mg/kg PO q6-8h or 10 mg/kg q6h as a slow (over 30 minutes) IV infusion (De Novo 1986) e) 10 mg/kg PO, IM, IV q8h (Matz 1995) For gastrinoma:a) 5-10 mg/kg PO, SC, IV q6-8h (Zerbe and Washabau 2000) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
196 CIm ETIDINE T o prevent histamine-mediated gastric hyperacidity/ulceration secondary to mast cell tumors:a) 5 mg/kg q8h (Fox 1995) b) 5 mg/kg PO, IV, three to four times daily (Stann 1988) T o decrease gastric acid hypersecretion during the treatment of alkalosis: a) 5-10 mg/kg three to four times daily (Hardy and Robinson 1986) As an immunomodulating agent (reverses suppressor T-cell-me-diated immune suppression):a) 10-25 mg/kg PO twice daily (Desiderio and Rankin 1986) CATS:T! a) 5-10 mg/kg PO q6-8h or 10 mg/kg q6h as a slow (over 30 minutes) IV infusion (De Novo 1986) FERRETS:T! For stress induced ulcers: a) 5-10 mg/kg PO, SC, IM or IV 3 times daily (Williams 2000) RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Rabbits: For GI ulcers: 5-10 mg/kg PO, SC, IM or IV q8-12h (Ivey and Morrisey 2000) b) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 5-10 mg/kg PO, IM or SC q6-12h (Adamcak and Otten 2000) HORSES: T! (Note : ARCI UCGFS Class 5 Drug) For foals:a) 1000 mg divided twice daily or three times daily PO, IV or IM (Robinson 1987) b) 300-600 mg PO or IV 4 times a day (Clark and Becht 1987) For adjunctive treatment of melanomas: a) 48 mg/kg/day (dosing interval not specified) PO for 2-3 weeks following resolution of tumor growth; regression should be seen evident within 3 months of initiating treatment; if no improvement seen it will probably not be effective and should be discontinued. Some horses may require treatment their en-tire life. (Rashmir-Raven, Foy et al. 2006) SWINE:T! T o treat gastric ulcers: a) 300 mg per animal twice daily (Wass et al. 1986b) REPTIl ES:T! In most species:a) 4 mg/kg PO q8-12h (Gauvin 1993) monitoring Clinical efficacy (dependent on reason for use); monitored by T! decrease in symptomatology, endoscopic examination, blood in feces, etc. Adverse effects if noted T! Client Information T o maximize the benefit of this medication, it must be adminis-T! tered as pre scribed by the veterinarian; signs may reoccur if dos-ages are missed. Chemistry/Synonyms An H 2-receptor antagonist, cimetidine occurs as a white to off-white, crystalline pow der. It has what is described as an “unpleasant” odor and a p K a of 6. 8. Cimetidine is sparingly solu ble in water and soluble in alcohol. Cimetidine HCl occurs as white, crystalline pow-der and is very soluble in water and soluble in alcohol. It has a p K a of 7. 11 and the commercial injection has a p H of 3. 8-6. Cimetidine may also be known as: cimetidinum, or SKF-92334; many trade names are available. Storage/Stability/Compatibility Cimetidine products should be stored protected from light and kept at room temperature. Do not refrigerate the injectable product as precipitation may occur. Oral dosage forms should be stored in tight containers. The cimetidine injectable product is compatible with the com-monly used IV infusions solutions, including amino acid (TPN) so-lutions, but should be used within 48 hours of dilution. Cimetidine is also reported to be compatible with the following drugs: acetazol-amide sodium, amikacin sulfate, at ropine sulfate, carbenicillin diso-dium, cefoxitin sodium, chlorothiazide sodium, clindamycin phos-phate, colistimethate sodium, dexamethasone sodium phosphate, digoxin, epinephrine, erythromycin lactobionate, furosemide, gen-tamicin sulfate, heparin sodium, insulin (regular), isoproterenol HCl, lidocaine HCl, lincomycin HCl, methylprednisolone sodium succinate, nafcillin sodium, nore pinephrine bitartrate, penicillin G potassium/sodium, phytonadione, polymyxin B sulfate, potassium chloride, protamine sulfate, quinidine gluconate, sodium nitroprus-side, tetracycline HCl, van comycin HCl, verapamil HCl, and vita-min B complex (with or without C). The following drugs are reported to be either incompatible with cimetidine or data conflicts: amphotericin B, ampicillin sodium, cefamandole naftate, cefazolin sodium, cephalothin sodium, and pentobarbital sodium. Compatibility is dependent upon factors such as p H, concentration, tempera ture and diluent used; consult specialized references or a hospital pharmacist for more specific in formation. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 5 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Cimetidine Tablets: 200 mg, 300 mg, 400 mg, & 800 mg; Tagamet® & Tagamet® HB 200 (Glaxo Smith Kline & GSK Consumer); Acid Re-ducer 200® (Major); generic; (Rx, OTC) Cimetidine HCl Oral Solution: 300 mg (as HCl)/5 m L in 240 m L, 480 m L & UD 5 m L; generic; (Rx) Cimetidine HCl Injection: 150 mg/m L (as hydrochloride) in 2 m L vials and 8 m L multiple-dose vials; Cimetidine in 0. 9% Sodium Chloride: 6 mg (as hydrochloride)/m L in premixed 50 m L con-tainer; (Hospira); generic; (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CIPROFl Ox ACIN 197 ciproflox Acin (sip-roe-flox-a-sin) Cipro® flu Or Oquin Ol One antibi O tic Prescriber Highlights Human-label fluoroquinolone antibiotic T T In dogs, oral T T bioavailability lower than enrofloxacin Available as a true IV product T T Contraindications: Hypersensitivity. Relatively contra-T T indicated for young, growing animals due to cartilage abnormalities Caution: Hepatic or renal insufficiency, dehydration T T Adverse Effects: GI distress, CNS stimulation, crystalluria, T T & hypersensitivity Administer PO preferably on an empty stomach T T Drug interactions T T Uses/Indications Because of its similar spectrum of activity, ciprofloxacin could be used as an al ternative to enrofloxacin when a larger oral dosage form or intravenous product is desired. But the two compounds cannot be considered equivalent because of pharmacokinetic dif-ferences (see be low). Pharmacology/Actions Ciprofloxacin is a bactericidal and a concentration dependent agent, with susceptible bacteria cell death occurring within 20-30 minutes of ex posure. Ciprofloxacin has demonstrated a significant post-antibiotic effect for both gram-negative and gram-positive bacteria and is active in both stationary and growth phases of bac-terial replication. Its mechanism of action is not thoroughly under-stood, but it is believed to act by inhibiting bacterial DNA-gyrase (a type-II topoisomerase), thereby preventing DNA supercoiling and DNA synthesis. Both enrofloxacin and ciprofloxacin have similar spectrums of activity. These agents have good activity against many gram-negative bacilli and cocci, including most species and strains of Pseu domonas aeruginosa, Klebsiella spp., E. coli, Enterobacter, Campylobacter, Shigella, Salmonella, Aeromonas, Haemophilus, Proteus, Y ersinia, Serratia, and Vibrio species. Of the currently com mercially available quinolones, ciprofloxacin and enrofloxacin have the lowest MIC values for the majority of these pathogens treated. Other organ-isms that are generally susceptible include Brucella spp. Chlamydia trachomatis, Staphylococci (including penicillinase-producing and methicillin-resis tant strains), Mycoplasma, and Mycobacterium spp. (not the etiologic agent for Johne's disease). The fluoroquinolones have variable activity against most Strep-tococci and are not usually recom mended for use in treating these infections. These drugs have weak activity against most anaerobes and are ineffective in treating anaerobic infections. Resistance does occur by mutation, particularly with Pseudomonas aeruginosa, Klebsiella pneu monia, Acinetobacter, and enterococci, but plasmid-mediated resistance does not seem to occur. Pharmacokinetics Both enrofloxacin and ciprofloxacin are well absorbed after oral ad-ministration in most species; in dogs however, enrofloxacin's bio-availability is at least twice that of ciprofloxacin after oral dosing. In humans, the oral bioavailability of ciprofloxacin has been reported to be between 50-85%. Studies of the oral bioavailability in ponies have shown that ciprofloxacin is poorly absorbed (2-12%) while enrofloxacin in foals apparently is well absorbed. In humans, the volume of distribution in adults for ciprofloxa-cin is about 2-3. 5 L/kg and it is ap proximately 20-40% bound to serum proteins. Ciprofloxacin is one of the metabolites of enrofloxacin. Approximately 15-50% of the drugs are eliminated unchanged into the urine by both tubular secretion and glomerular filtration. En rofloxacin/ciprofloxacin are metabolized to various metabolites that are less active than the parent compounds. Approximately 10-40% of circulating enrofloxacin is metabolized to ciprofloxacin in most species. These metabolites are eliminated in both the urine and feces. Because of the dual (renal and hepatic) means of elimi-nation, patients with severely impaired renal function may have slightly prolonged half-lives and higher serum levels but may not require dosage adjustment. The pharmacokinetics of ciprofloxacin has been studied in dogs, calves, and pigs. Oral bioavail ability is approximately 50% in calves and 40% (only one pig studied) in pigs and it has an elimina tion half-life of about 2. 5 hours in both species. Protein binding was sig-nificantly different for each species, with calves having about 70% of the drug bound and pigs only about 23% bound to plasma proteins. Elimination half-life is reported to be about 2. 5 hours in dogs. Contraindications/Precautions/Warnings Ciprofloxacin, as is enrofloxacin, should be considered contraindi-cated in small and medium breed dogs from 2-8 months of age. Bubble-like changes in articular cartilage have been noted when the drug was given at 2-5 times rec ommend doses for 30 days, although clinical signs have only been seen at the 5X dose. T o avoid cartilage damage, large and giant breed dogs may need to wait longer than the recommended 8 months since they may be in the rapid-growth phase past 8 months of age. Quinolones are also contraindi cated in patients hypersensitive to them. Because ciprofloxacin has occasionally been reported to cause crystalluria, animals should not be allowed to become dehydrated during therapy with either ciprofloxacin or enrofloxacin. In hu-mans, ciprofloxacin has been associated with CNS stimulation and should be used with caution in patients with seizure disorders. Patients with severe renal or hepatic impairment may require dos-age adjust ments to prevent drug accumulation. Use high dose ciprofloxacin in cats with caution. No reports of retinal toxicity (as can be seen with high dose enrofloxacin) second-ary to ciprofloxacin in cats were located and retinal toxicity appears to be less likely since it is less lipophilic than enrofloxacin; however caution is advised. Adverse Effects With the exception of potential cartilage abnormalities in young ani mals (see Contraindications above), the adverse effect profile of fluoroquinolones appears to be minimal. GI distress (vomiting, anorexia) is the most frequently, yet uncommon, reported adverse ef fect. Although not reported thus far in animals, hypersensitiv-ity reactions, crystalluria, and CNS ef fects (dizziness, stimulation) could potentially occur. 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. ) Ciprofloxacin is distributed into milk, but oral absorption should be negligible. No adverse effects have been reported in nurs-ing human infants of mothers receiving ciprofloxacin. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
198 CIPROFl Ox ACIN Overdosage Little specific information is available. See the enrofloxacin mono-graph for more in formation. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving ciprofloxacin and may be of significance in veterinary patients: ANTACIDS/DAIR y PRODUCTS T! containing cations (Mg++, Al+++, Ca++) may bind to ciprofloxacin and prevent its absorption; separate doses of these products by at least 2 hours from ciprofloxacin ANTIb IOTICS, OTHERT! (aminoglycosides, 3rdgenera tion cephalosporins, penicillins—extendedspectrum : Synergism may occur, but is not predictable, against some bacteria (particularly Pseudomonas aeruginosa) with these compounds. Although en rofloxacin/cipro-floxacin has minimal activity against anaerobes, in vitro synergy has been reported when used with clindamycin against strains of Peptostreptococcus, Lactobacillus and Bacteroides fragilis. Cy Cl OSPORINET! : Fluoroquinolones may exacerbate the nephrotoxic-ity, and reduce the metabolism of, cy closporine (used systemically) glyb URIDET! : Severe hypoglycemia possible IRON, z INCT! (oral): Decreased ciprofloxacin absorption; separate doses by at least two hours m ETHOTREx ATET! : Increased MTX levels possible with resultant toxicity NITROFURANTOINT! : May antagonize the antimicrobial activity of the fluoroquinolones; concomitant use is not recommended PHENy TOINT! : Ciprofloxacin may alter phenytoin levels PROb ENECIDT! : Blocks tubular secretion of ciprofloxacin and may increase its blood level and half-life SUCRAl FATET! : May inhibit absorption of ciprofloxacin; separate doses of these drugs by at least 2 hours THEOPHyll INET! : Ciprofloxacin may increase theophylline blood lev-els WARFARINT! : Potential for increased warfarin effects laboratory Considerations In some human patients, the fluoroquinolones have caused in-T! creases in liver enzymes, b UN, and creatinine and decreases in hema tocrit. The clinical relevance of these mild changes is not known at this time. Doses DOg S:T! For susceptible infections: a) 5-15 mg/kg PO q12h; Avoid or reduce dosage of these drugs in animals with severe re nal failure; avoid in young animals or in pregnant or breeding animals. (Vaden and Papich 1995) b) For UTI: 10 mg/kg PO once daily (q24h) for 7-14 days For skin, soft tissue infections: 10-15 mg/kg PO once daily (q24h) for 7-14 days For bone systemic infections, bacteremia and more resistant pathogens (e. g., Enterobac ter): 20 mg/kg PO once daily (q24h) for 7 -14 days (Greene, Hartmannn et al. 2006) c) For pyoderma: 11 mg/kg PO q12h (Miller 2005b) CATS:T! For susceptible infections: a) Ciprofloxacin: 5-15 mg/kg PO q12h Avoid or reduce dosage of these drugs in animals with severe re-nal failure; avoid in young animals or in pregnant or breeding animals. (Vaden and Papich 1995)FERRETS:T! For susceptible infections:a) 5-15 mg/kg PO twice daily (Williams 2000) RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Rabbits: 5-20 mg/kg PO q12h (Ivey and Morrisey 2000) b) Chinchillas, Gerbils, Guinea Pigs, Hamsters, Mice, Rats: 7-20 mg/kg PO q12h (Adamcak and Otten 2000) b IRDS:T! For susceptible gram-negative infections:a) Using ciprofloxacin 500 mg tablets: 20-40 mg/kg PO twice daily. Crushed tablet goes into sus pension well, but must be shaken well before administering. (Mc Donald 1989) b) Ciprofloxacin (using crushed tablets): 20 mg/kg PO q12h (Bauck and Hoefer 1993) c) Ciprofloxacin (using crushed tablets or suspend) 10-15 mg/ kg PO q12h (Hoeffer 1995) d) R atites: 3-6 mg/kg PO twice daily (Jenson 1998) monitoring Clinical efficacy T! Adverse effects T! Chemistry/Synonyms A fluoroquinolone antibiotic, ciprofloxacin HCl occurs as a faintly yellowish to yellow, crystalline powder. It is slightly soluble in water. Ciprofloxacin is related structurally to the veteri nary-approved drug enrofloxacin (enrofloxacin has an additional ethyl group on the pip-erazinyl ring). Ciprofloxacin may also be known as ciprofloxacine, ciprofloxaci-num, ciprofloxacino, Bay-q-3939, or Cipro ®. Storage/Stability/Compatibility Unless otherwise directed by the manufacturer, ciprofloxacin tab-lets should be stored in tight containers at temperatures less than 30°C. Protect from strong UV light. The injection should be stored at 5°-25°C and protected from light and freezing. Ciprofloxacin injection is reportedly compatible with the fol-lowing IV solutions and drugs: Dextrose 5%, D5 and G or H Na Cl, Ringer's, LRS, normal saline, amikacin sulfate, aztreonam, cimeti-dine, cyclosporine, dobutamine, dopamine, fluconazole, gentami-cin, lidocaine, midazolam, KCl, ranitidine, tobramycin, and vitamin B complex. Ciprofloxacin injection is reportedly incompatible with amino-phylline, amphotericin B, azithromycin, ceftazidime, cefuroxime, clindamycin, heparin sodium, sodium bicarbonate, and ticarcillin. Compatibility is dependent upon factors such as p H, concentra-tion, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific in formation. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Ciprofloxacin Oral Tablets: 100 mg, 250 mg, 500 mg & 750 mg; Cip-ro® (Bayer); generic; (Rx) Ciprofloxacin Extended-Release Tablets: 500 mg & 1000 mg; Cipro XR® (Bayer); generic; (Rx) Ciprofloxacin Powder for Oral Suspension: 50 mg/m L (5%), 100 mg/m L (10%) when reconstituted; Cipro ® (Bayer); generic; (Rx) Ciprofloxacin Injection: 200 mg in 20 m L vials, 100 m L in 5% dex-trose flexible containers (0. 2%) and 120 m L bulk; 400 mg in 40 m L vials (1%), 200 m L in 5% dextrose flexible containers (0. 2%) and 120 m L bulk; Cipro ® I. V. (Bayer); generic; (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CISAPRIDE 199 cis Apride (sis-a-pride) pr Om O tility agent Prescriber Highlights Oral GI prokinetic agent, used in several species for T T GI stasis, reflux esophagitis, & constipation/megacolon (cats) No longer commercially available, must be obtained from T T a compounding pharmacy Contraindications: Hypersensitivity, GI perforation or T T obstruction, hemorrhage Caution: Pregnancy T T Adverse effects appear to be minimal in veterinary T T patients Drug interactions T T Uses/Indications Proposed uses for cisapride in small animals includes esophageal reflux and treat ment of primary gastric stasis disorders. Cisapride has been found to be useful in the treatment of constipation and megacolon in cats. Pharmacology/Actions Cisapride increases lower esophageal peristalsis and sphincter pres-sure and accel erates gastric emptying. The drug's proposed mecha-nism of action enhances the release of acetyl choline at the myen-teric plexus, but does not induce nicotinic or muscarinic receptor stimulation. Acetylcholinesterase activity is not inhibited. Cisapride blocks dopaminergic receptors to a lesser extent than does metoclo-pramide and does not increase gastric acid secretion. Pharmacokinetics Human data: After oral administration, cisapride is rapidly ab-sorbed with an absolute bioavailability of 35-40%. The drug is highly bound to plasma proteins and apparently ex tensively distrib-uted throughout the body. Cisapride is extensively metabolized and its elimination half-life is about 8-10 hours. Contraindications/Precautions/Warnings Cisapride is contraindicated in patients in whom increased gastro-intestinal motility could be harmful (e. g., perforation, obstruction, GI hemor rhage) or those who are hypersensitive to the drug. Adverse Effects Cisapride appears to be safe in cats at the dosages rec ommended. Occasionally vomiting, diarrhea, and abdominal discomfort may be noted. Although considered very rare in veterinary patients, pro-longed QT intervals or other cardiac arrhythmias are possibilities. In humans, the primary adverse effects are gastrointestinal re-lated with di arrhea and abdominal pain most commonly reported, but the drug was removed from the market due to concerns with QT-interval prolongation. Dosage may need to be decreased in patients with severe hepatic impairment. Reproductive/Nursing Safety Cisapride at high dosages (>40 mg/kg/day) caused fertility impair-ment in female rats. At doses 12 to 100 times the maximum recom-mended, cisapride caused embryotoxicity and fetotoxicity in rab-bits and rats. Its use during pregnancy should occur only when the benefits outweigh the risks. Cisapride is excreted in maternal milk in low levels; use with caution in nursing mothers. Overdosage/Acute Toxicity In one reported human overdose of 540 mg, the patient devel-oped GI distress and urinary frequency. LD 50 doses in various lab animals range from 160-4000 mg/kg. Adverse effects reported for overdoses in dogs include diarrhea, hypotonia, dyspnea, catalepsy, loss of righting reflex, tremors, or seizures. Significant overdoses should be handled using standard gut emptying protocols when appropriate; supportive therapy should be initiated when required. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving cisapride and may be of significance in veterinary patients: ANTICHOl INERg IC Ag ENTST! : Use of anticholinergic agents may di-minish the effects of cisapride b ENz ODIAz EPINEST! : Cisapride may enhance the sedative effects of alcohol or benzodi azepines WARFARINT! : Cis apride may enhance anticoagulant effects; addi-tional monitoring and anticoagulant dosage ad justments may be required ORAl DRUg S WITH A NARROW THERAPEUTIC INDEx T! : May need serum levels moni tored more closely when adding or discontinuing cisapride as cisapride can decrease GI transit times and poten-tially affect the absorption of other oral drugs As cisapride is metabolized via cytochrome P450 (3A4 in hu-mans), the following medications/foods that can inhibit this en-zyme may lead to increased cisapride levels with an increased risk for cisapride cardiotoxicity: Am IODARONE!! ANTIFUNg Al S!! (ketoconazole, itraconazole, fluconazole ) CHl ORAm PHENICOl!! CIm ETIDINE!! Fl UVOx Am INE!! g RAPEFRUIT JUICE/POWDER!! m ACROl IDE ANTIb IOTICST! (except azithromycin ) Note: In one study in dogs erythromycin did not alter cisapride pharmacokinetics The following drugs may increase QT interval and use with cisap-ride may increase this risk: Am IODARONE!! Cl ARITHROmy CIN!! m Ox IFl Ox ACIN!! PROCAINAm IDE!! QUINIDINE!! SOTAl Ol T! TRICy Cl IC ANTIDEPRESSANTST! (amitriptyline, imipramine ) Doses DOg S:T! As a promotility agenta) 0. 5 mg/kg three times daily; decrease dose if abnormal GI signs or abdominal pain result (Hall 1994) b) T o reduce regurgitation associated with megaesophagus: 0. 55 mg/kg PO once to three times daily. Practically: 2. 5 mg per dose for dogs weighing between 5-10 lbs. ; 5 mg per dose for dogs weighing between 11-40 lbs; and 10 mg per dose for dogs greater than 40 lbs. Administer no closer than 30 minutes before feeding. (Tams 1994) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
200 CISPl ATIN c) As an antiemetic: 0. 1-0. 5 mg/kg q8h PO (Washabau and Elie 1995) d) For esophagitis: 0. 25 mg/kg PO q8-12h. Particularly effec-tive in preventing recurrence once esophagitis brought under control. (Willard and Weyrauch 2000) e) For adjunctive treatment (with H-2 blockers or proton pump inhibitors such as omeprazole—preferred) for esophageal re-flux: 0. 1-0. 5 mg/kg PO q8-24h (Willard 2006c) T o stimulate detrusor contraction for micturition disorders:a) 0. 5 mg/kg PO q8h (Coates 2004) CATS:T! As a promotility agent: a) For chronic constipation (e. g., megacolon): In combination with a stool softener (author recommends lactulose at a start-ing dose of 2-3 m L PO three times a day; then adjust as need-ed) and a bulk agent (e. g., psyllium or pumpkin pie filling) cis apride is given initially at 2. 5 mg (for cats up to 10 pounds) or 5 mg (for cats 11 pounds or heavier) three times daily, 30 minutes before food. Cats weighing greater than 16 pounds may re quire 7. 5 mg. (Tams 1994) b) For chronic constipation (e. g., megacolon): Used adjunctive-ly with conventional dietary therapeutics: 1. 25-2. 5 mg per cat two to three times a day; cats with hepatic insufficiency should be treated with half the usual dose; probably most ef-fective when given 15 minutes before a meal. (Nixon 1994) c) For chronic constipation (e. g., megacolon): 0. 1-1 mg/kg q8-12h PO (Washabau and Holt 2000) d) For chronic constipation (e. g., megacolon): 5 mg per cat (total dose) PO q8-12h (Scherk 2003b) e) For gastric stasis: 0. 1 mg/kg PO two to three times daily; cats tolerate 2. 5 mg doses without problems (Twedt 2005b) RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 0. 1-0. 5 mg/kg PO q12h (Adamcak and Otten 2000) b) Rabbits for GI stasis: 0. 5 mg/kg PO q6-12h. With IV or SC fluids depending on amount of dehydration, feeding a high fiber slurry and with or without metoclopramide (0. 2-1 mg/ kg PO, SC q6-8h). (Hess 2002b) c) For ileus if GI tract not obstructed in Guinea pigs, chinchillas: 0. 5 mg/kg q8-12h (Route not specified; assume PO) (Orcutt 2005) HORSES:T! As a promotility agent:a) Foals with periparturient asphyxia: 10 mg (total dose) PO q6-8h. Adequate time for healing of damaged bowel before using prokinetic agents is essential. (Vaala 2003b) monitoring Efficacy T! Adverse effects profile T! Client Information Inform client to watch carefully and report any adverse effects T! noted. Chemistry/Synonyms An oral GI prokinetic agent, cisapride is a substituted piperidinyl benzamide and is structurally, but not pharmacologically, related to procainamide. It is available commercially as a monohydrate, but potency is expressed in terms of the anhydrate. Cisapride may also be known as: cisapridum, or R-51619; many trade names are registered. Storage/Stability Unless otherwise instructed by the manufacturer, store cisapride tablets in tight, light-resistant containers at room temperature. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: None Because of adverse effects in humans, cisapride has been removed from the US market. It may be available from compounding pharmacies. cispl A tin (sis-pla-tin) Platinol-AQ® antine Oplastic Prescriber Highlights Platinum antineoplastic agent used for a variety of T T carcinomas & sarcomas; palliative control of neoplastic pulmonary effusions with intracavitary administration; intralesional injection for skin tumors in horses Contraindications: Cats; history of hypersensitiv-T T ity; preexisting significant renal impair ment or myelosuppression Primary adverse effects: Vomiting (pretreat with antie-T T metic); nephrotoxicity (use forced saline diuresis); myelo-suppression; many other adverse effects possible Drug related deaths possible T T Teratogenic, fetotoxic; may cause azoospermia T T Must be handled with care by dosage preparer/ T T administerer Must be given as slow IV infusion; fast administration T T (<5 minutes) may increase toxicity Uses/Indications In veterinary medicine, the systemic use of cisplatin is presently limited to use in dogs. The drug has been, or may be, useful in a variety of neoplastic diseases including squamous cell car cinomas, transitional cell carcinomas, ovarian carcinomas, mediastinal carci-nomas, osteosarcomas, pleural adenocarcinomas, nasal carcinomas, and thyroid adenocarcinomas. Cisplatin may be useful for the palliative control of neoplastic pulmonary effusions after intracavi tary administration. In horses, cisplatin has been used for intralesional injection for skin tumors. Pharmacology/Actions While the exact mechanism of action of cisplatin has not been de-termined, its prop erties are analogous to those of bifunctional alky-lating agents producing inter-and intrastrand crosslinks in DNA. Cisplatin is cell cycle nonspecific. Pharmacokinetics After administration, the drug concentrates in the liver, intestines and kidneys. Platinum will accumulate in the body and may be detected 6 months after a course of therapy has been completed. Cisplatin is highly bound (90%) to serum proteins. In dogs, cisplatin exhibits a biphasic elimination profile. The ini-tial plasma half-life is short (approximately 20-50 minutes), but the | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CISPl ATIN 201 terminal phase is very long (about 60-80 hours). Approximately 80% of a dose can be recovered as free platinum in the urine within 48 hours of dosing in dogs. Contraindications/Precautions/Warnings The drug is contraindicated in cats because of severe dose-related primary pulmonary toxicoses (dyspnea, hydrothorax, pulmonary edema, mediastinal edema, and death). Cisplatin is also contrain-dicated in patients with preexisting significant renal impairment, myelosuppression, or a history of hypersensitivity to platinum-containing compounds. Because of the fluid loading required prior to dosing, it should be used with caution in patients with congestive heart failure. When preparing the product for injection, wear gloves and pro-tective clothing as local reactions may occur with skin or mucous membrane contact. Should accidental exposure occur, wash the area thoroughly with soap and water. Adverse Effects In dogs, the most frequent adverse effect seen after cisplatin treat-ment is vomiting, which usually occurs within 6 hours after dosing and persists for 1-6 hours. This is because of direct effects on the chemoreceptor trigger zone (CTZ). Butorphanol (0. 4 mg/kg IM), dex amethasone (0. 25 mg/kg IV) and metoclopramide (0. 1 mg/kg IV) have all been used successfully as antiemetics when given before cisplatin administration. Nephrotoxicity may occur unless the animal is adequately diure-sed with sodium chloride prior to, and after therapy; diuresis will generally significantly reduce the incidence and severity of nephro-toxicity in the majority of dogs. Intravenous methimazole (40 mg/kg) has been demonstrated to protect cisplatin-induced nephrotox-icity in dogs in experimental models. Other adverse effects that have been reported include hemato-logic abnormalities (thrombocytopenia and/or granulocytopenia), ototoxicity (high-frequency hearing loss and tinnitus), anorexia, diarrhea (including hemorrhagic diarrhea), seizures, peripheral neuropathies, electrolyte abnormalities, hype ruricemia, increased hepatic enzymes, anaphylactoid reactions, and death. Direct IV infusion over 1-5 minutes should be avoided as it may cause increased nephrotoxicity or ototoxicity. Reproductive/Nursing Safety Cisplatin's safe use in pregnancy has not been established. It is teratogenic and embryotoxic in mice. In human males, the drug may cause azoospermia and impaired spermatogenesis. In humans, the FDA categorizes this drug as category D for use during preg-nancy (There is evidence of human fetal risk, but the potential ben-efits 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 outweighs the risks. ) Overdosage/Acute Toxicity The minimum lethal dose of cisplatin in dogs is reportedly 2. 5 mg/kg (≈80 mg/m 2). Because of the potential for serious toxicity as-sociated with this agent, dosage calcu lations should be checked thoroughly to avoid overdosing. See Adverse Effects above for more in formation. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving cisplatin and may be of significance in veterinary patients:Am INOgly COSIDEST! : Potential for increased risk for nephrotoxicity and/or nephrotoxicity; if possible, delay aminoglycoside admin-istration by at least two weeks after cisplatin Am PHOTERICINT! b: Potential for increased risk for nephrotoxicity; if possible, delay amphotericin B administration by at least two weeks after cisplatin FUROSEm IDET! (and other loop diuretics ): Potential for increased ototoxicity PHENy TOINT! : Cisplatin may reduce serum levels of phenytoin Doses For more information on using chlorambucil as part of chemo-therapy protocols, refer to the protocols found in the appendix or other dosages/protocols found in numerous references, including: Withrow and Mac Ewen's Small Animal Clinical Oncology, 4th Ed. (Withrow and Vail 2007); Canine and Feline Geriatric Oncology (Villalobos 2007); Small Animal Internal Medicine, 3rd Edition (Nelson and Couto 2003); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edition (Ettinger and Feldman 2005); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. (Tilley and Smith 2004). WARNINg: Dogs must undergo saline diuresis before and after cis-platin therapy to reduce the poten tial for nephrotoxicity develop-ment. Some clinicians also recommend using either mannitol or furosemide with saline, but this is somewhat controversial. DOg S:T! For potentially susceptible carcinomas and sarcomas:a) As part of an accepted protocol: 60-70 mg/m2 IV over 20 minutes after a 4-hour IV saline diuresis (normal saline at a rate of 18. 3 m L/kg/hr). After cisplatin infused, continue sa-line diuresis for another 2 hours. Pretreat with antiemetics. (Kitchell and Dhaliwal 2000) b) 30-50 mg/m2 every 3 weeks. Pretreat with fluids at 60 m L/ kg for 12 hours before dosing. Give mannitol 0. 5 mg/kg 30 minutes before cisplatin. Give cisplatin as a slow drip over 1-6 hours and follow with another 12 hours of fluids at 60 m L/kg. (Macy 1986) c) 60-70 mg/m2 IV drip q3-5 weeks. Perform saline diuresis before and after treatment. (Mac Ewen and Rosenthal 1989) Intracavitary administration for palliative control of neoplastic pulmonary effusions:a) Give dog IV normal saline at 10 m L/kg/hr for 4 hours prior to treating. Dose cisplatin at 50 mg/m2 (diluted in normal saline to a total volume of 250 m L/m 2). Warm solution to body temperature; place a 16-gauge over-the-needle cath-eter into the pleural space using sterile technique. Remove as much pleural fluid as possible and then slowly infuse cis platin solution through same catheter. Once completed, remove catheter. May repeat ev ery 3-4 weeks as needed to control effusion. If resolves completely, discontinue therapy after the 4th treatment. Reinstitute if effusion recurs. (Hawk-ins and Fossum 2000) HORSES:T! For intralesional injection of skin tumors:a) Add 10 mg of cisplatin powder (if available) to 1 m L of wa-ter and 2 m L of medical-grade sesame oil. Resultant solution contains 3. 3 mg of cisplatin per m L. Inject 1 mg per cm 3 of tumor/tumor bed intralesionally with a small gauge needle (22-25 gauge) attached to an extension set with Luer-lock connections. Inject in multiple planes no further than 0. 6 to 1 cm apart. Because the volume of tumor is difficult to mea-sure, the rule of thumb is to discontinue injection when fluid | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
202 CITRATE SAl TS is extruded from the skin surface. Because recurrence at the periphery of the treated area is the primary cause of treatment failure, injection into 1-2 cm of normal tissue surrounding the tumor has been recommended. Intralesional injection is generally repeated at 2-week intervals for 4 total treatments. (Moll 2002) monitoring Adapted primarily from the reference by Shapiro (Shapiro 1989). T oxicity. Baseline laboratory data: urinalysis, hemogram, platelet T! count, serum biochemi cal and electrolyte determination. Repeat tests before each dose if animal is receiving high-dose therapy (≈monthly) or as needed if signs/symptoms of toxicity develop. Animals receiving frequent small doses should be monitored at least weekly. Not recommended to use cis platin if WBC is <3200/ mcl, platelets <100,000, creatinine clearance is <1. 4 m L/min/kg, or uremia, electrolyte or acid-base imbalance is present. Reduce dose if rapid decreases occur with either WBC or platelets, chang-es in urine specific gravity or serum electrolytes, ele vated serum creatinine or BUN, or if creatinine clearance is >1. 4 but <2. 9 m L/ min/kg. Efficacy. Tumor measurement and radiography at least month-T! ly. In one study (Knapp et al. 1988), the authors state that dogs should be evaluated at 42 days into therapy. Dogs demonstrat-ing complete or partial remission or stable disease should receive additional therapy. Dogs whose disease has progressed should have cisplatin therapy stopped and re ceive alternate therapies if warranted. Client Information Clients must be briefed on the possibilities of severe toxicity de-T! veloping from this drug, including drug-related mortality. Chemistry/Synonyms An inorganic platinum-containing antineoplastic, cisplatin occurs as white powder. One mg is soluble in 1 m L of water or normal sa-line. The drug is available commercially as a solution for injection. Cisplatin injection (premixed solution) has a p H of 3. 7-6. Cisplatin may also be known as: cis-Platinum II, cis-DDP, CDDP, cis-diamminedichloroplati num, cisplatina, cisplatinum, cis-plati-num, DDP, NSC-119875, Peyrone's salt, or platinum diamminodi-chloride; many trade names are available. Storage/Stability/Compatibility The injection should be stored at room temperature and away from light; do not refrigerate as a precipitate may form. During use, the injection should be protected from direct bright sunlight, but does not need to be protected from normal room incandescent or fluo-rescent lights. Do not use aluminum hub needles or aluminum containing IV sets as aluminum may displace plat inum from the cisplatin mol-ecule with the resulting formation of a black precipitate. Should a precip itate form from either cold temperatures or aluminum con-tact, discard the solution. Cisplatin is reportedly compatible with the following intravenous solutions and drugs: dex trose/saline combinations, sodium chloride 0. 225%-0. 9%, magnesium sulfate, and mannitol. It is also compatible in syringes or at Y-sites with: bleomycin sulfate, cyclophosphamide, doxorubicin HCl, droperidol, fluorouracil, furosemide, heparin so-dium, leucovorin calcium, methotrexate, mito mycin, vinblastine sulfate, and vincristine sulfate. Cisplatin compatibility information conflicts or is dependent on di-luent or concentration factors with the following drugs or solutions: dextrose/saline combinations, dextrose 5% in water, and metoclo-pramide. Compatibility is dependent upon factors such as p H, con-centration, temperature and diluent used; consult specialized refer-ences or a hospital pharmacist for more specific in formation. Cisplatin is reportedly incompatible with the following solutions or drugs: sodium chloride 0. 1% and sodium bicarbonate 5%. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Cisplatin Injection: 1 mg/m L in 50 m L, 100 m L and 200 m L multi-dose vials; generic; (Rx) Cisplatin powder or compounded formulations appropriate for intralesional injection may be available from compounding pharmacies. citr A te s Alts pot Assium citr A te sodium citr A te And citric Acid (si-trate) Nutrived®, Urocit-K® urinary alkalinizer Prescriber Highlights Oral administered precursor to bicarbonate; used for uri-T T nary alkalization & treatment of chronic metabolic aci-dosis; may be useful to prevent calcium oxalate urolith formation Many contraindications to therapy, including heart failure, T T severe renal impairment, UTI with calcium or struvite stones Contraindications for potassium citrate alone include T T hy perkalemia, ulcer disease; tablets in patients with delayed gastric emptying conditions, esophageal compression, or intestinal obstruction Most prevalent adverse effect is GI distress but, poten-T T tially, hyperkalemia, fluid retention & metabolic alkalosis possible Adequate lab monitoring mandatory T T Uses/Indications Citrate salts serve as source of bicarbonate; they are more pleasant tasting than bicarbonate preparations making them more palatable. They are used as urinary alkalinizers when an alkaline urine is desir-able and in the management of chronic metabolic acidosis accompa-nied with conditions such as renal tubular acidosis or chronic renal insufficiency. Potassium citrate alone (Uracit-K®) has been used for the prevention of calcium oxalate uroliths. The citrate can complex with calcium thereby decreasing urinary concentrations of calcium oxalate. The urinary alkalinizing effects of the citrate also increase the solubility of calcium oxalate. Pharmacology/Actions Citrate salts are oxidized in the body to bicarbonate thereby acting as alkalinizing agents. The citric acid component of multi-component products is converted only to carbon dioxide and water and has only a temporary effect on systemic acid-base status. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CITRATE SAl TS 203 Pharmacokinetics Absorption and oxidation are nearly complete after oral adminis-tration; less than 5% of a dose is excreted unchanged. Contraindications/Precautions/Warnings Contraindications for products containing sodium citrate and/or potassium citrate: aluminum toxicity, heart failure, severe renal im-pairment (with azotemia or oliguria), UTI associated with calcium, or struvite stones. Additional contraindica tions for potassium cit-rate alone include hyperkalemia (or conditions that predispose to hyperkalemia such as adrenal insufficiency, acute dehydration, renal failure, uncontrolled diabetes mellitus), or peptic ulcer (particularly with the tablets). The potassium citrate tablets are contraindicated in patients with delayed gastric emptying conditions, esophageal compression, or intestinal obstruction or stricture. These products should be used with caution (weigh risks vs. benefit) in severe re-nal tubular acidosis or chronic diarrheal syndromes as they may be ineffective. Sodium citrate products should be used with caution in patients with congestive heart disease. In dosages not resulting in hypernatremia, hyperkalemia or metabolic alkalosis, these products should not cause fetal harm. Adverse Effects The primary adverse effects noted with these agents are gastrointesti-nal in nature, however, most dogs receiving these products tolerate them well. Potassium citrate products have the potential of caus-ing hyperkalemia, especially in susceptible patients. Sodium cit rate products may lead to increased fluid retention in patients with car-diac disease. Rarely, metabolic alkalosis could occur. Reproductive/Nursing Safety In humans, the FDA categorizes potassium citrate as a category C drug for use during pregnancy (Animal studies have shown an ad-verse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). No specific data is available on the safety of citrates during nurs-ing, but no documented adverse effects have been reported. Overdosage/Acute Toxicity Overdosage and acute toxicity would generally fall into 4 categories: gastrointestinal distress and ulceration, metabolic alkalosis, hyper-natremia (sodium citrate), or hyper kalemia (potassium citrate). Should an overdose occur and there are reasonable expectations of pre venting absorption (especially with the tablets), gut-emptying protocols should be employed if not contraindicated. Otherwise, treat GI effects, if necessary, with intravenous fluids or other sup-portive care. Hyperkalemia, hypernatremia, and metabolic alkalosis should be treated if warranted. It is sug gested to refer to an animal poison control center, an internal medicine text or other references for addi tional information for specific treatment modalities for these conditions. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving citrates and may be of significance in veterinary patients: Am PHETAm INES; PSEUDOEPHEDRINE; EPHEDRINET! : Alkalinized urine can decrease excretion ANTACIDST! : Citrate alkalinizers used with antacids (particularly those containing bicarbonate or aluminum salts) may cause sys-temic alkalosis, and aluminum toxicity (aluminum antacids only) particularly in patients with renal insufficiency. Sodium citrate combined with sodium bicarbonate may cause hypernatremia, and may cause the development of calcium stones in patients with preex isting uric acid stones. ASPIRINT! : Alkalinized urine can increase the excretion of salicylates Fl UOROQUINOl ONEST! : The solubility of ciprofloxacin & enrofloxa-cin is decreased in an alkaline environment. Patients with alka-line urine should be monitored for signs of crystalluria. l ITHIUm T! : Alkalinized urine can decrease excretion m ETHENAm INET! : Concurrent use with methenamine is not recom-mended as it requires an acidic urine for efficacy. QUINIDINET! : Alkalinized urine can decrease excretion TETRACy Cl INEST! : Alkalinized urine can decrease excretion With potassium citrate products, the following agents may lead to increases in serum potassium levels (including severe hyper-kalemia), particularly in patients with renal insufficiency: ACE INHIb ITORS !! (e. g., enalapril, lisinopril ) Cy Cl OSPORINE!! DIg Ox IN!! HEPARIN!! NONS TEROIDAl ANTIINFl Amm ATOR y DRUg S !! (NSAIDS ) POTASSIUmCONTAININg DRUg S/FOODS!! SPIRONOl ACTONE; TRIAm TERENET! Doses DOg S:T! For adjunctive therapy to inhibit calcium oxalate crystal forma-tion in dogs with hypocitraturia: a) Potassium citrate: 40-75 mg/kg PO q12h; avoid overzealous urinary alkalinization as calcium phosphate uroliths may form (Grauer 2003) b) Potassium citrate: Initially 50 mg/kg PO q12h. Monitor urine p H; goal is to obtain values of 7-7. 5 (Bartges 2000) c) T o help decrease the possibility of calcium oxalate stone for-mation using Nutrived ® Potassium Citrate Granules: 1 scoop mixed or sprinkled on food per 10 lb. body weight per day. (Label information; Nutrived ® Potassium Citrate Granules for Dogs & Cats—Vedco) d) If calcium oxalate crystalluria is persistent or calcium oxalate uroliths occur and dietary and hydrochlorothiazide (2 mg/kg PO q12h) therapy have been implemented, give potassium citrate to effect to achieve a urine p H of 6. 5-7 using a start-ing dose of 50-75 mg/kg PO q12h. If urine p H already above 7-7. 5, do not use potassium citrate. Monitor serum potas-sium levels monthly and reduce dose if hyperkalemia occurs. (Adams and Syme 2005) For adjunctive therapy of chronic renal failure as a potassium supplement and alkalinizing agent:a) Potassium citrate: Initially, 75 mg/kg PO q12h (Bartges 2002a) CATS:T! For adjunctive therapy to inhibit calcium oxalate formation: a) Potassium citrate: initially 50-100 mg kg PO q12h. Goal is to achieve a urine p H of approximately 7. 5 (Bartges 2002a) b) T o help decrease the possibility of calcium oxalate stone for-mation using Nutrived® Potassium Citrate Granules: 1 scoop mixed or sprinkled on food per day. (Label information; Nu-trived ® Potassium Citrate Granules for Dogs & Cats—Vedco) c) Recommended dose is 100-150 mg/kg/day PO, but it is un-clear whether this dose will actually increase urinary citrate in cats. (Westropp, Buffington et al. 2005) For adjunctive therapy of chronic renal failure as a potassium supplement and alkalinizing agent: a) Potassium citrate: Initially, 75 mg/kg PO q12h (Bartges 2002a) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
204 Cl ARITHROmy CIN b) If cat is significantly acidemic: 2. 5 m Eq (total dose) potas-sium or 15-30 mg/kg as potassium citrate PO q12h (Wolf 2006b) c) When cats with CRF are hypokalemic: 2-4 m Eq (total dose) of potassium per day as potassium citrate or potassium glu-conate. (Di Bartola and Chew 2006a) monitoring Depending on patient's condition, product chosen and reason for use: Serum potassium, sodium, bicarbonate, chloride T! Acid/base status T! Urine p H, Urinalysis T! Serum creatinine, CBC, particularly in chronic renal failure T! Chemistry/Synonyms Generally used as alkalinizing agents, citric acid and citrate salts are available in sev eral commercially available dosage forms. Citric acid occurs as an odorless or practically odorless, colorless, trans-lucent crystal with a strong acidic taste. It is very soluble in water. Potassium citrate occurs as odorless, transparent crystals or a white, granular powder having a cooling, saline taste. It is freely soluble in water. 108 mg of potassium citrate contains approximately 1 m Eq of potassium. Sodium citrate occurs as colorless crystals or a white, granular powder. The hydrous form is freely soluble in water. Potassium citrate may also be known as citrate of potash, or citric acid tripotassium salt monohydrate. Sodium citrate and citric acid solutions may also be known as Shohl's solution. Storage/Stability Store solutions and potassium citrate tablets in tight containers at room temperature unless otherwise recommended by manufacturer. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Potassium Citrate and Fatty Acids Granules: each 5 grams (one scoop) contains 300 mg potassium citrate (approximately 2. 8 m Eq of potassium) and 423 mg total fatty acids; also contains several amino acids—quantities not labeled; Nutrived ® Potassium Citrate Granules for Cats and Dogs (Vedco); (OTC) HUm ANl Ab El ED PRODUCTS: Potassium Citrate Tablets: 5 m Eq (540 mg), 10 m Eq (1080 mg); Urocit-K®; (Mission); (Rx) Potassium Citrate/Sodium Citrate Combinations: Tablets: 50 mg potassium citrate and 950 mg sodium citrate. Citro-lith® (Beach Pharm); (Rx) Syrup: 550 mg potassium citrate, 500 mg sodium citrate, 334 mg citric acid/5 m L (1m Eq K, 1 m Eq Na per m L equivalent to 2 m Eq bicarbonate); in 120 and 480 m L, Polycitra ® (Willen); (Rx) Solution: 550 mg K citrate, 500 mg sodium citrate, 334 mg citric acid/5 m L (1 m Eq K, 1 m Eq Na per m L; equiv to 2 m Eq bicarbonate) in 120 and 480 m L. Polycitra-LC® (Willen); (Rx). 1100 mg potassium citrate, 334 mg citric acid/5 m L, (2 m Eq K/m L; equiv. to 2 m Eq bicarbonate) in 120 and 480. Polycitra-K® (Willen); (Rx) Crystals for Reconstitution: 3300 mg K citrate, 1002 mg citric acid per UD packet (equiv. T o 30 m Eq bicarbonate) in single dose pack-ets. Polycitra-K® (Willen); (Rx) Citric Acid/Sodium Citrate Combinations: Solutions: Sodium Citrate Dihydrate 490 mg sodium citrate and Citric Acid 640 mg per 5 m L (1 m Eq sodium equiv to 1 m Eq bicar-bonate/m L) in 500 m L and UD 15 and 30 m L, Oracit®; (Carolina Medical); (Rx) Sodium Citrate Dihydrate 500 mg sodium citrate and Citric 334 mg per 5 m L (1 m Eq sodium equiv to 1 m Eq bicarbonate/m L) in 120 and 473 m L and UD 15 and 30 m L; Bicitra®; (Alza Corp); (Rx) Potassium Citrate, Sodium Citrate/Citric Acid Solutions: 550 mg potassium citrate monohydrate, 500 mg sodium citrate dihy-drate, 334 mg citric acid monohydrate per 5 m L (1 m Eq potassium and 1 m Eq sodium per m L and is equivalent to 2 m Eq bicarbonate in 60 oz bottles; Cytra-LC® (Cypress); (Rx) 1100 mg potassium citrate monohydrate and 334 mg citric acid monohydrate per 5 m L (2 m Eq potassium per m L and is equivalent to 2 m Eq bicarbonate) in 473 m L; Cytra-K® (Cypress); (Rx) 20 m Eq potassium, 30 m Eq citrate (20 g dextrose, 5 g fructose, 35 m Eq chloride, 45 m Eq sodium)/L in 1 liter; Naturalyte® Oral Elec-trolyte Solution (Unico); (OTC) cl Arithromycin (klar-ith-ro-my-sin) Biaxin® macr Olide antibi O tic Prescriber Highlights Macrolide antibiotic that may useful for treating atypical T T mycobacterial infections or treatment of Helicobacter spp. infections in dogs, cats, & ferrets; Rhodococcus equi infections in foals Appears to be well tolerated by domestic animals, but T T clinical experience is limited Many potential drug interactions T T Expense may be an issue T T Uses/Indications In small animal medicine, clarithromycin is primarily of inter-est in treating atypical mycobacterial infections or treatment of Helicobacter spp. infections in cats and ferrets. In equine medicine, clarithromycin may be useful in treating Rhodococcus equi infections in foals. Pharmacology/Actions Clarithromycin, like other macrolide antibiotics, penetrate suscep-tible bacterial cell walls and bind to the 50S ribosomal subunit inhib-iting protein synthesis. The drug is usually bacteriostatic, but may be bactericidal at high concentrations in very susceptible organisms. Clarithromycin's spectrum of activity is similar to that of eryth-romycin, but it also has activity against a variety of bacteria that are not easily treated with other antibiotics (e. g., atypical mycobacte-ria). Activity against gram-positive aerobic cocci is similar to that of erythromycin, but lower concentrations are required to be effec-tive against susceptible organisms. The drug is typically not effec-tive against oxacillin-resistant Staph or coagulase-negative Staph. Clarithromycin also has activity against Rhodococcus equi. Activity against gram-negative aerobic bacteria includes Haemophilus influ-enzae, Pasturella multocida, Legionella pneumophilia, Bordetella per-tussis and Campylobacter spp. Clarithromycin has inhibitory activ-ity against a variety of atypical mycobacteria, including M. avium complex and M. leprae. Clarithromycin has good activity against Mycoplasma pneumoniae and Ureaplasma ureatlyticum. Other or- | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl ARITHROmy CIN 205 ganisms where clarithromycin may have therapeutic usefulness in-clude: Nocardia spp. Toxoplasma gondii, Helicobacter pylori, Borrelia burgdorferi, and Cryptosporidium parvum. Pharmacokinetics In horses (foals), the drug is apparently well absorbed after intra-gastric administration with peak serum concentrations occurring about 1. 5 hours after dosing. Elimination half-life is about 4. 8 hours. In dogs, clarithromycin bioavailability ranges from 60-83% with the higher values obtained when given to fasted animals. Contraindications/Precautions/Warnings In humans, clarithromycin is contraindicated in patients hyper-sensitive to it or other macrolide antibiotics (e. g., erythromycin, azithromycin). Adverse Effects The adverse effect profile for clarithromycin in domestic animals is not well described. With limited clinical experience, it appears to be well tolerated in dogs, cats, ferrets, and foals. Like all orally admin-istered antibiotics, GI disturbances are possible. Pinnal or general-ized erythema may be associated with this drug when used in cats. Adverse effects in humans include gastrointestinal adverse ef-fects (primarily nausea, vomiting, abdominal pain, abnormal taste, diarrhea) that, when compared with erythromycin, are milder and occur less frequently. Approximately 4% of treated humans develop transient, mildly elevated BUN levels. Rarely, prolonged QT inter-val (torsades de pointes), hepatotoxicity, thrombocytopenia, or hy-persensitivity reactions have been reported. Pseudomembranous colitis secondary to Clostridium difficile has been reported after clarithromycin use. Reproductive/Nursing Safety In humans, the FDA categorizes clarithromycin as a category C drug for use during pregnancy (Animal studies have shown an ad-verse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). T eratogenic studies in rats and rabbits failed to docu-ment any teratogenic effects in some studies, but, at high dosages (yielding plasma levels 2-17 times achieved in humans with maxi-mum recommended dosages) in pregnant rats, rabbits and mon-keys, some effects (cleft palate, cardiovascular abnormalities, fetal growth retardation) were noted. Clarithromycin is excreted into milk of lactating animals and levels may be higher in milk than in the dam's plasma, but this is unlikely to be of clinical significance. Overdosage/Acute Toxicity Generally, overdoses of clarithromycin are usually not serious with only gastrointestinal effects seen. Patients ingesting large overdoses may be given activated charcoal/cathartic to remove any unab-sorbed drug. Forced diuresis, peritoneal dialysis, or hemodialysis do not appear to be effective in removing the drug from the body. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clarithromycin and may be of significance in veterinary patients: CISAPRIDET! : Clarithromycin can inhibit the metabolism of cisap-ride and the manufacturer states that use of these drugs together (in humans) is contraindicated Fl UCONAz Ol ET! : Possible increased clarithromycin levels DIg Ox INT! : Clarithromycin may increase the serum levels of digoxin Om EPRAz Ol ET! : Clarithromycin and omeprazole can increase the plasma levels of one another WARFARINT! : Clarithromycin may potentiate the effects of oral an-ticoagulant drugs z IDOVUDINET! : Clarithromycin may decrease serum concentrations of zidovudine Clarithromycin, like erythromycin, can inhibit the metabolism of other drugs that use the CYP3A subfamily of the cytochrome P450 enzyme system. Depending on the therapeutic index of the drug(s) involved, therapeutic drug monitoring and/or dosage reduction may be required if the drugs must be used together. These drugs include: Al FENTANIl T! b ROm OCRIPTINET! b USPIRONET! CARb Am Az EPINET! DISOPy RAm IDE T! (also risk of increased QT interval) m ETHyl PREDNISOl ONET! m IDAz Ol Am, Al PRAz Ol Am, TRIAz Ol Am T! QUINIDINE T! (also risk of increased QT interval) RIFAb UTINT! TACROl Im US T! (systemic ) THEOPHyll INET! laboratory Considerations No clarithromycin-related laboratory interactions noted. T! Doses DOg S:T! For treatment of severe or refractory cases of canine leproid granuloma syndrome:a) Using a combination of clarithromycin 15-25 mg/kg total daily dose PO given divided q8- 12h; and rifampin 10-15 mg/kg PO once daily. Usually treatment should be continued for 4 -8 weeks until lesions are at least substantially reduced in size and ideally have resolved completely. (Malik, Martin et al. 2001) For susceptible infections: a) 2. 5-10 mg/kg PO twice daily (Boothe 1999) b) 5-10 mg/kg PO q12h (Greene and Watson 1998) CATS:T! For treatment of feline leprosy: a) Using a regimen of either two or three of the following drugs: clarithromycin: 62. 5 mg per cat q12h; clofazimine: 25-50 mg once per day or 50 mg every other day; rifampin: 10-15 mg/kg once a day. (Malik, Hughes et al. 2002) For treatment of Nocardia (N. nova) infections: a) Combination therapy with: amoxicillin 20 mg/kg PO twice daily with clarithromycin 62. 5-125 mg (total dose per cat) PO twice daily and/or doxycycline 5 mg/kg or higher PO twice daily. (Malik 2006a) For treatment of H. pylori infections: a) Combination therapy with: clarithromycin 7. 5 mg/kg PO twice daily; metronidazole 10-15 mg/kg PO twice daily; amoxicillin 20 mg/kg PO twice daily for 14 days. (Simpson 2003b) For treatment of M. tuberculosis-bovis variant infections: a) Using all three drugs: Clarithromycin 5- 10 mg/kg PO q12h; rifampin 10-20 mg/kg PO once daily, enrofloxacin 5-10 mg/kg PO q12- 24h. Treatment must continue for at least 2 months. Maintenance for additional 4 months using (at same dosages enrofloxacin and clarithromycin or rifampin and enrofloxacin). (Greene and Gunn-Moore 1998) For susceptible infections: a) 7. 5 mg/kg PO q12h (Greene and Watson 1998) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
206 Cl Em ASTINE FUm ARATE FERRETS:T! For treatment of Helicobacter mustelae infections: a) Clarithromycin 12. 5 mg/kg PO q8h with ranitidine bismuth citrate ( Note : not currently available in the USA) 24 mg/kg PO q8h. Mild to moderate antral gastritis may persist even if H. mustelae eradicated. (Marini, Fox et al. 1999) b) 12. 5-50 mg/kg q8-24h with omeprazole at 0. 7 mg/kg PO once daily (q24h) (Fisher 2005) HORSES:T! For treatment of Rhodococcus equi infection in foals:a) 7. 5 mg/kg PO q12h (Jacks, Giguere et al. 2002), (Chaffin 2006b) b) 7. 5 mg/kg PO q12h in combination with rifampin at 5 mg/kg PO q12h or 10 mg/kg PO q24h. (Giguere 2003b) monitoring Antibacterial efficacy T! Adverse effects T! Client Information If using the oral suspension, do T! not refrigerate; keep at room tem-perature and discard 14 days after reconstituting This drug may be given without regard to meals T! Clarithromycin can interact with many other drugs; do not give T! any drugs to the animal without the veterinarian's knowledge Chemistry/Synonyms Clarithromycin is a semi-synthetic macrolide antibiotic related to erythromycin. It differs from erythromycin by the methylation of position 6 in the lactone ring. Clarithromycin occurs as a white to off-white crystalline powder. It is practically insoluble in water, slightly soluble in ethanol, and soluble in acetone. It is slightly solu-ble in a phosphate buffer at p H's of 2-5. Clarithromycin may also be known as: 6-O-Methylerythromycin, TE-031, A-56268, Adel ®, Biaxin®, Biclar®, Bremon®, Clamicin®, Clamycin®, Claribid®, Clarimac®, Clarimax®, Claritab®, Cyllind®, Gervaken®, Heliclar®, Helicodid®, Karin®, Klacid®, Klaciped®, Klaricid®, Klaridex®, Kofron®, Lagur®, Mabicrol®, Macladin®, Maclar®, Mavid ®, Monaxin®, Monocid®, Naxy®, Veclam®, and Zeclar®. Storage/Stability The conventional 250 mg tablets should be protected from light and stored in well-closed containers at 15-30°C (59-86°F). The con-ventional or extended-release 500 mg tablets should be stored in well-closed containers at controlled room temperature (20-25°C; 68-77°F). The granules for reconstitution into an oral suspension should be stored in well-closed containers at 15-30°C. After recon-stitution, it should be stored at room temperature (do not refriger-ate) and any unused drug discarded after 14 days. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Clarithromycin Film-coated Tablets: 250 mg & 500 mg; Extended-release Tablets: 500 mg & 1000 mg; Clarithromycin (T eva; Ranbaxy); Biaxin® & Biaxin® XL (Abbott), generic; (Rx) Clarithromycin Granules for Oral Suspension: 25 mg/m L, 50 mg/ m L in 50 m L and 100 m L; Biaxin® (Abbott), generic; (Rx) A pre-packaged combination containing lansoprazole, amoxicillin and clarithromycin for H. pylori is marketed as Prevpak® (TAP); (Rx) Clavulanate/Amoxicillin — See Amoxicillin/Clavulanate Clavulanate/Ticarcillin — See Ticarcillin /Clavulanate clem Astine fum Ar A te (klem-as-teen) Tavist® antihistamine Prescriber Highlights Oral antihistamine with greater anticholinergic, but less T T sedative activity Poor pharmacokinetic profile for oral administration in T T dogs or horses Contraindications: Hypersensitivity T T Caution: Prostatic hypertrophy, bladder neck obstruc tion, T T severe cardiac failure, angle-closure glaucoma, or pyelo-duodenal obstruction Most likely adverse effects: T T DOGS: Sedation, paradoxical hyperactivity & anticholinergic effects (dryness of mu-cous membranes, etc. ); CATS: Diarrhea Uses/Indications Clemastine may be used for symptomatic relief of histamine 1-relat-ed allergic conditions. Pharmacology/Actions Like other H 1-receptor antihistamines, clemastine acts by compet-ing with his tamine for sites on H 1-receptor sites on effector cells. They do not block histamine release, but can antagonize its effects. Clemastine has greater anticholinergic activity, but less sedation than average. Pharmacokinetics In dogs, oral bioavailability is very low (3%). Clemastine has a high volume of distribution (13. 4 L/kg; 98% protein bound) and clear-ance (2. 1 L/hr/kg). After IV administration, elimination half-life is about 4 hours and completely inhibited wheal formation for 7 hours. Oral administration at 0. 5 mg/kg only yielded minor inhibition of wheal formation. The authors of the study (Hansson, Bergvall et al. 2004) concluded that most oral dosage regimens in the literature are likely to give too low a systemic exposure of the drug to allow effective therapy. In horses, clemastine has poor oral bioavailability (3-4%), a vol-ume of distribution at steady-state of 3. 8 L/kg, a clearance (TBC) of 0. 79 L/hr/Kg and a terminal half-life of about 5. 4 hours. The authors concluded that the drug is not appropriate for oral administration in the horse and must be dosed at least 3-4 times a day intrave-nously to maintain therapeutic plasma concentrations. (T orneke, Ingvast-Larsson et al. 2003) In humans, clemastine has a variable bioavailability (20-70%); its dis tribution is not well characterized, but does distribute into milk. Metabolic fate has not been clearly determined, but it appears to be extensively metabolized and those metabolites are eliminated in the urine. In humans, its duration of action is about 12 hours. Contraindications/Precautions/Warnings Clemastine is contraindicated in patients hypersensitive to it. It should be used with caution in patients with prostatic hypertrophy, bladder neck obstruction, severe cardiac failure, angle-closure glau-coma, or pyeloduodenal obstruction. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl ENb UTEROl HCl 207 Adverse Effects The most likely adverse effects seen in dogs receiving clemastine are sedation, paradoxical hyperactivity, and anticholinergic effects (dryness of mucous membranes, etc. ). In cats, diarrhea has been noted most commonly; one cat reportedly developed a fixed drug reaction while on this medication. Reproductive/Nursing Safety Clemastine has been tested in pregnant lab animals in doses up to 312 times labeled without evi dence of harm to fetuses. However, be-cause safety has not been established in other species, its use during pregnancy should be weighed carefully. In humans, the FDA cat-egorizes 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. ) Clemastine enters maternal milk and may potentially cause adverse effects in offspring. Use with caution, especially with newborns. Overdosage/Acute Toxicity There are no specific antidotes available. Significant overdoses should be handled using standard gut emptying protocols, when appropriate, and supportive therapy initiated when required. The adverse effects seen with overdoses are an extension of the drug's side effects; principally CNS depression (although CNS stimula-tion may be seen), anticholinergic effects (severe drying of mucous membranes, tachycardia, urinary retention, hyperthermia, etc. ), and possi bly hypotension. Physostigmine may be considered to treat serious CNS anticholinergic effects and diazepam employed to treat seizures, if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clemastine and may be of significance in veterinary patients: CNS DEPRESSANT m EDICATIONS T! : Additive CNS depression may be seen if combining clemastine with other CNS depressant medi-cations such as barbiturates, tranquilizers, etc. m ONOAm INE Ox IDASE INHIb ITORS T! (including furazolidone, amitraz, and possibly selegiline ) may intensify the anticholinergic effects of clemastine laboratory Considerations Because antihistamines can decrease the wheal and flair response to skin allergen testing, antihistamines should be discontinued 3-7 days (depending on the antihis tamine used and the reference) be-fore intradermal skin tests. Doses DOg S:T! Note : Recently published information (Hansson, Bergvall et al. 2004) on the pharmacokinetics of clemastine in dogs puts the effi-cacy of previously published doses for this drug in doubt, but some veterinary dermatologists still recommend its use. Usual doses pub-lished are approximately 0. 05-0. 1 mg/kg PO q12h; however oral bioavailability (see Pharmacokinetics above) in dogs is less than 5% versus approximately 20-70% in humans, and an oral dose of 0. 5 mg/kg (10X most published doses) in dogs only inhibited histamine-induced wheal formation to a slight degree, while IV ad-ministration inhibited it for 7 hours. Further dosing studies must be performed before this drug can be recommended for therapeutic use in the dog. CATS:T! As an antihistamine:a) 0. 68 mg per cat PO twice daily (Miller 2005a) b) 0. 34-0. 68 mg per cat PO q12h (Messinger 2000) c) For atopy: 0. 15 mg/kg PO q 12 hrs. Efficacy may be increased by combining with omega 3 fatty acids. (Campbell 1999) monitoring Efficacy T! Adverse Effects, if any T! Client Information Clients should understand that antihistamines may be useful for T! symptomatic relief of allergic signs, but are not a cure for the underlying disease. Chemistry/Synonyms Also known as meclastine fumarate or mecloprodin fumarate, cle-mastine fumarate is an ethanolamine antihistamine. It occurs as an odorless, faintly yellow, crystalline powder. It is very slightly soluble in water and sparingly soluble in alcohol. Tavist-D® contains clemastine fumarate in an immediate release outer shell and phenyl propanolamine HCl in a sustained release in-ner matrix. Clemastine fumarate may also be known by the following syn-onyms and internationally registered trade names: clemastini fu-maras, HS-592, meclastine fumarate, mecloprodine fumarate, Agasten®, Aller-Eze®, Antihist-1®, Clamist®, Contac 12 Hour Allergy®, Dayhist-1®, Tave g il ®, Tave g y l ® or Tavist®. Storage/Stability Oral tablets and solution should be stored in tight, light resistant containers at room temperature. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Clemastine Fumarate Tablets: 1. 34 mg (equivalent to 1 mg clemas-tine), 2. 68 mg (equivalent to 2 mg clemastine); Dayhist-1® (Major); Tavist® Al l e r g y (Novartis Consumer Health); generic; (Rx & OTC) Clemastine Syrup: 0. 67 mg/5 m L (equivalent to 0. 5 mg/5m L clem-astine) in 120 m L; generic; (Rx) clenbuterol hcl (klen-byoo-ter-ol) Ventipulmin® Prescriber Highlights Beta-2-adrenergic agonist used in horses as a bronchodi-T T lator in the management of airway obstruction Banned in food animals T T In pregnancy, antagonizes the effects of dinoprost (pros-T T taglandin F2alpha) & oxytocin & can diminish normal uterine contractility May cause tachycardia, muscle tremors, sweating, rest-T T lessness, & urticaria | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
208 Cl ENb UTEROl HCl Uses/Indications Clenbuterol is approved for use in horses as a bronchodilator in the management of airway obstruction, such as recurrent airway ob-struction (RAO; formerly COPD). It has been used as a partitioning agent in food producing ani-mals, but its use for this purpose is banned in the USA as relay toxic-ity in humans has been documented. Pharmacology/Actions Like other beta-2 agonists, clenbuterol is believed to act by stimu-lating production of cyclic AMP through the activation of adenyl cyclase. By definition, beta-2 agonists have more smooth muscle re-laxation activity (bronchial, vascular, and uterine smooth muscle) versus its cardiac effects (beta-1). Clenbuterol appears to have sec-ondary modes of action in horses as it can inhibit the release from macrophages of pro-inflammatory cytokines such as interleukin-1(beta) and tumor necrosis factor (alpha), and increase ciliary beat frequency to enhance mucous clearance. Pharmacokinetics After oral administration to horses, peak plasma levels of clenbuterol occur 2 hours after administration and the average half-life is about 10-13 hours. The manufacturer states that the duration of effect varies from 6-8 hours. After multiple oral doses, the drug's volume of distribution is approximately 1. 6 L/kg and clearance was 94 m L/kg/hr. Urinary concentrations of clenbuterol are approximately 100X those found in plasma and can persist at quantifiable levels for 288 hours (12 days) in urine after the last oral dose (Soma, Uboh et al. 2004). Contraindications/Precautions/Warnings The drug is contraindicated in food produc ing animals (legal rami-fications). The label states that the drug should not be used in horses suspected of having cardio vascular impairment as tachycardia may occur. Adverse Effects Muscle tremors, sweating, restlessness, urticaria, and tachycardia may be noted, particularly early in the course of therapy. Creatine kinase elevations have been noted in some horses and, rarely, ataxia can oc-cur. Clenbuterol is reported to induce abortion in pregnant ani mals. Clenbuterol has been touted in some body building circles as an alternative to anabolic steroids for muscle development and body fat reduction; however, its safe use for this purpose is in serious ques-tion. Be alert for scams to divert legitimately obtained clenbuterol for this purpose. Reproductive/Nursing Safety Clenbuterol's safety in breeding stallions and brood mares has not been established. Clenbuterol should not be used in pregnant mares near full-term as it antago nizes the effects of dinoprost (prosta-glandin F2alpha) and oxytocin and can diminish normal uterine contractility. Overdosage/Acute Toxicity Some case reports of clenbuterol overdoses have been reported in various species. In recent years, clenbuterol has been used as an adulterant in illicit heroin. Depending on dosage and species, emp-tying gut may be appropriate, otherwise supportive therapy and ad-ministration of parenteral beta-blockers to control heart rate and rhythm and elevated blood pressure may be considered. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clenbuterol and may be of significance in veterinary patients:ANESTHETICS, INHAl ANTT! : Use with inhalation anesthetics (e. g., ha lothane, isoflu rane, methoxyflurane ), may predispose the patient to ventricular arrhythmias, particularly in pa tients with preexisting cardiac disease—use cautiously b ETAbl OCKERST! (e. g., propranolol ): May antag onize clenbuterol's ef-fects DIg Ox INT! : Use with digitalis glycosides may increase the risk of car-diac arrhythmias DINOPROSTT! : Clenbuterol may antagonize the effects of dinoprost (prostaglandin F2alpha) Oxy TOCINT! : Clenbuterol may antagonize the effects of oxytocin Sym PATHOm Im ETIC Am INES, OTHERT! (e. g., terbutaline, albuterol ): Con-comitant administration with other sympathomimetic amines) may enhance the adverse effects of clenbuterol TRICy Cl IC ANTIDEPRESSANTS T! or m ONOAm INE Ox IDASE INHIb ITORS : May po tentiate the vascular effects of clenbuterol Doses HORSES:T! (Note: ARCI UCGFS Class 3 Drug) As a bronchodilator: a) Initially, 0. 8 micrograms/kg (practically: 0. 5 m L of the com-mercially available syrup/100 lb. BW) twice daily for 3 days; if no improvement increase to 1. 6 micrograms/kg (practically: 1 m L of the commercially available syrup/100 lb. BW) twice daily for 3 days; if no improvement increase to 2. 4 micro-grams/kg (practically: 1. 5 m L of the commercially available syrup/100 lb. BW) twice daily for 3 days; if no improvement increase to 3. 2 mi crograms/kg (practically: 2 m L of the com-mercially available syrup/100 lb. BW) twice daily for 3 days; if no improvement discontinue therapy. Recommended du-ration of ther apy is 30 days; then withdraw therapy and re-evaluate. If signs return, reinitiate therapy as above. (Package Insert; Ventipulmin®) monitoring Clinical efficacy T! Adverse effects (primarily cardiac rate)T! Client Information Clients should be instructed on the restricted use requirements of T! this medica tion and to keep it secure from children or those who may “abuse” it. The drug may be prohibited from use by various equine associa-T! tions (e. g., racing or show). Chemistry/Synonyms A beta-2-adrenergic agonist, clenbuterol HCl's chemical name is 1-(4-Amino-3,5-dichlorophenyl)-2-tert-butyl aminoethanol HCl. Clenbuterol HCl may also be known as: NAB-365, Aeropulmin®, Broncodil®, Broncoterol®, Bronq-C®, Cesbron®, Clembumar®, Clenasma®, Clenbutol®, Contrasmina®, Contraspasmin®, Monores®, Novegam®, Oxibron®, Oxyflux®, Prontovent®, Spiropent®, Ventilan®, Ventipulmin® or Ventolase®. Storage/Stability The commercially available syrup is colorless and should be stored at room temperature (avoid freezing). The manufacturer warns to re place the safety cap on the bottle when not in use. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Clenbuterol HCl Oral Syrup: 72. 5 mcg/m L in 100 m L, 330 m L, 460 m L bottles; Ventipulmin® Syrup (Boehringer Ingelheim); Aeropul-min® Syrup (Butler, Phoenix); (Rx). Approved for use in horses not intended for use as food. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl INDAmy CIN 209 Extra-label clenbuterol use in food animals is prohibited by federal (USA) law. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: None clind Amycin hcl clind Amycin p Almit Ate hcl clind Amycin phosph A te (klin-da-mye-sin) An tirobe®, Cleocin® linc Osamide antibi O tic Prescriber Highlights Lincosamide antibiotic, broad spectrum against many T T anaerobes, gram-positive aerobic cocci, Toxoplasma, etc. Contraindications: Horses, rodents, ruminants, lago-T T morphs; patients hypersensitive to lin cosamides Caution: Liver or renal dysfunction; consider reducing T T dosage if severe Adverse Effects: gastroenteritis, esophageal injuries pos-T T sible if “dry pilled”, pain at injection site if given IM Uses/Indications Clindamycin products are approved for use in dogs and cats. The labeled indica tions for dogs include wounds, abscesses and osteo-myelitis caused by Staphylococcus aureus. Be cause clindamycin has excellent activity against most pathogenic anaerobic organisms, it is also used extensively for those infections. Clindamycin is used for a variety of protozoal infections, including toxoplasmosis. For fur-ther information, refer to the Dosage or Pharmacology sections. Pharmacology/Actions The lincosamide antibiotics, lincomycin and clindamycin, share mechanisms of ac tion and have similar spectrums of activity, al-though lincomycin is usually less active against sus ceptible organ-isms. Complete cross-resistance occurs between the two drugs; at least partial cross-resistance occurs between the lincosamides and erythromycin. They may act as bacteriostatic or bactericidal agents, depending on the concentration of the drug at the infection site and the sus ceptibility of the organism. The lincosamides are be-lieved to act by binding to the 50S ribosomal subunit of susceptible bacteria, thereby inhibiting peptide bond formation. Most aerobic gram-positive cocci are susceptible to the lin-cosamides (Strep. faecalis is not) includ ing Staphylococcus and Streptococci. Other organisms that are generally susceptible include: Corynebacterium diphtheriae, Nocardia asteroides, Erysepelothrix, T oxoplasma, and Mycoplasma spp. Anaerobic bacteria that are generally susceptible to the lincosamides include: Clostridium per fringens, C. tetani (not C. difficile), Bacteroides (including many strains of B. fragilis), Fusobac terium, Peptostreptococcus, Actinomyces, and Peptococcus. Pharmacokinetics In dogs, oral bioavailability is about 73%, elimination half-life is reportedly 2 -5 hours after oral administration and 10-13 hours after subcutaneous administration. Volume of distribution is about 0. 9 L/kg. In humans, the drug is rapidly absorbed from the gut and about 90% of the total dose is absorbed. Food de creases the rate of ab-sorption, but not the extent. Peak serum levels are attained about 45-60 minutes after oral dosing. IM administration gives peak lev-els about 1-3 hours post injection. Clindamycin is distributed into most tissues. Therapeutic levels are achieved in bone, synovial fluid, bile, pleural fluid, peritoneal fluid, skin, and heart muscle. Clindamycin also penetrates well into abscesses and white blood cells. CNS levels may reach 40% of those in the serum if meninges are inflamed. Clindamycin is about 93% bound to plasma proteins. The drug crosses the placenta and can be distributed into milk at concentrations equal to those in plasma. Clindamycin is partially metabolized in the liver to both active and inactive metabolites. Un changed drug and metabolites are ex-creted in the urine, feces, and bile. Half-lives can be prolonged in patients with severe renal or hepatic dysfunction. Contraindications/Precautions/Warnings Although there have been case reports of parenteral administration of lincosamides to horses, cattle, and sheep, the lincosamides are considered to be contraindicated for use in rabbits, hamsters, chin-chillas, guinea pigs, horses, and ruminants be cause of serious gas-trointestinal effects that may occur, including death. Clindamycin is contraindi cated in patients with known hypersensitivity to it or lincomycin. Patients with very severe renal and/or hepatic disease should re-ceive the drug with caution and the manufacturer sug gests moni-toring serum clindamycin levels during high-dose therapy; consider dosage reduction. Clindamycin use is generally avoided in neonatal small animals. Adverse Effects Adverse effects after oral administration reported in dogs and cats include gastroenteritis (emesis, loose stools, and infrequently bloody diarrhea in dogs). There have been case reports of esopha-geal injuries (esophagitis, strictures) occurring in cats when solid dosage forms were given without food or a water bolus. Cats may occasional show hypersalivation or lip smacking after oral adminis-tration. IM injections reportedly cause pain at the injection site. C. difficile-associated pseudomembranous colitis has been re-ported in some species, but does not appear to be a significant risk when clindamycin is used in dogs or cats. Reproductive/Nursing Safety Clindamycin crosses the placenta, and cord blood concentrations are approximately 46% of those found in maternal serum. Safe use during pregnancy has not been established, but neither has the drug been implicated in causing teratogenic effects. 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 sys-tem 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 the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) Because clindamycin is distributed into milk, nursing puppies or kittens of mothers receiving clin damycin may develop diarrhea. However, in humans, the American Academy of Pediatrics consid-ers clindamycin compatible with breastfeeding. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
210 Cl INDAmy CIN Overdosage/Acute Toxicity There is little information available regarding overdoses of this drug. In dogs, oral doses of up to 300 mg/kg/day for up to one year did not result in toxicity. Dogs receiv ing 600 mg/kg/day, developed anorexia, vomiting, and weight loss. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clindamycin and may be of significance in veterinary patients: Cy Cl OSPORINET! : Clindamycin may reduce levels ERy THROmy CINT! : in vitro antagonism when used with clindamycin; concomitant use should probably be avoided NEUROm USCUl AR bl OCKINg Ag ENTS T! (e. g., pancuronium ): Clindamycin possesses intrinsic neuromuscular blocking activity and should be used cautiously with other neuromuscular blocking agents laboratory Considerations Slight increases in T! liver function tests (AST, ALT, Alk. Phosph. ) may occur. There is apparently not any clinical significance associated with these increases. Doses DOg S:T! For susceptible bacterial infections:a) For infected wounds, abscesses and dental infections: 5. 5-33 mg/kg PO q12h; for osteomyelitis: 11-33 mg/kg PO q12h. Treatment may continue for up to 28 days. If no response after 3-4 days, discontinue. (Package insert; Antirobe®—Pfizer) b) For staphylococcal pyoderma: 11 mg/kg PO once daily for 7-28 days For wounds, abscesses, dental infections, stomatitis: 5-11 mg/kg PO q12h for 7-28 days. For osteomyelitis: 11 mg/kg PO q12h for 28 days For systemic, bacteremia: 3-10 mg/kg IV, IM SC, PO q8h as long as needed (Greene and Watson 1998) c) 5-11 mg/kg IM, SC or PO q12h avoid or reduce dose in pa-tients with severe liver failure (Vaden and Papich 1995) d) For sepsis: 11 mg/kg IV q12h (Hardie 2000) e) For recurrent superficial pyodermas: 11 mg/kg PO once daily to twice a day; resistance can develop quickly (Logas 2005b) f) For actinomycosis: 5 mg/kg SC q12h (Edwards 2006) g) For susceptible hepatobiliary infections: 10-16 mg/kg SC once daily or 5-10 mg/kg PO q12h. In patients with liver function impairment: 5 mg/kg PO q12h or SC q24h (Center 2006b) h) For anaerobic infections: 5-10 mg/kg PO, IV q12h (Greene and Jang 2006a) i) For intra-abdominal sepsis 5-11 mg/kg IV, SC, PO q8 -12h for 5-7 days combined with gentamicin or a parenteral 3rd gen-eration cephalosporin (such as cefotaxime) or enrofloxacin. For pancreatitis: 5-11 mg/kg IV, SC, PO q8-12h for 3-5 days. (Greene 2006) j) For susceptible respiratory infections: 10 mg/kg PO, SC q12h (Greene and Reinero 2006) k) For surgical prophylaxis for gram-positive aerobes and anaer-obic coverage: 5-11 mg/kg PO 16-60 minutes preoperatively (Greene and Jang 2006b)For susceptible protozoal infections:a) For T oxoplasmosis: 12. 5 mg/kg PO or IM q12h for 28 days For Neospora: 10 mg/kg q12h for 4 weeks. Used concurrently with trimethoprim/sulfa (15 mg/kg PO q12h for 4 weeks) For Hepatozoon canis: 10 mg/kg PO q8h for 2-4 weeks. Use concurrently with pyrimethamine (0. 25 mg/kg PO once daily for 2 -4 weeks) and trimethoprim/sulfa (15 mg/kg PO q12h for 2 -4 weeks) For Babesia spp. : 12. 5 mg/kg q12h PO for 2 weeks (Lappin 2000) c) For Babesia infections if specific antibabesial drugs (e. g., di-minazene, imidocarb, pentamidine) are not available: 25 mg/kg PO q12h for 7-21 days (Taboada and Lobetti 2006) d) For Hepatozoon americanum infections: 10 mg/kg PO q8h for 14 days. Use concurrently with trimethoprim/sulfa (15 mg/kg PO q12h 14 days) and pyrimethamine (0. 25 mg/kg PO once daily for 14 days) and then follow with decoquinate (for 2 years) once clinical signs have resolved. (Macintire, Vincent-Johnson et al. 2006) CATS: T! For susceptible bacterial infections:a) 5-10 mg/kg PO q12h (Jenkins 1987b); (Trepanier 1999) b) For infected wounds, abscesses and dental infections: 11-33 mg/kg PO once a day (q24h). Do not treat acute infections for more than 3- 4 days if no clinical response is seen. Maxi-mum labeled treatment period = 14 days (Package insert; Antirobe®—Pfizer) c) For sepsis: 11 mg/kg IV q12h (Hardie 2000) d) For anaerobic infections: 5-10 mg/kg PO, IV q12h (Greene and Jang 2006a) e) For intra-abdominal sepsis 5-11 mg/kg IV, SC, PO q8 -12h for 5-7 days combined with gentamicin or a parenteral 3rd gen-eration cephalosporin (such as cefotaxime) or enrofloxacin. For pancreatitis: 5-11 mg/kg IV, SC, PO q8-12h for 3-5 days. (Greene 2006) f) For susceptible respiratory infections: 10-15 mg/kg PO, SC q12h (Greene and Reinero 2006) g) For surgical prophylaxis for gram-positive aerobes and anaer-obic coverage: 5-11 mg/kg PO 16-60 minutes preoperatively (Greene and Jang 2006b) For susceptible protozoal infections:a) T oxoplasmosis: T o decrease zoonotic risk to susceptible humans by reducing shedding period in cats suspected of toxoplasmosis after fe-cal exam: 25-50 mg/kg PO daily; alternative medications in-clude sulfonamides at 100 mg/kg PO daily, or pyrimethamine at 2 mg/kg daily PO. For treatment of clinical toxoplasmosis: Clindamycin at 10 mg/kg PO q12h, trimethoprim-sulfonamide combination at 15 mg/kg PO q12h, and azithromycin at 10 mg/kg once daily for at least 28 days. Institute supportive care as needed. Pa-tients with uveitis should receive topical, oral or parenteral glucocorticoids to reduce risk for secondary glaucoma and lens luxations. (Lappin 2004) b) For enteroepithelial toxoplasmosis: 8-16 mg/kg PO or SC q8h for 14-28 days. For systemic toxoplasmosis: 12. 5-25 mg/kg PO or SC q12h for 14-28 days (Greene and Watson 1998) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl INDAmy CIN 211 FERRETS:T! For susceptible infections: a) 5-10 mg/kg PO twice daily (Williams 2000) b IRDS:T! For susceptible infections:a) 25 mg/kg PO q8h (Tully 2002) b) For mild spore-forming enteric bacterial infections: 50 mg/kg PO q12h for 5-10 days (Flammer 2006) REPTIl ES:T! For susceptible infections (anaerobes):a) 5 mg/kg PO once daily (Lewbart 2001) b) For respiratory infections (anaerobes, mycoplasma): 5 mg/kg PO once daily for 14 days (Klaphake 2005b) monitoring Clinical efficacy T! Adverse effects; particularly severe diarrhea T! Manufacturer recommends doing periodic liver and kidney T! function tests and blood counts if therapy persists for more than 30 days Client Information Clients should be instructed to report the incidence of severe, T! protracted, or bloody diarrhea to the veterinarian If using oral tablets or capsules, especially in cats, give medica-T! tion followed by at least 6 m L (a little more than a teaspoonful) of liquid Chemistry/Synonyms A semisynthetic derivative of lincomycin, clindamycin is available as the hydrochloride hydrate, phosphate ester, and palmitate hydro-chloride. Potency of all three salts is expressed as milligrams of clin-damycin. The hydrochloride occurs as a white to practically white, crystalline powder. The phosphate occurs as a white to off-white, hygroscopic crystalline powder. The palmitate HCl occurs as a white to off-white amorphous powder. All may have a faint characteristic odor and are freely soluble in water. With the phosphate, about 400 mg are soluble in one m L of water. Clin damycin has a p K a of 7. 45. The commercially available injection has a p H of 5. 5-7. Clindamycin HCl may also be known as: chlorodeoxylincomy-cin hydrochloride, (7S)-chloro-7-deoxy-lincomycin hydrochloride, clindamycini hydrochloridum, U-28508, or U-25179E; many trade names are available. Storage/Stability/Compatibility Clindamycin capsules and the palmitate powder for oral solution should be stored at room temperature (15-30°C). After reconstitu-tion, the palmitate oral solution (human-product) should not be refrigerated or thickening may occur. It is stable for 2 weeks at room temperature. The veterinary oral solution should be stored at room temperature and has an extended shelf life. Clindamycin phosphate injection should be stored at room tem-perature. If refrigerated or frozen, crystals may form which resol-ubolize upon warming. Clindamycin for injection is reportedly compatible for at least 24 hours in the following IV infu sion solutions: D 5W, Dextrose com-binations with Ringer's, lactated Ringer's, sodium chloride, D 10W, sodium chloride 0. 9%, Ringer's injection, and lactated Ringer's in-jection. Clindamycin for injection is reportedly compatible with the following drugs: amikacin sulfate, ampicillin sodium, aztreonam, carbenicillin disodium, cefazolin sodium, cefonicid sodium, cefop-erazone sodium, cefotaxime sodium, ceftazidime sodium, ceftizoxi-me sodium, cefuroxime sodium, cimetidine HCl, gentamicin sul-fate, heparin sodium, hydrocortisone sodium succinate, kanamycin sulfate, methylprednisolone sodium succinate, magnesium sulfate, meperidine HCl, metoclopramide HCl, metronidazole, morphine sulfate, penicillin G potassium/sodium, piperacillin sodium, potas-sium chloride, sodium bicarbonate, tobramycin HCl (not in syring-es), ver apamil HCl, and vitamin B-complex with C. Drugs that are reportedly incompatible with clindamycin include: aminophylline, ciprofloxacin, ranitidine HCl, and ceftriaxone so-dium. Compatibility is dependent upon factors such as p H, con-centration, tempera ture, and diluent used; consult specialized ref-erences or a hospital pharmacist for more specific in formation. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Clindamycin (as the HCl) Oral Capsules: 25 mg, 75 mg, 150 mg, 300 mg; An tirobe® Capsules (Pfizer) Approved for use in dogs and cats). Also available in 25 mg, 75 mg, 150 mg, and 300 mg capsules as Amtech® Clindamycin HCl Capsules (IVX), Clincaps® (Butler), Clindamycin Hydrochloride Capsules (Phoenix), Clindacure® Cap-sules (no 300 mg caps—Vedco); (Rx). Approved for use in dogs. Clindamycin (as the HCl) Oral Tablets: 25 mg, 75 mg, 150 mg; Clintabs® (Virbac). Approved for use in dogs. Clindamycin (as the HCl) Oral Solution 25 mg/m L in 30 m L bottles. Amtech® Clindamycin Hydrochloride Oral Liquid (Butler, IVX), An-tirobe ® Aquadrops (Pfizer), Clindacure® (Vedco), Clindrops® (But-ler), Clindamycin Hydrochloride Drops (Phoenix Pharmaceutical), Clinda-Guard® (RXV), Clinsol® (Virbac); (Rx). Approved for use in cats (not Clinda-Guard® or Clindacure®) and dogs. HUm ANl Ab El ED PRODUCTS: Clindamycin (as the HCl) Capsules: 75 mg, 150 mg, & 300 mg; Cleocin® (Upjohn); generic; (Rx) Clindamycin (as the palmitate HCl) Granules for Oral Solution: 75 mg/5 m L (15 mg/m L) in 100 m L; Cleocin® Pediatric (Upjohn); (Rx) Clindamycin (as the Phosphate) Injection: 150 mg/m L in 2 m L, 4 m L, 6 m L, 60 m L and 100 m L vials; 2 m L, 4 m L and 6 m L ADD-Vantage vials, 50 m L Galaxy containers and 60 m L bulk packages; Cleocin® Phosphate (Upjohn); (Rx); generic; (Rx) Clindamycin Phosphate Suppositories: 100 mg (as base) Cleocin® (Pfizer); (Rx) Also available in topical and vaginal preparations. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
212 Cl OFAz Im INE clof Azimine (kloe-fa-zi-meen) Lamprene® antimyc Obacterial antibi O tic Prescriber Highlights May be difficult for veterinarians to obtain & accurately T T dose Antimycobacterial antibiotic that may be used as part T T of multi-drug therapy for leprosy-like or M. avium-related diseases in small animals Very limited clinical experience & documentation sup-T T porting its use in veterinary patients Skin, eye, excretion staining noted & dose limiting gastro-T T intestinal adverse effects Treatment usually must continue for weeks to months T T Uses/Indications In small animals, clofazimine is sometimes used as part of multi-drug therapy against mycobacterial diseases, primarily leprosy-like or M. avium-related disease states. In humans, clofazimine is used primarily as part of a multi-drug regimen in the treatment of all forms of leprosy (with rifampin and dapsone), or the treatment of Mycobacterium avium complex (MAC) (with at least two of the following agents: clarithromycin or azithromycin, rifampin or rifabutin, and ethambutol). It has also been used in some treatment regimens for Crohn's disease, pyoder-ma gangrenosum, etc. Pharmacology/Actions Clofazimine binds to mycobacterial DNA and inhibits growth. It is considered to be slowly bactericidal against susceptible organisms. Clofazimine has activity against a variety of mycobacteria includ-ing: M. leprae, M. tuberculosis, M. avium complex (MAC), M. bovis, and M. chelonei. Resistance is thought to occur only rarely; cross-resistance with dapsone or rifampin apparently does not occur. Clofazimine may have some antileishmanial activity. Clofazimine has antiinflammatory and immunosuppressive effects, but the mechanisms of action for these effects are not understood. Pharmacokinetics Clofazimine's pharmacokinetics have apparently not been deter-mined in domestic animals. In humans, the microcrystalline form of the drug is variably absorbed after oral administration; bioavail-ability ranges from 45-70%. Food enhances absorption but increas-ing the dosage decreases the percentage absorbed. Clofazimine is highly lipid soluble and is distributed primarily to lipid tissue and the reticuloendothelial system. Throughout the body macrophages take up clofazimine. The drug crosses the placenta and is distrib-uted into milk, but does not apparently cross into the CNS or CSF. Clofazimine is retained in the body for a long period; its elimination half-life is at least 70 days long. Bile excretion may be responsible for the majority of the drug's excretion, but excretion in sputum, sebum, and sweat may also contribute. Contraindications/Precautions/Warnings It is suggested that clofazimine be used with caution in patients with pre-existing gastrointestinal conditions such as diarrhea or abdomi-nal pain. Adverse Effects There is very limited clinical experience with this medication in do-mestic animals and its adverse effect profile is not well documented. Apparently, the skin, eye, and excretion discoloration (described below) also occurs in animals. One case of a dog receiving clofaz-imine and rifampin to treat canine leproid granuloma resulted in hepatotoxicity. In humans, clofazimine is usually well tolerated, particularly at dosages of 100 mg/day or less. The most troubling adverse effect in many patients is the dose-related skin, eye, and body fluid discolor-ation (pink to brownish-black) that occurs in most patients, as it may cause severe psychosocial effects; other drug regimens, not including clofazimine, are often chosen in patients with light skin color. This discoloration can persist for months to years after clofazimine has been discontinued. In dosages greater than 100 mg/day, gastrointes-tinal effects (pain, nausea, vomiting, diarrhea) become more likely and often limit the dosage that can be administered. Other adverse effects (CNS, increased liver enzymes, etc. ) are reported in less than 1% of patients receiving the drug. Reproductive/Nursing Safety In humans, the FDA categorizes clofazimine 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). Very large doses (12-25X) demonstrated no teratogenic effects in rats or rabbits, but some effects were noted in mice. The World Health Organization (WHO) states that the drug is safe to use during pregnancy when used as part of one of their treatment protocols for leprosy. Clofazimine does enter maternal milk and skin discoloration of nursing offspring can occur. Overdosage/Acute Toxicity Very limited data is available; the LD50 for rabbits is 3. 3 g/kg and is greater than 5 g/kg in mice, rats, and guinea pigs. Treatment, if required, would include gut emptying and supportive care. Contact an animal poison control center for additional guidance. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clofazimine and may be of significance in veterinary patients: ISONIAz IDT! : May reduce the clofazimine levels in the skin and in-crease the amounts in plasma and urine; clinical significance unclear DAPSONET! : There is sketchy evidence that suggests dapsone may re-duce the antiinflammatory effects of clofazimine; clinical signifi-cance unclear laboratory Considerations No clofazimine-related laboratory interactions noted T! Doses DOg S:T! For Mycobacterium avium complex (MAC) as part of a multi-drug regimen: a) 4 mg/kg PO once daily. Other drugs that may be used in com-bination include doxycycline, clarithromycin, and/or enro-floxacin. (Greene and Gunn-Moore 1998) For M. avium intracellularae complex infections, leprosy, or op-portunistic mycobacteriosis: a) 4-8 mg/kg PO once a day for 4 weeks usually as part of a multi-drug protocol. (Greene and Watson 1998) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl Om IPRAm INE HCl 213 CATS:T! For treatment of feline leprosy: a) Using a regimen of either two or three of the following drugs: clarithromycin: 62. 5 mg per cat q12h, clofazimine: 25-50 mg once per day or 50 mg every other day, Rifampin: 10-15 mg/kg once a day. (Malik, Hughes et al. 2002) For treatment of localized atypical mycobacterial infections:a) Perform wide surgical excision of lesion if possible. Give long-term systemic antibacterial therapy, continued at least 4 weeks beyond complete clinical resolution. Base antibi-otic selection on culture and susceptibility results, if avail-able: Clofazimine 8 mg/kg PO once daily. Other doses listed in reference for marbofloxacin, doxycycline, minocycline, or clarithromycin. (Hnilica 2003a) For M. avium intracellularae complex infections, leprosy or op-portunistic mycobacteriosis: a) 4-8 mg/kg PO once a day for 4 weeks usually as part of a multi-drug protocol. (Greene and Watson 1998) monitoring Efficacy against mycobacterial disease T! Adverse effects (primarily GI, but consider monitoring hepatic T! function in dogs) Client Information Unless otherwise instructed give this medication with food T! This medication may cause your animal's skin to turn color (usu-T! ally pink, but from red to orange to brown). It may also cause dis-coloring of tears, urine, feces, and other body fluids to a brown-ish-black color. This discoloration may persist for many months after therapy is concluded. Chemistry/Synonyms Clofazimine, a phenazine dye antimycobacterial agent, occurs as an odorless or nearly odorless, reddish-brown powder that is highly insoluble in water. In room temperature alcohol, clofazimine's solu-bility is 1 mg/m L. Clofazimine may also be known as: B-663, G-30320, NSC-141046, Chlofazimine, Clofozine®, Hansepran®, Lamcoin®, Lamprene®, or Lampren®. Storage/Stability/Compatibility Clofazimine oral capsules should be stored in tight containers, pro-tected from moisture at temperatures less than 30°C. The commer-cially available capsules are a micronized form of the drug in a wax matrix base; it may be difficult to obtain an accurate dosage for small animals. It is suggested to contact a compounding pharmacist for advice. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: None In November 2004, clofazimine (Lamprene®) became available in the USA only on a limited basis. The FDA now restricts its use to physicians enrolled as investigators under an Investigational New Drug (IND) for treating Hansen's Disease (Leprosy) or multi-drug resistant tuberculosis. Its status for use in veterinary patients is un-certain at the time of writing; contact the FDA Center for Veteri-nary Medicine (see appendix) for more information. clomipr Amine hcl (kloe-mi-pra-meen) Clomicalm®, Anafranil® tricyclic antidepressant Prescriber Highlights Tricyclic antidepressant used in dogs & cats for obsessive T T compulsive disorders, but may be useful for other behav-ior disorders Contraindications: Hypersensitivity to clomipramine or T T other tricyclics Caution: Seizure disorders, liver disease, cardiac rate/ T T rhythm disorders, urinary retention or reduced GI motility Not a teratogen, but may affect testicular size/function T T Adverse Effects: Emesis, diarrhea, sedation, anticholin-T T ergic effects (dry mouth, tachycardia, etc. ); cats may be more sensitive than dogs Uses/Indications In veterinary medicine, clomipramine is used primarily in dogs as a treatment for obsessive-compulsive disorders (ritualistic stereo-typical behaviors) and may be useful for domi nance aggression and anxiety (separation). Clomipramine may also be useful in cats, particularly for be-haviors such as urine spraying. One prospective, double-blinded controlled study in cats with psychogenic alopecia comparing clo-mipramine (0. 5 mg/kg PO daily) versus placebo showed no statistic differences in study parameters (Mertens, T orres et al. 2006). Pharmacology/Actions While the exact mechanism of action of tricyclic antidepressants is not completely understood, it is believed that their most significant effects result from their action in prevent ing the reuptake of norepi-nephrine and serotonin at the neuronal membrane. Clomipramine is appar ently a selective inhibitor of serotonin (5-HT) reuptake. Clomipramine has an active metabolite, desmethylclomipramine which has primarily noradrenergic activity and, at least in humans, may be responsible for the majority of the drug's adverse effects. Pharmacokinetics In dogs, after absorption, clomipramine is rapidly converted in the liver to its active metabolite desmethylclomipramine. Both the parent drug and the active metabolite are highly bound to plasma proteins (96%). Repeated oral dosing increases clomipramine con-centrations but not desmethylclomipramine. The presence of food decreases the area under the curve for the parent compound by about 25% but not the metabolite. Giving without food probably is not necessary for efficacy. After a single dose in dogs, the elimina-tion half-life of clomipramine averages 5 hours. In cats, wide interpatient variability in pharmacokinetic param-eters have been shown after single oral doses; there may be inher-ent differences in pharmacokinetic parameters between male and female cats. In a limited (6 subject) pharmacokinetic study, oral bioavailability averaged 90%. In humans, the drug is well absorbed from the GI tract but a substantial first pass effect reduces its systemic bioavailability to ap-proximately 50%. The presence of food in the gut apparently does not significantly alter its ab sorption. Clomipramine is highly lipophilic and widely distributed throughout the body with an apparent volume of distribution of 17 L/kg. The drug crosses the placenta and into maternal milk. Plasma | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
214 Cl Om IPRAm INE HCl levels have been detected in nursing babies of mothers taking the drug. Both clomipramine and its active metabolite (desmethylclo-mipramine) cross the blood-brain barrier and significant levels are found in the brain. It should be noted that although therapeutic ef-fects may take several weeks to be seen, adverse effects can occur early on in treatment. Clomipramine is metabolized principally in the liver to several metabolites including desmethyl clomipramine, which is active. About two-thirds of these metabolites are eliminated in the urine and the rest in the feces. After a single dose, the elimination half-life of clomipramine averages 32 hours and desmethylclomipramine av-erages 69 hours, but there remains wide interpatient variation. Contraindications/Precautions/Warnings These agents are contraindicated if prior sensitivity has been noted with any other tricyclic. Concomitant use with monoamine oxi-dase in hibitors is generally contraindicated. As aged cheeses can contain high levels of tyramine, avoid giving to animals receiving clomipramine. In humans, these drugs (tricyclic antidepressants) may lower sei-zure threshold. Use with caution in animals with preexisting seizure disorders. Because of their anticholinergic effects, use with caution in patients with decreased GI motility, urinary retention, cardiac rhythm disturbances, or increased in traocular pressure. One study in dogs however, showed little effect on intra-ocular pressure or car diac rhythm. In humans, tricyclic antidepressants have caused hepatic abnormalities. Baseline and annual monitoring of liver enzymes is suggested for animals receiving clomipramine long-term. Tri cyclics should be used cautiously in patients with hyperthyroidism or those that are receiving thyroid supplementation as there may be an in-creased risk of cardiac rhythm abnormalities developing. Adverse Effects The primary adverse effects reported thus far with the use of clo-mipramine in dogs are anorexia, emesis, diarrhea, elevation of liver enzymes, and sedation/lethargy/depression. At therapeutic dosages dogs rarely develop anticholinergic (dry mouth, etc. ) ef fects. Cardiac effects such as tachycardia secondary to the drugs anticholinergic activity may also re sult. Cats have been reported to be more susceptible to the adverse ef-fects (anticholinergic effects, sedation) of clomipramine than dogs. This may be the result of slower elimination of the desmethyl me-tabolite in cats. Reproductive/Nursing Safety No teratogenic effects were noted in mice and rats given clomip-ramine at dosages of up 20X usual maximum human dosage. Data in other domestic species appear to be lacking. The manufacturer warns not to use in breeding male dogs as high dose (12. 5X) toxicity studies demonstrated testicular atrophy. 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. ) Overdosage/Acute Toxicity Clomipramine has a narrow margin of safety; significant clinical signs can be seen at or slightly above therapeutic range (at 2-3 mg/ kg, APCC database). Overdosage with tricyclics can be life-threat-ening (arrhythmias, seizures, cardiorespi ratory collapse). In dogs, lethal doses are approximately between 50 and 100 mg/kg/day PO (12. 5-25X recommended dose). There were 99 exposures to clomipramine reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2005-2006. In these cases 69 were dogs with 12 showing clinical signs and the remaining 30 cases were cats with 6 showing clinical signs. Common findings in dogs recorded in decreasing frequency included lethargy, tachycardia, agitation, bounding pulse and de-pression. Common findings in cats recorded in decreasing frequen-cy included mydriasis, bradycardia, disorientation, hypothermia and lethargy. Because the toxicities and therapies for treatment are compli-cated and con troversial, contact an animal poison control center for further information in any poten tial overdose situation. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clomipramine and may be of significance in veterinary patients: ANTICHOl INERg IC Ag ENTST! : Because of additive effects, use with clo-mipramine cautiously CIm ETIDINET! : May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity CISAPRIDET! : Increased risk for prolonged QT interval Cl ONIDINET! : May cause increased blood pressure CNS DEPRESSANTST! : Because of additive effects, use with clomip-ramine cautiously m EPERIDINE, PENTAz OCINE, DEx TROm ETHORPHANT! : Increased risk for serotonin syndrome RIFAm PINT! : May decrease tricyclic blood levels SSRIs T! (e. g., fluoxetine, paroxetine, sertraline, etc. ): Increased risk for serotonin syndrome Sym PATHOm Im ETIC Ag ENTST! : Use in combination with sympathomi-metic agents may increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia) m ONOAm INE Ox IDASE INHIb ITORST! (including amitraz and possibly, selegiline ): Concomitant use (within 14 days) with monoam-ine oxidase inhibitors is generally contraindicated (serotonin syndrome) laboratory Considerations ECg T! : Tricyclics can widen QRS complexes, prolong PR intervals and in vert or flatten T-waves on ECG m ETAPy RONE TESTT! : The response to metapyrone may be decreased by clomipramine gl UCOSE, bl OOD T! : Tricyclics may alter (increase or decrease) blood glucose levels THy ROID TESTST! : Clomipramine may decrease T3 and free T4 levels in dogs Doses DOg S:T! a) 2-4 mg/kg once daily or divided twice daily PO. (Label direc-tions; Clomicalm®) b) For adjunctive treatment of compulsive disorders: 2-3 mg/kg PO twice daily (Landsberg 2004) c) 3 mg/kg q12h; start at a low dose (e. g., 1 mg/kg for 2 weeks, then 2 mg/kg for 2 weeks, then 3 mg/kg) (Reisner and Houpt 2000) d) 2-6 mg/kg PO q24h. Begin at lower dose and increase ev-ery 1 -2 weeks as necessary. Emesis less likely if given with food and the total daily dose is divided into a twice a day dose (Crowell-Davis 1999) e) For treatment of male dimorphic behaviors (urine marking, mounting, roaming, inter-male aggression); fearful/fear ag-gression behaviors; noise phobias; obsessive/compulsive be-haviors (self-mutilation, excessive grooming, stereotypies): 1 mg/kg PO every 12 hours for 2 weeks; then 2 mg/kg PO q12h | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl ONAz EPAm 215 for 2 weeks, then 3 mg/kg PO q12h for 4 weeks and maintain. May take 4-6 weeks to see apparent improvement. (Overall 1997) f) For adjunctive treatment (with alprazolam and behavior modification) of storm phobia: Clomipramine 2 mg/kg PO q12h for 3 months, then 1 mg/kg PO q12h, then 0. 5 mg/kg PO q12h for 2 weeks. Alprazolam 0. 02 mg/kg PO as needed 1 hour before anticipated storms and q4h as needed (Crowell-Davis 2003d) CATS:T! a) For urine marking/spraying; inter-cat aggression related to social hierarchy; redirected aggression; compulsive groom-ing/wool sucking: 0. 5 mg/kg once daily PO (Overall 1997) b) For adjunctive treatment of compulsive disorders: 0. 5-1 mg/ kg PO once daily (Landsberg 2004) c) 0. 5-1 mg/kg once daily (Reisner & Houpt 2000) d) 0. 25-0. 5 mg/kg PO daily (Crowell-Davis 1999) monitoring Clinical efficacy T! Adverse Effects: Baseline liver function tests; EKGT! Client Information Generally used in combination with behavior modification T! treatments May take several weeks before beneficial effects are seen T! May be given with or without food; if patient vomits from the T! medication, give with food Do not stop therapy without veterinarian's guidance T! Keep well out of reach of pets and children; overdoses can be T! very toxic Chemistry/Synonyms A dibenzazepine-derivative tricyclic antidepressant, clomipramine HCl occurs as a white to off-white crystalline powder and is freely soluble in water. Clomipramine HCl may also be known as: chlorimipramine hydrochloride, clomipramini hydrochloridum, G-34586, mono-chlorimipramine hydrochloride, Clofranil®, Clomi calm®, Clopram®, Clopress®, Equinorm®, Hydiphen®, Maronil®, Novo-Clopamine®, Placil®, Tranquax®, or Zoiral®. Storage/Stability The commercially available veterinary tablets should be stored in a dry place at controlled room temperature (15-30°C) in the origi-nal closed container. The (human label) capsules should be stored at temperatures less than 30°C in tight containers and protected from moisture. An expiration date of 3 years from the date of man-ufacture is assigned to the commercially available capsules. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Clomipramine HCl Oral Tablets: 5 mg, 20 mg, 40 mg, & 80 mg; Ap-proved for dogs. Clomi calm® (Novartis); (Rx) The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Clomipramine Oral Capsules: 25 mg, 50 mg, & 75 mg; Anafranil® (Novartis); generic; (Rx)clon Azep Am (kloe-na-ze-pam) Klonopin® benz Odiazepine Prescriber Highlights Benzodiazepine anticonvulsant, used primarily as adjunc-T T tive therapy for short-term treatment of epilepsy in dogs & for longer-term adjunctive treatment of epilepsy in cats; may also be used as an anxiolytic Contraindications: Hypersensitivity to benzodiazepines, T T narrow angle glaucoma, significant liver disease May exacerbate myasthenia gravis T T Adverse Effects: Sedation & ataxia most prevalent; T T Cats: Possible hepatic necrosis Dogs: T T Tolerance to efficacy may occur (over a few weeks) Controlled substance (C-IV)T T Uses/Indications Clonazepam is used primarily as an short-term adjunctive anticon-vulsant for the treatment of epilepsy in dogs. It has been consid-ered as long-term adjunctive therapy in dogs not controlled with other, more standard therapies, but like diazepam, tolerance tends to develop in a few weeks of treatment. It can also be used as an anxiolytic agent. Clonazepam has been used as an anxiolytic and in the treatment of epilepsy in cats. Pharmacology/Actions The subcortical levels (primarily limbic, thalamic, and hypotha-lamic) of the CNS are depressed by diazepam and other benzodi-azepines thereby producing the anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects seen. The exact mechanism of action is un known, but postulated mechanisms include: antago-nism of serotonin, increased release of and/or fa cilitation of gam-ma-aminobutyric acid (GABA) activity, and diminished release or turnover of acetylcholine in the CNS. Benzodiazepine specific receptors have been located in the mammalian brain, kidney, liver, lung, and heart. In all species studied, receptors are lacking in the white matter. Pharmacokinetics In dogs, clonazepam's oral bioavailability is variable (20-60%) but absorption is rapid. Protein binding is about 82% and the drug rap-idly crosses into the CNS. Clonazepam exhibits saturation kinetics in dogs as elimination rates are dose dependent. In humans, the drug is well absorbed from the GI tract, crosses the blood-brain barrier and placenta and is metabolized in the liver to several metabolites that are excreted in the urine. Peak serum levels occur about 3 hours after oral dosing. Half-lives range from 19-40 hours. Contraindications/Precautions/Warnings Clonazepam is contraindicated in patients who are hypersensitive to it or other benzodiazepines, have significant liver dysfunction, or acute narrow angle glaucoma. Benzodiazepines have been reported to exacerbate myasthenia gravis. Adverse Effects There is very limited information on the adverse effect profile of this drug in domestic animals. Sedation (or excitement) and ataxia | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
216 Cl ONAz EPAm may occur. Clonazepam has been re ported to cause a multitude of various adverse effects in humans. Some of the more significant effects include increased salivation, hypersecretion in upper respi-ratory passages, GI effects (vomiting, con stipation, diarrhea, etc. ), transient elevations of liver enzymes, and hematologic effects (ane-mia, leukopenia, thrombocytopenia, etc. ). T olerance (usually noted after several weeks) to the anti convulsant effects has been reported in dogs. In cats, clonazepam may cause sedation, ataxia and acute hepatic necrosis. Patients discontinuing clonazepam, particularly those who have been on the drug chronically at high dosages, should be tapered off or status epilepticus may be precipitated. Vomiting and diarrhea may occur during this process. Reproductive/Nursing Safety Safe use during pregnancy has not been established; adverse terato-genic effects have been seen in rabbits and rats. 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. ) It is not known if clonazepam drug is excreted into milk, but several other benzodiazepines have been documented to enter milk. Theoretically, accumulation of the drug and its metabolites to toxic levels are possible; use with caution in nursing dams. Overdosage/Acute Toxicity When used alone, clonazepam overdoses are generally limited to sig-nificant CNS depression (confusion, coma, decreased reflexes, etc. ). Treatment of significant oral overdoses consists of standard proto-cols for removing and/or binding the drug in the gut and support ive systemic measures. The use of analeptic agents (CNS stimulants such as caffeine, amphetamines, etc. ) is generally not recommended. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clonazepam and may be of significance in veterinary patients: ANTIFUNg Al S, Az Ol ET! (itraconazole, ketoconazole, etc. ): May increase clonazepam levels CIm ETIDINET! : May decrease metabolism of ben zodiazepines CNS DEPRESSANT DRUg ST! : If clonazepam administered with other CNS depressant agents (barbiturates, narcotics, anesthetics, etc. ) additive effects may occur ERy THROmy CINT! : May decrease the metabolism of ben zodiazepines PHENOb ARb ITAl T! : May decrease clonazepam concentrations PHENy TOINT! : May decrease clonazepam concentrations PROPANTHEl INET! : May decrease clonazepam concentrations RIFAm PINT! : May induce hepatic microsomal enzymes and decrease the pharmacologic effects of ben zodiazepines laboratory Considerations Benzodiazepines may decrease the thyroidal uptake of IT!123 or I131. Doses DOg S:T! As an adjunctive medication in the treatment of seizures: a) For status: 0. 05-0. 2 mg/kg IV ( Note : IV prep not available in USA) (Boothe 1999) b) 0. 5 mg/kg PO two to three times a day; may need to lower phenobarbital dose by 10-20% (Neer 1994) As an anxiolytic: a) 0. 05-0. 25 mg/kg PO q12-24h (Virga 2005a) b) 0. 1-1 mg/kg PO two to three times a day (Landsberg 2005b) CATS:T! As an anxiolytic: a) 0. 05-0. 25 mg/kg PO q12-24h (Virga 2005a) b) 0. 02-0. 2 mg/kg PO once to two times a day (Landsberg 2005b) As an adjunctive medication in the treatment of seizures: a) 0. 5 mg (total dose) PO q12-24h; may cause ataxia, sedation and acute hepatic necrosis. (Podell 2006a) b) Jth to G of a 0. 5 mg tablet PO two to three times daily; anec-dotally more effective for maintenance and to decrease cluster seizures; acute hepatic necrosis possible (Pearce 2006b) monitoring Efficacy T! Adverse effects T! The therapeutic blood level has been re ported as 0. 015-0. 07 T! micrograms/m L. Cats: Liver function tests T! Client Information A major factor in anticonvulsant therapy failure is lack of compli-T! ance with the prescribed therapy; it is very important to give doses regularly Cats: If patient develops lack of appetite, vomits, or yellowish T! whites of eyes, contact veterinarian immediately Chemistry/Synonyms A benzodiazepine anticonvulsant, clonazepam occurs as an off-white to light yellow, crystalline powder having a faint odor. It is insoluble in water and slightly soluble in alcohol. Clonazepam may also be known as: clonazepamum, Ro-5-4023, Antelepsin®, Clonagin®, Clonapam®, Clonax®, Clonex®, Diocam®, Epitril®, Iktorivil®, Kenoket ®, Klonopin®, Kriadex®, Neuryl ®, Paxam®, Rivatril®, Rivotril®, or Solfidin®. Storage/Stability Tablets should be stored in airtight, light resistant containers at room temperature. After manufacture, a 5-year expiration date is assigned. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Clonazepam Oral Tablets: 0. 5 mg, 1 mg, & 2 mg; Klonopin® (Roche); generic; (Rx, C-IV) Clonazepam Orally Disintegrating Tablets: 0. 125 mg, 0. 25 mg, 0. 5 mg, 1 mg & 2 mg (with mannitol); Klonopin® Wafers (Roche); Clon-azepam (Barr); (Rx, C-IV) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl ONIDINE 217 clonidine (kloe-ni-deen) Duraclon®, Catapres® central alpha-2 ag Onist Prescriber Highlights Centrally acting alpha-adrenergic agonist used as a diag-T T nostic for growth hormone deficiency or pheochromocy-toma in dogs, adjunctive treatment for IBD, &, potentially, epidurally as an adjunct for pain &/or anesthesia Limited experience in veterinary species for therapeutic T T purposes Potential adverse effects include: Transient hyperglyce-T T mia, dry mouth, constipation, sedation, aggressive behav-ior, hypotension, collapse, & bradycardia Uses/Indications Clonidine is of interest in veterinary medicine as a diagnostic agent to determine growth hormone deficiency or pheochromocytoma in dogs, and as an adjunctive treatment for refractory inflammatory bowel disease, particularly in cats. It is being investigated in a vari-ety of species as an epidural adjunct with or without opiates in the treatment of severe pain or for surgical procedures using epidural anesthesia. Pharmacology/Actions Clonidine acts centrally (brain stem), stimulating alpha-adreno-receptors, thereby reducing sympathetic outflow from the CNS; decreased renal vascular resistance, peripheral resistance, cardiac rate, and blood pressure result. Renal blood flow and glomerular filtration rates are not affected. Clonidine stimulates growth hor-mone release by stimulating release of GHRH, but this effect does not persist with continued dosing. Clonidine possesses centrally acting analgesic effects probably at presynaptic and postjunctional alpha2-adrenoreceptors in the spinal cord thereby blocking pain signal transmission to the brain. It may also increase seizure thresh-old but the clinical significance for this effect is unclear. Pharmacokinetics Limited information is available on the pharmacokinetics of clo-nidine in domestic animals. In cats, clonidine exhibits a two-com-partment open model and penetrates into tissues rapidly. In humans, the drug is well absorbed after oral administration. Peak plasma concentrations occur approximately 3-5 hours after oral administration. After epidural administration, maximal anal-gesia occurs within 30-60 minutes. Clonidine is apparently widely distributed into body tissues; tissue concentrations are higher than in plasma. Clonidine does enter into the CSF, but brain concentra-tions are low compared with other tissues. In humans with normal renal function, clonidine's half-life is 6-20 hours. Elimination may be prolonged with higher dosages (dose-dependent elimination ki-netics) or in patients with renal dysfunction. Up to 60% of a dose is eliminated unchanged in the urine, but the remainder is metabo-lized in the liver; one active metabolite (p-hydroxyclonidine) has been identified. Contraindications/Precautions/Warnings Clonidine is contraindicated in patients known to be hypersensitive to it. It should be used with caution in patients with severe cardio-vascular disease, including conduction disturbances or heart fail-ure; it should be used very cautiously in patients with renal failure. Adverse Effects Reported adverse effects most likely to occur include: transient hy-perglycemia, dry mouth, constipation, sedation, aggressive behav-ior, hypotension, collapse, and bradycardia (responsive to atropine). T olerance to its therapeutic effects has been reported in humans. Reproductive/Nursing Safety At reasonable dosages no significant teratogenic effects have been described in laboratory animals, but at very high dosages some ef-fects (increased perinatal mortality, growth retardation, cleft pal-ates) have been seen. In humans, the FDA categorizes clonidine as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate stud-ies in humans; or there are no animal reproduction studies and no adequate studies in humans). Clonidine does enter maternal milk at concentrations of about 20% of those found in plasma; clinical significance to nursing off-spring is unknown, but clonidine was undetectable in plasma of an infant one hour after nursing from a mother taking clonidine. Overdosage/Acute Toxicity The LD50 values reported for oral clonidine in rats are 465 mg/ kg and mice, 206 mg/kg. Expected signs after clonidine overdose include: transient hypertension followed by hypotension, bradycar-dia, somnolence to agitation to coma, vomiting, respiratory depres-sion, constricted pupils, and cardiac arrhythmias. There were 43 exposures to clonidine reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 20 were dogs with 8 showing clinical signs and the remaining 23 cases were cats with 6 showing clinical signs. Common findings in dogs recorded in decreasing frequen-cy included lethargy, bradycardia, agitation, hypotension, weak-ness and ataxia. Common findings in cats recorded in decreasing frequency included depression, vomiting, ataxia, agitation and bradycardia. Treatment for large overdoses includes gut evacuation using standard protocols. Use of emetics should be carefully considered, as level of consciousness may deteriorate rapidly. Treatment of sys-temic effects is primarily symptomatic and supportive. Hypotensive effects may be treated, if necessary, using fluids or pressors (e. g., do-pamine); bradycardia may be treated with IV atropine, if required. Treatment may be required for many hours, depending on cloni-dine dosage. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clonidine and may be of significance in veterinary patients: ANTIHy PERTENSIVE DRUg S, OTHERT! : Possible additive hypotensive effects b ETAADRENERg IC bl OCKINg Ag ENTST! (i. e., propranolol ) may enhance bradycardia when given with clonidine. In patients receiving clo-nidine and beta-adrenergic blocking agents together: if clonidine is to be discontinued, the beta-blocker should be discontinued prior to clonidine and clonidine gradually discontinued, other-wise rebound hypertension may occur. CNS DEPRESSANT DRUg ST! (opiates, barbiturates, etc. ): Clonidine may exacerbate the actions of other CNS depressant drugs DIg Ox INT! : Possible additive bradycardia PRAz OSINT! : May decrease the antihypertensive effects of clonidine TRICy Cl IC ANTIDEPRESSANTS T! (e. g., amitriptyline ): May block the an-tihypertensive effects of clonidine | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
218 Cl OPIDOg REl b ISUl FATE laboratory Considerations No specific laboratory interactions were noted for clonidine. Doses DOg S:T! For diagnosing hyposomatotropism: a) Dosage may be variable depending on the laboratory's proto-col. Contact lab prior to test to determine protocol and sam-ple handling instructions. Usual dose is 10 mcg/kg IV. Obtain plasma for growth hormone (GH) levels, prior to clonidine dosing and at 15, 30, 45, 60, and 120 minutes. Larger dosages may cause a more pronounced and prolonged hyperglycemia and a higher incidence of other adverse reactions that may include sedation, aggressive behavior, hypotension, collapse, and bradycardia (responsive to atropine). Adverse effects may persist for 15-60 minutes post dose. Healthy dogs should demonstrate GH levels of 10 ng/m L after clonidine adminis-tration. (Feldman and Nelson 1996) CATS:T! For adjunctive antidiarrheal therapy for refractory cases of in-flammatory bowel disease:a) As fourth line therapy after prostaglandin synthetase inhibi-tors ( i. e., sulfasalazine, bismuth subsalicylate), opioid agonists (i. e., loperamide), and 5-HT3 serotonergic antagonists (i. e., ondansetron) are being used: clonidine 5-10 mcg/kg two to three times a day, SC or PO. (Washabau 2000) CATTl E:T! For epidural analgesia/analgesia:a) 2-3 mcg/kg diluted to 8 m L with sterile normal saline epidu-rally; onset/duration of analgesia = 19 minutes/192 minutes with 2 mcg/kg dose and = 9 minutes/311 minutes with 3 mcg/kg dose; peak effects from 60-180 minutes (De Rossi, Bucker et al. 2003) monitoring Dependent upon purpose for use. When used for determining T! GH levels, adverse effects (noted in dosage section) should be evaluated. Blood pressure and cardiac rate are most likely to be affected, but T! effects usually only persist for an hour after dose. When used for ongoing diarrhea treatment, evaluation of efficacy T! and adverse effect profile should be monitored. Client Information When used for chronic therapy, have clients report signs that may T! indicate adverse effects (weakness, lethargy, behavioral changes, etc. ); caution not to alter or discontinue treatment without vet-erinarian's advice. Chemistry/Synonyms An imidazoline derivative centrally acting alpha-adrenergic agonist, clonidine HCl occurs as an odorless, bitter, white or almost white crystalline powder. It is soluble in water and alcohol. It is also con-sidered highly lipid soluble. The commercially available injection for epidural use has its p H adjusted to between 5 to 7. Clonidine may also be known as: ST-155, clonidini hydro-chloridum, Adesipress-TTS®, Arkamin®, Aruclonin®, Atensina®, Barclyd®, Cantanidin®, Caprysin®, Catanidin®, Catapresan®, Catapresan®, Catapres®, Catapressan®, Clonistada®, Clonnirit®, Dispaclonidin®, Dixarit®, Duraclon®, Epiclodina®, Glausine®, Haemiton®, Menograine®, Mirfat®, Normopresan®, Paracefan®, or Tenso-Timelets®. Storage/Stability Clonidine tablets should be stored in tight, light-resistant containers at room temperature; excursions permitted to 15-30°C (59-86°F). The preservative-free injection for epidural use should be stored at controlled room temperature (25°C). Because it contains no preser-vative, unused portions of the injection should be discarded. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Clonidine HCl Injection for epidural use: 100 mcg/m L, 500 mcg/m L preservative-free in 10 m L vials; Duraclon® (aai Pharma); (Rx) Clonidine HCl Tablets: 0. 1 mg, 0. 2 mg & 0. 3 mg; Catapres® (Boeh-ringer Ingelheim); generic; (Rx)Clonidine HCl Transdermal: 0. 1 mg/24hrs (2. 5 mg total cloni-dine content), 0. 2 mg/24hrs (5 mg total clonidine content), & 0. 3 mg/24hrs (7. 5 mg total clonidine content); Catapres-TTS-1®, 2 ® or 3® (Boehringer Ingelheim); (Rx) clopidogrel bisulf Ate (kloe-pid-oh-grel) Plavix® platelet aggregati On inhibit Or Prescriber Highlights Oral, once-daily platelet aggregation inhibitor that may T T be useful in preventing thromboembolic disease in cats Limited clinical experience in feline medicine; but T T appears well tolerated Potentially may cause vomiting or bleeding T T Uses/Indications Clopidogrel, a platelet aggregation inhibitor, may be useful for pre-venting thrombi in susceptible cats. It may also improve pelvic limb circulation in cats after a cardiogenic embolic event via a vasomodu-lating effect secondary to inhibition of serotonin release from plate-lets. Research is ongoing. Pharmacology/Actions Clopidogrel is metabolized to an active, highly unstable compound (not yet identified) that is responsible for its inhibitory platelet-ag-gregation (both primary and secondary aggregation) activity. This compound binds selectively to platelet surface low-affinity ADP-receptors and inhibits ADP binding to the site. This inhibits activa-tion of the platelet glycoprotein Ib/IIIa complex that is necessary for platelet-fibrinogen binding and inhibits the release from platelets other compounds that enhance platelet aggregation (e. g., serotonin, calcium, fibrinogen, thromobospondin, ADP). Clopidogrel's active metabolite irreversibly alters the ADP receptor; the platelet is af-fected for its lifespan. Clopidogrel's mechanism of action on platelet aggregation is dif-ferent than aspirin's effects. Aspirin acetylates and inactivates COX-1 in platelets, thereby preventing formation of thromboxane A 2. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl OPROSTENOl SODIUm 219 Pharmacokinetics No specific information was located for the pharmacokinetics of clopidogrel in cats. In a pharmacodynamic study in cats (Hogan, Andrews et al. 2004), doses as low as 18. 75 mg were as effective as higher dosages in reducing platelet aggregation; maximal effects were seen after 3 days of therapy and platelet function returned to normal 7 days after stopping treatment. While lower dosages may be effective in cats, they have not been evaluated and are not practi-cal to administer with the presently available 75 mg human-labeled dosage form (tablets). In humans, clopidogrel is rapidly absorbed with a bioavailabil-ity of about 50%. Food does not alter its absorption. Clopidogrel is highly bound to plasma proteins in humans and is rapidly hy-drolyzed to a carboxylic acid derivative inactive metabolite that is excreted via the urine and feces. The 2% of drug that is covalently bound to platelets has an approximate elimination half-life of 11 days. Contraindications/Precautions/Warnings No specific information is available for cats. In humans, clopidogrel is contraindicated in patients with active pathologic bleeding or known hypersensitivity to the drug. Adverse Effects Clopidogrel appears well tolerated by cats, but numbers treated have been relatively few. Some cats may vomit or develop anorexia; giving the drug with food may alleviate these effects. In humans, the primary adverse effects reported have been bleeding related. In a major pre-clinical study, major bleeding oc-curred in approximately 2% of patients treated. Use of aspirin with clopidogrel may increase this incidence. Rashes and gastrointesti-nal effects (diarrhea) have also been reported. Rarely, thrombotic thrombocytopenic purpura (TTP) has been noted; onset can occur after a short period of treatment (<2 weeks). Reproductive/Nursing Safety In pregnant rats and rabbits, dosages of approximately 65X and 78X respectively, of the human dose when compared on mg/m2 basis, caused no teratogenic effects. In humans, the FDA categorizes clopidogrel as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrat-ed a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In rats, clopidogrel or its metabolites are distributed into milk. Although probably safe to use in nursing veterinary patients, weigh the potential risks to nursing offspring before allowing patients re-ceiving the drug to nurse their young, or use a milk replacer. Overdosage/Acute Toxicity Limited information is available. Reported lethal oral doses for mice and rats were 1500 mg/kg and 2000 mg/kg (460X human adult dose on a mg/m2 basis), respectively. Acute toxic signs may include bleeding or vomiting. Platelet transfusions have been suggested if rapid reversal is required. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clopidogrel and may be of significance in veterinary patients: ASPIRINT! : Increased risk for bleeding, however many human pa-tients take both medications HEPARIN; l OW m Ol ECUl AR WEIg HT HEPARINS T! : Clopidogrel appears safe to use with heparin (both unfractionated and LMW)NSAIDST! : Increased risk for bleeding; clopidogrel may interfere with metabolism PHENy TOINT! : Clopidogrel may interfere with metabolism TORSEm IDET! : Clopidogrel may interfere with metabolism WARFARINT! : Increased risk for bleeding; clopidogrel may interfere with metabolism laboratory Considerations None noted Doses CATS:T! T o prevent thrombus formation:a) 18. 75 mg (practically, G of a 75 mg tablet) PO once daily (Hogan 2006) monitoring Clinical efficacy T! Adverse effects (vomiting, bleeding)T! Client Information May be given without regard to feeding status T! Potential adverse effects include vomiting, lack of appetite or T! bleeding If vomiting occurs, give with food T! Report any bleeding or black, tarry stools to veterinarian T! Chemistry/Synonyms Clopidogrel bisulfate, a thienopyridine, occurs as a white to off-white powder that is practically insoluble in water at a p H of 7, but freely soluble at a p H of 1. Clopidogrel may also be known as: SR-259990C, PCR-4099, or clopedogreli. Internationally registered trade names for clopidogrel include: Antiplaq, Clodian, Cloflow, Clopact, Clopivas, Clopod, Iscover, Iskimil, Nabratin, Noklot, Plavix®, Pleyar, or Troken. Storage/Stability Clopidogrel tablets should be stored at 25°C; excursions are permit-ted to 15-30°C. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Clopidogrel Bisulfate Tablets: 75 mg (as base); Plavix® (Bristol-Myers Squibb); (Rx) cloprostenol sodium (kloe-pros-te-nol) Estru mate® pr Ostaglandin (f-class) Prescriber Highlights Synthetic F-class prostaglandin used in cattle to induce T T luteolysis, induce abortion, treat pyometra, endometritis, etc. Contraindications: Pregnancy (when abortion or induced T T parturition are not desired)Can cause cholinergic-like adverse effects in dogs T T Do not give IVT T Pregnant women should not handle; caution handling in T T humans with asthma & women of childbearing age | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
220 Cl OPROSTENOl SODIUm Uses/Indications Cloprostenol is approved for use in beef or dairy cattle to induce luteolysis. It is recommended by the manufacturer for unobserved or undetected estrus in cows cycling normally, pyometra or chronic endometritis, expulsion of mummified fetus, luteal cysts, induced abortions after mismating, and to schedule estrus and ovulation for controlled breed ing. Cloprostenol has been used in dogs for pregnancy termination and treatment of open pyometra. The use of cloprostenol for py-ometra is controversial as some believe dinoprost (PGF2alpha) is more effective and has fewer adverse effects than cloprostenol. Pharmacology/Actions Prostaglandin F alpha and its analogues cloprostenol and flupros-tenol are powerful luteolytic agents. They cause rapid regression of the corpus luteum and arrest its secretory activity. These prostaglan-dins also have direct stimulating effect on uterine smooth muscle causing contrac tion and a relaxant effect on the cervix. In normally cycling animals, estrus will generally occur 2-5 days after treatment. In pregnant cattle treated between 10-150 days of gestation, abortion will usually occur 2-3 days after injection. Pharmacokinetics No information was located on the pharmacokinetics of cloprostenol. Contraindications/Precautions/Warnings Should not be administered to pregnant animals when abortion is not desired. Women of child-bearing age, persons with asthma or other respi-ratory diseases should use extreme caution when handling clopros-tenol as the drug may induce abortion or acute bronchoconstric-tion. Cloprostenol is readily absorbed through the skin and must be washed off immediately with soap and water. Do not administer IV. Adverse Effects The manufacturer does not list any adverse effects for this product when used as labeled. If used after the 5th month of gestation, in-creased risk of dystocia and de creased efficacy occur. In dogs, cloprostenol can cause increased salivation, tachycardia, increased urination and defecation, gagging, vomiting, ataxia, and mild depression. Pretreatment with an anticholinergic drug (such as atropine) may reduce the severity of these effects. Reproductive/Nursing Safety Cloprostenol is contraindicated in pregnant animals when abortion or induced parturition is not desired. Overdosage/Acute Toxicity The manufacturer states that at doses of 50 and 100 times those rec-ommended, cattle may show signs of uneasiness, slight frothing, and milk let-down. Overdoses of cloprostenol or other synthetic prostaglandin F2alpha analogs in small animals re portedly can result in shock and death. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving cloprostenol and may be of significance in veterinary patients: Oxy TOCIC Ag ENTS, OTHER T! : Activity may be enhanced by cloprostenol Doses DOg S:T! For adjunctive treatment of open cervix pyometra: a) 1-5 mcg/kg (0. 001-0. 005 mg/kg) (route not specified) once per day. May require up to 2-3 weeks of treatment. When starting treatment, start with one-half the normal dosage and gradually achieve the full dose within 2-3 days. (Romagnoli 2002a) b) Cloprostenol at 1 mcg/kg SC (not during feeding) every 5 days for 15 days (if not cured earlier) with aglepristone at 10 mg/kg SC every 5 days until cured. Give Clavamox® (12. 5 mg/ kg PO twice daily and supportive hydration throughout pro-tocol, if indicated. (Threlfall 2006) For pregnancy termination: a) 1-2. 5 mcg/kg SC once daily for 4-7 days has been success-ful in terminating pregnancy in dogs after 30 days gestation (Davidson 2004c) b) 1-2. 5 mcg/kg SC every 48 hours for three doses. At higher dose (2. 5 mg/kg); appears very effective starting at 30 days of pregnancy. Anticholinergic drug administration (e. g., at-ropine) 15 minutes prior to dosing appears to lessen adverse effects. (Romagnoli 2006a) CATTl E:T! For treatment of pyometra: a) 500 micrograms IM (up to 97% efficacy) (Mc Cormack 1986) For pyometra or chronic endometritis, mummified fetus (manual assistance may be required to remove from vagina), luteal cysts: a) 500 micrograms IM (Package Insert; Estrumate®—Miles/ Mobay) For unobserved or undetected estrus in cows with continued ovarian cyclicity and a mature cor pus luteum: a) 500 micrograms IM; estrus should commence in 2-5 days at which time the animal may be inseminated. If estrus detec-tion is not possible or practical, animal may be inseminat-ed twice at 72 and 96 hours post injection. (Package Insert; Estrumate®—Miles/Mobay) For abortion, from one week after mating to approximately the 150th day of gestation: a) 500 micrograms IM; abortion generally takes place in 4-5 days after injection (Package Insert; Estrumate®—Miles/ Mobay) For controlled breeding:a) Single injection method: Use only animals with mature corpus luteum. Examine rectally to determine corpus luteum matu-rity, anatomic normality, and lack of pregnancy. Give 500 mi-crograms cloprostenol IM. Estrus should occur in 2-5 days. Inseminate at usual time after detecting estrus, or inseminate once at 72 hours post injection, or twice at 72 and 96 hours post injection. Double injection method: Examine rectally to determine if ani-mal is anatomically nor mal, not pregnant, and cycling nor-mally. Give 500 micrograms IM. Repeat dose 11 days later. Estrus should occur in 2-5 days after second injection. In-seminate at usual time after detecting estrus, or inseminate once at 72 hours post second injection, or twice at 72 and 96 hours post second injection. Animals that come into estrus after first injection may be in-seminated at the usual time af ter detecting estrus. Any controlled breeding program should be completed by ei-ther observing animals and re-inseminating or hand mating after returning to estrus, or turning in clean-up bull(s) five to seven days after the last injection of cloprostenol to cover any | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl ORAz EPATE DIPOTASSIUm 221 animals returning to es trus. (Package Insert; Estrumate®— Miles/Mobay) HORSES:T! T o cause abortion prior to the twelfth day of gestation: a) 100 micrograms IM, most effective day 7 or 8 post estrus. Mare will usually return to es trus within 5 days. (Lofstedt 1986) SWINE:T! T o induce parturition in sows: a) 175 micrograms IM; give 2 days or less before anticipated date of farrowing. Farrowing generally occurs in approxi-mately 36 hours after injection. (Pugh 1982) SHEEP & g OATS:T! T o induce parturition in does: a) 62. 5-125 micrograms IM at 144 days of gestation in early morning. Deliveries will peak at 30-35 hours after injection. Maintain goat in usual surroundings and minimize outside disturbances. (Williams 1986) Client Information Cloprostenol should be used by individuals familiar with its use T! and precau tions Pregnant women, asthmatics or other persons with bronchial T! diseases should handle this prod uct with extreme caution Any accidental exposure to skin should be washed off T! immediately Chemistry/Synonyms A synthetic prostaglandin of the F class, cloprostenol sodium oc-curs as a white or al most white, amorphous, hygroscopic powder. It is freely soluble in water and alcohol. Potency of the commercially available product is expressed in terms of cloprostenol. Cloprostenol sodium may also be known as ICI-80996, Estru-mate®, or estro PLAN®. Storage/Stability Cloprostenol sodium should be stored at room temperature (15-30°C); protect from light. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Cloprostenol Sodium Injection equivalent to 250 micrograms/m L cloprostenol in 20 m L vials; Estru mate® (Schering-Plough); estro-PLAN® Injection (Pharmacia & Upjohn); (Rx). Approved for use in beef and dairy cattle. No preslaughter withdrawal or milk with-drawal is required; no specific tolerances for cloprostenol residues have been published. HUm ANl Ab El ED PRODUCTS: Noneclor Azep Ate dipot Assium (klor-az-e-pate) Tranxene-SD®, Gen-Xene® benz Odiazepine Prescriber Highlights Benzodiazepine anxiolytic, sedative-hypnotic, & anticon-T T vulsant used in dogs & cats Contraindications: Hypersensitivity to benzodiazepines, T T narrow angle glaucoma, or signifi cant liver disease Use extreme caution in aggressive animals (especially T T fear induced)May exacerbate myasthenia gravis T T Can interact with phenobarbital T T Adverse Effects: Sedation & ataxia most prevalent T T Uses/Indications Clorazepate has been used in dogs both as an adjunctive anticon-vulsant (usually in conjunction with phenobarbital) and in the treatment of behavior disorders, primarily those that are anxiety or phobia-related. In dogs, clorazepate has been reported to develop tol-erance to its anticonvulsant effects less rapidly than clonazepam. Clorazepate may be useful as an anxiolytic agent in cats. Pharmacology/Actions The subcortical levels (primarily limbic, thalamic, and hypotha-lamic) of the CNS are depressed by clorazepate and other benzo-diazepines thus producing the anxiolytic, sedative, skeletal muscle relaxant and anticonvulsant effects seen. The exact mechanism of action is unknown, but postulated mechanisms include: an-tagonism of serotonin, increased release of and/or facilitation of gamma-aminobutyric acid (GABA) activity and diminished release or turnover of acetylcholine in the CNS. Benzodiazepine specific receptors have been located in the mammalian brain, kidney, liver, lung and heart. In all species studied, receptors are lacking in the white matter. Pharmacokinetics In dogs, clorazepate peak serum levels generally occur within 1-2 hours. Volume of distribution is about 1. 8 L/kg after multiple dos-ing. Clorazepate is metabolized to nordiazepam and other metabo-lites. Nordiazepam is active and has a very long half-life (in humans up to 100 hours). In dogs, the sustained release preparation appar-ently offers no pharma cokinetic advantage over the non-sustained preparations (Brown and Forrester 1989). Contraindications/Precautions/Warnings Clorazepate is contraindicated in patients who are hypersensitive to it or other benzodiazepines, have significant liver dysfunction or have acute narrow angle glaucoma. Clorazepate should be used very cautiously, if at all, in aggressive pa tients as it may disinhibit the anxiety that may help prevent these animals from aggressive behavior. Benzodiazepines have been reported to exacerbate myas-thenia gravis. Use with caution in dogs displaying fear-induced aggression; these drugs may actually provoke dogs to attack. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
222 Cl ORAz EPATE DIPOTASSIUm Adverse Effects In dogs, the most likely adverse effects seen include sedation and ataxia. These effects apparently occur infrequently, are mild and usually transient. Physical dependence may occur and abrupt with-drawal of clorazepate may precipitate seizures. In cats, clorazepate may cause sedation, ataxia and, potentially, acute hepatic necrosis. Reproductive/Nursing Safety Safe use during pregnancy has not been established; teratogenic ef-fects of similar benzodiazepines have been noted in rabbits and rats. 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 benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Nordiazepam is distributed into milk and may affect nursing neonates. Overdosage/Acute Toxicity When used alone, clorazepate overdoses are generally limited to sig-nificant CNS depression (confusion, coma, decreased reflexes, etc. ). Treatment of significant oral overdoses consists of standard proto-cols for removing and/or binding the drug in the gut and support-ive systemic measures. The use of analeptic agents (CNS stimulants such as caffeine, amphetamines, etc. ) is generally not recommend-ed. Flumazenil may be considered for very serious overdoses. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving clorazepate and may be of significance in veterinary patients: ANTIFUNg Al S, Az Ol ET! (itraconazole, ketoconazole, etc. ): May increase levels CIm ETIDINET! : May decrease metabolism of ben zodiazepines CNS DEPRESSANT DRUg ST! : If clorazepate is administered with other CNS depressant agents ( barbiturates, narcotics, anesthetics, etc. ) additive effects may occur ERy THROmy CINT! : May decrease the metabolism of ben zodiazepines PHENOb ARb ITAl T! : While used together in the treatment of seizures in dogs, can inter act with one another. Clorazepate (especially high serum concentrations), may increase the serum levels of pheno-barbital, particularly if added to patients who received phenobar-bital long-term. In time, clorazepate levels may decrease, leading to decreased phenobarbital levels. PHENy TOINT! : May decrease clorazepate concentrations RIFAm PINT! : May induce hepatic microsomal enzymes and decrease the pharmacologic effects of ben zodiazepines laboratory Considerations Benzodiazepines may decrease the thyroidal uptake of T! I123 or I131. Clorazepate may increase T! serum alkaline phosphatase and serum cholesterol levels; clinical signifi cance is unclear. Doses DOg S:T! As an adjunctive medication in the treatment of seizures: a) In combination with phenobarbital: Clorazepate: 1-2 mg/ kg PO q12h, but may need to divide q12h dose and give q8h to minimize adverse effects and maintain therapeutic lev els (Boothe 1999) b) In combination with phenobarbital: Clorazepate: 0. 5-1 mg/ kg PO q8h. No advantage gained with using sustained release products over regular caps or tabs. May affect pheno barb lev-els; monitor 2 and 4 weeks later. (Thomas 2000)c) 1-2 mg/kg PO q12h (Podell 2006a) d) 2-4 mg/kg PO twice daily, some dogs may require three times daily (Dowling 2003c) e) As a third-line agent: 1-2 mg/kg PO q8-12h (Quesnel 2001) f) For management of cluster seizures: Immediately after first seizure give clorazepate at 0. 5-2 mg/kg two to three times daily for the next 48-96 hours and then stop clorazepate. It may be used in addition to the existing anticonvulsant main-tenance therapy, but it is used only during the time of seizure activity and not as maintenance therapy. (Hoskins 2005c) As adjunctive therapy for the treatment of fears and phobias:a) 11. 25-22. 5 mg per dog PO once to twice daily (recommends the sustained-delivery product (Tranxene®-SD). (Marder 1991) b) Using the sustained delivery product (Tranxene®-SD), ini-tially give 22. 5 mg for large dogs, 11. 25 mg for medium dogs and 5. 6 mg for small dogs PO; adjust dosage according dog's response (Shull-Selcer and Stagg 1991) c) 0. 55-2. 2 mg/kg PO as needed up to q8h; titrate to clinical sedation—dose may vary for indi vidual dogs (Reisner and Houpt 2000) d) 0. 2-1 mg/kg PO q12-24h (Virga 2002) CATS:T! As an anxiolytic or for compulsive behaviors: a) 0. 2-0. 5 mg/kg PO q12-24h (Virga 2002) monitoring Efficacy T! Adverse effects T! Client Information A major factor in anticonvulsant therapy failure is lack of compli-T! ance with the prescribed therapy; it is very important to give doses regularly Do not stop giving this drug abruptly as convulsions may occur; T! contact veterinarian for guidance in stopping treatment Cats: If patient develops lack of appetite, vomits, or yellowish T! whites of eyes, contact veterinarian immediately Chemistry/Synonyms A benzodiazepine anxiolytic, sedative-hypnotic, and anticonvulsant, clorazepate dipotassium occurs as a light yellow, fine powder that is very soluble in water and slightly soluble in alcohol. Clorazepate dipotassium may also be known as Abbott-35616, AH-3232, 4306-CB, clorazepic acid, dipotassium clorazepate, dikalii clorazepas, or potassium clorazepate; many trade names are avail-able. Storage/Stability Clorazepate dipotassium is unstable in the presence of water. It has been recommended to keep the dessicant packets in with the original container of the capsules and tablets and to consider adding a dessi-cant packet to the prescription vial when dispensing large quantities of tablets or capsules to the client. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cl ORSUl ON 223 HUm ANl Ab El ED PRODUCTS: Clorazepate Dipotassium Tablets (single dose; sustained release): 11. 25 mg & 22. 5 mg; Tranxene-SD® & Half Strength (Abbott); (Rx, C-IV) Clorazepate Dipotassium Tablets: 3. 75 mg, 7. 5 mg, & 15 mg; Tranx-ene® T-tab (Ovation); generic; (Rx, C-IV) clorsulon (klor-su-lon) Curatrem®, Ivomec Plus® antiparasitic (flukicide) Prescriber Highlights Adult flukicide T T (Fasciola hepatica) Not for female dairy cattle T T Slaughter withdrawal 8 days at labeled doses for T T Cura-trem®, 49 days for Ivomec Plus® Uses/Indications Clorsulon is approved for use in the treatment of immature and adult forms of Fasciola hepatica (Liver fluke) in cattle. It is not effec-tive against immature flukes less than 8 weeks old. It also has activ-ity against Fasciola gigantica. Although not approved, the drug has been used in practice in various other species (e. g., sheep, llamas). It has activity against F. magna in sheep, but is not completely ef-fective in eradicating the organism after a single dose, thus severely limiting its clinical usefulness against this parasite. Clorsulon is also not effective against the rumen fluke (Paramphistomum). Pharmacology/Actions In susceptible flukes, clorsulon inhibits the glycolytic enzymes 3-phosphoglycerate kinase and phosphoglyceromutase, thereby blocking the Emden-Myerhof glycolytic pathway; the fluke is de-prived of its main metabolic energy source and dies. Clorsulon at 7 mg/kg is effective against migrating F. hepatica 8 weeks post-infec-tion, but at 2 mg/kg is effective only against adult flukes (14 weeks post infection). Pharmacokinetics After oral administration to cattle, the drug is absorbed rapidly with peak levels occurring in about 4 hours. Approximately 75% of the circulating drug is found in plasma and 25% in erythrocytes. At 8-12 hours after administration, clorsulon levels peak in the fluke. Contraindications/Precautions/Warnings No milk withdrawal time has been deter mined, and the drug is la-beled not for use in female dairy cattle of breeding age. The combination injectable product (Ivomec Plus®) must be ad-ministered subcutaneously only; do not give IV or IM. The manu-facturer warns to use in cattle only as severe reactions, including fatalities in dogs, may occur. Adverse Effects When used as directed adverse effects are unlikely to occur with the oral suspension (Curatrem®). Local swelling may occur at injection sites with Ivomec Plus®. Reproductive/Nursing Safety Clorsulon is considered safe to use in pregnant or breeding animals. Overdosage/Acute Toxicity Clorsulon is very safe when administered orally to cattle or sheep. Doses of up to 400 mg/kg have not produced toxicity in sheep. A dose that is toxic in cattle has also not been determined. Drug Interactions/laboratory Considerations None identified Doses CATTl E:T! For Fasciola hepatica infections: a) 7 mg/kg PO; deposit suspension over the back of the tongue (Label directions; Cura trem®—Merial) For Fasciola hepatica infections, round worms, lungworms, cattle grubs, sucking lice, mange mites (see Ivermectin monograph or product label for more information on species covered):a) Inject 1m L per 110 lb. body weight SC behind the shoulder (Label directions; Ivomec Plus®—Merial) SHEEP:T! For Fasciola hepatica infections: a) 7 mg/kg PO (Roberson 1988a) ll Am AS:T! For Fasciola hepatica infections: b) 7 mg/kg PO (Fowler 1989) monitoring Clinical efficacy T! Client Information Shake well before using (T! Curatrem®) Follow withdrawal times for slaughter (8 days for T! Curatrem®, 49 days for Ivomec Plus®) Do not use in female dairy cattle of breeding age T! Chemistry/Synonyms A benzenesulfonamide, clorsulon has a chemical name of 4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide. Clorsulon may also be known as MK-401, Curatrem®, o r Ivomec®. Storage/Stability Unless otherwise instructed by the manufacturer, clorsulon should be stored at room temperature (15-30°C). Dosage Forms/Regulatory Status VETERINAR y APPROVED PRODUCTS: Clorsulon 8. 5% (85 mg/m L) Oral Drench in quarts or gallons; Curatrem® (Merial); (OTC). Ap proved for use in cattle. Slaughter withdrawal = 8 days (when used as labeled); Because a with drawal time in milk has not been established, do not use in female dairy cattle of breeding age. Clorsulon 10% (100 mg/m L) and Ivermectin 1% (10 mg/m L) In-jection in 50 m L, 200 m L, 500 m L, & 1000 m L. Ivomec® Plus (Me-rial); (OTC). Approved for subcutaneous injection use in cattle. Do not use within 49 days of slaughter; do not use in female dairy cattle of breeding age. HUm AN APPROVED PRODUCTS: None | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
224 Cl Ox ACIll IN clox Acillin sodium clox Acillin benz A thine (klox-a-sill-in) Orbenin-DC®, Dry-Clox®, Dariclox® anti-staphyl Oc Occal penicillin Prescriber Highlights Intramammary isoxazolyal (anti-staphylococcal) penicillin T T Contraindicated: Hypersensitivity to penicillins T T Oral dosage forms (human) no longer marketed in USAT T Uses/Indications Cloxacillin is used via intramammary infusion in dry and lactating dairy cattle. Pharmacology/Actions Cloxacillin, dicloxacillin and oxacillin have nearly identical spec-trums of activity and can be considered therapeutically equiva-lent when comparing in vitro ac tivity. These penicillinase-resistant penicillins have a narrower spectrum of activity than the nat ural penicillins. Their antimicrobial efficacy is aimed directly against penicillinase-producing strains of gram-positive cocci, particularly Staphylococcal species. They are sometimes called anti-staphy-lococcal penicillins. There are documented strains of Staphylococci that are resistant to these drugs (so-called methicillin-resistant Staph), but these strains have not yet become a major problem in vet erinary species. While this class of penicillins does have activity against some other gram-positive and gram-negative aerobes and anaerobes, other antibiotics (penicillins and otherwise) are usually better choices. The penicillinase-resistant penicillins are inactive against Ri ckettsia, mycobacteria, fungi, Mycoplasma, and viruses. Pharmacokinetics Cloxacillin is only available in intramammary dosage forms in the USA. 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, car-bapenems). 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 agents and can manifest as rashes, fever, eosinophilia, neutropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, lymph-adenopathy, or full-blown anaphylaxis. In humans, it is estimated that 1-15% of patients hy persensitive to cephalosporins will also be hypersensitive to penicillins. The incidence of cross-reac tivity in veterinary patients is unknown. 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 the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) Overdosage/Acute Toxicity Overdosage of intramammary infusions is unlikely to pose much risk to the patient, but may prolong withdrawal times. Drug Interactions No significant interactions are likely when intramammary dosage forms are used as labeled. laboratory Considerations No specific concerns noted Doses Note : Oral dosage forms are no longer available commercially in the USA—see Dicloxacillin for oral use DOg S:T! For susceptible infections:a) 20-40 mg/kg PO q8h (Vaden and Papich 1995) b) For Staph. pyoderma, diskospondylitis, osteoarthritis or skin infections: 10-15 mg/kg PO q6h for 14-84 days c) For systemic infections, bacteremia: 10-40 mg/kg PO q6-8h for 7 -14 days (Greene and Watson 1998) CATS:T! For susceptible infections:a) 20-40 mg/kg PO or IM q6-8h (Papich 1988) b) For Staph. pyoderma, diskospondylitis, osteoarthritis or skin infections: 10-15 mg/kg PO q6h for 14-84 days c) For systemic infections, bacteremia: 10-40 mg/kg PO q6-8h for 7 -14 days (Greene and Watson 1998) CATTl E:T! For mastitis (treatment or prophylaxis) caused by susceptible or-ganisms:a) Lactating cow (using lactating cow formula; Dari-Clox®): Af-ter milking out and disin fecting teat, instill contents of sy-ringe; massage. Repeat q12h for 3 total doses. Dry (non-lactating) cows (using dry cow formula; benza-thine): After last milking (or early in the dry period), instill contents of syringe and massage into each quarter. (Package inserts; Dari-Clox®, Orbenin-DC®—Beecham; Dri-Clox®— Fort Dodge) monitoring Because penicillins usually have minimal toxicity associated with T! 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. Client Information Dry cow products (benzathine; T! Orbenin-DC®, Dry-Clox®) slaugh-ter withdrawal = 28-30 days (depending on product used) Lactating cow product (T! Dariclox®) withdrawal times when used as labeled; milk withdrawal = 48 hours; slaughter withdrawal = 10 days | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CODEINE 225 Chemistry/Synonyms An isoxazolyl-penicillin, cloxacillin sodium is a semisynthetic, penicillinase-resistant penicillin. It is available commercially as the monohydrate sodium salt that occurs as an odorless, bitter-tasting, white, crystalline powder. It is freely soluble in water and soluble in alcohol and has a p K a of 2. 7. One mg of cloxacillin sodium contains not less than 825 micrograms of cloxacillin. Cloxacillin benzathine occurs as white or almost white powder that is slightly soluble in water and alcohol. A 1% (10 mg/m L) sus-pension has a p H from 3-6. 5. Cloxacillin sodium may also be known as: BRL-1621, sodium cloxacillin, chlorphenylmethyl isoxazolyl peni cillin sodium, meth-ylchlorophenyl isoxazolyl penicillin sodium, cloxacilina sodica, cloxacillinum natricum, or P-25; many trade names are available. Storage/Stability Unless otherwise instructed by the manufacturer, cloxacillin ben-zathine or cloxacillin sodium mastitis syringes should be stored at temperatures less than 25°C in tight containers. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Cloxacillin Benzathine 500 mg (of cloxacillin) in a peanut-oil gel; 10 m L syringe for intramam mary infusion: Orbenin-DC® (Schering-Plough), Dry-Clox® (Fort Dodge); (Rx). Approved for use in dairy cows during the dry period (immediately after last milking or early in the dry period). Do not use within 30 days prior to calving (28 days for Orbenin-DC®). Slaughter withdrawal = 30 days (28 days for Orbenin-DC®). A tolerance of 0. 01 ppm has been established for negligible residues in uncooked edible meat and milk from cattle. Cloxacillin Sodium 200 mg (of cloxacillin) in vegetable oils; 10 m L syringe for intramammary in fusion: Dariclox® (Schering-Plough); (Rx). Approved for use in lactating dairy cows. When used as la-beled, Milk withdrawal = 48 hours; Slaughter withdrawal = 10 days. HUm ANl Ab El ED PRODUCTS: Nonecodeine phosph A te codeine sulf Ate (koe-deen) Opiate Prescriber Highlights Opiate used for analgesia, cough, & sometimes diarrhea T T in dogs & cats Contraindications: Hypersensitivity to narcotics, receiv-T T ing MAOI's (amitraz, selegiline?), or diarrhea caused by a toxic ingestion until the toxin is eliminated Conditions where narcotics must be used with caution: T T Hypothyroidism, se vere renal insufficiency, Addison's, head injuries or increased intracranial pressure, or acute abdominal conditions (e. g., colic) as it may obscure the diagnosis or clinical course of these conditions; in geriat-ric or severely debilitated patients; use extreme caution in patients with respiratory disease or acute respiratory dysfunction Adverse Effects most likely noted include: Sedation, con-T T stipation, high doses may cause respiratory depression. Cats may also show CNS stimulation. Controlled Substance (Class-II when used as a sole T T agent) Uses/Indications In small animal medicine, codeine is used principally as an oral analgesic when salicylates are not effective and parenteral opiates are not warranted. It may also be useful as an anti tussive or an antidiarrheal. Pharmacology/Actions Codeine possesses activity similar to other opiate agonists. It is an effective antitussive and a mild analgesic. It produces similar re-spiratory depression, as does morphine at equianalgesic dosages. For further information on opiate pharmacology, refer to: Opiate Agonists, Pharmacology. Pharmacokinetics No information was located specifically for domestic animals; the following information is human data unless otherwise noted. After oral administration, codeine salts are rapidly absorbed. Codeine is about 2/3's as effective after oral administration when compared with parenteral ad ministration. After oral dosing, onset of action is usually within 30 minutes and analgesic effects persist for 4-6 hours. Codeine is metabolized in the liver and then excreted into the urine. Contraindications/Precautions/Warnings All opiates should be used with caution in patients with hypothy-roidism, severe renal insufficiency, adrenocortical insufficiency (Addison's disease), and in geriatric or severely debilitated patients. Codeine is contraindicated in cases where the patient is hypersen-sitive to narcotic analgesics, or in patients taking monamine oxi-dase inhibitors (MAOIs). It is also contraindicated in patients with diarrhea caused by a toxic ingestion (until the toxin is eliminated from the GI tract) or when used repeatedly in patients with severe inflammatory bowel disease. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
226 CODEINE Codeine should be used with caution in patients with head in-juries or increased intracranial pressure, and in those with acute abdominal conditions (e. g., colic) as it may obscure the diagnosis or clinical course of these conditions. Use with extreme caution in patients suffering from respiratory dis ease or from acute respiratory dysfunction (e. g., pulmonary edema secondary to smoke inhala-tion). Opiate analgesics are contraindicated in patients who have been stung by the scorpion species Centruroides sculpturatus Ewing and C. gertschi Stahnke as they may potentiate these venoms. Do not use the combination product containing acetaminophen in cats. Adverse Effects Codeine generally is well tolerated, but adverse effects are possible, particularly at higher dosages or with repeated use. Sedation is the most likely effect seen. Potential gastrointestinal effects include an-orexia, vomiting, constipation, ileus, and biliary and pancreatic duct spasms. Respiratory depression is generally not noted unless the pa-tient receives high doses or is at risk (see contraindications above). In cats, opiates may cause CNS stimulation with hyperexcitabil-ity, tremors, and seizures are pos sible. Reproductive/Nursing Safety Opiates cross the placenta. Very high doses in mice have caused de-layed ossification. Use during pregnancy only when the benefits out-weigh the risks, particularly with chronic use. 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 ad-equate 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 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. ) Although codeine enters maternal milk, no documented prob-lems have been associated with its use in nursing mothers. Overdosage/Acute Toxicity Opiate overdosage may produce profound respiratory and/or CNS de pression in most species. Other effects can include cardiovascu-lar collapse, hypothermia, and skele tal muscle hypotonia. Oral in-gestions of codeine should be removed when possible using stan-dard gut removal protocols. Because rapid changes in CNS status may occur, inducing vomiting should be attempted with caution. Naloxone is the agent of choice in treating respiratory depression. In massive overdoses, naloxone doses may need to be repeated and animals should be closely observed because naloxone's effects may diminish before subtoxic levels of codeine are attained. Mechanical respi ratory support should also be considered in cases of severe re-spiratory depression. Serious overdoses involving any of the opiates should be closely monitored; it is suggested to contact an animal poison control center for further information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving codeine and may be of significance in veterinary patients: ANTICHOl INERg IC DRUg S T! : Use with codeine may increase the chanc-es of constipation developing ANTIDEPRESSANTST! (tricyclic/monoamine oxidase inhibitors ): May po-tentiate CNS depressant effects CNS DEPRESSANTS, OTHERT! (e. g., anesthetic agents, antihistamines, phenoth iazines, barbiturates, tranquilizers, alcohol, etc. ) May cause in-creased CNS or respiratory depression when used with codeine QUINIDINET! : May inhibit the transformation of codeine to morphine in the liver thereby decreasing it efficacy laboratory Considerations As they may increase biliary tract pressure, opiates can increase T! plasma amylase and lipase values up to 24 hours following their administration. Doses DOg S:T! As an antitussive:a) 1-2 mg/kg PO q6-12h (Fenner 1994) b) Starting doses have been as low as 0. 1-0. 3 mg/kg PO q8-12h and as high as 1-2 mg/kg PO q6-12h. Whatever the starting point, the dose may need to be increased to achieve a satisfac-tory effective. (Church 2003) As an analgesic:a) For mild to moderate acute pain: 0. 5-2 mg/kg PO titrated to effect q6-12h. May use for chronic pain at lowest effective dose (Mathews 2000) b) In combination with acetaminophen: Using a 60 mg codeine and 300 mg acetaminophen fixed-dose tablet (e. g., Tylenol® #4), give 1-2 mg/kg (of the codeine) PO q6-8h. Using co-deine alone: 1-4 mg/kg PO q1- 6 hours (Hansen 1994); (Hardie 2000) Note : Do not use in cats. As an antidiarrheal:a) 0. 25-0. 5 mg/kg PO q6-8h (Sherding and Johnson 1994) CATS: T! Note : Do NOT use the combination product containing acetaminophen As an analgesic: a) For mild to moderate acute pain: 0. 5-2 mg/kg PO titrated to effect q6-12h. May use for chronic pain at lowest effective dose (Mathews 2000) b) 0. 5-2 mg/kg PO q6-8h (Scherk 2003a) RAbb ITS: T! Using acetaminophen and codeine elixir: a) 1 m L in 10-20 m L of drinking water (add dextrose to en-hance palatability) (Ivey and Morrisey 2000) monitoring Efficacy T! Adverse effects (see above)T! Client Information Keep out of reach of children T! Do not use any product containing acetaminophen (T! e. g., Tylenol #3) in cats Report any significant changes in behavior or activity level, or GI T! effects (constipation, lack of appetite, vomiting) to veterinarian Chemistry/Synonyms A phenanthrene-derivative opiate agonist, codeine is available as the base and three separate salts. Codeine base is slightly soluble in wa-ter and freely soluble in alcohol. Codeine phos phate occurs as fine, white, needle-like crystals or white, crystalline powder. It is freely soluble in water. Codeine sulfate's appearance resembles codeine phosphate, but it is soluble in water. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
COl CHICINE 227 Codeine phosphate may also be known as: codeine phosphate hemihydrate, codeini phosphas; codeini phosphas hemihydricus, or codeinii phosphas; many trade names are available. Storage/Stability/Compatibility Codeine phosphate and sulfate tablets should be stored in light-resistant, well-closed containers at room temperature. Codeine phosphate injection should be stored at room temperature (avoid freezing) and protected from light. Do not use the injection if it is discol ored or contains a precipitate. Codeine phosphate injection is reportedly compatible with glycopyrrolate or hydroxyzine HCl. It is reportedly incompatible with aminophylline, ammonium chloride, amobarbital sodium, chloroth iazide sodium, heparin sodium, methicillin sodium, pen-tobarbital sodium, phenobarbital sodium, phenytoin sodium, seco-barbital sodium, sodium bicarbonate, sodium iodide, and thiopen-tal sodium. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None. The ARCI (Racing Commissioners International) has designated this drug as a class 1 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: There are many products available containing codeine. The follow-ing is a partial listing: Codeine Phosphate Solution: 15 mg/5 m L in 500 m L & UD 5 m L; Codeine Phosphate (Roxane); (Rx, C-II) Codeine Sulfate Tablets: 15 mg, 30 mg & 60 mg; generic; (Rx, C-II)Codeine Phosphate Parenteral Injection: 15 mg/m L & 30 mg/m L in 2 m L Carpuject syringe; generic; (Rx, C-II) Codeine Phosphate Antitussives with expectorants: 10 mg codeine phosphate and 200 mg guaifen esin; 10 mg codeine phosphate and 100 mg guaifenesin; Many different trade names available; (C-V; C-III; certain states may restrict at a higher level; OTC or Rx) Codeine Phosphate 7. 5 mg (#1), 15 mg (#2), 30 mg (#3), 60 mg (#4) with Acetaminophen 300 mg tablets; Tylenol® with Codeine #'s 1, 2, 3, 4 (Mc Neil); generic; (Rx, C-III) WARNINg: Do not use in cats. Codeine Phosphate 15 mg (#2), 30 mg (#3), 60 mg (#4) with Aspi-rin 320 mg tablets; Empirin® with Codeine #'s 2, 3, 4 (Glaxo Well-come); generic; (Rx, C-III) Note : Codeine-only products are Class-II controlled substances. Combination products with as pirin or acetaminophen are Class-III. Codeine containing cough syrups are either Class-V or Class-III, depending on the state. colchicine (kol-chi-seen) antiinflammat Ory Prescriber Highlights Unique antiinflammatory occasionally used in dogs for T T hepatic cirrhosis/fibrosis; rela tively experimental Contraindications: Serious renal, GI, or cardiac T T dysfunction Caution: Geriatric or debilitated patients T T Teratogenic, reduces spermatogenesis T T Most likely adverse effects are GI distress (may be an T T early sign of toxicity), but several serious effects are possible including bone marrow suppression Uses/Indications In veterinary medicine, colchicine has been proposed as a treat-ment in small animals for amyloido sis. For colchicine to be effec-tive, however, it must be given early in the course of the disease and it will be ineffective once renal failure has occurred. At the time of writing, no conclusive evidence exists for its efficacy for this indica-tion in dogs. Colchicine has also been proposed for treating chronic hepatic fibrosis presumably by decreasing the formation and increasing the breakdown of collagen. Pharmacology/Actions Colchicine in hibits cell division during metaphase by interfering with sol-gel formation and the mitotic spindle. The mechanism for its antifibrotic activity is believed secondary to collagenases activity stimulation. Colchicine apparently blocks the synthesis and secretion of se-rum amyloid A (SAA; an acute-phase reactant protein) by hepato-cytes thereby preventing the formation of amyloid-enhancing fac-tor and preventing amyloid disposition. Colchicine is best known in human medicine for its antigout ac-tivity. The mechanism for this effect is not fully understood, but it probably is related to the drug's ability to reduce the inflammatory response to the disposition of monosodium urate crystals. Pharmacokinetics No information was located specifically for domestic animals; the following in formation is human/lab animal data unless otherwise noted. After oral administration, colchicine is absorbed from the GI tract. Some of the absorbed drug is metabolized in the liver (first-pass effect). These metabolites and unchanged drug are re-secreted into the GI tract via biliary secretions where it is reabsorbed. This “recycling” phenomena may explain the intestinal manifestations noted with colchicine toxicity. Colchicine is distributed into sev-eral tissues, but is concentrated in leukocytes. Plasma half-life is about 20 minutes, but leukocyte half-life is approximately 60 hours. Colchicine is deacetylated in the liver and metabolized in other tis-sues. While most of a dose (as colchicine and metabolites) is excret-ed in the feces, some is excreted in the urine. More may be excreted in the urine in patients with hepatic disease. Patients with severe renal disease may have prolonged half-lives. Contraindications/Precautions/Warnings Colchicine is contraindicated in patients with serious renal, GI, or cardiac dysfunction and should be used with caution in patients in | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
228 COl CHICINE early stages of these disorders. It should also be used with caution in geriatric or debilitated patients. Colchicine use in veterinary medicine is somewhat controversial as safety and efficacy have not been well documented. Adverse Effects There has been very little experience with colchicine in domestic ani-mals. There are reports that colchicine can cause nausea, vomiting, and diarrhea in dogs, but these are thought to occur infrequently at doses used. Neutropenia is a rare adverse effect. In humans, GI effects have been noted (abdominal pain, anorex-ia, vomiting, diarrhea) and can be an early indication of toxicity; it is recommended to discontinue therapy (in humans) should these occur. Prolonged administration has caused bone marrow depres-sion. Severe local irritation has been noted if extrava sation occurs after intravenous administration; thrombophlebitis has also been reported. Reproductive/Nursing Safety Because colchicine has been demonstrated to be teratogenic in labo-ratory animals (mice and ham sters) it should be used during preg-nancy only when its potential benefits outweigh its risks. Colchicine may de crease spermatogenesis. In humans, the FDA categorizes this drug as category C (ORAL) for use during pregnancy (Animal stud-ies 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 humans, the FDA categorizes this drug as category D (PARENTERAL) 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. ) It is un known if colchicine enters maternal milk; use cautiously in nursing mothers. Overdosage/Acute Toxicity Colchicine can be a very toxic drug after relatively small overdoses. Deaths in humans have been reported with a single oral ingestion of as little as 7 mg, but 65 mg is considered the lethal dose in an adult human. GI manifestations are usually the presenting signs seen. These can range from anorexia and vomiting to bloody diarrhea or paralytic ileus. Renal fail ure, hepatotoxicity, pancytopenia, paralysis, shock, and vascular collapse may also occur. There is no specific antidote to colchicine. Gut removal tech-niques should be employed when ap plicable. Because of the exten-sive GI “recycling” of the drug, repeated doses of activated charcoal and a saline cathartic may reduce systemic absorption. Other treat-ment is symptomatic and support ive. Dialysis (peritoneal) may be of benefit. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving colchicine and may be of significance in veterinary patients: b ONE m ARROW DEPRESSANT m EDICATIONS T! (e. g., antineoplastics, im munosuppressants, chloramphenicol, amphotericin b): May cause ad-ditive myelosuppression when used with colchicine laboratory Considerations Colchicine may cause false-positive results when testing for T! erythro cytes or hemoglobin in urine. Colchicine may interfere with T! 17hydroxycorticosteroid determina-tions in urine if using the Reddy, Jenkins, and Thorn procedure. Colchicine may cause increased serum values of T! alkaline phosphatase. Doses Colchicine may have some efficacy in the treatment of amyloidosis, but veterinary dosages are ap parently unavailable at this time. DOg S:T! For the adjunctive treatment of hepatic cirrhosis/fibrosis: a) 0. 03 mg/kg PO once daily (Leveille-Webster and Center 1995); (Twedt 1999); (Richter 2002); (Willard 2006b) b) 0. 025-0. 03 mg/kg PO once daily (probenecid-free drug). Not recommended for initial use with azathioprine, chloram-bucil or methotrexate due to similar side effects (GI toxicity, bone marrow suppression). Used in many dogs and fewer cats without problems. (Center 2002), (Center 2006a) For amyloidosis:a) For periodic fever syndrome in Shar Pei dogs: 0. 03 mg/kg PO once daily. (Scherk and Center 2005) b) T o reduce the frequency and severity of fever and prevent the development of amyloidosis in dogs with Shar Pei Fe-ver: 0. 025-0. 03 mg/kg PO q24h; no evidence supports use of colchicine once amyloidosis has resulted in renal failure (Vaden 2006a) monitoring Efficacy T! Adverse effects (see above)T! CBCT! Client Information Clients should be informed of the “investigational” nature of T! colchicine use in dogs and should be informed of the potential adverse effects that may be seen Report changes in appetite or other GI effects immediately to vet-T! erinarian Keep well out of reach of children or pets T! Pregnant women should avoid exposure to the drug or urine of T! animals being treated Chemistry/Synonyms An antigout drug possessing many other pharmacologic effects, colchicine occurs as a pale yellow, amorphous powder or scales. It is soluble in water and freely soluble in alcohol. Colchicine may also be known as: colchicinum, Artrex ®, Colchily®, Colchicquim®, Colchis®, Colcine®, Colgout ®, Goutichine®, Goutnil®, Reugot ®, Ticolcin®, or Tolchicine®. Storage/Stability Colchicine tablets should be stored in tight, light resistant con tainers. The injection should be diluted only in 0. 9% sodium chloride for injection or sterile water for injection. Do not use D 5W or bacterio-static sodium chloride for injection as precipitation may occur. Do not use solutions that have become turbid. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
CORTICOTROPIN (ACTH) 229 HUm ANl Ab El ED PRODUCTS: Colchicine Tablets: 0. 6 mg (1/100 gr); generic; (Rx); Colchicine Injection: 0. 5 mg/m L in 2 m L vials; Colchicine (Bed-ford); (Rx) A combination oral product (tablets) containing colchicine 0. 5 mg and probenecid 500 mg is also available (not likely to be useful in veterinary patients) Co-Trimoxazole; Co-trimazine — See Sulfa/Trimethoprim corticotropin (Acth) (kor-ti-koe-troe-pin) Acthar® h Orm Onal diagn Ostic agent Prescriber Highlights Stimulates cortisol release; used primarily to test for T T hyper-or hypoadrenocorticism (ACTH-stimulation test) Adverse Effects: Unlikely unless using chronically T T Do not administer gel form IVT T Issues include availability & expense T T Uses/Indications Availability of corticotropin in FDA-approved products is an issue as no commercially products were commercially available for vet-erinary use at the time writing and either cosyntropin (see mono-graph) or compounded ACTH products are required. In veterinary medicine, an ACTH product (Adrenomone®— Summit Hill) was ap proved for use in dogs, cats, and beef or dairy cattle for stimulation of the adrenal cortex when there is a defi-ciency of ACTH and as a therapeutic agent in primary bovine keto-sis, but apparently is no longer commercially available. In practice, ACTH tends to be used most often in the diagnosis of hyper-or hypoadrenocorticism (ACTH-stimulation test) and to monitor the response to mitotane therapy in Cushing's syndrome. One reference (Behrend 2003a) recommends using the ACTH stimulation test if the dog has non-adrenal illness, received any form of exogenous glucocorticoids (including topicals), or received phenobarbital. If the dog has no known non-adrenal illness and moderate to severe clinical signs of hyperadrenocorticism, use the low-dose dexamethasone suppression test. If using the ACTH-stim test, the author states that cosyntropin is the agent of choice (see that monograph). ACTH has been used for several purposes in human medicine for its corticosteroid stimulating properties, but as it must be in-jected, it is not commonly employed in veterinary patients. Pharmacology/Actions ACTH stimulates the adrenal cortex (principally the zona fascic-ulata) to stimulate the production and release of glucocorticoids (primarily cortisol in mammals and corticosterone in birds). ACTH release is controlled by corticotropin-releasing factor (CRF) activated in the central nervous system and via a negative feedback pathway, whereby either endogenous or exogenous glu cocorticoids suppresses ACTH release. Pharmacokinetics Because it is rapidly degraded by proteolytic enzymes in the gut, ACTH cannot be administered PO. It is not effective if adminis-tered topically to the skin or eye. After IM injection in humans, repository corticotropin injection is absorbed over 8-16 hours. The elimination half-life of circulat-ing ACTH is about 15 minutes but because of the slow absorption after IM injection of the gel, effects may persist up to 24 hours. Contraindications/Precautions/Warnings When used for diagnostic purposes, it is unlikely that increases in serum cortisol levels induced by ACTH will have significant delete-rious effects on conditions where increased cortisol levels are con-traindicated (e. g., systemic fungal infections, osteoporosis, peptic ul cer disease, etc. ). ACTH gel should not be used in patients hyper-sensitive to porcine proteins. Adverse Effects Prolonged use may result in fluid and electrolyte disturbances and other adverse effects; if using on a chronic basis, refer to the human literature for an extensive listing of potential adverse reactions. The veterinary manufacturer suggests giving potassium supplementa-tion with chronic therapy. Do not administer the repository form (gel) IV. Reproductive/Nursing Safety ACTH should only be used during pregnancy when the potential benefits outweigh the risks. It may be embryocidal. Neonates born from mothers receiving ACTH should be observed for signs of adrenocortical insufficiency. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate stud-ies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Overdosage/Acute Toxicity When used for diagnostic purposes, acute inadvertent overdoses are unlikely to cause any significant adverse effects. Monitor as re-quired and treat symptomatically if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving corticotropin for diag-nostic purposes and may be of significance in veterinary patients: ANTICHOl INESTERASEST! (e. g., pyridostigmine ): ACTH may antago-nize effects in patients with myasthenia gravis DIURETICST! : ACTH may increase electrolyte loss laboratory Considerations Patients should not receive T! hydrocortisone or cortisone on test day ACTH may decrease T!131I uptake by the thyroid gland ACTH may suppress T! skin test reactions ACTH may interfere with T! urinary estrogen determinations Obtain specific information from the laboratory on sample han-T! dling and laboratory normals for cortisol when doing ACTH stimulation tests Doses Note : When using compounded ACTH products, it is recommend-ed to get several post-ACTH samples, at a minimum one and two hours following injection. (Behrend 2005) DOg S:T! ACTH Stimulation T est:a) Draw baseline blood sample for cortisol determination and administer 2. 2 Units/kg of ACTH gel IM. Draw sample 120 minutes after injection. (Feldman and Peterson 1984), (Kemppainen and Zerbe 1989b) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
230 COSy NTROPIN b) Draw baseline blood sample for cortisol determination and administer 0. 5 Units/kg of ACTH gel IM. Draw sample 120 minutes after injection. Normals: Pre-ACTH 1. 1-8 micrograms/dl; Post-ACTH 6. 2-16. 8 micrograms/dl. Hyper adrenocorticism: Pre-ACTH 4-10. 8 micrograms/dl; Post-ACTH 11. 7-50 micrograms/dl. Hypoadrenocorticism: Pre-ACTH and Post-ACTH: ≤ 1 mi-crograms/dl (Morgan 1988) CATS:T! ACTH Stimulation T est: a) Draw baseline blood sample for cortisol determination and administer 2. 2 Units/kg of ACTH gel IM. Draw samples at 60 minutes and 120 minutes after injection. (Peterson and Ran-dolph 1989), (Kemppainen and Zerbe 1989b) b) Draw baseline blood sample for cortisol determination and administer 0. 5 Units/kg of ACTH gel IM. Draw sample 120 minutes after injection. Normals: Pre-ACTH 0. 33-2. 6 micrograms/dl; Post-ACTH 4. 8-7. 6 micrograms/dl. Hyper adrenocorticism: Pre-ACTH 4-10. 8 micrograms/dl; Post-ACTH 11. 7-50 micrograms/dl. Hypoadrenocorticism: Pre-ACTH and Post-ACTH: ≤ 1 mi-crograms/dl (Morgan 1988) CATTl E:T! For ACTH deficiency or for primary bovine ketosis: a) 200-600 Units initially followed by daily or semi-daily dose of 200-300 Units (Package Insert; Adrenomone®—Summit Hill) b) 200 Units IM daily (Howard 1986) HORSES:T! ACTH Stimulation T est:a) Draw baseline blood sample for cortisol determination and administer 1 Unit/kg IM of ACTH gel. Draw second sample 8 hours later. Normal stimulation will result in serum cortisol levels will increase 2-3 times. Horses with pituitary tumors will increase cortisol fourfold after ACTH. (Beech 1987b) b) Obtain pre-dose level. Administer 1 Unit/kg IM of ACTH gel between 8 and 10 AM; take post ACTH cortisol levels at 2 and 4 hours post dose. Horses with a functional adrenal gland should have a 2-to 3-fold increase in plasma cortisol when compared with baseline. (T oribio 2004a) b IRDS:T! ACTH Stimulation T est:a) Draw baseline blood sample for corticosterone (not cortisol) determination and adminis ter 16-25 Units IM. Draw second sample 1-2 hours later. Normal baseline corticosterone levels vary with regard to species, but generally range from 1. 5-7 ng/m L. After ACTH, corticosterone levels generally increase by 5-10 times those of baseline. Specific values are listed in the reference. (Lothrop and Harrison 1986) Chemistry/Synonyms A 39 amino acid polypeptide, corticotropin is secreted from the anterior pituitary. The first 24 amino acids (from the N-terminal end of the chain) define its biologic activity. While human, sheep, cattle and swine corticotropin have different structures, the first 24 amino acids are the same and, therefore, biologic activity is thought to be identical. Commercial sources of ACTH have generally been obtained from porcine pituitaries. One USP unit of corticotropin is equivalent to 1 mg of the in ternational standard. Corticotropin may also be known as: ACTH, adrenocorti-cotrophic hormone, adrenocorticotrophin, corticotrophin, corti-cotropinum, Acethropan®, Acortan simplex®, Actharn®, Acthelea®, Acton prolongatum®, H. P. Acthar® or Cortrophin-Zinc®. Storage/Stability/Compatibility Corticotropin in the past has been available commercially as cor-ticotropin for injection, repository corticotropin for injection, and corticotropin zinc hydroxide suspension. Corticotropin is common-ly called ACTH (abbreviated from adrenocorticotropic hormone). Repository corticotropin is often called ACTH gel and is the most commonly used ACTH product in veterinary medicine. Corticotropin for injection (aqueous) can be stored at room tem perature (15-30°C) before reconstitution. After reconstitution, it should be refrigerated and used within 24 hours. Repository cor-ticotropin injection should be stored in the refrigerator (2-8°C). T o allow ease in withdrawing the gel into a syringe, the vial may be warmed with warm water prior to use. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None Compounded ACTH products may be available from compounding pharmacies. HUm ANl Ab El ED PRODUCTS: Corticotropin, Repository for Injection: 80 Units/m L in m L 5 m L multi-dose vials; H. P. Acthar® Gel (Questcor); (Rx) Note : This prod-uct is only available through a specialty pharmacy distribution sys-tem and is not available via regular retail pharmacies or drug whole-salers. cosyntropin (koh-sin-troh-pin) Cortrosyn®, Synacthen® h Orm Onal diagn Ostic agent Prescriber Highlights Alternative to ACTH for adrenal function tests T T Drug-lab interactions T T Availability & expense have been issues T T Uses/Indications Cosyntropin is used primarily as an alternative to ACTH to test for adrenocorti cal insufficiency (Addison's), or hyperadrenocorticism, particularly in animals who have reacted im munologically to corti-cotropin in the past or if ACTH gel is unavailable. Pharmacology/Actions Like endogenous corticotropin, cosyntropin stimulates the adrenal cortex (in nor mal patients) to secrete cortisol, corticosterone, etc. Because of its structure, corticotropin is not as immunogenic as en-dogenous corticotropin. Apparently, the bulk of immunogenicity resides in the C-terminal portion of corticotropin (22-39 amino acids) and cosyntropin ends after amino acid #24. Pharmacokinetics Cosyntropin must be given parenterally because it is inactivated by gut enzymes. It is rapidly absorbed after being given IM. After giv-ing IM or rapid IV, plasma cortisol levels reach their peak within an hour. It is unknown how cosyntropin is inactivated or eliminated. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
COSy NTROPIN 231 Contraindications/Precautions/Warnings Contraindicated in patients with known hy persensitivity to co-syntropin. Use caution in patients who have shown hypersensitive reactions to ACTH in the past; there is a distinct possibility that cross-reactivity could occur. Adverse Effects When used short-term, the only real concern is hypersensitivity reac tions. 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 Unlikely to be of clinical consequence if used one-time only. laboratory Considerations Patients should not receive T! hydrocortisone or cortisone on test day; dexamethasone sodium phosphate does not interfere with corti-sol assays If using a fluorometric analysis: Falsely high values may be ob-T! served if the patient is taking spironolactone Falsely high values may be observed in patients with high T! bilirubin or if free plasma hemoglobin present Doses DOg S:T! For testing (screening) adrenal function: a) For tentative diagnosis of Addison's disease: 1) Draw blood for hemogram, serum biochemistry and basal cortisol; 2) Begin IV fluids and give 2-5 mg/kg dexamethasone sodium phosphate; 3) Immediately give 0. 25 mg of cosyntropin IV or IM; 4) Draw a second blood sample for plasma cortisol 45-60 minutes later. Blood levels of <1 mcg/d L are typical for hypoadrenocorticism, while those stimulating to only 2-3 mcg/d L are also suggestive. (Schaer 2006) b) 5 mcg/kg IV; measure serum cortisol at 0 and 1 hour. (Wat-son, Church et al. 1998) c) 5 mcg/kg with a maximum of 250 mcg IV. Once reconsti-tuted, the solution may be frozen for up to six months and used. (Behrend 2003a) d) For ACTH Stimulation test: Two different protocols: 1 mcg/kg or 250 mcg/dog IV or IM with serum cortisol measured before and 1 hour post injection. 80-85% of dogs with pi-tuitary-dependent hyperadrenocorticism (PD) and 60% of dogs with adrenal tumor/hyperplasia (AT) will have an exag-gerated response. Unfortunately, just about any other extra-adrenal illness can cause an exaggerated post-ACTH level. (Reine 2006) CATS:T! For testing (screening) adrenal function:a) For tentative diagnosis of Addison's disease: 1) Draw blood for hemogram, serum biochemistry and basal cortisol; 2) Begin IV fluids and give 2-5 mg/kg dexamethasone sodium phosphate; 3) Immediately give 0. 125 mg of cosyntropin IV or IM; 4) Draw a second blood sample for plasma cortisol 45-60 minutes later. Blood levels of <1 mcg/d L are typical for hypoadrenocorticism, while those stimulating to only 2-3 mcg/d L are also suggestive. (Schaer 2006)b) 0. 125 mg (total dose—125 mcg) IM or IV. Begin test between 8-9 AM; obtain preinjec tion cortisol level and 30 minutes and 1 hour post. (Feldman 2000) c) For diagnosis of hyperadrenocorticism in cats: 125 mcg/cat IM or IV with cortisol measurements before and at 30 and 60 minutes post. (Reine 2006) HORSES:T! For testing (screening) adrenal function:a) For relative adrenal insufficiency (RIA) evaluation in criti-cally ill horses: Draw blood for baseline cortisol and give co-syntropin at 0. 1 mcg/kg; cortisol will peak after 30 minutes. (Stewart 2006) b) Obtain pre-dose level. Administer 1 mg IV of cosyntropin between 8 and 10 AM; take post ACTH cortisol levels at 2 hours post dose. Horses with a functional adrenal gland should have at least a two-fold increase in plasma cortisol when compared with baseline. (T oribio 2004a) monitoring See specific protocols for test procedures T! Chemistry/Synonyms A synthetic polypeptide that mimics the effects of corticotropin (ACTH), cosyntropin is commercially available as a lyophilized white to off-white powder containing mannitol. Cosyntropin's structure is identical to the first 24 (of 39) amino acids in natural corticotropin. 0. 25 mg of cosyn tropin is equivalent to 25 units of corticotropin. Cosyntropin may also be known as: tetracosactide, al-pha(1-24)-corticotrophin, beta(1-24)-corticotrophin, tetracosac-tido, tetracosactidum, tetracosactrin, tetracosapeptide, Cortrosina®, Cortrosyn®, Nuvacthen Depot®, Synacthen®, Synacthen Depot®, Synacthen Retard®, or Synacthene®. Storage/Stability/Compatibility After reconstituting with sterile normal saline, the solution is stable for 24 hours at room temperature; 21 days if refrigerated. Do not add the drug to blood or plasma infusions. One study (Frank and Oliver 1998) showed that cosyntropin can be reconsti tuted and stored frozen (-20°C) in plastic syringes for up to 6 months and still show biologic activity in the dog. It is recommended to freeze in small aliquots as it is unknown what effect thawing and refreezing has on potency. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Cosyntropin Powder for Injection: 0. 25 mg lyophilized (250 mcg) in vials with 10 mg mannitol with diluent; Cortrosyn® (Ampha-star); (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
232 CROm Oly N SODIUm cromolyn sodium ( systemic) (kroh-mah-lin) Disodium Cromoglycate, Sodium Cromoglicate, Intal® mast cell stabilizer For ophthalmic use, see the monograph in the Ophthalmic Drug Appendix Prescriber Highlights Inhaled mast cell stabilizer that may be useful adjunctive T T treatment in preventing airway hyper-reactivity in horses with type 2 (high mast cell count in BAL) IAD or with RAO (heaves) Not for treatment of acute bronchoconstriction; used as T T a preventative agent May take several days or weeks for efficacy T T Uses/Indications Cromolyn sodium is a mast cell stabilizer that may be useful in re-ducing airway hyper-reactivity in horses with type 2 (high mast cell count in bronchoalveolar lavage fluid; mast cells of >2% of the to-tal cell count) inflammatory airway disease (IAD) or with recurrent airway obstruction (RAO; heaves). Use of this agent is somewhat controversial; studies have yielded conflicting efficacy results. Pharmacology/Actions Cromolyn inhibits the release of histamine and leukotrienes from sensitized mast cells found in lung mucosa, nasal mucosa and eyes. Its exact mechanism of activity is not understood, but it is thought to be a result from blocking indirect entry of calcium ions into cells. Other effects of cromolyn include inhibiting neuronal reflexes in the lung, inhibiting bronchospasm secondary to tachykins, inhibit-ing the movement of other inflammatory cells (neutrophils, mono-cytes, eosinophils), and preventing the down-regulation of beta-2 adrenergic receptors on lymphocytes. Cromolyn does not possess antihistaminic, anticholinergic, antiserotonin, corticosteroid-like, or antiinflammatory actions. Pharmacokinetics Limited information is available for horses. The amount of cromo-lyn reaching the distal airways is probably variable and dependent on the type of nebulizer used and the amount of concurrent bron-choconstriction present. Absorbed cromolyn is eliminated in the urine and via the bile into the feces. In humans, less than 2% is absorbed from the GI tract after oral dosing. Approximately 8% is absorbed when inhaled into the lung. Absorbed drug is eliminated via the feces and urine as unchanged drug. Contraindications/Precautions/Warnings Do not use in patients with documented hypersensitivity to cromolyn. Unlikely to be of benefit in treating horses with types 1and 3 IAD. Cromolyn has no efficacy in treating acute bronchospasm. Adverse Effects Adverse effects associated with inhaled cromolyn use in horses are not well documented. Cough and treatment avoidance (secondary to bad taste?) have been reported. It has been proposed that pre-treatment with albuterol may reduce the incidence of cough. Humans can occasionally develop cough, throat irritation or complain of unpleasant taste. Rarely, bronchoconstriction and ana-phylaxis (<0. 0001%) have been reported. Reproductive/Nursing Safety Laboratory animal studies have shown no effect on fertility. T eratogenicity studies in mice, rats and rabbits have not demon-strated any teratogenic effects and it is likely safe to use during preg-nancy. Extremely low (or undetectable) levels have been detected in milk; cromolyn is most likely safe to use during nursing. Overdosage/Acute Toxicity Because of the drug's low systemic bioavailability after inhalation or oral administration, acute overdoses are unlikely to cause significant morbidity. Drug Interactions No notable drug interactions have been reported. laboratory Considerations No notable laboratory interactions or alterations have been r e p o r t e d. Doses HORSES:T! a) For type 2 inflammatory airway disease: Using a jet nebulizer: 200 mg (total dose) q12 hours; using an ultrasonic nebulizer 80 mg once daily (q24h). (Couetil 2002) b) For RAO/IAD (either as long-term therapy or before exposure to allergens): Using the aerosol (800 mcg/puff) and a suitable delivery system: 8-12 mg (10-15 puffs) once to twice daily. (Mazan 2003) monitoring Clinical efficacy T! For horses with type 2 IAD, reductions in mast cell counts in T! bronchoalveolar lavage fluid could help confirm efficacy Client Information This medication does not treat airway constriction but used to T! prevent airway constriction by reducing the release of substances from cells that can cause it; it should not be used to treat acute bronchoconstriction (difficulty breathing). This medicine must be must be dosed once to twice daily and it T! may take several days or weeks before it can be determined if it is working. Proper use of the drug delivery device is very important; if any T! questions arise regarding proper use, contact the veterinarian. Chemistry/Synonyms Cromolyn sodium occurs as a white, odorless, hygroscopic, crystal-line powder that is soluble in water and insoluble in alcohol. Cromolyn sodium may also be known as cromoglicic acid, cro-moglycic acid, sodium cromoglicate, disodium cromoglycate, sodi-um cromoglycate, DSCG, SCG, FPL-670, or DNSG; there are many international trade names. Storage/Stability/Compatibility Cromolyn sodium solution for inhalation should be stored below 40°C (104°F); preferably between 15-30°C. Protect from freezing, light and humidity. Store in foil pouch until ready for use. Do not use solution if it is cloudy or contains a precipitate. Solution remain-ing in nebulizers after use should be discarded. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cy ANOCOb Al Am IN (VITAm IN b12) 233 Cromolyn solution is reportedly compatible with acetylcysteine, albuterol, epinephrine, isoetherine, isoproterenol, metaproterenol, or terbutaline solutions for up to 60 minutes. It is not compatible with bitolterol. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Cromolyn Sodium Solution for Inhalation: 20 mg/2 m L vials or amps; Intal® (Aventis), generic; (Rx) Cromolyn Sodium Aerosol for Inhalation: 800 mcg/actuation in 8. 1 g (112 sprays) and 14. 2 g (200 sprays) canisters; Intal® (Aventis); (Rx) There is also an OTC nasal solution (Nasalcrom®), and an oral con-centrate (Gastrocrom®) indicated for mastocystosis available, but these dosage forms are unlikely to be of use in veterinary medicine. cy Anocob Al Amin (vit Amin b 12) (sye-an-oh-koe-bal-ah-min) vitamin/nutriti Onal Prescriber Highlights Used for parenteral treatment of vitamin B12 deficiency T T Very safe T T Uses/Indications Cyanocobalamin is used for treating deficiencies of vitamin B12. Malabsorption of the nutrient secondary to gastrointestinal tract disease, or dietary chromium deficiencies (in ruminants) can be as-sociated with dietary deficiencies of vitamin B12. As there appears to be a high percentage of cats with exocrine pancreatic insufficien-cy or gastrointestinal disease that are deficient in cobalamin, there is considerable interest in evaluating serum cobalamin (vitamin B12) in these patients. Giant schnauzers may have a genetic defect af-fecting the location of the cobalamin-intrinsic factor, causing coba-lamin deficiency. Dogs with inflammatory bowel disease may also develop cobalamin deficiency. Pharmacology/Actions Vitamin B12 (cobalamin), a cobalt-containing water-soluble vita-min, serves as an important cofactor for many enzymatic reactions in mammals that are required for normal cell growth, function and reproduction, nucleoprotein and myelin synthesis, amino acid me-tabolism, and erythropoiesis. Cobalamin is required for folate utili-zation; B12 deficiency can cause functional folate deficiency. Unlike humans, macrocytic anemias do not appear to be a significant com-ponent to cobalamin deficiency in dogs or cats. Clinical signs associated with cobalamin deficiency in cats may include weight loss, poor haircoat, vomiting, or diarrhea. Increases in serum methionine and methylmalonic acid, and decreased se-rum cystathionine and cysteine values may be noted. Homocysteine levels do not appear to be affected. In dogs, cobalamin deficiency may cause or contrib-ute to inappetance, diarrhea, weight loss, leukopenia, or methylmalonylaciduria. In ruminants, vitamin B12 appears to be synthesized by rumen microflora and requires dietary cobalt to be present for its forma-tion. Clinical signs seen with cobalamin deficiency states associated with cobalt deficiency in cattle and sheep include inappetance, las-situde, poor haircoat/fleece, poor milk production, weight loss, or failure to grow. Pharmacokinetics After food is consumed in monogastric mammals, cobalamin in food is bound to a protein (haptocorrin) in the stomach. Haptocorrin/cobalamin is degraded by pancreatic proteases in the duodenum, but cobalamin is then bound by Intrinsic factor (IF), a protein pro-duced in the stomach and pancreas in dogs, in the pancreas (only) in cats, and in the stomach (only) in humans. The cobalamin-IF complex is absorbed in the small intestine where it binds to cubu-lin, which facilitates its entry into the portal circulation. A protein called transcobalamin 2 (TCII) then binds to cobalamin allowing its entry into target cells. Some cobalamin is rapidly excreted into the bile where entero-hepatic recirculation occurs. Dogs and cats, unlike humans, do not possess cobalamin-binding protein TC1. This means that dogs and cats with B12 dietary deficiency or ma-labsorption can rapidly deplete their stores of B12 in one to two months, whereas in humans it may require 1-2 years. In normal cats, circulating half-life of cobalamin is approxi-mately 13 days, but in two cats with inflammatory bowel disease, it was only 5 days (Simpson, Fyfe et al. 2001). Contraindications/Precautions/Warnings For injectable use, no contraindications are documented for do-mestic animals. In humans, cyanocobalamin is contraindicated in patients hypersensitive to it or hydroxocobalamin. Adverse Effects Cyanocobalamin appears very well tolerated when used parenter-ally in animals. In humans, anaphylaxis has been reported rarely after parenteral use. Some human patients complain of pain at the injection site, but this is uncommon. Reproductive/Nursing Safety Studies documenting safety during pregnancy have apparently not been done in humans or animals, but it is likely safe to use. Vitamin B12 deficiency states are thought to cause teratogenic effects. While vitamin B12 can be excreted into milk, it is safe to use while nursing. Overdosage/Acute Toxicity No overdose information was located, but an inadvertent overdose of cyanocobalamin given via SC or IM injection is unlikely to cause significant morbidity. Drug Interactions No significant drug interactions have been identified when cyano-cobalamin is administered parenterally. laboratory Considerations Serum samples to be analyzed for cobalamin and/or folate should T! be protected from bright light and excessive heat If a microbiologic method assay is used to determine cobalamin T! values, concurrent use of antibiotics can cause falsely low serum or red blood cell values Doses DOg S:T! a) Cobalamin deficiency in dogs with severe GI disease: Inject-able cyanocobalamin at 25 mcg/kg once per week for 4-6 weeks, then once monthly thereafter to maintain normal se-rum levels. (Zoran 2006d) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
234 Cy Cl OPHOSPHAm IDE b) Cobalamin deficiency associated with GI disease: Based on body size, 250-800 mcg SC once weekly for 6 weeks, one more dose a month later and a re-check one month after that. Re-evaluation is important to determine if continued cobala-min supplementation is indicated. (Stiener 2005) c) Cobalamin deficiency associated with exocrine pancreatic insufficiency: 250-500 mcg parenterally; repeat treatment based upon serum levels. (Westermarck, Wiberg et al. 2005) CATS:T! a) Cobalamin deficiency in cats with IBD: 250-500 mcg (total dose per cat) SC once per week for 6 weeks, then every 1-2 months. (Marks 2003) b) Cobalamin deficiency associated with GI disease: Based on body size, 150-250 mcg SC once weekly for 6 weeks, one more dose a month later and a re-check one month after that. Re-evaluation is important to determine if continued cobala-min supplementation is indicated. (Stiener 2005) c) Cobalamin deficiency associated with exocrine pancreatic insufficiency: 100-250 mcg SC once weekly; periodically as-sess cobalamin and folate levels. (Westermarck, Wiberg et al. 2005) HORSES:T! a) For vitamin B12 deficiency: 1-2 m L of a 1000 mcg/m L in-jection (1000-2000 mcg) injected IM or SC; dosage may be repeated once or twice weekly, as indicated by condition or response. (Label information; Amtech Vitamin B12 1000 mcg—IVX) CATTl E, SHEEP:T! a) For treatment of vitamin B12 deficiency associated with co-balt deficiency: Lambs: 100 mcg injected once weekly. Adult sheep: 300 mcg injected once weekly. (Baxter 1986) b) For treatment of vitamin B12 deficiency associated with co-balt deficiency: Cattle and sheep: 0. 2-0. 4 m L of a 5000 mcg/ m L injection (1000-2000 mcg) injected IM or SC; dosage may be repeated in weekly intervals if necessary. (Label infor-mation; Vitamin B12 5000 mcg—Butler) SWINE:T! a) For vitamin B12 deficiency: 0. 1-0. 4 m L of a 5000 mcg/m L injection (500-2000 mcg) injected IM or SC; dosage may be repeated in weekly intervals if necessary. (Label information; Amtech Vitamin B12 5000 mcg—IVX) monitoring Cobalamin levels T! In small animals: folate status; both before and after treatment T! with cyanocobalamin Clinical signs associated with deficiency T! CBC, baseline and ongoing if abnormal T! Client Information Several weeks after starting B12 therapy may be required before T! improvement is seen Vitamin B12 deficiency in animals may require life-long T! treatment As cyanocobalamin may be administered SC, clients can be in-T! structed to administer at home, but the importance of ongoing follow-up with the veterinarian must be stressed Chemistry/Synonyms Cyanocobalamin occurs as dark red crystals or crystalline powder. It is sparingly soluble in water (1 in 80) and soluble in alcohol. When in the anhydrous form, it is very hygroscopic and can absorb sub-stantial amounts of water from the air. Vitamin B12 may also be known as cobalamins. Cyanocobalamin may also be known as: cyanocobalamine, cyanocobalaminum, co-bamin, cianokobalaminas, cianocobalamina, or cycobemin; many internationally registered trade names. Storage/Stability/Compatibility Cyanocobalamin injection should be stored below 40°C; protect from light and freezing. Cyanocobalamin injection is reportedly compatible with all commonly used intravenous fluids. Dosage Forms VETERINAR yl Ab El ED PRODUCTS: Cyanocobalamin (Vitamin B 12) Injection 1000, 3000 and 5000 mcg/ m L in 100 m L, 250 m L and 500 m L multi-dose vials depending on source; generic; (Rx). Products may be labeled as cyanocobalamin or vitamin B12, and be labeled for use in cattle, horses, dogs, cats, sheep, or swine. There are many combination products, both oral and injectable, con-taining cyanocobalamin as one of the ingredients. These are not rec-ommended for use when cobalamin deficiency states exist. HUm ANl Ab El ED PRODUCTS: Cyanocobalamin (crystalline, Vitamin B 12) Injection 100 mcg (0. 1 mg) per m L and 1000 (1 mg) per m L, vial sizes range from 1 m L single-use to 10 and 30 m L multi-dose; generic; (Rx). Besides ge-nerically labeled products, there are several products available with a variety of trade names, including Cyanoject®, Rubesol®, Crysti ®, or Crystamine®. Oral tablet dosage forms are also available, but are not appropriate for therapy of cobalamin deficient states in small animal medicine. A nasally administered product is marketed, but there is no infor-mation on its use in dogs or cats. cyclophosph Amide (sye-kloe-foss-fa-mide) Cytoxan®, Neosar® immun Osuppressive/antine Oplastic Prescriber Highlights Antineoplastic/immunosuppressive used in dogs & cats T T for a variety of conditions Contraindications: Prior anaphylaxis; caution in patients T T with leukopenia, thrombocytopenia, previous radio-therapy, impaired hepatic or renal function, or in those for whom immuno suppression may be dangerous (e. g., infection) Potentially teratogenic, fetotoxic T T Primary adverse effects are myelosuppression, GI effects, T T alopecia (especially Poodles, Old English Sheepdogs, etc. ), & hemorrhagic cystitis Adequate monitoring essential T T Uses/Indications In veterinary medicine, cyclophosphamide is used primarily in small animals (dogs and cats) in combination with other agents both as an antineoplastic agent (lymphomas, leukemias, carcinomas, and sarcomas) and as an immunosuppressant (SLE, ITP, IMHA, pem-phigus, rheumatoid arthritis, proliferative urethritis, etc. ). Its use in treating acute immune-mediated hemolytic anemia is controversial; | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cy Cl OPHOSPHAm IDE 235 there is some evidence that it does not add beneficial effects when used with prednisone. Cy clophosphamide has been used as a chemical shearing agent in sheep. Pharmacology/Actions While commonly categorized as an alkylating agent, the parent compound (cyclophosphamide) is a prodrug and cyclophosph-amide's metabolites, such as phosphoramide mustard, act as alky-lating agents interfering with DNA replication, RNA transcription and replication, and ul timately disrupting nucleic acid function. The cytotoxic properties of cyclophosphamide are also en hanced by the phosphorylating activity the drug possesses. Cyclophosphamide has marked immunosuppressive activity and both white cells and antibody pro duction are decreased, but the ex-act mechanisms for this activity have not been fully elucidated. Pharmacokinetics While the pharmacokinetics of cyclophosphamide apparently have not been detailed in dogs or cats, it is presumed that the drug is handled in a manner similar to humans. The drug is well absorbed after oral administration with peak levels occurring about 1 hour after dosing. Cyclophosphamide and its metabolites are distributed throughout the body, including the CSF (albeit in subtherapeutic levels). The drug is only minimally protein bound and is distrib-uted into milk and presumed to cross the placenta. Cyclophosphamide is metabolized in the liver to several metabo-lites. Which metabolites account for which portion of the cytotoxic properties of the drug is a source of controversy. After IV injec tion, the serum half-life of cyclophosphamide is approximately 4-12 hours, but drug/metabolites can be detected up to 72 hours after administration. The majority of the drug is excreted as metabolites and unchanged drug in the urine. Contraindications/Precautions/Warnings Cyclophosphamide should not be used in patients with prior ana-phylactic reactions to the drug otherwise, there are no absolute con-traindications to the use of cyclophosphamide. It must be used with caution, however in patients with leukopenia, thrombo cytopenia, previous radiotherapy, impaired hepatic or renal function, or in those for whom immuno suppression may be dangerous (e. g., in-fected patients). Patients who develop myelosuppression should have subsequent doses delayed until adequate recovery occurs. Because of the potential for development of serious adverse ef-fects, cyclophosphamide should only be used in patients who can be adequately and regularly monitored. Adverse Effects Primary adverse effects in animals associated with cyclophosph-amide are myelosuppression, gastroenterocolitis (anorexia, nausea, vomiting, diarrhea), alopecia (especially in breeds where haircoat continually grows, e. g., Poodles, Old English Sheepdogs), and hem-orrhagic cystitis. Cyclophosphamide's myelosuppressant effects primarily impact the white cells lines, but may also affect red cell and platelet produc-tion. The nadir for leukocytes generally occurs between 7-14 days after dosing and may require up to 4 weeks for recovery. When used with other drugs causing myelosuppression, toxic effects may be exacerbated. Sterile hemorrhagic cystitis induced by cyclophosphamide is thought to be caused by the metabolite acrolein. Up to 30% of dogs receiving long-term (>2 months) cyclophosphamide can develop this problem. Furosemide administered with cyclophosphamide may reduce the occurrence of this adverse effect. In cats, cyclophosphamide-induced-cystitis (CIC) is rare. Initial signs may present as hematuria and dysuria. Because bacterial cys-titis is not uncommon in immunosuppressed patients, it must be ruled out by taking urine cultures. Diagnosis of CIC is made by a negative urine culture and inflammatory urine sediment found during urinalysis. Because bladder fibrosis and/or transitional cell carcinoma of the bladder is also associated with cyclophosphamide use, these may need to be ruled out by contrast radiography. It is believed that the incidence of CIC may be minimized by in creasing urine production and frequent voiding. The drug should be given in the morning and ani mals should be encouraged to drink/urinate whenever possible. Recommendation for treatment of CIC includes discontinuing cyclophosphamide, furosemide, and corticosteroids. Refractory cases have been treated by surgical debridement, 1% for-malin or 25% DMSO instillation in the bladder. Other adverse effects that may be noted with CTX therapy in-clude pulmonary infiltrates and fibro sis, depression, immune-sup-pression with hyponatremia, and leukemia. In recovering dogs with immune-mediated hemolytic anemia, taper the withdrawal of the drug slowly over several months and monitor for early signs of relapse. Rapid withdrawal can lead to a rebound hyperimmune response. Reproductive/Nursing Safety Cyclophosphamide's safe use in pregnancy has not been established and it is potentially teratogenic and embryotoxic. Cyclophosphamide may induce sterility (may be temporary) in male animals. In hu-mans, 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 accept-able 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 outweighs the risks. ) Cyclophosphamide is distributed in milk and nursing is gener-ally not recommended when dams are receiving the drug. Overdosage/Acute Toxicity There is only limited information on acute overdoses of this drug. The lethal dose in the dogs has been reported as 40 mg/kg IV. If an oral overdose occurs, gut emptying should proceed if indicated and the animal should be hospitalized for supportive care. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving cyclophosphamide and may be of significance in veterinary patients: All OPURINOl T! : May increase the myelosuppression caused by cyclophos phamide CARDIOTOx IC DRUg S T! (e. g., doxorubicin ): Use caution when using cy-clophosphamide with other cardiotoxic agents as potentiation of cardiotoxicity may occur CHl ORAm PHENICOl T! : May inhibit cyclophosphamide metabolism Im IPRAm INET! : May inhibit cyclophosphamide metabolism PHENOb ARb ITAl T! (or other barbiturates ) given chronically may increase the rate of metabolism of cyclophosphamide to active metabolites via microsomal enzyme induction and increase the likelihood of toxicity development PHENOTHIAz INEST! : May inhibit cyclophosphamide metabolism POTASSIUm IODIDET! : May inhibit cyclophosphamide metabolism SUCCINyl CHOl INET! : Metabolism may be slowed with resulting pro-longation of effects, as cyclophos phamide may decrease the levels of circulating pseudocholinesterases | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
236 Cy Cl OPHOSPHAm IDE THIAz IDE DIURETICS T! : May increase the myelosuppression caused by cyclophos phamide VITAm IN AT! : May inhibit cyclophosphamide metabolism laboratory Considerations Uric acid T! levels (blood and urine) may be increased after cy-clophosphamide use. The immunosuppressant properties of cyclophosphamide may T! cause false negative antigenic skin test results to a variety of anti-gens, including tuberculin, Candida, and Trichophyton. Doses For more information on using cyclophosphamide as part of che-motherapy protocols, refer to the protocols found in the appendix or other dosages/protocols found in numerous references, includ-ing: Withrow and Mac Ewen's Small Animal Clinical Oncology, 4th Ed. (Withrow and Vail 2007); Canine and Feline Geriatric Oncology (Villalobos 2007); Small Animal Internal Medicine, 3rd Edition (Nelson and Couto 2003); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edition (Ettinger and Feldman 2005); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. (Tilley and Smith 2004). Note : In oral tablets, the active ingredient is contained within an inner tablet surrounded by an in ert flecked outer tablet. Accurate dosing may be difficult if splitting or crushing tablets. When dosing in very small dogs or cats, compounding pharmacies may be able to compound oral dosage forms containing less than 25 mg. DOg S:T! For susceptible neoplastic diseases:a) 50 mg/m2 PO 4 days/week or a single dose of 250 mg/m2 PO once every 3 weeks; IV doses range from 100-300 mg/m2 weekly, depending on the protocol used (Kitchell 2005) As an immunosuppressant:a) For adjunctive therapy for immune-mediated hemolytic ane-mia (probably should be re served for dogs with fulminant in-travascular hemolysis, autoagglutination or those that re quire repeated transfusion or have persistent reticulocytopenia): Initially at 2 mg/kg/day IV or PO for 4 days; no treatment for 3 days and then repeat cycle. (Bucheler and Cotter 1995) b) For immune-mediated thrombocytopenia: If corticosteroid therapy is ineffective, may use either vincristine, azathioprine, or cyclophosphamide. CTX dose: 50 mg/m2 PO once daily for 3-4 days/week. May give initial doses IV. Decrease dose if re-nal or hepatic impairment exists. After 1-4 weeks, taper dose and discontinue after platelet count is >100,000/µl. Serious bleeding secondary to thrombocytopenia and hemorrhagic cystitis can occur; use cautiously. (Y oung 1988) c) For rheumatoid arthritis: In conjunction with a glucocorti-coid (predniso(lo)ne); give CTX PO once daily in the AM for 4 consecutive days each week at 2. 5 mg/kg if weighs <10 kg, 2 mg/kg if 10-35 kg, and 1. 5 mg/kg if >35 kg. Discontinue: 1 month after remission of synovial inflammation (determined from joint tap), after 4 months of treatment, or if hemorrhag-ic cystitis develops. If cystitis develops, switch to azathioprine. (Tangner and Hulse 1988) d) For polymyositis: In conjunction with steroids, if steroids alone are ineffective: 1 mg/kg PO once daily for 4 days, then off 3 days. Decrease concurrent prednisone dose to 1 mg/kg/day. (Knaack 1988) e) For polyarthritis: In most cases initial treatment is to attempt immunosuppression with high doses of corticosteroids (pred-nisolone at 2-4 mg/kg in a daily divided dose for 2 weeks and then gradually reduced over the next 4-8 weeks); maintain therapy to help prevent relapses. If relapses occur or the re-sponse to prednisolone is poor, add cyclophosphamide given PO daily at a dose of 1. 5 mg/kg for dogs over 30 kg, 2 mg/kg for dogs 15-30 kg, and 2. 5 mg/kg for dogs for dogs under 15 kg. Give cyclophosphamide doses on 4 consecutive days each week as close to the above dosing regimen as possible, allowing that tablets cannot be split. Oral prednisolone also given each day at 0. 25-0. 5 mg/kg. Continue treatment for 2-4 months, but do not treat with cyclophosphamide longer than 4 months because of bladder toxicity. T est urine weekly for blood, stop if overt blood detected. Monitor CBC q7-14 days; if white count falls below 6,000/mm3 or platelet count is <125,000/mm3 reduce dosage by G th; if white count falls be-low 4,000/mm3 or platelet count is <100,000/mm3 stop drug for 2 weeks and the resume at H prior dose. If relapses occur or response still poor, may add levamisole (5-7 mg/kg PO every other day; max dose of 150 mg). Goal is to stop therapy in 3-6 months. (Bennett 2005) f) As an alternative immunosuppressive agent for glomerulone-phritis: 2. 2 mg/kg PO q24h for 4 days, discontinue for 3 days and then repeat. (Labato 2006) CATS:T! For susceptible neoplastic diseases:a) For advanced mammary carcinoma: Doxorubicin: 30 mg/m2 IV every 3 weeks up to 4-8 treatments. Cyclophosphamide: 100 mg/m2 PO once daily on days 3, 4, 5, and 6 after doxoru-bicin (Loar 1988) As an immunosuppressant:a) Give 2. 5 mg/kg once daily PO for 4 consecutive days out of 7 for up to 3 weeks. Alterna tively, 7 mg/kg IV may be given once a week. (Hurvitz and Johnessee 1985) b) For immune-mediated hemolytic anemia: 50 mg/m2 for 4 consecutive days per week. May be over-treatment; efficacy not proven. (Weiser 1989a) c) For rheumatoid arthritis: In conjunction with a glucocor-ticoid (predniso(lo)ne); give CTX PO once daily in the AM for 4 consecutive days each week at 2. 5 mg/kg. Discontinue 1 month after remission of synovial inflammation (determined from joint tap), after 4 months of treatment, or if hemorrhag-ic cystitis develops. If cystitis develops, switch to azathioprine. (Tangner and Hulse 1988) d) T o slow progression of FIP: 2-4 mg/kg PO four times a week. (Foley 2005) SHEEP:T! As a chemical defleecing agent:a) 25 mg/kg, PO once (Mc Connell and Hughey 1989) monitoring Efficacy; See the Protocol section or refer to the references from T! the Dosage section above for more information T oxicity, see Adverse Effects above. Regular hemograms and uri-T! nalyses are mandatory. Client Information Clients must be briefed on the possibilities of severe toxicity de-T! veloping from this drug, including drug-related mortality. Clients should contact veterinarian should the animal ex hibit any T! signs of abnormal bleeding and/or bruising. Although no special precautions are necessary when handling in-T! tact tablets, direct exposure should be avoided with crushed tab-lets, oral elixir, or the animal's urine or feces. Should exposure oc cur, wash the area thoroughly with soap and water. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cy Cl OSPORINE 237 Chemistry/Synonyms A nitrogen-mustard derivative, cyclophosphamide occurs as a white, crystalline powder that is soluble in water and alcohol. The commercially available injection has p H of 3 to 7. 5. Cyclophosphamide may also be known as: CPM, CTX, CYT, B-518, ciclofosfamida, cyclophosphamidum, cyclophosphanum, NSC-26271, WR-138719, Alkyloxan®, Carloxan®, Ciclosmida®, Cicloxal®, Cyclan®, Cyclo-cell®, Cycloblastin®, Cycloblastine®, Cyclostin®, Cycloxan®, Cytophosphan®, Cytoxan®, Endoxan®, Endoxana®, Enduxan®, Fosfaseron®, Genoxal®, Genuxal®, Ledoxina®, Neosar®, Procytox®, or Sendoxan®. Storage/Stability/Compatibility Cyclophosphamide tablets and powder for injection should be stored at temperatures less than 25°C. They may be exposed to tem-peratures up to 30°C for brief pe riods, but should not be exposed to temperatures above 30°C. Tablets should be stored in tight con-tainers. The commercially available tablets (Cytoxan®) are manu-factured in a bi-level manner with a white tablet containing the cyclophosphamide found within a surrounding flecked outer tab-let. Therefore, the person administering the drug need not protect their hands from cyclophosphamide exposure unless the tablets are crushed. Because of their construction, accurately splitting tablets is problematic and cannot be recommended. Cyclophosphamide injection may be dissolved in aromatic elixir to be used as an oral solution. When refrigerated, it is stable for 14 days. After reconstituting the powder for injection with either sterile water for injection or bacteriostatic water for injection, the product should be used within 24 hours if stored at room temperature; 6 days if refrigerated. Cyclophosphamide is reportedly compatible with the following intravenous solutions and drugs: Amino acids 4. 25%/dextrose 25%, D5 in normal saline, D 5W, sodium chloride 0. 9%. It is also compat ible in syringes or at Y-sites for brief periods with the following: bleomycin sulfate, cisplatin, doxorubicin HCl, droperidol, fluorou-racil, furosemide, heparin sodium, leucovorin calcium, methotrex-ate sodium, metoclopramide HCl, mitomycin, vinblastine sulfate, and vincristine sulfate. Compatibility is dependent upon factors such as p H, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific in-formation. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Cyclophosphamide Tablets: 25 mg & 50 mg; Cytoxan® (Mead John-son Oncology); Cyclophosphamide (Gensia Sicor); (Rx) Cyclophosphamide Powder for Injection: 75 mg mannitol/100 mg cyclophosphamide and 82 mg sodium bicarbonate/100 mg cyclo-phosphamide in 100 mg, 200 mg, 500 mg, 1 g and 2 g vials; Cytox-an® Lyophilized (Mead Johnson Oncology); (Rx), Neosar® (Gensia Sicor); (Rx)cyclosporine (systemic) (sye-kloe-spor-een) Atopica®, Neoral®, Sandimmune® immun Osuppressive Note : Cyclosporine topical ophthalmic information is found in the oph-thalmology section in the ap pendix. Prescriber Highlights Immunosuppressant (primarily cellular immunity)T T Adverse Effects: Primarily GI related, but uncommon T T at usual dosages If using human-labeled products, don't confuse T T Sand-immune® with Atopica®/Neoral®/Gengraf® dosages; they are not bioequivalent. When using generically la-beled products, determine with which product they are bioequivalent & dose appropriately. Serum levels should be measured to assure efficacy & T T minimize adverse effect po tential Cost may be an issue T T Drug-drug interactions T T Uses/Indications Cyclosporine may be useful as an immunosuppressant for immune-mediated dis eases (see dosage section) and as part of a protocol to reduce the rejection of allografts in transplant medicine in dogs and cats. Pharmacology/Actions Cyclosporine is an immunosuppressant that focuses on cell-me-diated immune re sponses (but it has some humoral immunosup-pressive action). While cyclosporine's exact mecha nism of action is not known, it is believed that it acts by a specific, reversible inhi-bition of immuno competent lymphocytes in the G 0-or G 1-phase of the cell cycle. T-helper lymphocytes are the pri mary target, but T-suppressor cells are also affected. Lymphokine production and release (including interleukin-2, T-Cell Growth factor) are also in-hibited by cyclosporine. Pharmacokinetics Cyclosporine is poorly absorbed after oral administration and bio-availability can vary widely between patients. The emulsion form oral product ( Neoral®) reportedly achieves much higher blood lev-els in dogs and cats for a given dose and dosage recommendations change accordingly. Note : Neoral®/Atopica® and Sandimmune® are NOT bioequivalent. In dogs, the veterinary-labeled oral product (Atopica®) is rap-idly absorbed, but bioavailability is variable and can range from 23-45%. Food in the GI increases variability of bioavailability and reduces it by about 20%. Cyclosporine is distributed in high levels into the liver, fat and blood cells (RBC's lymphocytes). It does not appreciably enter the CNS. The drug is primarily metabolized in the liver via the cyto-chrome P450 system and excreted into the bile. Less than 1% of a dose is excreted unchanged into the urine. Elimination half-life in the dog is approximately 9-12 hours. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
238 Cy Cl OSPORINE Contraindications/Precautions/Warnings Cyclosporine is contraindicated in patients hypersensitive to it or any component (e. g., polyoxyethylated castor oil) in the injectable micro-emulsion products. It is labeled as being contraindicated in dogs with a history of malignant neoplasia. Cyclosporine should be used with caution in patients with hepatic or renal disease. Adverse Effects In dogs, vomiting, anorexia, and diarrhea are most commonly seen; gingival hyperplasia, hypertrichosis, excessive shedding, and papil-lomatosis have been reported. In order to reduce the incidence of vomiting in dogs when start-ing therapy, some clinicians will start at a low dose, give with food and gradually increase oral doses over the first week or so. One pro-tocol (Bloom 2006a) is: 1-2 mg/kg PO once daily for 2 days, 2-3 mg/kg PO once daily for 2 days, 3-4 mg/kg PO once daily for 3 days, and then 5 mg/kg PO once daily for 30 days. For the first 10 days metoclopramide is given 30 minutes prior to cyclosporine. For the first 14 days cyclosporine is given with a meal and after that, 2 hours prior to a meal. Cats with high blood levels (1,000 ng/m L) may develop anorex-ia. Increased hair growth has been noted in feline patients on cy-closporine. A case of a cat developing fatal systemic toxoplasmosis while on cyclosporin therapy has been reported. While nephrotoxicity and hepatotoxicity are potentially an is sue in dogs and cats, it appears that extremely high blood levels (>3,000 ng/m L) are necessary before this is a significant problem. Animals who have levels greater than 1,000 ng/m L that persist for weeks or months may be more sus ceptible to bacterial or fungal infections. Long-term use, particularly in combination with other im munosuppressants (steroids), may predispose the patient to de-velop neoplastic diseases. Because the drug has an unpleasant taste, it has been suggested that compounded dosages be placed in gelatin capsules. Reproductive/Nursing Safety Cyclosporine has been shown to be fetotoxic and embryotoxic in rats in rabbits at dosages 2-5 times normal. Use during pregnancy only when the risks outweigh the benefits. In humans, the FDA cat-egorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no ad-equate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Cyclosporine is distributed into milk and safety cannot be as-sured for nursing offspring. In humans, it is not recommended that women nurse while taking cyclosporine. Overdosage/Acute Toxicity Acute overdoses may cause transient renal-or hepato-toxicity. Over doses may be treated with gut evacuation (emesis is apparently effective in humans if used within 2 hours of ingestion); otherwise, treat supportively and symptomatically. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving cyclosporine and may be of significance in veterinary patients: The following drugs may increase cyclosporine blood levels and increase the risk for cyclosporine tox icity: All OPURINOl!! Am IODARONE!! Az Ol E ANTIFUNg Al S!! (e. g., ketoconazole, fluconazole ), b ROm OCRIPTINE!! CAl CIUm CHANNEl bl OCKERS!! (e. g., verapamil, diltiazem ) CIm ETIDINE!!CISAPRIDE!! CORTICOSTEROIDS!! DANAz Ol!! DIg Ox IN!! g RAPEFRUIT JUICE/g RAPEFRUIT JUICE POWDER!! l OSARTAN, V Al SARTAN !! m ACROl IDE ANTIb IOTICS!! (e. g., erythromycin, clarithromycin ) m ETOCl OPRAm IDE!! Om EPRAz Ol E!! SERTRAl INE!! The following drugs may decrease the blood levels of cyclosporine: NAFCIll INT! RIFAm PINT! PHENOb ARb ITAl!! PHENy TOIN!! S!!t. JOHN'S WORT DIg Ox INT! : Cyclosporine can cause increased digoxin levels with pos-sible toxicity KETOCONAz Ol ET! and other azole antifungals : Have been shown that they can substantially reduce the metabolism of cyclosporine in dogs or cats and many clinicians are using this interaction to re-duce the dose and resultant cost of cyclosporine treatment. At-tempt this with caution only, and with the realization that moni-toring of cyclosporine levels may be required. m ETHOTREx ATET! : Cyclosporine may increase MTX levels NEPHROTOx IC DRUg S, OTHERT! (e. g., acyclovir, amphotericin b, aminogly cosides, colchicine, vancomycin, NSAIDs ): Possible additive nephro-toxicity SPIRONOl ACTONET! and other potassium sparing diuretics : Increased risk for hyperkalemia VACCINATIONST! : May be less effective while patients are receiving cy-closporine; avoid the use of live attenuated vaccines Doses Note : Dosages are for Sandimmune® unless otherwise noted. Atopica® or Neoral® are not interchangeable with Sandimmune® dosages. DOg S:T! For control of atopic dermatitis using Atopica® in dogs weighing at least 1. 8 kg: a) 5 mg/kg (3. 3-6. 7 mg/kg) PO once daily for 30 days. Follow-ing this initial treatment period, dosage may be tapered to every other day, and then 2 times per week, until a minimum frequency is reached that will maintain the desired therapeu-tic effect. Give at least one hour before, or two hours after meals. (Label information; Atopica®—Novartis) b) 5-7 mg/kg/day or less. Ideally should be given on an empty stomach, but if causes GI upset, administration with food may help. In large dogs, administration of cyclosporine at 2. 5 mg/kg/day with ketoconazole (5 mg/kg/day) may give good results and reduce expenses. (White 2007) For inflammatory bowel disease using Neoral® or modified cy-closporine (Atopica®): a) 2-5 mg/kg PO q12h; dose can be very individual, so it is rec-ommended to monitor trough levels (aim for 500 ng/m L) (Moore 2004) For severe immune-mediated hemolytic anemia that has not re-sponded to other treat ments: a) Initiate dose at 10 mg/kg PO one to two times a day; usu-ally in combination with cy clophosphamide and prednisone. May consider discontinuing cyclosporine when remis sion has been maintained for 2 weeks. (Miller 2000) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cy Cl OSPORINE 239 As an immunosuppressant (usually as part of an immunosup-pressive protocol): a) 10-25 mg/kg/day PO divided q12h. Neoral®: 5-10 mg/kg/ day PO divided q12h. Trough level of approximately 500 ng/m L is goal (values are dependent on methodology used); may check level 24-48 hours after starting therapy. T o re duce the cost of treatment in large dogs, may give ketoconazole at 10 mg/kg/day divided q12h with cyclosporine. (Gregory 2000) b) For inflammatory bowel disease refractory to azathioprine and prednisone: 5 mg/kg PO once daily (Marks 2007b) c) For pemphigus: Using Atopica® or Neoral®: 5-10 mg/kg PO q24h with ketoconazole (5 mg/kg PO q24h). May be used as a sole agent or in combination with glucocorticoids. (Rosen-krantz 2004) d) As an alternative immunosuppressive agent for glomerulo-nephritis: 15 mg/kg PO q24h (Labato 2006) e) As an alternative immunosuppressive agent for refractory IMHA, especially those that are non-regenerative: 5-10 mg/ kg PO divided twice daily to achieve plasma trough levels of >200 ng/m L (Note : reference states >200 mg/m L, but it is be-lieved this is a typo). Large breed dogs can be dosed concur-rently with ketoconazole (10 mg/kg/day) to allow reduction of cyclosporine dose. (Macintire 2006d) For perianal fistulas: a) 5-7. 5 mg/kg PO q12h until lesions heal and then taper (Campbell 1999) For anal furunculosis: a) Week 1: Tuesday: Hospitalization. Clip perineum to monitor healing and improve hygiene. Wednesday: Start treatment with: Cyclosporine (Cy A) 10 mg/kg/day (Neoral®, 100 mg cap sules) and Ketoconazole (KC) 5 mg/kg/day (Nizoral®, 200 mg tablets); Thursday: Maintain Cy A dose; Friday: Check Cy A plasma concentration, Maintain Cy A dose; Sat urday: Adjust Cy A dose to obtain a trough plasma concentration of 240-400 ng/m L; Maintain KC dose during the entire period of treatment; Sunday: Maintain Cy A dose Week 2: Monday: Check Cy A plasma concentration, Main-tain Cy A dose; Tuesday: Adjust Cy A dose if needed; Wednes-day: Maintain Cy A dose; Thursday: Check Cy A plasma concentra tion; Maintain Cy A dose; Friday: Adjust Cy A dose if needed; Discharge from hospital Week 3-Week 8: Check Cy A plasma concentration every Tuesday. Check for possible side effects: Hair loss and hyper-trichosis (Cy A), pruritus (KC), gingival hyperplasia (Cy A), vomiting (Cy A, KC), diarrhea (Cy A), kidney (Cy A) and liver (Cy A, KC) damage, cholestasis (KC), cu taneus papillomato-sis (Cy A), and viral and fungal infections (Cy A). Cy A dose is adjusted if needed, KC dose is maintained. Discontinue treatment after 8 weeks. Serious cases that are not healed but show substantial improvement may be treated for another 4 weeks. (van Sluijs 1999) CATS:T! Note : Dosages are for Sandimmune® unless otherwise noted. As an immunosuppressant (usually as part of an immunosup-pressive protocol): a) 4-15 mg/kg/day PO divided q12h. Neoral®: 1-5 mg/kg/day PO divided q12h. Trough level of approximately 250-500 ng/m L is goal; may check level 24-48 hours after starting therapy. (Gregory 2000)For feline asthma (in chronic severe cases where patients either require large doses of steroids or are steroid resistant): a) Initial dose of 10 mg/kg PO q12h. Check blood levels at least weekly until a stable dose achieves trough blood levels of 500-1,000 ng/m L. (Padrid 2000) For inflammatory bowel disease using Neoral® or modified cy-closporine (Atopica®): a) 1-4 mg/kg PO q12-24h; dose can be very individual, so it is recommended to monitor trough levels (aim for 500 ng/m L). (Moore 2004) monitoring Therapeutic efficacy T! Adverse effects T! Consider therapeutic drug monitoring, particularly when re-T! sponse is poor or adverse effects occur; ideally after 24-48 hours after starting therapy and then every 2-4 weeks; target trough levels (12 hours after last dose) have been suggested as 100-500 ng/m L in dogs and 250-1,000 ng/m L for cats (see dosage refer-ences) for immunosuppression. Because different methodologies may yield different results; contact the labora tory for recommen-dations on the evaluation of levels CBC and biochem profile: baseline and then monthly to every 3 T! months has been suggested; others believe this is not warranted Client Information Clients should be briefed on the expense of this medication be-T! fore prescribing Give to an animal with an empty stomach (one hour before or T! two hours after meals). Importance of regular dosing must be stressed. If a dose is missed, the next dose should be administered (without doubling) as soon as possible, but dosing should be no more frequent than once daily. Chemistry/Synonyms Also known as Cyclosporin A, cyclosporine is a naturally produced immunosuppres sant agent. It is a non-polar, cyclic, polypeptide antibiotic consisting of 11 amino acids and occurs as a white, fine crystalline powder. It is relatively insoluble in water, but generally soluble in organic solvents and oils. Commercially cyclosporine is available in several dosage forms, including an oral liquid, capsules, and a concentrate for injection. T o increase oral absorption, a micro emulsion forming preparation (Neoral®) is also available in capsules and oral liquid. The veteri-nary product, Atopica®, is a micro-emulsion product equivalent to Neoral®. Cyclosporine may also be known as: ciclosporin, 27-400, ciclosporinum, cyclosporine, cyclosporine A, OL-27-400, Atopica®, Cermox ®, Ciclohexal®, Cicloral®, Colosina®, Consupren®, Cysporin®, Deximune®, Gengraf®, Immulem®, Imusporin®, Neoral-Sandimmun®, Panimun Bioral®, Restasis®, Sandimmun®, Sandimmun Neoral®, Sandimmune®, Sangcya®, or Sigmasporin®. Storage/Stability/Compatibility The veterinary product (Atopica®), should be stored and dispensed in the original unit-dose container at controlled room temperature (15-35°C; 59-77°C). The oral liquid and oral capsules (Sandimmune®) should be stored in their original containers at temperatures less than 30°C; protect from freezing and do not refrigerate. After opening the oral liquid, use within 2 months. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
240 Cy PROHEPTADINE HCl The oral liquid and capsules for emulsion (Neoral®) should be stored in their original containers at 25°C. T emperatures below 20°C may cause the solution to gel or flocculate. Rewarming to 25° can reverse this process without harm. The injection should be stored at temperatures less than 30°C and be protected from light. After diluting to a concentration of ap-proximately 2 mg/m L, the resultant solution is stable for 24 hours in D5W or normal saline; if diluting with normal saline it would be wise to use the solution within 12 hours. It does not need to be protected from light after diluting. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Cyclosporine (Modified) Capsules: 10 mg, 25 mg, 50 mg, & 100 mg; Atopica® (Novartis); (Rx). Approved for use in dogs. See the appendix for more information on the topical ophthalmic preparation. HUm ANl Ab El ED PRODUCTS: Note : Determining bioequivalence between cyclosporine products is complicated; for the latest information see the FDA 's Orange Book Website http://www. fda. gov/cder/ob/ and search on cyclosporine. Cyclosporine Capsules (Soft-gelatin): 25 mg, 50 mg & 100 mg; San-dimmune® (Novartis); generic; (Rx) Cyclosporine (Microemulsion) Oral Capsules (Soft-gelatin): 25 mg, & 100 mg; Neoral® (Novartis); Gengraf® (Abbott); generic; (Eon Labs), (Pliva); (Rx) Cyclosporine Oral Solution: 100 mg/m L in 50 m L btls with syringe; Sandimmune® (Novartis); (Rx) Cyclosporine Oral Solution Microemulsion: 100 mg/m L in 50 m L btls; Neoral® (Novartis); generic, (Abbott; Pliva); (Rx) Cyclosporine Injection: 50 mg/m L in 5 m L amps; Sandimmune® (Novartis); Cyclosporine Injection (Bedford Labs); (Rx) cyprohept Adine hcl (sip-roe-hep-ta-deen) Periactin® antihistamine Prescriber Highlights Serotonin antagonist antihistamine used as an appetite T T stimulant in cats & as an an tipruritic/antihistamine in dogs & cats; used in horses for photic head shaking or treatment of equine Cushing's; may be useful for treating serotonin-syndrome in small animals Contraindications: Hypersensitivity to cyproheptadine T T Caution: Urinary or GI obstruction, severe CHF, narrow T T angle glaucoma Adverse Effects: Sedation (cats may demonstrate para-T T doxical hyperexcitability) & an ticholinergic effects; some reports of hemolytic anemia in cats Uses/Indications Cyproheptadine may be useful in cats as an appetite stimulant. It po-tentially may be of benefit in the treatment of feline asthma or pruri-tus in cats, but clinical experience is marginal for this indication. Cyproheptadine is an antihistamine but its efficacy is question-able for this indication in dogs. The drug may be useful as adjunctive therapy for Cushing's syndrome probably as result of its antis erotonin activity, however one study demonstrated efficacy in less than 10% of dogs treated for pituitary dependent hyperadrenocorticism. Cyproheptadine may be useful as adjunctive treatment in dogs or cats with serotonin syndrome. In horses, cyproheptadine has been used for treating photic head shaking and pars intermedia dysfunction (Equine Cushing's Disease). Pharmacology/Actions Like other H 1-receptor antihistamines, cyproheptadine acts by com-peting with histamine for sites on H 1-receptor sites on effector cells. Antihistamines do not block histamine re lease, but can antagonize its effects. Cyproheptadine also possesses potent antiserotonin activ-ity and, reportedly, has calcium channel blocking action as well. Pharmacokinetics Limited data is available. Cyproheptadine is well absorbed after oral administra tion. Its distribution characteristics are not well described. Cyproheptadine is apparently nearly com pletely metabolized in the liver and these metabolites are then excreted in the urine; elimina-tion is reduced in renal failure. Contraindications/Precautions/Warnings Cyproheptadine is contraindicated in pa tients hypersensitive to it. It should be used with caution in patients with prostatic hypertrophy, blad der neck obstruction, severe cardiac failure, angle-closure glau-coma, or pyeloduodenal obstruction. Adverse Effects The most likely adverse effects seen with cyproheptadine are related to its CNS depressant (sedation) and anticholinergic effects (dryness of mucous membranes, etc. ). Cats can develop a paradoxical agitat-ed state that resolves upon dose reduction or discontinuation. There have been reports of cyproheptadine induced hemolytic anemia in cats. Horses may show mild depression, anorexia, or lethargy. At higher dosages, cyproheptadine has caused significant polyphagia in dogs. Reproductive/Nursing Safety Cyproheptadine has been tested in pregnant lab animals in dos-es up to 32X labeled dose with out evidence of harm to fetuses. Nevertheless, because safety has not been established in other spe-cies, its use during pregnancy should be weighed carefully. In hu-mans, the FDA categorizes this drug as category B for use during 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 not known if cyproheptadine is distributed into milk. Overdosage/Acute Toxicity There are no specific antidotes available. Significant overdoses should be handled using standard gut emptying protocols when appropri-ate and supportive therapy when required. The adverse effects seen with overdoses are an extension of the drug's side effects, principally CNS depression (although CNS stimulation may be seen), anticho-linergic effects (severe drying of mucous membranes, tachycardia, urinary retention, hyperthermia, etc. ) and possibly hy potension. Physostigmine may be considered to treat serious CNS anticholin-ergic effects, and di azepam employed to treat seizures, if necessary. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
Cy TARAb INE 241 Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving cyproheptadine and may be of significance in veterinary patients: CNS DEPRESSANT m EDICATIONS T! : Additive CNS depression may be seen if combining cyproheptadine with other CNS depressant medications, such as barbiturates, tranquilizers, etc. SSRIT! s (including sertraline, fluoxetine, paroxetine, etc. ): Cyprohep-tadine may decrease the efficacy of the SSRI laboratory Considerations Because antihistamines can decrease the wheal and flair response T! to skin allergen testing, antihistamines should be discontinued from 3- 7 days (depending on the anti histamine used and the reference) before intradermal skin tests. Cyproheptadine may increase amylase and prolactin serum levels T! when administered with thy rotropinreleasing hormone. Doses DOg S:T! As an antihistamine: a) 0. 3-2 mg/kg PO twice daily (Bevier 1990), (Mac Donald 2002a) As an appetite stimulant:a) 0. 2 mg/kg PO q12h. May be dosed less frequently if inap-petance is mild. (Moore 2005) For adjunctive treatment of serotonin syndrome: a) 1. 1 mg/kg PO; doses may be repeated q4-6h as needed until signs have resolved. In cases where PO dosing not possible (severe vomiting), may crush tablets and mix with saline and give rectally. (Wismer 2006b) CATS:T! As an appetite stimulant:a) 2-4 mg per cat PO once or twice daily (Davenport 1994), (Ogilvie 2003b) b) 1-4 mg/cat PO, or 0. 35-1 mg/kg PO once or twice a day (Frimberger 2000) c) 2 mg per cat PO q12h (Smith 2003a) d) 0. 35-1 mg/kg PO q12h. May be dosed less frequently if inap-petance is mild. (Moore 2005) As an antihistamine/antipruritic:a) 2 mg per cat PO q12h (Messinger 2000) b) 2 mg per cat or 1. 1 mg/kg PO q12h (Hnilica 2003b) c) For feline asthma (particularly when cats are maxed out on dosages of corticosteroids and terbutaline): 2 mg PO q12h. Therapeutic response may not be seen for 4-7 days, but CNS depression can occur in 24 hours. (Padrid 2000) For adjunctive treatment of serotonin syndrome: a) 2-4 mg (total dose) PO; doses may be repeated q4-6h as needed until signs have resolved. In cases where PO dosing not possible (severe vomiting), may crush tablets and mix with saline and give rectally. (Wismer 2006b) HORSES:T! (Note : ARCI UCGFS Class 4 Drug) For photic head shaking: a) 0. 3-0. 6 mg/kg PO q12h (Dowling 1999) b) 0. 3 mg/kg PO twice daily (Mealey 2004) For treatment of equine Cushing's: a) 0. 25 mg/kg PO once a day for 4-8 weeks; if no response (clinical signs and plasma ACTH), increase dosage frequency to twice daily. Approximately N of horses may benefit, non-responders should be switched to pergolide. (T oribio 2004b)monitoring Efficacy (weight if used for anorexia)T! Adverse effects, if any T! With long-term use, should occa sionally monitor serum BUN in T! cats Client Information Possible side effects include sedation/lethargy and mucous mem-T! brane dryness Cats may respond with agitation; contact veterinarian if this oc-T! curs; if cat becomes very lethargic, weak or develops pale mucous membranes contact veterinarian immediately Horses may show mild depression, anorexia, or lethargy T! Chemistry/Synonyms An antihistamine that also possesses serotonin antagonist proper-ties, cyproheptadine HCl occurs as a white to slightly yellow crystal-line powder. Approximately 3. 64 mg are soluble in one m L of water and 28. 6 mg in one m L of alcohol. Cyproheptadine HCl may also be known as: cyproheptadini hydrochloridum, Ciplactin®, Cyheptine®, Cyprogin®, Cyprono®, Cyprosian®, Klarivitina®, Nuran®, Periactine®, Periactinol®, Periatin®, Peritol ®, Polytab®, Practin®, Preptin ®, Supersan®, or Trimetabol®. Storage/Stability Cyproheptadine HCl tablets and oral solution should be stored at room temperature and freezing should be avoided. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more informa-tion. HUm ANl Ab El ED PRODUCTS: Cyproheptadine HCl Tablets: 4 mg; generic; (Rx) Cyproheptadine HCl Syrup: 2 mg/5 m L in 473 m L; generic; (Rx) cyt Ar Abine (sye-tare-a-bean) Cytosine arabinoside, Cytosar-U® antine Oplastic Prescriber Highlights Parenteral antineoplastic (lymphoreticular neoplasms, T T leukemias) for dogs & cats Contraindications: Hypersensitivity; potentially, embryo-T T toxic & teratogenic Adverse Effects: Primarily myelosuppression, but GI & T T other toxicities can occur Adequate monitoring essential T T Uses/Indications In veterinary medicine, cytarabine is used primarily in small ani-mals as an anti neoplastic agent for lymphoreticular neoplasms, myeloproliferative disease (leukemias), and CNS lymphoma. Refer to the Dosages below or the Protocols (in the appendix), for more infor mation. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
242 Cy TARAb INE Pharmacology/Actions Cytarabine is converted intracellularly into cytarabine triphosphate that appar ently competes with deoxycytidine triphosphate, thereby inhibiting DNA polymerase with resulting inhibition of DNA syn-thesis. Cytarabine is cell phase specific, and acts principally during the S-phase (DNA synthesis). It may also, under certain conditions, block cells from the G 1 phase to the S phase. Pharmacokinetics Cytarabine has very poor systemic availability after oral administra-tion and is only used parenterally. Following IM or SC injections, the drug peaks in plasma within 20-60 minutes, but levels attained are much lower than with an equivalent IV dose. Cytarabine is distributed widely throughout the body, but crosses into the CNS in only a limited manner. If given via continuous IV infusion, CSF levels are higher than with IV bolus injection and can reach 20- 60% of those levels found in plasma. Elimination half-life in the CSF is signifi cantly longer than that of serum. In humans, cytarabine is only about 13% bound to plasma proteins. The drug apparently crosses the placenta, but it is not known if it enters milk. Circulating cytarabine is rapidly metabolized by the enzyme cy-tidine deaminase, principally in the liver but also in the kidneys, in-testinal mucosa, and granulocytes, to the inactive metabolite ara-U (uracil arabinoside). About 80% of a dose is excreted in the urine within 24 hours as both ara-U (≈90%) and unchanged cytarabine (≈10%). Contraindications/Precautions/Warnings Cytarabine is contraindicated in patients hypersensitive to it. Because of the potential for development of serious adverse reac-tions, cytara bine should only be used in patients who can be ad-equately and regularly monitored. The person preparing or administering cytarabine for injection, need not observe any special han dling precautions other than wear-ing gloves, however, should any contamination occur, thoroughly wash off the drug from skin or mucous membranes. Adverse Effects The principal adverse effect of cytarabine is myelosuppression (with leukopenia being most prevalent), but anemia and thrombocytope-nia can also be seen. Myelosup pressive effects are more pronounced with IV administration and reach a nadir at 5-7 days, and gen erally recover at 7-14 days. GI disturbances (anorexia, nausea, vomiting, diarrhea), conjunc-tivitis, oral ulceration, neurotoxicity, hepatotoxic ity and fever may also be noted with cytarabine therapy, but occur rarely in veterinary patients. Anaphylaxis has been reported, but is be lieved to occur very rarely. Cytarabine is a mutagenic and, potentially, carcinogenic agent. Reproductive/Nursing Safety Cytarabine's safe use in pregnancy has not been established and it is potentially teratogenic and embryotoxic. In humans, the FDA cat-egorizes 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. ) It is unknown if cytarabine enters milk; safe use during nursing cannot be assured. Overdosage/Acute Toxicity Cytarabine efficacy and toxicity (see Adverse Effects) are dependent not only on the dose, but also the rate the drug is given. In dogs, the IV LD 50 is 384 mg/kg when given over 12 hours and 48 mg/kg when infused IV over 120 hours. Should an inadvertent overdose occur, supportive therapy should be instituted. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving cytarabine and may be of significance in veterinary patients: DIg Ox INT! : Presumably due to causing alterations in the intestinal mucosa, cytarabine may decrease the amount of digoxin (tablets only) absorbed after oral dosing; this effect may per sist for several days after cytarabine has been discontinued Fl UCy TOSINE T! (5FC): Limited studies have indicated that cytara-bine may antagonize the anti-infective activity of fluorocytosine; moni tor for decreased efficacy g ENTAm ICINT! : Limited studies have indicated that cytarabine may antagonize the anti-infective activity of gentam icin; moni tor for decreased efficacy laboratory Considerations None reported Doses For more information on using cytarabine as part of chemotherapy protocols, refer to the protocols found in the appendix or other dos-ages/protocols found in numerous references, including: Withrow and Mac Ewen's Small Animal Clinical Oncology, 4th Ed. (Withrow and Vail 2007); Canine and Feline Geriatric Oncology (Villalobos 2007); Small Animal Internal Medicine, 3rd Edition (Nelson and Couto 2003); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edition (Ettinger and Feldman 2005); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. (Tilley and Smith 2004). DOg S:T! For susceptible neoplastic diseases:a) 100 mg/m2 IV (continuous infusion) for 48-96 hours, or 100 mg/m2 divided three times daily to four times daily SC for 48-96 hours (Kitchell and Dhaliwal 2000) b) 100 mg/m2 IV (continuous infusion) for 2-4 days (up to 4 days depending on myelosuppression), or 100 mg/m2 divided three times daily to four times daily SC over 4 days; continu-ous infusion results in both increased efficacy and myelosup-pression (Kitchell 2005) c) 100 mg/m2 IV or SC once daily for 2-4 days; repeat as needed 20 mg/m2 intrathecally for 1-5 days (Thompson 1989a) d) 100 mg/m2 IV (slowly), IM, or SC once daily for 4 days, if no toxicity develops may in crease dose by 50% (Coppoc 1988) For granulomatous meningoencephalitis:a) 50 mg/m2 IV (continuous infusion) SC or IV twice daily for 2 days, then 100 mg/m2 SC once a week; rarely effective. (Taylor 2003b) CATS:T! For susceptible neoplastic diseases:a) 100 mg/m2 IV (continuous infusion) for 2 days or 100 mg/m2 divided three times daily to four times daily SC over 4 days; continuous infusion results in both increased efficacy and myelosuppression (Kitchell 2005) b) 100 mg/m2 IV or SC once daily for 2-4 days; repeat as needed 20 mg/m2 intrathecally for 1-5 days (Thompson 1989a) c) 100 mg/m2 once daily for 2 days; 10 mg/m2 once daily for 2 weeks (Couto 1989b) monitoring Efficacy; see the Protocol section or refer to the references from T! the Dosage section above for more information T oxicity; see Adverse Effects above. Regular hemograms are man-T! datory. Periodic liver and kidney function tests are suggested. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DACARb Az INE (DTIC) 243 Client Information Clients must be briefed on the possibilities of severe toxicity de-T! veloping from this drug, including drug-related mortality Clients should contact the veterinarian should the patient ex-T! hibit any signs of profound depression, abnormal bleeding and/ or bruising Chemistry/Synonyms A synthetic pyrimidine nucleoside antimetabolite, cytarabine oc-curs as an odorless, white to off-white, crystalline powder with a p K a of 4. 35. It is freely soluble in water and slightly soluble in alcohol. Cytarabine may also be known as: 1-beta-d-arabinofuranosyl-cytosine, arabinosylcytosine, ara-C, cytarabine liposome, cytara-binum, cytosine arabinoside, liposomal cytarabine, NSC-63878, U-19920, U-19920A, WR-28453, ARA-cell®, Alexan®, Arabine®, Aracytin®, Aracytine®, Citab®, Citagenin®, Citaloxan®, Cylocide Cytarbel®, Cytarine®, Depo Cyt ®, Depo Cyte ®, Erpalfa®, Ifarab®, Laracit®, Medsara®, Novutrax®, Serotabir®, Starasid®, Tabine®, Tarabine® or Udicil®. Storage/Stability/Compatibility Cytarabine sterile powder for injection should be stored at room temperature (15-30°C). After reconstituting with bacteriostatic water for injection, solutions are sta ble for at least 48 hours when stored at room temperature. One study, however, demonstrated that the reconstituted solution retains 90% of its potency for up to 17 days when stored at room temperature. If the solution develops a slight haze, the drug should be discarded. Cytarabine is reportedly compatible with the following intra-venous solutions and drugs: amino acids 4. 25%/dextrose 25%, dextrose containing solutions, dextrose-saline combinations, dex-trose-lactated Ringer's injection combinations, Ringer's injection, lactated Ringer's injection, sodium chloride 0. 9%, sodium lac-tate 1/6 M, corticotropin, lincomycin HCl, methotrexate sodium, metoclo pramide HCl, potassium chloride, prednisolone sodium phosphate, sodium bicarbonate, and vin cristine sulfate. Cytarabine compatibility information conflicts or is dependent on diluent or concentration factors with the following drugs or so-lutions: cephalothin sodium, gentamicin sulfate, hydrocortisone sodium succinate, and methylprednisolone sodium succinate. Compatibility is dependent upon fac tors such as p H, concentra-tion, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific in formation. Cytarabine is reportedly incompatible with the following solu-tions or drugs: carbenicillin dis odium, fluorouracil, regular insulin, nafcillin sodium, oxacillin sodium, and penicillin G sodium. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Cytarabine Powder for Injection: 100 mg, 500 mg, 1 g and 2 g in vials; generic; (Rx) Cytarabine Injection: 10 mg/m L (liposomal) preservative free in 5 m L vials; Depo Cyt ® (Enzon); (Rx); Cytarabine Injection: 20 mg/m L in 5 m L single-& multi-dose vials & preservative free 50 m L bulk package vials; Tarabine® PFS (Adria); Cy tarabine (Mayne); (Rx) d-Panthenol — see Dexpanthenold Ac Arb Azine (dtic) (da-kar-ba-zeen) antine Oplastic Prescriber Highlights Parenteral antineoplastic used in dogs for relapsed T T lymphomas, soft tissue sarcomas, & melanoma Not recommended for use in cats T T Contraindications: Hypersensitivity; potentially T T ter atogenic. Primary adverse effects are GI (can be severe & dose T T limiting) & bone marrow suppression; adequate monitor-ing essential Must give diluted IV; extravasation injuries can be serious T T Uses/Indications Dacarbazine has been used to treat relapsed canine lymphoma, soft tissue sarco mas and melanoma in dogs. In combination with doxo-rubicin, dacarbazine has been evaluated to treat dogs with relapsed lymphosarcoma. Ongoing studies evaluating various protocols are ongoing for this indication. Pharmacology/Actions The mechanism for dacarbazine's antineoplastic activity has not been precisely determined, but it is believed the drug acts as an al-kylating agent through the formation of reactive carbonium ions. Dacarbazine also possesses antimetabolic activity by inhibiting DNA 's of purine nucleoside. It possesses minimal immunosuppres-sant activity and is probably not a cell cycle-phase specific drug. Pharmacokinetics Dacarbazine (DTIC) is poorly absorbed from the GI tract and is administered intravenously. It is converted into an active form of the drug in the liver. The drug's distribution characteristics are not well known, but it is only slightly bound to plasma proteins and probably concentrates in the liver. Only limited amounts cross the blood-brain barrier; it probably crosses the placenta, but it is un-known if it is distributed into milk. Dacarbazine is extensively me-tabolized in the liver and is excreted in the urine via tubular secre-tion. Elimination half-life is about 5 hours. Contraindications/Precautions/Warnings Dacarbazine is not recommended for use in cats as it is unknown whether the feline liver can adequately metabolize it. Dacarbazine (DTIC) is contraindicated in patients who are hypersensitive to it. DTIC can cause life-threatening toxicity. It should only be used where adequate monitoring and support can be adminis tered. It should be used with caution in patients with preexisting bone marrow depression, hepatic or renal dysfunction, or infection. Adverse Effects Gastrointestinal toxicity (including vomiting, anorexia, diarrhea) can commonly be seen after administration and is dose limiting. Pretreatment with an antiemetic (e. g., dolasetron, ondansetron) is used by some oncologists. Bone marrow toxicity is usually asymp tomatic with leukocyte and platelet nadirs seen several weeks after therapy. Occasionally | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
244 DACARb Az INE (DTIC) severe hematopoietic toxicity can occur with fatal consequences. Other delayed toxic effects can include, alopecia, severe hepatotoxic-ity, renal impairment, and photosensitivity reactions. These delayed re actions appear rarely. Because DTIC can cause extensive pain and tissue damage, avoid extravasation injuries. Venous spasm and phlebitis may occur dur-ing IV administration. Severe pain at the injection site can occur if giving the concentrated drug; dilution and administration by IV infusion is recommended. Pretreatment with dexamethasone and/or butorphanol has been suggested to reduce vasospasm, phlebitis and pain. There is increasing evidence that chronic exposure by health care givers to antineoplastic drugs in creases the mutagenic, teratogenic, and carcinogenic risks associated with these agents. Proper pre-cautions in the handing, preparation, administration, and disposal of these drugs and supplies associ ated with their use are strongly recommended. Reproductive/Nursing Safety DTIC is teratogenic in rats at higher than clinically used dosages. It should be used during preg nancy only when the potential benefits outweigh its risks. In humans, the FDA categorizes this drug as cat-egory C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) While it is unknown if DTIC enters milk, the potential carcino-genicity of the drug warrants using extreme caution in allowing the mother to continue nursing while receiving DTIC. Overdosage/Acute Toxicity Because of the toxic potential of this agent, iatrogenic overdoses must be avoided. Recheck dosage calculations. See Adverse Effects above for additional information on toxicity. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dacarbazine and may be of significance in veterinary patients: my El OSUPPRESSIVE DRUg S, OTHERT! (e. g., other antineoplastics, immu nosuppressives, chloramphenicol, flucytosine, colchicine, etc. ): May cause additive myelosuppres sion when used with DTIC RIFAm PIN!! : May increase the metabolism of DTIC PHENOb ARb ITAl!! : May increase the metabolism of DTIC PHENy TOIN!! : May increase the metabolism of DTIC Doses For more information on using dacarbazine as part of chemotherapy protocols, refer to the protocols found in the appendix or other dos-ages/protocols found in numerous references, including: Withrow and Mac Ewen's Small Animal Clinical Oncology, 4th Ed. (Withrow and Vail 2007); Canine and Feline Geriatric Oncology (Villalobos 2007); Small Animal Internal Medicine, 3rd Edition (Nelson and Couto 2003); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edition (Ettinger and Feldman 2005); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. (Tilley and Smith 2004). DOg S:T! a) With doxorubicin as a lymphoma rescue protocol: Doxoru-bicin at 30 mg/m2 (for dogs >1 m 2) or at 1 mg/kg (for dogs <1 m2) IV slowly over 30 minutes. DTIC is given at 800 mg/ m2 IV slowly over 5 hours. Dilute DTIC in 0. 9% Na Cl: Dogs >1 m2 in 1 liter; Dogs > 0. 4 m 2, but less than 1 m2 in 250 m L; and dogs < 0. 4 m2 in 100 m L. For acute and delayed vomit-ing, we administer dolasetron at 0. 6 mg/kg IV immediately before DTIC and send home oral metoclopramide for 7 days. Check CBC on day 7 and protocol can be repeated on day 21 if the dog achieves complete or partial response. Consult with cardiologist if lifetime doxorubicin dose exceeds 180 mg/ m2 (Rassnick 2006) b) 800-1,000 mg/m2 IV over an 8-hour period (no difference in efficacy or toxicity with this regimen when compared with giving the drug divided (200 mg/m2 per day) over 5 days. ) May repeat every 21 days provided that the bone marrow has recovered. It is recommended that dogs be pretreated with dexamethasone through the IV catheter to prevent vasospasm and phlebitis associated with DTIC. Treatment with butor-phanol for injection discomfort may be helpful if using the high dose 8-hour infusion protocol. (Kitchell and Dhaliwal 2000), (Kitchell 2005) monitoring Efficacy T! T oxicity, including CBC with differential and platelets; renal and T! hepatic function tests Client Information Inform clients of the potential toxicities and risks associated with T! this therapy and report immediately any signs associated with se-rious toxicity (e. g., bloody vomiting or diar rhea, abnormal bleed-ing, bruising, urination, depression, infection, shortness of breath, etc. ). Chemistry/Synonyms An antineoplastic agent, dacarbazine occurs as a colorless to ivory colored crystalline solid. It is slightly soluble in water or alcohol. After reconstituting with sterile water, the injection has a p H of 3- 4. Storage/Stability/Compatibility Dacarbazine may also be known as: dacarbazinum, DIC, DTIC, imidazole carboxamide, diemthyl triazeno imadazol carbox-amide, NSC-45388, WR-139007, Asercit ®, DTI®, DTIC-Dome®, Dacarb®, Dacarbaziba®, Dacatic®, Deticene®, Detilem®, Detimedac®, Fauldetic®, Ifadac®, or Oncocarbil®. The powder for injection should be protected from light and kept refrigerated. If exposed to heat, the powder may change color from ivory to pink indicating some de composition. After reconstituting with sterile water for injection the resultant solution is stable for up to 72 hours if kept refrigerated; up to 8 hours at room temperature. If further diluted (up to 500 m L) with either D 5W or normal saline, the solution is stable for at least 24 hours when refrigerated; 8 hours at room temperature under nor-mal room lighting. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Dacarbazine Powder for Injection: 100 mg & 200 mg (may contain mannitol) vials; DTIC-Dome® (Bayer); generic; (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DACTINOmy CIN 245 d Actinomycin Actinomycin d (dak-ti-noe-mye-sin) Cosmegen® antine Oplastic Prescriber Highlights Parenteral antibiotic antineoplastic used in dogs & cats T T Contraindications: Hypersensitivity. Caution: Preexist-T T ing bone marrow depression, hepatic dysfunction, or infection Teratogenic T T Primary adverse effects are GI & bone marrow depres-T T sion (may be life threatening); adequate monitoring essential Specific administration techniques required, avoid T T extravasation injuries Uses/Indications Dactinomycin has been used as adjunctive treatment of lymphore-ticular neo plasms, bone and soft tissue sarcomas, and carcinomas in small animals. It appears to have low efficacy against most carci-nomas and sarcomas. It is being investigated as a part of protocols for rescue therapy for canine lymphomas. Pharmacology/Actions Dactinomycin is an antibiotic antineoplastic. While it has activity against gram-positive bacteria, the drug's toxicity precludes its use for this purpose. Dactinomycin's exact mecha nism of action for its antineoplastic activity has not been determined, but it apparently inhibits DNA-dependent RNA synthesis. Dactinomycin forms a complex with DNA and interferes with DNA 's template activity. Dactinomycin also possesses immunosuppressing and some hy-pocalcemic activity. Pharmacokinetics Because dactinomycin is poorly absorbed it must be given IV. It is rapidly dis tributed and high concentrations may be found in bone marrow and nucleated cells. Dactinomycin crosses the placenta, but it is unknown whether it enters maternal milk. The majority of the drug is excreted unchanged in the bile and urine. Contraindications/Precautions/Warnings Dactinomycin can cause life-threatening toxicity. It should only be used where adequate monitoring and support can be administered. Dacti nomycin is contraindicated in patients who are hypersensitive to it. It should be used with caution in patients with preexisting bone marrow depression, hepatic dysfunction, or infection. Dactinomycin is actively transported by the p-glycoprotein pump and certain breeds susceptible to MDR1-allele mutation (Collies, Australian Shepherds, Shelties, Long-haired Whippet) are at higher risk for toxicity. It is suggested to test susceptible breeds prior to treating (test available at Washington State Univ. Vet. School). Adverse Effects Adverse effects that may be seen more frequently include: anemia, leukopenia, thrombocytopenia (or other signs of bone marrow de-pression), diarrhea, and ulcerative stomatitis or other GI ulceration. Because dactinomycin may cause increased serum uric acid levels, allopurinol may be required to prevent urate stone formation in susceptible patients. Hepatotoxicity is potentially possible with this agent. Because dactinomycin can cause extensive pain and tissue dam-age, avoid extravasation injuries. Di lution and administration by IV infusion is recommended or to administer slowly into a running IV line; use the “two-needle” technique. There is increasing evidence that chronic exposure by health care givers to antineoplastic drugs in creases the mutagenic, teratogenic and carcinogenic risks associated with these agents. Proper pre-cautions in the handing, preparation, administration, and disposal of these drugs and supplies associ ated with their use are strongly recommended. Reproductive/Nursing Safety Dactinomycin has been demonstrated to be embryotoxic and teratogenic in rats, rabbits, and ham sters at higher than clinically used dosages. It should be used during pregnancy only when the po tential benefits outweigh its risks. 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. ) While it is unknown if dactinomycin enters maternal milk, the potential mutagenicity and carcinogenicity of the drug warrants using extreme caution in allowing the mother to continue nursing while receiving dactinomycin. Overdosage/Acute Toxicity Because of the toxic potential of this agent, iatrogenic overdoses must be avoided; recheck dosage calculations. See Adverse Effects above for additional information on toxicity. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dactinomycin and may be of significance in veterinary patients: DOx ORUb ICINT! : Additive cardiotoxicity may occur if used concur-rently or sequentially with doxorubicin my El OSUPPRESSIVE DRUg S, OTHERT! (e. g., other antineoplastics, chloramphenicol, flucytosine, colchicine, etc. ): May cause additive myelosuppres sion when used with dactinomycin VITAm IN KT! : Patients requiring vitamin K may require higher dos-ages when receiving dactino mycin laboratory Considerations Dactinomycin may interfere with determination of antibacterial T! drug levels if using bioassay techniques. Doses For more information on using dactinomycin as part of chemo-therapy protocols, refer to the protocols found in the appendix or other dosages/protocols found in numerous references, including: Withrow and Mac Ewen's Small Animal Clinical Oncology, 4th Ed. (Withrow and Vail 2007); Canine and Feline Geriatric Oncology (Villalobos 2007); Small Animal Internal Medicine, 3rd Edition (Nelson and Couto 2003); Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat 6th Edition (Ettinger and Feldman 2005); and The 5-Minute Veterinary Consult Canine & Feline, 3rd Ed. (Tilley and Smith 2004). DOg S:T! a) 0. 5-0. 9 mg/m2 IV over 20 minutes every 2-3 weeks (Kitch-ell and Dhaliwal 2000) b) 0. 7-1 mg/m2 IV every 3 weeks (Moore 2005) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
246 DAl TEPARIN SODIUm c) For lymphoma rescue using the DOPP protocol (particularly when mechlorethamine is not available): Dactinomycin: 0. 5 mg/m2 IV days 0 and 7; Vincristine: 0. 7 mg/m2 IV days 0 and 7; Procarbazine: 50 mg/m2 (for dogs > 0. 8 mg/m2 give dose to the nearest 50 mg; >0. 4 mg, but <0. 8 mg/m2 give to the near-est 50 mg, but give every other day; dogs < 0. 4 mg/m2 (refor-mulate into 10 mg capsules and give to the nearest 20 mg) PO daily days 0-13; Prednisone: 30-40 mg/m2 PO daily days 0-13. No treatment given days 15-28 and then protocol is repeat-ed at 4 weeks. Protocol may be severely myelosuppressive. If neutrophil count is <2,000 cells/mc L, delay treatment for 3 days and recheck; monitor for cumulative thrombocytopenia. (Rassnick 2006) monitoring Efficacy T! T oxicity: including CBC with differential and platelets; hepatic T! function tests; check inside patient's mouth for ulceration Client Information Inform clients of the potential toxicities and risks associated with T! this therapy and to report immediately any signs associated with serious toxicity (e. g., bloody vomiting or diar rhea, abnormal bleeding, bruising, urination, depression, infection, shortness of breath, etc. ). Chemistry/Synonyms An antibiotic antineoplastic agent, dactinomycin (also known as ac-tinomycin D) occurs as a bright red, crystalline powder. It is some-what hygroscopic and soluble in water at 10°C and slightly soluble at 37°C. The commercially available preparation is a yellow lyophilized mixture of dactinomycin and mannitol. Dactinomycin may also be known as: DTIC, ACT, actinomy-cin C(1), actinomycin D, meractinomycin, NSC-3053, Ac-De®, Bioact-D®, or Dacmozen®. Storage/Stability/Compatibility The commercially available powder should be stored at room tem-perature and protected from light. When reconstituting, sterile wa-ter for injection without preser vatives must be used as preservatives may cause precipitation. After reconstituting, the manufacturer recommends using the solution immediately and discarding any unused portion (no preservatives). When stored in the refrigera-tor, reconstituted solution loses 2-3% potency over 6 hours. The reconstituted solution may be added to D 5W or normal saline IV infusions. IV fluid sterilizing filters (cellulose ester membrane) may partially remove dactinomycin. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Dactinomycin Powder for Injection, lyophilized: 500 mcg with man-nitol 20 mg in vials; Cosmegen® (Merck); (Rx)d Altep Arin sodium (dahl-tep-ah-rin) Fragmin® antic Oagulant Prescriber Highlights Low molecular weight (fractionated) heparin that may be T T useful for treatment or prophylaxis of thromboembolic disease Preferentially inhibits factor Xa & usually only minimally T T impacts thrombin & clotting time (TT or a PTT)Hemorrhage unlikely, but possible T T Must be given subcutaneously T T Cats & dogs may require very frequent dosing making T T outpatient administration impractical Expense may be an issue, particularly in large dogs/ T T horses Uses/Indications Dalteparin may be useful for prophylaxis or treatment of deep vein thrombosis or pulmonary embolus. Recent pharmacokinetic work in dogs and cats, raises questions whether the drug can be effec-tively and practically administered long-term. In humans, it is also indicated for prevention of ischemic complications associated with unstable angina/non Q-wave MI. Pharmacology/Actions By binding to and accelerating antithrombin III, low molecular weight heparins (LMWHs) enhance the inhibition of factor Xa and thrombin. The potential advantage to using these products over standard (unfractionated) heparin is that they preferentially inhibit factor Xa and only minimally impact thrombin and clotting time (TT or a PTT). Pharmacokinetics In dogs, dalteparin is completely absorbed after SC injection. It has a volume of distribution of 50-70 m L/kg and a half-life of about 2 hours. Dogs have a shorter half-life than do humans. Cats appear to have a much shorter duration of activity (anti-Xa) associated with LMWHs than do humans and to maintain a thera-peutic target of anti-XA activity of 0. 5-1 IU/m L requires 150 Units/ kg SC q4h dosing of dalteparin. (Alwood, Downend et al. 2007) In horses, dalteparin's pharmacokinetics are similar to humans. In humans, after subcutaneous injection, dalteparin is absorbed rapidly with a bioavailability of about 87%; peak plasma levels (ac-tivity) occur in about 4 hours. Anti-factor Xa activity persists for up to 24 hours and doses are usually given once to twice a day. Dalteparin is excreted via the kidneys in the urine; elimination half-life is about 3-5 hours. Half-life may be prolonged in patients with renal dysfunction. Contraindications/Precautions/Warnings Dalteparin is contraindicated in patients who are hypersensitive to it, heparin, or pork products. It is also contraindicated in patients with major bleeding, or thrombocytopenia associated with posi-tive in vitro tests for anti-platelet in the presence of dalteparin. Use dalteparin cautiously in patients with significant renal dysfunction as drug accumulation could result. It should be used with extreme caution in patients with heparin-induced thrombocytopenia or in-creased risk of hemorrhage. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DAl TEPARIN SODIUm 247 Adverse Effects In humans adverse effects do not routinely occur, but hemorrhage is a possibility. Injection site hematomas or pain, allergic reactions, and neurologic sequelae secondary to epidural or spinal hemato-mas have been reported. Do not administer via IM or IV routes; dalteparin must be given via subcutaneous injection only. Dalteparin cannot be used inter-changeably with other LMWHs or heparin sodium, as dosages dif-fer for each. Reproductive/Nursing Safety In humans, dalteparin is designated by the FDA as a category B drug (Animal studies have not demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus during the first trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Dalteparin is likely safe to use during nursing. Overdosage/Acute Toxicity Overdosage may lead to hemorrhagic complications. If treatment is necessary, protamine sulfate via slow IV may be administered. 1 mg of protamine sulfate can inhibit the effects of 100 units of adminis-tered anti-Xa dalteparin. Avoid overdoses of protamine. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dalteparin and may be of significance in veterinary patients: ANTICOAg Ul ANTS, ORAl T! (warfarin ): Increased risk for hemorrhage Pl ATEl ETAgg REg ATION INHIb ITORST! (aspirin, clopidogrel ): Increased risk for hemorrhage THROmb Oly TIC Ag ENTST! : Increased risk for hemorrhage laboratory Considerations Low molecular weight heparins may cause asymptomatic, ful-T! ly-reversible increases in AST or Al T; bilirubin is only rarely in-creased in these patients, therefore, interpret these tests with caution, as increases do not necessarily indicate hepatic damage or dysfunction. Doses DOg S:T! a) Dogs: 150 Units/kg SC three times daily; twice daily dosing may be effective. Studies are ongoing to clarify efficacy and dosages. (Dunn 2006) CATS:T! a) Cats appear to have a much shorter duration of activity (anti-Xa) associated with LMWHs than do humans and to maintain a therapeutic target of anti-XA activity of 0. 5-1 IU/m L requires 150 Units/kg SC q4h dosing of dalteparin. (Alwood, Downend et al. 2007) b) For cardiogenic embolism: Current recommended protocols are 100 Units/kg SC q12-24h. (Hogan 2006) HORSES:T! a) For prophylaxis of coagulation disorders in colic patients: 50 IU/kg SC once daily (q24h) (Feige, Schwarzwald et al. 2003) monitoring Baseline and ongoing during therapy CBC (with platelet count)T! Urinalysis T! Stool occult blood test T! Routine coagulation tests (a PTT, PT) are usually insensitive mea-T! sures of activity and normally not warranted Factor Xa activity (available at Cornell Coagulation Laboratory) T! may be useful, particularly if bleeding occurs or patient has re-nal dysfunction. Note : T o measure peak anti-Xa activity in cats, sample at 2 hours post-dose Client Information If this drug is to be used on an outpatient basis, clients must be T! instructed in proper injection technique for subcutaneous injec-tion and to immediately report any signs associated with bleed-ing or pulmonary thrombosis. If not using the pre-filled syringes, use a very small gauge insulin or tuberculin syringe and needle (e. g., 27 gauge). Clients must understand that if they do not use the drug regu-T! larly (as prescribed), clots may form. Chemistry/Synonyms A low molecular weight heparin (LMWH), dalteparin sodium is obtained by nitrous acid depolymerization of heparin derived from pork intestinal mucosa. The average molecular weight is about 5000 and 90% ranges from 2000-9000 daltons (heparin sodium has a molecular weight around 12000). 1 mg of dalteparin is equivalent to not less than 110 units and not more than 210 units of anti-factor Xa. Dalteparin sodium may also be known by as: Daltaparinum natricum, Kabi-2165, Boxol ®, Fragmine®, Ligofragmin®, or Low Liquemine®. Storage/Stability/Compatibility The manufacturer of the commercially available injection states the product should be stored at controlled room temperature (20-25°C, 68-77°F). Do not use if particulate matter or discolor-ation occur. Once the multi-dose vial is punctured, store at room temperature; discard any unused solution after 2 weeks. A study showed that commercially available dalteparin solution was stable when drawn into syringes for up to 30 days when stored at room temperature or refrigerated. (Laposata and Johnson 2003) Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Dalteparin Sodium Injection (Anti-factor Xa international units): 2500 units (16 mg/0. 2 m L), preservative free, in 0. 2 m L single-dose syringes; 5000 IU (32 mg/0. 2 m L), preservative free, in 0. 2 m L sin-gle-dose syringes; 7500 units (48 mg/0. 3 m L), preservative free, in 0. 3 m L single-dose syringes; 10,000 units (64 mg/m L), preservative free, in 1 m L single-dose graduated syringes & 9. 5 m L multi-dose vials; 25,000 units (160 mg/m L), contains 14 mg/m L benzyl alcohol in 3. 8 m L multidose vials; Fragmin® (Pfizer); (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
248 DANAz Ol d An Azol (da-na-zole) Danocrine® andr Ogen Prescriber Highlights Synthetic androgen; suppresses the pituitary-ovarian T T axis. Used primarily for adjunctive treatment of auto-immune hemolytic anemia/thrombocytopenia in dogs & cats Caution: Severe cardiac, renal or hepatic function impair-T T ment, or undiagnosed abnormal vaginal bleeding Teratogenic T T Rare hepatotoxicity in dogs T T Expense may be an issue T T Uses/Indications Because of expense and unpredictable efficacy, danazol is not com-monly used in veterinary medicine, but has been used as adjunctive therapy (with corticosteroids) in the treatment of canine immune-mediated thrombocytopenia and hemolytic ane mia, particularly if the patient becomes refractory to glucocorticoids and other im-munosuppressive therapy. There is apparently synergism when da-nazol is combined with corticosteroids for these indica tions. Once remission is attained, some dogs may have their dosage reduced or other medications may be eliminated and be controlled with dana-zol alone. In humans, danazol has been used for the treatment of en-dometriosis, fibrocystic breast disease, idiopathic thrombocytopenic purpura and a variety of other conditions. Pharmacology/Actions Danazol is a synthetic androgen with weak androgenic effects. It suppresses the pituitary-ovarian axis. Danazol probably directly in-hibits the synthesis of sex steroids and binds to sex steroid receptors in tissues where it may express anabolic, weak androgenic, and an-tiestrogenic effects. Danazol appears to reduce affinity of antibody with the mononuclear phagocytic system Fc receptor. It also may compete with glucocorticoids on steroid-binding globulin, thereby allowing greater free glucocorticoid to act. Pharmacokinetics There is very limited data available. Danazol is absorbed from the GI tract, but appears to be a rate limited process as increasing the dosage does not yield a corresponding increase in serum level. Distribution information is practically nonexistent; the drug apparently crosses the placenta. Danazol is believed to be principally metabolized in the liver. In humans, half-lives aver age about 4-5 hours. Contraindications/Precautions/Warnings Danazol should be used in patients with se vere cardiac, renal, or hepatic function impairment, or undiagnosed abnormal vaginal bleeding only when its benefits outweigh its risks. Adverse Effects Hepatotoxicity (incidence is rare) is the most significant of the ad-verse effects that have been reported thus far in dogs. Otherwise vi-rilization in females is the most likely other effect that may be seen. Rarely, danazol may cause weight gain or lethargy. Human patients have developed vaginitis. Other potential adverse effects include edema, testicular atrophy, hirsutism, or alopecia. Reproductive/Nursing Safety Because of documented teratogenic effects, danazol is contraindi-cated during preg nancy. 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 out-weighs any possible benefit. ) While it is unknown if danazol enters milk, the potential adverse effects associated with androgens in young animals warrants cau-tion. In humans, breastfeeding is contraindicated in patients taking danazol. Overdosage/Acute Toxicity No information was located. Significant overdoses should initially be handled by contacting an animal poison control center and initi-ate gut emptying protocols when ap plicable. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving danazol and may be of significance in veterinary patients: Cy Cl OSPORINET! : May significantly increase cyclosporine levels INSUl INT! : By affecting carbohy drate metabolism, danazol may af-fect insulin requirements (doses may need to be increased) in dia-betic patients WARFARINT! : Concomitant use of danazol with anticoagulants may enhance the anticoagu lant effect as danazol may decrease the syn-thesis of procoagulant factors in the liver laboratory Considerations Danazol may decrease T! total serum thyroxine (T4) and increase T3 uptake; because thyroid-binding globulin is decreased, free T4 and TSH remain normal. Al TT! (SGPT) and AST (SGOT) may increase early in therapy but decrease towards baseline later in ther apy. After discontinuation of danazol, levels usually return to baseline. Doses DOg S:T! For adjunctive treatment of immune-mediated hemolytic ane-mia or thrombocytopenia:a) As adjunctive therapy with glucocorticoids in non-regener-ative forms of IMHA: 5 mg/kg PO three times daily. Used to reduce the dose of glucocorticoids needed for long-term therapy. (Chabanne 2006) b) 5 mg/kg PO q12h; usually used for the first two weeks of ther-apy in combination with corticosteroids (Thompson 1994) c) 5 mg/kg PO twice daily; can taper dose once patient is on low dose alternate day pred nisone (Trepanier 1999) d) Initially, (in addition to prednis(ol)one) danazol may be given at 10 mg/kg/day PO. Once anemia improves, corticosteroids may be slowly tapered and eventually DC'd. When remis-sion maintained by danazol alone, may lower to 5 mg/kg/day. Slowly taper after 2-3 months of normal hemograms with frequent monitoring of hemograms. (Bucheler and Cotter 1995) CATS:T! For adjunctive treatment of immune-mediated hemolytic anemia: a) 5 mg/kg PO twice daily (Loar 1994) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DANOFl Ox ACIN m ESyl ATE 249 monitoring For autoimmune hematologic disorders: Efficacy (CBC, platelets, etc. ) T! Hepatic function, baseline and at regular intervals while on T! therapy Client Information Clients should be informed that it may take several (2T! -3) months to see a posi tive response with this drug Clients should monitor for hepatotoxicity (jaundice) or changes T! in hema tologic status (bleeding, tarry stools, etc. ) Chemistry/Synonyms A synthetic derivative of ethisterone (ethinyl testosterone), danazol occurs as a white to pale yellow, crystalline powder. It is practically insoluble in water and sparingly soluble in alcohol. Danazol may also be known as: Win-17757, Anargil®, Azol ®, Cyclomen®, D-Zol®, Danalem®, Danatrol®, Danazant®, Danogen®, Danocrine®, Danokrin®, Danol®, Ectopal®, Gonablok®, Kendazol®, Ladazol®, Ladogal®, Lisigon®, Mastodanatrol®, Norciden®, Vabon®, Winobanin®, Zendol®, or Zoldan-A®. Storage/Stability Danazol capsules should be stored in well-closed containers at room temperature. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Danazol Capsules: 50 mg, 100 mg, & 200 mg; generic; (Rx) d Anoflox Acin mesyl A te (dan-oh-floks-a-sin) A180®, Advocin® injectable flu Or Oquin Ol One Prescriber Highlights Parenteral fluoroquinolone antibiotic labeled for use in T T cattle (not dairy or veal) to treat BRD associated with Mannheimia (Pasturella) hemolytica & P. multocida; may also be of benefit in treating fluoroquinolone-susceptible infections in non-food producing species (horses, cam-elids, exotics) Labeled in cattle for two SC injections 48 hours apart T T FDA prohibits extra-label use in food animals T T Monograph by Elaine Lust, Pharm D Uses/Indications Danofloxacin mesylate injection is indicated for the treatment of Bovine Respiratory Disease (BRD) associated with Mannheimia (Pasturella) hemolytica and P. multocida in cattle (not dairy or veal). Because of the drug's spectrum of activity, it may also be of benefit in the treatment of infections caused by Histophilus somni (Haemophilus somnus) or M. bovis, but the drug is not labeled (at the time of writing) for treating these pathogens. In other coun-tries, danofloxacin may be labeled for use in swine and chickens (non-laying), but in the USA it is illegal to use the drug in an extra-label manner in food-producing species. Danofloxacin may be of benefit in treating susceptible infections in adult horses, camelids and other non-food producing species. Pharmacology/Actions Danofloxacin is a fluoroquinolone bactericidal antibiotic that in-hibits bacterial DNA-gyrase, preventing DNA supercoiling and DNA synthesis. Fluoroquinolones have good activity against many gram-negative bacilli and some gram-positive cocci (Staphylococcus aureus and Staphylococcus intermedius). In general, fluoroquinolo-nes have a dose or concentration dependant effect rather than a time-dependant bactericidal effect. MIC 90 values for Mannheimia ( Pasturella) hemolytica and Pasturella multocida average 0. 06 mcg/m L and 0. 015 mcg/m L, respectively. Pharmacokinetics After subcutaneous injection in the neck in cattle, danofloxacin is reportedly rapidly absorbed with high bioavailability (≈90%). Peak serum levels occur about 2-3 hours after dosing. Steady-state vol-ume of distribution is approximately 2. 7 L/kg; lung levels exceed those in plasma. T erminal elimination half-life ranges from 3-6 hours. In cattle, elimination is primarily unchanged drug into the urine. Other species may metabolize greater percentages of the drug into a desmethyl metabolite (desmethyldanofloxacin). In horses, a research study on the pharmacokinetics of IM, IV and IG (intragastric) administration of danofloxacin at 1. 25 mg/kg to healthy mature horses revealed favorable bioavailability with the IM route at 89% and poor bioavailability of the IG route at 22%. The authors reported good tolerability of the IG route (Fernandez-Varon, Ayala et al. 2006). In sheep, the drug quickly reaches high tissue concentrations. One hour after IM administration, the concentration peaks in lung tissue and interdigital skin. A study dosing sheep at 1. 25 mg/kg IV and IM resulted in similar levels for serum, exudates and transu-dates (Aliabadi, Landoni et al. 2003). In goats, a study of danofloxacin administered at 1. 25 mg/kg IV or IM, revealed similar half-lives of 4. 67 and 4. 41 hours after IV and IM, respectively. Volume of distribution was high via either route with 100% bioavailability reported after IM administration. The drug's penetration into both exudates and transudates were slightly slower after IM administration (Aliabadi and Lees 2001). Another study found that goats challenged with E. coli endotoxin receiving danofloxacin at 1. 25 mg/kg IV or IM had an altered clearance of the drug with significant increases in plasma concentrations and AUC (Ismail 2006). In camels, IV administration of the drug at 1. 25mg/kg results in a high volume of distribution, a half-life of 5. 37 hours and rapid clearance. The IM administration of the drug at the same dose re-sulted in rapid and near complete absorption, with a half life of 5. 71 hours (Aliabadi, Badrelin et al. 2003). In pigs, the drug has been shown to reach a high concentration in lung tissue and gastrointestinal tissue, including mucosa. In the first 24-hours after an intramuscular dose of 2 mg/kg, 43% of the dose is eliminated in the urine. Elimination half-life in swine is about 7 hours. Contraindications/Precautions/Warnings The FDA prohibits extra-label usage of this drug in food ani-mals. The manufacturer cautions use of danofloxacin in animals with known or suspected CNS disorders as quinolones have rarely caused CNS stimulation. Adverse Effects Hypersensitivity reactions and lameness have been reported after administration to calves at labeled dosages. Incidence rates are not | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
250 DANTROl ENE SODIUm known, but they are believed to occur uncommonly. In cattle, sub-cutaneous injections can cause a local tissue reaction that may result in trim loss. Reproductive/Nursing Safety Studies documenting safety during pregnancy in cattle are not avail-able. In studies performed in rats (100 mg/kg/day), mice (50 mg/kg/day) and rabbits (15 mg/kg/day), no teratogenic effects were ob-served. Danofloxacin safety during nursing is not known, but it is pro-hibited from use in lactating dairy cattle where the milk is for hu-man consumption. Overdosage/Acute Toxicity Limited information is available for cattle. High dosages, 18-60 mg/ kg for 3-6 days in feeder calves reportedly can cause arthropathies/ lameness (consistent with other fluoroquinolones), CNS stimulation (ataxia, nystagmus, tremors), inappetance, recumbency, depression, and exophthalmos. Some (3/6) 21-day-old calves receiving 18 mg/kg twice 48 hours apart developed nasal pad erythema. Studies performed in adult dogs given 2. 4 mg/kg/day PO for 90 days developed no observable effects. Drug Interactions No specific interactions have been reported when danofloxacin is used in cattle. In humans: THEOPHyll INET! (aminophylline ): Some injectable fluoroquinolones (e. g., ciprofloxacin) can potentially increase serum concentra-tions; increased monitoring of theophylline concentrations is rec-ommended laboratory Considerations No issues identified Doses CATTl E:T! For labeled indications: a) 6 mg/kg (1. 5 m L per 100 lb body weight) SC. Repeat once in approximately 48 hours. Administered dosage volume should not exceed 15 m L. (Label directions; A180®—Pfizer) monitoring Clinical efficacy T! Client Information If clients are to administer this product to food animals, they T! should be advised on proper injection technique and the impor-tance of using the product per the label only Chemistry/Synonyms Danofloxacin mesylate is a synthetic fluoroquinolone that occurs as a white to off-white crystalline powder. Approximately 180 grams are soluble in 1 liter of water. Danofloxacin may also be known by the following synonyms: CP-76136-27, danofloxacine or danofloxacino. Internationally registered trade names include: Advocin®, Advocine®, Danocin®, Advocid®, and Advovet ®. Storage/Stability/Compatibility Danofloxacin mesylate for injection should be stored at or below 30° C and protected from light and freezing. The color of the injectable solution is yellow to amber and does not affect potency. Danofloxacin injection for SC use should not be mixed with oth-er medications or diluents. Fluoroquinolone injectable products can be very sensitive to p H changes or chelation with cationic substances (calcium, magnesium, zinc, etc. ). Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Danofloxacin Mesylate 180 mg/m L (of danofloxacin) in 100 & 250 m L multi-dose vials; A180® (Pfizer); (Rx). Approved for use in cattle only. Not for use in cattle intended for dairy product or calves to be processed for veal. When administered per the label directions, slaughter withdrawal is 4 days from the time of the last treatment. HUm ANl Ab El ED PRODUCTS: None d Antrolene sodium (dan-troe-leen) Dantrium® skeletal muscle rela Xant Prescriber Highlights Direct acting muscle relaxant T T Primary indications: T T HORSES: post-anesthesia myosi tis/ acute rhabdomyolysis; DOGS & CATS: functional urethral obstruction; SWINE: malig nant hyperthermia Extreme caution: Hepatic dysfunction T T Caution: Severe cardiac dysfunction or pulmonary T T disease Adverse Effects: Weakness, sedation, increased urinary T T frequency, GI effects; hepato toxicity possible especially with chronic use. Injectable is very expensive T T Uses/Indications In humans, oral dantrolene is indicated primarily for the treatment associated with upper motor neuron disorders (e. g., multiple sclero-sis, cerebral palsy, spinal cord injuries, etc. ). In veterinary medicine, its proposed indications include: the prevention and treatment of malignant hyperthermia syndrome in various species, the treatment of functional urethral obstruction due to in creased external urethral tone in dogs and cats, the prevention and treatment of equine post-anes thetic myositis (PAM), and equine exertional rhabdomyolysis. It has also been recommended for use in the treatment of bites from Black Widow Spiders in small animals and the treatment of porcine stress syndrome. Pharmacology/Actions Dantrolene exhibits muscle relaxation activity by direct action on muscle. While the exact mechanism is not well understood, it prob-ably acts on skeletal muscle by interfering with the release of calcium from the sarcoplasmic reticulum. It has no discernible effects on the respira tory or cardiovascular systems, but can cause drowsiness and dizziness. The reasons for these CNS effects are not known. Pharmacokinetics The bioavailability of dantrolene after oral administration in hu-mans is only about 35% and after intragastric administration to horses, approximately 39%. The drug is fairly slowly absorbed, with peak levels occurring about 5 hours after oral administration (hu-mans) and 1. 5 hours in horses. The drug is substantially bound to plasma proteins (principally albumin), but many drugs may displace it from such (see Drug Interactions). Dantrolene is rapidly eliminated from the horse (half-life≈130 minutes). The elimination half-life in humans is approximately 8 hours. Dantrolene is metabolized in the liver and the metabolites are | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DANTROl ENE SODIUm 251 ex creted in the urine. Only about 1% of the parent drug is excreted unchanged in the urine and bile. In horses, oral dantrolene absorption is affected by food and must be given to fasted horse orally to achieve therapeutic levels. Contraindications/Precautions/Warnings Because dantrolene can cause hepatotoxicity, it should be used with extreme caution in patients with preexisting liver disease. It should be used with caution in pa tients with severe cardiac dysfunction or pulmonary disease. Adverse Effects The most significant adverse reaction with dantrolene therapy is hepa totoxicity. In humans, it is most commonly associated with high dose chronic therapy, but may also be seen after short high dose therapy. The incidence of this reaction is unknown in veteri-nary medicine, but monitor for its occurrence. More common, but less significant are the CNS associated signs of weakness, sedation, dizziness, headache, and GI effects (nausea, vomiting, constipation). Also seen are increased urinary fre quency and, possibly, hypotension. Reproductive/Nursing Safety The safe use of dantrolene during preg nancy has not been deter-mined. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or labora-tory animals have uncovered risks, and these drugs should be used cautiously as a last resort when the benefit of therapy clearly outweighs the risks. ) Dantrolene is distributed into milk; safe use cannot be assured during nursing. Overdosage/Acute Toxicity There is no specific antidotal therapy to dantrolene overdoses, therefore, remove the drug from the gut if possible and treat sup-portively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dantrolene and may be of significance in veterinary patients: b ENz ODIAz EPINES & OTHER CNS DEPRESSANTST! : Increased sedation may be seen if tranquilizing agents are used concomitantly with dantrolene CAl CIUmCHANNEl bl OCKERS T! : Rare reports of cardiovascular col-lapse in humans; concomitant use with dantrolene during malig-nant hyperthermia crises not recommended ESTROg ENST! : Increased risks of hepatotoxicity from dantrolene have been seen in women >35 years of age who are also receiving estrogen therapy; veterinary significance is unknown WARFARINT! : Dantrolene may be displaced from plasma proteins by warfarin with increased effects or adverse reactions resulting Doses DOg S:T! For treatment of functional urethral obstruction due to in-creased external urethral tone: a) 1-5 mg/kg PO q8h (Polzin and Osborne 1985), (Chew, Di Bartola, and Fenner 1986) b) 1-5 mg/kg PO q8-12h (Lane 2000), (Coates 2004) c) 1 mg/kg PO q8h (Lulich 2004) For canine stress syndrome (CSS)/Malignant Hyperthermia (MH): a) T o treat an acute attack: 0. 2-3 mg/kg IV (Axlund 2004a) b) For MH-like syndrome associated with hops (Humulus lu-pulus) ingestion: 2-3 mg/kg IV or 3. 5 mg/kg PO as soon as possible after ingestion. (Wismer 2004) For adjunctive treatment of Black Widow Spider bite: a) 1 mg/kg IV; followed by 1 mg/kg PO q4h (Bailey 1986a) CATS:T! For treatment of functional urethral obstruction due to in-creased external urethral tone: a) 0. 5-2 mg/kg PO q8h OR 1 mg/kg IV (Lane 2000); (Osborne, Kruger et al. 2000) b) 0. 5-2 mg/kg PO three times daily (Coates 2004) c) 2-10 mg (total dose) PO three times daily with either pra-zosin (0. 5 mg/cat once to twice daily) or phenoxybenzamine (2. 5-7. 5 mg/cat once to twice daily) (Sparkes 2006b) HORSES:T! For treatment of acute rhabdomyolysis:a) 15-25 mg/kg slow IV four times daily (Robinson 1987) b) 2-4 mg/kg PO via nasogastric tube once daily (Hanson 1999) For prevention of rhabdomyolysis:a) For prevention of recurrent exertional rhabdomyolysis in Thoroughbreds: 4 mg/kg PO in horses fasted (12-hour fast in study) prior to administration. (Mc Kenzie, Valberg et al. 2003) b) Several dosage regimens have been recommended, but take care as use and efficacy are uncertain: 2 mg/kg PO once daily for 3 -5 days and then every 3rd day for a month has been recommended. Drug is diluted in normal saline and given via stomach tube. Another dosage recommendation is 300 mg (total dose) PO once daily (may be preferable because the drug is hepatotoxic). Another recommendation is 500 mg (total dose) PO for 3-5 days and then 300 mg PO ev-ery third day. Monitor hepatic function and status. (Mac Leay 2004) For prevention of post-anesthetic myositis (PAM):a) 10 mg/kg PO (intragastric) 1. 5 hours before surgery. This should give peak levels at the time surgery begins and main-tain postulated therapeutic levels for an additional 2 hours. The intragastric preparation was made by dissolving/sus-pending the contents of oral cap sules into 500 m L of normal saline. Should further doses be warranted, additional doses of 2. 5 mg/kg PO (intragastric) q60 minutes can be given. Alternatively, IV doses of 1. 9 mg/kg loading will give thera-peutic levels but will only persist for about 20 minutes. An IV dose of 4 mg/kg will maintain therapeutic levels for about 2 hours, but peak levels will be quite high. (Court et al. 1987) SWINE:T! Prevention or treatment of malignant hyperthermia: a) 3. 5 mg/kg IV (Booth 1988a) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
252 DAPSONE monitoring Depending on the reason for use: Baseline and periodic liver function tests (ALT, AST, Alk Phos, T! etc. ) if projecting to be used chronically or using high dosages Body temperature (malignant hyperthermia)T! Urine volume, frequency, continence T! Client Information Dantrolene can cause GI upset (vomiting, lack of appetite), in-T! creased urinary frequency, and sedation (drowsiness) Rarely, dantrolene can cause liver toxicity; contact veterinarian T! if patient develops persistent vomiting, lack of appetite, unex-plained profound lethargy, or yellowish whites of eyes or mucous membranes Intravenous use of this drug should only be used by professionals T! familiar with its use Chemistry/Synonyms A hydantoin derivative that is dissimilar structurally and pharma-cologically from other skeletal muscle relaxant drugs, dantrolene sodium is a weak acid with a p K a of 7. 5. It occurs as an odorless, tasteless, orange, fine powder that is slightly soluble in water. It rap-idly hydrolyzes in aqueous solutions to the free acid form that pre-cipitates out of solution. Dantrolene Sodium may also be known by the following syn-onyms and internationally registered trade names: F-440, F-368, Danlene®, Dantamacrin®, Dantralen®, or Dantrolen®. Storage/Stability/Compatibility Dantrolene capsules should be stored in well-closed containers at room temperature. Dantrolene powder for injection should be stored at temperatures less than 30°C and protected from prolonged exposure to light. After reconstitution, the powder for injection should be used within 6 hours when stored at room temperature and should be protected from direct light. It is not compatible with either normal saline or D 5W injection. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Dantrolene Sodium Capsules: 25 mg, 50 mg, & 100 mg; Dantrium® (Procter & Gamble Pharm. ); generic; (Rx) Dantrolene Sodium Powder for Injection: 20 mg/vial (approx. 0. 32 mg/m L after reconstitution; with mannitol 3 g/vial) in 70 m L vials; Dantrium® Intravenous (Procter & Gamble Pharm. ); (Rx). Note: Be-cause of the expense, minimum order quantity, and non-returnable nature of the commer cially available intravenous product, it may not be practical for veterinary use. d Apsone (dap-sone) DDS antimyc Obacterial antibi O tic Prescriber Highlights Potentially useful for treating mycobacterial & some pro-T T tozoal (Pneumocystis) infections May be used to treat Brown recluse spider bites & cuta-T T neous vasculitis Relatively contraindicated in cats T T Adverse effects: hepatotoxicity, anemia, thrombocytope-T T nia, neutropenias, gastrointestinal effects, neuropathies, & cutaneous drug eruptions; photosensitivity reactions are possible Uses/Indications Dapsone may be useful as a second-line agent in the treatment of my-cobacterial diseases in dogs and, possibly, cats. It potentially may be a useful treatment for Pneumocystis jiroveci (formerly Pneumocystis carinii) infections. Because of its leukocyte inhibitory characteristics, dapsone may be useful for adjunctive treatment of Brown recluse spider (Loxosceles rectusa recluse) bites, or when an underlying etiology causing cutaneous vasculitis cannot be determined. Pharmacology/Actions The exact mechanism for dapsone's actions are not known. It prob-ably has similar actions to that of the sulfonamides, primarily af-fecting folic acid synthesis in susceptible organisms. Dapsone also decreases neutrophil chemotaxis, complement activation, antibody production and lysosomal enzyme synthesis. The mechanisms for these actions are not well understood. Pharmacokinetics After oral administration to dogs, dapsone is rapidly and completely absorbed. Elimination half-life ranges from about 6-10 hours. In humans, the monoacetyl metabolite is almost completely bound to plasma proteins, but in dogs, it is only about 60% bound. Dapsone is primarily eliminated via the kidneys as conjugates and unidentified metabolites. Half-life in humans is widely variable and ranges from about 10-50 hours. Contraindications/Precautions/Warnings Because of increased incidences of neurotoxicity and hemolytic ane-mia, dapsone is generally not recommended for use in cats. Dapsone in contraindicated in patients hypersensitive to it or other sulfone drugs. It should not be used in patients with severe anemias or other preexisting blood dyscrasias. Because of its potential for causing he-patic toxicity, dapsone should be used with caution in animals with preexisting hepatic dysfunction. Adverse Effects Adverse effects include hepatotoxicity, hemolytic anemia, thrombo-cytopenia, neutropenias, gastrointestinal effects, neuropathies, and cutaneous drug eruptions. Photosensitivity is possible. Dapsone is a potential carcinogen. Reproductive/Nursing Safety In pregnant animals, dapsone should be used with caution. In hu-mans, the FDA categorizes dapsone as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DAPSONE 253 the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). Animal studies have apparently not been performed with dapsone to determine its effects in pregnancy. Dapsone is excreted into milk in concentrations equivalent to those found in plasma; and hemolytic reactions have been seen in human neonates. Consider switching to milk replacer if dapsone is required in a nursing dam. Overdosage/Acute Toxicity Because of its toxicity potential, specific species differences in sen-sitivity, and pharmacokinetics, it is recommended to contact an animal poison control center in cases of dapsone overdoses. In humans, dapsone overdoses generally cause nausea, vomiting, and hyperexcitability which can occur within minutes of an overdose. Methemoglobinemia with associated depression, seizures, and cy-anosis can occur. Hemolysis may be delayed, occurring from 7-14 days after the overdose. Treatment in humans includes removal of drug from the gut, methylene blue for methemoglobinemia and, sometimes, hemodialysis to enhance removal of the drug and the monoacetyl metabolite. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dapsone and may be of significance in veterinary patients: PROb ENECIDT! : May decrease the renal excretion of active metabo-lites of dapsone Py RIm ETHAm INET! : May increase risk of hematologic reactions oc-curring with dapsone RIFAm PINT! : May decrease plasma dapsone concentrations (7-10 fold) TRIm ETHOPRIm T! : May increase plasma dapsone concentrations (and vice versa) and potentially increase each other's toxicity laboratory Considerations No specific laboratory interactions or considerations noted Doses DOg S:T! a) As an alternative treatment for pemphigus: Dapsone at 1 mg/kg PO q8h; with sulfasalazine at 10-40 mg/kg q8h. (Rosenk-rantz 2004) b) For post-vaccination alopecia/vasculitis resistant to predni-sone therapy: 1 mg/kg PO q8h (Lemarie 2003c) c) For treating mycobacteriosis: 1. 1 mg/kg PO q6h until remis-sion, then 0. 3 mg/kg q8-12h after recovery (Greene and Watson 1998) d) For adjunctive therapy of vasculitis: 1 mg/kg PO q8h (Hillier 2006d) e) For adjunctive treatment of Brown Recluse spider (Loxosceles sp. ) bite: 1 mg/kg PO three times daily for 10 days (Peterson 2006d) CATS: T! CAUTION: Dapsone can potentially cause serious side effects in cats (e. g., blood dyscrasias, and hepatic or neuro toxicities); many consider its use relatively contraindicated in cats. If this drug is to be used, clients must accept the risks associated with its use; intensive monitoring for adverse effects must be performed. a) As an alternative to clofazimine for treating feline leprosy (see caution above): 1 mg/kg once daily PO. (Lemarie 2003a) b) For treating mycobacteriosis: 8 mg/kg PO once daily for 6 weeks (Greene and Watson 1998) c) For aural chondritis: 1 mg/kg PO q24h (Griffin 2006) HORSES:T! a) As an alternative treatment for Pneumocystis carinii pneu-monia: 3 mg/kg PO once daily (q24h). Note : From one case report of treatment of a foal; treatment period was 56 days. (Clark-Price, Cox et al. 2004) monitoring CBC with platelets every 2T! -3 weeks during first 4 months of treatment and then every 3-4 months Liver function tests T! Other adverse effects (GI, drug eruptions, neurotoxicity, etc. )T! Efficacy T! Client Information Clients should understand that limited experience has occurred T! with dapsone in domestic animals and that toxicity may occur. Because photosensitivity can occur, exposed skin should be pro-T! tected from prolonged exposure to sunlight. Chemistry/Synonyms A sulfone antimycobacterial/antiprotozoan, dapsone occurs as a white or creamy-white, odorless, crystalline powder. It is very slightly soluble in water, freely soluble in alcohol, and insoluble in fixed or vegetable oils. Dapsone may also be known as: DADPS, dapsonum, DDS, di-aminodiphenylsulfone, NSC-6091, diaphenylsulfone, disulone, sulfonyldianiline, Avlosulfone®, Daps®, Dapsoderm-X®, Dopsan®, Novasulfone®, Servidapsone®, and Sulfona®. Storage/Stability Dapsone tablets should be stored protected from light at controlled room temperature (20-25°C, 68-77°F). Dapsone tablets may be compounded into a stable liquid dosage form. The simplest method is to use a 1:1 ratio of Ora-Plus®:Ora-Sweet® and use crushed tablets to make a concentration of 2 mg/m L. This preparation is stable either stored refrigerated or at room temperature for 90 days. See the following reference for spe-cific information: Nahata, MC et al, Ann Pharmacotherapy 2000; 34:848-50. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Dapsone Tablets: 25 mg & 100 mg (scored); generic (Jacobus); (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
254 DARb EPOETIN Al FA d Arbepoetin Alf A (dar-beh-poe-eh-tin al-fah) Aranesp® erythr Op Oietic agent Prescriber Highlights Biosynthetic erythropoietic agent potentially useful for T T treating anemia of chronic kidney disease in dogs & cats May be less immunogenic (not proven) in dogs or cats T T than epoetin alfa (r Hu EPO)Longer duration of effect, initially only dosed once per T T week Treatment expense may be formidable T T Uses/Indications Darbepoetin may potentially be useful in treating anemia of chronic kidney disease in dogs and cats. It may be less immunogenic than epoetin, but this is only theoretical and has not been documented. Another advantage is that doses may be administered less often to maintain PCV. Treatment costs may be higher than using epoetin, however. Pharmacology/Actions Darbepoetin is a recombinant DNA-produced protein related to erythropoietin. It stimulates erythropoiesis using the same mecha-nism as endogenous erythropoietin by interacting with progenitor stem cells to increase RBC production. Darbepoetin may be less im-munogenic in animals than epoetin secondary to its formulation utilizing carbohydrates as part of its structure. Theoretically, car-bohydrates may “shield” the sites on the drug of greatest antigenic potential from immune cell detection. Carbohydrates also increase the solubility and stability of the compound, causing less aggregate formation and, therefore, potentially less immunogenicity. Pharmacokinetics No information was located on the pharmacokinetics in dogs or cats. In humans with chronic renal failure after subcutaneous injection, bioavailability is about 37% and the drug is absorbed slowly with a distribution half-life of about 1. 4 hours. It is extensively metabolized and terminal elimination half-life averages 21 hours. T erminal half-life is about 3 times greater than that of epoetin alfa. Contraindications/Precautions/Warnings Darbepoetin should not be used in dogs or cats with documented anti-r Hu EPO antibodies. Antibody formation diagnosis is based upon high myeloid:erythroid ratio on bone marrow cytology and exclusion of other causes of anemia. In humans, darbepoetin is con-traindicated in patients hypersensitive to it or excipients in the for-mulation and in those with uncontrolled hypertension. Adverse Effects The adverse effect profile for darbepoetin is unknown, but adverse effects reported with r Hu EPO (epoetin) therapy in animals include: anti-r Hu EPO antibody formation with resultant pure red blood cell aplasia (PRCA), hypertension, seizures, or iron deficiency. Reproductive/Nursing Safety Studies performed in pregnant rats and rabbits demonstrated no overt teratogenicity at IV dosages of up to 20 mg/kg/day. Decreased body weights were noted in some rat pups. It is unknown if darbepoetin is distributed into milk, but it is unlikely to pose much risk to animals nursing. Overdosage/Acute Toxicity Little information is available. Humans have received therapeutic dosages of up to 8 mcg/kg every week for 12 weeks. Polycythemia is possible and therapeutic phlebotomy may be required. Drug Interactions None have been identified. For epoetin (a related compound): ANDROg ENST! : May increase the sensitivity of erythroid progenitors and this interaction has been used for therapeutic effect DESm OPRESSINT! : With EPO can decrease bleeding times laboratory Considerations No specific lab issues were identified; see Contraindications and Monitoring for more information. Doses DOg ST! /CATS: Doses and dosing intervals for darbepoetin in dogs and cats have not been well established. Anecdotally it has been suggested to use the initial human dose of 0. 45 mcg/kg of darbepoetin in dogs and cats and adjust using clinical judgment and careful monitoring. Alternatively, animals that have received epoetin alfa (RHu EPO) can have their total weekly dosages converted using the following guidelines: T otal weekly dose of epoetin in units divided by 200 = once weekly dose in mcg darbepoetin. Example: animal gets 400 Units of epoetin 3 times weekly = 1200 Units. Divide by 200 = 6 mcg of darbepoetin once weekly. monitoring Before re-dosing check PCV each time T! Monitor patient's iron stores or supplement with iron T! Blood pressure T! Client Information Clients must be committed to the expense and associated moni-T! toring required for this treatment Therapeutic effects may not be noted for several weeks after start-T! ing treatment Chemistry/Synonyms Darbepoetin alfa is a 165-amino acid protein that is produced us-ing recombinant DNA technology in Chinese hamster ovary cells. Two additional N-linked oligosaccharide chains are added to human erythropoietin yielding a glycoprotein with an approximate molecu-lar weight of 37,000 daltons. Darbepoetin may also be known by the following synonyms: NESP, novel erythropoiesis stimulating protein, darbepoetina or darbepoetinum. Internationally registered trade names include: Aranesp® and Nespo®. Storage/Stability The commercially available injection solutions (polysorbate or al-bumin-based) should be stored at 2-8°C and protected from light. Do not freeze or shake. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. It is also prohibited on the premises of a racing facility. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DECOQUINATE 255 HUm ANl Ab El ED PRODUCTS: Darbepoetin Alfa Solution for Injection (preservative free); Aranesp® (Amgen); (Rx) Each size is available in polysorbate or albumin-based solutions: 25 mcg/0. 42 m L prefilled syringes25 mcg per 1 m L single-dose vials40 mcg/0. 4 m L prefilled syringes40 mcg per 1 m L single-dose vials60 mcg/0. 3 m L prefilled syringes60 mcg per 1 m L single-dose vials100 mcg/0. 5 m L prefilled syringes100 mcg per 1 m L single-dose vials150 mcg/0. 3 m L prefilled syringes150 mcg per 1 m L single-dose vials200 mcg/0. 4 m L prefilled syringes200 mcg per 1 m L single-dose vials300 mcg/0. 6 m L prefilled syringes300 mcg per 1 m L single-dose vials500 mcg per 1 m L single-dose vials and prefilled syringes decoquin A te (de-koe-kwin-ate) Deccox® antipr Ot Oz Oal/c Occidi Ostat Prescriber Highlights Coccidiostat T T Not approved for lactating dairy animals, laying chickens T T Not effective against adult coccidia; no effect on clinical T T coccidiosis Uses/Indications Decoquinate is labeled for use in cattle for the prevention of coccid-iosis in either ruminating or non-ruminating calves, cattle or young goats caused by the species E. christenseni or E. ninakohlyakimoviae. It is used for prevention of coccidiosis in broilers caused by E. tenel-la, E. necatrix, E. acervulina, E. mivati, E. maxima or E. burnetti. It may be useful in dogs as prophylactic treatment for coccidiosis and hepatozoonosis relapse. Pharmacology/Actions Decoquinate is 4-hydroxy quinolone agent that has anticoccidial activity. Deco quinate acts on the sporozoite stage of the life cycle. The sporozoite apparently can still penetrate the host intestinal cell, but further development is prevented. The mechanism of action for decoquinate is to disrupt electron transport in the mitochondrial cytochrome system of coccidia. Pharmacokinetics No information was located. Contraindications/Precautions/Warnings Decoquinate is not effective for treating clinical coccidiosis and has no efficacy against adult coccidia. Decoquinate is not approved for use in animals producing milk for food or in laying chickens. Adverse Effects No adverse effects listed when given as directed. Overdosage/Acute Toxicity No specific information located. Decoquinate is considered to have a wide safety margin. Drug Interactions/laboratory Considerations None noted Doses DOg S:T! For coccidiosis prophylaxis: a) 50 mg/kg PO once daily (Matz 1995) For canine hepatozoonosis (Hepatozoon americanum): Note : When using decoquinate for this indication, obtain the decoqui-nate 6% (27. 2 gram/lb. ) powder. An approximate conversion is G teaspoonful is equivalent to approximately 45 mg decoquinate and 1 teaspoonful (5 m L) is equivalent to approximately 180 mg decoquinate. a) For 14 days: Use TMP/Sulfa 15 mg/kg PO q12h; Clindamy-cin 10 mg/kg PO q8h; Pyrimethamine 0. 25 mg/kg PO once daily); Then to prevent relapse after TCP therapy: Decoquinate at 20 mg/kg PO q12h long-term. Recommend treating for 2 years and then performing muscle biopsy. If negative, may dis continue. When using the 27. 2 gram/lb (6%) feed additive (Deccox ®) the decoquinate powder can be administered at a rate of 1 teaspoon per 10 kg (22 lb) of body weight and fed twice daily. (Macintire, Vincent-Johnson et al. 2006), (Ma-cintire 2007) b) TMP/Sulfa 15 mg/kg PO daily for 14 days; Clindamycin 10 mg/kg PO q8h For 14 days; Pyrimethamine 0. 25 mg/kg PO once daily For 14 days; Then give Decoquinate: 10-20 mg/kg PO q12h for 24 months. (Blagburn 2005a) CATTl E:T! a) For prophylaxis of coccidiosis: Using the 6% premix: 0. 5 mg/kg per day in feed for at least 28 days (Penzhorn and Swan 1993) (Mc Dougald and Roberson 1988) g OATS:T! For prophylaxis of coccidiosis: a) 0. 5 mg/kg per day in feed during periods of exposure (Bret-zlaff 1993) b) 0. 5-1 mg/kg of body weight PO (de la Concha 2002) ll Am AS:T! a) For prophylaxis of coccidiosis: Using the 6% premix: 0. 5 mg/kg per day in feed for at least 28 days (Johnson 1993) Client Information Decoquinate should be used for at least 4 weeks when used for T! preventing coccidiosis outbreaks When used in dogs for Hepatazoonosis treatment may be for up T! to two years Mix well into food T! Chemistry/Synonyms A coccidiostat, decoquinate occurs as a cream to buff-colored fine amorphous powder having a slight odor. It is insoluble in water. Decoquinate may also be known as HC-1528, M&B-15497, or Deccox ®. Storage/Stability/Compatibility Decoquinate is reportedly incompatible with strong bases or ox-idizing material. Follow label storage directions; store in a cool, dry place, preferably in airtight containers. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
256 DEFEROx Am INE m ESyl ATE Deccox ® is labeled as being compatible (and cleared for use) with bacitracin zinc (with or without roxarsone), chlortetra cycline, and lincomycin. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Decoquinate 6% (27. 2 gram/lb. ) Feed Additive (with corn meal, soybean oil, lecithin and silicon dioxide) in 50 lb bags; Deccox ® (Al-pharma); (OTC). Approved for use in cattle, sheep, goats (Do NOT feed to cows, goats or sheep producing milk for food), and chickens (not laying chickens). Decoquinate 0. 5% (2. 271 grams/lb) Feed Additive in 50 lb bags; Doccox ®-L (Alpharma), (OTC). Approved for use in ruminating and non-ruminating calves and cattle. Do NOT feed to cows pro ducing milk for food. Decoquinate 0. 8% (3. 632 grams/lb) in 5 lb and 50 lb bags. Deccox ®M (Alpharma) (OTC). Approved for use in ruminating and non-rumi-nating calves including veal calves. Also available are calf milk replacers that contain 22. 7 mg decoqui-nate per pound. For the prevention of coccidiosis in non-ruminating and calves and cattle. Advance® Calvita® Supreme 20/21 (and 18/21) Medicated with Decoquinate (MS Specialty Nutrition); (OTC) HUm ANl Ab El ED PRODUCTS: None deferox Amine mesyl A te (de-fer-ox-a-meen) Desferal®, DFO Prescriber Highlights Parental iron chelating agent used primarily for treat-T T ment of iron or aluminum intoxication in dogs/cats; has been used as a ferric ion chelator in cardiac arrest/GDV Contraindications: Severe renal failure unless dialysis T T used Caution: Pregnancy T T Adverse Effects: Allergic reactions, auditory neurotoxicity, T T pain or swelling at injection sites, GI distress When used IV, must be given slowly T T Uses/Indications Deferoxamine is used for the treatment of either acute or chronic iron toxicity. It is being evaluated as an iron chelator for adjunctive treatment of acute cardiac ischemia and as a chelator for aluminum toxicity. Its efficacy in treating reperfusion injuries has been disap-pointing. Pharmacology/Actions Deferoxamine (DFO) binds ferric (Fe+++) ions to its three hydroxam-ic groups forming ferrioxamine. This forms a stable, water-soluble compound that is readily excreted by the kidneys. DFO does not ap-pear to chelate other trace metals (except aluminum) or electrolytes in clin ically significant quantities. Pharmacokinetics DFO is poorly absorbed from the GI and is usually given parenteral-ly. The drug is widely distributed in the body. DFO and ferrioxamine are excreted primarily in the urine. Ferriox amine will give the urine a reddish color (“vin rosé”) that indicates iron removal. Contraindications/Precautions/Warnings DFO is contraindicated in patients with se vere renal failure, unless dialysis is used to remove ferrioxamine. Adverse Effects There is little veterinary experience with this drug. Potential adverse effects include, allergic reactions, auditory neurotoxicity (particu-larly with chronic, high-dose ther apy), pain or swelling at injection sites, and GI distress. T oo rapid IV injection may cause rapid heart rates, convulsions, hypotension, hives, and wheezing. Oral administration of DFO is controversial. Some have recom-mended oral administration after oral iron ingestions, but DFO may actually increase the amount of iron absorbed from the gut. At pres-ent, oral sodium bicarbonate solution 5% given as a gastric lavage is probably a better treatment in reducing oral absorption of iron. Reproductive/Nursing Safety Because deferoxamine has caused skeletal abnormalities in animals at dosages just above those recommended for iron toxicity, it should be used during pregnancy only when its benefits outweigh it 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. ) Overdosage/Acute Toxicity See Adverse Effects above. Chronic high dose use may also lead to hypocalcemia and thrombocytopenia. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving deferoxamine and may be of significance in veterinary patients: PROCHl ORPERAz INET! : Use with deferoxamine may cause temporary impairment of consciousness VITAm IN CT! : May be synergistic with deferoxamine in removing iron, but could lead to increased tissue iron toxicity especially in cardiac muscle; it should be used with cau tion, particularly in pa-tients with preexisting cardiac disease laboratory Considerations DFO may interfere (falsely low values) with colorimetric T! iron as says DFO may cause falsely high total iron binding capacity (T! TIb C ) measurements Doses DOg S & CATS:T! In dogs at risk for, or exhibiting signs of severe iron toxicosis; cat dosages not well established:a) Most effective within the first 24 hours. Extrapolated animal dose is 40 mg/kg IM q4-8 hours. IM route is preferred as too rapid IV administration can cause hypotension and pul-monary edema. Efficacy can be increased by giving ascorbic acid after the gut has been cleared of iron. Deferoxamine-iron complex gives a salmon pink (“vin rose”) color to urine. Con-tinue to chelate until urine clears or serum iron levels return to normal. (Wismer 2004) b) Initiate ASAP or at least within 12 hours of ingestion; give as a constant rate infusion at 15 mg/kg/hour. More rapid infu-sion may precipitate arrhythmias or aggravate hypoten sion. If constant rate infusion is not possible or are unable to monitor patient during infusion, give 40 mg/kg IM q4-8h, depend-ing on clinical status. Continue therapy until serum iron lev-els are below 300 microliters/dl or decrease below the TIBC, | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DERACOx Ib 257 whichever is lower. Chelation therapy may require 2-3 days of therapy. Following recovery, monitor for signs of GI ob-struction, which may develop 4-6 weeks post-ingestion. (Greentree and Hall 1995) c) 10 mg/kg IM or IV q8h for 24 hours (Firth 2000) Experimentally, as a ferric ion chelator during treatment of car-diac arrest:a) 5-15 mg/kg IV, IM or SC (Muir 1994) b) 10 mg/kg IV, IM q2h twice, then three times daily for 24 hours (Hackett and Van pelt 1995) monitoring For iron overload: Efficacy (serum ferritin, serum iron, TIBC are rec ommended to T! monitor iron overload) Adverse effects (see above); additionally, if chronic iron overload: T! eye examinations (iron toxicity and its subsequent removal may adversely affect vision) Chemistry/Synonyms An iron-chelating agent, deferoxamine mesylate occurs as a white to off-white powder that is freely soluble in alcohol or water. Deferoxamine mesylate may also be known as: desferoxam-ine mesy late, DFO, Ba-33112, Ba-29837, deferoxamini mesilas, desferrioxamine mesylate, desferrioxamine methanesulphonate, NSC-527604, Desferal® or Desferin®. Storage/Stability/Compatibility Store at room temperature. After aseptic reconstitution (2-5 m L for 500 mg vial; 8-20 m L for 2 gram vial) with sterile water for injection, the solution may be stored for up 24 hours at room tem-perature and protected from light. It is recommended not to mix this agent with other drugs; do not use if solution is turbid. Di-lution in normal saline, lactated Ringer's or dextrose 5% has been recommended when admin istering as an intravenous infusion. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Deferoxamine Mesylate Powder for Injection (lyophilized): 500 mg & 2 g in vials; Desferal® (Novartis); Deferoxamine Mesylate (Hos-pira); (Rx)der Acoxib (dare-a-cox-ib) Deramaxx® n On-ster Oidal antiinflammat Ory agent Prescriber Highlights Coxib-class NSAID approved for use in dogs for treatment T T of post-operative pain (higher dose, 7 day maximum) & for treatment of pain & inflammation associated with osteoarthritis (lower dose, ongoing dosing) May be useful alternative to piroxicam in adjunctive T T treatment of transitional cell carcinoma of bladder At lower doses, appears to cause predominantly COX-2 T T inhibition Adverse effect profile still being fully determined, but GI T T & renal effects are possible Uses/Indications Deracoxib is indicated for the treatment of post-operative pain (higher dose, 7 day maximum), and for the treatment of pain and inflammation associated with osteoarthritis (lower dose, ongoing dosing) in dogs. Like piroxicam, deracoxib is of interest in adjunctive treatment of transitional cell carcinoma of the bladder; investigations into this use are ongoing. Pharmacology/Actions Deracoxib is a coxib-class, nonsteroidal antiinflammatory drug (NSAID). It is believed to predominantly inhibit cyclooxygenase-2 (COX-2) and spare COX-1 at therapeutic dosages. This, theoreti-cally, would inhibit production of the prostaglandins that contrib-ute to pain and inflammation (COX-2) and spare those that main-tain normal gastrointestinal and renal function (COX-1). However, COX-1 and COX-2 inhibition studies are done in vitro and do not necessarily correlate perfectly with clinical effects seen in actual patients. Pharmacokinetics After oral administration to dogs, bioavailability is greater than 90%; the time to peak serum concentration occurs at approximate-ly 2 hours. The presence of food in the gut can enhance bioavail-ability. The drug has an apparent volume of distribution of 1. 5 L/kg in dogs and is at least 90% bound to canine plasma proteins. Deracoxib is hepatically metabolized to four primary metabolites. These metabolites and unchanged drug are principally eliminated in the feces. Some excretion of metabolites occurs via renal mecha-nisms. T erminal elimination half-life in the dog is dependent upon dose. In dosages up to approximately 8 mg/kg, half-life is about 3 hours (clearance ≈ 5 m L/min/kg). Half-life at a dose of 20 mg/kg is approximately 19 hours (clearance ≈ 1. 7 m L/min/kg). Drug accu-mulation can occur with higher dosages, leading to increased toxic effects as increased COX-1 inhibition can occur at higher concen-trations. In cats, after 1 mg oral doses of deracoxib, peak levels (0. 28 mcg/ m L) occurred about 3. 6 hours after administration. Elimination half life was about 8 hours. Contraindications/Precautions/Warnings Deracoxib is contraindicated in patients known to be hypersensi-tive to it. It should be used with caution in patients with concurrent GI ulcerative diseases, renal or hepatic dysfunction, those in hypo- | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
258 DERACOx Ib proteinemic states, or with conditions that may predispose them to hypercoagulability. Adverse Effects In the majority of dogs treated, deracoxib appears to be well toler-ated, particularly when dosed as labeled and not in conjunction with other NSAIDs or corticosteroids. However, like other NSAIDs used in dogs, many adverse effects associated with deracoxib have been re-ported and include: gastrointestinal (vomiting, anorexia/weight loss, diarrhea, melena, hematemesis, hematochezia, GI ulceration/perfo-ration); urinary (azotemia, polydipsia, polyuria, UTI, hematuria, incontinence, renal failure); hematologic (anemia, thrombocytope-nia); hepatic (increased hepatic enzymes, changes in total protein, etc. ); neurologic (lethargy/weakness, seizures, etc. ); cardiovascular/respiratory (tachypnea, bradycardia, cough); and dermatologic/im-munologic (fever, facial/muzzle edema, urticaria, dermatitis). Rare occurrences of death associated with these effects are possible. As additional clinical experience is gained with this agent, relative in-stances of these effects and the potential risk for them to occur in a given patient population should be clarified. Reproductive/Nursing Safety No information on the drug's safety in pregnancy or in nursing pups was located. Use with caution in these animals. Overdosage/Acute Toxicity There is little data available regarding this drug's acute toxicity. A 14-day study in dogs demonstrated no clinically observable adverse effects in the dogs that received 10 mg/kg. Dogs who received 25 mg/kg, 50 mg/kg or 100 mg/kg per day for 10-11 days survived, but showed vomiting and melena; no hepatic or renal lesions were demonstrated in these dogs. There were 211 exposures to deracoxib reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) dur-ing 2005-2006. In these cases 204 were dogs with 19 showing clinical signs and the remaining 7 cases were cats with 2 showing clinical signs. Common findings in dogs recorded in decreasing fre-quency included vomiting, anorexia, diarrhea, lethargy and anemia. Common findings in cats recorded included vomiting. Because non-linear elimination occurs in dogs at dosages of 10 mg/kg and above, dogs acutely ingesting dosages above this amount should be observed for gastrointestinal erosion or ulceration and treated symptomatically for vomiting and GI bleeding. Dogs ingest-ing dosages above 100 mg/kg should be considered for gut evacua-tion techniques if ingested deracoxib can be safely removed before substantial absorption occurs. Although the manufacturer states that the drug was clinically well tolerated at doses up to 10 mg/kg/day for 26 weeks, dose-dependent increases in BUN values and focal tubular degeneration/regeneration were seen at doses of 6 mg/kg/day and greater. This medication is a NSAID. As with any NSAID, overdosage can lead to gastrointestinal and renal effects. Decontamination with emetics and/or activated charcoal is appropriate. For doses where GI effects are expected, the use of gastrointestinal protectants is war-ranted. If renal effects are also expected, fluid diuresis is warranted. Drug Interactions No specific drug interactions were noted, but the manufacturer warns that use in conjunction with other NSAIDs or corticosteroids be avoided, or monitored carefully. If switching from one NSAID to another or replacing with/or subtracting corticosteroid treatment, it is recommended to observe a “wash out” period to reduce the chances of adverse effects occurring. It is also possible deracoxib may cause increased renal dysfunction if used with other drugs that can cause or contribute to renal dysfunction (e. g., diuretics, aminoglycosides ), but the clinical significance of this potential interaction is unclear. The following drug interactions have either been reported or are theoretical in humans or animals receiving coxib-class NSAIDs and may be of significance in veterinary patients: ACE INHIb ITORST! (e. g., enalapril, benazepril ): Some NSAIDs can re-duce effects on blood pressure ASPIRINT! : May increase the risk of gastrointestinal toxicity (e. g., ul-ceration, bleeding, vomiting, diarrhea) CORTICOSTEROIDST! (e. g., prednisone ): May increase the risk of gastro-intestinal toxicity (e. g., ulceration, bleeding, vomiting, diarrhea) DIg Ox INT! : NSAIDS may increase serum levels Fl UCONAz Ol ET! : Administration has increased plasma levels of cele-coxib in humans and potentially could also affect firocoxib levels in dogs FUROSEm IDET! : NSAIDs may reduce saluretic and diuretic effects m ETHOTREx ATET! : Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate; use together with extreme caution NEPHROTOx IC DRUg ST! (e. g., furosemide, aminoglycosides, amphotericin b, etc. ): May enhance the risk of nephrotoxicity development NSAIDS, OTHERT! : May increase the risk of gastrointestinal toxicity (e. g., ulceration, bleeding, vomiting, diarrhea) laboratory Considerations No specific laboratory interactions were noted for deracoxib. De-T! racoxib does not appear to affect thyroid function tests in dogs. Doses DOg S:T! a) For the control of pain and inflammation associated with os-teoarthritis: 1-2 mg/kg PO once a day as needed. For treatment of post-operative pain: 3-4 mg/kg PO once a day as needed, not to exceed 7 days of therapy at this dosage. (Package insert; Deramaxx®) monitoring Baseline and periodic CBC and serum chemistry (including BUN/T! serum creatinine, and liver function assessment) Baseline history and physical T! Efficacy of therapy T! Adverse effect monitoring via client T! Client Information Note : The manufacturer provides a client information sheet they rec-ommend be given with every prescription for this medication. Since dogs may find the chewable tablets' taste desirable, the drug T! should be stored out of reach of animals and children Owners should immediately report to the veterinarian if any of T! the following adverse effects occur: bloody stool/diarrhea or vom-it, or allergic reaction (facial swelling face, hives, red, itchy skin) Owners should contact the veterinarian if any of the following T! adverse effects persist or are severe: loss of appetite, vomiting, change in bowel movements (e. g., stool color), change in behavior, decrease in water consumption, or urination The manufacturer recommends that although the drug can be T! given on an empty stomach, it is preferable to be given with food; water should be available at all times to avoid dehydration Other drugs for pain or inflammation should not be used with T! this medication without the approval of the veterinarian Do not increase or alter the dose of this medication without the T! approval of the veterinarian. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DESl OREl IN ACETATE 259 Chemistry/Synonyms Deracoxib is a diaryl-substituted pyrazole that is chemically related to other coxib-class NSAIDs such as celecoxib. Its molecular weight is 397. 38. Deracoxib's chemical name is: 4-[3-(difluoromethyl)-5-(3-fluo-ro-4-methoxyphenyl)-1H-pyrazole-1-yl] benzenesulfonamide. Storage/Stability The commercially available chewable tablets for dogs should be stored at room temperature between 15-30°C (59-86°F). Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Deracoxib Chewable (scored) Tablets: 25 mg, 75 mg, & 100 mg in bottles of 7, 30 and 90 tablets; Deramaxx® (Novartis) (Rx). Ap-proved for use in dogs. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: None Dermcaps® — see Fatty Acids DES — see Diethylstilbestrol deslorelin Acet Ate (dess-lor-a-lin) Ovuplant® HORMONAL A GENT Prescriber Highlights Synthetic Gn RH analog for estrual mares to induce & T T time ovulation No labeled contraindications T T Adverse Effects: May cause some local swelling, pain, T T etc; interovulatory period may be prolonged if implant not removed Availability may be an issue T T Uses/Indications Deslorelin is approved for inducing ovulation in estrual mares. There is also interest in developing dosages and dosage forms as a long-term, reversible contraceptive in a variety of animal species, as a treatment for prostatic disease in male dogs, and incontinence in ovariectomized dogs. At the time of writing, deslorelin in not avail-able in the USA, but is marketed in Canada. In humans, deslorelin has been investigated for treating children with precocious puberty, and in adults for prostate carcinoma, dys-menorrhea, fibroids, and endometriosis. Pharmacology/Actions Deslorelin increases the levels of endogenous luteinizing hormone (LH), thereby inducing ovulation. When developing follicles are greater than 30 mm in diameter, deslorelin induces ovulation in ap-proximately 85% of mares within 48 hours of administration. Pharmacokinetics In horses after implantation of a 2. 1 mg pellet, concentrations of LH and FSH peak about 12 hours after implant and return to pre-treatment levels approximately 3-4 days after implantation. Oral dosing of 100 mcg/kg to Beagles, demonstrated no increase in LF or FSH. Contraindications/Precautions/Warnings When used as indicated, the manufacturer lists no contraindications. Adverse Effects Minor local swelling, sensitivity to touch, and elevated skin temper-ature at injection site may occur; these effects should resolve within 5 days of implantation. There is some evidence that deslorelin implants can suppress pi-tuitary FSH secretion and decrease follicular development in subse-quent diestrus, leading to a prolonged interovulatory period. Some clinicians (see the dose recommendation by Mc Cue 2003, below), recommend removing the implant to negate this possibility. Reproductive/Nursing Safety Abnormalities in foal viability or behavior related to the use of deslorelin have not been observed in foals born to treated mares. Overdosage/Acute Toxicity Overdosage is unlikely. If inadvertent administration of additional implant is done, it should be removed upon detection if within 96 hours of implant. Drug Interactions No specific interactions noted laboratory Considerations None noted Doses HORSES:T! For induction of ovulation:a) If follicle is greater than 30 mm in diameter (as determined by rectal palpation or ultrasound), and breeding is to take place within 48 hours, place one implant subcutaneously in the neck. Implant site should be midway between head and shoulder over the muscle mass of the neck and away for subcutaneous nerves and vessels. Thoroughly disinfect site of implant. Insert the entire length of needle SC and fully depress the implanter plunger. Slowly withdraw needle while pressing skin at injection site. Examine implanter to as-sure that implant has been administered. Do not reuse im-planter. Implant will be absorbed with time. (Package insert; Ovuplant®) b) As above, but because interovulatory interval may be pro-longed if implant is left in the mare, remove after approxi-mately 48 hours. Alternative dosing/removal method: Restrain mare and briefly wash vulva with soap and water and then dry. One m L of lidocaine is infused into the edge of the vulva. The im-plant is inserted just beneath the epithelium in the blocked area. When the lidocaine is absorbed, the implant can be pal-pated. After ovulation, the implant can be gently “squeezed” out of the original opening created by the implant device. No treatment is required at the site after removal of the implant. (Mc Cue 2003a) monitoring None required T! | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
260 DESm OPRESSIN ACETATE Chemistry/Synonyms Deslorelin acetate is a synthetic gonadotropin-releasing hormone (Gn RH, gonadorelin) analog. It is a nonapeptide and has chemi-cal modifications in the amino aide composition at positions 6 and 9/10. Storage/Stability Deslorelin implants should be stored refrigerated (2-8°C, 36-46°F). Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None in the USA In Canada: Deslorelin 2. 1 mg cylindrical implant with implanter; 5 per box Ovuplant® (Wyeth. Approved for ovulation induction in mares. Not for use in horses intended for food. The FDA may allow legal importation of this medication for com-passionate use in animals; for more information, see the Instructions for Legally Importing Drugs for Compassionate Use in the USA found in the appendix. HUm ANl Ab El ED PRODUCTS: None desmopressin Acet Ate (des-moe-press-in) Stimate®, DDAVP® h Orm Onal agent Prescriber Highlights Synthetic vasopressin analogue used to treat diabetes T T insipidus & Von Willebrand's disease (limited usefulness) Contraindications: Hypersensitivity to desmopressin, type T T IIB or platelet-type (pseudo) Von Willebrand's (German shorthair pointers?) Use caution in patients susceptible to thrombosis T T Adverse Effects: Eye irritation after conjunctival adminis-T T tration; hypersensitivity possible Overdoses can cause fluid retention/hyponatremia T T Uses/Indications Desmopressin has been found to be useful in the treatment of cen-tral diabetes in sipidus in small animals. It may be useful in treat-ing Von Willebrand's disease, but its short duration of activity (2- 4 hours) in this condition, resistance development, and expense limit its usefulness for this disorder. Desmopressin may be useful periop-eratively to reduce lymph node involvement and metastatic disease in canine mammary gland cancer. Pharmacology/Actions Desmopressin is related structurally to arginine vasopressin, but it has more antidi uretic activity and less vasopressor properties on a per weight basis. Desmopressin increases water reabsorption by the collecting ducts in the kidneys, thereby increasing urine osmolality and decreas ing net urine production. Therapeutic doses do not di-rectly affect either urinary sodium or potassium excretion. Desmopressin causes a dose-dependent increase in plasma factor VIII and plasminogen factor and also causes smaller increases in fac-tor VIII-related antigen and ristocetin cofactor activities. Pharmacokinetics Because desmopressin is destroyed in the GI tract, it usually is given parenterally or topically. Oral tablets have been used in those dogs that cannot tolerate ophthalmic administration, but bioavailability is very low. In humans, intranasal administration is commonly used, while in veterinary medicine topical administration to the conjunc-tiva is preferred. The onset of antidiuretic action in dogs usually oc-curs within one hour of administration, peaks in 2-8 hours, and may persist for up to 24 hours. Dis tribution characteristics of des-mopressin are not well described, but it does enter maternal milk. The metabolic fate is also not well understood. T erminal half lives in humans after IV administration are from 0. 4-4 hours. Contraindications/Precautions/Warnings Desmopressin is contraindicated in patients hypersensitive to it. It should not be used for treatment of type IIB or platelet-type (pseu-do) Von Willebrand's disease as platelet-aggregation and thrombo-cytopenia may occur. German shorthair pointers apparently can have this type of v WD. Desmopressin should be used with caution in patients susceptible to thrombotic events. When desmopressin is used to stimulate von Willebrand factor, with repeated administration tachyphylaxis (increasing lack of ef-ficacy) will occur to a variable extent within 24 hours. Adverse Effects Side effects in small animals apparently are uncommon. Occasionally eye irritation may occur after conjunctival administration. Hypersensitivity reactions are possible. Humans using the drug have complained about increased headache frequency. Reproductive/Nursing Safety Safe use during pregnancy has not been established; however safe doses of up to 125 times the av erage human antidiuretic dose have been given to rats and rabbits without demonstration of fetal harm. 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. ) Desmopressin is likely safe to use during nursing. Overdosage/Acute Toxicity Oral doses of 0. 2 mg/kg/day have been administered to dogs for 6 months without any significant drug-related toxicities reported. Dosages that are too high may lead to fluid retention and hypona-tremia; dosage reduction and fluid restriction may be employed to treat. Adequate monitoring should be performed. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving desmopressin and may be of significance in veterinary patients: CHl ORPROPAm IDE, Fl UDROCORTISONE, UREA T! : May enhance the an-tidiuretic effects of desmopressin laboratory Considerations See Monitoring Parameters | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DESm OPRESSIN ACETATE 261 Doses Note : When doses listed below use “drops” of the nasal solution they are referencing the 0. 1 mg/m L product and NOT the 1. 5 mg/m L product (Stimate®). Do not confuse the two. DOg S:T! a) One drop placed twice daily in the conjunctival sac suffi-ciently controls polyuria in most dogs with central DI. Using one drop three times a day usually returns urine production to normal. (Rijnberk 2005) b) For treatment of diabetes insipidus (central): 1-4 drops of the intranasal solution in the conjunctival sac once to twice daily; may use intranasal solution parenterally at 2-5 mcg SC once to twice daily (Nichols 2000) c) For treatment of complete and partial central diabetes insipi-dus: 1-4 drops of the intranasal solution in the conjunctival sac once a day to twice a day (Behrend 2003b) d) 1-2 drops into the conjunctival sac or 0. 01-0. 05 m L SC once a day to twice a day (Bruyette 2002b) e) As a trial in place of water deprivation test: one-half to one 0. 1 or 0. 2 mg DDA VP tablet PO q8h or 1-4 drops of nasal spray from an eye dropper into the conjunctival sac every 12 hours for 5-7 days. If central DI, owners should notice a decrease in PU/PD by the end of treatment period. Increase in urine specific gravity by 50% or more, compared with pre-treatment values, also support diagnosis of central DI. (Nel-son 2002b) For treatment of Von Willebrand's disease:a) 1 microgram/kg SC gives a duration of action of 3-4 hours; repeated dosages within 24 hours do not prolong response time (Brooks 1994) b) May be particularly useful to help prevent or control bleed-ing in association with surgery. Intranasal product is given subcutaneously at 1-4 mcg/kg. Onset of activity occurs in 30 minutes and duration of effect is approximately 2 hours. (Carr and Panciera 2000) c) For preoperative prophylaxis:1 mcg/kg SC one-half hour before surgery. Close monitoring needed to determine ex-tent and duration of response. Transfusion should be readily available. Desmopressin not effective for treatment or pre-operative prophylaxis of severe Types 2 and 3 v WD. (Brooks 2003) CATS:T! a) T o help differentiate central diabetes insipidus from the nephrogenic form: 1 drop into the conjunctival sac twice daily for 2-3 days; a dramatic reduction in water intake or a 50% or greater increase in urine concentration gives strong evidence for a deficit in ADH pro duction. For treatment of central DI: 1-2 drops into the conjunctival sac once or twice a day; duration of activity is 8-24 hours. (Bruyette 1991) b) For treatment of diabetes insipidus (central): 1- 4 drops of the intranasal solution in the conjunctival sac once to twice daily; may use intranasal solution parenterally at 2-5 mcg SC once to twice daily (Nichols 2000) HORSES: T! a) For diagnosis of diabetes insipidus: 20 mcg IV (Barnes, Schott II et al. 2002) monitoring For Central DI: Serum electrolytes T! Urine osmolality and/or urine volume T! For Von Willebrand's disease: Bleeding times T! Client Information Keep solutions refrigerated whenever possible. T! Instruct clients on the impor tance of compliance with adminis-T! tering this drug as directed. It is a treatment, not a cure for the condition. Clients should be counseled on the expense associated with using T! this drug long-term. Chemistry/Synonyms A synthetic polypeptide related to arginine vasopressin (antidiuret-ic hormone), desmo pressin acetate occurs as a fluffy white powder with a bitter taste. The commercially available nasal solution has HCl added and the p H is approximately 4. This preparation also contains chlorob utonal 0. 5% as a preservative. Desmopressin Acetate may also be known as: 1-Deamino-8-D-Arginine Vasopressin, DDA VP®, Concentraid®, D-Void®, Defirin®, Desmogalen®, Desmospray®, Desmotabs®, Emosint®, Minirin®, Minirin/DDA VP®, Minrin®, Minurin®, Nocutil®, Octim ®, Octostim®, Presinex®, or Stimate®. Storage/Stability The nasal solution should be refrigerated (2-8°C). It has an expira-tion date of one year after manufacture. While the nasal solution should be stored in the refrigerator, it is stable at room tempera-ture for 3 weeks in the unopened bottle. The product for in jection should be stored refrigerated (4°C); do not freeze. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Desmopressin Acetate Nasal Solution: 0. 1 mg/m L (10 mcg/spray) in 5 m L nasal pump dispenser; Desmopressin Acetate (Bausch and Lomb); (Rx); 0. 1 mg/m L (0. 1 mg equals approx 400 units arginine vasopressin) in nasal spray pump: 7. 5 mg Na Cl/m L in 5 m L bottle (with 1. 7 mg citric acid monohydrate, 3 mg disodium phosphate dihyrdrate, 0. 2 mg benzalkonium chloride solution—50% per m L); & Rhinal tube delivery system: 9 mg Na Cl/m L (with 5 mg chlo-robutanol/m L) in 2. 5 m L vials; DDA VP® (Aventis); (Rx) Desmopressin Acetate Nasal Spray: 1. 5 mg/m L (150 mcg/spray) in 9 mg Na Cl/m L (with 5 mg chlorobutanol per m L) in 2. 5 m L bottle; Stimate® (ZLB Behring); (Rx); 0. 1 mg/m L (10 mcg/spray) in 5 m L (with 5 mg chlorobutanol, 9 mg sodium chloride & hydrochloric acid/m L); Minirin® (Ferring); (Rx) Desmopressin Acetate Injection: 4 mcg/m L (9 mg Na Cl/m L) in 1 m L single-dose amps and 10 m L multiple dose vials; DDA VP® (Aventis); (Rx); generic; (Rx) Desmopressin Acetate Tablets: 0. 1 mg & 0. 2 mg; DDA VP® (Aven-tis); Desmopressin Acetate (T eva); (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
262 DESOxy CORTICOSTERONE PIVAl ATE desoxycorticosterone piv Al Ate docp (de-sox-ee-kor-ti-kost-er-ohn pih-vah-late) Percorten-V® mineral Oc Ortic Oid Prescriber Highlights Parenteral mineralocorticoid used to treat Addison's in T T dogs/cats Relative contraindications: congestive heart failure, se-T T vere renal disease, or edema; Caution: pregnancy Addison's patients must receive glucocorticoid supple-T T mentation in periods of high stress/illness May cause irritation at injection site T T Adjust dosage based upon monitoring parameters T T Uses/Indications DOCP is indicated for the parenteral treatment of adrenocortical in-sufficiency in dogs. It is also used in an extra-label manner in cats. Pharmacology/Actions Desoxycorticosterone pivalate (DOCP) is a long-acting mineralo-corticoid agent. The site of action of mineralocorticoids is at the renal distal tubule where it increases the absorption of sodium. Mineralocorticoids also enhance potassium and hydrogen ion ex-cretion. T o be effective, mineralocorticoids require a functioning kidney. Pharmacokinetics Little information is available. It is injected IM (or subcutaneously) as a micro crystalline depot for slow dissolution into the circulation. DOCP usually has a duration of action in dogs for 21-30 days after injection. Contraindications/Precautions/Warnings The drug is contraindicated in dogs suffering from congestive heart failure, severe renal disease, or edema. Because some an imals may be more (or less) sensitive to the ef-fects of the drug, “cookbook” dosing without ongoing monitoring is inappropriate. Some animals may require additional supplementa-tion with a glucocor ticoid agent on an ongoing basis that may cause polydipsia, polyuria, or polyphagia if doses are too high. All animals with hypoadrenocorticism should receive additional glucocorticoids (2-10 times basal) during periods of stress or acute illness. Do not administer DOCP IV; acute collapse and shock may re-sult. If given IV, treat immediately for shock with IV fluids and glu-cocorticoids. Adverse Effects Occasionally, irritation at the site of injection may occur. Adverse ef fects of DOCP are generally a result of excessive dosage (see Overdosage below). Reproductive/Nursing Safety The manufacturer states that the drug should not be used in preg-nant dogs as safe use during preg nancy has not been established. Use in pregnant animals only when the potential benefits outweigh the risks. DOCP should be safe for offspring when administered to nurs-ing dams. Overdosage/Acute Toxicity Overdosage may cause polyuria, polydipsia, hypernatremia, hyper-tension, edema, and hypokalemia. Cardiac enlargement is possible with prolonged overdoses. Excessive weight gain may be indica-tive of fluid retention secondary to sodium retention. Elec trolytes should be aggressively monitored and potassium may need to be supplemented. Discontinue the drug in patients until clinical signs associated with overdosage have re solved and then restart the drug at a lower dosage. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving DOCP and may be of significance in veterinary patients: Am PHOTERICIN T! b: Patients may develop hypokalemia if mineralo-corticoids are administered con comitantly with amphotericin B ASPIRINT! : DOCP may reduce salicylate levels DIg Ox INT! : Because DOCP may cause hypokalemia, it should be used with caution and increased monitor ing when used in pa-tients receiving digitalis glycosides INSUl INT! : Potentially, DOCP could increase the insulin require-ments of diabetic patients POTASSIUmDEPl ETINg DIURETICST! (e. g., furosemide, thiazides ): Pa-tients may develop hypokalemia if mineralocorticoids are admin-istered con comitantly with potassium-depleting diuretics; as di-uretics can cause a loss of sodium, they may counteract the effects DOCP Doses DOg S:T! Note : Dosage requirements are variable and should be individual-ized to the patient. For hypoadrenocorticism:a) 2. 2 mg/kg IM every 25 days (Label information; Percorten ®-V) b) Initially, inject 2. 2 mg/kg IM or SC every 25 days. Reevaluate at 12 and 25 days after initial injection. If hyponatremia and/or hyperkalemia are noted at 12 days, increase dose by 10%. If they are noted at 25 days (but not on day 12), shorten dosing interval by 2 days. (Reusch 2000) c) 1. 5-2. 2 mg/kg IM q20-30 days (Lorenz and Melendez 2002c) d) Initially, 2. 2 mg/kg IM q25 days. If electrolytes remain in nor-mal range at 30 days, reduce dose by 10% a month. In our clinic, we have used a dose of DOCP as low as 1 mg/kg q30 days with good control of hypoadrenocorticism. (Scott-Mon-crieff 2006a) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DETOm IDINE HCl 263 CATS:T! For maintenance therapy of hypoadrenocorticism: a) 2. 2 mg/kg IM every 25 days plus prednisolone (0. 25-1 mg/ cat PO twice daily; if daily oral dosing not feasible, may give 10 mg of methylprednisolone acetate once a month IM) (Re-usch 2000) b) 10-12. 5 mg (total dose) IM per month. Adjust dose based-upon follow-up serum electrolyte concentrations monitored every 1 -2 weeks during initial maintenance period. Normal electrolyte values 2 weeks following injection, suggests ad-equate dosing, but does not provide information regarding duration of action. Prednisone at 1. 25 mg PO once a day or IM methylprednisolone acetate 10 mg once a month can pro-vide long-term glucocorticoid supplementation. (Bruyette 2002c) monitoring Serum electrolytes, BUN, creatinine; initially every 1T! -2 weeks, then once stabilized, every 3-4 months Weight, PE for edema T! Client Information Clients should be familiar with the symptoms associated with T! both hypoad renocorticism (e. g., weakness, depression, anorexia, vomiting, diarrhea, etc. ) and DOCP overdosage (e. g., edema) and report these to the veterinarian immediately. If client is injecting the drug at home, instruct in proper tech-T! nique for IM administration. Vial should be shaken vigorously to suspend the macrocrystals. Chemistry/Synonyms A mineralocorticoid, desoxycorticosterone pivalate (DOCP) occurs as a white or creamy white powder that is odorless and stable in air. It is practically insoluble in water, slightly soluble in alcohol and vegetable oils. The injectable product is a white aqueous suspension and has a p H between 5-8. 5. Desoxycorticosterone pivalate may also be known as: deoxycor-ticosterone pivalate, deoxycorticosterone trimethyl-acetate, deoxy-cortone pivalate, deoxycortone trimethylacetate, desoxycorticoster-one pivalate, desoxycorticosterone trimethyl-acetate, Cortiron®, o r Percorten-V®. Storage/Stability/Compatibility Store the injectable suspension at room temperature and protect from light or freezing. Do not mix with any other agent. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Desoxycorticosterone Pivalate Injectable Suspension: 25 mg/m L in 4 m L vials; Percorten-V® (Novartis); (Rx). Approved for use in dogs. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Nonedetomidine hcl (de-toe-ma-deen) Dormosedan® Prescriber Highlights Alpha T T 2 sedative analgesic used primarily in horses Contraindications: Heart block, severe coronary, cerebro-T T vascular, or respiratory disease, chronic renal failure Caution: Horses with endotoxic or traumatic shock or T T approaching shock, advanced hep atic or renal disease; stress due to temperature extremes, fatigue, or high alti-tude; pa tients treated for intestinal impactions; with sus-pected colic as it may mask abdominal pain or changes in respiratory & cardiac rates May respond ( T T i. e., kick) to external stimuli even after fully sedated; use caution, opioids may temper Adverse Effects: Initial blood pressure increase, then bra-T T dycardia/heart block, piloerection Uses/Indications At present, detomidine is only approved for use as a sedative analge-sic in horses, but it has been used clinically in other species. Pharmacology/Actions Detomidine, like xylazine, is an alpha 2-adrenergic agonist that produces a dose-de pendent sedative and analgesic effect, but it also has cardiac and respiratory effects. For more infor mation, re-fer to the xylazine monograph or the adverse effects section below. Detomidine is approximately 50-100 times as potent as xylazine. Pharmacokinetics Detomidine is well absorbed after oral administration, but is used only par enterally currently. The drug is apparently rapidly distrib-uted into tissues, including the brain after parenteral administra-tion and is extensively metabolized and then excreted primarily into the urine. Peak sedative actions can range from 5-20 minutes post injection in horses. Contraindications/Precautions/Warnings Detomidine is contraindicated in horses with preexisting A V or SA heart block, severe coronary insufficiency, cerebrovascular disease, res piratory disease or chronic renal failure. Use cautiously in ani-mals with endotoxic or traumatic shock or approaching shock, and advanced hepatic or renal disease. Horses who are stressed due to temperature extremes, fatigue, or high altitude should be given the drug carefully. Because this drug may inhibit gastrointestinal mo-tility, use with prudence in patients treated for intestinal impac-tions. In horses with suspected colic, the use of detomidine analge-sia should be used cautiously as it may mask abdominal pain and conceal changes in respiratory and cardiac rates, thereby making diagnosis more difficult. Although animals may appear to be deeply sedated, some may respond (kick, etc. ) to external stim uli; use appropriate caution. The addition of opioids (e. g., butorphanol) may help temper this effect. The manufacturer recommends allowing the horse to stand quietly for 5 minutes prior to injection and for 10-15 minutes af-ter injection to improve the effect of the drug. After administering detomi dine, protect the animal from temperature extremes. Adverse Effects Detomidine can cause an initial rise in blood pressure that is then followed by bradycardia and heart block. Atropine at 0. 02 mg/kg | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
264 DETOm IDINE HCl IV has been successfully used to prevent or correct the bradycardia that may be seen when the detomidine is used at labeled dosages. In addition, piloerection, sweating, ataxia, salivation, slight muscle tremors, and penile prolapse may all be noted after injection. When compared to xylazine, detomidine causes more pro-nounced bradycardia and bradyarrhythmias. Because the sedative and muscle-relaxing effects of detomidine in horses can persist for up to 90 minutes, it may influence the quality of recovery and con-tribute to post-anesthesia ataxia. Reproductive/Nursing Safety The manufacturer states that “Information on the possible effects of detomidine HCl in breeding horses is limited to uncontrolled clinical reports; therefore, this drug is not recommended for use in breeding animals. ” No other information was located. Overdosage/Acute Toxicity The manufacturer states that detomidine is tolerated by horses at doses 5X (0. 2 mg/kg) the high dose level (0. 04 mg/kg). Doses of 0. 4 mg/kg given daily for 3 consecutive days produced microscopic foci of myocardial necrosis in 1 of 8 horses tested. Doses of 10-40X rec-ommended can cause severe respiratory and cardiovascular changes that can become irreversible and cause death. Y ohimbine or atipam-ezole could be used to reverse some or all of the effects of the drug. Atipamezole, at a dose of 50-100 mcg/kg has been successfully used to treat inadvertent overdoses of detomidine in horses. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving detomidine and may be of significance in veterinary patients: Al PHA2 Ag ONISTS T!, OTHER (e. g., xylazine, medetomidine, romifidine, clonidine and including epinephrine ): Not recommended to be used together with detomidine as effects may be additive ANESTHETICS, OPIATES, SEDATIVE/Hy PNOTICST! : Effects may be addi-tive; dosage reduction of one or both agents may be required; po-tential for increased risk for arrhythmias when used in combina-tion with thiopental, ketamine or halothane PHENOTHIAz INEST! (e. g., acepromazine ): Severe hypotension can result SEDATIVES OR ANAlg ESICS, OTHER T! : The manufacturer warns to use with extreme caution in combination with other sedative or an-algesic drugs SUl FONAm IDES, POTENTIATEDT! (e. g., trimethoprim/sulfa ): The manu-facturer warns against using this agent with intravenous potenti-ated sulfonamides (e. g., trimethoprim/sulfa) as fatal dysrhythmias may occur Doses HORSES:T! (Note : ARCI UCGFS Class 3 Drug) For sedation/analgesia ( CAUTION : Do not confuse mcg/kg with mg/kg doses):a) 20-40 micrograms/kg (0. 02-0. 04 mg/kg) IV or IM (IV only for analgesia). Effects gen erally occur within 2-5 minutes. Lower dose will generally provide 30-90 minutes of se dation and 30- 45 minutes of analgesia. The higher dose will gener-ally provide 90-120 minutes of sedation and 45-75 minutes of analgesia. Allow animal to rest quietly prior to and after injection. (Package insert; Dormosedan®—SKB) b) For horses with marked abdominal pain that are either not candidates for exploratory surgery or must be transported long distances for surgery: 0. 01-0. 02 mg/kg (10-20 mcg/kg) IV or IM (Moore 1999) c) Detomidine at 0. 01-0. 02 mg/kg IV or IM with or without butorphanol (0. 02-0. 03 mg/kg) (Taylor 1999) d) For adjunctive treatment of moderate pain: 0. 03-0. 04 mg/kg IV For caudal epidural analgesia: 0. 06 mg/kg, given between S4-S5; duration of analgesia is 2- 3 hours or detomidine 0. 03 mg/kg with morphine (0. 2 mg mg/kg) given between S1-L6; duration of analgesia is >6 hours (Muir 2004) e) For oral administration when horse is not amenable to injec-tions: 0. 06 mg/kg PO; profound sedation occurs in about 45 minutes (Hubbell 2006) f) As a CRI for standing chemical restraint and analgesia: Two protocols have been described: 1) Loading dose of 7. 5 mcg/kg IV bolus, followed by a CRI rate of 0. 6 mcg/kg/minute for the first 15 minutes; after this CRI rate is halved every 15 minutes. In many cases did not provide adequate analgesia alone and needed to be supple-mented by local anesthetics, epidural analgesia, or supple-mental detomidine and/or butorphanol. Average duration of procedures was 40 minutes. 2) Loading dose of 8. 4 mcg/kg IV bolus, then 0. 5 mcg/kg/ minute for 15 minutes, then 0. 3 mcg/kg/minute for 15 min-utes, then 0. 15 mcg/kg/minute thereafter. A butorphanol CRI was used if additional sedation and analgesia was required. (Mogg 2006) CATTl E:T! a) For sedation/analgesia: 30-60 micrograms/kg (0. 03-0. 06 mg/kg) IV or IM (Not approved) (Alitalo 1986) b) For analgesia: 0. 01 mg/kg IV; short (1/2 hour) duration of action. Appropriate withdrawal times are: Milk = 72 hours; Slaughter = 7 days. (Walz 2006b) SHEEP, g OATS:T! a) For anesthesia: Detomidine at 0. 01 mg/kg IM, followed by propofol at 3-5 mg/kg IV. For analgesia: 0. 005-0. 05 mg/kg IV or IM q3-6 hours (once) (Haskell 2005b) ll Am AS, Al PACAS:T! a) For analgesia: 0. 005-0. 05 mg/kg IV or IM q3-6 hours (once) (Haskell 2005b) b IRDS:T! a) For sedation/analgesia: 0. 3 mg/kg IM; limited data available on duration of effect, adverse ef fects, etc. (Clyde and Paul-Murphy 2000) monitoring Level of sedation, analgesia T! Cardiac rate/rhythm; blood pressure if indicated T! Client Information This drug should be used in a professionally supervised setting by T! individuals familiar with its properties. Chemistry/Synonyms An imidazoline derivative alpha 2-adrenergic agonist, detomidine HCl occurs as a white crystalline substance that is soluble in water. Detomidine HCl may also be known as: demotidini hydrochlo-ridum, MPV-253-AII, or Dormosedan®. Storage/Stability Detomidine HCl for injection should be stored at room tempera ture (15-30°C) and protected from light. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DEx Am ETHASONE 265 Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Detomidine HCl for Injection: 10 mg/m L in 5 and 20 m L vials; Dormosedan® (Pfizer); (Rx). Approved for use in mature horses and yearlings. The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: None dex Ameth Asone dex Ameth Asone sodium phosph A te (dex-a-meth-a-zone) Azium®, Dexasone® gluc Oc Ortic Oid Prescriber Highlights Injectable, oral & ophthalmic glucocorticoid T T Long acting; 30X more potent than hydrocortisone; no T T mineralocorticoid activity If using for therapy, goal is to use as much as is required T T & as little as possible for as short an amount of time as possible Primary adverse effects are “Cushingoid” in nature with T T sustained use Many potential drug & lab interactions T T Uses/Indications Glucocorticoids have been used in an attempt to treat practically every malady that afflicts man or animal, but there are three broad uses and dosage ranges for use of these agents. 1) Replacement of glucocorticoid activity in patients with adrenal insufficiency, 2) as an antiinflammatory agent, and 3) as an immunosuppressive. Among some of the uses for glucocorticoids include treatment of: endocrine conditions (e. g., adrenal insufficiency), rheumatic diseases (e. g., rheumatoid arthritis), collagen diseases (e. g., systemic lupus), aller-gic states, respiratory diseases (e. g., asthma), dermatologic diseases (e. g., pemphigus, allergic dermatoses), hematologic disorders (e. g., thrombocytopenias, autoimmune hemolytic anemias), neoplasias, nervous system disorders (increased CSF pressure), GI diseases (e. g., ulcerative colitis exacerbations), and renal diseases (e. g., nephrotic syndrome). Some glucocorticoids are used topically in the eye and skin for various conditions or are injected intra-articularly or intra-lesionally. The above listing is certainly not complete. For specific dosages and indications refer to the Doses section. High dose dexamethasone use for shock or CNS trauma is con-troversial; recent studies have not demonstrated significant benefit and it actually may cause increased deleterious effects. Pharmacology/Actions Glucocorticoids have effects on virtually every cell type and system in mammals. An overview of the effects of these agents follows: CARDIOVASCUl AR Sy STEm: Glucocorticoids can reduce capillary per-meability and enhance vasocon striction. A relatively clinically in-significant positive inotropic effect can occur after glucocorticoid administration. Increased blood pressure can result from both the drugs' vasoconstrictive properties and increased blood volume that may be produced. CEll S: Glucocorticoids inhibit fibroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lympho-cytes and the cellular response to mediators of inflammation. Glucocor ticoids stabilize lysosomal membranes. CNS/AUTONOm IC NERVOUS Sy STEm: Glucocorticoids can lower seizure threshold, alter mood and behavior, diminish the response to pyro-gens, stimulate appetite and maintain alpha rhythm. Glu cocorticoids are necessary for normal adrenergic receptor sensitivity. ENDOCRINE Sy STEm: When animals are not stressed, glucocorti-coids will suppress the release of ACTH from the anterior pituitary, thereby reducing or preventing the release of endogenous corticos-teroids. Stress factors (e. g., renal disease, liver disease, diabetes) may sometimes nullify the suppress ing aspects of exogenously admin-istered steroids. Release of thyroid-stimulating hormone (TSH), fol licle-stimulating hormone (FSH), prolactin, and luteinizing hor-mone (LH) may all be reduced when glucocorticoids are adminis-tered at pharmacological doses. Conversion of thyroxine (T 4) to triiodothy ronine (T 3) may be reduced by glucocorticoids; plasma levels of parathyroid hormone increased. Glucocorticoids may in-hibit osteoblast function. Vasopressin (ADH) activity is reduced at the renal tubules and diuresis may occur. Glucocorticoids inhibit insulin binding to insulin-receptors and the post-receptor effects of insulin. HEm ATOPOIETIC Sy STEm: Glucocorticoids can increase the numbers of circulating platelets, neu trophils and red blood cells, but platelet aggregation is inhibited. Decreased amounts of lymphocytes (pe-ripheral), monocytes and eosinophils are seen as glucocorticoids can sequester these cells into the lungs and spleen and prompt de-creased release from the bone marrow. Removal of old red blood cells becomes diminished. Glucocorticoids can cause involution of lymphoid tissue. g I TRACT AND HEPATIC Sy STEm: Glucocorticoids increase the secretion of gastric acid, pepsin, and trypsin. They alter the structure of mu-cin and decrease mucosal cell proliferation. Iron salts and cal cium absorption are decreased while fat absorption is increased. Hepatic changes can include increased fat and glycogen deposits within he-patocytes, increased serum levels of alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT). Significant increases can be seen in serum alkaline phosphatase levels. Glucocorticoids can cause minor increases in BSP (bromosulfophthalein) retention time. Imm UNE Sy STEm (also see Cells and Hematopoietic System): Gluco-corticoids can decrease circulat ing levels of T-lymphocytes; inhibit lymphokines; inhibit neutrophil, macrophage, and monocyte mi-gration; reduce production of interferon; inhibit phagocytosis and chemotaxis; antigen processing; and diminish intracellular killing. Specific acquired immunity is affected less than nonspecific im-mune re sponses. Glucocorticoids can also antagonize the comple-ment cascade and mask the clinical signs of infection. Mast cells are decreased in number and histamine synthesis is suppressed. Many of these ef fects only occur at high or very high doses and there are species differences in response. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
266 DEx Am ETHASONE m ETAb Ol IC EFFECTS: Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body (e. g., abdomen) and adipose tissue can be redistributed away from the extremities to the trunk. Fatty acids are mobilized from tissues and their oxidation is increased. Plasma levels of triglycerides, cholesterol, and glycerol are increased. Protein is mobilized from most areas of the body (not the liver). m USCUl OSKEl ETAl: Glucocorticoids may cause muscular weakness (also caused if there is a lack of glucocorticoids), atrophy, and os-teoporosis. Bone growth can be inhibited via growth hormone and somatomedin inhibition, increased calcium excretion and inhibi-tion of vitamin D activation. Resorption of bone can be enhanced. Fibrocartilage growth is also inhibited. OPHTHAlm IC: Prolonged corticosteroid use (both systemic or topi-cally to the eye) can cause increased intraocular pressure and glau-coma, cataracts, and exophthalmos. RENAl, Fl UID, & El ECTROly TES: Glucocorticoids can increase potas-sium and calcium excretion, sodium and chloride reabsorption, and extracellular fluid volume. Hypokalemia and/or hypocalcemia rarely occur. Diuresis may develop following glucocorticoid ad-ministration. SKIN: Thinning of dermal tissue and skin atrophy can be seen with glucocorticoid therapy. Hair fol licles can become distended and alo-pecia may occur. Pharmacokinetics Pharmacokinetics of dexamethasone do not translate into pharma-cologic effect. The half-life of dexamethasone in dogs is about 2- 5 hours, but biologic activity can persist for 48 hours or more. Contraindications/Precautions/Warnings Because dexamethasone has negligible mineralocorticoid effect, it should generally not be used alone in the treatment of adrenal in-sufficiency. Do not administer the propylene glycol base injectable product rapidly intravenously; hypotension, collapse, and hemolytic anemia can occur. Many clinicians only use dexamethasone sodium phos-phate when giving the drug intravenously. Systemic use of glucocorticoids is generally considered contrain-dicated in systemic fungal infections (unless used for replacement therapy in Addison's), when administered IM in patients with idio-pathic thrombocytopenia and in patients hypersensitive to a partic-ular compound. Use of sustained-release injectable glucocorticoids is considered contraindicated for chronic corticos teroid therapy of systemic diseases. Animals that have received glucocorticoids systemically other than with “burst” therapy, should be tapered off the drugs. Patients who have received the drugs chronically should be tapered off slowly as endogenous ACTH and corticosteroid function may return slow-ly. Should the animal undergo a “stressor” (e. g., surgery, trauma, ill-ness, etc. ) during the tapering process or until normal adrenal and pituitary function resume, additional glucocorticoids should be ad-ministered. Adverse Effects Adverse effects are generally associated with long-term administra-tion of these drugs, especially if given at high dosages or not on an alternate day regimen. Effects gener ally are manifested as clinical signs of hyperadrenocorticism. Glucocorticoids can retard growth in young animals. Many of the potential effects, adverse and other-wise, are outlined above in the Pharmacology section. In dogs, polydipsia (PD), polyphagia (PP) and polyuria (PU), may all be seen with short-term “burst” therapy as well as with alternate-day maintenance therapy on days when giving the drug. Adverse effects in dogs can include: dull, dry haircoat, weight gain, panting, vomiting, diarrhea, ele vated liver enzymes, pancreatitis, GI ulceration, lipidemias, activation or worsening of diabetes mel-litus, muscle wasting, and behavioral changes (depression, lethargy, viciousness). Discontinuation of the drug may be necessary; chang-ing to an alternate steroid may also alleviate the problem. With the exception of PU/PD/PP, adverse effects associated with antiinflam-matory therapy are relatively uncommon. Adverse effects associated with immunosuppressive doses are more common and, po tentially, more severe. Cats generally require higher dosages than dogs for clinical effect, but tend to develop fewer ad verse effects. Occasionally, polydipsia, polyuria, polyphagia with weight gain, diarrhea, or depres sion can be seen. Long-term, high dose therapy can lead to “Cushingoid” ef-fects, however. Administration of dexamethasone or triamcinolone may play a role in the development of laminitis in horses. Reproductive/Nursing Safety Corticosteroid therapy may induce parturition in large animal spe-cies during the latter stages of pregnancy. In humans, the FDA cat-egorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no ad-equate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) 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. ) Overdosage/Acute Toxicity Glucocorticoids when given short-term are unlikely to cause sig-nificant harmful effects, even in massive dosages. One incidence of a dog developing acute CNS effects after accidental ingestion of glucocorticoids has been reported. Should clinical signs occur, use supportive treatment if required. Chronic usage of glucocorticoids can lead to serious adverse ef-fects. Refer to Adverse Effects above for more information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dexamethasone and may be of significance in veterinary patients: Am PHOTERICIN b T! : Administered concomitantly with glucocorti-coids may cause hypokalemia ANTICHOl INESTERASE Ag ENTST! (e. g., pyridostigmine, neostigmine, etc. ): In patients with myasthenia gravis, concomitant glucocorticoid and anticholinesterase agent administration may lead to profound muscle weakness. If possi ble, discontinue anticholinesterase med-ication at least 24 hours prior to corticosteroid administration ASPIRINT! : Glucocorticoids may reduce salicylate blood levels b ARb ITURATEST! : May increase the metabolism of glucocorticoids and decrease dexamethasone blood levels Cy Cl OPHOSPHAm IDET! : Glucocorticoids may also inhibit the hepatic metabolism of cyclophos phamide; dosage adjustments may be required Cy Cl OSPORINET! : Concomitant administration of glucocorticoids and cyclosporine may increase the blood levels of each, by mutu-ally inhibiting the hepatic metabolism of each other; the clinical significance of this interaction is not clear DIAz EP Am T! : Dexamethasone may decrease diazepam levels | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DEx Am ETHASONE 267 DIURETICS, POTASSIUmDEPl ETINg T! (e. g., spironolactone, triamterene ): Administered concomitantly with glucocorticoids may cause hy-pokalemia EPHEDRINET! : May reduce dexamethasone blood levels and interfere with dexamethasone suppression tests INDOm ETHACINT! : Can cause false negative test results in the dexam-ethasone suppression test INSUl INT! : Insulin requirements may increase in patients receiving glucocorticoids KETOCONAz Ol E AND OTHER Az Ol E ANTIFUNg Al S T! : May decrease the metabolism of glucocorticoids and increase dexamethasone blood levels; ketoconazole may induce adrenal insufficiency when glucocorticoids are withdrawn by inhibiting adrenal cor-ticosteroid synthesis m ACROl IDE ANTIb IOTICST! (erythromycin, clarithromycin ): May de-crease the metabolism of glucocorticoids and increase dexam-ethasone blood levels m ITOTANET! : May alter the metabolism of steroids; higher than usu-al doses of steroids may be neces sary to treat mitotane-induced adrenal insufficiency NSAIDST! : Administration of ulcerogenic drugs with gluco corticoids may increase the risk of gastrointestinal ulceration PHENy TOINT! : May increase the metabolism of glucocorticoids and decrease dexamethasone blood levels RIFAm PINT! : May increase the metabolism of glucocorticoids and decrease dexamethasone blood levels VACCINEST! : Patients receiving corticosteroids at immunosuppres-sive dosages should generally not receive live at tenuated-virus vaccines as virus replication may be augmented; a diminished immune response may occur after vaccine, toxoid, or bacterin administration in patients receiving glucocorticoids laboratory Considerations Glucocorticoids may increase T! serum cholesterol Glucocorticoids may increase T! urine glu cose levels Glucocorticoids may decrease T! serum potassium Glucocorticoids can suppress the release of thyroid stimulating T! hormone (TSH) and reduce T3 & T4 values. Thyroid gland atro-phy has been reported after chronic glucocorticoid administra-tion. Uptake of I 131 by the thyroid may be decreased by gluco-corticoids. Reactions to T! skin tests may be suppressed by glucocorticoids False-negative results of the T! nitroblue tetrazolium test for systemic bacterial infections may be induced by glucocorticoids Glucocorticoids may cause T! neutrophilia within 4-8 hours after dosing and return to baseline within 24-48 hours after drug dis-continuation Glucocorticoids can cause T! lymphopenia in dogs which can persist for weeks after drug discontinuation Doses DOg S:T! For labeled indications (antiinflammatory; glucocorticoid agent):a) Injection: 0. 5-1 mg IV or IM; may be repeated for 3-5 days; Tablets: 0. 25-1. 25 mg PO daily in single or two divided dos-es (Package Insert; Azium®— Schering) Low-Dose Dexamethasone Suppression T est:a) Draw pre-sample. Inject 0. 01-0. 015 mg/kg dexametha-sone IV (may dilute dexametha sone 1:10 with sterile saline to insure accurate dosing). Collect samples at 4 hrs. and 8 hrs. post dexamethasone. Usual pre-dose cortisol normals: 0. 5-4. 0 micrograms/dl; post-dexamethasone normals: less than 1. 5 micrograms/dl (Kemppainen and Zerbe 1989a) b) Draw pre-sample in AM. Inject 0. 01 mg/kg dexamethasone sodium phosphate IV. Draw sample 8 hours post injection. (Feldman 1989), (Morgan 1988), (Feldman, Schrader, and Twedt 1988) High-Dose Dexamethasone Suppression T est:a) Draw pre-dose sample. Inject 0. 1 or 1 mg/kg IV dexametha-sone. Draw post-dose sam ples at 4 hours and 8 hours. Use 1 mg/kg dose if not suppressed at lower dose (0. 1 mg/kg). Use 1 mg/kg dose with caution in patients with diabetes mel-litus and if cortisol values are greater than 12 micrograms/dl (Kemppainen and Zerbe 1989a) b) Draw pre-dose sample. Administer 0. 1 mg/kg IV dexametha-sone sodium phosphate. Draw second sample 8 hours post injection (Feldman 1989) c) Draw pre-dose sample. Administer 0. 1 mg/kg IV dexametha-sone sodium phosphate. Draw second sample 4 hours post injection (Morgan 1988) d) Draw pre-dose sample. Administer 0. 1 mg/kg IV dexametha-sone sodium phosphate. Draw second sample 4 or 8 hours post injection (Feldman, Schrader, and Twedt 1988) Combined Dexamethasone Suppression-ACTH Stimulation test: a) Draw pre-dose sample. Administer 0. 1 mg/kg IV dexametha-sone; collect post-dexam ethasone sample 4 hours later. Im-mediately give ACTH (gel) 2. 2 IU/kg IM. Collect post-ACTH sample 2 hours later. (Kemppainen and Zerbe 1989a) For tentative diagnosis of Addison's disease: a) 1) Draw blood for hemogram, serum biochemistry and basal cortisol; 2) Begin IV fluids and give 2-5 mg/kg dexametha-sone sodium phosphate; 3) Immediately give 0. 25 mg of cosyntropin IV or IM; 4) Draw a second blood sample for plasma cortisol 45-60 minutes later. Blood levels of <1 mcg/ d L are typical for hypoadrenocorticism, while those stimu-lating to only 2-3 mcg/d L are also suggestive. (Schaer 2006) For toy breed dogs with hydrocephalus: a) 0. 25 mg/kg three to four times daily; reduce dose slowly over 2-4 weeks (Simpson 1989) For adjunctive therapy of craniocerebral/spinal trauma:a) If patient's condition is not improved 30 minutes after re-ceiving water-soluble glucocorti coids: 2 mg/kg by slow IV in-fusion. If patient continues to deteriorate, additional therapy is warranted. (Shores 1989) b) Initially, 0. 2 mg/kg bolus, then 0. 2 mg/kg daily in 2-3 divid-ed doses. If animal is in shock, give 2 mg/kg initially. (Fenner 1986a) c) Fo r spinal cord trauma: 2-3 mg/kg IV followed in 6-8 hours by 1 mg/kg SC or IV two to three times daily for 24 hours. Then 0. 2 mg/kg SC or IV two to three times daily for 2-3 days. Then 0. 1 mg/kg IV or SC two to three times daily for 3-5 days (Schunk 1988a) T o reduce intracerebral pressure and edema:a) In the palliative therapy of intracranial neoplasms: 0. 25-2 mg/kg q6h IV in acute episodes (Le Couteur and Turrel 1986) b) In the adjunctive therapy of status epilepticus: 2 mg/kg IV initially; repeat in 6-8 hours with 1 mg/kg. Follow with ta-pering doses. (Schunk 1988b) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
268 DEx Am ETHASONE For adjunctive therapy of fibrocartilaginous embolic myopathy: a) 2. 2 mg/kg IV, then 6-8 hours later give 1 mg/kg SC. Repeat 1 mg/kg SC in 12 hours, then give 0. 1 mg/kg SC twice daily for 3-5 days (Schunk 1988a) For patients with thoracolumbar intervertebral disk disease and acute onset of paraparesis: a) 2 mg/kg IV followed in 6-8 hours with 0. 5-1 mg/kg SC, two to three times daily for 24 hours, then 0. 1 mg/kg SC or PO twice daily for 3-5 days (Schunk 1988a) For medical therapy of cervical spondylopathy: a) With an acute onset or sudden worsening with moderate to marked tetraparesis: 2. 2 mg/kg IV once followed in 6-8 hours by 1 mg/kg SC twice daily for two doses. Then 0. 1-0. 2 mg/kg PO or SC twice a day for 3-5 days (Schunk 1988a) For adjunctive therapy of shock: a) Dexamethasone sodium phosphate: 4-6 mg/kg IV (Kemp-painen 1986) For initial adjunctive treatment of acute adrenocortical collapse: a) Dexamethasone: 0. 5-1 mg/kg IV or Dexamethasone Sodium phosphate 2-4 mg/kg IV (Schrader 1986), (Feldman, Schrad-er, and Twedt 1988) For treatment of acquired thrombocytopenia: a) 0. 25-0. 3 mg/kg IV or SC once, then 0. 1-0. 15 mg/kg SC or PO twice a day for 7 days. Decrease oral dose by H every 5-7 days for 3 weeks, then go to alternate day therapy for 6 weeks. (Dodds 1988) For adjunctive therapy of endotoxemia secondary to acute gastric dilatation-volvulus: a) 5 mg/kg slowly IV (Bellah 1988) For adjunctive therapy of cholecalciferol (Quintox®, Rampage®) toxicity: a) 1 mg/kg SC divided four times daily (Grauer and Hjelle 1988b) CATS:T! For labeled indications (antiinflammatory; glucocorticoid agent): a) Injection: 0. 125-0. 5 mg IV or IM; may be repeated for 3-5 days; Tablets: 0. 125-0. 5 mg daily in single or divided doses (Package Insert; Azium®— Schering) High-Dose Dexamethasone Suppression T est: a) As a screening test for feline hyperadrenocorticism: 0. 1 mg/kg IV. A dose of 1 mg/kg IV may differentiate pituitary-depen-dent hyperadrenocorticism (PDH) from an adrenal tu mor. (Zerbe 1989) Combined Dexamethasone Suppression-ACTH Stimulation T est: a) Collect blood sample, then give dexamethasone 0. 1 mg IV, collect sample 2 hours after dexamethasone. Immediately give ACTH (2. 2 IU/kg) and collect samples 1 and 2 hours post ACTH. (Zerbe 1989) For endotoxic or septicemic shock: a) Dexamethasone sodium succinate: 5 mg/kg IV (Jenkins 1985) As adjunctive therapy for feline neoplasias (lymphosarcoma, acute lymphoid leukemia, mast cell neoplasms): a) 2-6 mg/m2 q24-48h PO, SC or IV (Couto 1989) For adjunctive emergency treatment of feline asthma: a) 1 mg/kg IV (sodium phosphate salt) (Noone 1986) For chronic therapy of feline allergic bronchitis: a) 0. 25 mg PO one to three times daily. Once patient stabilizes, attempt to reduce dose; keep on alternate-day therapy for at least 1-2 months after symptoms have initially resolved. (Bauer 1988) For alternative therapy for idiopathic feline miliary dermatitis: a) 1 mg PO once daily for 7 days, then 1 mg PO twice a week. May need to add progesta tional agent. (Kwochka 1986) RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 0. 6 mg/kg IM (as an antiinflammatory) (Adamcak and Otten 2000) CATTl E:T! For adjunctive therapy of insect bites or stings: a) 2 mg/kg IM or IV q4h (use epinephrine if anaphylaxis devel-ops) (Fowler 1993) For adjunctive therapy of cerebral edema secondary to polioen-cephalomalacia: a) 1-2 mg/kg intravenously (Dill 1986) For adjunctive therapy of radial nerve injury, or femoral nerve paralysis: a) Adult cattle (400-800 kg and not pregnant): 20-40 mg IM or IV; Calves: 10 mg IM or IV. Taper or discontinue therapy in 2-3 days. Many cases require only a single dose. (Rebhun 1986) For adjunctive therapy of obturator nerve paralysis: a) 10-40 mg parenterally once daily for 2-3 days, then discon-tinue (Rebhun 1986) For adjunctive therapy of peroneal nerve injuries: a) 10-30 mg parenterally for acute cases when not contraindi-cated due to pregnancy or in fection (Rebhun 1986) For elective inducement of parturition or termination of pregnancy: a) For abortion: 25 mg parenterally with 25 mg prostaglandin F2alpha after 150 days of gesta tion. For inducement or par-turition from 8th month of gestation on: 20 mg IM. (Drost 1986) b) Fo r inducement of parturition when given within 2 weeks of normal term: 20-30 mg IM (Barth 1986) For adjunctive therapy of aseptic laminitis: a) 5-20 mg IM or IV; continue therapy for 2-3 days (Berg 1986) For primary bovine ketosis: a) 5-20 mg IV or IM (Package Insert; Azium®— Schering) HORSES:T! (Note : ARCI UCGFS Class 4 Drug) For labeled indications (antiinflammatory; glucocorticoid agent):a) Dexamethasone Injection: 2. 5-5 mg IV or IM (Package In-sert; Azium®— Schering) Dexamethasone sodium phosphate injection: 2. 5-5 mg IV (Package Insert; Azium® SP— Schering) For recurrent airway obstruction (heaves): a) For a 500 kg horse give 40 mg IM once every other day for 3 treatments, followed by 35 mg IM once every other day for 3 treatments, followed by 30 mg IM once every other day for 3 treatments, etc., until horse is weaned off dexamethasone. Corticosteroid use may be contraindicated in horses predis-posed to laminitis or exhibiting endocrinopathies. (Ains-worth and Hackett 2004) For glucocorticoid therapy: a) 0. 05-0. 2 mg/kg once daily IV, IM or PO (Robinson 1987) Dexamethasone suppression test: a) 20 mg IM. Normal values: Cortisol levels decrease 50% in 2 hours, 70% in 4 hours, and 80% at 6 hours. At 24 hours, levels are still depressed about 30% of original value. (Beech 1987b) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DEx Am ETHASONE 269 SWINE:T! For glucocorticoid therapy: a) 1-10 mg IV or IM (Howard 1986) ll Am AS:T! For adjunctive therapy of anaphylaxis: a) 2 mg/kg IV (Smith 1989) b IRDS:T! For shock, trauma, gram-negative endotoxemia: a) Dexamethasone 2 mg/m L injection: 2-4 mg/kg IM or IV once, twice or three times daily. Taper off drug when using long-term. (Clubb 1986) REPTIl ES:T! For septic shock in most species: a) Using Dexamethasone Sodium Phosphate: 0. 1-0. 25 mg/kg IV or IM (Gauvin 1993) monitoring Monitoring of glucocorticoid therapy is dependent on its reason for use, dosage, agent used (amount of mineralocorticoid activity), dosage schedule (daily versus alternate day therapy), duration of therapy, and the animal's age and condition. The following list may not be appropriate or complete for all animals; use clinical assess-ment and judgment should adverse ef fects be noted: Weight, appetite, signs of edema T! Serum and/or urine electrolytes T! T otal plasma proteins, albumin T! Blood glucose T! Growth and development in young animals T! ACTH stimulation test if necessary T! Client Information Clients should carefully follow the dosage instructions and should T! not discon tinue the drug abruptly without consulting with vet-erinarian beforehand. Clients should be briefed on the potential adverse effects that can T! be seen with these drugs and instructed to contact the veterinar-ian should these effects become severe or progress. Chemistry/Synonyms A synthetic glucocorticoid, dexamethasone occurs as an odorless, white to practically white, crystalline powder that melts with some decomposition at about 250°C. It is practically insol uble in water and sparingly soluble in alcohol. Dexamethasone sodium phos-phate occurs as an odorless or having a slight odor, white to slightly yellow, hygroscopic powder. One gram is solu ble in about 2 m L of water; it is slightly soluble in alcohol 1. 3 mg of dexamethasone sodium phosphate is equivalent to 1 mg of dexamethasone; 4 mg/m L of dexamethasone sodium phosphate injection is approximately equivalent to 3 mg/m L of dexametha sone. Dexamethasone may also be known as: desamethasone, dexam-etasone, dexamethasonum, 9alpha-Fluoro-16alpha-methylpredni-solone; hexadecadrol; many trade names are available. Storage/Stability/Compatibility Dexamethasone is heat labile and should be stored at room tem-perature (15-30°C) unless otherwise directed by the manufacturer. Dexamethasone sodium phos phate injection should be protected from light. Dexamethasone tablets should be stored in well-closed containers. Dexamethasone sodium phosphate for injection is reportedly compatible with the following drugs: amikacin sulfate, aminophyl-line, bleomycin sulfate, cimetidine HCl, glycopyrrolate, lidocaine HCl, nafcillin sodium, netilmicin sulfate, prochlorperazine edisy-late and verapamil. Dexamethasone sodium phosphate is reportedly incompatible with: daunorubicin HCl, doxorubicin HCl, metaraminol bitartrate, and vancomycin. Compatibility is dependent upon factors such as p H, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Dexamethasone Injection: 2 mg/m L; Amtech® Dexamethasone So-lution (Phoenix Scientific), Azium® Solution (Schering-Plough), Dexamethasone 2 mg Injection (Vedco, RXV), Dexamethasone Injection (Bimeda, Pro Labs, Vet T ek, Dexamethasone Solution (As-pen, Butler, Phoenix Pharmaceutical), Dexasone® (RXV); (Rx). Ap-proved for use in dogs, cats, horses (those not intended for food) and cattle. There are no withdrawal times required when used in cattle. A withdrawal period has not been established for this prod-uct in preruminal calves; do not use in veal calves. Dexamethasone Oral Powder: 10 mg crystalline in 10 mg pack-ets. Approved for use in cattle and horses (not horses intended for food). Azium® Powder (Schering-Plough); (Rx) Dexamethasone Sodium Phosphate Injection: 4 mg/m L (equiva-lent to 3 mg/m L dexamethasone); Dexaject SP® (Vetus), Dexame-thasone Sodium Phosphate Injection (Butler, Vedco); generic; (Rx). Approved for use in horses. Dexamethasone 5 mg and trichlormethiazide 200 mg oral bolus: in boxes of 30 and 100 boluses; Naquasone® Bolus (Schering-Plough); (Rx). Approved for use in cattle. Milk withdrawal = 72 hours. The ARCI (Racing Commissioners International) has designated dexamethasone as a class 4 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Dexamethasone Tablets: 0. 25 mg, 0. 5 mg, 0. 75 mg, 1 mg, 1. 5 mg, 2 mg, 4 mg, & 6 mg; Decadron® (Merck); generic; (Rx) Dexamethasone Oral Elixir/Solution: 0. 5 mg/5 m L in 100 m L, 237 m L, 500 m L and UD 5 and UD 20 m L, 1 mg/m L (concentrate) in 30 m L with dropper; Dexamethasone Intensol® (Roxane); generic; (Rx) Dexamethasone Sodium Phosphate Injection: 4 mg/m L (as sodium phosphate solution) in 1, 5, 10 and 30 m L vials, 1 m L syringe and 1 m L fill in 2 m L vials; generic; (Rx); 10 mg/m L (as sodium phos-phate solution) in 1m L and 10 m L vials and 1 m L syringes; generic; (Rx); 20 mg/m L (as sodium phosphate solution) in 5 m L vials (IV) (with sodium sulfite & benzyl alcohol); Hexadrol® Phosphate (Or-ganon), (Rx) Dexamethasone is also available in topical ophthalmic (see ophthal-mic products in the appendix) and inhaled aerosol dosage forms. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
270 DExm EDETOm IDINE dexmedetomidine (deks-mee-deh-toe-mih-deen) Dexdomitor® alpha-2 adrenergic ag Onist Prescriber Highlights Alpha-2 agonist similar to medetomidine used as a pre-T T anesthetic & for sedation, analgesia in dogs & cats Contraindications: cardiac disease, liver or kidney dis-T T eases, shock, severe debilitation, or animals stressed due to heat, cold or fatigue; caution in very old or young animals, animals with seizure disorders, respiratory, renal or kidney disorders Adverse Effects: Bradycardia, occasional AV blocks, de-T T creased respiration, hy pothermia, urination, vomiting, hy-perglycemia, & pain on injection (IM). Rarely: pro longed sedation, paradoxical excitation, hypersensitivity, apnea & death from circu latory failure Dosed in dogs based upon body surface area, not weight T T Effects may be reversed with atipamezole T T Note : This compound has been approved for use in dogs in the USA, but at the time of writing (Autumn 2007) it had not yet been marketed in the USA and the package insert was not available for review. The fol-lowing should be considered a preliminary monograph. Uses/Indications In the USA, dexmedetomidine for dogs is approved for use as a seda-tive and analgesic to facilitate clinical examinations, clinical proce-dures, minor surgical procedures, and minor dental procedures, and as a preanesthetic to general anesthesia. In Europe, dexmedetomidine is additionally indicated for use in cats similarly to dogs above, but when used as premed it is indicated for use prior to ketamine general anesthesia. Pharmacology/Actions Dexmedetomidine is the dextrorotatory enantiomer of the alpha-2 adrenergic agonist, medetomidine. The other enantiomer, levome-detomidine is thought to be pharmacologically inactive so dexme-detomidine is about two times more potent than medetomidine. Dexmedetomidine is much more specific than xylazine for al-pha2 receptors versus alpha 1 receptors. The pharmacologic effects of dexmedetomidine include: depression of CNS (sedation, anxioly-sis), analgesia, GI (decreased secretions, varying affects on intestinal muscle tone) and endocrine functions, peripheral and cardiac va-soconstriction, bradycardia, respiratory depression, diuresis, hypo-thermia, analgesia (somatic and visceral), muscle relaxation (but not enough for intubation), and blanched or cyanotic mucous mem-branes. Effects on blood pressure are variable, but dexmedetomidine can cause hypertension longer than does xylazine. Pharmacokinetics In dogs after IM administration, dexmedetomidine is absorbed (bioavailability 60%) and reaches peak plasma levels in about 35 minutes. Volume of distribution is 0. 9 L/kg and elimination half-life is approximately 40-50 minutes. The drug is primarily metabolized in the liver via glucuronidation and N-methylation. No metabolites are active and they are eliminated primarily in the urine and to lesser extent in the feces. In cats after IM administration, dexmedetomidine is absorbed and reaches peak plasma levels of about 17 ng/m L occur in about 15 minutes. Volume of distribution is 2. 2 L/kg and elimination half-life is approximately 1 hour. Metabolites are eliminated primarily in the urine and to lesser extent in the feces. In humans after IV administration, dexmedetomidine is rapidly distributed, undergoes almost complete biotransformation via both glucuronidation and CY-450 enzymes systems and has a terminal elimination half-life of about 2 hours. Metabolites are eliminated in the urine and feces. Contraindications/Precautions/Warnings The European labeling states not to use in puppies less than 6 months old or in kittens less than 5 months old; in animals with cardiovascular disorders; in animals with severe systemic disease or that are moribund; or in animals known to be hypersensitive to the active substance or any of the excipients. Use with caution in animals with, or prone to developing, sei-zures. Dexmedetomidine lowered the seizure threshold in cats un-dergoing anesthesia with enflurane. Adverse Effects The adverse effects reported with medetomidine or dexmedetomi-dine are essentially extensions of their pharmacologic effects includ-ing bradycardia, muscle tremors, transient hypertension, occasional A V blocks, decreased respiration, hypothermia, urination, vomiting, hyperglycemia, and pain on injection (IM). Rare effects that have been reported, include: prolonged sedation, paradoxical excitation, hypersensitivity, pulmonary edema, apnea, and death from circula-tory failure. Reproductive/Nursing Safety The drug is not recommended for use in pregnant dogs or those used for breeding purposes because safety data for use during preg-nancy is insufficient; therefore use only when the benefits clearly outweigh the drug's risks. However, no teratogenic effects were ob-served when rats were given up to 200 mcg/kg SC from days 5- 16 of gestation or when rabbits were given up 96 mcg/kg IV from days 6-18 of gestation. In humans, the FDA categorizes this drug as cat-egory C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in hu-mans; or there are no animal reproduction studies and no adequate studies in humans. ) Dexmedetomidine is distributed into the milk of lactating rats; safe use during nursing has not been established. Overdosage/Acute Toxicity Single doses of up to 5X (IV) and 10X (IM) were tolerated in dogs, but adverse effects can occur (see above). Because of the poten-tial of additional adverse effects occurring (heart block, PVC's, or tachycardia), treatment of medetomidine-induced bradycardia with anticholinergic agents (atropine or glycopyrrolate) is usually not recommended. Atipamezole is probably a safer choice to treat any medetomidine-induced effect. Drug Interactions Note : Before attempting combination therapy with dexmedetomi-dine, it is strongly advised to access references from veterinary anes-thesiologists familiar with the use of this product. ANESTHETICS, OPIATES, SEDATIVE/Hy PNOTICST! : Effects may be addi-tive; dosage reduction of one or both agents may be required The following drug interactions have either been reported or are theoretical in humans or animals receiving medetomidine (a related compound) and may be of significance in veterinary patients: ATROPINE, gly COPy RROl ATE T! : The use of atropine or glycopyrrolate to prevent or treat medetomidine-caused bradycardia is contro-versial as tachycardia and hypertension may result. This is more | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DEx PANTHENOl 271 important when using higher doses of medetomidine and con-comitant use is discouraged. y OHImb INET! : May reverse the effects of medetomidine; but atipam-ezole is preferred for clinical use to reverse the drug's effects laboratory Considerations Medetomidine (and presumably dexmedetomidine) can inhibit T! ADP-induced platelet aggregation in cats. Doses DOg S:T! a) For sedation and analgesia: 375 mcg/m2 body surface area (BSA) IV; 500 mcg/m2 BSA IM. The mcg/kg dosage decreases as body weight increases. As a preanesthetic: Depending on duration and severity of the procedure and anesthetic regimen: 125 -375 mcg/m2 IM. (FOI Summar y; Dexdomitor®—Orion) CATS:T! a) For sedation and analgesia, or as a preanesthetic: 40 mcg/kg IM. Expected sedative and analgesic effects are reached within 15 minutes and maintained for up to 60 minutes. (Dexdomitor®—Pfizer U. K. ) monitoring Level of sedation and analgesia; heart rate; body temperature T! Heart rhythm, blood pressure, respiration rate, and pulse oxim-T! etry should be considered, particularly in higher risk patients Client Information This drug should be administered and monitored by veterinary T! professionals only Clients should be made aware of the potential adverse effects as-T! sociated with its use, particularly in dogs at risk (older, preexist-ing conditions) Chemistry/Synonyms Dexmedetomidine is the dextrorotatory enantiomer of medetomidine. Dexmedetomidine HCl may also be known as (S)-medetomidine, (+)-medetomidine, MPV 1440, MPV 295, or MPV 785. Trade names include: Precedex® or Dexdomitor®. Storage/Stability/Compatibility Store the injection at room temperature (15-30°C); do not freeze. Dexmedetomidine is not compatible with butorphanol when mixed in the same syringe. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Dexmedetomidine HCl 0. 5 mg/m L (500 mcg/m L) in 10 m L mul-tidose vials; Dexdomitor® (Orion); (Rx). Note : At time of writing, approved but not marketed in the USA. HUm ANl Ab El ED PRODUCTS: Dexmedetomidine HCl 100 mcg/m L, preservative free in 2 m L vi-als; Precedex® (Abbott); (Rx)dexp Anthenol d-p Anthenol (dex-pan-the-nole) Ilopan® Prescriber Highlights Precursor to Coenzyme A that ostensibly aids in produc-T T tion of acetylcholine Potentially may be useful in the prevention of post-surgi-T T cal ileus, but efficacy is in doubt Contraindications: Ileus secondary to mechanical ob-T T struction or in cases of colic caused by the treatment of cholinergic anthelmintics Uses/Indications Dexpanthenol has been suggested for use in intestinal atony or dis-tension, post operative retention of flatus and feces, prophylaxis and treatment of paralytic ileus after abdominal surgery or traumatic injuries, equine colic (not due to mechanical obstruction) and any other condi tion when there is an impairment of smooth muscle function. Controlled studies are lacking with re gard to proving the efficacy of the drug for any of these indications. Pharmacology/Actions A precursor to pantothenic acid, dexpanthenol acts as a precursor to coenzyme A that is necessary for acetylation reactions to occur during gluconeogenesis and in the production of acetylcholine. It has been postulated that post-surgical ileus can be prevented by giving high doses of dexpanthenol, thereby assuring adequate lev-els of acetylcholine. However, one study in normal horses (Adams, Lamar, and Masty 1984) failed to demonstrate any effect of dexpan-thenol on peristalsis. Pharmacokinetics Dexpanthenol is rapidly converted to pantothenic acid in vivo, which is widely distributed throughout the body, primarily as co-enzyme A. Contraindications/Precautions/Warnings Dexpanthenol is contraindicated in ileus secondary to mechanical obstruction, or in cases of colic caused by the treatment of cholin-ergic anthelmintics. It is also con traindicated in humans with he-mophilia as it may exacerbate bleeding. Adverse Effects Adverse reactions are reportedly rare. Hypersensitivity reactions have been reported in humans, but may have been due to the pre-servative agents found in the injectable product. Potentially, GI cramping and diarrhea are possible. Reproductive/Nursing Safety Safety in use during pregnancy has not been established. In hu-mans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Overdosage/Acute Toxicity The drug is considered non-toxic even when administered in high doses. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
272 DEx RAz Ox ANE Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dexpanthenol and may be of significance in veterinary patients: NEOSTIgm INE; SUCCINyl CHOl INET! : The manufacturers have recom-mended that dexpanthenol not be administered within 12 hours of neostigmine or other parasympathomimetic agents or within 1 hour of patients receiving succinylcholine. The clinical signifi-cance of these potential interactions has not been documented, however. Doses DOg S & CATS:T! a) 11 mg/kg IM; repeat if indicated at 4-6 hour intervals (Ros-soff 1974) b) 11 mg/kg IM; may be repeated in 2 hours after initial injection and followed every 6-8 hours until condition is alleviated. The time interval and duration of therapy will depend upon the degree of severity that the animal is exhibiting from the clinical standpoint. (Label Instructions; d-Panthenol® Inject-able—Vedco) HORSES:T! a) 2. 5 grams IV or IM; repeat if indicated at 4-6 hour intervals (Rossoff 1974), (Label In structions; d-Panthenol® Injectable— Vedco) monitoring Clinical efficacy T! Client Information Should be used in a professionally monitored situation where gas-T! trointestinal motility can be monitored. Chemistry/Synonyms The alcohol of D-pantothenic acid, dexpanthenol occurs as a slightly bitter-tasting, clear, viscous, somewhat hygroscopic liquid. It is freely soluble in water or alcohol. Dexpanthenol may also be known as: D-panthenol, dexpanthe-nolum, dextro-pantothenyl alcohol, pantothenol; many trade names are available. Storage/Stability/Compatibility Dexpanthenol should be protected from both freezing and exces sive heat. It is incompatible with strong acids and alkalis. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Dexpanthenol Injection: 250 mg/m L in 100 m L vials; Amtech® D-Panthenol In jection (IVX), D-Panthenol® Injectable (Vedco), generic (Butler, Phoenix Pharmaceutical); (Rx). Labeled for use in dogs, cats, and horses. HUm ANl Ab El ED PRODUCTS: Dexpanthenol Injection: 250 mg/m L in 2 m L and 10 m L vials, UD Stat-Pak 2 m L disp sy ringes; Ilopan® (Adria); generic; (Rx) Dextrose — see the Tables of Parenteral Fluids in the Appendixdexr Azox Ane (dex-ra-zox-ane) Zinecard® antid Ote Prescriber Highlights May be useful in attenuating the cardiotoxic effects of T T doxorubicin in patients (dogs) showing signs of anthra-cycline cardiotoxicity, have cardiac disease, or are at maximum cumulative dosages of doxorubicin; also used to treat extravasation injuries associated with doxorubicin Potentially may reduce efficacy of doxorubicin & increase T T myelosuppression For extravasation treatment, must be administered T T within hours of injury Very expensive T T Uses/Indications Dexrazoxane may be useful to attenuate the cardiotoxic effects of doxorubicin in patients who are showing signs of anthracycline cardiotoxicity, have cardiac disease, or are at maximum cumulative dosages of doxorubicin. It is also used to treat extravasation injuries associated with doxorubicin. While dexrazoxane has been shown to be cardioprotective when given at dosages of 10 times the doxorubicin dose, there is evidence that it may also partially protect the cancer cells being treated. Pharmacology/Actions Dexrazoxane is hydrolyzed to an active metabolite that chelates intracellular iron that is believed to prevent the formation of an anthracycline-iron complex thought to be the primary cause of an-thracycline-induced cardiomyopathy. Pharmacokinetics In dogs, dexrazoxane's pharmacokinetics fit a two compartment open model. Steady-state volume of distribution is 0. 67 L/kg, ter-minal half life is about 1. 2 hours, and clearance about 11 m L/min/kg. Clearance was dose-independent and the drug showed low tissue and protein binding. Dexrazoxane is primarily excreted in the urine as unchanged drug and metabolites. Contraindications/Precautions/Warnings Dexrazoxane should not be used unless an anthracycline antine-oplastic agent is being used. Efficacy and safety for use in cats is not known. Adverse Effects Dexrazoxane may cause additive myelosuppression when used with other myelosuppressive agents. There is some evidence in humans, that dexrazoxane may reduce the efficacy of anthracycline antitu-mor agents. Clinical significance in veterinary patients is unknown. Wear gloves when handling and use normal procedures for han-dling and disposal of anti-cancer medications. If unreconstituted powder contacts skin or mucous membranes, wash off thoroughly with soap and water. Reproductive/Nursing Safety Dexrazoxane has been shown to cause testicular atrophy in dogs when administered at usual doses for 13 weeks. In humans, the FDA categorizes dexrazoxane as a category C drug for use during preg-nancy (Animal studies have shown an adverse effect on the fetus, but | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DEx TRAN 70 273 there are no adequate studies in humans; or there are no animal re-production studies and no adequate studies in humans). In rats and rabbits, dexrazoxane was teratogenic at doses lower than those ad-ministered to humans. It is unknown if dexrazoxane enters maternal milk; human mothers are advised to discontinue nursing if given the drug. Overdosage/Acute Toxicity Because of the method of administration and drug expense, over-doses are unlikely in veterinary medicine. As there is no known an-tidote, treatment would be supportive. Potentially, the drug could be removed via hemodialysis. Drug Interactions Dexrazoxane does not influence the pharmacokinetics of doxorubicin. The following drug interactions have either been reported or are theoretical in humans or animals receiving dexrazoxane and may be of significance in veterinary patients: my El OSUPPRESSIVE Ag ENTS, OTHERT! : Additive myelo-suppression may occur when used with other myelosuppressive agents. laboratory Considerations No specific laboratory interactions or considerations were noted. Doses DOg S:T! For treatment of anthracycline (doxorubicin, epirubicin, etc. ) extravasation: a) T erminate doxorubicin infusion immediately, and infuse in-travenously 1000 mg/m2 of dexrazoxane in a separate infu-sion within 6 hours and again on day 2. Infuse 500 mg/m2 on day 3. Acute surgical evaluation is performed. Note : Dosage recommendations are for human patients, but may apply to veterinary patients. (Langer, Sehested et al. 2000) b) Anecdotally; IV administration of dexrazoxane at 10 times the doxorubicin dose with 3 hours and again at 24 and 48 hours after extravasation significantly reduces local tissue in-jury. (Vail 2006) For prevention of doxorubicin-induced cardiomyopathy:a) Dexrazoxane to doxorubicin dose ratio is 10:1 (e. g., 300 mg/m2 of dexrazoxane to 30 mg/m2 doxorubicin) given as slow IV bolus, starting 30 minutes of, and prior to the doxorubicin dose (as a short, IV bolus. ) (Selting 2005) b) Use can be considered in breeds at risk (Shelties, Collies, Australian Shepherds, etc. ), dogs that are exceeding the usual cumulative dose cut-off, and in cases where there is preex-isting cardiac disease and no effective chemo options exist: Dexrazoxane to doxorubicin dose ratio is 10:1 (e. g., 300 mg/m2 of dexrazoxane to 30 mg/m2 doxorubicin) given as slow IV bolus, starting 30 minutes before doxorubicin is adminis-tered. (Vail 2006) monitoring CBCT! If used for cardioprotection: echocardiogram, ECG, etc T! Client Information Clients should understand and accept the potential costs associ-T! ated with this drug and that when used for extravasation injuries, may not be fully effective. Chemistry/Synonyms A derivative of EDTA, dexrazoxane occurs as a white crystalline powder that is soluble in water and slightly soluble in ethanol and practically insoluble in nonpolar organic solvents. It has a p Ka of 2. 1 and degrades rapidly at p H's above 7. Dexrazoxane may also be known as: 2,6-Piperazinedione, ADR-529, ICRF-187, NSC-169780, Zinecard®, Cardioxane® or Eucardion®. Storage/Stability/Compatibility Unreconstituted dexrazoxane vials should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Once reconstituted with the supplied diluent, it is stable for 6 hours at room tempera-ture or refrigerated. Unused solutions after that time should be dis-carded. After reconstitution, the resulting solution may be diluted with either 0. 9% sodium chloride injection or D5W in concentra-tions of 1. 3-5 mg/m L. Inspect visually for particulate matter and discoloration prior to administering. The manufacturer states that it should not be mixed with any other drug. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Dexrazoxane Lyophilized Powder for Injection: 250 mg (10 mg/m L when reconstituted in vials with 25 m L sodium lactate injection); and 500 mg (10 mg/m L when reconstituted with 50 m L sodium lactate injection); Zinecard® (Pfizer); Dexrazoxane (Bedford); (Rx) dextr An 70 (dex-tran) plasma v Olume e Xpander Note : Dextran is also available as Dextran 40 and Dextran 75. As Dextran 70 is the most com monly used version in veterinary medicine, the fol-lowing monograph is limited to it alone. Prescriber Highlights Branched polysaccharide plasma volume expander T T Contraindications: Preexisting coagulopathies T T Caution: Patients susceptible to circulatory overload T T (severe heart or renal failure), thrombocytopenia Adverse Effects: Quite rare in dogs. Increased bleeding T T times, acute renal failure & anaphylaxis possible (but very rare) Must monitor for fluid overload T T Uses/Indications Dextran 70 is a relatively low cost colloid for the adjunctive treat-ment of hypov olemic shock. Hetastarch is the more commonly em-ployed synthetic colloid used today. Pharmacology/Actions Dextran 70 has osmotic effects similarly to albumin. Dextran's col-loidal osmotic effect draws fluid into the vascular system from the interstitial spaces, resulting in increased circulat ing blood volume. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
274 DEx TRAN 70 Pharmacokinetics After IV infusion, circulating blood volume is increased maximal-ly within one hour and effects can persist for 24 hours or more. Approximately 20-30% of a given dose remains in the intravascular compartment at 24 hours and it may be detected in the blood 4-6 weeks after dos ing. Dextran 70 is slowly degraded to glucose by dex-tranase in the spleen and then metabolized to carbon dioxide and water. A small amount may be excreted directly into the gut and eliminated in the feces. Contraindications/Precautions/Warnings Patients overly susceptible to circulatory overload (severe heart or renal failure) should receive dextran 70 with great caution. Dextran 70 is contraindicated in patients with severe coagulopathies and should be used with caution in patients with thrombocytopenia as it can interfere with platelet function. Do not give dextran IM. Patients on strict sodium restriction should receive dextran cautiously as a 500 m L bag contains 77 m Eq of sodium. Adverse Effects Dex tran 70 may increase bleeding time and decrease von Willebrand's factor antigen and factor VIII ac tivity. This does not usually cause clinical bleeding in dogs. While anaphylactoid reactions are not rare in humans, they do occur rarely in dogs, but at a higher rate than with hetastarch. Unlike dextran 40, dextran 70 has rarely been associated with acute renal failure. In humans, GI effects (abdominal pain, nausea/vomiting) have been reported with use of dextran 70. 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 The drug should be dosed and monitored carefully as volume over-load may result. Drug Interactions Dextran reportedly has no drug interactions that are clinically sig-nificant. laboratory Considerations Dextran 70 may interfere with T! blood crossmatching as it can cross-link with red blood cells and appear as rouleaux formation. Iso-tonic saline may be used to negate this effect. blood glucose!! levels may be increased as dextran is degraded. Falsely elevated T! bilirubin levels may be noted; reason unknown. Doses DOg S:T! a) Up to 40 m L/kg/day; not to be infused faster than 5 m L/kg/hr (Haskins 1992) b) 20 m L/kg; bolus to effect (Eastlake and Snyder 1998) c) 20 m L/kg/day; when acute resuscitation is required, may be given as a slow bolus over 30 minutes to an hour. May also be given as a constant rate infusion over a longer period to augment colloid oncotic pressure or decrease the volume of crystalloids infused, thereby reducing hemodilution. (Martin 2004) CATS:T! a) 10 m L/kg/day; when acute resuscitation is required. May be given as a slow bolus over 30 minutes to an hour. May also be given as a constant rate infusion over a longer period to augment colloid oncotic pressure or decrease the volume of crystalloids infused, thereby reducing hemodilution. (Martin 2004) CATTl E:T! a) For dehydrated (secondary to diarrhea) calves given as 6% Dextran 70 in 7. 2% sodium chloride: T o prepare solution, add 31. 6 g sodium chloride into the barrel of a 60 m L syringe. Draw 60 m L of 6% dextran 70 in 0. 9% Na Cl from the bag/bottle to dilute the Na Cl crystals. Re-inject the dissolved solu-tion into the bag/bottle through a 0. 22 micron filter giving a 6% dextran 70 in 7. 2% Na Cl solution. Resultant solution may be refrigerated for up to 3 months. Inject IV 4-5 m L/ kg of this solution over 4-5 minutes, followed immediately by oral administration of isotonic electrolyte solution. Give dextran 70 solution one time only or hypernatremia may re-sult and follow-up with isotonic fluids (oral or IV) are critical. (Sweeney 2003) monitoring Other than the regular monitoring performed in patients that T! would re quire volume expansion therapy, there is no inordinate monitoring required specific to dextran ther apy. Chemistry/Synonyms A branched polysaccharide used intravenously as a plasma volume expander, dextran 70 occurs as a white to light yellow amorphous powder. It is freely soluble in water and insoluble in alcohol. Dextran 70 contains (on average) molecules of 70,000 daltons. Each 500 m L of the com mercially available 6% dextran 70 in normal saline pro-vides 77 m Eq of sodium. Dextran 70 in normal saline has a viscosity of 3. 68 centipose (blood is 3 centipose) and a colloid osmotic pres-sure of 65. 8 mm Hg (blood is 25-30 mm Hg). Dextran 70 may also be known as: dextranum 70, polyglu-cin, Dextran 70®, Fisiodex 70®, Gentran 70®, Hyskon®, Lomodex 70®, Longasteril 70®, Macrodex®, Macrohorm 70®, Neodextril 70®, Plander®, Rescue Flow®, or Solplex 70®. Storage/Stability/Compatibility Dextran 70 injection should be stored at room temperature; prefer-ably in an area with little temperature variability. While only clear solutions should be used, dextran flakes can form but may be resol-ubolized by heating the solution in a boiling water bath until clear, or autoclaving at 110°C for 15 minutes. Dextran 70 is compatible with many other solutions and drugs; refer to specialized references or a hospital pharmacist for more information. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: Dextran High Molecular Weight Injection: 6% dextran 70 in 0. 9% sodium chloride in 500 m L; Dextran 70® (Mc Gaw); (Rx), Gen-tran70® (Baxter); (Rx), Macrodex® (Medisan); (Rx) Dextran High Molecular Weight Injection: 6% dextran 70 in 5% dextrose in 500 m L; Macrodex® (Medisan); (Rx) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DIAz EPAm 275 di Azep Am (dye-az-e-pam) Valium®, Diastat® benz Odiazepine Prescriber Highlights Benzodiazepine used for a variety of indications T T (anxiolytic, muscle relaxant, hypnotic, appetite stimulant, & anticonvulsant) in several species Contraindications: Hypersensitivity to benzodiazepines, T T cats exposed to chlorpyrifos, sig nificant liver disease (especially in cats) Caution: hepatic or renal disease, aggressive, debilitated T T or geriatric patients; patients in coma, shock or with sig-nificant respiratory depression Adverse Effects: Sedation & ataxia most prevalent. T T DOGS: CNS excitement; CATS: Hepatic failure or behavior changes; HORSES: Muscle fasciculations Inject IV slowly T T May be teratogenic T T Drug interactions T T Controlled substance (C-IV)T T Uses/Indications Diazepam is used clinically for its anxiolytic, muscle relaxant, hyp-notic, appetite stimulant, and anticonvulsant activities. Refer to the Dosage section for those and other suggested in dications and doses for each species. Pharmacology/Actions The subcortical levels (primarily limbic, thalamic, and hypotha-lamic), of the CNS are depressed by diazepam and other benzo-diazepines thus producing the anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects seen. The exact mechanism of action is un known, but postulated mechanisms include: antago-nism of serotonin, increased release of and/or fa cilitation of gam-ma-aminobutyric acid (GABA) activity, and diminished release or turnover of acetylcholine in the CNS. Benzodiazepine specific receptors have been located in the mammalian brain, kidney, liver, lung, and heart. In all species studied, receptors are lacking in the white matter. Pharmacokinetics Diazepam is rapidly absorbed following oral administration. Peak plasma levels occur within 30 minutes to 2 hours after oral dosing. The drug is slowly (slower than oral) and in completely absorbed following IM administration. In dogs, rectally administered diaz-epam has an average bioavailability of 50%, but significant inter-patient variation occurs. When administered intranasally to dogs, bioavailability is about 80%. Diazepam is highly lipid soluble and is widely distributed throughout the body. It readily crosses the blood-brain barrier and is fairly highly bound to plasma proteins. In the horse at a serum con centration of 75 ng/m L, 87% of the drug is bound to plasma proteins. In humans, this value has been reported to be 98-99%. Diazepam is metabolized in the liver to several metabolites, in-cluding desmethyldiazepam (nordiazepam), temazepam, and ox-azepam, all of which are pharmacologically active. These are even-tually conjugated with glucuronide and eliminated primarily in the urine. Because of the active metabolites, serum values of diazepam are not useful in predicting efficacy. Serum half-lives (approximat-ed) have been reported for diazepam and metabolites in dogs, cats, and horses: DOg S CATS HORSES HUm ANS Diazepam 2. 5-3. 2 hrs5. 5 hrs 7-22 hrs 20-50 hrs Nordiazepam 3 hrs 21. 3 hrs 30-200 hrs Contraindications/Precautions/Warnings Inject intravenously slowly. This is particularly true when using a small vein for access or in small animals; diazepam may cause sig-nificant thrombophlebitis. Rapid injection of intravenous diazepam in small animals or neonates may cause cardiotoxicity secondary to the propylene glycol in the formulation. Intra-carotid artery injec-tions must be avoided. Use cautiously in patients with hepatic or renal disease and in debilitated or geriatric patients. The drug should be administered to patients in coma, shock, or with significant respiratory depres-sion very cautiously. It is contraindicated in patients with known hypersensitivity to the drug. Diazepam should be used very cau-tiously, if at all, in aggressive patients, as it may disinhibit the anxi-ety that may help prevent these animals from aggressive behavior. Benzodiazepines may impair the abilities of working animals. If ad-ministering the drug IV, be prepared to administer cardiovascular or respi ratory support. It is recommended not to use diazepam for seizure control in cats exposed to chlorpyrifos as organophosphate toxicity may be potentiated. Adverse Effects In horses, diazepam may cause muscle fasciculations, weakness and ataxia at doses sufficient to cause sedation. Doses greater than 0. 2 mg/kg may induce recumbency as a result of its muscle relaxant properties and general CNS depressant effects. Cats may exhibit changes in behavior (irritability, depression, aberrant demeanor) after receiving diazepam. There have been reports of cats developing hepatic failure after receiving oral di-azepam (not dose dependent) for several days. Clinical signs (an-orexia, lethargy, increased ALT/AST, hyperbilirubinemia) have been reported to occur 5-11 days after beginning oral therapy. Cats that receive diazepam should have baseline liver function tests. These should be repeated and the drug discontinued if emesis, lethargy, inappetence or ataxia develops. Dogs may exhibit a contradictory response (CNS excitement) following administration of di azepam. The effects with regard to sedation and tranquilization are extremely variable with each dog. Because of this individual variation, diazepam is not an ideal sedat-ing agent for this species. Reproductive/Nursing Safety Diazepam has been implicated in causing congenital abnormalities in humans if administered dur ing the first trimester of pregnancy. Infants born of mothers receiving large doses of benzodiazepines shortly before delivery have been reported to suffer from apnea, impaired metabolic response to cold stress, difficulty in feeding, hyperbilirubinemia, hypotonia, etc. Withdrawal symptoms have occurred in infants whose mothers chronically took benzodiaz-epines during pregnancy. The veterinary signifi cance of these ef-fects is unclear, but the use of these agents during the first trimester of pregnancy should only occur when the benefits clearly outweigh the risks associated with their use. 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 | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
276 DIAz EPAm 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 outweighs the risks. ) Benzodi azepines and their metabolites are distributed into milk and may cause CNS effects in nursing neonates. Overdosage/Acute Toxicity When administered alone, diazepam overdoses are generally limited to significant CNS depression (confusion, coma, decreased reflexes, etc. ). Hypotension, respiratory depression, and cardiac arrest have been reported in human patients, but apparently are quite rare. Treatment of acute toxicity consists of standard protocols for re-moving and/or binding the drug in the gut if taken orally, and sup-portive systemic measures. The use of analeptic agents (CNS stimu-lants such as caffeine) is generally not recommended. Flumazenil may be considered for adjunctive treatment of overdoses of benzo-diazepines. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving diazepam and may be of significance in veterinary patients: Am ITRIPTyl INET! : Diazepam may increase levels ANTACIDST! : May decrease oral diazepam absorption ANTIFUNg Al S, Az Ol ET! (itraconazole, ketoconazole, etc. ): May increase diazepam levels CIm ETIDINET! : May decrease metabolism of ben zodiazepines CNS DEPRESSANT DRUg S T! (barbiturates, narcotics, anesthetics, etc. ): If diazepam administered with other CNS depressant agents addi-tive effects may occur DEx Am ETHASONET! : May decrease diazepam levels DIg Ox INT! : Diazepam may increase digoxin levels ERy THROmy CINT! : May decrease the metabolism of ben zodiazepines m INERAl OIl T! : May decrease oral diazepam absorption PHENOb ARb ITAl T! : May decrease diazepam concentrations PHENy TOINT! : May decrease diazepam concentrations QUINIDINET! : May increase diazepam levels RIFAm PINT! : May induce hepatic microsomal enzymes and decrease the pharmacologic effects of ben zodiazepines laboratory Considerations Patients receiving diazepam, may show false negative T! urine glucose re sults if using Diastix® or Clinistix® tests. Doses DOg S:T! For treatment of seizures: a) For cluster seizures or status epilepticus (for client treatment at home): If on phenobarbi tal, use diazepam at 2 mg/kg (us-ing diazepam parenteral solution) per rectum. Administer at the onset of seizure and up to 3 times in a 24-hour period, but should not be given within 10 minutes of the prior dose. Owners should stay with dog for one hour after administra-tion. (Podell 2000), (Podell 2006b) b) For refractory status epilepticus using constant rate IV infu-sion: 0. 1-0. 5 mg/kg diluted in D5W. Rate administered per hour should be equal to the maintenance fluid requirement for the patient. Use with caution as diazepam can crystallize in solution and adsorb to PVC tubing. For status or cluster seizure treatment at home: 0. 5-2 mg/kg per rectum (Platt and Mc Donnell 2000) c) For status epilepticus: 0. 5-1 mg/kg IV, 1-2 mg/kg per rec-tum; may need to be re-dosed, a long-acting anticonvulsant (e. g., phenobarbital) must be administered to gain complete control. (Knipe 2006b) d) For metaldehyde, strychnine, or brucine induced seizures/tremors: 2-5 mg/kg IV (Bailey 1986a) e) For methylxanthine (e. g., theophylline) induced seizures: 0. 5-2 mg/kg IV (if unsuc cessful, use phenobarbital at 6 mg/ kg IV q6-12h) (Hooser and Beasley 1986) f) For salicylate toxicity induced seizures: 2. 5-20 mg (total dose) IV or PO (Handagama 1986) g) Seizures secondary to CNS trauma: 0. 25-0. 5 mg/kg IV (Fenner 1986) For white shaker dog syndrome: a) 0. 25 mg/kg PO three to four times daily (Morgan 1988) For Scotty cramp: a) 0. 5-2 mg/kg IV to effect or PO three times daily (Morgan 1988) As a preanesthetic: a) 0. 1 mg/kg IV slowly (Morgan 1988) For irritable colon syndrome: a) 0. 15 mg/kg PO three times daily (Morgan 1988) For functional urethral obstruction/urethral sphincter hypertonus: a) 2-10 mg q8h (Polzin and Osborne 1985); (Lane 2000) b) 2-10 mg PO three times a day; 0. 5 mg/kg IV (Chew, Di Bar-tola, and Fenner 1986) c) 0. 2 mg/kg PO q8h or 2-10 mg (total dose) PO q8h (Bartges 2003a) As a restraining agent/sedative: a) 0. 2- 0. 6 mg/kg IV (Morgan 1988) b) 0. 25 mg/kg PO q8h (Davis 1985a) For separation anxiety: a) 0. 5-2. 2 mg/kg PO as needed (Morgan 1988) For adjunctive treatment of metronidazole toxicity (CNS): a) Doses of diazepam averaged 0. 43 mg/kg in the study and were given as an IV bolus once, and then PO q8h for 3 days. (Evans, Levesque et al. 2002) CATS:T! As an appetite stimulant:a) 0. 05-0. 15 mg/kg IV once daily to every other day or 1 mg PO once daily (Morgan 1988) b) 0. 05-0. 4 mg/kg IV, IM or PO. After IV administration, eat-ing may begin in a few seconds; have food readily available. (Booth 1988a) Urine marking and anxiety:a) 0. 2-0. 4 mg/kg PO q12-24h (start at 0. 2 mg/kg PO q12h) (Overall 2000) b) For spraying: 1-2. 5 mg per cat PO q8-12h; sedation and ataxia should abate within sev eral days (Reisner and Houpt 2000) For adjunctive treatment of feline psychogenic alopecia and dermatitis: a) 1-2 mg PO twice daily (Walton 1986) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DIAz EPAm 277 For treatment of seizure disorders: a) 0. 25-0. 5 mg/kg PO q8-12h. T o halt an ongoing seizure, di-azepam may be administered at 0. 5-1 mg/kg IV. If cat has a history of receiving insulin, glucose may be more benefi cial. Do not use if cat has been exposed to chlorpyrifos as organo-phosphate toxicity may be potentiated. (Shell 2000) b) For oral maintenance therapy of seizures: As a second choice drug (after phenobarb): 0. 5-1 mg/kg PO q12h (Quesnel 2000) c) 0. 5-1 mg/kg/day PO dose is divided every 8-12 hours. Drug has a wide margin of safety and dosages as high as 2 mg/kg may be required in some cats. (Munana 2004c) d) For salicylate toxicity induced seizures: 2. 5-5 mg IV or PO (Handagama 1986) Functional urethral obstruction/urethral sphincter hypertonus:a) 1-2. 5 mg (total dose) PO q8h (Osborne, Kruger et al. 2000) b) 1-2. 5 mg (total dose) PO q8h OR 0. 5 mg/kg IV (Lane 2000) c) 2. 5-5 mg (total dose) PO q8h or as needed, or 0. 5 mg/kg IV (Bartges 2003a) FERRETS:T! For premedication/sedation: a) 1-2 mg/kg IM; may be given with ketamine (10-20 mg/kg) (Morrisey and Carpenter 2004) RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Rabbits: Pre-anesthetic: 2-10 mg/kg IM; 1-5 mg/kg IM or IV. Give IV to effect for seizures. (Ivey and Morrisey 2000) b) Rabbits: As a tranquilizer (to increase relaxation of lightly anesthetized animals and permit ET intubation): 1 mg/kg IV as needed (Huerkamp 1995) c) Hamsters, Gerbils, Mice, Rats: 3-5 mg/kg IM. Guinea pigs: 0. 5-3 mg/kg IM (Adamcak and Otten 2000) CATTl E:T! a) Sedative in calves: 0. 4 mg/kg IV (Booth 1988a) b) As a tranquilizer: 0. 55-1. 1 mg/kg IM (Lumb and Jones 1984) c) Treatment of CNS hyperactivity and seizures: 0. 5-1. 5 mg/kg IM or IV (Bailey 1986b) HORSES: T! (Note : ARCI UCGFS Class 2 Drug) For field anesthesia:a) Sedate with xylazine (1 mg/kg IV; 2 mg/kg IM) given 5-10 min utes (longer for IM route) before induction of anesthe-sia with ketamine (2 mg/kg IV). Horse must be adequately sedated (head to the knees) before giving the ketamine (ket-amine can cause muscle rigidity and seizures). If adequate sedation does not occur, either 1) Redose xy-lazine: up to half the original dose; 2) Add butorphanol (0. 02-0. 04 mg/kg IV). Butorphanol can be given with the original xylazine if you suspect that the horse will be difficult to tranquilize (e. g., high-strung Thoroughbreds) or added before the ketamine. This combination will improve induc-tion, increase analgesia and increase re cumbency time by about 5-10 minutes; 3) Diazepam (0. 03 mg/kg IV). Mix the diazepam with the ketamine. This combination will improve induction when sedation is marginal, improve muscle re-laxation during anesthesia and prolong anesthesia by about 5-10 min utes; 4) Guaifenesin (5% solution administered IV to effect) can also be used to increase sedation and muscle relaxation. (Mathews 1999)For seizures: a) Foals: 0. 05-0. 4 mg/kg IV; repeat in 30 minutes if necessary b) Adults: 25-50 mg IV; repeat in 30 minutes if necessary (Sweeney and Hansen 1987) Treatment of seizures secondary to intra-arterial injection of xy-lazine or other similar agents: a) 0. 10-0. 15 mg/kg IV (Thurmon and Benson 1987) As an appetite stimulant: a) 0. 02 mg/kg IV; immediately after dosing, offer animal food. Keep loud noises and distrac tions to a minimum. If effective, usually only 2-3 treatments in a 24-48 hour period are re-quired. (Ralston 1987) SWINE:T! For tranquilization: a) 5. 5 mg/kg IM (will develop posterior ataxia in 5 minutes and then recumbency within 10 minutes) (Booth 1988a) b) 0. 55-1. 1 mg/kg IM (Lumb and Jones 1984) c) For sedation prior to pentobarbital anesthesia: 8. 5 mg/kg IM (maximized at 30 minutes; reduces pentobarbital dose by 50%) (Booth 1988a) For treatment of CNS hyperactivity and seizures: a) 0. 5-1. 5 mg/kg IM or IV (Howard 1986) SHEEP:T! As a tranquilizer: a) 0. 55-1. 1 mg/kg IM (Lumb and Jones 1984) g OATS:T! For Bermuda grass induced toxicosis and tremors: a) 0. 8 mg/kg IV (Booth 1988a) T o stimulate appetite: a) 0. 04 mg/kg IV; offer food immediately, duration of effect may last up to 45 minutes (Booth 1988a) b IRDS:T! For adjunctive therapy of pain control (with analgesics): a) 0. 5-2 mg/kg IV or IM (Clyde and Paul-Murphy 2000) monitoring Horses should be observed carefully after receiving this drug. T! Cats receiv ing diazepam should have baseline liver function tests. T! Repeat and discontinue drug if emesis, lethargy, inappetence, or ataxia develop. When used for seizure control in cats, one author (Quesnel 2000) recommends obtaining serum level 5 days after beginning therapy. Goal is to achieve levels in the therapeutic range of 500-700 nmol/L (500-700 ng/m L). Client Information Keep out of reach of children and in tightly closed containers T! Cats: If patient develops lack of appetite, vomits, or yellowish T! whites of eyes contact veterinarian immediately Chemistry/Synonyms A benzodiazepine, diazepam is a white to yellow, practically odor-less crystalline pow der with a melting point between 131°-135°C and p K a of 3. 4. Diazepam is tasteless initially, but develops a bitter after-taste. One gram is soluble in 333 m L of water, 25 m L of alco-hol, and it is spar ingly soluble in propylene glycol. The p H of the commercially prepared injectable solution is ad justed with benzoic acid/sodium benzoate to 6. 2-6. 9. It consists of a 5 mg/m L solution with 40% propylene glycol, 10% ethanol, 5% sodium benzoate/ benzoic acid buffer, and 1. 5% benzyl alcohol as a preservative. Diazepam may also be known as: diazepamum, LA-III, NSC-77518, or Ro-5-2807; many trade names are available. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
278 DIAz Ox IDE Storage/Stability/Compatibility All diazepam products should be stored at room temperature (15°-30°C). The injection should be kept from freezing and pro-tected from light. The oral dosage forms (tablets/capsules) should be stored in tight containers and protected from light. Because diazepam may adsorb to plastic, it should not be stored drawn up into plastic syringes. The drug may also significantly ad-sorb to IV solution plastic (PVC) bags and to the infusion tubing. This adsorption appears to be dependent on several factors (tem-perature, concentration, flow rates, line length, etc. ). The manufacturers of injectable diazepam do not recommend the drug be mixed with any other medication or IV diluent. The drug has been successfully diluted to concentrations of 5 mg/50 m L or 5 mg/100 m L in normal saline, lactated Ringer's and D 5W. Differing results have occurred with dif ferent manufacturer's prod-ucts. Do not administer if a precipitate forms and does not clear. While mixing diazepam with ketamine in a single syringe is not recommended, it is often done in veterinary medicine with apparent success; however, it should be used immediately after mixing and excess medication should not be saved. Do not use if a visible pre-cipitate forms. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Diazepam Tablets: 2 mg, 5 mg, & 10 mg; Valium® (Roche); generic; (Rx, C-IV) Diazepam Oral Solution: 1 mg/m L in 30 m L with dropper, 500 m L, and 5 mg and 10 mg patient cups; generic, Diazepam Intensol® (Rox-ane); (Rx, C-IV) Diazepam Injection: 5 mg/m L in 2 m L Carpuject cartridges; generic; (Rx, C-IV) Diazepam Rectal Gel: 2. 5 mg, 10 mg, 20 mg; Diastat® (Xcel); (Rx, C-IV) di Azoxide, or Al (di-az-ok-side) Proglycem®, Hyperstat IV® direct vas Odilat Or/hyperglycemic Prescriber Highlights Orally administered drug used to treat insulinomas in T T small animals Contraindications/Cautions: Functional hypoglycemia or T T hypoglycemia secondary to in sulin overdosage (diabet-ics); hypersensitive to thiazide diuretics; CHF or renal disease Adverse Effects: Most likely are anorexia, vomiting &/T T or diarrhea (may be reduced by giving with food). Less likely: tachycardia, hematologic abnormalities, diabetes mellitus, cataracts, & sodium & water retention. Adverse effects are more likely in dogs with hepatic disease. Availability & expense issues T TUses/Indications Oral diazoxide is used in canine and ferret medicine for the treat-ment of hypoglycemia sec ondary to hyperinsulin secretion (e. g., in-sulinoma). Insulinomas are apparently very rare in the cat; there is little experience with this drug in that species. In human medicine, intravenous diazoxide is sometimes used for treating severe hypertension. Pharmacology/Actions Although related structurally to the thiazide diuretics, diazoxide does not possess any appreciable diuretic activity. By directly caus-ing a vasodilatory effect on the smooth muscle in peripheral arte-rioles, diazoxide reduces peripheral resistance and blood pressure. T o treat malignant hypertension, intravenous diazoxide is generally required for maximal response. Diazoxide exhibits hyperglycemic activity by directly inhibiting pancreatic insulin secretion. This action may be a result of the drug's capability to decrease the intracellular release of ionized calcium, thereby preventing the release of insulin from the insulin granules. Diazoxide does not ap parently affect the synthesis of insulin, nor does it possess any antineoplastic activity. Diazoxide also enhances hyperglycemia by stimulating the beta-adrenergic system thereby stimulating epinephrine release and inhibiting the uptake of glucose by cells. Pharmacokinetics The serum half-life of diazoxide has been reported to be about 5 hours in the dog; other pharmacokinetic parameters in the dog ap-pear to be unavailable. In humans, serum dia zoxide (at 10 mg/kg PO) levels peaked at about 12 hours after dosing with capsules. It is unknown what blood levels are required to obtain hyperglyce-mic effects. Highest concentrations of diazoxide are found in the kidneys with high levels also found in the liver and adrenal glands. Approximately 90% of the drug is bound to plasma proteins and it crosses the placenta and into the CNS. It is not known if diazoxide is distributed into milk. Diazoxide is partially metabolized in the liver and is ex creted as both metabolites and unchanged drug by the kidneys. Serum half-life of the drug is pro longed in patients with renal impairment. Contraindications/Precautions/Warnings Diazoxide should not be used in patients with functional hypo-glycemia or for treating hypoglycemia secondary to insulin overdos-age in diabetic patients. Unless the potential advantages outweigh the risks, do not use in patients hypersensitive to thiazide diuret ics. Because diazoxide can cause sodium and water retention, use cautiously in patients with congestive heart failure or renal disease. Adverse Effects When used to treat insulinomas in dogs, the most commonly seen adverse reactions include hypersalivation, anorexia, vomiting and/or diarrhea; these effects may be lessened by administering the drug with food. Other effects that may be seen include: tachycar-dia, hematologic abnormalities (agranulocytosis, aplastic anemia, thrombocytopenia), diabetes mellitus, cataracts (secondary to hy-perglycemia?), and sodium and water retention. Administering the drug with meals or temporarily reducing the dose may alleviate the gastrointesti nal side effects. Adverse effects may be more readily noted in dogs with concurrent hepatic disease. Adverse effects reported with diazoxide use in ferrets include: in-appetence, vomiting, diarrhea, and bone marrow suppression. The drug is reportedly very bitter. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DIAz Ox IDE 279 Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is unknown if diazoxide enters milk. Overdosage/Acute Toxicity Acute overdosage may result in severe hyperglycemia and ketoaci-dosis. Treatment should include insulin (see insulin monograph), fluids and electrolytes. Intensive and prolonged monitoring is rec-ommended. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving diazoxide and may be of significance in veterinary patients: Al PHAADRENERg IC Ag ENTS T! (e. g., phenoxybenzamine ): May decrease the effectiveness of diazoxide in increasing glucose levels Hy POTENSIVE Ag ENTS, OTHER T! (e. g., hydralazine, prazosin, etc. ): Diaz-oxide may enhance the hypotensive actions of other hypotensive agents PHENOTHIAz INEST! (e. g., acepromazine, chlor promazine ): May enhance the hyperglycemic effects of diazoxide PHENy TOINT! : Diazoxide may increase the metabolism, or decrease the protein binding of phenytoin THIAz IDE DIURETICS T! : May potentiate the hyperglycemic effects of oral diazoxide. Some clinicians have recommended using hydro-chlorothiazide (2-4 mg/kg/day PO) in combination with diaz-oxide, if diazoxide is ineffective alone to increase blood glucose levels; Caution: hypoten sion may occur laboratory Considerations Diazoxide will cause a false-negative insulin response to the T! glu cagonstimulation test. Diazoxide may displace T! bilirubin from plasma proteins Doses DOg S:T! For hypoglycemia secondary to insulin secreting islet cell tumors:a) 10 mg/kg divided twice daily PO with meals; may increase dose up to 60 mg/kg to allevi ate signs of hypoglycemia, if tolerated (Lothrop 1989) b) Initially, 5 mg/kg PO twice daily; increase to a maximum of 30 mg/kg PO twice daily to control clinical signs (Meleo and Caplan 2000) c) If after frequent feedings (4-6 small meals per day) and glu-cocorticoids (prednisone 1. 1-4. 4 mg/kg/day) alone fail to control hypoglycemia or dog develops “Cushingoid” appear-ance, add diazoxide (reduce prednisone dose if “Cushin-goid”) initially at 10 mg/kg di vided twice a day. May gradu-ally increase dosage to 60 mg/kg/day as tolerated and add hydrochlorothiazide (2-4 mg/kg/day). (Feldman and Nel-son 1987c) For adjunctive therapy of hypoglycemia secondary to insulin se-creting non-islet cell (extra-pan creatic) tumors: a) Diazoxide 5-13 mg/kg PO three times daily (may add hy-drochlorothiazide 2-4 mg/kg/day) (Weller 1988) CATS:T! For hypoglycemia secondary to insulin secreting islet cell tumors:a) Initially, 5 mg/kg PO twice daily; increase to a maximum of 30 mg/kg PO twice daily to control clinical signs (Meleo and Caplan 2000)FERRETS:T! For hypoglycemia secondary to insulin secreting islet cell tumors:a) Initially, 5 mg/kg PO twice daily; increase to a maximum of 30 mg/kg PO twice daily to control clinical signs (Meleo and Caplan 2000) b) Ferrets: 5 mg PO twice daily to start; increase as needed up to 30 mg twice daily. Expen sive; use with prednisone (0. 5-2 mg/kg PO or IM) (Williams 2000) c) After surgical resection of pancreatic nodules or partial pan-createctomy: Prednisone at 0. 5-2 mg/kg PO q12h will usu-ally control mild to moderate clinical signs. Begin at lowest dose and gradually increase as needed. Add diazoxide when clinical signs cannot be controlled with prednisone alone. Begin at 5-10 mg/kg PO q12h. At same time prednisone dosage may be lowered. (Johnson 2006c) monitoring Blood (serum) glucose T! CBC (at least every 3T! -4 months) Physical exam (monitor for clinical signs of other adverse ef-T! fects—see above) Client Information Clients should be instructed to monitor for symptoms of hyper-T! or hypo glycemia, abnormal bleeding, GI disturbances, etc. Chemistry/Synonyms Related structurally to the thiazide diuretics, diazoxide occurs as an odorless, white to creamy-white, crystalline powder with a melting point of about 330°. It is practically insoluble to sparingly soluble in water and slightly soluble in alcohol. Diazoxide may also be known as: diazoxidum, NSC-64198, Sch-6783, SRG-95213, Eudemine®, Glicemin®, Hypertonalum®, Hyperstat IV®, Proglicem®, Sefulken®, or Tensuril®. Storage/Stability/Compatibility Diazoxide capsules and oral suspensions should be stored at 2-30°C and protected from light. Protect solutions/suspensions from freezing. Do not use darkened solutions/suspensions, as they may be subpotent. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUm ANl Ab El ED PRODUCTS: Finding a supply of oral dosage forms for this medication may be a problem, it may be available from compounding pharmacies. Diazoxide Injection: 15 mg/m L in 20 m L amps; Hyperstat IV® (Schering); (Rx) Also available as 50 mg tablets in the U. K. as Eudemine® (Allan and Hanburys) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
280 DICHl ORPHENAm IDE dichlorphen Amide (dye-klor-fen-a-mide) Daranide® carb Onic anhydrase inhibit Or Prescriber Highlights Used primarily for open angle glaucoma T T Contraindicated in patients with significant hepatic, renal, T T pulmonary or adrenocortical in sufficiency, hyponatremia, hypokalemia, hyperchloremic acidosis or electrolyte imbal ance Give oral doses with food if GI upset occurs T T Monitor with tonometry for glaucoma; check electrolytes T T Availability issues; may need to be obtained from a com-T T pounding pharmacy Uses/Indications Dichlorphenamide is used for the medical treatment of glaucoma. Because of availability issues and toxic effects associated with sys-temic therapy, human (and many veterinary) ophthalmologists are using topical carbonic anhydrase inhibitors (e. g., dorzolamide or brinzolamide) in place of acetazolamide, dichlorphenamide or met-hazolamide. Pharmacology/Actions The carbonic anhydrase inhibitors act by a noncompetitive, revers-ible inhibition of the enzyme carbonic anhydrase. This reduces the formation of hydrogen and bicarbonate ions from carbon dioxide and reduces the availability of these ions for active transport into body secretions. Pharmacologic effects of the carbonic anhydrase inhibitors in-clude decreased formation of aqueous humor, thereby reducing in-traocular pressure; increased renal tubular secretion of sodium and potas sium and, to a greater extent, bicarbonate, leading to increased urine alkalinity and volume; and anticon vulsant activity, which is independent of its diuretic effects (mechanism not fully understood, but may be due to carbonic anhydrase or a metabolic acidosis ef-fect). Pharmacokinetics The pharmacokinetics of this agent have apparently not been stud-ied in domes tic animals. One report (Roberts 1985) states that after a dose of 2. 2 mg/kg, the onset of action is 30 minutes, maximal ef-fect in 2-4 hours, and duration of action is 6-12 hours in small animals. Contraindications/Precautions/Warnings Carbonic anhydrase inhibitors are contraindicated in patients with significant hepatic disease (may precipitate hepatic coma), renal or adrenocortical insufficiency, hy ponatremia, hypokalemia, hyper-chloremic acidosis, or electrolyte imbalance. They should not be used in patients with severe pulmonary obstruction unable to in-crease alveolar ventilation or those who are hypersensitive to them. Long-term use of carbonic anhydrase inhibitors is contraindicated in patients with chronic, noncongestive, angle-closure glaucoma as angle closure may occur and the drug may mask the condition by lowering intra-ocular pressures. Adverse Effects Potential adverse effects that may be encountered include GI distur-bances, CNS effects (sedation, depression, excitement, etc. ), hema-tologic effects (bone marrow de pression), renal effects (crystalluria, dysuria, renal colic, polyuria), hypokalemia, hyperglycemia, hy-ponatremia, hyperuricemia, hepatic insufficiency, dermatologic ef-fects (rash, etc. ), and hyper sensitivity reactions. 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 Information regarding overdosage of this drug is not readily avail-able. It is suggested to monitor serum electrolytes, blood gases, vol-ume status, and CNS status during an acute overdose. Treat symp-tomatically and supportively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dichlorphenamide and may be of significance in veterinary patients: ANTIDEPRESSANTS, TRICy Cl ICT! : Alkaline urine cause by dichlo-rphenamide may decrease excretion ASPIRINT! (or other salicylates ): Increased risk of dichlorphenamide accumulation and toxicity; increased risk for metabolic acidosis; dichlorphenamide increases salicylate excretion DIg Ox INT! : As dichlorphenamide may cause hypokalemia, increased risk for toxicity INSUl INT! : Rarely, carbonic anhydrase inhibitors interfere with the hypoglycemic effects of insulin m ETHENAm INE COm POUNDS T! : Dichlorphenamide may negate effects in the urine POTASSIUm, DRUg S AFFECTINg T! (corticosteroids, amphotericin b, cor ticotropin, or other diuretics ): Concomitant use may exacerbate potassium depletion PHENOb ARb ITAl T! : Increased urinary excretion, may reduce pheno-barbital levels PRIm IDONET! : Decreased primidone concentrations QUINIDINET! : Alkaline urine cause by dichlorphenamide may de-crease excretion laboratory Considerations By alkalinizing the urine, carbonic anhydrase inhibitors may cause T! false positive results in determining urine protein using bromphe-nol blue reagent (Albustix®, Albutest®, Labstix®), sulfosalicylic acid (Bumintest®, Exton's T est Reagent), nitric acid ring test, or heat and acetic acid test methods. Carbonic anhydrase inhibitors may decrease T! iodine uptake by the thyroid gland in hyperthyroid or euthyroid patients. Doses DOg S:T! For adjunctive treatment of glaucoma: a) 2. 2-4. 4 mg/kg PO two to three times daily (q8-12h) (Nasisse 2005), (Milller 2005) b) 10-15 mg/kg per day divided 2-3 times daily (Brooks 2002b) c) 2-5 mg/kg PO q8-12h (Wilkie 2003) CATS:T! For adjunctive treatment of glaucoma:a) 0. 5-1. 5 mg/kg PO two to three times daily (Powell 2003) b) 1-2 mg/kg PO q8-12h (Milller 2005) | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DICHl ORVOS 281 monitoring Intraocular pressure/tonometry T! Serum electrolytes T! Baseline CBC with differential and periodic retests if using T! chronically Other adverse effects T! Client Information If GI upset occurs, give with food. T! Notify veterinarian if abnormal bleeding or bruising occurs or if T! animal develops tremors or a rash. Chemistry/Synonyms A carbonic anhydrase inhibitor, dichlorphenamide occurs as a white or nearly white, crystalline powder with a melting range of 235-240°C, and p K as of 7. 4 and 8. 6. It is very slightly soluble in water and soluble in alcohol. Dichlorphenamide may also be known as: dichlorphenamide, diclofenamidum, Antidrasi®, Fenamide®, Glaucol®, Glauconide®, Glaumid®, Oralcon®, Oratrol®, or Tensodilen®. Storage/Stability Store tablets in well-closed containers and at room temperature. An expiration date of 5 years after the date of manufacture is assigned to the commercially available tablets. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: None HUm ANl Ab El ED PRODUCTS: None Dichlorphenamide availability has been an issue and it may not be available commercially; if not, contact a compounding pharmacy for information. dichlorvos (dye-klor-vose) Atgard® Organ Oph Osphate antiparasitic Prescriber Highlights Organophosphate used orally as a wormer (primarily T T roundworms) in pigs & as ectoparasiti cide (“No Pest Strip”) for small mammals, etc. Contraindications: Anticholinesterase drugs; do not allow T T fowl access to medicated feed or manure from treated animals Adverse Effects (dose related): Vomiting, tremors, brady-T T cardia, respiratory distress, hy perexcitability, salivation, & diarrhea Drug Interactions T T Uses/Indications Dichlorvos is effective in swine against Ascaris, Trichuris, Ascarops strongylina and Oesophagostomum spp. Dichlorvos as a “No Pest Strip” is used as an ectoparasiti cide for small mammals. It is also used as a premise spray to keep fly popu-lations controlled. In horses, dichlorvos is labeled as be ing effective for the treat-ment and control of bots, pinworms, large and small bloodworms, and large roundworms, but no systemic equine products are cur-rently being marketed in the USA. Dichlorvos was available for use internally in dogs and cats for the treatment of roundworms and hookworms, but no products are currently being marketed since newer, safer and more effective anthelmintics have replaced dichlorvos. Pharmacology/Actions Like other organophosphate agents, dichlorvos inhibits acetylcho-linesterase inter fering with neuromuscular transmission in suscep-tible parasites. Pharmacokinetics Specific information was not located for this agent. Contraindications/Precautions/Warnings For the product (Atgard®) for use in swine, no absolute contrain-dications are labeled, but it should not be used within a few days of any other cholinesterase inhibiting drug, pesticide or chemical. Do not allow fowl access to medicated feed or manure from treated animals. Unused medication or medicated feed should be buried 18 inch-es below the ground and covered so that it is unavailable to any other animal. Avoid contact with the skin and keep out of reach of children. Adverse Effects When used as labeled, the are no listed adverse effects in swine. Adverse effects are generally dose-related and may include those listed below in the Overdosage/Acute T oxicity section. Reproductive/Nursing Safety Studies performed in target species have demonstrated no terato-genic effects at usual doses. In pigs, no effects have been noted on reproductive capability, performance or litter survivability. Overdosage/Acute Toxicity If overdoses occur, vomiting, tremors, bradycardia, respiratory dis-tress, hyperexcitability, salivation, and diarrhea may occur. Atropine (see atropine and pralidoxime monographs for more information) may be antidotal. Use of succinylcholine, theophylline, amino-phylline, reserpine, or respiratory depressant drugs (e. g., narcotics, phenothiazines) should be avoided in patients with organophos-phate toxicity. If ingestion occurs by a human, contact a poi son control center, physician, or hospital emergency room. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving dichlorvos and may be of significance in veterinary patients: ACEPROm Az INET! or other phenothiazines : Should not be given with-in one month of worming with an organophosphate agent as their effects may be potentiated ANTICHOl INESTERASE DRUg ST! (e. g., neostigmine, physostigmine, and pyridostigmine ): Avoid use when using organophosphates as they can inhibit cholinesterase Dm SOT! : Because of its anti cholinesterase activity, avoid the use of organophosphates with DMSO m ORPHINET! : Avoid use when using organophosphates as it can in-hibit cholinesterase Py RANTEl P Am OATE T! (or tartrate ): Adverse effects could be intensi-fied if used concomitantly with an organophosphate | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
282 DICl Az URIl SUCCINyl CHOl INET! : Patients receiving organophosphate anthelm-intics should not receive succinylcholine or other depolarizing muscle relaxants for at least 48 hours Doses RAbb ITS/RODENTS/Sm All m Amm Al S:T! a) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: Hang 5 cm of a dichlorvos strip (e. g., Vapona No Pest Strip) 6 inches above cage for 24 hours, twice weekly for 3 weeks (Anderson 1994); (Adamcak and Otten 2000) or hang in room for 24 hours once a week for 6 weeks or a 1 inch square laid on cage for 24 hours once a week for 6 weeks (Adamcak and Otten 2000) SWINE:T! a) For Atgard® Swine Wormer: Dosing for pigs is accomplished by adding to feed (crumble-type or dry meal). Specific amounts of feed per packet are dependent on pig weight. See the label for specific recommendations. monitoring Efficacy T! Adverse effects T! Client Information Keep out of reach of children. Handling of dichlorvos liquid prep-T! arations (e. g., premise spray) must be done with extreme care; fol-low all label directions! Oral pellets are non-di gestible and may be seen in the animals' T! feces. Chemistry/Synonyms An organophosphate insecticide, dichlorvos may also known as: 2,2,-dichlorovinyl dimethyl phosphate DDVP, NSC-6738, OMS-14, SD-1750, Atgard®, or Ravap E. C. ®. Storage/Stability Store Atgard® swine wormer at less than 80°F. Dichlorvos feed addi-tives should not be stored at temperatures below freezing. Dichlorvos is sensitive to hydrolysis if exposed to moisture or oxidizing agents. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Dichlorvos Feed Additives: Atgard® C (Boehringer Ingelheim); (OTC); Atgard® Swine Wormer (Boehringer Ingelheim); (OTC). When used as labeled there are no slaughter withdrawal times re-quired in swine. Dichlorvos with T etrachlorvinphos (Rabon®) Premise and T opical Insecticide: Ravap E. C. ® (Boehringer Ingelheim); (OTC) Dichlorvos may also be found in premise insecticidal products. HUm ANl Ab El ED PRODUCTS: Nonedicl Azuril (dye-klaz-yoor-il) Protazil®, Clinicox® antipr Ot Oz Oal Prescriber Highlights Approved (in USA) for EPM in horses & as a coccidiostat T T in broiler chickens Adverse effect profile not well known T T Uses/Indications Diclazuril is indicated for the treatment of equine protozoal myelo-encephalitis (EPM) caused by Sarcocystis neurona and as a coccid-iostat in broiler chickens. Diclazuril could potentially be useful in treating coccidiosis, Neospora caninum and T oxoplasma infections in dogs or cats. Pharmacology/Actions The triazine class of antiprotozoals are believed to target the “plas-tid” body, an organelle found in the members of the Apicomplexa phylum, including Sarcocystis neurona. The actual mechanism of ac-tion is not well described. In vitro levels required to inhibit (95%) Sarcocystis neurona are about 1 ng/m L. Pharmacokinetics In horses, oral bioavailability is about 5%. CSF levels are approxi-mately 1-5% of those found in plasma. Elimination half-life is prolonged (43-65 hours). Doses of 1 mg/kg/day should give mean steady-state plasma levels of about 2-2. 5 mg/m L with correspond-ing CSF levels of 20-70 ng/m L which is in excess of the in vitro IC 95 (1 ng/m L). Contraindications/Precautions/Warnings The drug is contraindicated in patients known to be hypersensitive to diclazuril. The safe use of Protazil® in horses used for breeding purposes, during pregnancy, in lactation, or with other therapies has not been evaluated. Adverse Effects The adverse effect profile in horses is not well known. In field trials, no adverse effects could be ascribed to the drug. Reproductive/Nursing Safety The manufacturer states that the safe use of Protazil® in horses used for breeding purposes, during pregnancy, or in lactation has not been evaluated. Overdosage/Acute Toxicity Limited information is available, but the drug appears to have large safety margin in normal horses. Normal horses dosed up to 50 mg/kg/day (50X) for 42 days developed only marginal effects (decreased weight gain, increased creatinine, BUN). Drug Interactions None were noted. The manufacturer states that the safety of Protazil® with concomitant therapies in horses has not been evaluated. laboratory Considerations None were noted. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
DICl OFENAC SODIUm 283 Doses HORSES:T! a) For treatment of equine protozoal myeloencephalitis (S. neurona): Using the oral pellets and the provided cup: T op dress at the rate of 1 mg/kg bodyweight for 28 days. If horse's bodyweight is in between two graduations on the dosing cup, fill the cup to the higher of the two marks. (Label informa-tion; Protazil®—Schering-Plough) DOg ST! /CATS: a) For coccidiosis: 25 mg/kg PO once. (Greene, Hartmannn et al. 2006) monitoring Clinical efficacy (neuro exams)T! Client Information Must be dosed daily as prescribed to be effective T! Will not necessarily return a horse to “normal”T! Chemistry/Synonyms Diclazuril occurs as a white to light yellow powder. It is practically insoluble in water and alcohol. Diclazuril may also be known as diclazurilo, diclazurilum, R 64433 and by the trade names, Clinicox®, Protazil®, and Vecoxan®. Storage/Stability/Compatibility Diclazuril pellets should be stored at room temperature (15-30°C). Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Diclazuril Oral Pellets 1. 56% in 2 lb. and 10 lb. containers: Protazil® (Schering-Plough); (Rx) Approved for use in horses not intended for food. One 2 lb. bucket will treat an 1100 lb. horse for 28 days. Note : At the time this monograph was written (Summer 2007), this product was approved, but not yet marketed. Diclazuril 0. 2% Type A Medicated Feed Article in 50 lb. containers; Clinicox® (Schering-Plough). Approved for use in broiler chickens. HUm ANl Ab El ED PRODUCTS: None diclofen Ac sodium (dye-kloe-fen-ak) Surpass® n On-ster Oidal antiinflammat Ory (nsaid) Prescriber Highlights NSAID approved for topical use in horses for local control T T of joint pain & inflammation Appears well-tolerated at recommended dosage T T Uses/Indications The equine topical cream (Surpass®) is labeled for the control of pain and inflammation associated with osteoarthritis in tarsal, car-pal, metacarpophalangeal, metarsophalangeal, and proximal inter-phalangeal (hock, knee, fetlock, pastern) joints for use up to 10 days duration. While, theoretically, diclofenac could be used systemically (orally) in other veterinary species, there are approved and safer alternatives. Pharmacology/Actions Diclofenac is a non-specific inhibitor of cyclooxygenase (both COX-1 and COX-2). It may also have some inhibitory effects on li-pooxygenase. By inhibiting COX-2 enzymes, diclofenac reduces the production of prostaglandins associated with pain, hyperpyrexia, and inflammation. Pharmacokinetics When diclofenac is administered topically to horses via the 1% li-posomal cream, it is absorbed locally, but specific bioavailability data was not located. Peak levels in transudate obtained from tissue cages were about 80 ng/m L; levels stay increased from 6 hours to at least 18 hours after administration. At the dosages recommended for the topical cream, most of the drug remains in the tissues local to the administration point, but detectable levels in the systemic circulation may occur. In humans, diclofenac is more than 99% bound to plasma proteins. It is metabolized in the liver and the me-tabolites are excreted primarily into the urine. Contraindications/Precautions/Warnings T opical diclofenac should not be used in horses hypersensitive to it or any component of the cream. It has not been evaluated in horses less than one year old. Exceeding the recommended dosage or treating multiple joints may cause adverse effects. Adverse Effects The topical cream in horses appears to be well tolerated. One case of a horse developing colic during therapy has been reported. Other adverse effects that may be seen include weight loss, gastric ulcers, diarrhea, or uterine discharge. In the FDA 's adverse reaction data-base local reactions (inflammation, swelling, alopecia) have been reported. Reproductive/Nursing Safety Reproductive safety for topical diclofenac has not been investigated in breeding, pregnant or lactating horses. Overdosage/Acute Toxicity When overdoses are administered topically to horses, adverse ef-fects may occur including weight loss, gastric ulcers, colic, diarrhea, and uterine discharge. Treatment is supportive. For small animals, there were 255 exposures to diclofenac sodi-um reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org) during 2000-2006. In these cases 241 were dogs with 24 showing clinical signs, 12 reported cat exposures with no reported clinical signs, and the remaining 2 cases were birds with no reported clinical signs. Common findings in dogs recorded in decreasing frequency included vomiting, diarrhea, bloody diarrhea, melena and polydipsia. This medication is a NSAID. As with any NSAID, overdosage can lead to gastrointestinal and renal effects. Decontamination with emetics and/or activated charcoal is appropriate. For doses where GI effects are expected, the use of gastrointestinal protectants is warrant-ed. If renal effects are also expected, fluid diuresis is warranted. Drug Interactions When used topically at recommended dosages, there are no report-ed drug interactions in horses. laboratory Considerations No specific laboratory interactions or considerations were noted. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |
284 DICl Ox ACIll IN SODIUm Doses HORSES:T! a) For the control of pain and inflammation associated with osteoarthritis in tarsal, carpal, metacarpophalangeal, metar-sophalangeal, and proximal interphalangeal (hock, knee, fet-lock, pastern) joints using Surpass® topical cream: Apply a five inch ribbon twice daily over the affected joint for up to 10 days. Wear rubber gloves and rub cream thoroughly into the hair covering the joint until cream disappears. (Label infor-mation; Surpass®—Idexx) monitoring Efficacy T! Adverse effects T! Client Information Clients should be instructed to use as directed, not to increase the T! dose (area applied) or duration (not too exceed 10 days), or ad-verse effects may occur. Clients should wear protective gloves (non-permeable) when ap-T! plying the cream. A client information sheet is supplied with the medication and T! should be given to the client. Chemistry/Synonyms A phenyl-acetic acid derivative non-steroidal antiinflammatory agent, diclofenac sodium occurs as a white to off-white, hygroscopic, crystalline powder. It is sparingly soluble in water, soluble in alcohol and practically insoluble in chloroform and ether. Diclofenac may also be known as: GP-45840, diclofenacum or diclophenac; many trade names are available for diclofenac products outside of the USA. Storage/Stability/Compatibility Unless otherwise labeled, diclofenac sodium products should be stored in airtight containers and protected from light. The commer-cially available 1% cream (Surpass®) should be stored at tempera-tures up to 25°C (77°F); protect from freezing. Dosage Forms/Regulatory Status VETERINAR yl Ab El ED PRODUCTS: Diclofenac sodium (liposomal) 1% topical cream in 124 gram tubes, Surpass® (Idexx); (Rx). Approved for use in horses. HUm ANl Ab El ED PRODUCTS: Diclofenac Tablets: 50 mg (as potassium); Cataflam® (Novartis); ge-neric; (Rx) Diclofenac Delayed-release Tablets: 25 mg, 50 mg, 75 mg & 100 mg (as sodium); Voltaren-XR® (Novartis); generic; (Rx) Diclofenac Sodium Gel: 3% (1 g contains 30 mg diclofenac sodium) with benzyl alcohol in 25 g & 50 g; Solaraze® (Skye Pharma); (Rx) Diclofenac Sodium/Misoprostol Tablets: (each tablet consists of an enteric-coated core containing diclofenac sodium surrounded by an outer mantle containing misoprostol) 50 mg/misoprostol 200 mcg & 75 mg/misoprostol 200 mcg; Arthrotec® (Searle) (Rx) Diclofenac sodium is also approved as a topical ophthalmic agent (see the ophthalmology drug appendix). diclox Acillin sodium (di-klox-a-sill-in) Dynapen® anti-staphyl Oc Occal penicillin Prescriber Highlights Oral isoxazolyl (anti-staphylococcal) penicillin T T Contraindications: hypersensitivity to penicillins; do not T T use oral medications in critically ill patients Most predominant adverse effects are GI in nature T T Must dose orally quite often (q6T T -8h); expense, efficacy & owner compliance may be issues Uses/Indications The veterinary use of dicloxacillin has been primarily in the PO treatment of bone, skin, and other soft tissue infections in small animals when penicillinase-producing Staphylococcus species have been isolated. Because of its low oral bioavailability and short half-life, other drugs with good staph coverage are usually employed. Pharmacology/Actions Cloxacillin, dicloxacillin and oxacillin have nearly identical spectrums of activity and can be considered therapeutically equivalent when comparing in vitro ac tivity. These penicillinase-resistant penicillins have a narrower spectrum of activity than the nat ural penicillins. Their antimicrobial efficacy is aimed directly against penicillinase-producing strains of gram-positive cocci, particularly Staphylococcal species. They are sometimes called anti-staphy lococcal penicillins. There are documented strains of Staphylococcus that are resistant to these drugs (so-called methicillin-resistant Staph, MRSA), but these strains have not yet been a major problem in vet erinary spe-cies. While this class of penicillins does have activity against some other gram-positive and gram-negative aerobes and anaerobes, other antibiotics (penicillins and others) are usually better choices. The penicillinase-resistant penicillins are inactive against Rickettsia, mycobacteria, fungi, Mycoplasma and viruses. Pharmacokinetics Dicloxacillin is only available in oral dosage forms. Dicloxacillin so-dium is resistant to acid inactivation in the gut but is only partially absorbed. The bioavailability after oral administration in dogs is only about 23% and in humans has been reported to range from 35-76%. If given with food, both the rate and extent of absorption is decreased. The drug is distributed to the liver, kidneys, bone, bile, pleural, synovial and ascitic fluids. However, one manufacturer states that levels of the drug that are achieved in ascitic fluid are not clinically therapeutic. As with the other penicillins, only minimal amounts are distributed into the CSF. In humans, approximately 95-99% of the drug is bound to plasma proteins. Dicloxacillin is partially metabolized to both active and inactive metabolites. These metabolites and the parent compound are rap-idly excreted in the urine via both glomerular filtration and tubular se cretion mechanisms. A small amount of the drug is also excreted in the feces via biliary elimination. The serum half-life in humans with normal renal function ranges from about 24-48 minutes. In dogs, 20-40 minutes to 2. 6 hours have been reported as the elimi-nation half-life. | ctl5q-Veterinary_drug_hand_book_Plumbs.pdf |