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METHYLPREDNISOLONE 601 drugs' vasoconstrictive properties and increased blood volume that may be produced. CELLS : Glucocorticoids inhibit ﬁbroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lympho-cytes, and the cellular response to mediators of inﬂammation. Glucocorticoids stabilize lysosomal membranes. CNS/AUTONOMIC NERV OUS SYSTEM: Glucocorticoids can lower seizure threshold, alter mood and behavior, diminish the response to py-rogens, stimulate appetite, and maintain alpha rhythm. Glucocor-ticoids are necessary for normal adrenergic receptor sensitivity. ENDOCRINE SYSTEM: When animals are not stressed, 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 suppressing aspects of exogenously admin-istered steroids. Release of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), prolactin, and luteinizing hormone (LH) may all be reduced when glucocorticoids are ad-ministered at pharmacological doses. Conversion of thyroxine (T 4) to triiodothyronine (T 3) may be reduced by glucocorticoids; and plasma levels of parathyroid hormone increased. Glucocorticoids may inhibit osteoblast function. Vasopressin (ADH) activity is re-duced at the renal tubules and diuresis may occur. Glucocorticoids inhibit insulin binding to insulin-receptors and the post-receptor effects of insulin. HEMATOPOIETIC SYSTEM: Glucocorticoids can increase the numbers of circulating platelets, neutrophils, and red blood cells, but inhibit platelet aggregation. Decreased amounts of lymphocytes (peripher-al), monocytes, and eosinophils are seen as glucocorticoids can se-quester these cells into the lungs and spleen and prompt decreased release from the bone marrow. Removal of old red blood cells is diminished. Glucocorticoids can cause involution of lymphoid tis-sue. GI TRACT AND HEPATIC SYSTEM: Glucocorticoids increase the secre-tion of gastric acid, pepsin, and trypsin. They alter the structure of mucin and decrease mucosal cell proliferation. Iron salts and cal-cium absorption decrease while fat absorption increases. Hepatic changes can include increased fat and glycogen deposits within he-patocytes, increased serum levels of alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT). Signiﬁcant increases can be seen in serum alkaline phosphatase levels. Glucocorticoids can cause minor increases in BSP (bromosulfophthalein) retention time. IMMUNE SYSTEM (also see Cells and Hematopoietic System): Glucocorticoids can decrease circulating levels of T-lymphocytes; inhibit lymphokines; inhibit neutrophil, macrophage, and mono-cyte migration; reduce production of interferon; inhibit phagocyto-sis and chemotaxis; antigen processing; and diminish intracellular killing. Speciﬁc acquired immunity is affected less than nonspeciﬁc immune responses. Glucocorticoids can also antagonize the com-plement cascade and mask the clinical signs of infection. Mast cells are decreased in number and histamine synthesis is suppressed. Many of these effects only occur at high or very high doses and there are species differences in response. METABOLIC EFFECTS: Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body (e. g., abdomen) and adipose tissue can be redistributed away from the extremities to the trunk. Fatty acids are mobilized from tissues and their oxi-dation is increased. Plasma levels of triglycerides, cholesterol, and glycerol are increased. Protein is mobilized from most areas of the body (not the liver). MUSCULOSKELETAL : Glucocorticoids may cause muscular weakness (also caused if there is a lack of glucocorticoids), atrophy, and os-teoporosis. Bone growth can be inhibited via growth hormone and somatomedin inhibition, increased calcium excretion, and inhibi-tion of vitamin D activation. Resorption of bone can be enhanced. Fibrocartilage growth is also inhibited. OPHTHALMIC: Prolonged corticosteroid use (both systemic or topi-cally to the eye) can cause increased intraocular pressure and glau-coma, cataracts, and exophthalmos. RENAL, FLUID, & ELECTROLYTES : Glucocorticoids can increase potas-sium and calcium excretion; sodium and chloride reabsorption, and extracellular ﬂuid volume. Hypokalemia and/or hypocalcemia occur rarely. Diuresis may occur following glucocorticoid admin-istration. SKIN: Thinning of dermal tissue and skin atrophy can be seen with glucocorticoid therapy. Hair follicles can become distended and alopecia may occur. Contraindications/Precautions/Warnings The manufacturer (Upjohn Veterinary) states that the drug (tab-lets) should not be used in dogs or cats “in viral infections,... animals with arrested tuberculosis, peptic ulcer, acute psychoses, corneal ulcer, and Cushingoid syndrome. The presence of diabetes, osteoporosis, chronic psychotic reactions, predisposition to throm-bophlebitis, hypertension, CHF, renal insufﬁciency, and active tu-berculosis necessitates carefully controlled use. ” The injectable acetate product is contraindicated as outlined above when used systemically. When injected intrasynovially, in-tratendinously, or by other local means, it is contraindicated in the “presence of acute local infections. ” Systemic use of glucocorticoids is generally considered con-traindicated in systemic fungal infections (unless used for replace-ment therapy in Addison's), when administered IM in patients with idiopathic thrombocytopenia, and in patients hypersensitive to a particular compound. Use of sustained-release injectable gluco-corticoids is considered contraindicated for chronic corticosteroid therapy of systemic diseases. Animals that have received glucocorticoids systemically other than with “burst” therapy, should be tapered off the drugs. Patients who have received the drugs chronically should be tapered off slowly as endogenous ACTH and corticosteroid function may re-turn slowly. Should the animal undergo a “stressor” (e. g., surgery, trauma, illness, etc. ) during the tapering process or until normal adrenal and pituitary function resume, additional glucocorticoids should be administered. Adverse Effects Adverse effects are generally associated with long-term administra-tion of these drugs, especially if given at high dosages or not on an alternate day regimen. Effects generally are manifested as clini-cal signs of hyperadrenocorticism. When administered to young, growing animals, glucocorticoids can retard growth. Many of the potential effects, adverse and otherwise, are outlined above in the Pharmacology section. In dogs, polydipsia (PD), polyphagia (PP), and polyuria (PU) may all be seen with short-term “burst” therapy as well as with al-ternate-day maintenance therapy on days when administering the drug. Adverse effects in dogs can include dull, dry haircoat, weight gain, panting, vomiting, diarrhea, elevated liver enzymes, pancrea-titis, GI ulceration, lipidemias, activation or worsening of diabetes mellitus, muscle wasting, and behavioral changes (depression, leth-argy, viciousness). Discontinuation of the drug may be necessary; changing to an alternate steroid may also alleviate the problem. With the exception of PU/PD/PP, adverse effects associated with	pppbs.pdf
602 METHYLPREDNISOLONE antiinﬂammatory therapy are relatively uncommon. Adverse effects associated with immunosuppressive doses are more common and, potentially, more severe. Cats generally require higher dosages than dogs for clinical effect, but tend to develop fewer adverse effects. Occasionally, polydipsia, polyuria, polyphagia with weight gain, diarrhea, or depression can be seen. Long-term high dose therapy can lead to “Cushingoid” ef-fects, however. Administration of dexamethasone or triamcinolone may play a role in the development of laminitis in horses. Reproductive/Nursing Safety Glucocorticoids are probably necessary for normal fetal develop-ment. They may be required for adequate surfactant production, myelin, retinal, pancreas and mammary development. Excessive dosages early in pregnancy may lead to teratogenic effects. In hors-es and ruminants, exogenous steroid administration may induce parturition when administered in the latter stages of pregnancy. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Use with caution in nursing dams. Glucocorticoids unbound to plasma proteins will enter milk. High dosages or prolonged admin-istration to mothers may, potentially, inhibit growth, interfere with endogenous corticosteroid production or cause other unwanted effects in nursing offspring. However, in humans, several studies suggest that amounts excreted in breast milk are negligible when methylprednisolone doses are less than or equal to 8 mg/day. Larger doses for short periods may not harm the infant. Overdosage/Acute Toxicity Glucocorticoids when given short-term are unlikely to cause harm-ful effects, even in massive dosages. One incidence of a dog develop-ing acute CNS effects after accidental ingestion of glucocorticoids has been reported. Should clinical signs occur, use supportive treat-ment if required. Chronic usage of glucocorticoids can lead to serious adverse ef-fects. Refer to Adverse Effects above for more information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving methylprednisolone and may be of signiﬁcance in veterinary patients: !TAMPHOTERICIN B : Administered concomitantly with glucocorti-coids may cause hypokalemia; in humans, there have been cases of CHF and cardiac enlargement reported after using methyl-prednisolone to treat Amphotericin B adverse effects !TANALGESICS, OPIATE and/or ANESTHETICS, LOCAL (epidural injections ): Combination with glucocorticoids in epidurals has caused seri-ous CNS injuries and death; do not use more volume than very small intrathecal test doses of these agents with glucocorticoids !TANTICHOLINESTERASE AGENTS (e. g., pyridostigmine, neostigmine, etc. ): In patients with myasthenia gravis, concomitant gluco-corticoid and anticholinesterase agent administration may lead to profound muscle weakness. If possible, discontinue anticho-linesterase medication at least 24 hours prior to corticosteroid administration !TASPIRIN : Glucocorticoids may reduce salicylate blood levels !TBARBITURATES : May increase the metabolism of glucocorticoids and decrease blood levels !TCYCLOPHOSPHAMIDE : Glucocorticoids may inhibit the hepatic metabolism of cyclophosphamide; dosage adjustments may be required !TCYCLOSPORINE : Concomitant administration of glucocorticoids and cyclosporine may increase the blood levels of each, by mutu-ally inhibiting the hepatic metabolism of each other; the clinical signiﬁcance of this interaction is not clear !TDIURETICS, POTASSIUM-DEPLETING (e. g., spironolactone, triamterene ): Administered concomitantly with glucocorticoids may cause hypokalemia !TEPHEDRINE : May reduce methylprednisolone blood levels !TESTROGENS : The effects of methylprednisolone, and possibly oth-er glucocorticoids, may be potentiated by concomitant adminis-tration with estrogens !TINSULIN : Insulin requirements may increase in patients receiving glucocorticoids !TKETOCONAZOLE and other AZOLE ANTIFUNGALS : May decrease the metabolism of glucocorticoids and increase methylprednisolo-ne blood levels; ketoconazole may induce adrenal insufﬁciency when glucocorticoids are withdrawn by inhibiting adrenal corti-costeroid synthesis !TMACROLIDE ANTIBIOTICS (erythromycin, clarithromycin ): May de-crease the metabolism of glucocorticoids and increase methyl-prednisolone blood levels !TMITOTANE : May alter the metabolism of steroids; higher than usu-al doses of steroids may be necessary to treat mitotane-induced adrenal insufﬁciency !TNSAID s: Administration of ulcerogenic drugs with glucocorticoids may increase the risk of gastrointestinal ulceration !TPHENOBARBITAL : May increase the metabolism of glucocorticoids and decrease methylprednisolone blood levels !TRIFAMPIN : May increase the metabolism of glucocorticoids and decrease methylprednisolone blood levels !TVACCINES : Patients receiving corticosteroids at immunosuppres-sive dosages should generally not receive live attenuated-virus vaccines as virus replication may be augmented; a diminished immune response may occur after vaccine, toxoid, or bacterin administration in patients receiving glucocorticoid !TWARFARIN : Methylprednisolone may affect INR's; monitor Laboratory Considerations !TMethylprednisolone acetate may reduce post-ACTH cortisol c on-centrations by 20-50%. !TGlucocorticoids may increase serum cholesterol !TGlucocorticoids may increase serum and urine glucose levels !TGlucocorticoids may decrease serum potassium !TGlucocorticoids can suppress the release of thyroid stimulating hormone (TSH) and reduce T3 & T4 values. Thyroid gland atro-phy has been reported after chronic glucocorticoid administra-tion. Uptake of I131 by the thyroid may be decreased by glucocor-ticoids. !TReactions to skin tests may be suppressed by glucocorticoids !TFalse-negative results of the nitroblue tetrazolium test for systemic bacterial infections may be induced by glucocorticoids !TGlucocorticoids may cause neutrophilia within 4-8 hours after dosing and return to baseline within 24-48 hours after drug dis-continuation !TGlucocorticoids can cause lymphopenia which can persist for weeks after drug discontinuation in dogs	pppbs.pdf
METHYLPREDNISOLONE 603 Doses !TDOGS: As an antiinﬂammatory agent: a) Initially 1-2 mg/kg/day divided two to three times daily for 5 to 10 days. After clinical signs are suppressed, consolidate dose (1-2 mg/kg/day) and give at 7-10 AM once a day for 1 week. Then reduce dose to 0. 5-1 mg/kg/day for 5-7 days. Convert to alternate day dosing by giving 1-2 mg/kg on alternate mornings. Reduce dosage by H each week until a minimally effective dose is reached. (Kemppainen 1986) b) Methylprednisolone: 1 mg/kg PO q8h; methylprednisolone acetate: 1 mg/kg IM every 14 days (Jenkins 1985) c) Methylprednisolone acetate: 1. 1 mg/kg SC or IM; effects (for dermatologic indications) generally last for 1-3 weeks (Scott 1982) d) For labeled uses: Oral: Dogs weighing 5-15 lbs: 2 mg Dogs weighing 15-40 lbs: 2-4 mg Dogs weighing 40-80 lbs: 4-8 mg These total daily doses should be divided and given 6-10 hours apart. Intramuscularly: 2-120 mg IM (average 20 mg); depending on breed (size), severity of condition, and response. May re-peat at weekly intervals or in accordance with the severity of the condition and the response. (Package insert; Depo-Medrol®—Upjohn) The manufacturer has speciﬁc directions for use of the drug intrasynovially. It is recommended to re-fer directly to the package insert for more information. As an immunosuppressant: a) Pulse therapy to induce remission or control of autoimmune skin diseases: Methylprednisolone sodium succinate 11 mg/ kg in 250 m L D 5W infused IV over 1 hour for 3 consecu-tive days. Cimetidine 4 mg/kg PO q8h may also be given to reduce GI implications. After day 3, begin oral prednisone maintenance at 1. 1 mg/kg q24-48h. Azathioprine can also be added during maintenance phase. (White, Stewart, and Bernstein 1987) For adjunctive medical therapy of spinal cord trauma [ Note : At present (2007), use of corticosteroids for use in CNS/spinal chord trauma is very controversial]: a) Methylprednisolone sodium succinate: Initially, 30 mg/kg IV; 2 hours later give 15 mg/kg IV. Then give 10 mg/kg IV or SC 4 times a day for 24-36 hours. Reduce dosage gradually over next 7 days. Cimetidine may be helpful in preventing hemor-rhagic gastroenteritis associated with high dose glucocorti-coids. (Schunk 1988a) b) Two dosing schedules: 30 mg/kg IV followed 2 hours later with a constant IV infu-sion of 5. 4 mg/kg/hr for 24-48 hours 30 mg/kg IV loading dose, followed by 15 mg/kg IV 2 hours later then every 6 hours for 24-48 hours (Thomas 2002) For adjunctive therapy for various forms of shock [ Note : At pres-ent (2007), use of corticosteroids for use in shock is very con-troversial]: a) Methylprednisolone sodium succinate: 30-35 mg/kg IV (Kemppainen 1986) For intralesional (sub-lesional) use: a) A sufﬁcient volume of 20 mg/m L methylprednisolone ac-etate is used to undermine the lesion (10-40 mg total dose) (Scott 1982) !TCATS: As an antiinﬂammatory agent: a) Methylprednisolone acetate: 5. 5 mg/kg SC or IM (average sized cat = 20 mg); effects (for dermatologic indications) generally last for 1 week to 6 months (Scott 1982) b) For labeled uses: Oral: Cats weighing 5-15 lbs: 2 mg Cats weighing >15 lbs: 2-4 mg These total daily doses should be divided and given 6-10 hours apart Intramuscularly: up to 20 mg (average 10 mg) IM; depend-ing on breed (size), severity of condition, and response. May repeat at weekly intervals or in accordance with the severity of the condition and the response. (Package insert; Depo-Medrol®—Upjohn) For adjunctive treatment of cerebral ischemic necrosis: a) Methylprednisolone sodium succinate: 30 mg/kg IV (Korne-gay 2003a) For eosinophilic ulcer: a) Methylprednisolone acetate 20 mg SC every 2 weeks for 2-3 doses. If chronic case, maintenance therapy may be required at 20 mg SC as needed. May also consider adding megestrol acetate. (De Novo, Potter, and Woolfson 1988) As alternate adjunctive therapy for feline plasma cell gingivitis-pharyngitis: a) Methylprednisolone acetate 10-20 mg SC as needed. May also consider adding megestrol acetate. (De Novo, Potter, and Woolfson 1988) As an antiinﬂammatory for the adjunctive treatment of feline asthma: a) Methylprednisolone acetate: 2 mg/kg (dosage interval or route not speciﬁed) (Papich 1986) b) Methylprednisolone acetate: 1-2 mg/kg IM (dosage interval not speciﬁed) (Noone 1986) For adjunctive therapy of ﬂea allergy: a) Methylprednisolone acetate: 5 mg/kg SC; generally will keep animal comfortable for 3-6 weeks. Do not use more often than every 2 months. (Kwochka 1986) For adjunctive treatment of idiopathic feline miliary dermatoses: a) Methylprednisolone acetate: 5 mg/kg SC; if favorable re-sponse is noted, may repeat same dosage two times at 2-3 week intervals. Thereafter, do not use more often than every 2 months. (Kwochka 1986) For adjunctive treatment of pulmonary edema secondary to blood transfusion reactions: a) 30 mg/kg repeated every 6 hours (route not speciﬁed) (Auer and Bell 1986) For intralesional (sub-lesional) use: a) A sufﬁcient volume of 20 mg/m L methylprednisolone ac-etate is used to undermine the lesion (10-40 mg total dose) (Scott 1982) !THORSES: As an antiinﬂammatory (glucocorticoid effects): a) Methylprednisolone: 0. 5 mg/kg PO; Methylprednisolone so-dium succinate: 0. 5 mg/kg IV or IM (Robinson 1987) b) For labeled uses: Methylprednisolone acetate 200 mg IM repeated as necessary (Package insert; Depo-Medrol®— Upjohn). The manufacturer has speciﬁc directions for use of the drug intrasynovially. It is recommended to refer directly to the package insert for more information.	pppbs.pdf
604 METHYLTESTOSTERONE Tc) For intra-articular use: Methylprednisolone acetate 100 mg IA (Mc Clure 2002) For shock [ Note : At present (2007), use of corticosteroids for use in shock is very controversial]: Methylprednisolone sodium suc-cinate: a) 10-20 mg/kg IV (Robinson 1987) Monitoring Monitoring of glucocorticoid therapy is dependent on its reason for use, dosage, agent used (amount of mineralocorticoid activity), dosage schedule (daily versus alternate day therapy), duration of therapy, and the animal's age and condition. The following list may not be appropriate or complete for all animals; use clinical assess-ment and judgment should adverse effects be noted: T ! Weight, appetite, signs of edema T ! Serum and/or urine electrolytes T ! otal plasma proteins, albumin T ! Blood glucose T ! Growth and development in young animals T ! ACTH stimulation test if necessary Client Information T ! Clients should carefully follow the dosage instructions and should not discontinue the drug abruptly without consulting with vet-erinarian beforehand. T ! Clients should be briefed on the potential adverse effects that can be seen with these drugs and instructed to contact the veterinar-ian should these effects become severe or progress. Chemistry/Synonyms Methylprednisolone is a synthetically produced glucocorticoid. Both the free alcohol and the acetate ester occur as odorless, white or practically white, crystalline powder. They are practically insolu-ble in water and sparingly soluble in alcohol. Methylprednisolone sodium succinate occurs as an odorless, white or nearly white, hygroscopic, amorphous solid. It is very sol-uble in both water and alcohol. Methylprednisolone may also be known as: 6alpha-methyl-prednisolone, methylprednisolonum, NSC-19987, A-Methapred®, Alergolon®, Caberdelta M®, Cipridanol®, Cortisolona®, Depo-Medrol®, Esametone®, Firmacort®, Medrate®, Medrol®, Medrone®, Mega-Star®, Metilpren®, Metisona®, Methapred®, Metypred ®, Metysolon®, Predni M®, Prednilen®, Reactenol®, Sieropresol®, Solomet®, Solu-Medrol®, Summicort® and Urbason®. Storage/Stability/Compatibility Commercially available products of methylprednisolone should be stored at room temperature (15-30°C); avoid freezing the acetate injection. After reconstituting the sodium succinate injection, store at room temperature and use within 48 hours; only use solutions that are clear. Methylprednisolone sodium succinate injection is reportedly physically compatible with the following ﬂuids and drugs: amino acids 4. 25%/dextrose 25%, amphotericin B (limited amounts), chloramphenicol sodium succinate, cimetidine HCl, clindamy-cin phosphate, dopamine HCl, heparin sodium, metoclopramide, norepinephrine bitartrate, penicillin G potassium, sodium iodide/ aminophylline, and verapamil. The following drugs and ﬂuids have either been reported to be physically incompatible when mixed with methylprednisolone sodi-um succinate, compatible dependent upon concentration, or data conﬂicts: D 5/half normal saline, D 5 normal saline (80 mg/L re-ported compatible), D 5W (up to 5 grams/L reported compatible), Lactated Ringer's (up to 80 mg/L reported compatible), normal saline (data conﬂicts; some reports of up to 60 grams/liter com-patible), calcium gluconate, cephalothin sodium (up to 500 mg/L in D5W or NS compatible), glycopyrrolate, insulin, metaraminol bitartrate, nafcillin sodium, penicillin G sodium, and tetracycline HCl. Compatibility is dependent upon factors such as p H, concen-tration, temperature, and diluent used; consult specialized refer-ences or a hospital pharmacist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Methylprednisolone Tablets: 4 mg tablets, Medrol®; (Pﬁzer); (Rx). Approved for use in dogs and cats. Methylprednisolone Acetate Injection: 20 mg/m L in 10 m L and 20 m L vials, and 40 mg/m L in 5 m L vials; Depo-Medrol® (Pﬁzer); ge-neric; (Rx). Approved for IM and intrasynovial injection in dogs and horses; for IM injection in cats. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. A 10 ppb tolerance has been established for methylprednisolone in milk. HUMAN-LABELED PRODUCTS: Methylprednisolone Tablets: 2 mg, 4 mg, 8 mg, 16 mg, 24 mg & 32 mg; Medrol ® (Upjohn); generic; (Rx) Methylprednisolone Acetate Injection: 20 mg/m L, 40 mg/m L, 80 mg/ m L suspension in 1 m L, 5 m L and 10 m L vials; Depo-Medrol® (Up-john); generic; (Rx) Methylprednisolone Sodium Succinate Powder for Injection: 40 mg/ vial in 1 and 3 m L vials and 1 m L Univials and Act-O-Vials; 125 mg/ vial in 2 m L and 5 m L vials and 2 m L Univials and Act-O-Vials; 500 mg/vial in 1 m L, 4 m L, 8m L (with or without diluent) and 20 m L vi-als m L; 1 g/vial in 1 m L, 8 m L, 50 m L, & 1 g vials (with or without di-luent), 8 m L Act-O-Vials; 2 g/vial with diluent; Solu-Medrol® (Pﬁzer); A-Methapred® (Hospira); generic; (Rx) 4-Methylpyrazole — see Fomepizole METHYLTESTOSTERONE (meth-ill-tess-toss-ter-ohn) Android®, Methitest® ANDROGENIC/ANA BOLIC Prescriber Highlights TT Androgenic & anabolic agent that may be useful to sup-press estrus, treat testosterone-responsive alopecia, & pseudopregnancy in dogs TT Use in cats is controversial as hepatotoxicity may be more prevalent TT Contraindicated in pregnancy or hepatic dysfunction TT Most serious adverse effect is hepatotoxicity Uses/Indications In female dogs, methyltestosterone may be useful for suppression of estrus, treating estrogen-dependent mammary tumors, pseu-dopregnancy, or certain hormonal-dependent alopecias. In male dogs, it may be useful for treating deﬁcient libido and certain hor-monal alopecias. In cats, methyltestosterone may be useful for cer-tain hormonal-dependent alopecias and to increase libido in toms.	pppbs.pdf
METHYLTESTOSTERONE 605 Because of the potential for abuse by humans, and potential toxicity (especially hepatotoxicity) in animals, use of methyltestosterone is somewhat controversial in veterinary medicine, particularly in rac-ing Greyhounds and cats. Pharmacology/Actions Methyltestosterone is an androgen with anabolic effects. It has a methyl-group at the 17 position of the steroid nucleus of testos-terone, resulting in better oral absorption and slower hepatic me-tabolism than testosterone. Androgens are required for both the development and maintenance of male sexual characteristics and function. The anabolic effects of methyltestosterone include stim-ulating erythropoiesis, enhancing nitrogen balance and protein anabolism (in the presence of sufﬁcient protein and calories) and retention of potassium, sodium, and phosphorus. Pharmacokinetics Methyltestosterone is absorbed from the GI tract and oral mucosa. It undergoes less ﬁrst pass metabolism than orally administered tes-tosterone. In dogs, methyltestosterone is metabolized in the liver. Principle metabolites found in urine are glucuronidated forms (both conjugated and free) of methyltestosterone. Unlike in hu-mans, sulfated forms are not a major metabolic component. In humans, peak levels occur about 2 hours after oral dosing; elimination half-life is approximately 3 hours. Contraindications/Precautions/Warnings Methyltestosterone is contraindicated in patients with hepatic dysfunction and during pregnancy (see Reproductive Safety). It should be used with extreme caution in animals with heart failure. Prolonged use in young animals can cause premature epiphyseal closure. Adverse Effects Adverse effects in animals include: hepatotoxicity, virilization of females (clitoral hypertrophy), vaginal discharge, prostatic hyper-plasia and increased aggression in males. Chronic dosing in dogs of 2-6 mg/kg/day for 27 weeks caused hepatotoxicity characterized by enlarged periportal hepatocytes, and hemosiderin in macrophages. Cats may be more susceptible to hepatic injury than are dogs. Reproductive/Nursing Safety Spermatogenesis suppression in males may occur with high dosage methyltestosterone secondary to a negative feedback mechanism. Methyltestosterone may suppress estrus in females (see Uses). After the drug is discontinued, normal reproductive function usually re-turns in both males and females. Methyltestosterone is contraindicated during pregnancy. Dose-related genital masculinization of female fetuses is well described. In humans, the FDA categorizes this drug as category X for use during pregnancy (Studies in animals or humans demonstrate fetal abnormalities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any possible beneﬁt. ) Overdosage/Acute Toxicity Information on the acute toxicity of methyltestosterone is limited. Nausea and edema are the most likely effects of a single overdose. Consider liver function monitoring with large overdoses. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving methyltestosterone and may be of signiﬁcance in veterinary patients: !TCYCLOSPORINE : Methyltestosterone may increase serum cy-closporine levels !TINSULIN; ORAL ANTIDIABETIC AGENTS : Methyltestosterone may de-crease serum glucose levels !TWARFARIN : Methyltestosterone may increase anticoagulant effects Laboratory Considerations !TMethyltestosterone or other androgens can decrease thyroxine-binding globulin concentrations. This can cause decreased serum levels of total T 4 and increased resin uptake of T 4 and T 3. Clini-cally, this is unimportant, as free thyroid hormone concentra-tions are not affected. Doses !TDOGS/CAT S: a) Dogs: For pinnal alopecia in male dogs: 1 mg/kg PO every other day, to a maximum dose of 30 mg has had some suc-cess. (Brignac and Bevier 1997) b) Dogs: For treatment of testosterone-responsive dermatosis: 1 mg/kg PO every other day, to a maximum dose of 30 mg. Once dog responds, then every 4-7 days. (Nelson and Elliott 2003a) c) Dogs: T o suppress estrus in Greyhounds: 5 mg (total dose) once weekly or divided, two times a week. (Eilts 2005) d) Dogs: For estrus suppression: 25-50 mg (total dose) twice weekly PO. (Romagnoli 2003b) e) Dogs/Cats: For anti-estrogenic activity, development of male sexual characteristics (anatomical and behavioral), negative feedback on gonadotropin release from pituitary, and ana-bolic effects: 0. 5 mg/kg PO once daily; dose may need to be adjusted, but should not exceed 1 mg/kg. (Label information; Orandrone®—Intervet UK. Note : This product has reportedly been withdrawn from the U. K. market. ) Monitoring !THepatic function (liver enzymes, icterus, anorexia/weight loss/ vomiting) Client Information !TPotential adverse effects include: liver toxicity, masculinization or vaginal discharge in females, prostate problems and aggression in males !TContact veterinarian if any of the following occur: changes in be-havior, anorexia/weight loss/vomiting, or signs of icterus Chemistry/Synonyms Methyltestosterone occurs as white or creamy-white, odorless, crys-tals or crystalline powder. It is slightly hygroscopic, practically in-soluble in water, freely soluble in alcohol, and sparingly soluble in vegetable oils. Methyltestosterone may also be known as NSC-9701 or by its chemical name, 17beta-Hydroxy-17alpha-methyladrost-4-ene-3-one, Android®, Methitest®, Testred® and Virilon®. A tradename for a veterinary product formerly available in the U. K. is Orandrone® (Intervet). Storage/Stability Unless otherwise speciﬁed by the manufacturer, methyltestosterone tablets or capsules should be stored below 40°C, preferably between 15°-30°C in well-closed containers.	pppbs.pdf
606 METOCLOPRAMIDE HCL Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See appendix for more information. HUMAN-LABELED PRODUCTS: Methyltestosterone Tablets: 10 mg, & 25 mg; Methitest® (Global), ge-neric; (Rx, C-III) Methyltestosterone Buccal Tablets: 10 mg; Android® (Valeant), ge-neric; (Rx, C-III) Methyltestosterone Capsules: 10 mg; Testred® (Valeant), Virilon® (Star); (Rx, C-III) METOCLOPRAMIDE HCL (met-oh-kloe-pra-mide) Reglan® GI PROKINETIC AGENT Prescriber Highlights TT Stimulates upper GI motility & has antiemetic properties; more potent as an antiemetic than a prokinetic agent TT Contraindications: GI hemorrhage, obstruction or perfora-tion, hypersensitivity TT Relatively contraindicated: Seizure disorders, pheochromocytoma TT Adverse Effects: DOGS: Changes in mentation & behav-ior, constipation; CAT S: Signs of frenzied behavior or disorientation, constipation; HORSES: IV use, severe CNS effects, behavioral changes & abdominal pain; FOALS: Adverse effects less common Uses/Indications Metoclopramide has been used in veterinary species for both its GI stimulatory and antiemetic properties. It has been used clini-cally for gastric stasis disorders, gastroesophageal reﬂux, to allow intubation of the small intestine, as a general antiemetic (for par-vovirus, uremic gastritis, etc. ), and an antiemetic to prevent or treat chemotherapy-induced vomiting. Pharmacology/Actions The primary pharmacologic effects of metoclopramide are associ-ated with the GI tract and the CNS. In the GI tract, metoclopr-amide stimulates motility of the upper GI without stimulating gas-tric, pancreatic or biliary secretions. While the exact mechanisms for these actions are unknown, it appears that metoclopramide sensitizes upper GI smooth muscle to the effects of acetylcholine. Intact vagal innervation is not necessary for enhanced motil-ity, but anticholinergic drugs will negate metoclopramide's effects. Gastrointestinal effects seen include increased tone and amplitude of gastric contractions, relaxed pyloric sphincter, and increased duodenal and jejunal peristalsis. Gastric emptying and intestinal transit times can be signiﬁcantly reduced. There is little or no ef-fect on colon motility. Additionally, metoclopramide will increase lower esophageal sphincter pressure and prevent or reduce gastroe-sophageal reﬂux. The above actions evidently give metoclopramide its local antiemetic effects. In the CNS, metoclopramide apparently antagonizes dopamine at the receptor sites. This action can explain its sedative, central anti-emetic (blocks dopamine in the chemo-receptor trigger zone), extrapyramidal, and prolactin secretion stimulation effects. Pharmacokinetics Metoclopramide is absorbed well after oral administration, but a signiﬁcant ﬁrst-pass effect in some human patients may reduce sys-temic bioavailability to 30%. There apparently is a great deal of in-terpatient variation with this effect. Bioavailability after intramus-cular administration has been measured to be 74-96%. After oral dosing, peak plasma levels generally occur within 2 hours. The drug is well distributed in the body and enters the CNS. Metoclopramide is only weakly bound to 13-22% of plasma pro-teins. The drug also crosses the placenta and enters the milk in con-centrations approximately twice those of plasma. Metoclopramide is primarily excreted in the urine in humans. Approximately 20-25% of the drug is excreted unchanged in the urine. The majority of the rest of the drug is metabolized to glucuronidated or sulfated conjugate forms and then excreted in the urine. Approximately 5% is excreted in the feces. The half-life of metoclopramide in the dog has been reported to be approximately 90 minutes. Contraindications/Precautions/Warnings Metoclopramide is contraindicated in patients with GI hemor-rhage, obstruction or perforation, and in those hypersensitive to it. It is relatively contraindicated in patients with seizure disorders. In patients with pheochromocytoma, metoclopramide may induce a hypertensive crisis. Adverse Effects In dogs, the most common (although infrequent) adverse reactions seen are changes in mentation and behavior (motor restless and hyperactivity to drowsiness/depression). Cats may exhibit signs of frenzied behavior or disorientation. Both species can develop con-stipation while receiving this medication. In adult horses, IV metoclopramide administration has been as-sociated with the development of severe CNS effects. Alternating periods of sedation and excitement, behavioral changes and ab-dominal pain have been noted. These effects appear to be less com-mon in foals. Other adverse effects that have been reported in humans and are potentially plausible in animals include extrapyramidal effects, nausea, diarrhea, transient hypertension, and elevated prolactin levels. 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 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. ) Metoclopramide is excreted into milk and may concentrate at about twice the plasma level, but there does not appear to be signiﬁ-cant risk to nursing offspring.	pppbs.pdf
METOCLOPRAMIDE HCL 607 Overdosage/Acute Toxicity The oral LD 50 doses of metoclopramide in mice, rats, and rabbits are 465 mg/kg, 760 mg/kg and 870 mg/kg, respectively. Because of the high dosages required for lethality, it is unlikely an oral overdose will cause death in a veterinary patient. Likely clinical signs of over-dosage include sedation, ataxia, agitation, extrapyramidal effects, nausea, vomiting, and constipation. There is no speciﬁc antidotal therapy for metoclopramide in-toxication. If an oral ingestion was recent, the stomach should be emptied using standard protocols. Anticholinergic agents (diphen-hydramine 2. 2 mg/kg IV, benztropine, etc. ) that enter the CNS may be helpful in controlling extrapyramidal effects. Peritoneal dialysis or hemodialysis is not thought to be effective in enhancing the re-moval of the drug. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oral metoclopramide and may be of signiﬁcance in veterinary patients: !TANESTHETICS : If metoclopramide is used concurrently IV, acute hypotension has been reported !TATROPINE (and related anticholinergic compounds): May antago-nize the GI motility effects of metoclopramide !TCHOLINERGIC DRUGS (e. g., bethanechol ): May enhance metoclopr-amide's GI effects !TCNS DEPRESSANTS (e. g., anesthetic agents, antihistamines, phenoth-iazines, barbiturates, tranquilizers, alcohol, etc. ): Metoclopramide may enhance CNS depressant effects !TCYCLOSPORINE : Metoclopramide increase the rate and extent of GI absorption !TOPIATE ANALGESICS : May antagonize the GI motility effects of metoclopramide !TMAO INHIBITORS (including amitraz and potentially, selegiline ): Could cause hypertension !TPHENOTHIAZINES (e. g., acepromazine, chlorpromazine, etc. ) and BU-TYROPHENONES (e. g., droperidol, azaperone ): May potentiate the extrapyramidal effects of metoclopramide. The CNS effects of metoclopramide may be enhanced by other sedatives, tranquil-izers, and narcotics. !TTETRACYCLINES : Metoclopramide increase the rate and extent of GI absorption Doses !TDOGS: As an antiemetic: a) 0. 1-0. 4 mg/kg q6h PO, SC or IM; or 1-2 mg/kg/day as a continuous IV infusion (Washabau and Elie 1995) b) 0. 22-0. 55 mg/kg q8h parenterally; constant IV infusion of 1. 1-2. 2 mg/kg in 24 hours seems to be more effective than intermittent bolus therapy (Hall 2000) c) For bilious vomiting syndrome: 0. 2-0. 4 mg/kg PO once daily given late in the evening (Hall and Twedt 1988) d) T o help prevent vomiting in patients with laryngeal paralysis and resultant tracheostomy: 0. 05 mg/kg SC or slowly IV be-fore small feedings (O'Brien, 1986) e) T o treat vomiting associated with pancreatitis: 0. 01-0. 02 mg/kg/hr IV as a CRI or 0. 1-0. 5 mg/kg IM q8h (Waddell 2007c) For disorders of gastric motility: a) 0. 2-0. 4 mg/kg PO three times daily given 30 minutes before meals (Hall and Twedt 1988) b) 0. 2-0. 5 mg/kg PO or SC q8h; give 30 minutes prior to meals and at bedtime for gastro-motility disorders and esophageal reﬂux (De Novo 1986) c) 0. 2-0. 5 mg/kg PO q8h PO or parenterally (may be given as a constant rate IV infusion at 0. 01-0. 02 mg/kg/hr) (Hall and Washabau 2000) T o increase bladder contractility: a) 0. 2-0. 5 mg/kg PO q8h (Lane 2000) !TCATS: a) 0. 2-0. 4 mg/kg PO, SC 3-4 times daily; or as a continuous IV infusion (1-2 mg/kg per day) (Trepanier 1999) b) 0. 2-0. 5 mg/kg q8h PO or parenterally (may be given as a constant rate IV infusion at 0. 01-0. 02 mg/kg/hr) (Hall and Washabau 2000) c) T o increase bladder contractility: 0. 2-0. 5 mg/kg PO q8h (Lane 2000) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 0. 2-1 mg/kg PO or SC q6-8h (Ivey and Morrisey 2000) b) Rabbits: T o assist in removing gastric hairballs: 0. 5 mg/kg PO once a day (up to three times a day) (Burke 1999) c) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 0. 2-1 mg/kg PO, SC, IM q12h (Adamcak and Otten 2000) !THORSES: (Note : ARCI UCGFS Class 4 Drug) T o stimulate the gastrointestinal tract: a) 0. 04 mg/kg/hr as a CRI (Lester 2004) b) For reﬂux esophagitis: 0. 02-0. 1 mg/kg SC q4-12 hours; horses may be prone to the extrapyramidal neurologic side effects of metoclopramide. (Jones and Blikslager 2004) b) In foals: 0. 02-0. 1 mg/kg IM or IV 3-4 times a day (Clark and Becht 1987) Monitoring !TClinical efﬁcacy !TAdverse effects Client Information !TContact veterinarian if animal develops clinical signs of invol-untary movement of eyes, face, or limbs; or develops a rigid posture. Chemistry/Synonyms A derivative of para-aminobenzoic acid, metoclopramide HCl oc-curs as an odorless, white, crystalline powder with p K as of 0. 6 and 9. 3. One gram is approximately soluble in 0. 7 m L of water or 3 m L of alcohol. The injectable product has a p H of 3-6. 5. Metoclopramide HCl may also be known as: AHR-3070-C, DEL-1267, metoclopramidi hydrochloridum, and MK-745; many trade names are available. Storage/Stability/Compatibility Metoclopramide is photosensitive and must be stored in light resis-tant containers. All metoclopramide products should be stored at room temperature. Metoclopramide tablets should be kept in tight containers. The injection is reportedly stable in solutions of a p H range of 2-9 and with the following IV solutions: D 5W, 0. 9% sodium chlo-ride, D 5-H normal saline, Ringer's, and lactated Ringer's injection.	pppbs.pdf
608 METOPROLOL The following drugs have been stated to be physically compatible with metoclopramide for at least 24 hours: aminophylline, ascorbic acid, atropine sulfate, benztropine mesylate, chlorpromazine HCl, cimetidine HCl, clindamycin phosphate, cyclophosphamide, cytar-abine, dexamethasone sodium phosphate, dimenhydrinate, di-phenhydramine HCl, doxorubicin HCl, droperidol, fentanyl citrate, heparin sodium, hydrocortisone sodium phosphate, hydroxyzine HCl, insulin (regular), lidocaine HCl, magnesium sulfate, manni-tol, meperidine HCl, methylprednisolone sodium succinate, mor-phine sulfate, multivitamin infusion (MVI), pentazocine lactate, potassium acetate/chloride/phosphate, prochlorperazine edisylate, TPN solution (25% dextrose with 4. 25% Travasol® with or without electrolytes), verapamil, and vitamin B-complex with vitamin C. Metoclopramide is reported to be physically incompatible when mixed with the following drugs: ampicillin sodium, calcium glucon-ate, cephalothin sodium, chloramphenicol sodium succinate, cis-platin, erythromycin lactobionate, methotrexate sodium, penicillin G potassium, sodium bicarbonate, and tetracycline. Compatibility is dependent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references or a hospital phar-macist for more speciﬁc information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: All doses expressed in terms of metoclopramide monohydrate. Metoclopramide HCl Tablets: 5 mg & 10 mg; Maxolon® (SK-Bee-cham); Reglan® (Schwarz Pharma); generic; (Rx) Metoclopramide HCl Syrup: 1 mg/m L in 480 m L and UD 10 m L; generic; (Rx) Metoclopramide HCl Injection: 5 mg/m L in 2m L, 10 m L, 20m L, 30 m L vials, & 2 m L amps, and preservative free in 2 m L, 10 m L, 30 m L vials; and 2 m L and 10 m L amps; Reglan® (Wyeth-Ayerst); Octamide PFS® (Adria); generic; (Rx) METOPROLOL TARTRATE METOPROLOL SUCCINATE (me-toe-pro-lole) Lopressor®, Toprol XL® BETA-ADRENERGIC BLOCKER Prescriber Highlights TT Beta1-blocker used for supraventricular tachyarrhyth-mias, premature ventricular contractions (PVC's, VPC's), systemic hypertension, & treatment in cats with hypertro-phic cardiomyopathy TT Probably safer to use than propranolol in animals with bronchoconstrictive disease TT Contraindications: Overt heart failure, hypersensitivity beta-blockers, greater than ﬁrst-degree heart block, or sinus bradycardia TT Caution: Signiﬁcant hepatic insufﬁciency, bronchospastic lung disease, CHF, hyperthyroidism (masks clinical signs, but may be useful for treatment), labile diabetics, & si-nus node dysfunction TT Adverse Effects: Most common in geriatric animals or those that have acute decompensating heart disease, include: bradycardia, lethargy & depression, impaired AV conduction, CHF or worsening of heart failure, hypoten-sion, hypoglycemia, bronchoconstriction, syncope, & diarrhea TT Try to wean off drug gradually Uses/Indications Because metoprolol is relatively safe to use in animals with bron-chospastic disease, it is often chosen over propranolol. It may be ef-fective in supraventricular tachyarrhythmias, premature ventricular contractions (PVC's, VPC's), systemic hypertension, and treating cats with hypertrophic cardiomyopathy. There is increasing inter-est in using beta blockers in heart failure in dogs; one retrospec-tive study showed increased survival times when dogs were given metoprolol, but deﬁnitive prospective, double-blinded studies have not been reported documenting the beneﬁt (increased survival) of beta-blockers in dogs with heart failure. Pharmacology/Actions Metoprolol is a relatively speciﬁc beta 1-blocker and is sometimes characterized as a second generation beta blocker. At higher dos-ages, this speciﬁcity may be lost and beta 2 blockade can occur. Metoprolol does not possess any intrinsic sympathomimetic activ-ity like pindolol nor does it possess membrane-stabilizing activity like pindolol or propranolol. Cardiovascular effects secondary to metoprolol's negative inotropic and chronotropic actions include: decreased sinus heart rate, slowed A V conduction, diminished car-diac output at rest and during exercise, decreased myocardial oxy-gen demand, reduced blood pressure, and inhibition of isoprotere-nol-induced tachycardia. Pharmacokinetics Metoprolol tartrate is rapidly and nearly completely absorbed from the GI tract, but it has a relatively high ﬁrst pass effect (50%) so systemic bioavailability is reduced. The drug has very low protein binding characteristics (5-15%) and is distributed well into most tissues. Metoprolol crosses the blood-brain barrier and CSF levels	pppbs.pdf
METOPROLOL 609 T Tare about 78% of those found in the serum. It crosses the placenta and levels in milk are higher (3-4X) than those found in plasma. Metoprolol is primarily biotransformed in the liver; unchanged drug and metabolites are then principally excreted in the urine. Reported half-lives in various species: Dogs: 1. 6 hours; Cats: 1. 3 hours; Humans 3-4 hours. Contraindications/Precautions/Warnings Metoprolol is contraindicated in patients with overt heart failure, hypersensitivity to this class of agents, greater than ﬁrst-degree heart block, or sinus bradycardia. Non-speciﬁc beta-blockers are generally contraindicated in patients with CHF unless secondary to a tachyarrhythmia responsive to beta-blocker therapy. They are also relatively contraindicated in patients with bronchospastic lung disease. Metoprolol should be used cautiously in patients with signiﬁ-cant hepatic insufﬁciency or sinus node dysfunction. Metoprolol (at high dosages) can mask the clinical signs associ-ated with hypoglycemia. It can also cause hypoglycemia or hyperg-lycemia and, therefore, should be used cautiously in labile diabetic patients. Metoprolol can mask the clinical signs associated with thyro-toxicosis, but it may be used clinically to treat the clinical signs as-sociated with this condition. Adverse Effects It is reported that adverse effects most commonly occur in geriat-ric animals or those that have acute decompensating heart disease. Adverse effects considered clinically relevant include: bradycardia, lethargy and depression, impaired A V conduction, CHF or worsen-ing of heart failure, hypotension, hypoglycemia, and bronchocon-striction (less so with beta1 speciﬁc drugs like metoprolol). Syncope and diarrhea have also been reported in canine patients with beta-blockers. Exacerbation of clinical signs has been reported following abrupt cessation of beta-blockers in humans. It is recommended to withdraw therapy gradually in patients who have been receiving the drug chronically. Reproductive/Nursing Safety Safe use during pregnancy has not been established, but adverse ef-fects to fetuses have apparently not been documented. In humans, the FDA categorizes this drug as category C for use during preg-nancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal re-production studies and no adequate studies in humans. ) Metoprolol is excreted in milk in very small quantities and is unlikely to pose signiﬁcant risk to nursing offspring. Overdosage/Acute Toxicity There is limited information available on metoprolol overdosage. Humans have apparently survived dosages of up to 5 grams. The most predominant clinical signs expected would be extensions of the drug's pharmacologic effects: hypotension, bradycardia, bron-chospasm, cardiac failure, and, potentially, hypoglycemia. There were 8 exposures to metoprolol reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org ) dur-ing 2005-2006. In these cases 7 were dogs with 1 showing clini-cal signs and the remaining case was a cat that showed no clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included lethargy and tachycardia. If overdose is secondary to a recent oral ingestion, emptying the gut and charcoal administration may be considered. Use caution in-ducing emesis as coma and seizures may develop rapidly. Monitor: ECG, blood glucose, potassium, and, if possible, blood pressure. Treatment of the cardiovascular effects is symptomatic. Use ﬂuids and pressor agents to treat hypotension. Bradycardia may be treat-ed with atropine. If atropine fails, isoproterenol, given cautiously, has been recommended. Use of a transvenous pacemaker may be necessary. Cardiac failure can be treated with a digitalis glycosides, diuretics, and oxygen. Glucagon (5-10 mg IV—Human dose) may increase heart rate and blood pressure and reduce the cardiodepres-sant effects of metoprolol. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving metoprolol and may be of signiﬁcance in veterinary patients: !TANESTHETICS, GENERAL (with myocardial depressant effects ): In-creased risk for heart failure and hypotension !TCALCIUM-CHANNEL BLOCKERS (e. g., diltiazem, verapamil, amlodipine ): Concurrent use of beta-blockers with calcium channel blockers (or other negative inotropics) should be done with caution, par-ticularly in patients with preexisting cardiomyopathy or CHF !TDIGOXIN : Use with metoprolol may increase negative effects on SA or A V node conduction !TDIURETICS (thiazides, furosemide ): May increase hypotensive effect of metoprolol !THYDRALAZINE : May increase the risks for pulmonary hypertension in uremic patients !TQUINIDINE : May increase metoprolol plasma concentrations !TRESERPINE : Potential for additive effects (hypotension, bradycardia) !TSSRI ANTIDEPRESSANTS (e. g., ﬂuoxetine, sertraline, paroxetine ): May increase metoprolol plasma concentrations !TSYMP ATHOMIMETICS (metaproterenol, terbutaline, beta-effects of epinephrine, phenylpropanolamine, etc. ): May have their actions blocked by metoprolol and they may, in turn, reduce the efﬁcacy of atenolol Doses !TDOGS: As an oral beta blocker: a) 5-50 mg (total dose) two to three times a day; initial dose should be low followed by individual dosage titration (Ware 1992) b) 0. 2-0. 4 mg/kg PO q12h and if all is well after two weeks, increase dose to 0. 4 mg/kg twice daily. In dogs with chronic valvular disease, a third increment is made 2 weeks later to 0. 6 mg/kg twice a day. (Rush and Freeman 2003) c) T o decrease the incidence atrial ﬁbrillation and ﬂutter in dogs undergoing valve surgery: Using sustained release metoprolol (Toprol-XR®) at 0. 4-1 mg/kg PO q24h administered before and as soon as feasible after surgery. (Orton 2006) !TCATS: As an oral beta blocker: a) 2-15 mg (total dose) PO q8h (Papich 1992), (Brovida 2002) Monitoring !TCardiac function, pulse rate, ECG if necessary, BP if indicated !Toxicity (see Adverse Effects/Overdosage) Client Information !To be effective, the animal must receive all doses as prescribed !TNotify veterinarian if animal becomes lethargic or exercise intol-erant, has shortness of breath or cough, or develops a change in behavior or attitude	pppbs.pdf
610 METRONIDAZOLE Chemistry/Synonyms A beta1 speciﬁc adrenergic blocker, metoprolol tartrate occurs as a white, crystalline powder having a bitter taste. It is very soluble in water. Metoprolol succinate occurs as a white, crystalline powder and is freely soluble in water. Metoprolol may also be known as: CGP-2175E; H-93/26, and metoprolol; many trade names are available. Storage/Stability/Compatibility Store all products protected from light. Store tablets in tight, light-resistant containers at room temperature. Avoid freezing the injection. The injection is compatible with D5W and normal saline. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Metoprolol Tartrate Tablets: 25 mg, 50 mg & 100 mg; Lopressor® (No-vartis); generic; (Rx) Metoprolol Succinate Extended-Release Tablets (equivalent to meto-prolol tartrate): 25 mg, 50 mg, 100 mg & 200 mg; Toprol XL® (Astra-Zeneca); (Rx) Metoprolol Tartrate Injection: 1 mg/m L in 5 m L amps and Carpuject sterile cartridge units; Lopressor® (Novartis); (Rx); generic; (Hospi-ra); (Rx) METRONIDAZOLE (me-troe-ni-da-zole) Flagyl® ANTIBIOTIC, ANTIPARASITIC Prescriber Highlights TT Injectable & oral antibacterial (anaerobes) & antiproto-zoal agent TT Prohibited by the FDA for use in food animals TT Contraindications: Hypersensitivity to it or nitroimidazole derivatives. Extreme caution: in severely debilitated, preg-nant or nursing animals; hepatic dysfunction. TT Adverse Effects: Neurologic disorders, lethargy, weak-ness, neutropenias, hepatotoxicity, hematuria, anorexia, nausea, vomiting, & diarrhea TT May be a teratogen, especially in early pregnancy Uses/Indications Although there are no veterinary-approved metronidazole products, the drug has been used extensively in the treatment of Giardia in both dogs and cats. It is also used clinically in small animals for the treatment of other parasites (Trichomonas and Balantidium coli) as well as treating both enteric and systemic anaerobic infections. In horses, metronidazole has been used clinically for the treat-ment of anaerobic infections. Pharmacology/Actions Metronidazole is bactericidal against susceptible bacteria. Its exact mechanism of action is not completely understood, but it is taken-up by anaerobic organisms where it is reduced to an unidentiﬁed polar compound. It is believed that this compound is responsible for the drug's antimicrobial activity by disrupting DNA and nucleic acid synthesis in the bacteria. Metronidazole has activity against most obligate anaerobes including Bacteroides spp. (including B. fragilis), Fusobacterium, Veillonella, Clostridium spp., Peptococcus, and Peptostreptococcus. Actinomyces is frequently resistant to metronidazole. Metronidazole is also trichomonacidal and amebicidal in ac-tion and acts as a direct amebicide. Its mechanism of action for its antiprotozoal activity is not understood. It has therapeutic ac-tivity against Entamoeba histolytica, Trichomonas, Giardia, and Balantidium coli. It acts primarily against the trophozoite forms of Entamoeba rather than encysted forms. Finally, metronidazole has some inhibitive actions on cell-me-diated immunity. Pharmacokinetics Metronidazole is relatively well absorbed after oral administration. The oral bioavailability in dogs is high, but interpatient variable, with ranges from 50-100% reported. The oral bioavailability of the drug in horses averages about 80% (range 57-100%). If given with food, absorption is enhanced in dogs, but delayed in humans. Peak levels occur about one hour after dosing. Metronidazole is rather lipophilic and is rapidly and widely dis-tributed after absorption. It is distributed to most body tissues and ﬂuids, including bone, abscesses, the CNS, and seminal ﬂuid. It is less than 20% bound to plasma proteins in humans. Metronidazole is primarily metabolized in the liver via several pathways. Both the metabolites and unchanged drug are eliminated in the urine and feces. Elimination half-lives of metronidazole in patients with normal renal and hepatic function in various species are reported as: humans 6-8 hours, dogs 4-5 hours, and horses 2. 9-4. 3 hours. Contraindications/Precautions/Warnings Metronidazole is prohibited for use in food animals by the FDA. Metronidazole is contraindicated in animals hypersensitive to the drug or nitroimidazole derivatives. It has been recommended not to use the drug in severely debilitated, pregnant or nursing ani-mals. Metronidazole should be used with caution in animals with hepatic dysfunction. If the drug must be used in animals with sig-niﬁcant liver impairment, consider using only 25-50% of the usual dose. Adverse Effects Adverse effects reported in dogs include neurologic disorders, lethargy, weakness, neutropenias, hepatotoxicity, hematuria, an-orexia, nausea, vomiting, and diarrhea. Cats infrequently develop GI effects. Neurologic toxicity in dogs may be manifested after acute high dosages or, more likely, with chronic moderate to high-dose ther-apy. Clinical signs reported are described below in the Overdosage section. Metronidazole tablets have a sharp, metallic taste that animals ﬁnd unpleasant. Placing in capsules or using compounded oral sus-pensions may alleviate the problem of dosing avoidance. Reproductive/Nursing Safety Metronidazole's potential for teratogenicity is somewhat contro-versial; some references state that it has been teratogenic in some laboratory animal studies, but others state that it has not. However, unless the beneﬁts to the mother outweigh the risks to the fetus(es), it should not be used during pregnancy, particularly during the ﬁrst 3 weeks of gestation. 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	pppbs.pdf
METRONIDAZOLE 611 pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: 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. ) Because of the potential for tumorigenicity, consider using alter-native therapy or switching to milk replacer for nursing patients. Overdosage/Acute Toxicity Signs of intoxication associated with metronidazole in dogs and cats, include anorexia and/or vomiting, depression, mydriasis, nys-tagmus, ataxia, head-tilt, deﬁcits of proprioception, joint knuckling, disorientation, tremors, seizures, bradycardia, rigidity and stiffness. These effects may be seen with acute overdoses or in some animals on chronic therapy when using “recommended” doses. Diazepam has been used successfully to decrease the CNS effects associated with metronidazole toxicity; see the Diazepam monograph or the reference by Evans, Levesque, et al for more information. Acute overdoses should be handled by attempting to limit the absorption of the drug using standard protocols. Extreme caution should be used before attempting to induce vomiting in patients demonstrating CNS effects or aspiration may result. If acute tox-icity is seen after chronic therapy, the drug should be discontin-ued and the patient treated supportively and symptomatically. Neurologic clinical signs may require several days before showing signs of resolving. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving metronidazole and may be of signiﬁcance in veterinary patients: !TALCOHOL : May induce a disulﬁram-like (nausea, vomiting, cramps, etc. ) reaction when given with metronidazole. !TCIMETIDINE : May decrease the metabolism of metronidazole and increase the likelihood of dose-related side effects occurring. !TPHENOBARBITAL or PHENYTOIN : May increase the metabolism of metronidazole, thereby decreasing blood levels. !TWARFARIN : Metronidazole may prolong the PT in patients receiv-ing warfarin or other coumarin anticoagulants. Avoid concurrent use if possible; otherwise, intensify monitoring. Laboratory Considerations !TMetronidazole can cause falsely decreased readings of AST (SGOT) and ALT (SGPT) when determined using methods mea-suring decreases in ultraviolet absorbance when NADH is re-duced to NAD. Doses !TDOGS: For treatment of Giardia: a) 15-25 mg/kg PO q12-24h daily for 5-7 days (Lappin 2006b) b) 44 mg/kg PO initially, then 22 mg/kg PO q8h for 5 days (T odd, Paul, and Di Pietro 1985) c) 25-65 mg/kg PO once daily for 5 days (Longhofer 1988) d) 30-60 mg/kg PO once daily for 5-7 days (also for trichomo-niasis) (Chiapella 1988) For other protozoal infections: a) Entamoeba histolytica or Pentatrichomas hominis: 25 mg/kg PO q12h for 8 days (Lappin 2000) For anaerobic infections: a) For anaerobic bacterial meningitis: 25-50 mg/kg PO q12h (Schunk 1988) b) For suppurative cholangitis: 25-30 mg/kg PO two times a day; may be used with chloramphenicol. Therapy may be necessary for 4-6 weeks (Cornelius and Bjorling 1988) c) For sepsis: 15 mg/kg IV q12h (Hardie 2000) d) 44 mg/kg PO q12h (Aronson and Aucoin 1989) e) For anaerobic sepsis: 10 mg/kg IV three times daily as a CRI (T ello 2003a) For eliminating Helicobacter gastritis infections: a) Using triple therapy: Metronidazole 15. 4 mg/kg q8h, amoxi-cillin 11 mg/kg q8h and bismuth subsalicylate (original Pep-to-Bismol®) 0. 22 m L/kg PO q4-6h. Give each for 3 weeks. (Hall 2000) b) Using triple therapy: Metronidazole 33 mg/kg once daily, amoxicillin 11 mg/kg q12h and either sucralfate (0. 25-0. 5 grams q8h) or omeprazole 0. 66 mg/kg once daily (Hall 2000) For adjunctive therapy of plasmacytic/lymphocytic enteritis: a) 10 mg/kg PO three times daily for 2-4 weeks (Magne 1989) b) 10-30 mg/kg PO q8-24h for 2-4 weeks in refractory cases (Leib, Hay, and Roth 1989) For inﬂammatory bowel disease: a) For ulcerative colitis in dogs refractory to other therapies (e. g., sulfasalazine, immunosuppressants, diet, etc. ): 10-20 mg/kg PO twice daily-three times a day; may be beneﬁcial in treating for 2-4 weeks those dogs with chronic colitis having unexplained diarrhea (Leib 2000). b) Starting dose of 10-15 mg/kg PO q12h and then tapered to the lowest effective dose. (Moore 2004) c) 10-15 mg/kg PO q8-12h; combine with prednisone to manage moderate to severe cases. (Marks 2007b) For adjunctive therapy of hepatic encephalopathy: a) 20 mg/kg PO q8h (Hardy 1989) !TCATS: For treatment of Giardia: a) 15-25 mg/kg PO q12-24h daily for 5-7 days (Lappin 2006b) b) 25 mg/kg PO q12h for 7 days (Zoran 2007) For other protozoal infections: a) Entamoeba histolytica or Pentatrichomas hominis: 25 mg/kg PO q12h for 8 days (Lappin 2000) For treating H. pylori: a) Metronidazole 10-15 mg/kg PO two times a day; clarithro-mycin 7. 5 mg/kg PO two times a day; amoxicillin 20 mg/kg PO twice daily for 14 days (Simpson 2003b) For anaerobic infections: a) For sepsis: 15 mg/kg IV q12h (Hardie 2000)	pppbs.pdf
612 METRONIDAZOLE For adjunctive therapy of GI conditions: a) For inﬂammatory bowel disease: Initially, metronidazole at 11-22 mg/kg PO twice daily with prednisolone (initially at 1. 1-2. 2 mg/kg twice daily for ﬁrst 2-8 weeks until clinical signs improve). Usually at least several months of metron-idazole therapy is needed. (Taboada 2000) b) Starting dose of 10-15 mg/kg PO q12h and then tapered to the lowest effective dose. (Moore 2004) c) For inﬂammatory bowel disease: With a change of diet to “hypoallergenic”, may give metronidazole at 62. 5 mg (total dose) PO per cat once daily for 10-20 days. Resistant cats or those with severe disease are given immunosuppressive doses of prednisolone (1-2 mg/kg initially twice daily). (Gaschen 2006) d) 10-15 mg/kg PO q8-12h; combine with prednisone to manage moderate to severe cases. (Marks 2007b) e) For adjunctive therapy of hepatic lipidoses: 25-30 mg/kg PO twice daily for 2-3 weeks (unproven, but may be of beneﬁt) (Cornelius and Bjorling 1988) f) For hepatic encephalopathy: 7. 5 mg/kg PO q8-12h (Corne-lius, Bartges et al. 2000) !TFERRETS: For eliminating Helicobacter gastritis infections: a) Using triple therapy: Metronidazole 22 mg/kg, amoxicillin 22 mg/kg and bismuth subsalicylate (original Pepto-Bismol®) 17. 6 mg/kg PO. Give each 3 times daily for 3-4 weeks. (Hall 2000) For susceptible infections: a) 10-30 mg/kg PO once to twice daily. Very bitter; mask ﬂavor. (Williams 2000) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: For anaerobic infections: 20 mg/kg PO q12h for 3-5 days or 40 mg/kg PO once daily; 5 mg/kg slow IV q12h (Ivey and Morrisey 2000) b) Chinchillas: 10-40 mg/kg PO once daily as an antimicrobial; 50-60 mg/kg PO twice daily for 5 days as an antiparasiticide (Giardia) (Hayes 2000) c) Chinchillas, Gerbils, Guinea Pigs, Hamsters, Mice, Rats: 20-60 mg/kg PO q8-12h. Mice : 3. 5 mg/m L in water for 5 days. Rats: 10-40 mg per rat PO once daily. Chinchillas, Guinea pigs: 10-40 mg/kg PO once daily. Gerbils, Hamsters: 7. 5 mg/70-90 grams of body weight PO q8h. Add sucrose to improve palatability. (Adamcak and Otten 2000) !THORSES: For susceptible anaerobic infections: a) 20-25 mg/kg PO q8-12h; for treatment of colitis due to Clostridium spp., may dose at 15 mg/kg PO q8h. Can also dose at same dosages rectally if unable to dose PO. Metron-idazole is uncommonly associated with diarrhea and neuro-logic side effects. (Bentz 2007) b) 10-25 mg/kg PO 2-4 times a day (Chafﬁn 1999) c) Foals: 15 mg/kg PO or IV q6-12h (Brumbaugh 1999) d) Foals with C. perfringens: 10-15 mg/kg PO 3-4 times a day (dose depends on severity); if animal has an ileus and is in-tolerant of oral feeding give IV at 10 mg/kg IV 4 times a day (Slovis 2003a) e) For L. intracellularis infections: metronidazole 10-15 mg/ kg PO q8-12h with either oxytetracycline (10-18 mg/kg via slow IV q24h) or chloramphenicol (44 mg/kg PO q6-8h). (Frazer 2007) !TBIRDS: For susceptible infections (anaerobes): a) 50 mg/kg PO once daily for 5 days (Bauck and Hoefer 1993) b) Ratites (not to be used for food): 20-25 mg/kg PO twice daily (Jenson 1998) !TREPTILES: a) For anaerobic infections in most species: 150 mg/kg PO once; repeat in one week For amoebae and ﬂagellates in most species: 100-275 mg/kg PO once; repeat in 1-2 weeks. In Drymarchon spp., Lampropeltis pyromelana, and L. zonata: 40 mg/kg PO once; repeat in 2 weeks (Gauvin 1993) Monitoring !TClinical efﬁcacy !TAdverse effects (clients should report any neurologic symptoma-tology) Client Information !TReport any neurologic clinical signs to veterinarian (see Over-dose section). Chemistry/Synonyms A synthetic, nitroimidazole antibacterial and antiprotozoal agent, metronidazole occurs as white to pale yellow crystalline powder or crystals with a p K a of 2. 6. It is sparingly soluble in water or alcohol. Metronidazole base is commercially available as tablets or solution for IV injection and metronidazole HCl is available as injectable powder for reconstitution. The hydrochloride is very soluble in water. Metronidazole may also be known as: Bayer-5360, metronida-zolum, SC-32642, NSC-50364, RP-8823, and SC-10295; many trade names are available. Storage/Stability/Compatibility Metronidazole tablets and HCl powder for injection should be stored at temperatures less than 30°C and protected from light. The injection should be protected from light and freezing and stored at room temperature. Speciﬁc recommendations on the reconstitution, dilution, and neutralization of metronidazole HCl powder for injection are de-tailed in the package insert of the drug and should be referred to if this product is used. Do not use aluminum hub needles to recon-stitute or transfer this drug as a reddish-brown discoloration may result in the solution. The following drugs and solutions are reportedly physically compatible with metronidazole ready-to-use solutions for injec-tion: amikacin sulfate, aminophylline, carbenicillin disodium, ce-fazolin sodium, cefotaxime sodium, cefoxitin sodium, cefuroxime sodium, cephalothin sodium, chloramphenicol sodium succinate, clindamycin phosphate, disopyramide phosphate, gentamicin sul-fate, heparin sodium, hydrocortisone sodium succinate, hydromor-phone HCl, magnesium sulfate, meperidine HCl, morphine sulfate, moxalactam disodium, multielectrolyte concentrate, multivitamins, netilmicin sulfate, penicillin G sodium, and tobramycin sulfate. The following drugs and solutions are reportedly physically incompatible (or compatibility data conﬂicts) with metronidazole ready-to-use solutions for injection: aztreonam, cefamandole naf-tate, and dopamine HCl.	pppbs.pdf
MEXILETINE HCL 613 Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None Metronidazole is prohibited for use in food animals by the FDA. HUMAN-LABELED PRODUCTS: Metronidazole Tablets: 250 mg & 500 mg; Flagyl® (Pharmacia); ge-neric; (Rx) Metronidazole Capsules: 375 mg; Flagyl 375® (Pharmacia); generic (Able); (Rx) Metronidazole Extended-Release Tablets: 750 mg; Flagyl ER® (Phar-macia); generic (Able); (Rx) Metronidazole HCl Powder for Injection: 500 mg/vial; Flagyl®IV (Pharmacia); (Rx) Metronidazole Injection: 5 mg/m L in 100 m L vials and single-dose vials; Flagyl®I. V. (Pharmacia); generic; (B. Braun); (Rx) Bismuth Subsalicylate, Metronidazole & T etracycline HCl Combi-nation Tablets & Capsules: 262. 4 mg bismuth subsalicylate, 250 mg metronidazole; 500 mg tetracycline; Helidac® (Procter & Gamble); (Rx) Lotions, gels, vaginal products and creams also available. MEXILETINE HCL (mex-ill-i-teen) Mexitil® ORAL ANTIARRHYTHMIC Prescriber Highlights TT Oral antiarrhythmic with similar effects as lidocaine; used for V tach, PVC's; often used with atenolol TT Extreme caution: Pre-existing 2nd or 3rd degree AV block (without pacemaker), or in patients with cardiogenic shock TT Caution: Severe congestive heart failure or acute myocar-dial infarction, hepatic function impairment, hypotension, intraventricular conduction abnormalities, sinus node function impairment, seizure disorder, or sensitivity to the drug TT Adverse Effects: GI distress, including vomiting (give with meals to alleviate); Potentially: CNS effects (trembling, unsteadiness, dizziness, depression), shortness of breath, PVC's & chest pain could occur; rarely (reported in hu-mans): seizures, agranulocytosis, & thrombocytopenia TT Relatively expensive (compared to quinidine) TT Drug-drug; drug-lab interactions Uses/Indications Mexiletine may be useful to treat some ventricular arrhythmias, including PVC's and ventricular tachycardia in small animals. Ventricular tachycardias that have responded to lidocaine usually (but not always) respond to mexiletine as well. Mexiletine may have less cardiodepressant effects and appears to have fewer adverse ef-fects than either procainamide or quinidine, but it is much more costly. Mexiletine may be useful treating certain myopathies in dogs such as myotonia congenita (most studied in miniature schnauzers and Chow Chows) and myokymia in Jack Russell T erriers. Pharmacology/Actions Mexiletine is considered a class IB antiarrhythmic agent and is similar to lidocaine in its mechanism of antiarrhythmic activity. It inhibits the inward sodium current (fast sodium channel), thereby reducing the rate of rise of the action potential, Phase O. In the Purkinje ﬁbers, automaticity is decreased, action potential is short-ened and, to a lesser extent, effective refractory period is decreased. Usually conduction is unaffected, but may be slowed in patients with preexisting conduction abnormalities. Pharmacokinetics Mexiletine is relatively well absorbed from the gut and has a low ﬁrst-pass effect. In humans, it is moderately bound to plasma pro-teins (60-75%), and is metabolized in the liver to inactive metabo-lites with an elimination half-life of about 10-12 hours. Half-lives may be signiﬁcantly increased in patients with moderate to severe hepatic disease, or in those having severely reduced cardiac outputs. Half-lives may be slightly prolonged in patients with severe renal disease or after acute myocardial infarction. Contraindications/Precautions/Warnings Mexiletine should be used with extreme caution, if at all, in patients with pre-existing 2nd or 3rd degree A V block (without pacemaker), or with cardiogenic shock. It should be used only when the beneﬁts of therapy outweigh the risks when the following medical condi-tions exist: severe congestive heart failure or acute myocardial in-farction, hepatic function impairment, hypotension, intraventric-ular conduction abnormalities, sinus node function impairment, seizure disorder, or sensitivity to the drug. Adverse Effects The most likely adverse effect noted in animals is GI distress, includ-ing vomiting. Giving with meals may alleviate this. Potentially (re-ported in humans): CNS effects (trembling, unsteadiness, dizziness, depression), shortness of breath, PVC's and chest pain could occur. Rarely, seizures, agranulocytosis, and thrombocytopenia have been reported in humans. Reproductive/Nursing Safety Lab animal studies have not demonstrated teratogenicity. 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. ) Because mexiletine is secreted into maternal milk, it has been recommended to use milk replacer if the mother is receiving the drug. Overdosage/Acute Toxicity T oxicity associated with overdosage may be signiﬁcant. Case reports in humans have noted that CNS signs always preceded cardiovascu-lar signs. Treatment should consist of GI tract emptying protocols when indicated, acidiﬁcation of the urine to enhance urinary ex-cretion, and supportive therapy. Atropine may be useful if hypoten-sion or bradycardia occur.	pppbs.pdf
614 MIBOLERONE Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving mexiletine and may be of signiﬁcance in veterinary patients: T ! ANTACIDS, ALUMINUM-MAGNESIUM : May slow the absorption of mexiletine T ! ATROPINE : May reduce the rate of oral absorption T ! CIMETIDINE : May increase or decrease mexiletine blood levels T ! GRISEOFULV IN: May accelerate the metabolism of mexiletine T ! LIDOCAINE : May cause additive adverse effects T ! METOCLOPRAMIDE : May accelerate the absorption of mexiletine. T ! OPIATES : May slow the absorption of mexiletine T ! PHENOBARBITAL, PRIMIDONE, PHENYTOIN : May accelerate the me-tabolism of mexiletine T ! RIFAMPIN : May accelerate the metabolism of mexiletine T ! THEOPHYLLINE (aminophylline ): Metabolism may be reduced by mexiletine, thereby leading to theophylline toxicity T ! URINARY ACIDIFYING DRUGS (e. g., methionine, ammonium chloride, potassium phosphate, sodium phosphate ): May accelerate the renal excretion of mexiletine T ! URINARY ALKALINIZING DRUGS (e. g., citrates, bicarb, carbonic anhy-drase inhibitors ): May reduce the urinary excretion of mexiletine Laboratory Considerations T ! Some human patients (1-3%) have had AST values increase by as much as three times or more above the upper limit of normal. This is reportedly a transient effect and asymptomatic. Doses T ! DOGS: For treating or assisting in treatment of ventricular arrhythmias: a) 5-8 mg/kg PO q8h (Fox 2003a) b) 4-10 mg/kg PO q8h (Hogan 2004) c) For Boxers with ventricular arrhythmias: mexiletine at 5-7. 5 mg/kg three times daily with sotalol at 1. 5-3 mg/kg twice daily; was successful in 7/8 dogs treated in study, warrants further investigation. (Prosek, Estrada et al. 2006) d) 4-8 mg/kg PO q8h, combined with atenolol (0. 5 mg/kg PO q12-24h) (Moise 2000) e) For familial arrhythmic cardiomyopathy of Boxers: 5-8 mg/ kg PO q8h with atenolol at 12. 5 mg (total dose) q12h (Meurs 2003) f) 5-6 mg/kg PO q8h; always give with food to avoid nausea. (Meurs 2006a) For treating myotonia congenital (most studied in Chow Chows and miniature schnauzers) or myokymia in Jack Russell terriers: a) 8. 3 mg/kg PO q8h (Lorenz 2007) Monitoring T ! In humans, therapeutic plasma concentrations are: 0. 5-2 micro-grams/m L; toxicity may be noted at therapeutic levels T ! ECG T ! Adverse effects Client Information T ! Give with food to reduce risk for vomiting or nausea T ! Reinforce adherence to prescribed therapy. Chemistry/Synonyms A class IB antiarrhythmic, mexiletine HCl occurs as a white or almost white, odorless, crystalline powder. It is freely soluble in water. Mexiletine may also be known as: Ko-1173,mexiletini hydrochlo-ridum, Mexilen®, Mexitil®, Mexitilen®, Myovek®, and Ritalmex®. Storage/Stability Mexiletine capsules should be stored in tight containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Mexiletine Oral Capsules: 150 mg, 200 mg & 250 mg; Mexitil® (Boeh-ringer Ingelheim); (Rx) MIBOLERONE (mye-boe-le-rone) Cheque® Drops ANDROGEN; ANABOLIC Prescriber Highlights TT Availability an issue; now a controlled substance in the USA TT Androgenic, anabolic, antigonadotropic used to suppress estrus, treat pseudocyesis (false pregnancy) or severe galactorrhea in dogs TT Contraindications: Perianal adenoma, perianal adenocar-cinoma or other androgen-dependent neoplasias, preg-nant or lactating bitches, ongoing or history of liver or kidney disease. The manufacturer also recommends not using the drug in Bedlington terriers. TT NOT for use in cats TT Adverse Effects: Prepuberal females: premature epi-physeal closure, clitoral enlargement, & vaginitis. Adult bitch: mild clitoral hypertrophy, vulvovaginitis, increased body odor, abnormal behavior, urinary incontinence, voice deepening, riding behavior, enhanced clinical signs of seborrhea oleosa, epiphora (tearing), hepatic changes (intranuclear hyaline bodies), & increased kidney weight (without pathology), hepatic dysfunction (rare) Uses/Indications Cheque® Drops was labeled as indicated “for estrous (heat) preven-tion in adult female dogs not intended primarily for breeding pur-poses. ” In clinical trials it was 90% effective in suppressing estrus. Although not approved, mibolerone at dosages of 50 micro-grams per day will prevent estrus in the cat, but its use is generally not recommended because of the very narrow therapeutic index of the drug in this species (see the Adverse Effects and Overdosage sections for more information). Pharmacology/Actions Mibolerone acts by blocking the release of luteinizing hormone (LH) from the anterior pituitary via a negative feedback mecha-nism. Because of the lack of LH, follicles will develop to a certain point, but will not mature and hence no ovulation or corpus luteum development occurs. The net result is a suppression of the estrous cycle if the drug is given prior to (as much as 30 days) the onset of proestrus. After discontinuation of the drug, the next estrus may occur within 7-200 days (avg. 70 days).	pppbs.pdf
MIBOLERONE 615 Pharmacokinetics Mibolerone is reported to be well absorbed from the intestine after oral administration and is rapidly metabolized in the liver to over 10 separate metabolites. Excretion is apparently equally divided be-tween the urine and feces. Contraindications/Precautions/Warnings Mibolerone is contraindicated in female dogs with perianal ade-noma, perianal adenocarcinoma or other androgen-dependent neoplasias. It is also contraindicated in patients with ongoing, or a history of, liver or kidney disease. The manufacturer recommends not using the drug in Bedlington T erriers. Adverse Effects Immature females (dogs) may be more prone to develop adverse reactions than more mature females. In prepuberal females, mibo-lerone can induce premature epiphyseal closure, clitoral enlarge-ment, and vaginitis. Adverse effects that may be seen in the adult bitch include mild clitoral hypertrophy (may be partially reversible), vulvovaginitis, increased body odor, abnormal behavior, urinary incontinence, voice deepening, riding behavior, enhanced clinical signs of seborrhea oleosa, epiphora (tearing), hepatic changes (in-tranuclear hyaline bodies), and increased kidney weight (without pathology). Although reported, overt hepatic dysfunction would be considered to occur rarely in dogs. With the exception of residual mild clitoral hypertrophy, adverse effects will generally resolve after discontinuation of therapy. In the cat, dosages of 60 micrograms/day have caused hepatic dysfunction and 120 micrograms/day have caused death. Other ad-verse effects that have been noted in cats include clitoral hypertro-phy, thyroid dysfunction, os clitorides formation, cervical dermis thickening, and pancreatic dysfunction. Reproductive/Nursing Safety Mibolerone should not be used in pregnant bitches; masculiniza-tion of the female fetuses will occur. Alterations seen may include: changes in vagina patency, multiple urethral openings in the va-gina, a phallus-like structure instead of a clitoris, formation of testes-like structures, and ﬂuid accumulation in the vagina and uterus. Because it may inhibit lactation, it should not be used in nursing bitches. The manufacturer recommends discontinuing the product after 24 months of use. It should not be used to try to attempt to ab-breviate an estrous period or in bitches prior to their ﬁrst estrous period. Overdosage/Acute Toxicity Many toxicology studies have been performed in dogs. The drug did not cause death in doses up to 30,000 micrograms/kg/day when administered to beagles for 28 days. For a more detailed discussion of the toxicology of the drug, the reader is referred to the package insert for Cheque® Drops. In the cat, dosages as low as 120 micrograms/day have resulted in fatalities. Drug Interactions Increased seizure activity has been reported in a dog after re-ceiving mibolerone who was previously controlled on phenytoin. Mibolerone should generally not be used concurrently with proges-tins or estrogens. Laboratory Considerations !TMibolerone has been reported to cause thyroid dysfunction in cats. Doses !TDOGS: For suppression of estrus (treatment must begin at least 30 days prior to proestrus): a) Bitches weighing: 0. 5-11 kg: 30 micrograms (0. 3 m L) PO per day 12-22 kg: 60 micrograms (0. 6 m L) PO per day 23-45 kg: 120 micrograms (1. 2 m L) PO per day >45 kg: 180 micrograms (1. 8 m L) PO per day German shepherds or German shepherd crosses: 180 micro-grams (1. 8 m L) PO per day; regardless of weight (Package Insert; Cheque® Drops—Upjohn) b) As above, but should dog come into estrus after receiving the drug for 30 or more days, stop drug and determine that the dog is not pregnant before resuming therapy. If owner com-pliance has been determined, increase dosage by 20-50%. (Woody 1988), (Burke 1985) For pseudocyesis (false pregnancy): a) Use 10 times the dosage listed above for suppression of estrus PO once daily for 5 days (Barton and Wolf 1988) b) 16 micrograms/kg PO once daily for 5 days (Concannon 1986) For cystic endometrial hyperplasia (CEH): a) 30 mcg/25lb. body weight PO daily during 6 months. (Font-bonne 2006) For treatment of severe galactorrhea: a) 8-18 micrograms/kg PO once a day for 5 days. Once discon-tinued, prolactin may surge and galactorrhea resume. (Olson and Olson 1986) !TCATS: WARNING : Because of the very low margin of safety with this drug in cats, it cannot be recommended for use in this species. Monitoring !TClinical signs of estrus !TLiver function tests (baseline, annual, or as needed) !TPhysical examination of genitalia Client Information !TIt must be stressed to owners that compliance with dosage and administration direction is crucial for this agent to be effective. Chemistry/Synonyms A non-progestational, androgenic, anabolic, antigonadotropic, 19-nor-steroid, mibolerone occurs as a white, crystalline solid. Mibolerone may also be known as: dimethyl-nortestosterone, NSC-72260, and U-10997. Storage/Stability The manufacturer (Upjohn) states that the compound in Cheque® Drops is stable under ordinary conditions and temperatures. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Commercially prepared mibolerone preparations are apparently no longer being marketed. Mibolerone may be available from com-pounding pharmacies. Mibolerone is now categorized as a Class-III controlled substance in the USA. HUMAN-LABELED PRODUCTS: None	pppbs.pdf
616 MIDAZOLAM HCL MIDAZOLAM HCL (mid-ay-zoe-lam) Versed® PARENTERAL BENZODIAZEPINE Prescriber Highlights TT Injectable benzodiazepine used primarily as a pre-op med; unlike diazepam may be given IM TT Contraindications: Hypersensitivity to benzodiazepines; acute narrow-angle glaucoma. Caution: Hepatic or re-nal disease, debilitated or geriatric patients, & those in coma, shock, or with signiﬁcant respiratory depression. TT Adverse Effects: Potential for respiratory depression is of most concern TT Avoid intra-carotid injection TT Drug interactions Uses/Indications In veterinary patients, midazolam is used principally as a premedi-cant for general anesthesia. Alone, it does not appear to provide predictable sedation in animals. Animals may become sedated or dysphoric and excited. Cats may be more prone to develop the “ex-cited” effect more than dogs. When used in combination with other drugs (i. e., opioids or ketamine), midazolam does provide more predictable sedation. Midazolam may also be of beneﬁt to treat status epilepticus when given either IV or IM (not rectally). In humans, midazolam has been suggested for use as a premedi-cant before surgery, and as a conscious sedative when combined with potent analgesic/anesthetic drugs (e. g., ketamine or fenta-nyl). In humans, midazolam reduces the incidences of “dreamlike” emergence reactions and increases in blood pressure and cardiac rate caused by ketamine. When compared to the thiobarbiturate induction agents (e. g., thiamylal, thiopental), midazolam has less cardiopulmonary de-pressant effects, is water-soluble, can be mixed with several other agents, and does not tend to accumulate in the body after repeated doses. Pharmacology/Actions Midazolam exhibits similar pharmacologic actions as other benzo-diazepines. The subcortical levels (primarily limbic, thalamic, and hypothalamic), of the CNS are depressed by the benzodiazepines thus producing the anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects seen. The exact mechanism of action is unknown, but postulated mechanisms include: antagonism of se-rotonin, increased release of and/or facilitation of gamma-amin-obutyric 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. Midazolam's unique solubility characteristics (water soluble in-jection but lipid soluble at body p H) give it a very rapid onset of action after injection. When compared to diazepam, midazolam has approximately twice the afﬁnity for benzodiazepine receptors, is nearly 3 times as potent, and has a faster onset of action and a shorter duration of effect. Pharmacokinetics Following IM injection, midazolam is rapidly and nearly com-pletely (91%) absorbed. Midazolam is well absorbed after oral administration (no oral products are marketed), but because of a rapid ﬁrst-pass effect, bioavailabilities suffer (31-72%). The onset of action following IV administration is very rapid due to the high lipophilicity of the agent. In humans, the loss of the lash reﬂex or counting occurs within 30-97 seconds of administration. The drug is highly protein bound (94-97%) and rapidly crosses the blood-brain barrier. Because only unbound drug will cross into the CNS, changes in plasma protein concentrations and resultant protein binding may signiﬁcantly alter the response to a given dose. Midazolam is metabolized in the liver, principally by microsom-al oxidation. An active metabolite (alpha-hydroxymidazolam) is formed, but because of its very short half-life and lower pharma-cologic activity, it probably has negligible clinical effects. The se-rum half-life and duration of activity of midazolam in humans is considerably shorter than that of diazepam. Elimination half-lives in dogs average 77 minutes; in humans, approximately 2 hours (vs. approx. 30 hrs for diazepam). In dogs, rectal bioavailability of midazolam is very low and this route is not useful clinically. Contraindications/Precautions/Warnings The manufacturer lists the following contraindications for use in humans: hypersensitivity to benzodiazepines, or acute narrow-an-gle glaucoma. Additionally, intra-carotid artery injections must be avoided. Use cautiously in patients with hepatic or renal disease, and in debilitated or geriatric patients. Patients with congestive heart failure may eliminate the drug more slowly. The drug should be administered to patients in coma, shock, or with signiﬁcant respira-tory depression very cautiously. When used alone, midazolam does not possess signiﬁcant ef-fects on cardiorespiratory function, but in combination with other agents, cardiorespiratory effects may be noted. Increased heart rate and blood pressure may be noted when used with ketamine. If this combination is used after an opioid has been administered, these effects may be diminished. If isoﬂurane will be used as the general anesthetic, use ketamine/midazolam with caution as bradycardia, hypotension and reduced cardiac output are possible. Midazolam/opioid combinations can cause less cardiovascular depression, but greater respiratory depression, than acepromazine/ opioid. Midazolam and butorphanol used during isoﬂurane anesthesia can cause decreased blood pressure, heart rate and enhanced respi-ratory depression. Adverse Effects Few adverse effects have been reported in human patients receiv-ing midazolam. Most frequently, effects on respiratory rate, cardiac rate and blood pressure have been reported. Respiratory depression has been reported in patients who have received narcotics or have COPD. The following adverse effects have been reported in more than 1%, but less than 5% of patients receiving midazolam: pain on injection, local irritation, headache, nausea, vomiting, and hiccups. The principle concern in veterinary patients is the possibility of respiratory depression.	pppbs.pdf
MIDAZOLAM HCL 617 TReproductive/Nursing Safety Although midazolam has not been demonstrated to cause fetal abnormalities, in humans, other benzodiazepines have been impli-cated in causing congenital abnormalities if administered during 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 benzodiazepines during pregnancy. The veterinary signiﬁcance of these effects 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 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 acceptable despite its potential risks. ) Midazolam is excreted in milk and may cause CNS effects in nursing neonates. Exercise caution when administering to a nurs-ing mother. Overdosage/Acute Toxicity Very limited information is currently available. The IV LD 50 in mice has been reported to be 86 mg/kg. It is suggested that acci-dental overdoses be managed in a supportive manner, similar to diazepam. Flumazenil could be used to antagonize midazolam ef-fects, but because of midazolam's short duration of effect and ﬂu-mazenil's high cost, supportive therapy may be more suitable in all but the largest overdoses. Drug Interactions See the precautions noted above (Contraindications/Precautions) when using midazolam with other agents for preoperative use in small animals. The following drug interactions have either been re-ported or are theoretical in humans or animals receiving midazo-lam and may be of signiﬁcance in veterinary patients: !TANESTHETICS, INHALATIONAL : Midazolam may decrease the dosages required !TAZOLE ANTIFUNGALS (ketoconazole, itraconazole, ﬂuconazole ): May increase midazolam levels !TCALCIUM CHANNEL BLOCKERS (diltiazem, verapamil ): May increase midazolam levels !TCIMETIDINE : May increase midazolam levels !TCNS DEPRESSANTS, OTHER : May increase the risk of respiratory de-pression !TMACROLIDES (erythromycin, clarithromycin ): May increase midazo-lam levels !TOPIATES : May increase the hypnotic effects of midazolam and hy-potension has been reported when used with meperidine. !TPHENOBARBITAL : May decrease peak levels and AUC of midazolam !TRIFAMPIN : May decrease peak levels and AUC of midazolam !TTHIOPENTAL : Midazolam may decrease the dosages required Doses !TDOGS: As a preoperative agent: a) 0. 2-0. 4 mg/kg IV or IM with an opioid such as hydromor-phone (0. 1 mg/kg IV or 0. 2 mg/kg IM) (Day 2002) b) 0. 1-0. 3 mg/kg; may be used in combination with ketamine in a 50:50 mixture (volume/volume) at a dose of 1 m L/9. 1 kg (1 m L/20 lb), this equates to a dose of 0. 28 mg/kg of midazo-lam and 5. 5 mg/kg of ketamine (Reed 2002) c) 0. 1-0. 5 mg/kg IV (Hellyer 2005b) For status epilepticus: a) 0. 25 mg/kg IV (Knipe 2006b) b) 0. 2-0. 4 mg/kg IV or IM (not per rectum); may repeat once. (Hopper 2006a) !TCATS: As a preoperative agent: a) 0. 2-0. 4 mg/kg IV or IM with an opioid such as hydromor-phone (0. 1 mg/kg IV or 0. 2 mg/kg IM) (Day 2002) b) 0. 05-0. 5 mg/kg; a dose of 0. 3 mg/kg being the most effec-tive when mixed with ketamine to allow for intubation. May be used in combination with ketamine in a 50:50 mixture (volume/volume) at a dose of 1 m L/9. 1 kg (1 m L/20 lb), this equates to a dose of 0. 28 mg/kg of midazolam and 5. 5 mg/kg of ketamine. (Reed 2002) c) 0. 1-0. 5 mg/kg IV (Hellyer 2005b) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: As a tranquilizer (to increase relaxation of lightly anesthetized animals and permit ET intubation): 1 mg/kg IV as needed (Huerkamp 1995) b) Rabbits : 1-2 mg/kg IM, IV. (Ivey and Morrisey 2000) c) Hamsters, Gerbils, Mice, Rats, Guinea pigs, Chinchillas: 1-2 mg/kg IM (Adamcak and Otten 2000) d) Rodents: 5 mg/kg IV (in combination with fentanyl/dro-peridol or fentanyl-ﬂuanisone for neuroleptanesthesia) (Huerkamp 1995) !THORSES: As a preoperative agent: a) 0. 011-0. 0. 44 mg/kg IV (Mandsager 1988) For seizure control in foals: a) 2-5 mg (total dose) for a 50kg foal given IV; rapid IV admin-istration may result in apnea and hypotension. A CRI may be used at a dose of 1-3 mg/hour for a 50kg foal. (Bentz 2006b) b) 2-5 mg (total dose) for a 50kg foal given IV or IM; may be repeated to effect. (T oppin 2007) !TBIRDS: For adjunctive use (with an analgesic) for pain control: a) 1-2 mg/kg IM or IV (Clyde and Paul-Murphy 2000) Monitoring !TLevel of sedation !TRespiratory and cardiac signs Client Information !This agent should be used in an inpatient setting only or with direct professional supervision where cardiorespiratory support services are available. Chemistry/Synonyms Midazolam HCL is a benzodiazepine that occurs as a white or yel-lowish crystalline powder. Solubility in water is dependent upon p H. At a p H of 3. 4 (approximately the p H of commercial injection), 10. 3 mg are soluble in one m L of water. Midazolam HCl may also be known as Ro-21-3981/003, Versed ®, Dormicum®, Dormonid®, Fulsed®, Hypnovel ®, Midaselect®, and Zolamid®.	pppbs.pdf
618 MILBEMYCIN OXIME Storage/Stability/Compatibility It is recommended to store midazolam injection at room tem perature (15°-30°C) and protected from light. After being frozen for 3 days and allowed to thaw at room temperature, the injectable product was physically stable. Midazolam is stable at a p H from 3-3. 6. Midazolam is reportedly physically compatible when mixed with the following products: D 5W, normal saline, lactated Ringer's, at-ropine sulfate, fentanyl citrate, glycopyrrolate, hydroxyzine HCl, ketamine HCl, meperidine HCl, morphine sulfate, nalbuphine HCl, promethazine HCl, sufentanil citrate, and scopolamine HBr. 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 information. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Midazolam HCl Injection: 1 mg (as HCl)/m L in 1 m L, 2 m L, 5 m L vi-als and Carpuject vials, 10 m L vials; 5 mg (as HCl)/m L in 1 m L, 2 m L, 5 m L vials and Carpuject vials, 10 m L vials, 2 m L syringes; generic; (Rx, C-IV) Midazolam HCl Syrup: 2 mg/m L in 118 m L; generic; (Roxane); (Rx, C-IV) MILBEMYCIN OXIME (mil-beh-my-sin) Interceptor®, Sentinel® MACROLIDE ANTIPARASITIC For information on the combination product with lufenuron (Sentinel®), see the lufenuron monograph Prescriber Highlights TT GABA inhibitor in invertebrates used for heartworm pro-phylaxis, microﬁlaricide, & treat demodicosis, etc. TT Contraindications: No absolute contraindications TT Adverse Effects: Animals with circulating microﬁlaria may develop a transient shock-like syndrome; at higher doses, neuro signs become more likely Uses/Indications Milbemycin tablets are labeled as a once-a-month heartworm preventative (Diroﬁlaria immitis) and for hookworm control (Ancylostoma caninum). It has activity against a variety of other parasites, including adult hookworms (A. caninum), adult round-worms (T. canis, T. leonina) and whipworms (Trichuris vulpis). In cats, milbemycin has been used successfully to prevent larval infec-tion of Diroﬁlaria immitis. Milbemycin, like ivermectin can be used for treatment of gener-alized demodicosis in dogs, but treatment can be signiﬁcantly more expensive. It is likely safer to use in breeds susceptible to mdr1 ge-netic mutation (Collies, Shelties, Australian shepherds, etc. ) at the doses used for this indication, but neuro toxicity is possible. Older dogs, those that have had a long duration of disease prior to treat-ment, and dogs with pododemodicosis appear have a lower success rate with milbemycin treatment. Pharmacology/Actions Milbemycin is thought to act by disrupting the transmission of the neurotransmitter gamma amino butyric acid (GABA) in invertebrates. Pharmacokinetics No speciﬁc information was located. At labeled doses, milbemycin is considered effective for at least 45 days after infection by D. im-mitis larva. Contraindications/Precautions/Warnings Because some dogs with a high number of circulating microﬁlaria will develop a transient, shock-like syndrome after receiving milbe-mycin, the manufacturer recommends testing for preexisting heart-worm infections. The manufacturer states to not use the product (Interceptor®) in puppies less than 4 weeks of age or less than 2 lbs. of body weight or in kittens less than 6 weeks of age or less than 1. 5 lbs. of body weight. Adverse Effects At labeled doses, adverse effects appear to be negligible in microﬁ-laria-free dogs, including breeds susceptible to neurologic toxicity (see Overdosage below). At higher dosages (e. g., used for treating demodicosis) neurologic effects may be more likely particularly in dog breeds (Collies, etc. ) with the genetic mutation that affects P-glycoprotein. Eight week old puppies receiving 2. 5 mg/kg (5X label) for 3 consecutive days showed no clinical signs after the ﬁrst day, but af-ter the second or third consecutive dose, showed some ataxia and trembling. Reproductive/Nursing Safety The manufacturer states that safety in breeding, pregnant, and lac-tating queens and breeding toms has not been established. Studies in pregnant dogs at daily doses 3X those labeled showed no adverse effects to offspring or bitch. Milbemycin does enter maternal milk; at standard doses, no ad-verse effects have been noted in nursing puppies. Overdosage/Acute Toxicity Beagles have tolerated a single oral dose of 200 mg/kg (200 times monthly rate). Rough-coated collies have tolerated doses of 10 mg/kg (20 times labeled) without adversity. T oxic doses can cause mydriasis, hypersalivation, lethargy, ataxia, pyrexia, seizures, coma and death. There is no speciﬁc antidotal treatment and supportive therapy is recommended. Drug Interactions The manufacturer states that the drug was used safely during test-ing in dogs receiving other frequently used veterinary products, including vaccines, anthelmintics, antibiotics, steroids, ﬂea collars, shampoos and dips. The following drug interactions have either been reported or are theoretical in humans or animals receiving GABA agonists and may be of signiﬁcance in veterinary patients: T ! BENZODIAZEPINES : Effects may be potentiated by milbemycin; use together not advised in humans Caution is advised if using other drugs that can inhibit p-glycopro-tein particularly in those dogs at risk for MDR1-allele mutation (Collies, Australian Shepherds, Shelties, Long-haired Whippet, etc. “white feet”), unless tested “normal”: Drugs and drug classes in-volved include:	pppbs.pdf
MILBEMYCIN OXIME 619 !!AMIODARONE !!AZOLE ANTIFUNGALS (e. g., ketoconazole ) !!CARV EDILOL !!CYCLOSPORINE !!DILTIAZEM !!ERYTHROMYCIN; CLARITHROMYCIN !!QUINIDINE !!SPIRONOLACTONE !TTAMOXIFEN !TVERAPAMIL Doses !TDOGS: For prophylaxis and treatment of diroﬁlariasis it is suggested to re-view the guidelines published by the American Heartworm Society at www. heartwormsociety. org for more information As a parasiticide: a) For heartworm prophylaxis, control of adult hookworms (A. caninum), adult roundworms (T. canis, T. leonina) and whip-worms (Trichuris vulpis) in dogs 4 weeks of age or older and at least 2 lbs. body weight: Minimum dosage is 0. 5 mg/kg PO once a month. (Label information; Interceptor®—Novartis) b) 0. 5-0. 99 mg/kg PO once monthly (also controls hookworm, roundworm and whipworm infestations) (Calvert 1994) c) For control of ﬂeas (prevents egg development), heartworm prophylaxis, control of adult hookworms (A. caninum), adult roundworms (T. canis, T. leonina) and whipworms (Trichuris vulpis) in dogs 4 weeks of age or older and at least 2 lbs. body weight: Minimum dosage is 0. 5 mg/kg PO once a month. (Label directions; Sentinel®—Novartis) [ Note : when used with nitenpyram (Capstar®) adult ﬂeas are controlled as well] For microﬁlaricide chemotherapy: a) In adulticide-pretreated dogs: Use preventative/prophylaxis dosage; repeat in 2 weeks if necessary. If heartworm trans-mission season has started, continue monthly prophylaxis. (Knight 1995) b) In adulticide-pretreated dogs: Approximately one month after melarsomine give milbemycin at 0. 5 mg/kg PO. (Leg-endre and T oal 2000) For treatment of generalized demodicosis: a) 0. 5-2 mg/kg PO once daily. Higher dose seems to be more effective. (De Manuelle 2000) b) 2 mg/kg PO daily for 30 days past two consecutive negative skin scrapings obtained 4-6 weeks apart. At doses no higher than 2 mg/kg/day, breeds at high risk for toxicity (Collies, Shelties, Australian shepherds, etc. ) are apparently tolerant to milbemycin. (T orres 2007b) c) 1 mg/kg PO twice daily for at least 3 months (White 2000) For treatment of cheyletiellosis: a) 2 mg/kg PO every 7 days for 3 doses (White 2000) For treatment of scabies: a) 2 mg/kg PO every 7 days for 3 doses or 0. 75 mg/kg once daily for 30 days (White 2000) !TCATS: For prevention of heartworm; treat adult hookworm and adult roundworms: a) 2 mg/kg PO once monthly (Label directions; Interceptor® Flavor Tabs for Cats—Novartis) !TREPTILES: For nematodes: a) 0. 5-1 mg/kg PO; repeat in 2 weeks. If 14 days after sec-ond dose, fecal is positive a third dose is given and the cycle continued until parasites are cleared. Milbemycin appears to be safe in chelonians (unlike ivermectin). (de la Navarre 2003b) Client Information !TReview importance of compliance with therapy and to be certain that the dose was consumed. Chemistry/Synonyms Milbemycin oxime consists of approximately 80% of the A 4 d e-rivatives and 20% of the A 3 derivatives of 5-didehydromilbemycin. Milbemycin is considered to be a macrolide antibiotic structurally. Milbemycin may also be known as CGA-179246, Interceptor® and Sentinel®. Storage/Stability Store milbemycin oxime tablets at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Milbemycin Oxime Oral Tablets: 2. 3 mg (brown, 2-10 lbs), 5. 75 mg (green, 11-25 lbs), 11. 5 mg (yellow, 26-50 lbs), 23 mg (white, 51-100 lbs), dogs >100 lbs are provided the appropriate combina-tion of tablets; Interceptor® Flavor Tabs; (Novartis); (Rx). Approved for use in dogs and puppies >4 weeks of age and 2 lbs or greater. Milbemycin Oxime Oral Tablets: 5. 75 mg (1. 5-6 lbs), 11. 5 mg (6. 1-12 lbs), 23 mg (white, 12. 1-25 lbs); Interceptor® Flavor Tabs; (Novartis); (Rx). Approved for cats and kittens >6 wks old and >1. 5 lbs. Milbemycin/Lufenuron Oral Tablets (with Nitenpyram Oral Tablets in the combination ﬂea management system) for Dogs: For dogs 2-10 lb: 46 mg milbemycin/lufeneron, (11. 4 mg nitenpyram) For dogs 11-25 lb: 115 mg milbemycin/lufenuron, (11. 4 mg nitenpyram) For dogs 26-50 lb: 230 mg milbemycin/lufenuron, (57 mg nitenpyram) For dogs 51-100 lb: 460 mg milbemycin/lufenuron, (57 mg nitenpyram) For dogs 100-125 lb: (appropriate number supplied) milbemycin/ lufenuron, (57 mg nitenpyram) Sentinel® Flavor Tabs & Sentinel® Flavor Tabs with Capstar® Flea Management System (Novartis); (Rx). Approved for use in dogs and puppies 4 weeks of age or older. There is also a milbemycin 0. 1% otic solution (Milbemite®) available. HUMAN-LABELED PRODUCTS: None Milk Thistle—see Silymarin	pppbs.pdf
620 MINERAL OIL MINERAL OIL White Petrolatum LUBRICANT LAXATIVE Prescriber Highlights TT Lubricant laxative TT Cautions: Debilitated or pregnant patients, & patients with hiatal hernia, dysphagia, esophageal or gastric retention TT Use caution when administering by tube to avoid aspiration TT Adverse Effects: Lipid pneumonitis if aspirated; granu-lomatous reactions in liver etc. if signiﬁcant amounts are absorbed from gut; oil leakage from the anus; long-term use may lead to decreased absorption of fat-soluble vita-mins (A, D, E, & K) TT Drug interactions Uses/Indications Mineral oil is commonly used in horses to treat constipation and fecal impactions. It is also employed as a laxative in other species as well, but used less frequently. Mineral oil has been administered after ingesting lipid-soluble toxins (e. g., kerosene, metaldehyde) to retard the absorption of these toxins through its laxative and solu-bility properties. Petrolatum containing products (e. g., Felaxin®, Laxatone®, Kat-A-Lax®, etc. ) may be used in dogs and cats as a laxative or to pre-vent/reduce “hair-balls” in cats. Pharmacology/Actions Mineral oil and petrolatum act as laxatives by lubricating fecal ma-terial and the intestinal mucosa. They also reduce reabsorption of water from the GI tract, thereby increasing fecal bulk and decreas-ing intestinal transit time. Pharmacokinetics It has been reported that after oral administration, emulsions of mineral oil may be up to 60% absorbed, but most reports state that mineral oil preparations are only minimally ab sorbed from the gut. Contraindications/Precautions/Warnings No speciﬁc contraindications were noted with regard to veterinary patients. In humans, mineral oil (orally administered) is considered contraindicated in patients less than 6 yrs. old, debilitated or preg-nant patients, and patients with hiatal hernia, dysphagia, esopha-geal or gastric retention. Use caution when administering by tube to avoid aspiration, especially in debilitated or recalcitrant animals. T o avoid aspiration in small animals, orally administered mineral oil should not be attempted when there is an increased risk of vomit-ing, regurgitation, or other preexisting swallowing difﬁculty. Many clinicians believe that mineral oil should not be administered orally to small animals due to the risk for aspiration and, if used as a laxa-tive, should be administered rectally. Adverse Effects When used on a short-term basis and at recommended doses, mineral oil or petrolatum should cause minimal adverse effects. The most serious effect that could be encoun tered is aspiration of the oil with resultant lipid pneumonitis; prevent this by using the drug only in appropriate cases, when “tubing”, ascertain that the tube is in the stomach, and administrate the oil at a reason-able rate. Granulomatous reactions have occurred in the liver, spleen and mesenteric lymph nodes when signiﬁcant quantities of mineral oil are absorbed from the gut. Oil leakage from the anus may occur and be of concern in animals with rectal lesions or in house pets. Long-term administration of mineral oil/petrolatum may lead to decreased absorption of fat-soluble vitamins (A, D, E, and K). No reports were found documenting clinically signiﬁcant hypovita-minosis in cats receiving long-term petrolatum therapy, however. 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. ) Oral mineral oil should be safe to use during nursing. Overdosage/Acute Toxicity No speciﬁc information was located regarding overdoses of mineral oil; but it would be expected that with the exception of aspiration, the effects would be self-limiting. See adverse effects section for more information. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving mineral oil and may be of signiﬁcance in veterinary patients: T ! DOCUSATE : Theoretically, mineral oil should not be given with docusate (DSS) as enhanced absorption of the mineral oil could occur. However, this does not appear to be of signiﬁcant clinical concern with large animals. T ! VITAMINS A, D, E, K : Chronic administration of mineral oil may affect Vitamin K and other fat-soluble vitamin absorption. It has been recommended to administer mineral oil products between meals to minimize this problem. Doses T ! DOGS: As a laxative: a) 2-60 m L PO (Jenkins 1988), (Kirk 1989) b) 5-30 m L PO (Davis 1985a) c) 5-25 m L PO (Burrows 1986) T ! CATS: As a laxative (See speciﬁc label directions for “Cat Laxative” Products): a) 2-10 m L PO (Jenkins 1988), (Kirk 1989) b) 2-6 m L PO (Davis 1985a) c) 5 m L per day with food (Sherding 1989) T ! RABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: As a laxative/remove hairballs: Using feline laxa-tive product: 1-2 m L/day for 3-5 days (Ivey and Morrisey 2000) T ! CATTLE: Note : Administer via stomach tube. As a laxative: a) 1-4 liters (Howard 1986) b) Adults: 0. 5-2 liters; Calves: 60-120 m L (Jenkins 1988) For adjunctive treatment of metaldehyde poisoning: a) 8 m L/kg; may be used with a saline cathartic (Smith 1986) For adjunctive treatment of nitrate poisoning: a) 1 liter per 400 kg body weight (Ruhr and Osweiler 1986)	pppbs.pdf
MINOCYCLINE HCL 621 T ! HORSES: As a laxative (Administer via stomach tube): a) For large colon impactions: 2-4 quarts q12-24 hours, may take up to 5 gallons. Mix 1-2 quarts of warm water with the oil to ease administration and give more ﬂuid to the horse. Pumping in at a moderate speed is desirable over gravity ﬂow. (Sellers and Lowe 1987) b) Adults: 2-4 liters, may be repeated daily; Foals: 240 m L (Clark and Becht 1987) c) Adults: 0. 5-2 liters; Foals: 60-120 m L (Jenkins 1988) T ! SWINE: a) As a laxative: 50-100 m L; administer via stomach tube (Howard 1986) T ! SHEEP & GOATS: a) As a laxative: 100-500 m L; administer via stomach tube (Howard 1986) T ! BIRDS: Use as a laxative and to aid in the removal of lead from the gizzard: a) 1-3 drops per 30 grams of body weight or 5 m L/kg PO once. Repeat as necessary. Give via tube or slowly to avoid aspira-tion. (Clubb 1986) Monitoring T ! Clinical efﬁcacy T ! If possibility of aspiration: auscultate, radiograph if necessary Client Information T ! Follow veterinarian's instructions or label directions for “cat lax-ative” products. T ! Do not increase dosage or prolong treatment beyond veterinar-ian's recommendations. Chemistry/Synonyms Mineral oil, also known as liquid petrolatum, liquid parafﬁn or white mineral oil occurs as a tasteless, odorless (when cold), trans-parent, colorless, oily liquid that is insoluble in both water and al-cohol. It is a mixture of complex hydrocarbons and is derived from crude petroleum. For pharmaceutical purposes, heavy mineral oil is recommended over light mineral oil, as it is believed to have a lesser tendency to be absorbed in the gut or aspirated after oral ad-ministration. White petrolatum, also known as white petroleum jelly or white soft parafﬁn, occurs as a white or faintly yellow unctuous mass. It is insoluble in water and almost insoluble in alcohol. White petrola-tum differs from petrolatum only in that it is further reﬁned to re-move more of the yellow color. Mineral oil may also be known as: liquid parafﬁn, 905 (min-eral hydrocarbons), dickﬂussiges parafﬁn, heavy liquid petrolatum, huile de vaseline epaisse, liquid petrolatum, oleum petrolei, oleum vaselini, parafﬁnum liquidum, parafﬁnum subliquidum, vaselinol, vaselinum liquidum, and white mineral oil; many trade names are available. Storage/Stability Petrolatum products should be stored at temperatures less than 30°C. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Mineral oil products have not been formally approved for use in food animals. These products and preparations are available without a prescription (OTC). Petrolatum Oral Preparations Liquid Mineral Oil: available in gallons or 55 gallon drums. Cat “Laxative” Products: Products may vary in actual composition; some contain liquid petrolatum in place of white petrolatum and may have various ﬂavors (tuna, caviar, malt, etc. ). Trade names include (not necessarily complete): Laxatone®, Laxa-Stat® (Evsco and T om-lyn Health); Vedalax® (Vedco); Cat Lax® (Pharmaderm); Vetscrip-tion® Hairball Remedy (Sergeant's); Hairball Preparation® (Vet Solu-tions); Hartz® Health Measures Hairball Remedy (Hartz Mountain); Petromalt® (Virbac); Petrotone® (Butler); Felilax® (Vetus) HUMAN-LABELED PRODUCTS: Mineral Oil Liquid: in 180 m L and 473 m L; generic; (OTC) Mineral Oil Emulsions: There are several products available that are emulsions of mineral oil and may be more palatable for oral administration. Because of expense and with no increase in efﬁcacy, they are used only in small animals. They may be dosed as described above, factoring in the ac-tual percentage of mineral oil in the preparation used. Trade names include: Kondremul® Plain (Heritage Consumer Prod); (OTC) Vari-ous generic products are available. MINOCYCLINE HCL (mi-noe-sye-kleen) Minocin®, Dynacin® TETRACYCLINE ANTIBIOTIC Prescriber Highlights TT Oral & parenteral tetracycline antibiotic TT Contraindications: Hypersensitivity to it TT Less likely to cause bone & teeth abnormalities than other tetracyclines, but avoid use in pregnancy & young animals TT May be used in patients with renal insufﬁciency TT Adverse Effects are most commonly GI-related TT Drug-drug; drug-lab interactions Uses/Indications Minocycline may be useful for treating Brucellosis (in combination with aminoglycosides), Lyme disease, and certain nosocomial in-fections where other more commonly used drugs are ineffective. It has been investigated as adjunctive therapy for treating heman-giosarcomas, but early results have been disappointing. Pharmacology/Actions T etracyclines generally act as bacteriostatic antibiotics and inhibit protein synthesis by reversibly binding to 30S ribosomal subunits of susceptible organisms, thereby preventing binding to those ri-bosomes of aminoacyl transfer-RNA. T etracyclines are believed to reversibly bind to 50S ribosomes and additionally alter cytoplasmic membrane permeability in susceptible organisms. In high concen-trations, tetracyclines can also inhibit protein synthesis by mam-malian cells.	pppbs.pdf
622 MINOCYCLINE HCL T TAs a class, the tetracyclines have activity against most mycoplas-ma, spirochetes (including the Lyme disease organism), Chlamydia, and Rickettsia. Against gram-positive bacteria, the tetracyclines have activity against some strains of staphylococci 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 activity include Borde-tella spp., Brucella, Bartonella, Haemophilus spp., Pasturella mul-tocida, Shigella, and Yersinia pestis. Many or most strains of E. coli, Klebsiella, Bacteroides, Enterobacter, Proteus, and Pseudomonas aeruginosa are resistant to the tetracyclines. Pharmacokinetics Minocycline is well absorbed after oral absorption regardless of the presence of food. Minocycline is highly lipid soluble and is distrib-uted widely throughout the body. Therapeutic levels can be found in the CSF (whether meninges are inﬂamed or not), prostate, saliva, and eye. Minocycline is extensively metabolized in the liver and pri-marily excreted as inactive metabolites in the feces and urine. Less than 20% is excreted unchanged in the urine. The half-life in dogs is about 7 hours. Contraindications/Precautions/Warnings Minocycline should be considered contraindicated in patients hy-persensitive to tetracyclines, those that are pregnant or nursing, or in animals less than 6 months old. Minocycline is considered to be less likely to cause these abnormalities than other more water-sol-uble tetracyclines (e. g., tetracycline, oxytetracycline). Unlike either oxytetracycline or tetracycline, minocycline can be used in patients with moderate renal insufﬁciency without dosage adjustment. Oliguric renal failure may require dosage adjustment. Adverse Effects The most commonly reported side effects of oral minocycline ther-apy in dogs and cats are nausea and vomiting. T o alleviate these ef-fects, the drug could be given with food without clinically signiﬁcant reductions in drug absorption. Dental or bone staining can occur when minocycline exposure occurs in utero or in early life. More rarely, increases in hepatic en zymes and ototoxicity are possible. IV injections of minocycline in dogs have caused urticaria, shiv-ering, hypotension, dyspnea, cardiac arrhythmias, and shock when given rapidly. Give IV slowly. T etracycline therapy (especially long-term) may result in over-growth (superinfections) of non-susceptible bacteria or fungi. In humans, minocycline (or other tetracyclines) has also been associated with photosensitivity reactions and, rarely, hepatotox-icity or blood dyscrasias. CNS effects (dizziness, lightheadedness) have been reported in people taking minocycline. A blue-gray pig-mentation of skin and mucous membranes may occur. Reproductive/Nursing Safety Because tetracyclines can retard fetal skeletal development and dis-color deciduous teeth, they should only be used in the last half of pregnancy when the beneﬁts outweigh the fetal risks. Minocycline has been shown to impair fertility in male 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. ) T etracyclines are excreted in milk. Milk:plasma ratios vary be-tween 0. 25 and 1. 5. While minocycline probably has less effect on teeth and bones than other tetracyclines, its use should be avoided during nursing. Overdosage/Acute Toxicity Minocycline oral overdoses would most likely be associated with GI disturbances (vomiting, anorexia, and/or diarrhea). Although it is less vulnerable to chelation with cations than other tetracyclines, oral administration of divalent or trivalent cation antacids may bind some of the drug and reduce GI distress. Should the patient develop severe emesis or diarrhea, ﬂuids and electrolytes should be monitored and replaced if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving minocycline and may be of signiﬁcance in veterinary patients: !TANTACIDS, ORAL : When orally administered, tetracyclines can che-late divalent or trivalent cations that can decrease the absorption of the tetracycline or the other drug if it contains these cations. Oral antacids, saline cathartics, or other GI products containing aluminum, calcium, magnesium, zinc, or bismuth cations are most commonly associated with this interaction. Minocycline has a relatively low afﬁnity for divalent or trivalent cations, but it is recommended that all oral tetracyclines be given at least 1-2 hours before or after the cation-containing product. !TBISMUTH SUBSALICYLATE, KAOLIN, PECTIN : May reduce absorption !TIRON, ORAL : Oral iron products are associated with decreased tetracycline absorption, and administration of iron salts should preferably be given 3 hours before or 2 hours after the tetracy-cline dose. !TISOTRETINOIN : When used with minocycline may increase the risk for nervous system effects !TPENICILLINS : Bacteriostatic drugs, like the tetracyclines, may inter-fere with bactericidal activity of the penicillins, cephalosporins, and aminoglycosides. There is a fair amount of controversy regarding the actual clinical signiﬁcance of this interaction, however. !TWARFARIN : T etracyclines may depress plasma prothrombin ac-tivity and patients on anticoagulant therapy may need dosage adjustment. Laboratory Considerations !Tetracyclines reportedly can cause false-positive urine glucose results if using the cupric sulfate method of determination (Benedict's reagent, Clinitest®), but this may be the result of ascorbic acid that is found in some parenteral formulations of tetracyclines. !Tetracyclines reportedly have caused false-negative results in de-termining urine glucose when using the glucose oxidase method (Clinistix®, Tes-Tape®). Doses !TDOGS: a) For susceptible soft tissue and urinary tract infections: 5-12 mg/kg PO or IV q12h for 7-14 days. (Greene, Hartmannn et al. 2006) b) For Brucellosis: Gentamicin 5 mg/kg SC once daily (q24h) for 7 days; 2-courses of treatment, treating on weeks one and four; plus Minocycline at 25 mg/kg PO once daily (q24h) for 4 weeks. Eventually, doxycycline can be substituted for minocycline at the same dosage to lower cost. Infected ani-mals may need to be treated for two or more 4-week courses. Sequential antibody tests at 3 to 6 monthly intervals are rec-ommended to monitor treatment. Monitor renal function secondary to gentamicin therapy. (Hartmannn and Greene 2005)	pppbs.pdf
MIRTAZAPINE 623 c) For adjunctive treatment of Nocardiosis, Actinomycosis: 5-25 mg/kg PO, IV q12h (Lemarie 2003a) d) For Brucillosis in animals that are housed singly and neu-tered: Minocycline at 25 mg/kg PO once daily for 14 days with dihydrostreptomycin ( Note : not currently available in the USA) at 5 mg/kg IM twice daily for 7 days. (Root Kustritz 2007) T ! CATS: a) For hemotropic mycoplasmosis: 6-11 mg/kg PO q12h for 21 days. (Greene, Hartmannn et al. 2006) b) For adjunctive treatment atypical mycobacterial dermal in-fections: 5-12. 5 mg/kg PO, IV q12h (Hnilica 2003a) c) For adjunctive treatment of Nocardiosis, Actinomycosis: 5-25 mg/kg PO, IV q12h (Lemarie 2003a) Monitoring T ! Clinical efﬁcacy T ! Adverse effects Client Information T ! Oral minocycline products may be administered without regard to feeding. Milk or other dairy products do not signiﬁcantly alter the amount of minocycline absorbed. T ! Give as prescribed for as long as veterinarian recommends even if animal appears well. Chemistry/Synonyms A semisynthetic tetracycline, minocycline HCl occurs as a yellow, crystalline powder. It is soluble in water and slightly soluble in alcohol. Minocycline may also be known as: minocyclini hydrochlo-ridum, Asolmicina®, Cyclimycin®, Cyclomin®, Dermirex®, Meibi ®, Minogal®, and Minox®; many other trade names are available. Storage/Stability/Compatibility Store the oral preparations at room temperature in tight containers. Do not freeze the oral suspension. The injectable should be stored at room temperature and protected from light. After reconstituting with sterile water for injection, solutions with a concentration of 20 mg/m L are stable for 24 hours at room temperature. While minocycline is compatible with the usual intravenous ﬂu-ids (including Ringer's and lactated Ringer's) do not add any other calcium containing ﬂuid as precipitation could result. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Minocycline HCl Tablets: 50 mg, 75 mg, 100 mg; Extended-Release: 45 mg, 90 mg & 135 mg; Minocycline HCl (Par); Dynacin® (Medicis); Myrac® (Glades); Solodyn® (Medicis); (Rx) Minocycline HCl Capsules: 50 mg, 75 mg, 100 mg; Minocin® (Led-erle); Dynacin® (Medicis); generic; (Rx) Minocycline HCl Oral Suspension: 50 mg/5 m L in 60 m L; Minocin® (Lederle); (Rx) Minocycline HCl Powder for Injection cryodessicated: 100 mg per vial; Minocin® (Triax); (Rx) Minocycline HCl Microspheres, Sustained-Release: 1 mg; Arestin® (Cord Logistics); (Rx) MIRTAZAPINE (mir-taz-ah-peen) Remeron® TETRACYCLIC ANTIDEPRESSANT; 5-HT3 ANTAGONIST Prescriber Highlights TT Used in veterinary medicine primarily as an appetite stimulant & antiemetic in dogs & cats TT Can be used in conjunction with other antiemetics TT Primary side effect is sedation TT Use lowest effective dose to reduce sedative properties TT Do not exceed 30 mg per day when used for appetite stimulation Monograph by Dinah Jordan, Pharm D, DICVP Uses/Indications Currently, the only FDA approved indication for mirtazapine is depression in humans. Reported veterinary uses include treatment of chemotherapy-induced nausea and vomiting (CINV); anorexia associated with renal failure (azotemia), congestive heart failure, gastro-intestinal disorders, liver disease, or neoplasia. Other uses suggested include stress induced diseases; insomnia; post-pyometra symptoms; and post-operative inappetance. Studies have shown that mirtazapine also alleviated sleep apnea in rats and humans. There are case reports published in human literature of mir-tazapine use as treatment for non-mechanical vomiting after gas-tric bypass, CINV, obsessive-compulsive disorder, nocioception and chronic pain, migraine headache prophylaxis, anti-psychotic induced akathisia, idiopathic nausea and vomiting, serotonin syn-drome induced nausea, anorexia, irritable bowel syndrome, resis-tant hyperemesis gravidarum, and for the treatment of negative symptoms of schizophrenia. Studies in rats have also shown that mirtazapine signiﬁcantly improves memory. Pharmacology/Actions The antidepressant activity of mirtazapine appears to be mediat-ed by antagonism at central pre-synaptic alpha2-receptors, which normally act as a negative feedback mechanism that inhibits fur-ther norepinephrine (NE) release. By blocking these receptors, mirtazapine overcomes the negative feedback loop and results in a net increase in NE. This mechanism may also contribute to the appetite stimulating effects of the medication since NE acts at other a-receptors to increase appetite. Additionally, mirtazapine antago-nizes several serotonin (5HT) receptor subtypes. The drug is a po-tent inhibitor of the 5HT2 and 5HT3 receptors and of histamine (H1) receptors. Antagonism at the 5HT3 receptors accounts for the anti-nausea and antiemetic effects of the drug, and its action at H1-receptors produces prominent sedative effects. It is a moderate pe-ripheral alpha 1 adrenergic antagonist, a property that may explain the occasional orthostatic hypotension associated with its use; it is a moderate antagonist of muscarinic receptors, which may explain the relatively low incidence of anticholinergic effects. Pharmacokinetics Complete pharmacokinetic information has not been published for dogs and cats to date. Following oral administration in hu-mans, mirtazapine is rapidly and completely absorbed. Studies in rats showed a linear relationship between the effects of mirtazap-	pppbs.pdf
624 MIRTAZAPINE ine and measured plasma and brain concentrations. Peak plasma concentrations are reached within about 2 hours after an oral dose in humans. Food has minimal effects on both the rate and extent of absorption and does not require adjustments in the dose. Oral bioavailability of mirtazapine is about 20% for rats and dogs, and about 50% for humans. Mirtazapine is metabolized via multiple pathways and varies by species. In all species tested (humans and laboratory animals), the drug was metabolized via the following mechanisms: 8-hydroxlaton followed by conjugation, N-oxidation, and demethylation followed by conjugation. Humans and guinea pigs also produce metabolites via N+-glucuronidation, whereas mice were the only species found to utilize demethylation followed by CO2 addition and conjuga-tion, and 13-hydroxylation followed by conjugation as methods of mirtazapine breakdown. These processes are conducted primarily by CYP2D6, CYP1A2, and CYP3A4, yet mirtazapine exerts minimal inhibition on any of these cytochromes. Several metabolic pathways of mirtazapine involve conjugation with glucuronide (glucuroni-dation). Since cats have a limited capacity for glucuronidation, mir-tazapine is cleared less rapidly from the system and, therefore, an extended dosing interval is required. It is estimated that the active metabolite of mirtazapine contrib-utes only 3-6% of the total pharmacodynamic proﬁle of the drug since it is approximately 10-fold less active than mirtazapine and affects the AUC minimally. Therefore, only the levels of the parent compound are considered clinically relevant. The extent of binding of drugs to plasma proteins sometimes differs considerably among animal species. Plasma protein bind-ing (PPB) for mirtazapine appears to be approximately 70-72% for mice, rats, and dogs, whereas for humans and rabbits it is ap-proximately 85%. Despite the interspecies differences in PPB, no displacement interactions or dosage adjustments for mirtazapine are expected due to its large therapeutic window and nonspeciﬁc and relative low afﬁnity for plasma proteins. Human literature documents that elimination occurs via the urine (75%) and the feces (15%), renal impairment may reduce elimination by 30-50% compared to normal subjects, and hepatic impairment may reduce clearance by up to 30%. Human studies show the elimination half-life of mirtazapine to be long and range from 20-40 hours across age and gender subgroups, so dosage in-creases should take place no sooner than every 7-14 days. Females (both human and animal) of all ages exhibit signiﬁcantly longer elimination half-lives than males (mean half-life of 37 hours for females vs. 26 hours for males in humans). Contraindications/Precautions/Warnings Mirtazapine is contraindicated in patients with hypersensitivity to mirtazapine or who have taken monoamine oxidase inhibitors (e. g., selegiline) in the past 14 days. Mirtazapine has been associated with orthostatic hypotension in humans and should, therefore, be used with caution in patients with known cardiac disease or cerebrovascular disease that could be exacerbated by hypotension. Patients with renal impairment, renal failure, or hepatic disease should be monitored while on mirtazap-ine therapy. Abrupt discontinuation of mirtazapine after long-term admin-istration has resulted in withdrawal symptoms such as nausea, headache and malaise in humans. In general, antidepressants may affect blood glucose concentrations because of their indirect effects on the endocrine system; use with caution in patients with diabetes mellitus. Mirtazapine exhibits very weak anticholinergic activity, conse-quently, vigilance should be used in patients who might be more susceptible to these effects, such as those with urinary retention, prostatic hypertrophy, acute, untreated closed-angle glaucoma or in-creased intraocular pressure, or GI obstruction or ileus. Also, effects of mirtazapine may be additive to anticholinergic medications. Extra care should be taken with active animals as mirtazap-ine may impair concentration and alertness. Although extremely rare, mirtazapine has been associated with blood dyscrasias in hu-mans and should be used cautiously in patients with pre-existing hematological disease, especially leukopenia, neutropenia, or thrombocytopenia. Adverse Effects Mirtazapine appears to be well tolerated in both dogs and cats, but use has been limited and controlled trials are lacking. Besides the desirable side effect of appetite stimulation, other currently report-ed side effects in animals include drowsiness/sedation, vocalization, hypotension, tachycardia (all dose-dependent). Reproductive/Nursing Safety In humans, mirtazapine is FDA pregnancy category C (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). However, reproductive studies in rats, rabbits, and dogs have shown no evidence of teratogenicity. Additional studies in hamsters, rabbits, and rats showed no evi-dence of fetal genetic mutation or reduction in parental fertility, although there were increases in post-implantation losses and pup deaths, as well as decreased pup birth weight. No fetal harm was reported in any of several case reports of mirtazapine use during pregnancy nor in animal studies. In animals, mirtazapine is excreted in very small amounts in milk, the implications of which are currently unknown; con-sequently, it may be prudent to use caution in nursing mothers. Mirtazapine is distributed into human breast milk and safe use in humans during nursing cannot be assured. In one case report mir-tazapine concentrations were detected in breast milk, but the ex-amining neuropediatrician detected no adverse effects (including weight gain or sedation) in the infant. Overdosage/Acute Toxicity Mirtazapine ingestion of upwards of 10-fold therapeutic dose in humans exhibits minimal toxicity requiring no acute interven-tion and only 6 hours of observation. Similar effects were seen in patients receiving up to 30 times the recommended dose. Despite these reports, the package insert for mirtazapine recommends that activated charcoal be administered in addition to other standard monitoring activities in an overdose situation. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving mirtazapine and may be of signiﬁcance in veterinary patients: !TCLONIDINE : Mirtazapine may cause increases in blood pressure !TDIAZEPAM (and other benzodiazepines ): Minimal effects on mir-tazapine blood levels, but may cause additive impairment of mo-tor skills !TFLUVOXAMINE : May cause increased serum concentrations of mirtazapine !TLINEZOLID : Increased risk for serotonin syndrome !TSELEGILINE, AMITRAZ : Increased risk for serotonin syndrome; MAO inhibitors considered contraindicated with mirtazapine !TTRAMADOL : Increased risk for serotonin syndrome In vitro studies identify mirtazapine as a substrate for several hepat-ic cytochrome CYP450 isoenzymes including 2D6, 1A2, and 3A4. Mirtazapine is not a potent inhibitor of any of these enzymes; clini-	pppbs.pdf
MISOPROSTOL 625 cally signiﬁcant pharmacokinetic interactions are not likely with drugs metabolized by CYP enzymes. Laboratory Considerations No speciﬁc concerns noted. Doses Since no safety or efﬁcacy trials have been performed in animals to date, currently recommended doses are based on extrapolations from human medicine and clinical experience in veterinary prac-tice. According to the product package insert and several anecdotal reports, no adjustment is needed in liver disease or kidney dysfunc-tion, although starting at the lower end of the dosage range and titrating up if needed is recommended in such situations. Note: At doses exceeding 30 mg per day, mirtazapine loses its ap-petite stimulating properties in humans. Since the ceiling dose for cats and dogs is not currently known, total daily doses ≤30 mg are recommended for appetite stimulation depending upon the weight of the pet. T ! DOGS: As an appetite stimulant and/or antiemetic: a) 0. 6 mg/kg PO q 24 h not to exceed 30 mg per day for appetite stimulation (Jordan 2007) Dogs <20 lb. = 3. 75 mg PO q24h; 21-50 lb. = 7. 5 mg PO q 24h; 50-75 lb. = 15 mg PO q24h; >75 lb. = 15 mg PO q12h or 30 mg PO q24h (once daily) (Jordan 2007) T ! CATS: As an appetite stimulant and/or antiemetic: a) 3. 75 mg PO q72h (every 3 days) (Jordan 2007) b) 3 mg per cat PO q72h (every 3 days) (Churchill 2006) c) 3-4 mg per cat PO q72h (every 3 days) (Scherk 2006) Monitoring T ! Clinical efﬁcacy measured by the following parameters: increased appetite, decreased episodes of vomiting, and weight gain T ! Adverse Effects Client Information T ! Give only the prescribed dose. T ! Report excessive drowsiness or vocalization to your veterinarian. T ! If your pet is receiving the orally disintegrating tablets, make sure hands are dry before handling the tablet. Place the tablet under the animal's tongue and hold mouth closed for several seconds to allow it to dissolve (should occur quickly). After the tablet has melted, offer the patient water. T ! May be given without regard to food. Chemistry/Synonyms A member of the piperazino-azepine group of compounds, mir-tazapine is classiﬁed as an atypical tetracyclic antidepressant and is not chemically related to other antidepressants. Mirtazapine, with a molecular weight of 265. 36, occurs as a white to creamy white crystalline powder that is slightly soluble in water. Mirtazapine may also be known as 6-azamianserin, Org-3770, mepirzapine and Remeron®; many trade names for international products are available. Storage/Stability The coated tablets and the orally disintegrating tablets should be stored at 25$C (77$F) with excursions permitted to 15-30$C (59-86$F). Protect from light and moisture. The stability of the orally disintegrating tablets once removed from the tablet blister is unknown and immediate use is recommended. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Mirtazapine Oral Tablets: 7. 5 mg 15 mg, 30 mg, 45 mg; Remeron® (Organon), generic; (Rx) Mirtazapine Orally Disintegrating Tablets: 15 mg, 30 mg, 45 mg; Re-meron Sol Tab® (Organon), generic; (Rx) MISOPROSTOL (mye-soe-prost-ole) Cytotec® PROSTAGLANDIN E 1 ANALOG Prescriber Highlights TT Prostaglandin E 1 analog for treating or preventing gastric ulcers, especially associated with NSAIDs; may also be useful as an abortifacient, & to treat atopy or cyclosporine-induced nephrotoxicity TT Contraindications: Pregnancy, nursing mothers (diarrhea in the nursing offspring) TT Caution: Sensitivity to prostaglandins or prostaglandin analogs; patients with cerebral or coronary vascular disease TT Adverse Effects: GI distress (diarrhea, abdominal pain, vomiting, & ﬂatulence); Potentially, uterine contractions & vaginal bleeding in female dogs TT Pregnant women should handle with caution Uses/Indications Misoprostol may be useful as primary or adjunctive therapy in treating or preventing gastric ulceration, especially when caused or aggravated by non-steroidal antiinﬂammatory drugs (NSAIDs). Misoprostol is most useful to prevent GI ulceration or GI adverse effects (anorexia, vomiting) associated with NSAID therapy. While it can be used for treating gastric ulcers, other drugs are probably just as effective and less expensive. It does not appear to be very effective in reducing gastric ulceration secondary to high dose cor-ticosteroid therapy Misoprostol may be efﬁcacious in reducing or reversing cy-closporine-induced nephrotoxicity. More data is needed to conﬁrm this effect. One study demonstrated that misoprostol can reduce the clini-cal signs associated with atopy somewhat in dogs. Misoprostol's effects on uterine contractibility and cervical soft-ening/opening make it effective as an adjunctive treatment in preg-nancy termination. Pharmacology/Actions Misoprostol has two main pharmacologic effects that make it a po-tentially useful agent. By a direct action on parietal cells, it inhib-its basal and nocturnal gastric acid secretion as well as gastric acid	pppbs.pdf
626 MISOPROSTOL secretions that are stimulated by food, pentagastrin or histamine. Pepsin secretion is decreased under basal conditions, but not when stimulated by histamine. Misoprostol also has a cytoprotective effect on gastric mucosa. Probably by increasing production of gastric mucosa and bicarbon-ate, increasing turnover and blood supply of gastric mucosal cells, misoprostol enhances mucosal defense mechanisms and healing in response to acid-related injuries. Other pharmacologic effects of misoprostol include increased amplitude and frequency of uterine contractions, stimulating uter-ine bleeding, and causing total or partial expulsion of uterine con-tents in pregnant animals. Pharmacokinetics Approximately 88% of an oral dose of misoprostol is rapidly ab-sorbed from the GI tract, but a signiﬁcant amount is metabolized via the ﬁrst-pass effect. The presence of food and antacids will delay the absorption of the drug. Misoprostol is rapidly de-ester-iﬁed to misoprostol acid which is the primary active metabolite. Misoprostol and misoprostol acid are thought equal in their effects on gastric mucosa. Both misoprostol and the acid metabolite are fairly well bound to plasma proteins (approximately 90% bound). It is not believed that misoprostol enters maternal milk, but it is unknown whether the acid enters milk. Misoprostol acid is further biotransformed via oxidative mecha-nisms to pharmacologically inactive metabolites. These metabolites, the free acid and small amounts of unchanged drug are principally excreted into the urine. In humans, the serum half-life of misopros-tol is about 30 minutes and its duration of pharmacological effect is about 3-6 hours. Contraindications/Precautions/Warnings It should be used in patients with the following conditions only when its potential beneﬁts outweigh the risks: Sensitivity to prosta-glandins or prostaglandin analogs; patients with cerebral or coro-nary vascular disease (although not reported with misoprostol, some prostaglandins and prostaglandin analogs have precipitated seizures in epileptic human patients, and have caused hypotension which may adversely affect these patients). Adverse Effects The most prevalent adverse effect seen with misoprostol is GI dis-tress, usually manifested by diarrhea, abdominal pain, vomiting, and ﬂatulence. Adverse effects are often transient and resolve over several days or may be minimized by dosage adjustment or giv-ing doses with food. Potentially, uterine contractions and vaginal bleeding could occur in female dogs. Reproductive/Nursing Safety Misoprostol is contraindicated during pregnancy due to its abor-tifacient activity. In humans, the FDA categorizes this drug as cat-egory 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. ) In a separate system evaluating the safe-ty of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: D (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) It is unlikely that misoprostol is excreted in milk because it is rapidly metabolized, however, it is not known if the active metabo-lite (misoprostol acid) is excreted in milk. Misoprostol is not rec-ommended for nursing mothers as it potentially could cause sig-niﬁcant diarrhea in the nursing offspring. Overdosage/Acute Toxicity There is limited information available. Overdoses in laboratory ani-mals have produced diarrhea, GI lesions, emesis, tremors, focal car-diac, hepatic or renal tubular necrosis, seizures, and hypotension. Overdoses should be treated seriously and standard gut emptying techniques employed when applicable. Resultant toxicity should be treated symptomatically and sup portively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving misoprostol and may be of signiﬁcance in veterinary patients: !TANTACIDS, MAGNESIUM-CONTAINING : Magnesium-containing antac-ids may aggravate misoprostol-induced diarrhea. If an antacid is required, an aluminum-only antacid may be a better choice. Antacids and food do reduce the rate of misoprostol absorption and may reduce the systemic availability, but probably do not af-fect therapeutic efﬁcacy. Doses !TDOGS: For the prevention and treatment of GI ulcers: a) 1-5 mcg/kg PO q8h (Haskins 2000) b) 3-4 mcg/kg PO q12h (Burrows 2004) c) 2-5 mcg/kg PO q8-12h (Dowling 2003a) As an adjunctive therapy for the termination of mid-term preg-nancy in the bitch: a) Pregnancy is conﬁrmed with ultrasound and begun no soon-er than 30 days after breeding. 1-3 mcg/kg misoprostol giv-en intravaginally once daily concurrently with prostaglandin F2alpha (Lutalyse®) at 0. 1 mg/kg SC three times daily for 3 days and then 0. 2 mg/kg SC three times daily to effect. Moni-tor efﬁcacy with ultrasound. (Cain 1999) As an adjunctive therapy for atopic dermatitis: a) Target dosage of 5 mcg/kg PO three times daily. Modest improvement in clinical signs; relatively high cost. (Olivry, Dunston et al. 2003) b) 6 mcg/kg q8h PO for 30 days (Campbell 1999) Monitoring !TEfﬁcacy !TAdverse effects Client Information !TPregnant women should handle the drug with caution. !TIf diarrhea or other GI adverse effects become severe or persist, reduce dose or give with food or aluminum antacids to alleviate. Severe diarrheas may require supportive therapy. Chemistry/Synonyms A synthetic prostaglandin E 1 analog, misoprostol occurs as a yel-low, viscous liquid having a musty odor. Misoprostol may also be known as: SC-29333, Arthotec®, Arthrotec®, Artotec ®, Artrenac Pro®, Artrotec ®, Condrotec®, Corrigast®, Cyprostol®, Cytotec®, Cytolog®, Diclotec®, Glefos®, Menpros®, Misodex®, Misofenac®, Napratec®, Normulen®, Oxaprost®, and Symbol®. Storage/Stability/Compatibility Misoprostol tablets should be stored in well-closed containers at room temperature. After manufacture, misoprostol has an expira-tion date of 18 months.	pppbs.pdf
MITOTANE 627 Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 5 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Misoprostol Tablets: 100 mcg & 200 mcg; Cytotec® (Pﬁzer); generic; (Rx) MITOTANE (mye-toe-tane) Lysodren®, o,p'-DDD ADRENAL CYTOTOXIC; ANTINEOPLA STIC Prescriber Highlights TT Adrenal cytotoxic agent used for medical treatment of pituitary-dependent hyperadrenocorticism TT Caution: Pregnancy, diabetes, & preexisting renal or hepatic disease TT Adverse Effects: Lethargy, ataxia, weakness, anorexia, vomiting, &/or diarrhea; liver changes possible TT Relapses are not uncommon TT All dogs receiving mitotane therapy should receive ad-ditional glucocorticoid supplementation if undergoing a stress (e. g., surgery, trauma, acute illness) TT Monitoring is mandatory TT Avoid human exposure Uses/Indications In veterinary medicine, mitotane is used primarily for the medical treatment of pituitary-dependent hyperadrenocorticism (PDH), principally in the dog. It has also been used for the palliative treat-ment of adrenal carcinoma in humans and dogs. Pharmacology/Actions While mitotane is considered an adrenal cytotoxic agent, it appar-ently can also inhibit adrenocortical function without causing cell destruction. The exact mechanisms of action for these effects are not clearly understood. In dogs with pituitary-dependent hyperadrenocorticism (PDH), mitotane has been demonstrated to cause severe, progressive necro-sis of the zona fasciculata and zona reticularis. These effects occur quite rapidly (usually within 5-10 days of starting therapy). It has been stated that mitotane spares the zona glomerulosa and there-fore aldosterone synthesis is unaffected. This is only partially true, as the zona glomerulosa may also be affected by mitotane therapy, but it is uncommon for clinically signiﬁcant effects on aldosterone production to be noted with therapy. Pharmacokinetics In dogs, the systemic bioavailability of mitotane is poor. Oral ab-sorption can be enhanced by giving the drug with food (especially food high in oil/fat content). In humans, approximately 40% of an oral dose of mitotane is absorbed after dosing, with peak serum levels occurring about 3-5 hours after a single dose. Distribution of the drug occurs to virtually all tissues in the body. The drug is stored in the fat and does not accumulate in the adrenal glands. A small amount may enter the CSF. It is unknown if the drug crosses the placenta or is distributed into milk. Mitotane has a very long plasma half-life in humans, with values ranging from 18-159 days being reported. Serum half-lives may increase in a given patient with continued dosing, perhaps due to a depot effect from adipose tissue releasing the drug. The drug is metabolized in the liver and is excreted as metabolites in the urine and bile. Approximately 15% of an oral dose is excreted in the bile, and 10% in the urine within 24 hours of dosing. Contraindications/Precautions/Warnings Mitotane is contraindicated in patients known to be hypersensitive to it. Patients with concurrent diabetes mellitus may have rapidly changing insulin requirements during the initial treatment period. These animals should be closely monitored until they are clinically stable. Dogs with preexisting renal or hepatic disease should receive the drug with caution and with more intense monitoring. It has been stated that “... hyperadrenocorticism is a clinical condition. No dog should be treated for this condition unless there are obvious clinical signs, consistent with the diagnosis, that are worrisome to the owner. ” (Feldman 2007) Some clinicians recommend giving prednisolone at 0. 2 mg/kg/ day during the initial treatment period (0. 4 mg/kg/day to diabetic dogs) to reduce the potential for side effects from acute endogenous steroid withdrawal. Other clinicians have argued that routinely ad-ministering steroids masks the clinical markers that signify when the endpoint of therapy has been reached and must be withdrawn 2-3 days before ACTH stimulation tests can be done. Since in ad-equately observed patients adverse effects requiring glucocorticoid therapy may only be necessary in 5% of patients, the beneﬁts of routine glucocorticoid administration may not be warranted. Adverse Effects Most common adverse effects seen with initial therapy in dogs in-clude lethargy, ataxia, weakness, anorexia, vomiting, and/or diar-rhea. Adverse effects are commonly associated with plasma corti-sol levels of less than 1 micrograms/dl or a too rapid decrease of plasma cortisol levels into the normal range. Adverse effects may also be more commonly seen in dogs weighing less than 5 kg, which may be due to the inability to accurately dose. The incidence of one or more of these effects is approximately 25% and they are usually mild. If adverse effects are noted, it is recommended to temporar-ily halt mitotane therapy and supplement with glucocorticoids. Owners should be provided with a small supply of predniso(lo)ne tablets to initiate treatment. Should the clinical signs persist 3 hours after steroids are supplemented, consider other medical problems. Liver changes (congestion, centrolobular atrophy, and moderate to severe fatty degeneration) have been noted in dogs given mitotane. Although not commonly associated with clinical symptomatology, these effects may be more pronounced with long-term therapy or in dogs with preexisting liver disease. In perhaps 5% of dogs treated, long-term glucocorticoid and sometimes mineralocorticoid replacement therapy may be required. All dogs receiving mitotane therapy should receive additional glu-cocorticoid supplementation if undergoing a stress (e. g., surgery, trauma, acute illness). Relapses are not uncommon in canine patients treated for Cushing's with mitotane. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and fe-line pregnancy (Papich 1989), this drug is categorized as class: D	pppbs.pdf
628 MITOTANE (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) It is not known whether this drug is excreted in maternal milk. Because of the potential for adverse reactions in nursing offspring, decide whether to discontinue nursing or discontinue the drug. Overdosage/Acute Toxicity No speciﬁc recommendations were located regarding overdoses of this medication. Because of the drug's toxicity and long half-life, emptying the stomach and administering charcoal and a cathartic should be considered after a recent ingestion. It is recommended that the patient be closely monitored and given glucocorticoids if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving mitotane and may be of signiﬁcance in veterinary patients: !TCNS DEPRESSANT DRUGS : If mitotane is used concomitantly with drugs that cause CNS depression, additive depressant effects may be seen !TINSULIN : Diabetic dogs receiving insulin may have their insulin requirements decreased when mitotane therapy is instituted !TPHENOBARBITAL : Can induce enzymes and reduce the efﬁcacy of mitotane, conversely mitotane can induce hepatic microsomal enzymes and increase the metabolism of phenobarbital !TSPIRONOLACTONE : In dogs, spironolactone has been demonstrated to block the action of mitotane; it is recommended to use an al-ternate diuretic if possible Laboratory Considerations !TMitotane will bind competitively to thyroxine-binding globulin and decreases the amount of serum protein-bound iodine. Se-rum thyroxine concentrations may be unchanged or slightly de-creased, but free thyroxine values remain in the normal range. Mitotane does not affect the results of the resin triiodothyronine uptake test. !TMitotane can reduce the amounts measurable 17-OHCS in the urine, which may or may not reﬂect a decrease in serum cortisol levels or adrenal secretion. Doses !TDOGS: For medical treatment of pituitary-dependent hyperadreno-corticism (bilateral adrenal hyperplasia): Note : The information provided below (in “a and b”) is a synopsis of the referenced au-thors' treatment protocols. It is strongly recommended to refer to the original references or other detailed discussions on the treatment of hyperadrenocorticism before instituting therapy for the ﬁrst time. a) Beginning by reducing dog's food allotment by one-third the day before (Saturday) therapy. Owners should give 1/3 the daily allotment that morning and 1/3 the daily allotment that evening. This should make the dog quite hungry. No dog with a poor appetite should ever be treated medically for pituitary-dependent hyperadrenocorticism (PDH). Initiate therapy at home (on Sunday): 25 mg/kg twice a day, PO with food. Glucocorticoids are not routinely administered nor dispensed. Give until one of the following occurs: Polydipsic dogs' water consumption approaches 60 m L/kg/day of water, dog takes longer to consume a meal or it develops partial or complete anorexia, dog vomits, is unusually listless, or has diarrhea. Any of these observations demand the owner stop therapy and have the dog examined by a veterinarian. Any reduction in appetite indicates that the induction phase of therapy is completed. Water intake is a less-consistent pa-rameter in determining therapeutic end-point. Beginning on 2nd day of therapy, contact owner daily during the induction phase to monitor the situation and encourage. When dog's appetite is reduced or 8 days of induction thera-py have occurred (whichever comes ﬁrst), history and physi-cal repeated, ACTH response test, BUN, serum sodium, and potassium redone. If the dog has responded clinically, stop mitotane until ACTH response test can be evaluated. Suc-cessful therapy is indicated by pre-and post-ACTH serum cortisol concentrations >1. 5mcg/dl and <5 mcg/dl. Goals of therapy are to achieve resolution of clinical signs. Most dogs respond between 4 and 9 days of therapy. Maintenance therapy: Is begun once dog seems much im-proved or normal to owner or if post-ACTH serum cortisol is <5 mcg/d L ( Note : reference states 54g/d L, but this is an ob-vious “typo”). Each dog must be treated individually. Dogs generally receive 25-50 mg/kg per week. If <1 mcg/dl, with-hold medication for 2 weeks and restart at 25 mcg/kg/week. Whenever possible, the weekly dose of medication should be divided in as many doses as possible (e. g., if dog receiving 500 mg/week; divide tablet into quarters and give 4 times a week). Four weeks after therapy started, ACTH stimulation test rechecked. If post-ACTH results are 1-3. 5 mcg/dl, dog receives 25 mg/kg/week and recheck in 4 weeks. If 3. 5-7. 5 mcg/dl, dog receives 50 mg/kg/week and recheck in 4 weeks. If >7. 5 mcg/dl be sure the drug is being administered prop-erly. If given properly, may mix with corn oil and mixed with food. These animals should also be evaluated for other con-ditions (e. g., renal disease, diabetes mellitus). ACTH stimula-tion results should be used as a guide for dosage adjustment, but owner opinion is the most important factor. (Feldman 1989), (Feldman 2000), (Feldman 2007) b) Induction phase 30-50 mg/kg/day PO with a meal once daily or divided q12h for 7-10 days. If adverse effects (leth-argy, vomiting, weakness, diarrhea) occur, discontinue mito-tane and give glucocorticoids (prednis(ol)one at 0. 15-0. 25 mg/kg/day) until dog can be evaluated. If decreased appetite occurs discontinue mitotane and evaluate with an ACTH stimulation test. Perform ACTH stimulation test at end of 10 day period or sooner if adverse effects occur. Goal is to have basal and post-ACTH cortisol between 1-5 mcg/dl (normal for most labs). If basal and post ACTH cortisol falls below 1 mcg/dl, temporarily suspend mitotane and supplement with glucocorticoids until circulating cortisol normalizes (usually 2-4 weeks, but may take several weeks to months). If basal or post ACTH cortisol is above normal, continue daily mito-tane and recheck ACTH stimulation tests at 5-10 day inter-vals until serum cortisol falls within normal resting range. Begin maintenance when desired cortisol concentrations are documented by ACTH stimulation testing. Mitotane given initially at 35-50 mg/kg per week in 2-3 divided doses. Should adverse effects, discontinue mitotane and supple-ment with glucocorticoids until dog can be evaluated by se-rum electrolytes and ACTH stimulation test. (Kintzer 2007) c) Intentionally causing complete destruction of the adrenal cortex as an alternative to the traditional mitotane treatment: Mitotane at 75-100 mg/kg per day for 25 consecutive days, given in 3-4 doses per day with food. Lifelong prednisone at 0. 1-0. 5 mg/kg PO twice daily initially and mineralocorticoid therapy is begun at the start of mitotane therapy. Prednisone dose is tapered after completion of the 25-day protocol. Re-	pppbs.pdf
MITOXANTRONE HCL 629 Tlapse is common and periodic ACTH stimulation testing is necessary. May be considerably more expensive than tradi-tional therapy because of the expense associated with treat-ing Addisonian dogs. (Nelson 2003c) d) For total adrenal ablation for management of Cushing's: Mi-totane 100 mg/kg/day divided twice daily for 30 days. Sup-plemental cortisone acetate 2 mg/kg/day divided twice daily and ﬂudrocortisone acetate 0. 1 mg/ 10 lb of body weight PO once daily are begun on day 1 of mitotane therapy. Diet is supplemented with 1-5 grams of sodium chloride per day. One week after induction phase with mitotane, cortisone acetate is reduced to 1 mg/kg/day. Electrolytes and ACTH stimulation test are performed at end of induction, every 6 months, and at any time animal demonstrates signs compat-ible with either hypo-or hyperadrenocorticism. This form of management requires close patient monitoring and life-long daily therapy. Close attention during stress and non-adrenal illnesses required. (Bruyette 2002a) For palliative medical treatment of adrenal carcinomas or medi-cal treatment of adrenal adenomas: Initially, 50-75 mg/kg PO in daily divided doses for 10-14 days. May supplement with predniso(lo)ne at 0. 2 mg/kg/ day. Stop therapy and evaluate dog if adverse effects oc-cur. After initial therapy run ACTH-stimulation test (do not give predniso(lo)ne the morning of the test). If basal or post-ACTH serum cortisol values are decreased, but still above the therapeutic end-point (<1 micrograms/dl), repeat therapy for an additional 7-14 days and repeat testing. If post-ACTH serum cortisol values remain greatly elevated or unchanged, increase mitotane to 100 mg/kg/day and re-peat ACTH-stimulation test at 7-14 day intervals. If ACTH continues to remain greatly elevated, increase dosage by 50 mg/kg/day every 7-14 days until response occurs or drug intolerance ensues. Adjust dosage as necessary as patient tol-erates or ACTH-responsive dictates. Once undetectable or low-normal post-ACTH cortisol levels are attained, contin-ue mitotane at 100-200 mg/kg/week in divided doses with glucocorticoid supplementation (predniso(lo)ne 0. 2 mg/kg/ day). Repeat ACTH-stimulation test in 1-2 months. Con-tinue at present dose if cortisol remains below 1 micrograms/ dl. Should cortisol increase to 1-4 micrograms/dl, increase maintenance dose by 50%. If basal or post-ACTH cortisol goes above 4 micrograms/dl, restart daily treatment (50-100 mg/kg/day) as outlined above. Once patient is stabilized, repeat ACTH-stimulation tests at 3-6 month intervals. (Kintzer and Peterson 1989) T ! FERRETS: For medical treatment of hyperadrenocorticism where surgery has not been performed or tumor has not been fully resected: a) 50 mg per ferret PO once daily for one week, then 50 mg PO 2-3 times per week. Have a compounding pharmacy make 50 mg capsules. Capsules can be easily administered if coated with a substance such as Nutrical. (Rosenthal and Peterson 2000) Monitoring Initially and as needed (see doses above): T ! Physical exam and history (including water and food consump-tion, weight) T ! BUN, CBC, Liver enzymes, Blood glucose, ACTH response test, serum electrolytes (Na+/K+) Client Information T ! Clients must be clearly instructed in the adverse effects of the drug and the clinical signs of acute hypoadrenocorticism T ! his medication is best administered immediately after a meal T ! Because of the potential severe toxicity associated with this agent, clients should be instructed to wear gloves or wash their hands after administering and to keep the tablets out of reach of chil-dren or pets. Chemistry/Synonyms Mitotane, also commonly known in veterinary medicine as o,p'-DDD, is structurally related to the infamous insecticide, chloro-phenothane (DDT). It occurs as a white, crystalline powder with a slightly aromatic odor. It is practically insoluble in water and soluble in alcohol. Mitotane may also be known as: CB-313, o,p'DDD, NSC-38721, WR-13045, and Lisodren®. Storage/Stability Mitotane tablets should be stored at room temperature (15-30°C), in tight, light resistant containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Mitotane Tablets (scored): 500 mg; Lysodren® (Bristol-Myers Squibb Oncology); (Rx) MITOXANTRONE HCL (mye-toe-zan-trone) Novantrone® ANTINEOPLA STIC Prescriber Highlights TT Antineoplastic that may be useful for a variety of neo-plastic diseases TT Contraindications (relative): Myelosuppression, concur-rent infection, impaired cardiac function; those who have received prior cytotoxic drug or radiation exposure TT Caution: Sensitivity to drug, hyperuricemia or hyperuricu-ria, impaired hepatic function TT Adverse Effects: Dose-dependent GI distress, bone mar-row depression, lethargy, & seizures (cats) TT Relatively expensive TT Renal clearance of drug is minimal Uses/Indications Mitoxantrone may be useful in the treatment of several neoplas-tic diseases in dogs and cats, including lymphosarcoma mammary adenocarcinoma, squamous cell carcinoma, renal adenocarcinoma, ﬁbroid sarcoma, thyroid or transitional cell carcinomas, and he-mangiopericytoma. Because renal clearance of the drug is minimal (10%), it may be administered to cats with renal insufﬁciency much more safely than doxorubicin.	pppbs.pdf
630 MITOXANTRONE HCL Pharmacology/Actions By intercalation between base pairs and a nonintercalative electro-static interaction, mitoxantrone binds to DNA and inhibits both DNA and RNA synthesis. Mitoxantrone is not cell-cycle phase spe-ciﬁc, but appears to be most active during the S phase. Pharmacokinetics Mitoxantrone is rapidly and extensively distributed after intrave-nous infusion. Highest concentrations of the drug are found in the liver, heart, thyroid, and red blood cells. In humans, it is approxi-mately 78% bound to plasma proteins. Mitoxantrone is metabo-lized in the liver, but the majority of the drug is excreted unchanged in the urine. Half-life of the drug in humans averages about 5 days as a result of the drug being taken up, bound by, and then slowly released by tissues. Contraindications/Precautions/Warnings Mitoxantrone is relatively contraindicated (weigh risk vs. beneﬁt) in patients with myelosuppression, concurrent infection, impaired cardiac function, or those who have received prior cytotoxic drug or radiation exposure. It should be used with caution in patients with sensitivity to mitoxantrone, hyperuricemia or hyperuricuria, or impaired hepatic function. Adverse Effects In dogs and cats, effects include dose-dependent GI distress (vom-iting, anorexia, diarrhea) and bone marrow depression (sepsis). White cell nadirs generally occur on day 10. Some evidence exists that by giving recombinant granulocyte-colony stimulating factor bone marrow depression severity and duration may be reduced. Lethargy may also be noticed. Some cats receiving this drug have also developed seizures. Unlike doxorubicin, cardiotoxicity has not yet been reported in dogs and only rarely occurs in humans. Other adverse effects less frequently or rarely noted in humans and, potentially possible in dogs, include conjunctivitis, jaundice, renal failure, seizures, aller-gic reactions, thrombocytopenia, irritation or phlebitis at injection site. Tissue necrosis associated with extravasation has only been re-ported in a few human cases. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the po-tential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Mitoxantrone is excreted in maternal milk and signiﬁcant con-centrations (18 ng/m L) have been reported for 28 days after the last administration to humans. Because of the potential for serious ad-verse reactions in offspring, it is recommended to use milk replacer if mitoxantrone is administered. Overdosage/Acute Toxicity Because of the potential serious toxicity associated with this agent, dosage determinations must be made carefully. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving mitoxantrone and may be of signiﬁcance in veterinary patients: !TDOXORUBICIN, DAUNORUBICIN, or RADIATION THERAPY : Cardiotoxic-ity risks may be enhanced in patients that have previously re-ceived doxorubicin, daunorubicin, or radiation therapy to the mediastinum !TIMMUNOSUPPRESSANT DRUGS (e. g., azathioprine, cyclophosphamide, corticosteroids ): Use with other immunosuppressant drugs may increase the risk of infection !TMYELOSUPPRESSIVE DRUGS (e. g., chloramphenicol, ﬂucytosine, ampho-tericin B, or colchicine ): Use extreme caution when used concur-rently with other drugs that are also myelosuppressive, including many of the other antineoplastics and other bone marrow de-pressant drugs; bone marrow depression may be additive !TVACCINES, LIVE : Live virus vaccines should be used with caution, if at all, during therapy Laboratory Considerations !TMitoxantrone may raise serum uric acid levels. Drugs such as al-lopurinol may be required to control hyperuricemia. !TLiver function tests may become abnormal, indicating hepatotoxicity. !TMitoxantrone may discolor urine a green-blue. Doses For more information on using mitoxantrone 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). !TDOGS: As an alternative agent for the treatment of a variety of neoplas-tic diseases (see Indications above): a) For transitional cell carcinoma: 5 mg/m2 IV every 21 days with piroxicam (0. 3 mg/kg PO once daily). (Chun 2007a) b) For lymphoma, squamous cell carcinoma, transitional cell carcinoma, mammary gland tumors, etc. : Effective dose is 6 mg/m2 IV every 2-3 weeks (Ogilvie 2003a) c) As a single rescue agent for lymphoma: 5. 5-6 mg/m2 IV ev-ery 3 weeks (Meleo 2003) d) As a rescue agent for canine lymphoma: 6 mg/m2 IV every 2-3 weeks. Check CBC on day 7 after treatment and the protocol can be repeated on day 14 or 21 if the dog attains complete or partial response. Combining with DTIC (dacar-bazine) may improve the response rate for dogs with refrac-tory lymphoma, but there are no available studies. (Rassnick 2006) e) For lymphoproliferative disorders: 5-6 mg/m2 every 3 weeks (Gilson and Page 1994) f) For transitional cell carcinoma after laser ablation of the primary tumor: Mitoxantrone at 5 mg/m2 IV every 3 weeks for 4 treatments. Piroxicam was given at a dosage of 0. 3 mg/ kg PO once daily for the remaining life of the dog. (Upton, Tanger et al. 2006) !TCATS: a) For soft-tissue sarcomas: 6-6. 5 mg/m2 IV given every 3-4 weeks for 4-6 treatments. (Keller and Helfand 1994) b) Effective dose: 6. 5 mg/m2 IV every 2-3 weeks (Ogilvie 2003a) c) As a single rescue agent for lymphoma: 6-6. 5 mg/m2 IV ev-ery 3 weeks (Meleo 2003)	pppbs.pdf
MORANTEL TARTRATE 631 Monitoring T ! CBC with differential and platelets (see Adverse Effects section) T ! Efﬁcacy T ! Chest radiographs, ECG or other cardiac function tests if cardiac symptomatology present T ! Liver function tests if jaundice or other clinical signs of hepato-toxicity present T ! Serum uric acid levels for susceptible patients Client Information T ! Clients should understand the potential costs and toxicities as-sociated with therapy T ! A blue-green color to urine or a bluish color to sclera may be noted but is of no concern T ! Have clients report any clinical signs associated with toxicity im-mediately to veterinarian Chemistry/Synonyms Mitoxantrone HCl is a synthetic anthracenedione antineoplastic. It occurs as a dark-blue powder and is sparingly soluble in water, practically insoluble in acetone, acetonitrile, and chloroform, and slightly soluble in methyl alcohol. Mitoxantrone may also be known as: L-232315, DHAD, di-hydroxyanthracenedione dihydrochloride, mitoxantroni hydro-chloridum, NSC-301739, Formyxan®, Genefadrone®, Micraleve®, Misostol®, Mitoxal®, Mitoxgen®, Mitroxone®, Neotalem®, Novantron®, Novantrone®, Oncotron®, Onkotrone®, or Pralifan®. Storage/Stability/Compatibility Mitoxantrone HCl should be stored at room temperature. While the manufacturer recommends not to freeze, one study (Mauldin 2002) demonstrated that the drug maintained its cytotoxic effects when frozen and thawed at various intervals over a 12 month pe-riod. Do not mix or use the same IV line with heparin infusions (precipitate may form). At present, it is not recommended to mix with other IV drugs. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Mitoxantrone HCl for Injection: 2 mg (mitoxantrone free base)/m L, preservative free in 10 m L, 12. 5 m L, and 15 m L multi-dose vials; No-vantrone® (Serono); (Rx) MORANTEL TARTRATE (mor-an-tel) Rumatel® ANTIPARASITIC AGENT Prescriber Highlights TT Infrequently used anthelmintic for ruminants TT Contraindications: None TT Adverse Effects: Large safety margin; clinical signs of OD include increased respiratory rates, profuse sweating, ataxia or other cholinergic effects Uses/Indications Morantel is labeled for the removal of the following parasites in cattle: Mature forms of: Haemonchus spp., Ostertagia spp., Trichostrongylus spp., Nematodirus spp., Cooperia spp. and Oesophagostomum radia-tum. It is also used in other ruminant species. Pharmacology/Actions Like pyrantel, morantel acts as a depolarizing neuromuscular blocking agent in susceptible parasites, thereby paralyzing the or-ganism. The drug possesses nicotine-like properties and acts simi-larly to acetylcholine. Morantel also inhibits fumarate reductase in Haemonchus spp. Morantel is slower than pyrantel in its onset of action, but is ap-proximately 100 times as potent. Pharmacokinetics After oral administration, morantel is absorbed rapidly from the upper abomasum and small intestine. Peak levels occur about 4-6 hours after dosing. The drug is promptly metabolized in the liver. Within 96 hours of administration, 17% of the drug is excreted in the urine with the remainder in the feces. Contraindications/Precautions/Warnings There are no absolute contraindications to using this drug. Adverse Effects At recommended doses, adverse effects are not commonly seen. For more information, see Overdosage section below. Reproductive/Nursing Safety Morantel is considered generally safe to use during pregnancy. Overdosage/Acute Toxicity Morantel tartrate has a large safety margin. In cattle, dosages of up to 200 mg/kg (20 times recommended dose) resulted in no toxic reactions. The LD 50 in mice is 5 g/kg. Clinical signs of toxicity that might possibly be seen include increased respiratory rates, profuse sweating (in species with sweat glands), ataxia or other cholinergic effects. Chronic toxicity studies have been conducted in cattle and sheep. Doses of 4 times recommended were given to sheep with no detect-able deleterious effects. Cattle receiving 2. 5 times recommended dose for 2 weeks showed no toxic signs. Drug Interactions T ! BENTONITE : Do not add to feeds containing bentonite. T ! LEVAMISOLE, PYRANTEL : Because of similar mechanisms of action (and toxicity), morantel is not recommended for use concur-rently with pyrantel or levamisole. T ! ORGANOPHOSPHATES, DIETHYLCARBAMAZINE : Observation for ad-verse effects should be intensiﬁed if used concomitantly with an organophosphate or diethylcarbamazine. T ! PIPERAZINE : Has antagonistic mechanism of action; do not use with morantel. Doses T ! CATTLE: For susceptible parasites: a) 9. 68 mg/kg PO (Paul 1986) b) Feed at the rate of 0. 44 g of morantel tartrate per 100 lbs of body weight. 10 lbs of premix per ton of food per 100 lbs of body weight. (Label Directions; Rumatel®—Philbro) c) 8. 8 mg/kg PO (Roberson 1988b)	pppbs.pdf
632 MORPHINE SULFATE T ! SHEEP & GOATS: For susceptible parasites: a) Goats: As a single therapeutic treatment at 0. 44 grams mor-antel tartrate per 100 lb. body weight. Fresh water should be available at all times. Conditions of constant worm exposure may require retreatment in 2-4 weeks. (Label directions; Goat Care-2X®—Durvet) b) Sheep: 10 mg/kg PO (Roberson 1988b) c) Goats: 10 mg/kg PO (de la Concha 2002) Chemistry/Synonyms A tetrahydropyrimidine anthelmintic, morantel tartrate occurs as a practically odorless, off-white to pale yellow, crystalline solid that is soluble in water. It has a melting range of 167-171°C. The tartrate salt is equivalent to 59. 5% of base activity. Morantel tartrate may also be known as: CP-12009-18, moranteli hydrogenotartras, or UK-2964-18, Goat Care-2X® and Rumatel®. Storage/Stability Morantel tartrate products should be stored at room temperature (15-30°C, 59-86°F) and protected from light unless otherwise in-structed by the manufacturer. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Morantel Tartrate Medicated Pellets: 0. 194% (880 mg/lb) in 3 lb (treats 12-50 lb goats) and 10 lb. (treats 40-50 lb. goats). Goat Care-2X® (Durvet); (OTC); No withdrawal time noted on label. Do not mix in feeds containing bentonite. Morantel Tartrate Medicated Premix: 88 g morantel tartrate per lb. in 25 lb bags: Rumatel® Medicated Premix-88 (Philbro); (OTC). Ap-proved for use in beef or dairy cattle. Milk withdrawal (at labeled doses) = none; Slaughter withdrawal (at labeled doses) = 14 days HUMAN-LABELED PRODUCTS: None MORPHINE SULFATE (mor-feen) OPIATE AGONIST Prescriber Highlights TT Classic opiate analgesic TT Contraindications: Hypersensitivity to morphine, diarrhea caused by a toxic ingestion TT Extreme Caution: Respiratory disease or from acute re-spiratory dysfunction TT Caution: Hypothyroidism, severe renal insufﬁciency (acute uremia), adrenocortical insufﬁciency, geriatric or severely debilitated patients, head injuries or increased intracra-nial pressure, & acute abdominal conditions (e. g., colic) TT Adverse Effects: Histamine release, respiratory depres-sion, bronchoconstriction, CNS depression, physical dependence (chronic use), hyperthermia (cattle, goats, horses & cats), hypothermia (dogs, rabbits); GI Gastro-intestinal effects may include: (nausea, vomiting, & de-creased intestinal peristalsis), defecation (dogs) TT C-II controlled substance Uses/Indications Morphine is used for the treatment of acute pain in dogs, cats, hors-es, swine, sheep, and goats. It may be used as a preanesthetic agent in dogs and swine. Additionally, it has been used as an antitussive, antidiarrheal, and as adjunctive therapy for some cardiac abnor-malities (see doses) in dogs. Pharmacology/Actions The morphine-like agonists (morphine, meperidine, oxymor-phone) have primary activity at the mu receptors, with some ac-tivity possible at the delta receptor. The primary pharmacologic effects of these agents include: analgesia, antitussive activity, re-spiratory depression, sedation, emesis, physical dependence, and intestinal effects (constipation/defecation). Secondary pharma-cologic effects include: CNS: euphoria, sedation, and confusion. Cardiovascular: bradycardia due to central vagal stimulation, al-pha-adrenergic receptors may be depressed resulting in peripheral vasodilation, decreased peripheral resistance, and baroreceptor in-hibition. Orthostatic hypotension and syncope may occur. Urinary: Increased bladder sphincter tone can induce urinary retention. Morphine's CNS effects are irregular and are species speciﬁc. Cats, horses, sheep, goats, cattle, and swine may exhibit stimulatory effects after morphine injection, while dogs, humans, and other primates exhibit CNS depression. Both dogs and cats are sensitive to the emetic effects of morphine, but signiﬁcantly higher doses are required in cats before vomiting occurs. This effect is a result of a direct stimulation of the chemoreceptor trigger zone (CTZ). Other species (horses, ruminants, and swine) do not respond to the emetic effects of morphine. Like meperidine, morphine can affect the release of histamine from mast cells. Morphine is an effective centrally acting antitussive in dogs. Following morphine administration, hypothermia may be seen in dogs and rabbits, while hyperthermia may be seen in cattle, goats, horses, and cats. Morphine can cause miosis (pinpoint pupils) in humans, rabbits, and dogs. While morphine is considered a respiratory depressant, respi-rations are stimulated initially in dogs. Panting may ensue which may be a result of increased body temperature. Often however, body temperature may be reduced due to a resetting of the “body's thermostat. ” As CNS depression increases and the hyperthermia re-solves, respirations can become depressed. Morphine at moderate to high doses can also cause bronchoconstriction in dogs. The cardiovascular effects of morphine in dogs are in direct con-trast to its effects on humans. In dogs, morphine causes coronary vasoconstriction with resultant increase in coronary vascular resis-tance, and a transient decrease in arterial pressure. Both bradycar-dias and tachycardias have been reported in dogs. While morphine has been used for years as a sedative/analgesic in the treatment of myocardial infarction and congestive heart failure in people, its ef-fects on dogs make it a less than optimal choice in canine patients with clinical signs of cardiopulmonary failure. However, its use has been recommended by several clinicians in the initial treatment for cardiogenic edema. The effects of morphine on the gastrointestinal (GI) tract con-sist primarily of a decrease in motility and secretions. The dog, however, will immediately defecate following an injection of mor-phine, then exhibit the signs of decreased intestinal motility and, ultimately, constipation can result. Both biliary and gastric secre-tions are reduced following administration of morphine, but gas-tric secretion of HCl will later be compensated by increased (above normal) acid secretion. Initially, morphine can induce micturition, but with higher doses (>2. 4 mg/kg IV) urine secretion can be substantially reduced by an increase in anti-diuretic hormone (ADH) release. Morphine	pppbs.pdf
MORPHINE SULFATE 633 may cause bladder hypertonia which can lead to increased difﬁculty in urination. Pharmacokinetics Morphine is absorbed when given by IV, IM, SC, and rectal routes. Although absorbed when given orally, bioavailability is reduced, probably because of a high ﬁrst-pass effect. Morphine concentrates in the kidney, liver, and lungs; lower levels are found in the CNS. Although at lower levels then in the parenchymatous tissues, the majority of free morphine is found in skeletal muscle. Morphine crosses the placenta and narcotized newborns can result if mothers are given the drug before giving birth. These effects can be rapidly reversed with naloxone. Small amounts of morphine will also be distributed into the milk of nursing mothers. The major route of elimination of morphine is by metabolism in the liver, primarily by glucuronidation. Because cats are deﬁcient in this metabolic pathway, half-lives in cats are probably prolonged. The glucuronidated metabolite is excreted by the kidney. After IV administration in dogs, morphine has a volume of dis-tribution of about 7. 5 L/kg and a clearance of approximately 83 m L/ min/kg. Its elimination half-life is slightly longer than 1 hour. The oral bioavailability of the extended release tablets is widely variable and this dosage form of the drug is erratically absorbed in dogs. In horses, the serum half-life of morphine has been reported to be 88 minutes after a dose of 0. 1 mg/kg IV. At this dose the drug was detectable in the serum for 48 hours and in the urine for up to 6 days. The half-life in cats has been reported to be approximately 3 hours. Contraindications/Precautions/Warnings All opiates should be used with caution in patients with hypo-thyroidism, severe renal insufﬁciency, adrenocortical insufﬁcien-cy (Addison's), and in geriatric or severely debilitated patients. Morphine is contraindicated in cases where the patient is hyper-sensitive to narcotic analgesics, receiving monamine oxidase inhibi-tors (MAOIs), or with diarrhea caused by a toxic ingestion until the toxin is eliminated from the GI tract. Morphine should be used with extreme caution in patients with head injuries, increased intracranial pressure, and acute abdominal conditions (e. g., colic) as it may obscure the diagnosis or clinical course of these conditions. Morphine may also increase intrac-ranial pressure secondary to cerebral vasodilatation as a result of increased p a CO2 stemming from respiratory depression. It should be used with extreme caution in patients suffering from respira-tory disease or from acute respiratory dysfunction (e. g., pulmonary edema secondary to smoke inhalation). Because of its effects on vasopressin (ADH), morphine must be used cautiously in patients suffering from acute uremia. Urine ﬂow has been reported to decrease by as much as 90% in dogs given large doses of morphine. Neonatal, debilitated, or geriatric patients may be more sus-ceptible to the effects of morphine and may require lower dosages. Patients with severe hepatic disease may have prolonged duration of action of the drug. Opiate analgesics are contraindicated in patients who have been stung by the scorpion species Centruroides sculpturatus Ewing and C. gertschi Stahnke as they can potentiate these venoms. Adverse Effects At usual doses, the primary concern is the effect the opioids have on respiratory function. Decreased tidal volume, depressed cough reﬂex, and the drying of respiratory secretions may all have a det-rimental effect on a susceptible patient. Bronchoconstriction (sec-ondary to histamine release?) following IV doses has been noted in dogs. Gastrointestinal effects may include: nausea, vomiting, and de-creased intestinal peristalsis. Dogs will usually defecate after an ini-tial dose of morphine. Horses exhibiting signs of mild colic may have their clinical signs masked by the administration of narcotic analgesics. The CNS effects of morphine are dose and species speciﬁc. Animals that are stimulated by morphine may elucidate changes in behavior, appear restless and, at very high doses, have convulsions. The CNS depressant effects seen in dogs may encumber the abilities of working animals. Body temperature changes may be seen. Cattle, goats, horses, and cats may exhibit signs of hyperthermia, while rabbits and dogs may develop hypothermia. Chronic administration may lead to physical dependence. Reproductive/Nursing Safety Placental transfer of opiates is rapid. 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. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: B (Safe for use if used cautiously. Studies in laboratory animals may have 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. ) Morphine appears in maternal milk, but effects on offspring may not be signiﬁcant when used for short periods. Withdrawal symp-toms have occurred however in breastfeeding infants when mater-nal administration of an opioid-analgesic stopped. Decide whether to accept the risks, discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Overdosage/Acute Toxicity Overdosage may produce profound respiratory and/or CNS depres-sion in most species. Newborns may be more susceptible to these effects than adult animals. Parenteral doses greater than 100 mg/ kg are thought to be fatal in dogs. Other toxic effects can include cardiovascular collapse, hypothermia, and skeletal muscle hypoto-nia. Some species such as horses, cats, swine, and cattle may dem-onstrate CNS excitability (hyperreﬂexia, tremors) and seizures at high doses or if given rapidly intravenously. Naloxone is the agent of choice in treating respiratory depression. In massive overdoses, naloxone doses may need to be repeated. Animals should be close-ly observed as naloxone's effects might diminish before sub-toxic levels of morphine are attained. Mechanical respiratory support should be considered in cases of severe respiratory depression. Pentobarbital has been suggested as a treatment for CNS ex-citement and seizures in cats. Extreme caution should be used as barbiturates and narcotics can have additive effects on respiratory depression. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving morphine and may be of signiﬁcance in veterinary patients: !TCNS DEPRESSANTS, OTHER (e. g., anesthetic agents, antihistamines, phenothiazines, barbiturates, tranquilizers, alcohol, etc. ): May cause increased CNS or respiratory depression when used with morphine !TDIURETICS : Opiates may decrease efﬁcacy in CHF patients !TMONAMINE OXIDASE (MAO) INHIBITORS (e. g., amitraz, possibly sele-giline ): Use MAOI's with morphine with extreme caution as me-peridine (a related opiate) is contraindicated in human patients	pppbs.pdf
634 MORPHINE SULFATE receiving monamine oxidase (MAO) inhibitors for at least 14 days after receiving MAO inhibitors. Some human patients have exhibited signs of opiate overdose after receiving therapeutic doses of meperidine while taking MAOIs. !TMUSCLE RELAXANTS, SKELETAL : Morphine may enhance neuromus-cular blockade !TTRICYCLIC ANTIDEPRESSANTS (clomipramine, amitriptyline, etc. ): Morphine may exacerbate the effects of tricyclic antidepressants !TWARFARIN : Opiates may potentiate anticoagulant activity Laboratory Considerations !TAs they may increase biliary tract pressure, opiates can increase plasma amylase and lipase values up to 24 hours following their administration. Doses !TDOGS: For analgesia (acute pain): a) 0. 5-2 mg/kg IM or SC q3-4 hours. For SLOW IV adminis-tration use 10% of IM dose (Hendrix and Hansen 2000) b) For post-op pain: 0. 25-2 mg/kg IM, SQ; or as a CRI at 0. 05-0. 2 mg/kg/hr. (Grubb 2007) c) 0. 5-2. 2 mg/kg SC, IM q 4-6h; 0. 1-0. 2 mg/kg IV q1-2h (Gaynor 2007) d) 0. 05-1 mg/kg IV q1-4hrs; as a CRI at 0. 1-0. 5 mg/kg/hr; 0. 2-2 mg/kg IM, SC q2-4h; 0. 5-1 mg/kg PO q6-8h. (Han-sen 2007b) e) Using the oral sustained release product: 1. 5-3 mg/kg, PO q12h (Hardie 2000) ( Note : Recent research (Ku Kanich, Papi-ch et al. 2004) demonstrated that the oral sustained release form of morphine is erratically absorbed in dogs and the au-thors concluded that it cannot be practically dosed to dogs orally) Epidural administration for pain control: a) 0. 1 mg/kg. Dilution may be necessary for accurate measure-ment. T otal volume administered not to exceed 0. 3 m L/kg. (Mathews 1999) b) 0. 1 mg/kg preservative free morphine; duration of action 12-24 hours (Thomas 2000) c) Using regular morphine injection: 0. 1 mg/kg once; using preservative-free morphine: epidural at 0. 1-0. 2 mg/kg q8h; spinal at 0. 05 mg/kg q8h. (Hansen 2007b) As a preanesthetic: a) 0. 1-2 mg/kg SC (Booth 1988a) For adjunctive treatment of cardiogenic pulmonary edema: a) 0. 05-1 mg/kg IV q1-4 hours, or 0. 1-0. 5 mg/kg hr IV infu-sion, or 0. 2-2 mg/kg IM or SC q2-4hr (Hansen 2003a) For treatment of hypermotile diarrhea: a) 0. 25 mg/kg (Jones 1985a) As an antitussive: a) 0. 1 mg/kg q6-12h SC (Roudebush 1985) !TCATS: For analgesia: a) For post-op pain: 0. 1-0. 3 mg/kg IM, SC (Grubb 2007) b) 0. 05-0. 2 mg/kg SC, IM, may cause dysphoria if dose exces-sive (Carroll 1999) c) 0. 1-0. 4 mg/kg IM, SC q3-6h; concomitant tranquilization recommended (Hendrix and Hansen 2000) d) 0. 02-0. 1 mg/kg IV q1-4hrs; 0. 2-0. 5 mg/kg IM, SC q3-4h; 0. 2-0. 5 mg/kg PO q6-8h. (Hansen 2007b) Epidural administration for pain control: a) 0. 1 mg/kg preservative free morphine; duration of action 12-24 hours (Thomas 2000) b) Using preservative-free morphine: epidural at 0. 1-0. 2 mg/ kg q8h; spinal at 0. 05 mg/kg q8h. (Hansen 2007b) For adjunctive treatment of cardiogenic pulmonary edema: a) 0. 02-0. 1 mg/kg IV q1-4 hours, or 0. 2-0. 5 mg/kg IM or SC q3-4hr (Hansen 2003a) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 2-5 mg/kg IM or SC q2-4h for sedation and anal-gesia (Ivey and Morrisey 2000) !THORSES: (Note : ARCI UCGFS Class 1 Drug) Note : Narcotics may cause CNS excitement in the horse. Some clinicians recommend pretreatment with acepromazine (0. 02-0. 04 mg/kg IV), or xylazine (0. 3-0. 5 mg/kg IV) to reduce the behavioral changes these drugs can cause. Warning : Narcotic analgesics can mask the behavioral and cardiovascular clinical signs associated with mild colic. For analgesia: a) 0. 1 mg/kg IM q4h; this dose reduces morphine's impact on GI motility, but patients must be observed for problems fol-lowing morphine use. T o cover the excitatory effects of mor-phine, small doses of acepromazine (0. 011-0. 022 mg/kg IM, or 5-10 mg/450 kg) are generally included with the mor-phine injection. (Abrahamsen 2007a) b) For epidural: Adult horses: 0. 1-0. 2 mg/kg using convention-al morphine injection (15 mg/m L). Use a freshly opened vial. Suggest diluting with saline to a total volume of 0. 04 m L/kg or 20 m L/450kg. Foals: Using preservative free morphine at 0. 1 mg/kg. If no preservative free morphine available, dilute to a volume of 0. 2 m L/kg. (Abrahamsen 2007a) c) 0. 05-0. 12 mg/kg IV (Thurmon and Benson 1987) !TSWINE: As a preanesthetic/analgesic (prior to chloralose, barbiturate): a) 0. 2-0. 9 mg/kg IM. Note : may cause undesirable stimulation. (Booth 1988a) As an analgesic: a) 0. 2 mg/kg up to 20 mg total dose IM (Jenkins 1987) !TSHEEP & GOATS: As an analgesic: a) Up to 10 mg total dose, IM (Jenkins 1987) Monitoring !TRespiratory rate/depth !TCNS level of depression/excitation !TBlood pressure (especially with IV use) !TAnalgesic activity Client Information !TWhen given parenterally, this agent should be used in an inpa-tient setting or with direct professional supervision. Chemistry/Synonyms The sulfate salt of a natural (derived from opium) occurring opi-ate analgesic, morphine sulfate occurs as white, odorless, crystals. Solubility: 1 g in 16 m L of water (62. 5 mg/m L), 570 m L (1. 75 mg/ m L) of alcohol. It is insoluble in chloroform or ether. The p H of morphine sulfate injection ranges from 2. 5-6. Morphine sulfate may also be known as morphini sulfas, Astramorph PF®, Avinza®, Depo Dur®, Infumorph®, Kadian®, MSIR®, MS Contin®, Oramorph SR, RMS®, and Roxanol®.	pppbs.pdf
MOXIDECTIN 635 Storage/Stability/Compatibility Oral morphine products should be stored at in tight, light-resistant containers at room temperature unless otherwise labeled. Morphine injection should be stored at room temperature, protected from light; do not freeze. Morphine gradually darkens in color when exposed to light; protect from prolonged exposure to bright light. Morphine does not appear to adsorb to plastic or PVC syringes, tubing or bags. Morphine sulfate has been shown to be physically compatible at a concentration of 16. 2 mg/L with the following intravenous ﬂuids: Dextrose 2. 5%, 5%, 10% in water; Ringer's injection and Lactated Ringer's injection; Sodium Chloride 0. 45% and 0. 9% for injection. The following drugs have been shown to be physically incompatible when mixed with morphine sulfate: aminophylline, chlorothiaz-ide sodium, heparin sodium, meperidine, pentobarbital sodium, phenobarbital sodium, phenytoin sodium, sodium bicarbonate, and thiopental sodium. Morphine sulfate has been demonstrated to be generally physically compatible when mixed with the follow-ing agents: Atropine sulfate, benzquinamide HCl, butorphanol tartrate, chlorpromazine HCl, diphenhydramine HCl, dobutamine HCl, droperidol, fentanyl citrate, glycopyrrolate, hydroxyzine HCl, metoclopramide, pentazocine lactate, promazine HCl, scopolamine HBr, and succinylcholine chloride. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 1 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Morphine Sulfate for Injection: 0. 5 mg/m L, 1 mg/m L, 2 mg/m L, 4 mg/m L, 5 mg/m L, 8 mg/m L, 10 mg/m L, 15 mg/m L, 25 mg/m L, 50 mg/m L in amps, vials, syringes, and pre-ﬁlled IV bags in sizes that range from 1 m L to 250 m L depending on manufacturer and concen-tration. (Rx; C-II) Morphine Sulfate Liposomal Extended-release Injection: 15 mg/m L in 1, 1. 5, & 2 m L vials; Depo Dur® (Endo); (Rx, C-II) Morphine Sulfate for Injection (preservative-free): 0. 5 mg/m L: 2 m L amps, & 10 m L amps and vials; 1 mg/m L: 10 m L amps and vials; 10 mg/m L (200 mg) in 20 m L amps; 25 mg/m L (500 mg) in 20 m L amps; Infumorph® (Baxter); Astramorph PF® (Astra Zeneca); (Rx, C-II) Morphine Sulfate Soluble Tablets for Injection: 10 mg, 15 mg & 30 mg; generic; (Ranbaxy); (Rx, C-II) Morphine Sulfate Tablets: 15 mg & 30 mg; generic; (Rx, C-II) Morphine Sulfate Extended/Controlled Release Tablets: 15 mg, 30 mg, 60 mg, 100 mg & 200 mg; MS Contin® (Purdue Frederick); Oramorph SR® (aai Pharma); generic; (Rx, C-II) Morphine Sulfate Extended/Sustained Release Capsules: 20 mg, 30 mg, 50 mg, 60 mg, 80 mg, 90 mg, 100 mg & 120 mg; Avinza® (Li-gand); Kadian® (Alpharma); (Rx, C-II) Morphine Sulfate Oral Solution: 2 mg/m L in 100 m L, 500m L and UD 5m L and 10 m L; 4 mg/m L in 100m L, 120 m L and 500 m L; 20 mg/m L (concentrate) in 15 m L, 30 m L, 120 m L and 240 m L; MSIR® (Purdue Frederick); Morphine Sulfate (Roxane); Roxanol®,-T, &-100 (aai P-harma); generic; (Rx; C-II) Morphine Sulfate Rectal Suppositories: 5 mg, 10 mg, 20 mg, and 30 mg; RMS® (Upsher-Smith); generic; (various); (Rx, C-II) Note : All morphine products are Rx and a Class-II controlled sub-stance. Very accurate record keeping is required as to use and disposi-tion of stock. MOXIDECTIN (mox-i-dek-tin) Cydectin® A VERMECTIN ANTIPARASITIC Prescriber Highlights TT Avermectin antiparasitic with products approved for cattle, dogs, cats, sheep, & horses TT Contraindications: DOGS: Hypersensitive to it. CATTLE: Fe-male dairy cattle of breeding age; HORSES: Intended for food purposes or in foals younger than 4 months of age TT Adverse Effects: DOGS (potentially): Lethargy, vomit-ing, ataxia, anorexia, diarrhea, nervousness, weakness, increased thirst, & itching. CATTLE: Adverse effects mini-mal. HORSES: At labeled doses, appear minimal. TT Apparently safe to use in mdr1 gene mutation dog breeds a recommended doses Uses/Indications In dogs and cats, moxidectin with lufenuron is indicated as a once a month topical preventative for the prevention of heartworm, ﬂea adulticide, ear mites (cats) and treatment for hookworms, round-worms, and whipworms (dogs). It has also been successfully used as a treatment for generalized demodicosis. In cattle, moxidectin is indicated for the treatment and con-trol of the following internal [adult and fourth stage larvae (L4)] and external parasites: Gastrointestinal roundworms: Ostertagia ostertagi (adult and L4, including inhibited larvae), Haemonchus placei (adult), Trichostrongylus axei (adult and L4), Trichostrongylus colubriformis (adult), Cooperia oncophora (adult), Cooperia punc-tata (adult), Bunostomum phlebotomum (adult), Oesophagostomum radiatum (adult), Nematodirus helvetianus (adult); Lungworm: Dictyocaulus viviparus (adult and L4); Cattle Grubs: Hypoderma bovis, Hypoderma lineatum Mites: Chorioptes bovis, Psoroptes ovis (Psoroptes communis var. bovis); Lice: Linognathus vituli, Haematopinus eurysternus, Solenopotes capillatus, Damalinia bovis; Horn ﬂies: Haematobia irritans. T o control infections and to protect from reinfection from Ostertagia ostertagi for 28 days after treat-ment and from Dictyocaulus viviparus for 42 days after treatment. In sheep, oral moxidectin is indicated for the control of Haemonchus contortus (adult and L4), Teladosrsagia circumcincta & trifurcata (adult and L4), Trichostrongylus colubriformis, axei, & vitrinius (adult & L4), Cooperia curticei & oncophora (adult and L4), Oesophagostomum columbianum & venolosum (adult & L4), and Nematodirus battus, ﬁlicollis, & spathiger (adult & L4). In horses and ponies, moxidectin is indicated for the treat-ment and control of the following stages of gastrointestinal para-sites: Large strongyles: Strongylus vulgaris (adults and L4L5 ar-terial stages); Strongylus edentatus (adults and tissue stages); Triodontophorus brevicauda (adults); Triodontophorus serratus (adults); Small strongyles (adults and larvae): Cyathostomum spp. (adults); Cylicocyclus spp. (adults); Cylicostephanus spp. (adults); Gyalocephalus capitatus (adults); undifferentiated lumenal larvae; Encysted cyathostomes: late L3 and L4 mucosal cyathostome lar-vae; Ascarids: Parascaris equorum (adults and L4 larval stages); Pin worms: Oxyuris equi (adults and L4 larval stages); Hair worms: Trichostrongylus axei (adults); Large-mouth stomach worms: Habronema muscae (adults); Horse stomach bots: Gasterophilus in-testinalis (2nd and 3rd instars). When combined with praziquantel, additional coverage against Anoplocephala spp. occurs.	pppbs.pdf
636 MOXIDECTIN Pharmacology/Actions The primary mode of action of avermectins like moxidectin is to affect chloride ion channel activity in the nervous system of nema-todes and arthropods. The drug binds to receptors that increase membrane permeability to chloride ions. This inhibits the electri-cal activity of nerve cells in nematodes and muscle cells in arthro-pods and causes paralysis and death of the parasites. Avermectins also enhance the release of gamma amino butyric acid (GABA) at presynaptic neurons. GABA acts as an inhibitory neurotransmitter and blocks the post-synaptic stimulation of the adjacent neuron in nematodes or the muscle ﬁber in arthropods. Avermectins are generally not toxic to mammals, since they do not have glutamate-gated chloride channels and these compounds do not readily cross the blood-brain barrier where mammalian GABA receptors occur. Pharmacokinetics Minimal information was located. In cattle, the drug apparently has a long duration of plasma residence (14-15 days). After SC injec-tion, approximately 5% of the dose given to the cow can be passed to the suckling calf. Contraindications/Precautions/Warnings Dogs: Contraindicated in dogs hypersensitive to it. The manufac-turer warns to only use the oral product in dogs tested negative for heartworm infection. Adult heartworms and microﬁlaria should be removed prior to therapy. If more than two months pass be-tween dosages of this or other once a month heartworm preventa-tive medications, the dog should be tested for heartworm infection before receiving the next dose. Cattle: Not for use in female dairy cattle of breeding age. Horses: Not for horses intended for food purposes and is not labeled for use in foals younger than 4 months of age. Adverse Effects Dogs: While adverse reactions to this medication apparently oc-cur infrequently, after the injectable product (Pro Heart®6) was ad-ministered to heartworm positive dogs, a low number experienced coughing or cardiopulmonary signs and deaths have occurred (very rarely; 2. 5 per 100,000 doses). Additionally, the following adverse reactions may be seen: lethargy, vomiting, ataxia, anorexia, diar-rhea, nervousness, weakness, increased thirst, and itching. Studies done in Collies (up to 20X) demonstrated no notable adverse ef-fects. One Collie receiving doses of 30X demonstrated mild signs of depression, ataxia, and salivation. Cattle: Thus far at labeled doses, adverse effects appear to non-existent or minimal. Horses: Thus far at labeled doses, adverse effects appear to be nonexistent or minimal. A case report where three foals developed CNS depression and coma after receiving high dosages has been reported. Two of these three animals were less than 2 weeks of age and all received much higher than labeled dosages. Reproductive/Nursing Safety Dogs, Cats: Reproductive studies have demonstrated no evidence of adverse effects on fertility, reproductive performance, or offspring. Cattle & Horses: Reproductive studies performed thus far have demonstrated no evidence of adverse effects on fertility, reproduc-tive performance, or offspring in cattle or horses treated. Overdosage/Acute Toxicity Dogs: The drug apparently has a very wide margin of safety in dogs when administered orally. Dosages of up to 300X (1120 mcg/kg) demonstrated little or no effects. Dogs administered inadvertent overdoses during a clinical study treating demodicosis showed signs of dysorexia, hypersalivation, mydriasis, and fasiculations and ataxia of the pelvic limbs. There were 172 exposures to moxidectin reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org ) dur-ing 2005-2006. In these cases, 171 were dogs with 42 showing clinical signs and the remaining case was 1 cat that showed clinical signs. Common ﬁndings in dogs recorded in decreasing frequen-cy included tremors, ataxia, seizures, vomiting and hyperesthesia. Common ﬁndings in cats recorded included recumbency. Cattle: In studies done on cattle, application of the pour-on so-lution at 5X the recommended dose for ﬁve consecutive days, 10X for two consecutive days and 25X for one day did not produce any signiﬁcant adverse clinical or pathological effects. Horses: In one study, three of eight foals given the 3X dose be-came depressed or ataxic after one treatment. The author has re-ceived an anecdotal report of a miniature horse developing seizures after receiving a full tube of Quest®. Drug Interactions While no speciﬁc drug interactions for moxidectin have been re-ported, the following drug interactions have either been reported or are theoretical in humans or animals receiving ivermectin (a related compound) and may be of signiﬁcance in veterinary patients: !TBENZODIAZEPINES : Effects may be potentiated by moxidectin; use together not advised in humans Caution is advised if using other drugs that can inhibit p-glycoprotein. Those dogs at risk for MDR1-allele mutation (Collies, Australian Shepherds, Shelties, Long-haired Whippet, etc. “white feet”) should probably not receive moxidectin with the following drugs, unless tested “normal”: Drugs and drug classes involved include: !!AMIODARONE !!CARV EDILOL !!CLARITHROMYCIN !!CYCLOSPORINE !!DILTIAZEM !!ERYTHROMYCIN !!ITRACONAZOLE !!KETOCONAZOLE !!QUINIDINE !!SPIRONOLACTONE !!TAMOXIFEN !!VERAPAMIL Doses !TDOGS: a) For labeled indications (prevention of heartworm disease, adult ﬂeas, adult and immature hookworms, adult round-worms, and adult whipworms): Recommended minimum dose is 10 mg/kg imidacloprid/2. 5 mg/kg moxidectin once a month by topical administration ( Note : See package insert for speciﬁc instructions on application and safety). For dogs 3-9 lb = 0. 4 m L; 9. 1-20 lb = 1 m L; 20. 1-55 lb = 2. 5 m L, 55. 1-88 lb = 4 m L; dogs over 88 lb should be treated with appropriate combination for their weight. (Label directions; Advantage Multi® for Dogs—Bayer) b) For scabiocidal therapy: Where Cydectin® is available for injection: 0. 25 mg/kg SC every 7 days for three treatments. If using oral therapy 0. 4 mg/kg PO every 3-4 days for 3-6 weeks. (Foil 2003c) c) For generalized demodicosis: 0. 2-0. 4 mg/kg PO once a day. Clinical cure averages 75 days; parasitic cure averages 112 days. (Merchant 2000)	pppbs.pdf
MYCOBACTERIAL CELL WALL FRACTION IMMUNOMODULATOR 637 T ! CATS: a) For labeled indications (prevention of heartworm disease, adult ﬂeas, ear mites, adult and immature hookworms, and adult roundworms: Recommended minimum dose is 10 mg/ kg imidacloprid/1 mg/kg moxidectin once a month by topi-cal administration ( Note : See package insert for speciﬁc in-structions on application and safety). For cats 2-5 lb = 0. 23 m L; 5. 1-9 lb = 0. 4 m L; 9. 1-18 lb = 0. 8 m L; cats over 18 lb should be treated with appropriate combination for their weight. (Label directions; Advantage Multi® for Cats—Bay-er) T ! CATTLE: a) For labeled indications: 1 m L (5 mg)/10 kg (22 lb) body-weight applied directly to the hair and skin along the top of the back from the withers to the base of the tail. Applica-tion should be made to healthy skin avoiding mange scabs, skin lesions or extraneous foreign matter. (Label Directions; Cydectin® Pour-On—Fort Dodge) b) 0. 2 mg/kg [1 m L for each 110 lb (50 kg) of bodyweight] sub-cutaneously under the loose skin in front of or behind the shoulder. Needles 1/2-3/4 inch in length and 16-18 gauge are recommended. (Label Directions; Cydectin® Injection— Fort Dodge) T ! SHEEP: a) For labeled indications: 0. 2 mg/kg [1 m L per 11 lb (1 m L per 5 kg) bodyweight] PO (drench); Cydectin® Oral Drench for Sheep—Fort Dodge) T ! HORSES: a) For labeled indications using the combination oral gel with praziquantel: Dial in the weight of the animal on the syringe. Administer gel by inserting the syringe applicator into the animal's mouth through the interdental space and depositing the gel in the back of the mouth near the base of the tongue. Once the syringe is removed, the animal's head should be raised to insure proper swallowing of the gel. Horses weigh-ing more than 1250 lb require additional gel from a second syringe. (Label Directions; Quest® Plus—Fort Dodge) b) For mucosal stages of small strongyles: 400 mcg/kg PO (Ly-ons and Drudge 2000) Chemistry/Synonyms An avermectin-class antiparasitic agent, moxidectin is a semi-syn-thetic methoxime derivative of nemadectin. Moxidectin may also be known as CL-301423, Advantage Multi®, Combo Care®, Cydectin®, and Quest®. Storage/Stability The commercially available injection and the oral drench for sheep should be stored at, or below 77°F (25°C) and protected from light. The topical solution for cattle should be stored at or below room temperature. Do not allow prolonged exposure to temperatures above 77°F. If product becomes frozen, thaw completely and shake well before using. The oral gel for horses should be stored at or near room tem-perature (59°F-86°F); avoid freezing. If product becomes frozen, thaw completely before using. Partially used syringes should have the cap tightly secured. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Moxidectin 0. 5% (5 mg/m L) Pour-On for Cattle in 500 m L, 1 L, 2. 5 L, 5 L, and 10 L containers; Cydectin® (Fort Dodge); (OTC). Approved for use in cattle; not to be used in veal calves. No meat or milk with-drawal times required, but FDA has established tolerances of 50 ppb and 200 ppb for parent moxidectin in muscle and liver, respectively, for cattle. Moxidectin 10 mg/m L Injectable Solution in 200 m L and 500 m L; Cydectin® Injectable Solution (Fort Dodge); (OTC). Approved for cat-tle. Not to be used in female dairy cattle of breeding age, veal calves, and calves less than 8 weeks of age. Meat withdrawal = 21 days. Moxidectin 1 mg/m L Injectable Solution in 1 L and 4 L; Cydectin® Oral Drench for Sheep (Fort Dodge); (OTC). Approved for sheep. Not to be used in female sheep providing milk for human consumption. Meat withdrawal = 7 days. Moxidectin Oral Gel containing 20 mg/m L in 11. 3 g syringes (suf-ﬁcient to treat one 1150 lb horse); Quest® (Fort Dodge); (OTC). Ap-proved for use in horse or ponies not intended for food purposes. Oral Gel containing 20 mg/m L moxidectin and 125 mg/m L of prazi-quantel in 11. 6 g syringes (sufﬁcient to treat one 1150 lb horse); Quest Plus® (Fort Dodge), Combo Care® Equine Oral Gel (Farnam); (OTC). Approved for use in horse or ponies not intended for food purposes. Moxidectin 1% (10 mg/m L) and Imidacloprid 10% (100 mg/m L) T opical Solution in 3—0. 23m L tubes, 6—0. 4m L tubes & 6—0. 8m L tubes; Advantage Multi® for Cats (Bayer); (Rx). Approved for use on cats 9 weeks of age or greater, and more than 2 lb body weight. Moxidectin 2. 5% (25 mg/m L) and Imidacloprid 10% (100 mg/m L) T opical Solution in 6—0. 4m L tubes, 6—1m L tubes, 6—2. 5 m L tubes, & 6—4m L tubes; Advantage Multi® for Dogs (Bayer); (Rx). Approved for use on dogs 7 weeks of age or greater, and more than 3 lb body weight. HUMAN-LABELED PRODUCTS: None MYCOBACTERIAL CELL WALL FRACTION IMMUNOMODULATOR (my-koe-bak-tear-ee-al) Regressin®-V, Equimune® I. V. IMMUNOSTIMULANT Prescriber Highlights TT Biologic used as a locally inﬁltrated injection for immu-notherapy treatment of mixed mammary tumor & mam-mary adenocarcinomas in dogs TT In horses, used for immunotherapy treatment of sarcoids (local inﬁltration), ERCD (IV) or as an aid in the treatment of equine metritis caused by Streptococcus zooepidemic-us (IV, IU) TT Adverse effects include: Transient fever, depression, de-creased appetite, localized pain. Hypersensitivity & sys-temic inﬂammatory reactions possible. TT Efﬁcacy for systemic use is not well established	pppbs.pdf
638 MYCOBACTERIAL CELL WALL FRACTION IMMUNOMODULATOR TUses/Indications Mycobacterial cell wall fraction immunomodulator is commercial-ly available as three products with veterinary labeling, Regressin®-V, Equimune®-IV and Settle®. Regressin®-V is labeled as a locally inﬁl-trated injection for immunotherapy treatment of mixed mammary tumor and mammary adenocarcinomas in dogs, and for immuno-therapy treatment of sarcoids in horses. Equimune®-IV is labeled for use in horses only as an immunotherapeutic agent for the treat-ment of Equine Respiratory Disease Complex (ERDC). Settle® is labeled as an aid in the treatment of equine metritis caused by Streptococcus zooepidemicus (IV, IU) in horses. Although not labeled indications, Equimune®-IV has reportedly been used in horses as an adjuvant for EPM treatment and as an adjuvant for herpesvirus vaccines when injected IM at a separate site from the vaccine. Documentation of efﬁcacy for these uses was not located. Pharmacology/Actions Mycobacterial fractionated compounds require a functional im-mune system for efﬁcacy. They have a non-speciﬁc immune stimulatory primarily on cell-mediated immune mechanisms and macrophage activation. Interleukin-1 release from macrophages is thought to be the primary mediator for their actions. Pharmacokinetics No information was located. Contraindications/Precautions/Warnings These drugs should not be used in patients with prior hypersensi-tivity to mycobacterial cell wall compounds or those with mycobac-terial infections. The manufacturer warns that patients receiving cortisone or ACTH may not respond to treatment; in case of an anaphylactic reaction, administer epinephrine. Adverse Effects Horses: Adverse effects include fever, drowsiness and diminished appetite for 1-2 days after injection. Local inﬁltrations can cause pain and tenderness at injection site. Anaphylaxis and severe respi-ratory inﬂammatory reactions have also been reported. Dogs: Adverse effects include fever, drowsiness and diminished appetite for 1-2 days after injection. Local inﬁltrations can cause pain and tenderness at injection site. Later necrosis and draining may occur. Anaphylaxis or hypersensitivity reactions are possible. Reproductive/Nursing Safety The manufacturer states that Regressin®-V and Equimune®-I. V. are safe to use in pregnant mares. No other information was located. Overdosage/Acute Toxicity No information was located. Drug Interactions !TCORTICOSTEROIDS, ACTH, IMMUNOSUPPRESSIVE DRUGS (e. g., cy-closporine ): May reduce the effectiveness of mycobacterial cell wall immunostimulants Laboratory Considerations None identiﬁed Doses !TDOGS: a) Using Regressin®-V for immunotherapy of mixed mammary tumor and mammary adenocarcinoma: Using no larger than a 20-gauge needle, inﬁltrate entire tumor and a small region of adjacent and underlying tissue. Dosage varies with tumor size, but 1 m L should be considered a minimum dose. Be certain the emulsion is mixed thoroughly and inject quickly as emulsion can separate rapidly (see Stability information for more information on mixing. ) As pain may occur, addi-tional anesthetics or analgesics may be used. Tumors may be treated once, 2-4 weeks before surgery. If surgery is not to be used, repeat treatment every 1-3 weeks. If no response after 4 treatments, discontinue. (Label information; Regressin®-V—Bioniche) !THORSES: a) Using Regressin®-V for immunotherapy of sarcoids: Large pedunculated sarcoids should be de-bulked by partial exci-sion prior to treatment. Using no larger than a 20-gauge nee-dle, inﬁltrate entire tumor and a small region of adjacent and underlying tissue. Dosage varies with tumor size, but 1 m L should be considered a minimum dose. Be certain the emul-sion is mixed thoroughly and inject quickly as emulsion can separate rapidly (see Stability information for more informa-tion on mixing. ) As pain may occur, additional anesthetics or analgesics may be used. Repeat treatment every 1-3 weeks. If no response after 4 treatments, discontinue. (Label informa-tion; Regressin®-V—Bioniche) b) Using Equimune®I. V. as an immunotherapeutic agent for the treatment of Equine Respiratory Disease Complex (ERDC): 1. 5 m L (one syringe) IV into the jugular vein. May be re-peated in 1-3 weeks. (Label information; Equimune®I. V. — Bioniche) c) Using Settle® as an aid in the treatment of equine metritis caused by Streptococcus zooepidemicus: Intravenous use: 1. 5 m L (one syringe) IV into the jugular vein during the early estrus period. Or administer via intrauterine instillation: Dilute 1. 5 m L of Settle® in sterile LRS, normal saline, wa-ter for injection or semen extender to provide a ﬁnal volume of 25-50 m L. Aseptically administer the diluted solution into the uterus using a sterile catheter. (Label information; Settle®—Bioniche) Monitoring !TClinical Efﬁcacy (tumor size, metritis improvement, or respira-tory infection improvement) !TAdverse Effects (fever, local reactions, appetite) Client Information !TIntratumoral injection may cause pain or tenderness at the injec-tion site. Tumors may drain or become necrotic indicating ef-fectiveness; if this occurs and is bothersome, contact veterinarian for further instructions on management. !Treated animals may be depressed, develop fever, or have reduced appetite for a few days after treatment; if these persist or are severe, contact veterinarian Chemistry/Synonyms Regressin®-V, Equimune®-I. V. and Settle® are oil-in-water emulsions containing puriﬁed cell wall fractions obtained from Mycobacteria (species not described) that are non-pathogenic. Concentration is not listed for either product. Regressin®-V also contains procaine HCl 0. 2% w/v as a local anesthetic and a green tracking dye solu-tion (not identiﬁed) 0. 1% w/v used to indicate area inﬁltrated.	pppbs.pdf
MYCOPHENOLATE MOFETIL 639 Mycobacterial cell wall fraction may also be known as my-cobacterial cell wall extract, bacillus Calmette-Guerin, or BCG, Equimune®, Regressin®, and Settle®. Storage/Stability These products should be stored refrigerated (2-7°C), but not frozen. Unused product from vials not labeled for multi-dose use should be discarded after use. The emulsion “breaks” upon standing and the product must be re-emulsiﬁed before administration. T o re-emulsify to a milky appearance, shake vial, roll syringe between hands, or heat in hot water (150°F, 65°C). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Mycobacterial Cell Wall Fraction Immunomodulator for IV Injection in 1. 5 m L single use vials and 4. 5 m L multi-dose vials; Equimune®I. V. (Bioniche). Labeled for use in horses. Mycobacterial Cell Wall Fraction Immunomodulator for IV injec-tion of Intrauterine instillation in 1. 5 m L single use vials; Settle® (Bioniche). Contains gentamicin as a preservative. Labeled for use in horses. Mycobacterial Cell Wall Fraction Immunomodulator for Tumor In-ﬁltration in 10 m L vials; Regressin®-V (Bioniche). Also contains pro-caine and a green dye. Labeled for use in horses and dogs. Note : These products are USDA-licensed biologics and are not FDA-approved products. Equimune®I. V. and Regressin®-V are not to be used in food producing animals. The label for Settle® states that it should not be administered to horses within 21 days of slaughter. HUMAN-LABELED PRODUCTS: None MYCOPHENOLATE MOFETIL (my-koh-fen-oh-layt) Cellcept®, MMF IMMUNOSUPPRESSANT Prescriber Highlights TT Immunosuppressive drug that may be useful for treating dogs with IMHA, glomerulonephritis, myasthenia gravis, pemphigus folacious or inﬂammatory bowel disease in dogs; potentially useful in cats, but no information lo-cated on safety or efﬁcacy TT Very limited experience in veterinary medicine TT Gastrointestinal effects (diarrhea, vomiting, anorexia) most likely adverse effects & can be severe TT Treatment may be very expensive Uses/Indications While there has been very limited experience using mycophenolate in veterinary medicine, it potentially could be useful in the treat-ment of a variety of autoimmune diseases, including immune-mediated hemolytic anemia (IMHA), myasthenia gravis, glomeru-lonephritis, and pemphigus foliaceous. While mycophenolate has been suggested for use in treating inﬂammatory bowel disease in dogs, the drug's primary adverse effects in dogs are gastritis, diar-rhea, and intestinal inﬂammation. Mycophenolate is also used in anti-rejection protocols for organ transplants in animals. In humans, although it is used “off label” for a variety of autoim-mune disease indications, the drug is only labeled for use to prevent transplant rejection. Pharmacology/Actions Mycophenolate mofetil (MMF) is a prodrug that must be con-verted (hydrolyzed) in vivo to mycophenolic acid (MPA) for it to be pharmacologically active. MPA non-competitively, but revers-ibly, inhibits inosine monophosphate dehydrogenase (IMPDHA). This is the rate-limiting enzyme in de novo synthesis of guanosine nucleotides. As T-and B-cells are dependent on de novo synthesis of purines (e. g., guanosine) and unlike other cells cannot use salvage pathways, proliferative responses of T-and B-cells are inhibited and suppression of B-cell formation of antibodies occur. Via its effects, MPA can inhibit leukocyte recruitment to inﬂammatory sites and allotransplant tissues. Pharmacokinetics After oral administration mycophenolate mofetil is absorbed, but limited bioavailability studies in dogs have shown both a wide in-ter-patient and inter-dose variation. One study done in a single dog showed bioavailabilities of 54%, 65%, and 87% after doses of 10, 15, and 20 mg/kg of MMF were administered (Lupu, Mc Cune et al. 2006). In humans, oral bioavailability averages 94%; food reduces peak levels of MPA by up to 40%. After absorption, MMF is rapidly hydrolyzed to mycophenolic acid. In a study in dogs comparing mycophenolic acid's (MPA) phar-macokinetic parameters with its pharmacodynamic effects on inosine monophosphate dehydrogenase activity in lymphocytes (Langman, Shapiro et al. 1996), volume of distribution at steady-state was approximately 5 L/kg, but there was wide inter-patient variability (±4. 5). Elimination half-life for MPA was about 8 hours (±4 hours). Mycophenolic acid is primarily excreted in the urine, both unchanged (approximately 5%) and as the glucuronide me-tabolite (approximately 90%). In this study, the authors concluded that the pharmacokinetic/pharmacodynamic proﬁle of MMF in dogs suggests that an every 8-hour dosing schedule would be re-quired for optimization of immunosuppressive efﬁcacy. Contraindications/Precautions/Warnings Do not use in patients with documented hypersensitivity reactions to mycophenolate. Patients with severe renal dysfunction may re-quire dosage adjustment. Intravenous mycophenolate must be administered over at least two hours; it is not to be given as an IV bolus or via rapid IV infusion. For humans, mycophenolate has a “black box” warning regard-ing potential increased risk for lymphoma associated with its use. Adverse Effects Because of the limited numbers of veterinary patients who have re-ceived this drug, the adverse effect proﬁle is not well established. The primary adverse effects reported in dogs thus far include diar-rhea, vomiting, anorexia, lethargy/reduced activity, lymphopenia, and increased rates of dermal infections. Because of the drug's im-munosuppressive actions, increased systemic infection and malig-nancy rates are possible. A study (Chanda, Sellin et al. 2002) comparing adverse effects in dogs with mycophenolate mofetil capsules and mycophenolate sodium enteric-coated tablets demonstrated signiﬁcantly greater occurrences and severity of diarrhea, weight loss and hypo-activity in the dogs that received the sodium salt enteric-coated tablets. In humans, the most common adverse effects include GI ef-fects (constipation, diarrhea, nausea, vomiting) and headache. Hypertension and peripheral edema occur in about 30% of pa-	pppbs.pdf
640 MYCOPHENOLATE MOFETIL tients. Leukopenia has been reported in 25-45% of patients taking the medication. Other effects that occur more rarely include: GI bleeding, severe neutropenia, cough, confusion, tremor, infection and malignant lymphoma (0. 4-1%). Reproductive/Nursing Safety At doses signiﬁcantly lower than those used in humans, increased resorptions and malformations were noted in rabbits and rats; it is recommended that the drug be avoided, if at all possible, during pregnancy. Mycophenolic acid is distributed in rat milk. It is unknown if it is safe to use during nursing. Overdosage/Acute Toxicity In oral acute studies performed in mice and monkeys, no deaths oc-curred in dosages up to 4,000 mg/kg and 1,000 mg/kg, respectively. In small animals, acute GI disturbances could be expected. Treat supportively, if required. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving mycophenolate mofetil and may be of signiﬁcance in veterinary patients: !TACYCLOVIR : Increased serum concentrations of acyclovir and the phenolic glucuronide of mycophenolic acid !TANTACIDS (aluminum or magnesium containing ): Decreased absorp-tion of mycophenolate; separate dosing by at least 2 hours !TASPIRIN (or other salicylates ): Potentially increased concentrations of free mycophenolic acid !TAZATHIOPRINE : Increased risk for bone marrow suppression; use together not recommended in humans !TIRON (oral): Decreased absorption of mycophenolate; separate dosing by at least 2 hours !TPROBENECID : Potentially increased serum levels of mycophenolic acid and the phenolic glucuronide of mycophenolic acid !TVACCINES (live virus ): May be less effective; avoid use Laboratory Considerations No issues noted Doses !TDOGS: a) For IMHA: 12-17 mg/kg PO once daily or divided twice daily. Given with prednisolone (at 2 mg/kg q12-24h). Dogs also received ranitidine and sucralfate in the study. (Nielsen, Niessen et al. 2005) b) Limited use has shown a beneﬁcial response in dogs with IMHA, myasthenia gravis or glomerulonephritis: 12-17 mg/ kg PO once daily or divided twice daily. Given with predni-sone (at 2. 2 mg/kg q12-24h). (Macintire 2006d) c) For adjunctive treatment of glomerulonephritis: 10-20 mg/ kg PO q12h. Immunosuppressive treatment is controver-sial. Other immunosuppressive drugs suggested include: glucocorticoids, cyclophosphamide, azathioprine, and cy-closporine. Trial of single drug therapy for 3-4 weeks rec-ommended. (Labato 2006) d) For pemphigus foliaceous: 22-39 mg/kg/day divided into 3 daily doses. Success rates (limited use) of approximately 50%; most dogs require glucocorticoids to control signs. (Rosenkrantz 2004) e) For pemphigus foliaceous: 15 mg/kg PO twice daily. Dose is anecdotal at this time. Appears well tolerated. (Morris 2004) Monitoring !TEfﬁcacy !TCBC, renal and hepatic function, serum electrolytes; baseline and periodically (frequency depending on reason for treatment) !TGastrointestinal effects (weight, client's report) Client Information !TPreferably give on an empty stomach; if vomiting or lack of ap-petite occurs, give with food to see if it improves !TBecause of concerns that this drug can cause birth defects, the manufacturer recommends that tablets or capsules not be crushed, split, or opened. !TIf diarrhea persists or is severe, contact veterinarian Chemistry/Synonyms Mycophenolate mofetil occurs as a white or almost white, crystal-line powder. It is practically insoluble in water and sparingly soluble in alcohol. Mycophenolate mofetil may also be known as: RS-61443 or MMF. International trade names include: Cell Cept®, Cellmune®, Imuxgen®, Munotras®, Mycept®, Myfortic®, and Refrat®. Storage/Compatibility Mycophenolate mofetil tablets and capsules should be stored be-tween 15-30°C and protected from light. Mycophenolate mofetil powder for oral suspension should be stored between 15-30°C; preferably at 25°C. Once reconstituted with 94 m L of water it may be stored at room temperature or in the refrigerator; do not freeze. Unused drug should be discarded after 60 days. The injectable product should be stored between 15-30°C; pref-erably at 25°C. Each vial should be reconstituted with 14 m L of 5% dextrose injection; ﬁnal volume is approximately 15 m L. Gently agitate to dissolve the powder. For human use, the manufacturer recommends further diluting with dextrose 5% to a concentration of 6 mg/m L for IV administration. This would be an additional 70 m L of dextrose 5% per vial. Mycophenolate injection should not be mixed or given with any other medication or diluent. It is recom-mended to administer within 6 hours of dilution. The drug must be administered over at least two hours and is not to be given as an IV bolus or via rapid IV infusion. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Mycophenolate Mofetil Capsules: 250 mg; Cell Cept ® (Roche); (Rx) Mycophenolate Mofetil Tablets: 500 mg; Cell Cept ® (Roche); (Rx) Mycophenolate Mofetil Powder for Oral Suspension: 200 mg/m L in 225 m L bottles; Cell Cept® (Roche); (Rx) Mycophenolate Mofetil Lyophilized Powder for Injection: 500 mg in 20 m L vials; Cell Cept® (Roche); (Rx) Mycophenolate is also available as the sodium salt in oral, delayed-release tablets in 180 mg and 360 mg strengths. Trade name is Myfor-tic® (Novartis); (Rx). It does not appear that this dosage form will be useful for veterinary patients.	pppbs.pdf
NALOXONE HCL 641 NALOXONE HCL (nal-ox-one) Narcan® ANTIDOTE; OPIATE ANTAGONIST Prescriber Highlights TT Injectable opiate antagonist TT Contraindications: Hypersensitivity to it. Caution: Preex-isting cardiac abnormalities or opioid dependent TT Reversal effect may last for a shorter time than opioid effect; monitor & re-dose as needed Uses/Indications Naloxone is used in veterinary medicine almost exclusively for its opiate reversal effects, but the drug is being investigated for treat-ing other conditions (e. g., septic, hypovolemic or cardiogenic shock). Naloxone may also be employed as a test drug to see if endogenous opiate blockade will result in diminished tail chasing or other self-mutilating behaviors. It, potentially, could be useful for treating overdoses of clonidine or the CNS effects of benzodi-azepines (ivermectin?), but more research is necessary before rec-ommending its use. Pharmacology/Actions Naloxone is considered a pure opiate antagonist and it has no an-algesic activity. The exact mechanism for its activity is not under-stood, but it is believed that the drug acts as a competitive antago-nist by binding to the mu, kappa, and sigma opioid receptor sites. The drug apparently has its highest afﬁnity for the mu receptor. Naloxone reverses the majority of effects associated with high-dose opiate administration (respiratory and CNS depression). In dogs, naloxone apparently does not reverse the emetic actions of apomorphine. Naloxone may be useful in treating adverse effects associated with overdoses of propoxyphene, pentazocine, buprenorphine and loperamide, but larger naloxone doses may be required. Naloxone has other pharmacologic activity at high doses, in-cluding effects on dopaminergic mechanisms (increases dopamine levels) and GABA antagonism. Pharmacokinetics Naloxone is only minimally absorbed when given orally as it is rap-idly destroyed in the GI tract. Much higher doses are required if using this route of administration for any pharmacologic effect. When given IV, naloxone has a very rapid onset of action (usually 1-2 minutes). If given IM, the drug generally has an onset of action within 5 minutes of administration. The duration of action usually persists from 45-90 minutes, but may act for up to 3 hours. Naloxone is distributed rapidly throughout the body with high levels found in the brain, kidneys, spleen, skeletal muscle, lung, and heart. The drug also readily crosses the placenta. Naloxone is metabolized in the liver, principally via glucuroni-dative conjugation, with metabolites excreted into the urine. In hu-mans, the serum half-life is approximately 60-100 minutes. Contraindications/Precautions/Warnings Naloxone is contraindicated in patients hypersensitive to it. It should be used cautiously in animals that have preexisting cardiac abnor-malities or that may be opioid dependent. The veterinary manufac-turer of the product once marketed for veterinary use states to use the drug “... cautiously in animals who have received exceedingly large doses of narcotics... it may produce an acute withdrawal syn-drome and smaller doses should be employed. ” (Package Insert; P/ M® Naloxone HCl Injection—Mallinckrodt) Adverse Effects At usual doses, naloxone is relatively free of adverse effects in non-opioid dependent patients. Because the duration of action of naloxone may be shorter than that of the narcotic being reversed, animals that are being treated for opioid intoxication or with clinical signs of respiratory depres-sion should be closely monitored as additional doses of naloxone and/or ventilatory support may be required. 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 trimes-ter of pregnancy, and there is no evidence of risk in later trimesters. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: A (Probably safe. Although speciﬁc studies may not have proved he safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) It is not known whether the drug is excreted in maternal milk. Use caution when administering to nursing patients. Overdosage/Acute Toxicity Naloxone is considered a very safe agent with a very wide margin of safety, but very high doses have initiated seizures (secondary to GABA antagonism?) in a few patients. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving naloxone and may be of signiﬁcance in veterinary patients: T ! OPIOID PARTIAL-AGONISTS (e. g., butorphanol, pentazocine, or nalbu-phine ): Naloxone may also antagonize the effects these agents (re-spiratory depression, analgesia). It should not be relied upon to treat respiratory depression caused by buprenorphine. T ! CLONIDINE : Naloxone may reduce the hypotensive and bradycardic effects of clonidine; potentially useful for clonidine overdoses T ! YOHIMBINE : Naloxone may increase the CNS effects of yohimbine (anxiety, tremors, nausea, palpitations) and increase plasma cor-tisol levels Doses T ! DOGS & CAT S: For opioid reversal: a) 0. 002-0. 02 mg/kg IV or IM; duration of effect 0. 5-1 hour (Bednarski 1989) b) Dogs: 0. 04 mg/kg IV, IM or SC (Package Insert; P/M® Nalox-one HCl Injection—Mallinckrodt), (Kirk 1989) c) Cats: 0. 05-0. 1 mg/kg IV (Muir and Swanson 1989) d) 0. 02-0. 04 mg/kg IV (Morgan 1988) T ! RABBITS, RODENTS, SMALL MAMMALS: a) For opioid reversal in rodents: 0. 01-0. 1 mg/kg SC or IP as needed (Huerkamp 1995) b) Rabbits: 0. 005-0. 1 mg/kg IM or IV (Ivey and Morrisey 2000) c) Hamsters, Gerbils, Mice, Rats, Guinea pigs, Chinchillas: 0. 01-0. 1 mg/kg SC, IP (Adamcak and Otten 2000)	pppbs.pdf
642 NALTREXONE HCL T ! HORSES: (Note : ARCI UCGFS Class 3 Drug) For opioid reversal: a) 0. 01-0. 022 mg/kg to reverse sedative and excitatory effects of narcotic agonists (Clark and Becht 1987) b) 0. 01 mg/kg IV to limit increases in locomotor activity sec-ondary to narcotic agonists (Muir 1987) c) 0. 01-0. 02 mg/kg IV (Robinson 1987) Monitoring T ! Respiratory rate/depth T ! CNS function T ! Pain associated with opiate reversal Client Information T ! Should be used with direct professional supervision only Chemistry/Synonyms An opiate antagonist, naloxone HCl is structurally related to oxy-morphone. It occurs as a white to slightly off-white powder with a p K a of 7. 94. Naloxone is soluble in water and slightly soluble in alcohol. The p H ranges of commercially available injectable solu-tions are from 3-4. 5. Naloxone HCl may also be known as: N-allylnoroxymorphone hydrochloride; cloridrato de naloxona, EN-15304, naloxoni hydro-chloridum and Narcan®. Storage/Stability/Compatibility Naloxone HCl for injection should be stored at room temperature (15-30°C) and protected from light. Sterile water for injection is the recommended diluent for nalox-one injection. When given as an IV infusion, either D 5W or normal saline should be used. Naloxone HCl injection should not be mixed with solutions containing sulﬁtes, bisulﬁtes, long-chain or high molecular weight anions or any solutions at alkaline p H. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Naloxone HCl Injection: 0. 4 mg/m L in 1 m L amps, syringes and 1, 2, and 10 m L vials; Narcan® (Du Pont Pharm. ); generic; (Rx) Naloxone HCl Neonatal Injection: 0. 02 mg/m L in 2 m L vials; generic; (Rx) NALTREXONE HCL (nal-trex-ohne) Trexan®, Re Via® OPIATE ANTAGONIST Prescriber Highlights TT Oral opiate antagonist that might be useful in determin-ing if adverse behaviors have a signiﬁcant endorphin component & for the short-term treatment of same TT Contraindications: Patients physically dependent on opi-ate drugs, in hepatic failure, or with acute hepatitis. Cau-tion: hepatic dysfunction or who have had a history of allergic reaction to naltrexone or naloxone. TT Adverse Effects: Relatively free of adverse effects. Poten-tially: Abdominal cramping, nausea & vomiting, nervous-ness, insomnia, joint or muscle pain, skin rashes, & pruri-tus. Dose-dependent hepatotoxicity is possible. TT May cause withdrawal clinical signs in physically depen-dent patients TT Expensive Uses/Indications Naltrexone might be useful in determining if adverse behaviors (e. g., self-mutilating or tail-chasing) in dogs or cats have a signiﬁ-cant endorphin component. Its relative expense and other more ac-cepted treatments have largely supplanted the use of this drug in animals for treatment of behavioral disorders. Pharmacology/Actions Naltrexone is an orally available narcotic antagonist. It competi-tively binds to opiate receptors in the CNS, thereby preventing both endogenous opiates (e. g., endorphins) and exogenously ad-ministered opiate agonists or agonist/antagonists from occupying the site. Naltrexone may be more effective in blocking the euphoric aspects of the opiates and less effective at blocking the respiratory depressive or miotic effects. Naltrexone may also increase plasma concentrations of luteiniz-ing hormone (LH), cortisol, and ACTH. In dogs with experimen-tally-induced hypovolemic shock, naltrexone (like naloxone) given IV in high dosages increased mean arterial pressure, cardiac output, stroke volume, and left ventricular contractility. Pharmacokinetics In humans, naltrexone is rapidly and nearly completely absorbed, but undergoes a signiﬁcant ﬁrst-pass effect as only 5-12% of a dose reaches the systemic circulation. Naltrexone circulates throughout the body and CSF levels are approximately 30% of those found in plasma. Only about 20-30% is bound to plasma proteins. It is unknown whether naltrexone crosses the placenta or enters milk. Naltrexone is metabolized in the liver primarily to 6-beta-naltrexol, which has some opiate blocking activity. Naltrexone's metabolites are eliminated primarily via the kidney. In humans, serum half-life of naltrexone is about 4 hours and about 13 hours for 6-beta-naltrexol. Contraindications/Precautions/Warnings Naltrexone is contraindicated in patients physically dependent on opiate drugs, in hepatic failure, or with acute hepatitis. The beneﬁts of the drug versus its risks should be weighed in patients with he-patic dysfunction or with a history of allergic reaction to naltrexone or naloxone.	pppbs.pdf
NANDROLONE DECANOATE 643 Adverse Effects At usual doses, naltrexone is relatively free of adverse effects in non-opioid dependent patients. Some human patients have developed abdominal cramping, nausea and vomiting, nervousness, insomnia, joint or muscle pain, skin rashes, and pruritus. Dose-dependent he-patotoxicity has been described in humans on occasion. Naltrexone will block the analgesic, antidiarrheal, and antitussive effects of opiate agonist or agonist/antagonist agents. Withdrawal clinical signs may be precipitated in physically dependent patients. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, but the po-tential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Very high doses have caused increased embryotoxicity in some laboratory animals. It should be used during pregnancy only when the beneﬁts outweigh any po-tential risks. Naltrexone enters into milk of humans and sheep. Use caution when administering to nursing patients. Overdosage/Acute Toxicity Naltrexone appears to be relatively safe even after very large doses. The LD 50 in dogs after subcutaneous injection has been reported to be 200 mg/kg. Oral LD 50's in species tested range from 1. 1 g/kg in mice to 3 g/kg in monkeys (dogs or cats not tested). Deaths at these doses were a result of respiratory depression and/or tonic-clonic seizures. Massive overdoses should be treated using gut-emptying protocols when warranted and giving supportive treatment. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving naltrexone and may be of signiﬁcance in veterinary patients: T ! OPIOID PARTIAL-AGONISTS (e. g., butorphanol, pentazocine, or nalbu-phine ): Naloxone may also antagonize the effects these agents (re-spiratory depression, analgesia). T ! CLONIDINE : Naltrexone may reduce the hypotensive and brady-cardic effects of clonidine T ! YOHIMBINE : Naltrexone may increase the CNS effects of yohim-bine (anxiety, tremors, nausea, palpitations) and increase plasma cortisol levels Laboratory Considerations T ! Naltrexone reportedly does not interfere with TLC, GLC, or HPLC methods of determining urinary opiates, or quinine, but can interfere with some enzymatic assays T ! Naltrexone may cause increases in hepatic function tests (e. g., AST, ALT) (see Adverse Effects above). Doses T ! DOGS: As adjunctive therapy in behavior disorders: a) For tail chasing or excessive licking: First give 0. 01 mg/kg SC of naloxone to determine if narcotic antagonists may be ef-fective, if so give naltrexone PO at 1-2 mg/kg daily. Long-term therapy may be required. (Crowill-Davis 1992) b) 2-5 mg/kg, PO once daily (Line 2000) c) 1-2. 2 mg/kg, PO q8-12h (Crowell-Davis 1999) For the adjunctive treatment of acral pruritic dermatitis: a) 2. 2 mg/kg, PO once daily for one-month trial. Some dogs exhibit drowsiness and minor changes in behavior. 50-60% of patients have beneﬁted. Expense is of concern. (Rosychuck 1991) T ! CATS: As adjunctive therapy in behavior disorders: a) 25-50 mg/cat PO q24h. Note : has a bitter taste (Crowell-Da-vis 1999) Monitoring T ! Efﬁcacy T ! Liver enzymes if using very high dose with prolonged therapy Client Information T ! Stress the importance of compliance with prescribed dosing regimen T ! Additional behavior modiﬁcation techniques may be required to alleviate clinical signs Chemistry/Synonyms A synthetic opiate antagonist, naltrexone HCl occurs as white crys-tals having a bitter taste. 100 mg are soluble in one m L of water. Naltrexone may also be known as EN-1639A, Re Via® and Vivitrol®. Storage/Stability/Compatibility Naltrexone tablets should be stored at room temperature in well-closed containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Naltrexone HCl Tablets: 50 mg; Re Via® (Duramed); generic; (Rx) Naltrexone HCl Suspension Extended-Release Injection: 380 mg/vial in single-use vials; Vivitrol® (Alkermes, Inc. ); (Rx) NANDROLONE DECANOATE (nan-droe-lone) Deca-Durabolin® PARENTERAL ANABOLIC STEROID Prescriber Highlights TT Injectable anabolic steroid; may be useful to stimulate erythropoiesis or to stimulate appetite TT Contraindications: Hepatic dysfunction, hypercalcemia, history of myocardial infarction, pituitary insufﬁciency, prostate carcinoma, mammary carcinoma, benign prostatic hypertrophy, & during the nephrotic stage of nephritis TT Adverse Effects: Sodium, calcium, potassium, water, chlo-ride, & phosphate retention; hepatotoxicity, behavioral (androgenic) changes, & reproductive abnormalities (oli-gospermia, estrus suppression) TT Known teratogen TT Drug Interactions TT C-III Controlled Substance	pppbs.pdf
644 NANDROLONE DECANOATE Uses/Indications The principle use of nandrolone in veterinary medicine has been to stimulate erythropoiesis in patients with certain anemias (e. g., sec-ondary to renal failure, aplastic anemias). It has also been suggested for use as an appetite stimulant. Pharmacology/Actions Nandrolone exhibits similar actions as other anabolic agents. In the presence of adequate protein and calories, anabolic steroids pro-mote body tissue building processes and can reverse catabolism. As these agents are either derived from or closely related to testos-terone, the anabolics have varying degrees of androgenic effects. Endogenous testosterone release may be suppressed by inhibiting luteinizing hormone (LH). Large doses can impede spermatogen-esis by negative feedback inhibition of FSH. Anabolic steroids can stimulate erythropoiesis. The mechanism for this effect may occur by stimulating erythropoietic stimulat-ing factor. Anabolics can cause nitrogen, sodium, potassium, and phosphorus retention and decrease the urinary excretion of cal-cium. Many veterinary and human clinicians feel that nandrolone is clinically superior to other anabolics in its ability to stimulate erythropoiesis. It is believed that nandrolone may enhance red cell counts by directly stimulating red cell precursors in the bone mar-row, increasing red cell 2,3-diphosphoglycerate and erythropoietin production in the kidney. Pharmacokinetics No speciﬁc information was located for this agent. It is generally recommended for both small animals and humans to be dosed on a weekly basis. Contraindications/Precautions/Warnings No speciﬁc recommendations were located for this agent in veteri-nary species. In humans, anabolic agents are contraindicated in patients with hepatic dysfunction, hypercalcemia, patients with a history of myocardial infarction (can cause hypercholesterolemia), pituitary insufﬁciency, prostate carcinoma, in selected patients with breast carcinoma, benign prostatic hypertrophy, and during the nephrotic stage of nephritis. Adverse Effects Potential (from human data) adverse reactions of the anabolic agents in dogs and cats include: sodium, calcium, potassium, water, chloride, and phosphate retention; hepatotoxicity, behavioral (an-drogenic) changes, and reproductive abnormalities (oligospermia, estrus suppression). Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category X for use during pregnancy (Studies in animals or humans demonstrate fetal abnormalities or adverse reaction; reports indicate evidence of fetal risk. The risk of use in pregnant women clearly outweighs any possible beneﬁt. ) Anabolic steroids can cause masculinization of the fetus. It is not known whether anabolic steroids are excreted in ma-ternal milk. Because of the potential for serious adverse reactions in nursing offspring, decide whether to discontinue nursing or the drug. Overdosage/Acute Toxicity No information was located for this speciﬁc agent. In humans, so-dium and water retention can occur after overdosage of anabolic steroids. It is suggested to treat supportively and monitor liver func-tion should an inadvertent overdose be administered. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving nandrolone and may be of signiﬁcance in veterinary patients: !TANTICOAGUL ANTS (warfarin ): Anabolic agents as a class may potenti-ate the effects of anticoagulants; monitoring of INR and dosage adjustment of the anticoagulant (if necessary) are recommended !TCORTICOSTEROIDS, ACTH : Anabolics may enhance the edema that can be associated with ACTH or adrenal steroid therapy !TINSULIN : Diabetic patients receiving insulin may need dosage ad-justments if anabolic therapy is added or discontinued; anabolics may decrease blood glucose and decrease insulin requirements Laboratory Considerations !TConcentrations of protein bound iodine (PBI) can be decreased in patients receiving androgen/anabolic therapy, but the clinical sig-niﬁcance of this is probably not important !TAndrogen/anabolic agents can decrease amounts of thyroxine-binding globulin and decrease total T 4 concentrations and increase resin uptake of T 3 and T 4; free thyroid hormones are unaltered and, clinically, there is no evidence of dysfunction. !TBoth creatinine and creatine excretion can be decreased by ana-bolic steroids !TAnabolic steroids can increase the urinary excretion of 17-keto-steroids !TAndrogenic/anabolic steroids may alter blood glucose levels. !TAndrogenic/anabolic steroids may suppress clotting factors II, V, VII, and X. !TAnabolic agents can affect liver function tests (BSP retention, SGOT, SGPT, bilirubin, and alkaline phosphatase) Doses !TDOGS: For adjunctive treatment of chronic idiopathic myeloﬁbrosis: a) Prednisolone at 2-3 mg/kg PO once daily for 3-4 weeks, then every other day with a tapering of the dose as the ane-mia resolves. Nandrolone decanoate may be used at 2 mg/kg IM weekly for 3 weeks. If anemia does not respond to initial treatments, azathioprine at 2 mg/kg PO every other day can be given. (Raskin 2006) For disuse muscle atrophy secondary to immobilization: a) 1. 5 mg/kg IM once weekly from the day of surgery/immobi-lization for up to 8 weeks. (Yun, Lim et al. 2005) For treatment of anemia in patients with chronic renal failure: a) 1-1. 5 mg/kg IM once weekly; may require 2-3 months to achieve beneﬁcial effects (Polzin and Osborne 1985) b) 5 mg/kg IM (maximum of 200 mg/week) every 2-3 weeks (Ross et al. 1988) For treatment of metabolic and endocrine anemias: a) 5 mg/kg IM once weekly (maximum of 200 mg); most re-solve with correction of underlying disease process (Maggio-Price 1988) For aplastic anemia: a) 1-3 mg/kg IM weekly (Weiss 1986) As an appetite stimulant: a) 5 mg/kg IM (max. 200 mg/week) weekly (Macy and Ralston 1989)	pppbs.pdf
NAPROXEN 645 T ! CATS: For Fe LV-induced anemia or as a general bone marrow stimu-lant: a) 10-20 mg IM once weekly (is of questionable beneﬁt) (Mag-gio-Price 1988) For chronic anemia secondary to feline cardiomyopathy: a) 50 mg IM weekly (Harpster 1986) T ! REPTILES: T o reduce protein catabolism in renal disease of lizard species: a) 1 mg/kg IM every 7-28 days (de la Navarre 2003a) Monitoring T ! Androgenic side effects T ! Fluid and electrolyte status, if indicated T ! Liver function tests if indicated T ! Red blood cell count, indices, if indicated T ! Weight, appetite Client Information T ! Because of the potential for abuse of anabolic steroids by hu-mans, this agent is a controlled (C-III) drug. It should be kept in a secure area and out of the reach of children. Chemistry/Synonyms An injectable anabolic steroid, nandrolone decanoate occurs as a white, to creamy white, crystalline powder. It is odorless or may have a slight odor and melts between 33-37°C. Nandrolone de-canoate is soluble in alcohol and vegetable oils and is practically insoluble in water. The commercially available injectable products are generally solutions dissolved in sesame oil. Nandrolone decanoate may also be known as: nortestosterone decanoate, or nortestosterone decylate. Storage/Stability/Compatibility Nandrolone decanoate for injection should be stored at tempera-tures less than 40°C and preferably between 15-30°C (59-86°F); protect from freezing and light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Nandrolone Decanoate Injection (in oil): 100 mg/m L in 2 m L multi-dose vials & 200 mg/m L in 1 m L vials; generic; (Watson); (Rx, C-III) NAPROXEN (na-prox-en) Naprosyn®, Aleve® NONSTEROIDAL ANTIINFLAMMATORY AGENT Prescriber Highlights TT NSAID; use largely superceded by newer, less GI-toxic NSAIDs in dogs & by other NSAIDs in horses as the equine product is no longer marketed (in USA) TT Contraindications: Active GI ulcers or history of hypersen-sitivity to the drug. Relatively Contraindicated: Hemato-logic, renal or hepatic disease. Caution: History of gastric ulcers, heart failure TT Because of difﬁculty in accurately dosing, adverse ef-fects, & safer alternatives, usually not used in dogs TT Adverse Effects: Relatively uncommon in HORSES: Pos-sible GI (distress, diarrhea, ulcers), hematologic (hypopro-teinemia, decreased hematocrit), renal (ﬂuid retention), & CNS (neuropathies) DOGS: GI ulcers & perforation, renal effects (nephritis/nephrotic syndrome), & hepatic (increased liver enzymes) effects TT Drug Interactions Uses/Indications The manufacturer lists the following indications: “... for the relief of inﬂammation and associated pain and lameness exhibited with myositis and other soft tissue diseases of the musculoskeletal sys-tem of the horse. ” (Package Insert; Equiproxen®—Syntex). It has also been used as an antiinﬂammatory/analgesic in dogs for the treatment of osteoarthritis and other musculoskeletal inﬂamma-tory diseases (see adverse reactions below). Pharmacology/Actions Like other NSAIDs, naproxen exhibits analgesic, antiinﬂammatory, and antipyretic activity probably through its inhibition of cycloox-ygenase with resultant impediment of prostaglandin synthesis. Pharmacokinetics In horses, the drug is reported to have a 50% bioavailability after oral dosing and a half-life of approximately 4 hours. Absorption does not appear to be altered by the presence of food. It may take 5-7 days to see a beneﬁcial response after starting treatment. Following a dose, the drug is metabolized in the liver. It is detectable in the urine for at least 48 hours in the horse after an oral dose. In dogs, absorption after oral dosing is rapid and bioavailability is between 68-100%. The drug is highly bound to plasma proteins. The average half-life in dogs is very long at 74 hours. In humans, naproxen is highly bound to plasma proteins (99%). It crosses the placenta and enters milk in levels of about 1% of those found in serum. Contraindications/Precautions/Warnings Naproxen is relatively contraindicated in patients with a history of or preexisting hematologic, renal, or hepatic disease. It is contrain-dicated in patients with active GI ulcers, or with a history of hyper-sensitivity to the drug. It should be used cautiously in patients with a history of GI ulcers, or heart failure (may cause ﬂuid retention). Animals suffering from inﬂammation secondary to concomitant infection, should receive appropriate antimicrobial therapy.	pppbs.pdf
646 NAPROXEN Adverse Effects Adverse effects are apparently uncommon in horses. The possibil-ity exists for GI (distress, diarrhea, ulcers), hematologic (hypopro-teinemia, decreased hematocrit), renal (ﬂuid retention), and CNS (neuropathies) effects. Reports of GI ulcers and perforation associated with naproxen have occurred in dogs. Dogs may also be overly sensitive to the adverse renal (nephritis/nephrotic syndrome) and hepatic effects (increased liver enzymes) of naproxen. Because of the apparently very narrow therapeutic index and the seriousness of the potential adverse reactions that can be seen in dogs, many clinicians feel that the drug should not be used in this species. 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 trimes-ter of pregnancy, and there is no evidence of risk in later trimesters. ) In studies in rodents and in limited studies in horses, no evidence of teratogenicity or adverse effects in breeding performance have been detected following the use of naproxen. Weigh the potential beneﬁts of therapy against the potential risks of its use in pregnant animals. Most NSAIDs are excreted in maternal milk. Naproxen appears at approximately 1% of maternal serum concentration. Overdosage/Acute Toxicity There is very limited information regarding acute overdoses of this drug in humans and domestic animals. The reported oral LD 50 in dogs is >1000 mg/kg. One report of a dog that received 5. 6 mg/kg for 7 days has been published (Gilmour and Walshaw 1987). The dog presented with clinical signs of melena, vomiting, depression, regenerative anemia, and pale mucous membranes. Laboratory indices of note included neutrophilia with a left shift, BUN of 66 mg/dl, serum creatinine of 2. 1 mg/dl, serum protein to albumin of 4. 0:2. 1 g/dl. The dog recov-ered following treatment with ﬂuids/blood, antibiotics, vitamin/ iron supplementation, oral antacids, and cimetidine. There were 236 exposures to naproxen reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org ) dur-ing 2005-2006. In these cases 213 were dogs with 35 dogs showing clinical signs and the remaining 22 cases were cats with 4 cats show-ing clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included vomiting, bloody diarrhea, melena, ataxia and diarrhea. Common ﬁndings in cats recorded in decreasing frequen-cy included vomiting, azotemia, bloody vomitus, facial twitching and hypothermia. As with any NSAID, overdosage can lead to gastrointestinal and renal effects. Decontamination with emetics and/or activated char-coal is appropriate. For doses where GI effects are expected, the use of gastrointestinal protectants is warranted. If renal effects are also expected, ﬂuid diuresis should be considered. Supportive treat-ment should be instituted as necessary. Monitor electrolyte and ﬂuid balance carefully and manage renal failure using established guidelines. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving naproxen and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES (gentamicin, amikacin, etc. ): Increased risk for nephrotoxicity !TANTICOAGULANTS (heparin, LMWH, warfarin ): Increased risk for bleeding possible !TASPIRIN : When aspirin is used concurrently with naproxen, plas-ma levels of naproxen could decrease and an increased likelihood of GI adverse effects (blood loss) could occur. Concomitant ad-ministration of aspirin with naproxen cannot be recommended. !TBISPHOSPHONATES (alendronate, etc. ): May increase risk for GI ul-ceration !TCORTICOSTEROIDS : Concomitant administration with NSAIDs may signiﬁcantly increase the risks for GI adverse effects !TFUROSEMIDE : Naproxen may reduce the saluretic and diuretic ef-fects of furosemide !THIGHLY PROTEIN BOUND D RUGS (e. g., phenytoin, valproic acid, oral anti-coagulants, other antiinﬂammatory agents, salicylates, sulfonamides, and the sulfonylurea antidiabetic agents ): Because naproxen is highly bound to plasma proteins (99%), it potentially could dis-place other highly bound drugs; increased serum levels and dura-tion of actions may occur. Although these interactions are usually of little concern clinically, use together with caution. !TMETHOTREXATE : Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate; use together with extreme caution. !TPROBENECID : May cause a signiﬁcant increase in serum levels and half-life of naproxen. Doses !TDOGS: Note : Because of the difﬁculty in accurately dosing naproxen and its potential for adverse effects, the use of this drug in dogs should only be considered when approved and safer NSAIDs have been ineffective. a) 2 mg/kg PO every other day (q48h) (Hansen 2003b), (Har-die, Lascelles et al. 2003), (Hardie and Grauer 2007) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: For septic arthritis pain; inﬂammation: 2. 4 mg/m L in drinking water for 21 days (Ivey and Morrisey 2000) !THORSES: (Note : ARCI UCGFS Class 4 Drug) a) 5 mg/kg by slow IV, then 10 mg/kg, PO (top dressed in feed) twice daily for up to 14 days or 10 mg/kg, PO (top dressed in feed) twice daily for up to 14 consecutive days. (Package Insert; Equiproxen®—Syntex Animal Health; Note : No longer commercially available) b) 10 mg/kg PO daily (Trumble and Kawcak 2003) Monitoring !TAnalgesic/antiinﬂammatory efﬁcacy !TGI: appetite, feces (occult blood, diarrhea) !TPCV (packed cell volume), hematocrit if indicated or on chronic therapy !TWBC's if indicated or on chronic therapy Client Information !TNotify veterinarian if clinical signs of GI distress (anorexia, vom-iting, diarrhea, black feces, or blood in stool) occur, or if animal becomes depressed.	pppbs.pdf
NARCOTIC AGONIST ANALGESICS; N-BUTYLSCOPOLAMMONIUM BROMIDE 647 Chemistry/Synonyms Naproxen is a propionic acid derivative, having similar structure and pharmacologic proﬁles as ibuprofen and ketoprofen. It is a white to off-white crystalline powder with an apparent p K a of 4. 15. It is practically insoluble in water and freely soluble in alcohol. The sodium salt is also available commercially for human use. Naproxen may also be known as: naproxeneum, RS-3540, RS-3650, Aleve®, Anaprox®, EC-Naprosyn®, Midol®, Naprelan® and Naprosyn®. Storage/Stability/Compatibility Naproxen should be stored in well-closed, light resistant containers at room temperature. T emperatures above 40° C (104°F) should be avoided. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None; the equine product is no longer marketed in the USA. The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Naproxen Tablets: 200 mg (220 mg naproxen sodium), 250 mg (275 mg naproxen sodium), 375 mg, 500 mg (550 mg naproxen sodium); Naprosyn® (Roche); Anaprox® and Anaprox DS® (Roche); Aleve® & Midol® Extended Relief (Bayer); generic; (Rx and OTC) Naproxen Delayed/Controlled-release Tablets: 375 mg) & 500 mg; EC-Naprosyn® (Roche); Naprelan® (Blansett Pharmacal); generic; (Rx) Naproxen Oral Suspension: 125 mg/5 m L in 15 m L, 20 m L, 473 m L & 500 m L; Naprosyn® (Roche); generic; (Rx) NARCOTIC (OPIATE) AGONIST ANALGESICS, PHARMACOLOGY OF Receptors for opiate analgesics are found in high concentrations in the limbic system, spinal cord, thalamus, hypothalamus, striatum, and midbrain. They are also found in tissues such as the gastroin-testinal tract, urinary tract, and in other smooth muscle. Opiate receptors are further broken down into ﬁve main sub-groups. Mu receptors are found primarily in the pain regulating areas of the brain. They are thought to contribute to the analgesia, euphoria, respiratory depression, physical dependence, miosis, and hypothermic actions of opiates. Kappa receptors are located pri-marily in the deep layers of the cerebral cortex and spinal cord. They are responsible for analgesia, sedation, and miosis. Sigma receptors are thought to be responsible for the dysphoric effects (struggling, whining), hallucinations, respiratory and cardiac stimulation, and mydriatic effects of opiates. Delta receptors, located in the limbic areas of the CNS, and epsilon receptors have also been described, but their actions have not been well explained at this time. The morphine-like agonists (morphine, meperidine, oxymor-phone) have primary activity at the mu receptors, with some activ-ity possible at the delta receptor. The primary pharmacologic effects of these agents include: analgesia, antitussive activity, respiratory depression, sedation, emesis, physical dependence, and intestinal effects (constipation/defecation). Secondary pharmacologic effects include, CNS: euphoria, sedation, and confusion. Cardiovascular: bradycardia due to central vagal stimulation, alpha-adrenergic receptors may be depressed resulting in peripheral vasodilation, decreased peripheral resistance, and baroreceptor inhibition. Orthostatic hypotension and syncope may occur. Urinary: Increased bladder sphincter tone can induce urinary retention. Various species may exhibit contradictory effects from these agents. For example, horses, cattle, swine, and cats may develop excitement after morphine injections and dogs may defecate after morphine. These effects are in contrast to the expected effects of sedation and constipation. Dogs and humans may develop mio-sis, while other species (especially cats) may develop mydriasis. For more information see the individual monographs for each agent. N-BUTYLSCOPOLAMMONIUM BROMIDE (HYOSCINE BUTYLBROMIDE) (en-byoo-tel-skoe-pahl-ah-moe-nee-um broe-mide) Buscoban® QUATERNARY AMMONIUM ANTISPASMODIC & ANTICHOLINERGIC Prescriber Highlights TT Injectable anticholinergic used in horses for treating colic associated with spasmodic colic, ﬂatulent colic, & simple impactions TT Shorter acting than atropine; only labeled for a single (one-time) dose IV TT Not for use in patients with ileus or when decreased GI motility may be harmful TT Adverse effects include transient tachycardia, pupil dila-tion, decreased secretions & dry mucous membranes Uses/Indications N-butylscopolammonium bromide injection is indicated (per the label) for control of abdominal pain (colic) associated with spas-modic colic, ﬂatulent colic, and simple impactions in horses. It may also be of beneﬁt as an aid to performing rectal exams in horses. Pharmacology/Actions N-butylscopolammonium reduces gastrointestinal peristalsis and rec-tal pressure via its anti-cholinergic actions by competitively inhibiting muscarinic receptors on smooth muscle. N-butylscopolammonium has shorter duration of action than atropine. Pharmacokinetics Limited information is available for horses. After an intravenous dose, the drug is eliminated within 48 hours in urine and feces equally. Estimated elimination half-life is approximately 6 hours. Contraindications/Precautions N-butylscopolammonium is labeled as contraindicated in hors-es with impaction colics associated with ileus or those with glaucoma. This medication is not to be used in horses intended for food purposes. The manufacturer has not studied the safety of IM administration.	pppbs.pdf
648 NEOMYCIN SULFATE Adverse Effects Labeled adverse effects include transient tachycardia and decreased borborygmal sounds that last for approximately 30 minutes after IV dosing. Transient pupil dilation can be noted. Other effects in-clude decreased secretions and dry mucous membranes. Because this drug can cause increases in heart rate, heart rate can-not be used as a valid pain indicator for 30 minutes after injection. When used for labeled indications, a lack of response may in-dicate a more serious problem that may require surgery or more aggressive care (White 2005b). Reproductive/Nursing Safety As no data is available to document safety, the manufacturer does not recommend use in nursing foals or pregnant or lactating mares. Overdosage/Acute Toxicity Dosages up to 10X (3 mg/kg) were administered to horses as part of pre-approval studies. Clinical effects noted included dilated pu-pils (returned to normal in 4-24 hours), tachycardia (returned to normal within 4 hours) and dry mucous membranes (returned to normal in 1-2 hours). Gut motility was inhibited, but returned to baseline within 4 hours and normal feces were seen within 6 hours. Two of the four horses treated at 10X dosage developed mild signs of colic which resolved without further treatment. Drug Interactions The following drug interactions have either been reported or are theoretical in animals receiving N-butylscopolammonium bromide and may be of signiﬁcance in veterinary patients: T ! ATROPINE or other anticholinergic agents : May cause additive effects if used with N-butylscopolammonium T ! METOCLOPRAMIDE and other drugs that have cholinergic-like actions on the GI tract : These drugs and N-butylscopolammonium may counteract one another's actions on GI smooth muscle Laboratory Considerations No speciﬁc concerns noted. Doses T ! HORSES: For labeled indications: a) 0. 3 mg/kg (30 mg or 1. 5 m L per 100 kg of body weight) via slow IV, one time (Label Dosage; Buscopan®—BI) Monitoring T ! Heart rate ( Note: heart rate cannot be used as indicator for pain for the ﬁrst 30 minutes after administration) T ! GI motility via gut sounds and feces output Client Information T ! Because an accurate patient assessment must be performed prior to the use of this medication and intravenous administration and subsequent monitoring are required, this drug should only be administered by veterinarians Chemistry/Synonyms N-butylscopolammonium bromide, a derivative of scopolamine, is a synthetic, quaternary ammonium antispasmodic-anticholinergic agent. It occurs as a white crystalline substance that is soluble in water. N-butylscopolammonium bromide may also be known as: butylscopolamine bromide, hysocine butylbromide, hysocine N-butylbromide, scopolamini butylbromidum, hyoscini butylbro-midum, Buscopan® or Buscapina®. Storage/Stability The commercially available injection should be stored at room temperature (15-30°C). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: N-butylscopolammonium bromide Injection: 20 mg/m L in 50 m L multi-dose vials, Buscopan® (Boehringer Ingelheim); (Rx). Approved for use in horses. In the UK, Buscopan Compositum® (BI) is commercially available. This product contains metamizole (a form of dipyrone) 500 mg/m L and hyoscine butylbromide (synonym for N-butylscopolammonium Br) 4 mg/m L. It is labeled for use in horses, cattle and dogs. HUMAN-LABELED PRODUCTS: None in the USA. There are several products with the trade name Buscopan® or Buscapina® available in many countries. Refer to actual product labels as ingredients and concentrations may vary. NEOMYCIN SULFATE (nee-o-mye-sin) Biosol®, Neomix® AMINOGLYCOSIDE ANTIBIOTIC Prescriber Highlights TT Aminoglycoside antibiotic usually used orally (gut “steril-ization”) or in topical formulations TT Contraindications: Oral: Hypersensitive to aminoglyco-sides, intestinal blockage; rabbits TT Adverse Effects: Parenteral use can be very toxic (neph-rotoxic) & is not recommended. Chronic use can lead to GI superinfections. Rarely, oral neomycin may cause ototoxicity, nephrotoxicity, severe diarrhea, & intestinal malabsorption TT Minimal amounts absorbed via GI (if intact) Uses/Indications Because neomycin is more nephrotoxic and less effective against several bacterial species than either gentamicin or amikacin, its use is generally limited to topical formulations for skin, eyes, and ears, oral treatment of enteric infections, to reduce microbe numbers in the colon prior to colon surgery, and oral or enema administration to reduce ammonia-producing bacteria in the treatment of hepatic encephalopathy. Doses for parenteral administration are listed be-low, but should be used only with extreme caution due to the drug's toxic potential. Pharmacology/Actions Neomycin has a mechanism of action and spectrum of activity (primarily gram-negative aerobes) similar to the other aminoglyco-sides, but in comparison to either gentamicin or amikacin, it is sig-niﬁcantly less effective against several species of gram-negative or-ganisms, including strains of Klebsiella, E. coli, and Pseudomonas. However, most strains of neomycin-resistant bacteria of these spe-cies remain susceptible to amikacin. More detailed information on the aminoglycosides mechanism of action and spectrum of activity is outlined in the amikacin monograph.	pppbs.pdf
NEOMYCIN SULFATE 649 Pharmacokinetics Approximately 3% of a dose of neomycin is absorbed after oral or rectal (retention enema) administration, but this can be in-creased if gut motility is slowed or if the bowel wall is damaged. Therapeutic levels are not attained in the systemic circulation after oral administration. After IM administration, therapeutic levels can be attained with peak levels occurring within 1 hour of dosing. The drug apparently distributes to tissues and is eliminated like the other aminoglyco-sides (refer to Amikacin monograph for more details). Orally ad-ministered neomycin is nearly all excreted unchanged in the feces. Contraindications/Precautions/Warnings Oral neomycin is contraindicated in the presence of intestinal ob-struction or if the patient is hypersensitive to aminoglycosides. Chronic usage of oral aminoglycosides may result in bacterial or fungal superinfections. Because aminoglycosides can cause irreversible ototoxicity, they should be used with caution in “working” dogs. Aminoglycosides should be used with caution in patients with neuromuscular disorders (e. g., myasthenia gravis) due to their neu-romuscular blocking activity. Because aminoglycosides are eliminated primarily through re-nal mechanisms, they should be used cautiously, preferably with serum monitoring and dosage adjustment in neonatal or geriatric animals. Aminoglycosides are generally considered contraindicated in rabbits/hares, as they adversely affect the GI ﬂora balance in these animals. Adverse Effects Refer to the amikacin monograph for more information regarding these topics with parenteral neomycin; however, parenterally ad-ministered neomycin is much more nephrotoxic than is amikacin. Rarely, oral neomycin may cause ototoxicity, nephrotoxicity, se-vere diarrhea, and intestinal malabsorption. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and fe-line pregnancy (Papich 1989), this drug is categorized as class: A (Probably safe. Although speciﬁc studies may not have proved he safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) Neomycin is excreted in cow's milk following a single IM injec-tion. If used orally, it is unlikely neomycin poses signiﬁcant sys-temic risk to nursing offspring, but may negatively alter gut ﬂora and cause diarrhea. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oral neomycin and may be of signiﬁcance in veterinary patients: !TDIGOXIN : Oral neomycin with orally administered digoxin may result in decreased absorption. Separating the doses of the two medications may not alleviate this effect. Some human patients (<10%) metabolize digoxin in the GI tract and neomycin may in-crease serum digoxin levels in these patients. It is recommended that enhanced monitoring be performed if oral neomycin is add-ed or withdrawn from the drug regimen of a patient stabilized on a digitalis glycoside. !TMETHOTREXATE : Absorption may be reduced by oral neomycin but is increased by oral kanamycin (found in Amforal®) !TOTOTOXIC, NEPHROTOXIC DRUGS : Although only minimal amounts of neomycin are absorbed after oral or rectal administration, the concurrent use of other ototoxic or nephrotoxic drugs with neo-mycin should be done with caution !TPENICILLIN VK (oral): Oral neomycin should not be given concur-rently with oral penicillin VK as malabsorption of the penicillin may occur !TWARFARIN : Oral neomycin may decrease the amount of vitamin K absorbed from the gut; this may have ramiﬁcations for patients receiving oral anticoagulants Refer to the amikacin monograph for more information regarding drug interactions with parenteral neomycin. Laboratory Considerations No speciﬁc concerns noted Doses !TDOGS: For treatment of hepatic encephalopathy: a) 22 mg/kg PO three to four times daily (Hardy 1989) b) For emergency treatment of hepatic encephalopathy second-ary to portosystemic shunts: Following evacuation enema instill 10-20 mg/kg neomycin sulfate diluted in water. Oral neomycin not recommended. (Cornelius and Bjorling 1988) c) 15 mg/kg as an enema every 6 hours after a cleansing enema or 10-20 mg/kg, PO every 6 hours. May be used with lactu-lose. (Johnson 1986) For GI tract infections: a) For campylobacteriosis: 20 mg/kg PO q12h (Willard 2003c) For systemic therapy ( Caution : Very nephrotoxic): a) 3. 5 mg/kg IV, IM or SC q8h (Kirk 1989) !TCATS: For treatment of hepatic encephalopathy: a) Secondary to portosystemic shunts: 10-20 mg/kg PO two times a day. May be used in combination with lactulose or in cleansing enemas. (Center, Hornbuckle, and Scavelli 1986) b) 22 mg/kg q8h PO (Cornelius, Bartges et al. 2000) c) Lactulose at 0. 5-1 mg/kg PO q8h with or without neomycin at 20 mg/kg PO q8-12h. (Marks 2004a) For GI tract infections: For campylobacteriosis: a) 20 mg/kg PO q12h (Willard 2003c) For systemic therapy ( Caution : Very nephrotoxic): a) 3. 5 mg/kg IV, IM or SC q8h (Kirk 1989) !TFERRETS: For susceptible enteric infections: a) 10-20 mg/kg, PO twice to four times daily (Williams 2000) !TRODENTS, SMALL MAMMALS: Note : Contraindicated in rabbits/hares a) Chinchillas: 15 mg/kg, PO once daily. Gerbils : 100 mg/kg, PO once daily, Guinea Pigs: 8 mg/kg, PO once daily. Hamsters: 100 mg/kg, PO once daily, or 0. 5 mg/m L in drinking water. Mice, Rats: 50 mg/kg, PO once daily (Adamcak and Otten 2000) !TCATTLE: For oral administration to treat susceptible enteral infections: a) 4-7. 5 g/day PO divided 2-4 times daily at regular intervals. Calves: 2-3 g/day, PO divided 2-4 times daily at regular in-tervals. Doses are not standardized; use for general guidance only. (Brander, Pugh, and Bywater 1982)	pppbs.pdf
650 NEOMYCIN SULFATE b) 10-20 mg/kg q12h (general guideline only). (Jenkins 1986) c) 7-12 mg/kg, PO q12h (Howard 1986) d) Feed at levels of 70-140 g/ton of feed or mix the appropri-ate dose in the drinking water which will be consumed by animals in 12 hours to provide 11 mg/kg or mix with recon-stituted milk replacers to provide 200-400 mg/gallon. (Label directions; Neomix Ag® 325—Upjohn) !THORSES: For oral administration to treat susceptible enteral infections: a) Adults: 4-7. 5 g/day PO divided 2-4 times daily at regular intervals. Foals: 2-3 g/day PO divided 2-4 times daily at regular intervals. Doses are not standardized; use for general guidance only. (Brander, Pugh, and Bywater 1982) b) 5-15 mg/kg PO once daily (Robinson 1987) For intrauterine infusion: a) Neomycin alone: 3-4 grams. Combination of neomycin (2 gram) and procaine penicillin G (3,000,000 IU), Combina-tion of Neomycin (1 gram) and Polymyxin B (40,000 IU), Furaltadone (600 mg) and penicillin G (Sodium or potas-sium, 3,000,000-5,000,000 IU). Little science is available for recommending doses, volume infused, frequency, diluents, etc. Most intrauterine treatments are commonly performed every day or every other day for 3-7 days. (Perkins 1999) !TSWINE: For oral administration to treat susceptible enteral infections: a) Y oung pigs: 0. 75-1 g/day, PO divided 2-4 times daily at regular intervals. Doses are not standardized; use for general guidance only. (Brander, Pugh, and Bywater 1982) b) 7-12 mg/kg, PO q12h (Howard 1986) !TSHEEP & GOATS: For oral administration to treat susceptible enteral infections: a) Lambs: 0. 75-1 g/day PO divided 2-4 times daily at regular intervals. Doses are not standardized; use for general guid-ance only. (Brander, Pugh, and Bywater 1982) b) Feed at levels of 70-140 g/ton of feed or mix the appropri-ate dose in the drinking water which will be consumed by animals in 12 hours to provide 11 mg/kg or mix with recon-stituted milk replacers to provide 200-400 mg/gallon. (Label directions; Neomix Ag® 325—Upjohn) !TBIRDS: For bacterial enteritis: a) Chickens, turkeys, ducks: Feed at levels of 70-140 g/ton of feed or mix the appropriate dose in the drinking water which will be consumed by animals in 12 hours to provide 11 mg/ kg (Label directions; Neomix Ag® 325—Upjohn) !TSNAKES: For susceptible infections: a) For bacterial gastritis: gentamicin 2. 5 mg/kg IM every 72 hours with oral neomycin 15 mg/kg plus oral live lactobacil-lus (Burke 1986) Monitoring For oral use: !TClinical efﬁcacy !TSystemic and GI adverse effects with prolonged use. For parenteral use: Refer to Amikacin monograph Client Information !TClients should understand that the potential exists for severe tox-icity (nephrotoxicity, ototoxicity) developing from this medica-tion when used parenterally. Chemistry/Synonyms An aminoglycoside antibiotic obtained from Streptomyces fradiae, neomycin is actually a complex of three separate compounds, neo-mycin A (neamine; inactive), neomycin C, and neomycin B (framy-cetin). The commercially available product almost entirely consists of the sulfate salt of neomycin B. It occurs as an odorless or almost odorless, white to slightly yellow, hygroscopic powder or cryodes-sicated solid. It is freely soluble in water and very slightly soluble in alcohol. One mg of pure neomycin sulfate is equivalent to not less than 650 Units. Oral or injectable (after reconstitution with normal saline) solutions of neomycin sulfate have a p H from 5-7. 5. Neomycin sulfate may also be known as: fradiomycin sulfate, neomycin sulphate, or neomycini sulfas, Neo-325®, Neo-fradin®, Neo-Sol 50®, and Neovet®. Storage/Stability Neomycin sulfate oral solution should be stored at room tempera-ture (15-30°C) in tight, light-resistant containers. Unless other-wise instructed by the manufacturer, oral tablets/boluses should be stored in tight containers at room temperature. The sterile powder should be stored at room temperature and protected from light. In the dry state, neomycin is stable for at least 2 years at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Neomycin Sulfate Oral Liquid: 200 mg/m L (140 mg neomycin base/ m L); generic; (OTC). Depending on labeling approved for use in cattle, swine, sheep, goats, turkeys, laying hens, and broilers. Check labels for slaughter withdrawals; may vary with product. General withdrawal times (when used as labeled): Cattle = 1 day; Sheep = 2 days and swine and goats = 3 days. Withdrawal period has not been established in pre-ruminating calves. Do not use in calves to be pro-cessed for veal. A milk discard period has not been established in lac-tating dairy cattle. Do not use in female dairy cattle 20 months of age or older. Neomycin Sulfate Soluble Powder: 325 grams/lb: Neo-325® Soluble Powder (Bimeda); Neovet® 325/100 & Neo Vet® 325 AG Grade (in-cludes turkey label); (Agri Pharm) Neo-Sol 50® (Alpharma); (OTC). Approved for use in Cattle and goats (not veal calves), swine, sheep, goats and turkeys (some products). Check labels for slaughter with-drawals; may vary with product. General slaughter withdrawal times (when used as labeled): Cattle = 1 day; Turkeys = 0 days; Sheep = 2 days; Swine and Goats = 3 days. HUMAN-LABELED PRODUCTS: Neomycin Sulfate Tablets: 500 mg; generic; (Rx) Neomycin Sulfate Oral Solution: 25 mg/m L in 480 m L; Neo-fradin® (Pharma-T ek); (Rx)	pppbs.pdf
NEOSTIGMINE 651 NEOSTIGMINE BROMIDE NEOSTIGMINE METHYLSULFATE (nee-oh-stig-meen) Prostigmin® PARASYMPATHOMIMETIC (CHOLINERGIC) Prescriber Highlights TT Parasympathomimetic used to initiate peristalsis, empty the bladder, & stimulate skeletal muscle contractions. Also for diagnosis & treatment of myasthenia gravis & treatment of non-depolarizing neuromuscular blocking agents (curare-type) overdose; has been used for treating massive ivermectin overdoses in cats TT Contraindications: Peritonitis, mechanical intestinal or urinary tract obstructions, late stages of pregnancy, hy-persensitivity to this class of compounds, or if treated with other cholinesterase inhibitors TT Adverse Effects: Cholinergic in nature & dose related (nausea, vomiting, diarrhea, excessive salivation & drool-ing, sweating, miosis, lacrimation, increased bronchial secretions, bradycardia or tachycardia, cardiospasm, bronchospasm, hypotension, muscle cramps & weak-ness, agitation, restlessness, or paralysis) TT Cholinergic crisis & myasthenic crisis must not be confused Uses/Indications Neostigmine is indicated for rumen atony, initiating peristalsis, emptying the bladder, and stimulating skeletal muscle contractions in cattle, horses, sheep, and swine (Package insert; Stiglyn® 1:500-P/ M—Mallinckrodt). It has been used in the diagnosis and treatment of myasthenia gravis and in treating non-depolarizing neuromus-cular blocking agents (curare-type) overdoses in dogs. Neostigmine has also been used to treat massive ivermectin overdoses in cats. Pharmacology/Actions Neostigmine competes with acetylcholine for acetylcholinesterase. As the neostigmine-acetylcholinesterase complex is hydrolyzed at a slower rate than that of the acetylcholine-enzyme complex, ace-tylcholine will accumulate with a resultant exaggeration and pro-longation of its effects. These effects can include increased tone of intestinal and skeletal musculature, stimulation of salivary and sweat glands, bronchoconstriction, ureter constriction, miosis and bradycardia. Neostigmine also has a direct cholinomimetic effect on skeletal muscle. In horses, neostigmine may decrease jejunal activity and delay gastric emptying. Its use in treating colon impactions and ileus is controversial. Pharmacokinetics Information on the pharmacokinetics of neostigmine in veterinary species was not located. In humans, neostigmine bromide is poorly absorbed after oral administration with only 1-2% of the dose ab-sorbed. Neostigmine effects on peristaltic activity in humans begin within 10-30 minutes after parenteral administration and can per-sist for up to 4 hours. Neostigmine is 15-25% bound to plasma proteins. It has not been detected in human milk nor would it be expected to cross the placenta when given at usual doses. In humans, the half-life of the drug is approximately one hour. It is metabolized in the liver and hydrolyzed by cholinesterases to 3-OH PTM, which is weakly active. When administered parenter-ally, approximately 80% of the drug is excreted in the urine within 24 hours, with 50% excreted unchanged. Contraindications/Precautions/Warnings Neostigmine is contraindicated in patients with peritonitis, me-chanical intestinal or urinary tract obstructions, in animals hyper-sensitive to this class of compounds, or treated with other cholin-esterase inhibitors. Use neostigmine with caution in patients with epilepsy, peptic ulcer disease, bronchial asthma, cardiac arrhythmias, hyperthyroid-ism, vagotonia, or megacolon. Adverse Effects Adverse effects of neostigmine are dose-related and cholinergic in nature. See overdosage section below. 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. ) Because it is ionized at physiologic p H, neostigmine would not be expected to be excreted in maternal milk. Overdosage/Acute Toxicity Overdosage of neostigmine can induce a cholinergic crisis. Clinical signs can include: nausea, vomiting, diarrhea, excessive salivation and drooling, sweating (in animals with sweat glands), miosis, lacrimation, increased bronchial secretions, bradycardia or tachy-cardia, cardiospasm, bronchospasm, hypotension, muscle cramps and weakness, agitation, restlessness, or paralysis. In patients with myasthenia gravis, it may be difﬁcult to distinguish between a cho-linergic crisis and myasthenic crisis. A test dose of edrophonium should differentiate between the two. Treat cholinergic crisis by temporarily ceasing neostigmine ther-apy and instituting treatment with atropine (doses are listed in the Atropine monograph). Maintain adequate respirations using me-chanical assistance if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving neostigmine and may be of signiﬁcance in veterinary patients: T ! ATROPINE : Atropine will antagonize the muscarinic effects of neo-stigmine and some clinicians routinely use the two together, but concurrent use should be used cautiously as atropine can mask the early clinical signs of cholinergic crisis T ! CORTICOSTEROIDS : May decrease the anticholinesterase activity of neostigmine; after stopping corticosteroid therapy, neostigmine may cause increased anticholinesterase activity T ! DEXPANTHENOL : Theoretically, dexpanthenol may have additive ef-fects when used with neostigmine T ! MAGNESIUM : Anticholinesterase therapy may be antagonized by administration of parenteral magnesium therapy, as it can have a direct depressant effect on skeletal muscle T ! MUSCLE RELAXANTS : Neostigmine may prolong the Phase I block of depolarizing muscle relaxants (e. g., succinylcholine, decametho-nium ) and edrophonium antagonizes the actions of non-depolar-izing neuromuscular blocking agents (e. g., pancuronium, tubocura-rine, gallamine, vecuronium, atracurium, etc. )	pppbs.pdf
652 NIACINAMIDE TDoses T ! DOGS: a) For treatment of myasthenia gravis: 0. 04 mg/kg IM q6h to bypass the problem of oral medication in actively regurgitat-ing animals (Inzana 2000) b) For diagnosis of myasthenia gravis: 0. 05 mg/kg IM (diagnos-tic for MA if clinical improvement occurs in 15-30 minutes; pre-treat with atropine) (Le Couteur 1988) c) For treatment of curare overdoses: 0. 001 mg/kg SC, follow with IV injection of atropine (0. 04 mg/kg) (Bailey 1986) T ! CATS: For treatment of myasthenia gravis: a) 0. 04 mg/kg IM q6h to bypass the problem of oral medication in actively regurgitating animals (Inzana 2000) T ! CATTLE: a) 1 mg/100 lbs of body weight SC; repeat as indicated (Package Insert; Stiglyn® 1:500-P/M—Mallinckrodt) T ! HORSES: (Note : ARCI UCGFS Class 3 Drug) a) 1 mg/100 lbs of body weight SC; repeat as indicated (Package Insert; Stiglyn® 1:500-P/M—Mallinckrodt) For treatment of paralytic ileus of large colon: a) 2-4 mg SC q2h. Use after correction of large bowel displace-ment; discontinue when GI motility returns. May cause in-creased secretion into GI tract and, therefore, may be harm-ful in small intestinal disease. Does not produce progressive contractions of small intestine. (Stover 1987) b) 0. 02 mg/kg SC; duration of action may be very short (15-30 minutes); does not increase propulsive motility of jejunum and may delay gastric emptying time. (Clark and Becht 1987) c) 0. 44 mg/kg (approximately 2 mg total dose for a 450 kg horse) SC or IV; may be repeated every 1/2 to 2 hours. If ineffective and no adverse effects seen, may increase dose in 2 mg increments to a total of 10 mg per treatment. (Moore 1999) d) For ileus with marked colonic distension in foals secondary to C. perfringens type C: 1-2 mg (2 mg for foals greater than 250 lb) SC, 2-3 doses at 1-hour intervals then as needed. (Slovis 2003a) e) 0. 025 mg/kg SC q2-6h (Hassel 2005) T ! SWINE: a) 2-3 mg/100 lbs of body weight IM; repeat as indicated (Package Insert; Stiglyn® 1:500-P/M—Mallinckrodt) b) 0. 03 mg/kg (Davis 1986) T ! SHEEP: a) 1-1. 5 mg/100 lbs of body weight SC; repeat as indicated (Package Insert; Stiglyn® 1:500-P/M—Mallinckrodt) b) 0. 01-0. 02 mg/kg (goats also) (Davis 1986) Monitoring Dependent on reason for use. T ! Adverse reactions (see Adverse Effects and Overdosage above) T ! Clinical efﬁcacy Client Information T ! his product should only be used by professionals in locations where the drug's effects can be monitored. Chemistry/Synonyms Synthetic quaternary ammonium parasympathomimetic agents, neostigmine bromide and neostigmine methylsulfate both occur as odorless, bitter-tasting, white, crystalline powders that are very sol-uble in water and soluble in alcohol. The melting point of neostig-mine methylsulfate is from 144-149°. The p H of the commercially available neostigmine methylsulfate injection is from 5-6. 5. Neostigmine methylsulfate may also be known as: neostigmine metilsulfate, neostigmine methylsulphate, neostigmini metilsul-fas, proserinum, Glycostigmin®, Intrastigmina®, Neostig-Reu®, Normastigmin®, Prostigmin®, Prostigmina®, Prostigmine®, Stiglyn®, or Tilstigmin®. Storage/Stability/Compatibility Neostigmine bromide tablets should be stored at room temperature in tight containers. Neostigmine methylsulfate injection should be stored at room temperature and protected from light; avoid freezing. Neostigmine methylsulfate injection is reportedly physically compatible with the commonly used IV replacement solutions and the following drugs: glycopyrrolate, pentobarbital sodium, and thiopental sodium. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Neostigmine Methylsulfate Injection: 1:1000 (1 mg/m L), 1:2000 (0. 5 mg/m L), 1:4000 (0. 25 mg/m L) in 1 m L amps (only 1:2000 and 1:4000) and 10 m L vials; Prostigmin® (ICN); generic; (Rx) NIACINAMIDE (NICOTINAMIDE) (nye-a-sin-a-mide) IMMUNOMODULATOR; NUTRITIONAL Prescriber Highlights TT Used in canine medicine in combination with tetracy-cline for treatment of discoid lupus erythematosus; may be useful in other immune-mediated dermatologic conditions such as sterile pyogranulomas, idiopathic onychodystrophy, pemphigus foliaceous, & pemphigus erythematosus TT Possible Contraindications: Liver disease, active peptic ulcers, or hypersensitivity to it TT Adverse Effects: Anorexia, vomiting, & lethargy; occasion-ally increases in liver enzymes seen TT Improvement may be gradual & take 6-8 weeks TT Inexpensive Uses/Indications When used in conjunction with tetracycline, niacinamide may be useful for the treatment of discoid lupus erythematosus in dogs. It is occasionally been found to be useful in sterile pyogranulomas, idiopathic onychodystrophy, pemphigus foliaceous and pemphi-gus erythematous. It may make take 1-2 months before efﬁcacy is noted.	pppbs.pdf
NITAZOXANIDE 653 Pharmacology/Actions While niacinamide is an essential nutrient in humans (necessary for lipid metabolism. tissue respiration, and glycogenolysis) its prima-ry pharmacologic use (in combination with tetracycline for discoid lupus erythematosus) in dogs is secondary to its action of block-ing Ig E-induced histamine release and degranulation of mast cells. When used with tetracycline, niacinamide may suppress leukocyte chemotaxis secondary to complement activation by antibody-an-tigen complexes. It also inhibits phosphodiesterases and decreases the release of proteases. In combination with tetracycline's immu-nomodulating and antiinﬂammatory effects, efﬁcacy has been not-ed in up to two-thirds of dogs treated for DLE. While niacinamide and niacin act identically as vitamins, niacinamide does not affect blood lipid levels or the cardiovascular system. Pharmacokinetics Niacinamide is absorbed well after oral administration and widely distributed to body tissues. Niacinamide is metabolized in the liver to several metabolites that are excreted into the urine. At physi-ologic doses, only a small amount of niacinamide is excreted into the urine unchanged, but as dosages increase, larger quantities are excreted unchanged. Contraindications/Precautions/Warnings In humans, niacinamide therapy is contraindicated in patients with liver disease, active peptic ulcers, or hypersensitivity to the drug. Adverse Effects Adverse effects of niacinamide in dogs are uncommon, but may in-clude anorexia, vomiting, and lethargy. Occasionally, increases in liver enzymes may be noted. Reproductive/Nursing Safety While niacinamide alone should be safe to use in pregnant and lac-tating animals, its use in combination with tetracycline may not be safe. Overdosage/Acute Toxicity There is unlikely to be a problem with niacinamide overdoses other than acute GI distress. Drug Interactions Niacinamide and tetracycline treatment does not interfere with antibody production associated with routine vaccinations in dogs. Also see the tetracycline monograph for additional drug interac-tions if using combination therapy. The following drug interactions have either been reported or are theoretical in humans or animals receiving niacinamide and may be of signiﬁcance in veterinary patients: T ! INSULIN/ORAL ANTIDIABETIC AGENTS : In diabetic humans, dosage adjustments for insulin or oral antidiabetic agents have some-times been necessary after initiating niacinamide therapy. Doses T ! DOGS: For discoid lupus erythematosus: a) For dogs weighing 10 kg or more: 500 mg of niacinamide and 500 mg of tetracycline PO q8h. For dogs weighing from 5-10 kg: 250 mg of each drug PO q8h. For dogs weighing less than 5 kg: 100 mg of each drug PO q8h. Improvement is usually noted within 6 weeks. (White 2000) b) Dogs weighing more than 10 kg: 500 mg of niacinamide and 500 mg of tetracycline PO q8h. For dogs weighing less than 10 kg: 250 mg of each PO q8h. May use in combination with corticosteroids and Vitamin E. If adverse effects become a problem, reduce dose of niacinamide ﬁrst. May also try this regimen for pemphigus foliaceous or pemphigus erythema-tous (approximately (Campbell 1999) For various immune-mediated diseases (discoid lupus erythe-matosus, pemphigus erythematosus, pemphigus foliaceous, vasculitis, sterile pyelogranuloma, dermatomyositis, and lupoid onychodystrophy: a) For dogs less than 10 kg: 250 mg each of niacinamide and tetracycline PO three times daily. For dogs larger than 10 kg: 500 mg each of niacinamide and tetracycline PO three times daily. May substitute doxycycline for tetracycline at 5 mg/kg PO once a day. (Tapp 2002) Monitoring T ! Efﬁcacy T ! Adverse effects (baseline and occasional monitoring of liver en-zymes is suggested) Client Information T ! Give as directed. Improvement may not be noted for 6-8 weeks. T ! If dog's condition deteriorates or if adverse effects are a problem, contact veterinarian. Chemistry/Synonyms Niacinamide, also commonly known as nicotinamide, occurs as a white crystalline powder. It is odorless or nearly odorless and has a bitter taste. It is freely soluble in water or alcohol. Niacinamide may also be known as: nicotinamide, nicotin-amidum, nicotinic acid amide, nicotylamide, Vitamin B(3), or Vitamin PP. Storage/Stability/Compatibility Store niacinamide tablets in tight containers at room temperature unless otherwise labeled. Niacinamide is incompatible with alkalis or strong acids. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Niacinamide (Nicotinamide) Tablets: 100 mg & 500 mg; generic; (OTC); also available in bulk powder. NITAZOXANIDE (nye-tah-zox-ah-nide) Navigator® ANTIPARASITIC AGENT Prescriber Highlights TT Drug that has activity against a variety of protozoa, nematodes, bacteria, & trematodes, including Sarcocystis neurona, giardia, cryptosporidia, & Helicobacter pylori TT Approved for use in horses (EPM) & humans (Giardia & Cryptosporidia) TT Interest in using in other companion animals ( e. g., dogs, cats), but data is lacking to support use TT Adverse effects in horses may be therapy limiting; very well tolerated in humans	pppbs.pdf
654 NITAZOXANIDE Uses/Indications Nitazoxanide oral paste is indicated for the treatment of horses with equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona. In humans, nitazoxanide is approved (in the USA) for use in treating diarrhea caused by Cryptosporidium parvum and Giardia lamblia in pediatric patients from ages 1 to 11 years old. Because of the drug's spectrum of activity and apparent safety, there is considerable interest in using it in a variety of compan-ion animal species, but data is lacking for speciﬁc indications and dosages. Pharmacology While the precise mechanism of action of nitazoxanide is unknown, its active metabolites tizoxanide and tizoxanide glucuronide, are thought to inhibit the pyruvate: ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reactions essential to an-aerobic energy metabolism. Nitazoxanide has activity against a variety of protozoa, nematodes, bacteria, and trematodes, includ-ing Sarcocystis neurona, giardia, cryptosporidia, and Helicobacter pylori. Pharmacokinetics Following oral administration in horses, nitazoxanide is absorbed and rapidly converted to tizoxanide (desacetyl-nitazoxanide). Peak levels of tizoxanide are attained between 2-3 hours and are not detectable by 24 hours post dosing. In humans, nitazoxanide is not detectable in plasma, but peak levels of tizoxanide and tizoxanide glucuronide occur about 3-4 hours post dose. More than 99% of tizoxanide is bound to plasma proteins. Tizoxanide is excreted in the urine, bile, and feces; the glucuronide metabolite is secreted in the urine and bile. Contraindications/Precautions/Warnings In horses, the drug is labeled as contraindicated in horses less than one year of age and those that are sick or debilitated for reasons oth-er than EPM. The drug should be used with caution in stallions and other horses predisposed to developing laminitis. Safety for use in animals with compromised renal or hepatic function has not been established; use with caution. The manufacturer has not evaluated nitazoxanide in horses weighing more than 545 kg (1200 lbs). Adverse Effects In horses, the following adverse effects are most commonly report-ed: fever, reduced appetite/anorexia, and lethargy/depression. Other adverse effects include decreased gut sounds, scant feces, loose/ malodorous or discolored feces/diarrhea, colic, laminitis, increased water consumption, discolored urine, head and/or limb edema, or weight loss. The manufacturer states that stallions may be more prone to developing laminitis than either geldings or mares. Nitazoxanide may disrupt normal ﬂora in the horse leading to enterocolitis. If patient develops any of the following: a high fever (>103°F), scant or loose feces, diarrhea, colic, or signs of laminitis, nitazoxanide treatments should be stopped immediately and ap-propriate veterinary care be initiated. A so-called “treatment crisis” may develop, particularly early in therapy (ﬁrst two weeks) and is thought to be caused by CNS in-ﬂammation secondary to dead or dying protozoa. Common signs include neurological deﬁcits, fever, lethargy, and decreasing appe-tite. Treatment with antiinﬂammatory agents may be indicated. Treatment may continue if horse is closely monitored for other ad-verse reactions (e. g., anorexia, diarrhea, colic, laminitis). In humans, nitazoxanide appears to be well tolerated and ad-verse effect rates are similar to placebo. Rarely, sclera may turn yel-low secondary to drug disposition, but return to normal after drug discontinuation. Reproductive/Nursing Safety The reproductive safety of nitazoxanide has not been determined in breeding stallions or in breeding or lactating mares. In pregnant humans, nitazoxanide 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. ) Nitazoxanide did not affect male or female fertility in rats given approximately 66 times the human dose. It did not cause fetal harm in pregnant rats or rabbits given 48 times and 3 times the human dose, respectively. It is unknown if tizoxanide is excreted into milk. Overdosage/Acute Toxicity There is limited information available on the acute toxicity of nita-zoxanide. The oral LD50 for cats and dogs is greater than 10 g/kg. Repeated doses of 450 mg/kg in rats caused intense salivation and increased liver and spleen weights. In horses given approximately 5 times the labeled dose, all developed anorexia, diarrhea, and leth-argy, and testing was halted after 4 days of study. Human volunteers have taken doses of up to 4 grams without signiﬁcant adverse effects occurring. In the event of an overdose, it is suggested to observe the patient closely and treat adverse effects in a supportive manner. Drug Interactions No speciﬁc drug interactions have been noted to date, but the vet-erinary and human manufacturers warn to use with caution if the patient is receiving other drugs that are highly protein bound and with a narrow therapeutic index. Laboratory Considerations No speciﬁc laboratory interactions or considerations noted. Doses !THORSES: For equine protozoal myeloencephalitis (EPM) caused by Sarco-cystis neurona: a) For a 28 day course of therapy: Days 1-5: 25 mg/kg (11. 36 mg/lb) PO once daily; Days 6-28: 50 mg/kg (22. 72 mg/lb) PO once daily. See directions for use in client information section that follows. (Package insert; Navigator®—Idexx) Monitoring !TClinical efﬁcacy !TWeekly body weight !TAdverse reactions; if adverse reactions occur, the manufacturer recommends performing a physical exam, CBC, serum albumin, total serum protein and body weight. Client Information !TAlways provide the Client Information Sheet (found on the in-side of the upper ﬂap and inside the box of syringes) to the ani-mal owner or person treating the horse with each prescription. Clients must understand and accept the potential associated risks versus beneﬁts of therapy.	pppbs.pdf
NITENPYRAM 655 DIRECTIONS FOR USE (from package insert): T ! Step 1: Obtain an accurate body weight periodically (once a week) to ensure the correct dose is administered. Use a scale or the weight tape provided in the NA VIGATOR dispensing box. T ! Step 2: Open the foil pouch and remove the NA VIGATOR syringe. Set the dosage ring for the appropriate dose according to the fol-lowing schedule. T o set the dosage ring on the syringe plunger, rotate (dial) the top of the ring to the appropriate dosing mark. Day 1—Use the syringe in the space marked #1 and set the dos-age ring to one-half (1/2) the horse's weight in pounds. Day 2—Use the partially used syringe from Day 1 and set the dosage ring to the full weight of the horse in pounds (this will deliver the same amount as administered on Day 1). Day 3—Use the syringe in the space marked #2 and set the dos-age ring to one-half (1/2) the horse's weight in pounds. Day 4—Use the partially used syringe from Day 3 and set the dosage ring to the full weight of the horse in pounds (this will deliver the same amount as administered on Day 3). Day 5—Use the syringe in the space marked #3 and set the dos-age ring to one-half (1/2) the horse's weight in pounds. Syringe #3 will be only partially used. Save this syringe until dosing is complete and then discard it along with the other syringes. Days 6-28—Use the remaining syringes and set the dosage ring to the full weight of the horse in pounds. T ! Step 3: Ensure the horse's mouth contains no feed. Remove the cover from the tip of the syringe and insert the tip into the horse's mouth at the interdental space. Depress the plunger until it is stopped by the dosage ring. The dose should be deposited on the back of the tongue or deep into the cheek pouch. T ! Step 4: T o aid swallowing of paste, immediately raise the horse's head for a few seconds after dosing. T ! Step 5: Clean the tip of the syringe with a clean disposable towel and replace the cover on the tip of the syringe. Return the syringe to the original space in the NA VIGATOR dispensing box. T ! Step 6: Repeat until the horse has been treated for 28 days. Weigh the horse weekly and set the dose based upon the current body weight to ensure accurate dosing. T ! Step 7: At the end of the treatment period, all empty and par-tially empty syringes should be discarded. Do not reuse dosing syringes. T ! When used in horses, the manufacturer states to monitor for ad-verse reactions at least once daily for the duration of treatment. T ! Contact the veterinarian immediately if any of the following adverse effects occur: fever, reduced appetite/anorexia, lethargy/ depression, decreased gut sounds, scant feces, loose/malodor-ous or discolored feces/diarrhea, colic, laminitis, increased wa-ter consumption, discolored urine, head and/or limb edema, or weight loss. Chemistry/Synonyms A nitrothiazolyl-salicylamide derivative antiparasitic agent, nita-zoxanide occurs as a light yellow powder. It is slightly soluble in ethanol and practically insoluble in water. Nitazoxanide may also be known as: PH-5776, Alinia®, Daxon®, Heliton®, and Navigator®. Storage/Stability The equine-approved oral paste should be stored below 30°C (86°F); do not freeze. The human-approved powder for oral sus-pension should be stored at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Once suspended with tap water, the oral sus-pension should be kept in tightly closed containers at room tem-perature and discarded after 7 days. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Nitazoxanide oral paste (32%, 320 mg/gram of paste) oral dose sy-ringes; in boxes of 26 syringes. Each syringe contains 85 grams of paste. Each syringe will treat a horse weighing up to 1200 lbs and one box of syringes will treat a 1200 lb horse for 28 days. Naviga-tor® (Idexx); (Rx). Approved for horses not to be used for human consumption. HUMAN-LABELED PRODUCTS: Nitazoxanide Tablets: 500 mg; Alinia® (Romark Laboratories); (Rx) Nitazoxanide Powder for Oral Suspension: 20 mg/m L (100 mg/5 m L after reconstitution) in 60 m L; Alinia® (Romark Laboratories); (Rx) NITENPYRAM (nye-ten-pye-rum) Capstar®, Program® ORAL INSECTICIDE Prescriber Highlights TT Oral insecticide used primarily as a ﬂea adulticide in dogs & cats; may also have efﬁcacy for other conditions (e. g., maggots) TT Very safe TT Not effective alone for ﬂea eggs or other immature forms TT Over-the-counter Uses/Indications Nitenpyram is indicated as a ﬂea adulticide in dogs and cats. It does not kill ticks, ﬂea eggs, larvae or immature ﬂeas. Nitenpyram may be effective for treating ﬂy larvae (maggots) of various species. Pharmacology/Actions Nitenpyram enters the systemic circulation of the adult ﬂea after consuming blood from a treated animal. It binds to nicotinic ace-tylcholine receptors in the postsynaptic membranes and blocks ace-tylcholine-mediated neuronal transmission causing paralysis and death of the ﬂea. It does not inhibit acetylcholinesterase. Efﬁcacy ap-pears to be greater than 95% (kill rate) in dogs or cats within 6 hours of treatment. When combined with an insect growth regulator ( e. g., lufenuron), immature stages of ﬂeas may also be controlled. Pharmacokinetics Nitenpyram is rapidly and practically completely absorbed after oral administration. Peak levels occur about 80 minutes after dosing in dogs; about 40 minutes in cats. Elimination half-lives are about 3 hours for dogs; 8 hours for cats. Nitenpyram is excreted primarily unchanged in the urine. In dogs, about 3% of a dose is excreted in the feces; in cats about 5% is excreted in the feces. Contraindications/Precautions/Warnings Nitenpyram is not labeled to be used in animals under 2 pounds of body weight or under 4 weeks of age.	pppbs.pdf
656 NITROFURANTOIN Adverse Effects Nitenpyram is tolerated well. As ﬂeas begin to die, animal may be-gin scratching. This effect is temporary and due to the ﬂeas and not the medication. Reproductive/Nursing Safety Nitenpyram is probably safe to use in breeding, pregnant, or lactat-ing animals. Overdosage/Acute Toxicity Nitenpyram is relatively safe in high dosages to mammals. The oral LD 50 in rats is approximately 1. 6 grams/kg. Cats or dogs given 10 times the usual dose for 14 days showed no untoward effects. In the circumstance of a massive overdose, contact an animal poison control center for additional guidance. Drug Interactions No speciﬁc drug interactions were located. Nitenpyram has report-edly been used safely with a variety of other medications and other ﬂea products. Laboratory Considerations No speciﬁc laboratory interactions or considerations noted. Doses T ! DOGS: As a ﬂea adulticide: a) For dogs weighing 2-25 lb. (0. 9-11. 36 kg): Give one 11. 4 mg tablet PO. May be given as often as once per day. For dogs weighing 25-125 lb. (11. 36-56. 8kg): Give one 57 mg tablet PO. May be given as often as once per day. May be given with or without food. (Label directions; Capstar®—Novartis) T ! CATS: As a ﬂea adulticide: a) For cats weighing 2-25 lb. (0. 9-11. 36 kg): Give one 11. 4 mg tablet PO. May be given as often as once per day. May be given with or without food. (Label directions; Capstar®— Novartis) T ! REPTILES: a) For maggots: crush one 11. 4 mg tablet into powder and give PO, as an enema, or on wound one time. (Klaphake 2005a) Monitoring T ! Efﬁcacy Client Information T ! All animals in household should be treated. T ! Because nitenpyram does not kill immature ﬂeas, eggs, etc., it is usually used in combination with other products that will con-trol those forms of ﬂeas. T ! Keep tablets out of reach of children. Chemistry/Synonyms A neonicotinoid insecticide, nitenpyram occurs as a pale yellow crystalline powder and is very soluble in water (840 mg/m L) Nitenpyram may also be known as: TI-304, (E)-Nitenpyram, Bestguard®, and Capstar®. Storage/Stability/Compatibility Commercially available nitenpyram tablets should be stored at room temperature (15-30°C; 59-86°F). Shelf life is reported to be 3 years if stored below 25°C (76°F). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Nitenpyram Oral Tablets: 11. 4 mg and 57 mg in boxes containing blister packs of 6 tablets; Capstar® (Novartis); (OTC); Approved for use in dogs and cats. Also available in combination packs with Lufenuron [Program® Fla-vor Tabs and Capstar® Flea Management System for Dogs and Pro-gram® Flavor Tabs (OTC); and Capstar® Flea Management System for Cats (OTC)] and in combination with milbemycin and lufenuron [Sentinel® Flavor Tabs and Capstar® Flea Management System for Dogs (Rx)]. HUMAN-LABELED PRODUCTS: None NITROFURANTOIN (nye-troe-fyoor-an-toyn) Macrodantin®, Macrobid® URINARY ANTIMICROBIAL Prescriber Highlights TT Antibacterial used for susceptible UTI's TT Contraindications: Renal impairment; hypersensitivity to it TT Adverse Effects: Gastrointestinal disturbances & he-patopathy of most concern; may cause infertility in males or peripheral neuropathy TT Potentially teratogenic, may be toxic to neonates Uses/Indications Considered a urinary tract antiseptic, nitrofurantoin is used primar-ily in small animals, but also occasionally in horses in the treatment of lower urinary tract infections caused by susceptible bacteria. It is not effective in treating renal cortical or perinephric abscesses or other systemic infections. Pharmacology/Actions Nitrofurantoin usually acts as a bacteriostatic antimicrobial, but it may be bactericidal depending on the concentration of the drug and the susceptibility of the organism. The exact mechanism of ac-tion of nitrofurantoin has not been fully elucidated, but the drug apparently inhibits various bacterial enzyme systems, including acetyl coenzyme A. Nitrofurantoin has greater antibacterial activity in acidic environments. Nitrofurantoin has activity against several gram-negative and some gram-positive organisms, including many strains of E. coli, Klebsiella, Enterobacter, Enterococci, Staphylococcus aureus and epidermidis, Enterobacter, Citrobacter, Salmonella, Shigella, and Corynebacterium. It has little or no activity against most strains of Proteus, Serratia, or Acinetobacter and has no activity against Pseudomonas spp. Pharmacokinetics Nitrofurantoin is rapidly absorbed from the GI tract and the presence of food may enhance the absorption of the drug. Macrocrystalline forms of the drug may be absorbed more slowly with less GI upset. Because of its slower absorption, urine levels of the drug may be prolonged. Therapeutic levels in the systemic circulation are not main-tained due to the rapid elimination of the drug after absorption. Approximately 20-60% of the drug is bound to serum proteins.	pppbs.pdf
NITROFURANTOIN 657 Peak urine levels occur within 30 minutes of dosing. The drug crosses the placenta and only minimal quantities of the drug are found in milk. Approximately 40-50% of the drug is eliminated into urine un-changed via both glomerular ﬁltration and tubular secretion. Some of the drug is metabolized, primarily in the liver. Elimination half-lives in humans with normal renal function average 20 minutes. Contraindications/Precautions/Warnings Nitrofurantoin is contraindicated in patients with renal impair-ment as the drug is much less efﬁcacious and the development of toxicity is much more likely. The drug is also contraindicated in patients hypersensitive to it. Adverse Effects In dogs and cats, gastrointestinal disturbances (primarily vomit-ing) and hepatopathy can occur with this drug. Rarely, revers-ible myasthenic-like effects have been seen in dogs. Neuropathies, chronic active hepatitis, hemolytic anemia, and pneumonitis have been described in humans, but are believed to occur very rarely in animals. Reproductive/Nursing Safety In humans, the drug is contraindicated in pregnant patients at term and neonates as hemolytic anemia can occur secondary to imma-ture enzyme systems. Safe use of the drug during earlier stages of pregnancy has not been determined. Nitrofurantoin has been im-plicated in causing infertility in male dogs. Use only when the ben-eﬁts of therapy outweigh the potential risks. Nitrofurantoin is excreted into maternal milk in very low con-centrations. Safety for use in the nursing mother or offspring has not been established. Overdosage/Acute Toxicity No speciﬁc information was located. Because the drug is rapidly ab-sorbed and excreted, patients with normal renal function should re-quire little therapy when mild overdoses occur. If the ingestion was relatively recent, massive overdoses should be handled by emptying the gut using standard protocols; patient should then be monitored for adverse effects (see above). Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving nitrofurantoin and may be of signiﬁcance in veterinary patients: !TFLUOROQUINOLONES (e. g., enroﬂoxacin, ciproﬂoxacin ): Nitrofuran-toin may antagonize the antimicrobial activity of the ﬂuoroqui-nolones and concomitant use is best avoided !TFOOD or ANTICHOLINERGIC DRUGS may increase the oral bioavail-ability of nitrofurantoin !TMAGNESIUM TRISILICATE CONTAINING ANTACIDS : May inhibit the oral absorption of nitrofurantoin !TPROBENECID : May inhibit the renal excretion of nitrofurantoin potentially increasing its toxicity and reducing its effectiveness in urinary tract infections Laboratory Considerations !TNitrofurantoin may cause false-positive urine glucose determina-tions if using cupric-sulfate solutions (Benedict's reagent, Clinit-est®). T ests using glucose oxidase methods (Tes-Tape®, Clinistix®) are not affected by nitrofurantoin. !TNitrofurantoin may cause decreases in blood glucose, and increas-es in serum creatinine, bilirubin and alkaline phosphatase. Doses !TDOGS: For susceptible bacterial urinary tract infections: a) 4 mg/kg PO q6h (Osborne and Lulich 1987) b) For recurrent UTI: Conventional dose: 4 mg/kg, PO q8h; Prophylactic dose: 3-4 mg/kg, PO q24h (should be given at night after micturition and immediately before bedtime) (Polzin and Osborne 1985) c) 4 mg/kg PO q6-8h (Brovida 2003) d) 5 mg/kg PO q8h (Dowling 2007) e) 4. 4 mg/kg PO three times daily (Senior 2005) !TCATS: For susceptible bacterial urinary tract infections: a) 4 mg/kg, PO q6h (Osborne and Lulich 1987) b) For recurrent UTI: Conventional dose: 4 mg/kg, PO q8h; Prophylactic dose: 3-4 mg/kg, PO q24h (should be given at night after micturition and immediately before bedtime) (Polzin and Osborne 1985) c) 4 mg/kg PO q6-8h (Brovida 2003) !THORSES: For susceptible urinary tract infections: a) 2. 5-4. 5 mg/kg, PO three times daily (Robinson 1987) b) 10 mg/kg, PO daily (Huber 1988a) Monitoring !TClinical efﬁcacy !TAdverse effects !TPeriodic liver function tests should be considered with chronic therapy Chemistry/Synonyms A synthetic, nitrofuran antibacterial, nitrofurantoin occurs as a bit-ter tasting, lemon-yellow, crystalline powder with a p K a of 7. 2. It is very slightly soluble in water or alcohol. Nitrofurantoin may also be known as: furadoninum or nitro-furantoinum, Furadantin®, Macrobid®, and Macrodantin®. Storage/Stability/Compatibility Nitrofurantoin preparations should be stored in tight containers at room temperature and protected from light. The oral suspension should not be frozen. Nitrofurantoin will decompose if it comes into contact with metals other than aluminum or stainless steel. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Nitrofurantoin Macrocrystals Capsules: 25 mg, 50 mg, 100 mg (as macrocrystals) and 100 mg (as monohydrate/macrocrystals); Macro-dantin® and Macrobid® (Procter and Gamble Pharm); generic; (Rx) Nitrofurantoin Oral Suspension: 5 mg/m L (25 mg/5 m L) in 60 m L and 470 m L; Furadantin® (First Horizon); (Rx)	pppbs.pdf
658 NITROGLYCERIN NITROGLYCERIN, TOPICAL (nye-troe-gli-ser-in) NTG, Nitro-bid®, Minitran® VENODILATOR Prescriber Highlights TT Topical, oral, & injectable venodilator; usually used topi-cally in veterinary medicine for CHF or hypertension TT Contraindications: anemia or hypersensitivity to nitrates. Caution: cerebral hemorrhage or head trauma, diuretic-induced hypovolemia, or other hypotensive conditions. TT Adverse Effects: rashes at the application sites & ortho-static hypotension; transient headaches common in hu-mans & may be a problem for some animals TT Rotate application sites TT Wear gloves when applying; avoid human skin contact Uses/Indications T opical nitroglycerin in small animal medicine is used primarily as an adjunctive vasodilator in heart failure and cardiogenic edema. It is also used as an anti-anginal agent, antihypertensive (acute), and topically to treat Raynaud's disease in humans. Pharmacology/Actions Nitroglycerin relaxes vascular smooth muscle primarily on the ve-nous side, but a dose related effect on arterioles is possible. Preload (left end-diastolic pressure) is reduced from the peripheral pooling of blood and decreased venous return to the heart. Because of its arteriolar effects, depending on the dose, afterload may also be re-duced. Myocardial oxygen demand and workload are reduced and coronary circulation can be improved. Pharmacokinetics Nitroglycerin topical ointment is absorbed through the skin, with an onset of action usually within 1 hour and duration of action of 2-12 hours. It is generally dosed in dogs and cats q6-8 hours (three to four times a day). The transdermal patches have a wide inter-patient bioavailability. Nitroglycerin has a very short half-life (1-4 minutes in humans) and is metabolized in the liver. At least two metabolites have some vasodilator activity and have longer half-lives than NTG. Contraindications/Precautions/Warnings Nitrates are contraindicated in patients with severe anemia or those hypersensitive to them. They should be used with caution (if at all) in patients with cerebral hemorrhage or head trauma, diuretic-in-duced hypovolemia or other hypotensive conditions. Adverse Effects Most common side effects seen are rashes at the application sites and orthostatic hypotension. If hypotension is a problem, reduce dosage. Transient headaches are a common side effect seen in hu-mans and may be a problem for some animals. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as 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. ) It is not known whether nitrates are excreted in maternal milk; use with caution in nursing animals. Overdosage/Acute Toxicity If severe hypotension results after topical administration, wash the site of application to prevent any more absorption of oint-ment. Fluids may be administered if necessary. Epinephrine is contraindicated as it is ineffective and may complicate the animal's condition. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving nitroglycerin and may be of signiﬁcance in veterinary patients: T ! ANTIHYPERTENSIVE DRUGS, OTHER : Use of nitroglycerin with other antihypertensive drugs may cause additive hypotensive effects T ! PHENOTHIAZINES : May increase hypotensive effects T ! SILDENAFIL (and other PDE INHIBITORS ): May profoundly increase risk for hypotension Doses Note : For the treatment of heart failure, nitroglycerin is not gen-erally used alone. T ! DOGS: For adjunctive treatment of heart failure: a) 1/2 inch per 2. 27 kg (5 lbs) of body weight applied to a hair-less area (e. g., inside the earﬂap) every 12 hours. Person ap-plying should use gloves and avoid contact with the product. (Kittleson 2000) b) If nitroprusside not used, 2% NTG at 1/4 to 1 inch q6-12h; apply to hairless area in the axilla or groin. (Macintire 2006a) c) Using the 2. 5-10 mg/24hr transdermal patch: 12 hours on, 12 hours off (Fox 2003a) d) 1/4-2 inches applied directly to the patient's tongue every 8 hours during the ﬁrst 48 hours. All animals tolerate the oint-ment given orally. (Lichtenberger 2006b) e) For any patient with cardiogenic pulmonary edema that is headed for oxygen: 1/4 inch for small dogs up to 1 inch for large dogs on the inner ear pinnae, groin or axilla as needed q8h for the ﬁrst 24 hours. Wear gloves to apply. (De Francesco 2006) T ! CATS: For adjunctive treatment of heart failure: a) 1/8th to 1/4 inch applied to a hairless area (e. g., inside the earﬂap) every 4-6 hours. Person applying should use gloves and avoid contact with the product. (Kittleson 2000) b) T o enhance resolution of pulmonary edema: 1/4 to 1/2 inch topically q6h; to reduce nitrate tolerance, alternate 12 hrs with and 12 hrs without nitroglycerin therapy. (Fox 2007b) c) Using the 2. 5-5 mg/24hr transdermal patch: 12 hours on, 12 hours off (Fox 2003a) d) 1/4 inch applied directly to the patient's tongue every 8 hours during the ﬁrst 48 hours. All animals tolerate the ointment given orally. (Lichtenberger 2006b) e) For any patient with cardiogenic pulmonary edema that is headed for oxygen: 1/4 inch on the inner ear pinnae, groin or axilla as needed q8h for the ﬁrst 24 hours. Wear gloves to apply. (De Francesco 2006)	pppbs.pdf
NITROPRUSSIDE SODIUM 659 TFor adjunctive treatment of hypertension: a) 1/4 inch applied to pinna q6-8h (Norsworthy 2007) T ! FERRETS: For adjunctive therapy for heart failure: a) 1/8th inch strip applied to inside of pinna q12h for the ﬁrst 24 hours of therapy (Hoeffer 2000) b) For dilative cardiomyopathy: 1/8th of an inch applied to shaved skin once to twice daily. Apply to ear pinna or skin of thigh. May cause hypotension. (Williams 2000) Monitoring T ! Clinical efﬁcacy T ! Sites of application for signs of rash T ! Blood pressure, particularly if hypotensive effects are seen Client Information T ! Dosage is measured in inches of ointment; use papers supplied with product to measure appropriate dose. Wear gloves (non-permeable) when applying. T ! Do not pet animal where ointment has been applied T ! Rotate application sites. Recommended application sites include: groin, inside the ears, and thorax. Rub ointment into skin well. If rash develops, do not use that site again until cleared. T ! Contact veterinarian if rash persists or animal's condition deteriorates T ! here is no danger of explosion or ﬁre with the use of this product Chemistry/Synonyms Famous as an explosive, nitroglycerin (NTG) occurs undiluted as a thick, volatile, white-pale yellow ﬂammable, explosive liquid with a sweet, burning taste. The undiluted drug is soluble in alcohol and slightly soluble in water. Because of obvious safety reasons, nitro-glycerin is diluted with lactose, dextrose, propylene glycol, alcohol, etc. when used for pharmaceutical purposes. Nitroglycerin may also be known as: glyceryl trinitrate, glonoine, GTN; nitroglycerol, NTG, trinitrin, or trinitroglycerin, Minitran®, Nitro-bid®, Nitrek® and Nitro-Dur®. Storage/Stability The topical ointment should be stored at room temperature and the cap ﬁrmly attached. For storage/stability and compatibility for dosage forms other than the topical ointment, see specialized refer-ences or the package inserts for each product. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Note : Many dosage forms of nitroglycerin are available for human use, including sublingual tablets, buccal tablets, lingual spray, extend-ed-release oral capsules and tablets, and parenteral solutions for IV infusion. Because the use of nitroglycerin in small animal medicine is practically limited to the use of topical ointment or transdermal patches, those other dosage forms are not listed here. Nitroglycerin T opical Ointment: 2% in a lanolin-white petrolatum base in 30 g and 60 g tubes and UD 1 g; Nitro-bid® (Fougera); generic; (Rx) Nitroglycerin Transdermal Systems (patches): 0. 1 mg/hr 0. 2 mg/hr, 0. 3 mg/hr, 0. 4 mg/hr, 0. 6 mg/hr & 0. 8 mg/hr; Minitran® (3M); Nitro-Dur® (Key); Nitrek® (Bertek); generic; (Rx) Note: Various products contain differing quantities of nitroglycerin and patch surface area size, but release rates of drug are identical for a given mg/hr. NITROPRUSSIDE SODIUM (nye-troe-pruss-ide) Nitropress®, Sodium Nitroprusside V ASODILATOR Prescriber Highlights TT Vascular, smooth muscle relaxant used for acute/severe hypertension; acute heart failure secondary to mitral regurgitation & in combination with dopamine for refrac-tory CHF TT Contraindications: Compensatory hypertension, inad-equate cerebral circulation, or during emergency surgery in patients near death. Caution: Geriatric patients, hepat-ic insufﬁciency, severe renal impairment, hyponatremia, or hypothyroidism. TT Adverse effects: Hypotensive effects; potentially: nausea, retching, restlessness, apprehension, muscle twitching, dizziness TT May be irritating at the infusion site; avoid extravasation. TT Continued use may lead to potential thiocyanate & cya-nide toxicity TT Use only in an ICU setting; monitoring essential Uses/Indications In human medicine, nitroprusside is indicated for the management of hypertensive crises, acute heart failure secondary to mitral re-gurgitation, and severe refractory CHF (often in combination with dopamine). Its use in veterinary medicine is generally reserved for the treatment of critically ill patients with those conditions only when constant blood pressure monitoring can be performed. Pharmacology/Actions Nitroprusside is an immediate acting intravenous hypotensive agent that directly causes peripheral vasodilation (arterial and ve-nous) independent of autonomic innervation. It produces a low-ering of blood pressure, an increase in heart rate, a mild decrease in cardiac output, and a signiﬁcant reduction in total peripheral resistance. Unlike the organic nitrates, tolerance does not develop to nitroprusside. Pharmacokinetics After starting an IV infusion of nitroprusside, reduction in blood pressure and other pharmacologic effects begin almost immedi-ately. Blood pressure will return to pretreatment levels within 1-10 minutes following cessation of therapy. Nitroprusside is metabolized non-enzymatically in the blood and tissues to cyanogen (cyanide radical). Cyanogen is converted in the liver to thiocyanate where it is eliminated in the urine, feces, and exhaled air. The half-life of cyanogen is 2. 7-7 days if renal function is normal, but prolonged in patients with impaired renal function or with hyponatremia.	pppbs.pdf
660 NITROPRUSSIDE SODIUM Contraindications/Precautions/Warnings Nitroprusside is contraindicated in patients with compensatory hy-pertension (e. g., A V shunts or coarctation of the aorta; Cushing's re-ﬂex), inadequate cerebral circulation, or during emergency surgery in patients near death. Nitroprusside must be used with caution in patients with hepat-ic insufﬁciency, severe renal impairment, hyponatremia, or hypo-thyroidism. When nitroprusside is used for controlled hypotension during surgery, patients may have less tolerance to hypovolemia, anemia, or blood loss. Geriatric patients may be more sensitive to the hypotensive effects of nitroprusside. Adverse Effects Most adverse reactions from nitroprusside are associated with its hypotensive effects, particularly if blood pressure is reduced too rapidly. Clinical signs such as nausea, retching, restlessness, appre-hension, muscle twitching, and dizziness have been reported in hu-mans. These effects disappear when the infusion rate is reduced or stopped. Nitroprusside may be irritating at the infusion site; avoid extravasation. Continued use may lead to potential thiocyanate and cyanide toxicity (see Overdosage section). Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as 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. ) It is not known whether nitroprusside and its metabolites are excreted in maternal milk. Overdosage/Acute Toxicity Acute overdosage is manifested by a profound hypotension. Treat by reducing or stopping the infusion and giving ﬂuids. Monitor blood pressure constantly. Excessive doses, prolonged therapy, a depleted hepatic thiosulfate (sulfur) supply, or severe hepatic or renal insufﬁciency may lead to profound hypotension, cyanogen, or thiocyanate toxicity. Acid/base status should be monitored to evaluate therapy and to detect meta-bolic acidosis (early sign of cyanogen toxicity). T olerance to therapy is also an early sign of nitroprusside toxicity. Hydroxocobalamin (Vitamin B 12a) may prevent cyanogen toxicity. Thiocyanate toxic-ity may be exhibited as delirium in dogs. Serum thiocyanate levels may need to be monitored in patients on prolonged therapy, espe-cially in those patients with concurrent renal dysfunction. Serum levels >100 micrograms/m L are considered toxic. It is suggested to refer to other references or contact an animal poison control center for further information should cyanogen or thiocyanate toxicity be suspected. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving nitroprusside and may be of signiﬁcance in veterinary patients: !TANESTHETICS, GENERAL : The hypotensive effects of nitroprus-side may be enhanced by concomitant administration of gen-eral anesthetics (e. g., halothane, enﬂurane ), or other circulatory depressants !TDOBUTAMINE : Synergistic effects (increased cardiac output and reduced wedge pressure) may result if dobutamine is used with nitroprusside !THYPOTENSIVE AGENTS, OTHER : Patients receiving other hypotensive agents (e. g., beta-blockers, ACE inhibitors, etc. ) may be more sensi-tive to the hypotensive effects of nitroprusside Doses Directions for preparation of infusion: Add 2-3 m L D5W to 50 mg vial to dissolve powder. Add dissolved solution to 1000 m L of D 5W and promptly protect solution from light (using aluminum foil or other opaque covering). Resultant solution contains 50 mi-crograms/m L of nitroprusside. Higher concentrations may be nec-essary in treating large animals. The administration set need not be protected from light. Solution may have a slight brownish tint, but discard solutions that turn to a blue, dark red or green color. Solution is stable for 24 hours after reconstitution. Do not add any other medications to IV running nitroprusside. Avoid extravasation at IV site. If using a Mini-Drip IV set (for small animals) (60 drops ≈ 1 m L; 1 drop contains approximately 0. 83 micrograms of nitro-prusside). Use an accurate ﬂow control device (pump, controller, etc. ) for administration. !TDOGS: For hypertensive crisis (systolic arterial BP >200 mm Hg): a) Initiate dose at 1-2 mcg/kg/minute; increase dosage incre-mentally every 3-5 minutes until a predetermined target BP is attained. Reduce BP 25% over 4-hour period to allow readaptation of cerebral blood vessels. (Proulx and Dhupa 2000) For adjunctive treatment of heart failure (cardiogenic shock; ful-minant pulmonary edema): a) Goal is to decrease or maintain mean arterial pressure to support vital organ functions—approx. 70 mm Hg): Dose as above (in “a”); concurrent use of dobutamine (5-10 mcg/ kg/min) often indicated. (Proulx and Dhupa 2000) b) 0. 5-10 mcg/kg/min IV at a low ﬂuid rate (≤2 m L/kg/hr) using D5W or other low sodium ﬂuid. Usually start at 2 mcg/kg/min and increase the base concentration by 1 mcg/ kg every 20-30 minutes until there is an improvement in respiratory effort and thoracic auscultation. The patient is maintained on the effective dose for 48 hours. Monitor blood pressure; cyanide poisoning can occur if infusion lasts more than 3 days. After stabilized, drip is tapered as therapy with enalapril is initiated. (Macintire 2006a) c) For catastrophic pulmonary edema: As a CRI initiated at 1 mcg/kg/min and carefully titrated to effect by increasing by 1 mcg/kg/min increments every 15 minutes as long as BP remains stable and until perfusion and pulmonary function improves (usually requires between 2-5 mcg/kg/min with the upper limit being 8-10 mcg/kg/min). Maintain most effective dose for 12-15 hours until respiratory distress re-solves, lungs are clear, and the patient is stable with a normal blood pressure, pink mucous membranes, normal capillary reﬁll time, and normal heart rate. Most animals at our clinic require 12 hours of treatment. The systolic blood pressure must remain greater than 90 mm Hg. If hypotension devel-ops, the CRI should be stopped. Blood pressure will return to pretreatment levels within 1-10 minutes of discontinu-ing treatment and administration can be reinstituted at the previous lower dose. Administer with dobutamine to treat or prevent hypotension if severe myocardial failure is pres-ent based on an echocardiogram evaluation. Wean sodium nitroprusside over 6 hours ﬁrst and then dobutamine over 6	pppbs.pdf
NIZATIDINE 661 hours. ACE inhibitor is added before tapering the infusions over 3-6 hours. (Lichtenberger 2006b) T ! CATS: For hypertensive crisis (systolic arterial BP >200 mm Hg): a) Initiate dose at 0. 5 mcg/kg/minute; increase dosage incre-mentally every 3-5 minutes until a predetermined target BP is attained. Reduce BP 25% over 4-hour period to allow read-aptation of cerebral blood vessels. (Proulx and Dhupa 2000) For adjunctive treatment of heart failure (cardiogenic shock; ful-minant pulmonary edema: a) Goal to decrease or maintain mean arterial pressure to sup-port vital organ functions—approx. 70 mm Hg): Dose as above; concurrent use of dobutamine (1-5 mcg/kg/min) often indicated. (Proulx and Dhupa 2000) b) Initiate dose at 0. 5 mcg/kg/minute constant rate infusion and increase by 0. 5-1 mcg/minute every 5 minutes to desired systolic pressure (90-100 mm Hg). Cats are more sensitive to the oxidative damage that can be induced by nitroprus-side and total dosages should be kept to a minimum. Use a dedicated line with an infusion pump; IV line and catheter should never be ﬂushed. A nurse devoted for continuous monitoring should be in place during administration. Cover IV solution and IV line with opaque material and discard after 24 hours. (Proulx 2003) c) For catastrophic pulmonary edema: As a CRI initiated at 1 mcg/kg/min and carefully titrated to effect by increasing by 1 mcg/kg/min increments every 15 minutes as long as BP remains stable and until perfusion and pulmonary function improves (cats usually requires between 1-2 mcg/kg/min with the upper limit being 2 mcg/kg/min). Maintain most effective dose for 12-15 hours until respiratory distress re-solves, lungs are clear, and the patient is stable with a normal blood pressure, pink mucous membranes, normal capillary reﬁll time and normal heart rate. Most animals at our clinic require 12 hours of treatment. The systolic blood pressure must remain greater than 90 mm Hg. If hypotension devel-ops, the CRI should be discontinued. Blood pressure will return to pretreatment levels within 1-10 minutes of dis-continuing treatment and administration can be reinstituted at the previous lower dose. Administer with dobutamine to treat or prevent hypotension if severe myocardial failure is present based on an echocardiogram evaluation. Wean so-dium nitroprusside over 6 hours ﬁrst and then dobutamine over 6 hours. ACE inhibitor is added before tapering the in-fusions over 3-6 hours. (Lichtenberger 2006b) Monitoring T ! Blood pressure must be constantly monitored T ! Acid/base balance T ! Electrolytes (especially Na+) Client Information T ! Must only be used by professionals in a setting where precise IV infusion and constant blood pressure monitoring can be performed. Chemistry/Synonyms A vascular smooth muscle relaxant, nitroprusside sodium occurs as practically odorless, reddish-brown crystals or powder. It is freely soluble in water and slightly soluble in alcohol. After reconstitution in D 5W, solution may have a brownish, straw, or light orange color and have a p H of 3. 5-6. Nitroprusside sodium may also be known as: disodium (OC-6-22)-pentakis(cyano-C)nitrosylferrate dihydrate, natrii nitroprus-sias, sodium nitroferricyanide dihydrate, sodium nitroprusside, or sodium nitroprussiate, and Nitropress®. Storage/Stability/Compatibility Nitroprusside sodium powder for injection should be stored pro-tected from light and moisture and kept at room temperature (15-30°C). Nitroprusside solutions exposed to light will cause a reduction of the ferric ion to the ferrous ion with a resultant loss in potency and a change from a brownish-color to a blue color. Degradation is enhanced with nitroprusside solutions in Viaﬂex® (Baxter) plastic bags exposed to ﬂuorescent light. After reconstitu-tion, protect immediately by covering vial or infusion bag with alu-minum foil or other opaque material. Discard solutions that turn to a blue, dark red, or green color. Solutions protected from light will remain stable for 24 hours after reconstitution. IV infusion tubing need not be protected from light while the infusion is running. It is not recommended to use IV infusion solutions other than D 5W or to add any other medications to the infusion solution. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Nitroprusside Sodium Powder for Injection: 50 mg/vial in 2 m L Flip-top vials and 5 m L vials; Nitropress® (Abbott); generic; (Elkins-Sinn); (Rx) NIZATIDINE (ni-za-ti-dine) Axid® H2-RECEPTOR ANTAGONIST; PROKINETIC Prescriber Highlights TT H2 receptor antagonist similar to ranitidine; used primar-ily for its prokinetic activity; may be useful in preventing hemorrhagic necrosis in cats with pancreatitis TT Contraindications: Hypersensitivity to the drug; Cau-tion: Geriatric patients or those with hepatic or renal insufﬁciency TT Adverse Effects are rare Uses/Indications While nizatidine acts similarly to cimetidine and ranitidine as an H2 blocker to reduce gastric acid secretion in the stomach, in small animal medicine its use has been primarily for its prokinetic effects. It may be useful to treat delayed gastric emptying, pseudo-obstruc-tion of the intestine and constipation. H2 blockers may be useful in preventing hemorrhagic necrosis in feline pancreatitis. Pharmacology/Actions At the H 2 receptors of the parietal cells, nizatidine competitively in-hibits histamine, thereby reducing gastric acid output both during basal conditions and when stimulated by food, amino acids, penta-gastrin, histamine, or insulin. While nizatidine may cause gastric emptying times to be de-layed, it more likely will stimulate GI motility by inhibiting ace-tylcholinesterase (thereby increasing acetylcholine at muscarinic receptors). It may also have direct agonist effects on M 3 muscarinic	pppbs.pdf
662 NOVOBIOCIN SODIUM Treceptors. Lower esophageal sphincter pressures may be increased by nizatidine. By decreasing the amount of gastric juice produced, nizatidine decreases the amount of pepsin secreted. Pharmacokinetics In the dog, oral absorption is rapid and nearly complete with mini-mal ﬁrst pass effect. Food can enhance the absorption of nizati-dine, but this is not considered clinically important. The drug is only marginally bound to plasma proteins. It is unknown if it enters the CNS. Nizatidine is metabolized in the liver to several metabo-lites, including at least one that has some activity. In animals with normal renal function over half the drug is excreted in the urine unchanged. Contraindications/Precautions/Warnings Nizatidine is contraindicated in patients who are hypersensitive to it. It should be used cautiously and, possibly, at reduced dosage in patients with diminished renal function. Nizatidine has caused in-creased serum ALT levels in humans receiving high IV doses for longer than 5 days. The manufacturer recommends that in high dose, chronic therapy, serum ALT values be monitored. Adverse Effects Nizatidine appears to be very well tolerated. Very rarely, anemia has been reported in humans taking the drug. CNS effects have been noted (headache, dizziness) but incidence is similar to those tak-ing placebo. Rash and pruritus have also been reported in a few humans taking nizatidine. Reproductive/Nursing Safety Doses of up to 275 mg/kg per day in pregnant rabbits did not reveal any teratogenic or fetotoxic effects. Safety during pregnancy not ﬁrmly established, so use only when clearly warranted. In humans, the FDA categorizes this drug as category B for use during preg-nancy (Animal studies have not yet demonstrated risk to the fetus, but there 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 preg-nancy, and there is no evidence of risk in later trimesters. ) Nizatidine is excreted in maternal milk in a concentration of 0. 1% of the oral dose in proportion to plasma concentrations and unlikely to cause signiﬁcant effects in nursing offspring Overdosage/Acute Toxicity Single oral doses of up to 800 mg/kg were not lethal in dogs. Adverse effects could include cholinergic effects (lacrimation, sali-vation, emesis, miosis and diarrhea); suggest treating supportively and symptomatically. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving nizatidine and may be of signiﬁcance in veterinary patients: T ! ANTICHOLINERGIC AGENTS (atropine, propantheline etc. ): May negate the prokinetic effects of nizatidine T ! ASPIRIN : Nizatidine may increase salicylate levels in patients re-ceiving high doses of aspirin (or other salicylates ) Laboratory Considerations T ! False positive tests for urobilinogen may occur with patients re-ceiving nizatidine Doses T ! DOGS: As a prokinetic agent: a) 2. 5-5 mg/kg PO once daily (Hall and Washabau 2000) T ! CATS: As a colonic prokinetic agent: a) 2. 5-5 mg/kg PO once daily (Washabau and Holt 2000) b) In combination with cisapride: nizatidine 2. 5-5 mg/kg PO q12h (Scherk 2003b) Monitoring T ! Clinical efﬁcacy (dependent on reason for use); monitored by decrease in symptomatology, endoscopic examination, blood in feces, etc. Client Information T ! o maximize the beneﬁt of this medication, it must be adminis-tered as prescribed by the veterinarian; clinical signs may reoccur if dosages are missed. Chemistry/Synonyms Nizatidine occurs as an off-white to buff-colored crystalline pow-der. It has a bitter taste and a slight sulfur-like odor. Nizatidine is sparingly soluble in water. Nizatidine may also be known as: LY-139037, nizatidinum, and Axid®. Storage/Stability/Compatibility Nizatidine oral tablets and capsules should be stored in tight, light-resistant containers at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 5 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Nizatidine Tablets: 75 mg; Axid® AR (Wyeth Consumer); (OTC) Nizatidine Capsules: 150 mg & 300 mg; Axid® Pulvules (Lilly); ge-neric; (Rx) Nizatidine Oral Solution: 15 mg/m L; in 480 m L; Axid® (Braintree); (Rx) NOVOBIOCIN SODIUM (noe-ve-bye-oh-sin) Albaplex® Prescriber Highlights TT Antibiotic primarily effective against some gram-positive cocci TT Contraindications: hypersensitivity to it; Extreme caution: hepatic or hematopoietic dysfunction TT Adverse Effects: Systemic use: Fever, GI (nausea, vomit-ing, diarrhea), rashes, & blood dyscrasias Uses/Indications Novobiocin is approved as a single agent and in combination with penicillin G for use in dry dairy cattle as a mastitis tube. Novobiocin is available in combination with tetracycline and prednisolone for oral use in dogs.	pppbs.pdf
NOVOBIOCIN SODIUM 663 Pharmacology/Actions Novobiocin is believed to act in several ways in a bactericidal man-ner. It inhibits bacterial DNA gyrase, interfering with protein and nucleic acid synthesis and also interferes with bacterial cell wall synthesis. Activity of the drug is enhanced in an alkaline medium. The spectrum of activity of novobiocin includes some gram-positive cocci (Staphs, Streptococcus pneumonia, and some group A streps). Activity is variable against other streptococci and weak against the Enterococci. Most gram-negative organisms are resis-tant to the drug, but some Haemophilus spp., Neisseria spp., and Proteus spp. may be susceptible. Pharmacokinetics After oral administration, novobiocin is well absorbed from the GI tract. Peak levels occur within 1-4 hours. The presence of food can decrease peak concentrations of the drug. Novobiocin is only poorly distributed to body ﬂuids with con-centrations in synovial, pleural, and ascitic ﬂuids less than those found in plasma. Only minimal quantities of the drug cross the blood-brain barrier, even when meninges are inﬂamed. Highest concentrations of novobiocin are found in the small intestine and liver. The drug is approximately 90% protein bound and is distrib-uted into milk. Novobiocin is primarily eliminated in the bile and feces. Approximately 3% is excreted into the urine; urine levels are usu-ally less than those found in serum. Contraindications/Precautions/Warnings Novobiocin is contraindicated in patients hypersensitive to it. Additionally, the drug should be used with extreme caution in pa-tients with preexisting hepatic or hematopoietic dysfunction. Adverse Effects Adverse effects reported with the systemic use of this drug include fever, GI disturbances (nausea, vomiting, diarrhea), rashes, and blood dyscrasias. In humans, occurrences of hypersensitivity reac-tions, hepatotoxicity, and blood dyscrasias have signiﬁcantly lim-ited the use of this drug. Reproductive/Nursing Safety Safety during pregnancy has not been established; use only when clearly indicated. Overdosage/Acute Toxicity Little information is available regarding overdoses of this drug. It is suggested that large oral overdoses be handled by emptying the gut following standard protocols; monitor and treat adverse effects symptomatically if necessary. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving novobiocin and may be of signiﬁcance in veterinary patients: !TBETA-LACTAM ANTIBIOTICS : Novobiocin reportedly acts similarly to probenecid by blocking the tubular transport of drugs. Although the clinical signiﬁcance of this is unclear, the elimination rates of drugs excreted in this manner (e. g., penicillins, cephalosporins ) could be decreased and half-lives prolonged. Laboratory Considerations !TNovobiocin can be metabolized into a yellow-colored product that can interfere with serum bilirubin determinations. !TNovobiocin may interfere with the determination BSP (bromo-sulfophthalein, sulfobromophthalein) uptake tests by altering BSP uptake or biliary excretion. Doses !TDOGS: a) For susceptible infections using the combination product (with tetracycline and prednisolone): 22 mg/kg of each an-tibiotic and 0. 55 mg prednisolone PO q12h for 48 hours (Package insert; Delta Albaplex®—Upjohn) !TCATTLE: a) For treatment of subclinical mastitis in dry cows: Infuse con-tents of one syringe into each quarter at the time of drying off; not later than 30 days prior to calving. Shake well before using. (Package directions; Albadry Plus®—Pharmacia & Upjohn) b) For treatment of mastitis caused by susceptible strains of Staphylococcal aureas and agalactiae in dry cows: (Package Directions; Biodry®—Pharmacia & Upjohn) Monitoring !TClinical efﬁcacy !TAdverse effects !TPeriodic liver function tests and CBC's are recommended if using long-term systemically. Client Information !TShake mastitis tubes well before using !TDo not exceed dosage recommendations or length of treatment Chemistry/Synonyms An antibiotic obtained from Streptomyces niveus or spheroides, no-vobiocin sodium occurs as white to light yellow, crystalline powder and is very soluble in water. Novobiocin or novobiocin sodium may also be known as: crys-tallinic acid, PA-93, streptonivicin, U-6591, novobiocinum natri-cum, sodium novobiocin, Albadry Plus®, Albamycin®, Biodry® and Delta Albaplex®. Storage/Stability Novobiocin should be stored at room temperature in tight contain-ers unless otherwise directed. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Novobiocin Suspension: 400 mg/10 m L syringe; Biodry® (Pﬁzer); (OTC). Do not use 30 days prior to calving. Slaughter withdrawal (at labeled doses) = 30 days. Novobiocin Combination Products: Novobiocin (as the sodium salt): 400 mg and Penicillin G Procaine 200,000 IU per 10 m L Plastet® Syringe. Albadry Plus® (Pﬁzer); (OTC). Approved for use in dry cows only. Do not use 30 days prior to calv-ing. Milk must not be used for 72 hours after calving. Slaughter with-drawal (at labeled doses) = 30 days. Novobiocin Sodium 60 mg, T etracycline HCl 60 mg and Predniso-lone 1. 5 mg tablets; Novobiocin Sodium 180 mg, T etracycline HCl 180 mg and Prednisolone 4. 5 mg tablets; Delta Albaplex® and Delta Albaplex® 3X (Pﬁzer); (Rx). Approved for use in dogs. HUMAN-LABELED PRODUCTS: None	pppbs.pdf
664 NYSTATIN NYSTATIN (ORAL) (nye-stat-in) Nilstat®, Mycostatin® ANTIFUNGAL (CANDIDA) Prescriber Highlights TT Oral & topical antifungal (Candida); not absorbed sys-temically after PO TT Contraindications: Known hypersensitivity TT Adverse Effects: GI effects possible at high dosages; hy-persensitivity possible Uses/Indications Orally administered nystatin is used primarily for the treatment of oral or gastrointestinal tract Candida infections in dogs, cats, and birds; it has been used less commonly in other species for the same indications. Pharmacology/Actions Nystatin has a mechanism of action similar to that of amphotericin B. It binds to sterols in the membrane of the fungal cell altering the permeability of the membrane allowing intracellular potassium and other cellular constituents to “leak out. ” Nystatin has activity against a variety of fungal organisms, but is clinically used against topical, oropharyngeal, and gastrointestinal Candida infections. Pharmacokinetics Nystatin is not measurably absorbed after oral administration and almost entirely excreted unchanged in the feces. The drug is not used parenterally because it is reportedly extremely toxic to internal tissues. Contraindications/Precautions/Warnings Nystatin is contraindicated in patients with known hypersensitivity to it. Adverse Effects Occasionally, high dosages of nystatin may cause GI upset (anorex-ia, vomiting, diarrhea). Rarely, hypersensitivity reactions have been reported in humans. Reproductive/Nursing Safety Although the safety of the drug during pregnancy has not been ﬁrmly established, the lack of appreciable absorption or case re-ports associating the drug with teratogenic effects appear to make it safe to use. 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. ) It is not known whether nystatin is excreted in maternal milk, but because the drug is not absorbed after oral administration it is unlikely to be of concern. Overdosage/Acute Toxicity Because the drug is not absorbed after oral administration, acute toxicity after an oral overdose is extremely unlikely, but transient GI distress may result. Drug Interactions No signiﬁcant interactions reported for oral nystatin Doses T ! DOGS: For oral treatment of Candidal infections: a) 100,000 Units PO q6h (Kirk 1989) b) 50,000-150,000 Units PO q8h (Jenkins and Boothe 1987) c) 22,000 Units/kg/day (Huber 1988b) T ! CATS: For oral treatment of Candidal infections: a) 100,000 Units PO q6h (Kirk 1989) T ! HORSES: For intrauterine infusion: a) 250,000-1,000,000 IU; Mix with sterile water; precipitates in saline. Little science is available for recommending doses, volume infused, frequency, diluents, etc. Most intrauterine treatments are commonly performed every day or every oth-er day for 3-7 days. (Perkins 1999) T ! BIRDS: For crop mycosis and mycotic diarrhea (Candida albicans) in chickens and turkeys: a) Feed at 50 grams per ton (Mycostatin®-20) or at 100 g/ton for 7-10 days. (Label directions; Mycostatin®-20—Solvay) For enteric yeast (Candidal) infections: a) 200,000-300,000 units/kg PO q8-12h. Relatively large volume must be administered (2-3 m L). May also be used prophylactically to prevent yeast infection in nestling birds treated with broad-spectrum antibiotics. Oral lesions may be missed if bird is tubed. (Flammer 2003a) b) For neonates on antibiotic therapy: Crush one ﬂuconazole 100 mg tablet and mix with 20 m L of nystatin 100,000U/ m L oral suspension. Dose at 0. 5 m L/1000g of body weight PO twice daily for duration of antibiotic therapy. (Wissman 2003) c) For treatment of candidiasis after antibiotic or in conjunc-tion with antibiotics: One m L of the 100,000 U/m L suspen-sion per 300 g body weight PO 1-3 times daily for 7-14 days. If treating mouth lesions do not give by gavage. Hand-fed babies should receive antifungal therapy if being treated with antibiotics. (Clubb 1986) Ratites: a) 250,000-500,000 IU/kg PO twice daily (Jenson 1998) T ! REPTILES: For susceptible infections: a) For turtles with enteric yeast infections: 100,000 IU/kg PO once daily for 10 days (Gauvin 1993) b) All species: 100,000 units/kg PO once daily (Jacobson s1999) Monitoring T ! Clinical efﬁcacy Client Information T ! Shake suspension well before administering Chemistry/Synonyms A polyene antifungal antibiotic produced by Streptomyces noursei, nystatin occurs as a yellow to light tan, hygroscopic powder having a cereal-like odor. It is very slightly soluble in water and slightly to sparingly soluble in alcohol. One mg of nystatin contains not less than 4400 Units of activity. According to the USP, nystatin used in	pppbs.pdf
OCTREOTIDE ACETATE 665 the preparation of oral suspensions should not contain less than 5000 Units per mg. Nystatin may also be known as: fungicidin, nistatina, or nystati-num, Mycostatin®, and Nilstat®. Storage/Stability Nystatin tablets and oral suspension should be stored at room tem-perature (15-30°C) in tight, light-resistant containers. Avoid freez-ing the oral suspension or exposing to temperatures greater than 40°C. Nystatin deteriorates when exposed to heat, light, air or moisture. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None, for oral use. For topical use, see the topical dermatologic sec-tion in the appendix. HUMAN-LABELED PRODUCTS: Nystatin Oral Suspension: 100,000 Units/m L in 5 m L, 60 m L, 473 m L and 480 m L; Nilstat® (Lederle); generic; (Rx) Nystatin Bulk powder: 50 million, 150 million, 500 million units, 1 billion, 2 billion and 5 billion units; generic; (Paddock); Nilstat® (Lederle); (Rx) Nystatin Oral Tablets: 500,000 Units; Mycostatin® (Bristol-Myers Squibb), generic; (Rx) Also available in oral troches, vaginal tablets, topical creams, powders and ointments. OCTREOTIDE ACETATE (ok-trye-oh-tide) Sandostatin® SOMATOSTATIN ANALOG Prescriber Highlights TT Injectable long acting somatostatin analog that may be useful for adjunctive treatment of insulinomas & gastrinomas TT Limited experience, but appears safe TT Multiple daily SC injections are required TT No information for veterinary use of depot IM form TT Expensive (especially in large dogs) TT May affect GI fat absorption Uses/Indications Octreotide may be useful in the adjunctive treatment of hyperin-sulinemia in patients with insulinomas (especially dogs, ferrets). Response is variable, presumably dependent on whether the tumor cells have receptors for somatostatin. Octreotide may also be useful in the diagnosis and symptomatic treatment of gastrinomas in dogs or cats. It may be of use in the treatment of acute pancreatitis, but more research is needed before it can be recommended for this use in veterinary patients. Pharmacology/Actions Octreotide is a synthetic long acting analog of somatostatin. It in-hibits the secretion of insulin (in both normal and neoplastic beta cells), glucagon, secretin, gastrin and motilin. In humans, octreotide may bind to any one of 5 subtypes of somatostatin receptors found on neoplastic beta cells, but dogs only have one subtype. This, or octreotide's inhibition of glucagon and growth hormone secretion, may explain the variable response dogs have to treatment. Pharmacokinetics Octreotide is absorbed and distributed rapidly from the injection site after SC administration. Half lives in humans average about 2 hours with duration of effect up to 12 hours. Treated dogs or ferrets generally require 2-3 injections per day to maintain blood glucose. About 32% of a dose is excreted unchanged in the urine and pa-tients with severe renal dysfunction may need dosage adjustment. Contraindications/Precautions/Warnings Octreotide is contraindicated in patients hypersensitive to it. It should be used with caution in patients with biliary tract disorders. Adverse Effects Very limited experience in domestic animals, although it appears to be well tolerated thus far. GI effects (including biliary tract ef-fects) are most commonly noted in human patients, particularly acromegalics. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) It is not known whether this drug is excreted in maternal milk. Overdosage/Acute Toxicity Serious adverse effects are unlikely. Human subjects have received up to 120 mg IV over 8 hours with no untoward effects. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving octreotide and may be of signiﬁcance in veterinary patients: T ! BETA-BLOCKERS : Octreotide may cause additive bradycardic effects T ! BROMOCRIPTINE : Octreotide may increase oral bioavailability T ! CALCIUM-CHANNEL BLOCKERS : Octreotide may cause additive bra-dycardic effects T ! CYCLOSPORINE : Octreotide may reduce cyclosporine levels T ! DIURETICS (and other agents that affect ﬂuid/electrolyte balance ): Octreotide may enhance ﬂuid/electrolyte imbalances T ! FOOD : Octreotide may reduce fat absorption T ! INSULIN, ORAL HYPOGLYCEMICS : Octreotide may can inhibit insulin ! !QUINIDINE : Octreotide may reduce the quinidine clearance Doses T ! Dogs: For medical treatment of insulinoma (particularly in patients refractory to or unable to tolerate other medical or surgical therapy): a) 10-40 mcg (total dose per dog) SC 2-3 times a day. Used in combination with dietary, glucocorticoid, and diazoxide treatment. (Nelson 2000) b) Further studies needed to determine octreotide's efﬁcacy and safety; has been administered at 2-4 mcg/kg SC q8-12h (Hess 2005)	pppbs.pdf
666 OLSALAZINE SODIUM T TFor adjunctive treatment of gastrinoma: a) 2-20 mcg/kg SC three times daily; with omeprazole. (Simp-son 2005) b) 2-8 mcg/kg SC q8-12h For adjunctive treatment of chylothorax: a) 10-20 mcg/kg SC three times a day for 2-3 weeks; prolonged treatment should be discouraged because people treated for longer than 4 weeks are at risk for gallstones. (Fossom 2006) T ! CATS: For adjunctive treatment of chylothorax: a) 10-20 mcg/kg SC three times a day for 2-3 weeks; prolonged treatment should be discouraged because people treated for longer than 4 weeks are at risk for gallstones. (Fossom 2006) T ! FERRETS: For medical treatment of insulinoma (particularly in patients refractory to or unable to tolerate other medical or surgical therapy): a) 1-2 mcg/kg SC 2-3 times a day (Meleo and Caplan 2000) Monitoring T ! Blood glucose (for insulinoma treatment) T ! Clinical efﬁcacy Client Information T ! here is very limited experience with this medication in dogs and ferrets and therapy must be considered experimental. T ! Injections must be given 2-3 times a day per veterinarian instructions T ! he expense associated with this medication can be considerable. Chemistry/Synonyms Octreotide acetate is a synthetic polypeptide related to somatosta-tin. It is commercially available in injectable forms for subcutane-ous or IV injection, and as an extended release suspension for IM administration. Octreotide acetate may also be known as: SMS-201-995, Longastatina®, Samilstin®, Sandostatin®, Sandostatina®, or Sandostatine®. Storage/Stability When stored at room temperature and protected from light, oct-reotide acetate injection remains stable for 14 days. For long-term storage, keep refrigerated. If injecting solution that has been in the refrigerator, allow it to come to room temperature in the syringe before injecting. Do not use artiﬁcial warming techniques. It is rec-ommended to use multidose vials within 14 days of initial use. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Octreotide Acetate for Injection: 0. 05 mg/m L, 0. 1 mg/m L, 0. 2 mg/ m L, 0. 5 mg/m L 1 mg/m L in 1 mg amps, single-dose vials and 5 m L multi-dose vials; Sandostatin® (Novartis); generic (Sicor); (Rx) Octreotide Acetate Powder for Injectable Suspension: 10 mg/5 m L, 20 mg/5 m L, 30 mg/5m L in kits with 2 m L diluent and 1-1/2” 20-gauge needle; Sandostatin® LAR Depot (Novartis); (Rx) OLSALAZINE SODIUM (ole-sal-a-zeen) Dipentum® ANTIINFLAMMATORY (LOCAL GI TRACT) Prescriber Highlights TT Used for treatment of chronic colitis in dogs that either are unresponsive to or cannot tolerate sulfasalazine TT Keratoconjunctivitis sicca (KCS) has been reported in some dogs TT Converted to 2 molecules of 5-ASA (mesalamine) in colon TT Limited experience in dogs TT Expensive when compared to sulfasalazine Uses/Indications Olsalazine is used for treatment of dogs with chronic colitis that ei-ther cannot tolerate the adverse effects associated with sulfasalazine or the response to sulfasalazine has been ineffective. Pharmacology/Actions Olsalazine is cleaved in the intestine into 5-aminosalicylic acid (5-ASA, mesalamine) by bacteria in the gut. While its exact mecha-nism is unknown, mesalamine is thought to have efﬁcacy for chron-ic colitis secondary to its antiinﬂammatory activity. Pharmacokinetics Olsalazine is poorly absorbed; approximately 98% of a dose reaches the colon intact and what drug is absorbed is rapidly eliminated. Serum half-life is about one hour. Contraindications/Precautions/Warnings Olsalazine is contraindicated in patients hypersensitive to it or to salicylates. Use with caution in animals with renal disease as renal toxicity has developed, though rarely, in human patients. Adverse Effects While keratoconjunctivitis sicca (KCS) is occasionally reported in dogs receiving olsalazine, it probably occurs less frequently than with sulfasalazine therapy. In humans, approximately 17% of pa-tients developed more serious diarrhea (then they had prior to treatment) after receiving olsalazine. Reproductive/Nursing Safety In high dose rat studies, some fetal abnormalities were seen. Use during pregnancy only when beneﬁts outweigh the risks. In hu-mans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) Oral olsalazine given to lactating rats in doses 5-20 times the human dose produced growth retardation in their pups. Use with caution in nursing patients. Overdosage/Acute Toxicity Overdosage in dogs may cause vomiting, diarrhea and decreased motor activity; treat symptomatically and supportively. Dosages up to 2 g/kg were not lethal in dogs.	pppbs.pdf
OMEPRAZOLE 667 Drug Interactions The following drug interaction has either been reported or are the-oretical in humans or animals receiving olsalazine and may be of signiﬁcance in veterinary patients: T ! WARFARIN : Olsalazine may increase prothrombin times in patients receiving warfarin Laboratory Considerations T ! Olsalazine may cause increases in ALT or AST Doses T ! DOGS: a) For dogs who cannot tolerate sulfasalazine: 10-20 mg/kg PO three times daily (Leib 2000) b) When response is poor to initial sulfasalazine therapy: 11 mg/kg PO twice daily (Tams 2000) c) 10-15 mg/kg PO q8-12h (Hall 2004) d) Initially at 5-10 mg/kg PO three times daily, then reduce gradually. (Allensbach 2005) Monitoring T ! Clinical efﬁcacy T ! Adverse effects Client Information T ! Should be given with food in evenly spaced doses (if possible) T ! If diarrhea worsens or dogs eyes become dry, contact veterinar-ian Chemistry/Synonyms Olsalazine sodium occurs as a yellow crystalline powder that is soluble in water and stable under physiologic acidic and alkaline conditions. It is basically 2 molecules of mesalamine (5-ASA) con-nected at the azo bonding site. Olsalazine sodium may also be known as: azodisal sodium, dimesalamine, CI mordant yellow 5, CI No. 14130, CJ-91B, olsalazi-num natricum, sodium azodisalicylate, Dipentum® or Rasal®. Storage/Stability Store capsules at room temperature. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Olsalazine Sodium Capsules: 250 mg; Dipentum® (Celltech); (Rx) OMEPRAZOLE (oh-meh-prah-zahl) Gastrogard®, Prilosec® PROTON PUMP INHIBITOR Prescriber Highlights TT Proton pump inhibitor used for GI ulcers & erosions TT Contraindications: Known hypersensitivity; may need to adjust dosage with hepatic or renal disease TT Adverse Effects: HORSES: Unlikely; potential hypersen-sitivity. SMALL ANIMALS: Appears to be well tolerated. Potentially: GI distress (anorexia, colic, nausea, vomiting, ﬂatulence, diarrhea), hematologic abnormalities, urinary tract infections, proteinuria, or CNS disturbances TT Treatment is relatively expensive, but human gener-ics are now available & costs are decreasing for small animals Uses/Indications Omeprazole is potentially useful in treating both gastroduodenal ulcer disease and to prevent or treat gastric erosions caused by ulcerogenic drugs (e. g., aspirin). An oral paste product is labeled for the treatment and prevention of recurrence of gastric ulcers in horses. Pharmacology/Actions Omeprazole is a substituted benzimidazole gastric acid (proton) pump inhibitor. In an acidic environment, omeprazole is activated to a sulphenamide derivative that binds irreversibly at the secretory surface of parietal cells to the enzyme, H +/K+ ATPase. There it in-hibits the transport of hydrogen ions into the stomach. Omeprazole reduces acid secretion during both basal and stimulated conditions. Omeprazole also inhibits the hepatic cytochrome P-450 mixed function oxidase system (see Drug Interactions below). Pharmacokinetics Omeprazole is rapidly absorbed from the gut; the human com-mercial product is in an enteric-coated granule form as the drug is rapidly degraded by acid. The equine paste is not enteric coated. In humans, peak serum levels occur within 0. 5-3. 5 hours and on-set of action within 1 hour. Omeprazole is distributed widely, but primarily in gastric parietal cells. In humans, approximately 95% is bound to albumin and alpha 1-acid glycoprotein. It is unknown whether omeprazole enters maternal milk. Omeprazole is extensively metabolized in the liver to at least six different metabolites. These are excreted principally in the urine, but also via the bile into feces. Signiﬁcant hepatic dysfunction will reduce the ﬁrst pass effect of the drug. In humans and dogs with normal hepatic function, serum half-life averages about 1 hour, but the duration of therapeutic effect may persist for 24-72 hours or more. Effects on acid production in horses can last up to 27 hours, depending upon dose. Contraindications/Precautions/Warnings Omeprazole is contraindicated in patients hypersensitive to it. In patients with hepatic or renal disease, the drug's half-life may be prolonged and dosage adjustment may be necessary if the disease is severe.	pppbs.pdf
668 OMEPRAZOLE Adverse Effects The manufacturer does not note any adverse effects for use in hors-es at labeled dosages. There is an anecdotal case report of one horse developing urticaria after receiving omeprazole. The drug appears to be quite well tolerated in both dogs and cats at effective dosages. Potentially, GI distress (anorexia, colic, nausea, vomiting, ﬂatulence, diarrhea) could occur, as well as hematologic abnormalities (rare in humans), urinary tract infections, proteinuria, or CNS distur-bances. Chronic very high doses in rats caused enterochromafﬁn-like cell hyperplasia and gastric carcinoid tumors; effects occurred in dose related manner. The clinical signiﬁcance of these ﬁndings for long-term low-dose clinical usage is not known, however, at the current time in humans, dosing for longer than 8 weeks is rarely recommended unless the beneﬁts of therapy outweigh the potential risks. In dogs, omeprazole use is believed safe for at least 4 weeks of therapy. Treatment of horses for up to 90 days is believed safe. Reproductive/Nursing Safety Omeprazole's safety during pregnancy has not been established, but a study done in rats at doses of up to 345 times those recommended did not demonstrate any teratogenic effects; however, increased embryo-lethality has been noted in lab animals at very high dos-ages. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) It is not known whether these agents are excreted in maternal milk. In rats, omeprazole administration during late gestation and lactation at doses of 35-345 times the human dose resulted in de-creased weight gain in pups. In humans, because of the potential for serious adverse reactions in nursing infants, and the potential for tumorigenicity shown in rat carcinogenicity studies, nursing is discouraged if the drug is required. Overdosage/Acute Toxicity The LD 50 in rats after oral administration is reportedly >4 g/kg. Humans have tolerated oral dosages of 360 mg/day without signiﬁ-cant toxicity. Should a massive overdose occur, treat symptomati-cally and supportively. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving omeprazole and may be of signiﬁcance in veterinary patients: !TBENZODIAZEPINES : Omeprazole may potentially alter benzodiaz-epine metabolism and prolong CNS effects !TCLARITHROMYCIN : Increased levels of omeprazole, clarithromycin and 14-hydroxyclarithromycin are possible !TCYANOCOBALAMIN (oral): Omeprazole may decrease oral absorp-tion !TCYCLO SPOR INE: Omeprazole may reduce cyclosporine metabolism !TDRUGS REQUIRING DECREASED GASTRIC PH FOR O PTIMAL ABSORPTION (e. g., ketoconazole, itraconazole, iron, ampicillin esters ): Omeprazole may decrease drug absorption !TSUCRALFATE : May decrease bioavailability of orally administered omeprazole !TWARFARIN : Omeprazole may increase anticoagulant effect Laboratory Considerations !TOmeprazole may cause increased liver enzymes !TOmeprazole will increase serum gastrin levels early in therapy Doses Dose dependent on formulation, equine paste and human oral forms may not be interchangeable. Be wary of compounded for-mulations; bioequivalence is not assured. !TDOGS: For ulcer management: a) 0. 5-1 mg/kg PO once daily (Davenport 1992); (Haskins 2000) b) For adjunctive treatment of uremic gastropathy: 0. 5-1 mg/ kg PO q24h; dosage may need to be modiﬁed in moderate or severe renal failure. (Vaden 2007) c) For severe ulceration unresponsive to H 2 blockers; severe esophagitis unresponsive to metoclopramide and H 2 block-ers; gastrinoma (Zollinger-Ellison syndrome): 0. 75-1 mg/kg PO once daily (q24h)-OR-one 20 mg capsule for animals >20 kg, 10 mg (1/2 capsule) for animals weighing >5 kg but <20 kg, 5 mg (1/4 capsule for animals weighing <5 kg. When using less than a full capsule, repackage granules in a gelatin capsule to avoid gastric acid degradation. (Johnson, Sherding et al. 1994) d) 0. 7 mg/kg (>20 kg, 20 mg/dog; <20 kg, 10 mg/dog) PO once daily (Matz 1995) e) For adjunctive treatment of esophagitis or gastric ulcers: 0. 5-1 mg/kg PO q24h (Sellon 2007a), (Sellon 2007b) f) For some animals with gastrinomas or esophagitis (often H-2 receptor antagonists are adequate): 0. 7-1. 5 mg/kg PO q24h, but if severe esophagitis or gastrinomas may use up to 2 mg/kg PO q12h (Willard 2006d) g) For eliminating Helicobacter gastritis infections: Using triple therapy: Metronidazole 33 mg/kg once daily, amoxicillin 11 mg/kg q12h and either sucralfate (0. 25-0. 5 grams q8h) or omeprazole 0. 66 mg/kg once daily (Hall 2000) !TCATS: For ulcer management: a) 0. 7 mg/kg PO once a day (Johnson 1996) b) 0. 7-1. 5 mg/kg PO q12-24h (Willard 2003b) c) For adjunctive treatment of esophagitis or gastric ulcers: 0. 5-1 mg/kg PO q24h (Sellon 2007a), (Sellon 2007b) d) For adjunctive treatment of uremic gastropathy: 0. 7 mg/kg PO q24h; dosage may need to be modiﬁed in moderate or severe renal failure. (Vaden 2007) !THORSES: (Note : ARCI UCGFS Class 5 Drug) For gastric ulcers: a) For treatment of gastric ulcers: 4 mg/kg PO once daily for 4 weeks; to prevent recurrence treat for at least another 4 weeks at 2 mg/kg PO once daily (Label Directions; Gastrogard®) b) 4 mg/kg PO once daily for treatment; 2 mg/kg PO once daily to prevent recurrence in Thoroughbreds in race training (Andrews and Nadeau 1999) c) For treatment or prophylaxis of gastric ulcers in foals: 4 mg/ kg PO once daily for treatment, 1-2 mg/kg PO once daily for prophylaxis (Wilkins 2004b) !TSWINE: For ulcer management: a) 40 mg of PO daily for two days; fasted for 48 hours (De Mint 1999) Monitoring !TEfﬁcacy !TAdverse effects	pppbs.pdf
ONDANSETRON HCL 669 Client Information T ! Give before meals, preferably in the morning Chemistry/Synonyms A substituted benzimidazole proton pump inhibitor, omeprazole has a molecular weight of 345. 4 and p K a's of 4 and 8. 8. Omeprazole may also be known as: H-168/68, or omeprazolum, Gastrogard®, Prilosec®, Ulcergard® and Zegerid ®. Storage/Stability Omeprazole oral paste should be stored below 86°F. Transient ex-posure to temperatures up to 104°F is permitted. Omeprazole tab-lets should be stored at room temperature in light-resistant, tight containers. Omeprazole pellets found in the capsules are fragile and should not be crushed. If needed to administer as a slurry, it has been suggested to mix the pellets carefully with fruit juices, not wa-ter, milk or saline. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Omeprazole Oral Paste, 2. 28g per syringe; Gastrogard® (Merial), (Rx); Ulcergard® (Merial), (OTC) The ARCI (Racing Commissioners International) has designated this drug as a class 5 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Omeprazole Oral Delayed-Release Capsules: 10 mg, 20 mg (tablets & capsules) & 40 mg; Prilosec® (Astra Zeneca); Prilosec® OTC (Losec® in Canada) (Procter & Gamble); generic; (Rx & OTC) Omeprazole/Sodium Bicarbonate Oral Capsules (Immediate Re-lease): 20 mg omeprazole/1,100 mg sodium bicarbonate; 40 mg omeprazole/1,100 mg sodium bicarbonate; Zegerid® (Santarus); (Rx) Omeprazole/Sodium Bicarbonate Powder for Oral Suspension: 20 mg omeprazole/1,680 sodium bicarbonate; 40 mg omeprazole/1,680 sodium bicarbonate; in 30 unit-dose packets; Zegerid® (Santarus); (Rx) ONDANSETRON HCL (on-dan-sah-tron) Zofran® 5-HT 3 RECEPTOR ANTAGONIST Prescriber Highlights TT 5-HT3 receptor antagonist for severe vomiting TT Appears to be well tolerated in dogs TT Generic dosage forms now available Uses/Indications Used as an antiemetic when conventional antiemetics are ineffec-tive, such as when administering cisplatin or for other causes of intractable vomiting. The use of ondansetron in cats is somewhat controversial and some state it should not be used in this species. Pharmacology/Actions Ondansetron is a 5-HT 3 (serotonin type 3) receptor antagonist. 5-HT 3 receptors are found peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone (CTZ). It is not clear if ondansetron's effects are mediated centrally, peripherally or both. Pharmacokinetics No veterinary species data was located for ondansetron pharma-cokinetics. In humans, ondansetron is well absorbed from the GI tract, but exhibits some ﬁrst pass hepatic metabolism. Bioavailability is about 50-60%. Peak plasma levels occur about 2 hours after an oral dose. Ondansetron is extensively metabolized in the liver. Elimination half-lives are about 3-4 hours, but are prolonged in elderly patients. Contraindications/Precautions/Warnings Ondansetron is contraindicated in patients hypersensitive to it or other agents in this class. Ondansetron may mask ileus or gastric distention; it should not be used in place of nasogastric suction. Use with caution in patients with hepatic dysfunction as half-life may be prolonged. Because ondansetron is potentially a neurotoxic substrate of P-glycoprotein, it should be used with caution in those herding breeds (e. g., Collies, Shelties, Australian shepherds, etc. ) that may have the gene mutation that causes a nonfunctional protein. Adverse Effects Ondansetron appears to be well tolerated. Constipation, extrapy-ramidal clinical signs, arrhythmias and hypotension are possible (incidence in humans <10%). Reproductive/Nursing Safety Safety in pregnancy not clearly established, but high dose studies in rodents did not demonstrate overt fetal toxicity or teratogenicity. In humans, the FDA categorizes this drug as category B for use dur-ing pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) Ondansetron is excreted in the maternal milk of rats. Exercise caution when 5-HT3 antagonists are administered to nursing patients. Overdosage/Acute Toxicity Overdoses of up to 10X did not cause signiﬁcant morbidity in hu-man subjects. If an overdose occurs, treat supportively. Drug Interactions/Laboratory Considerations None reported Doses T ! DOGS: a) As an antiemetic for adjunctive treatment of pancreatitis: 0. 1-0. 2 mg/kg IV slowly (Webb 2007a) b) As an antiemetic when conventional antiemetics are inef-fective: 0. 1-1 mg/kg PO q12-24h, or 30 minutes prior to and 90 minutes after starting cisplatin infusion (Frimberger 2000) c) For intractable vomiting associated with Parvo enteritis: 0. 11-0. 176 mg/kg IV given as a slow IV push every 6-12 hours (based on patient response) (Tams 2003d) d) As an antiemetic: 0. 1-0. 2 mg/kg IV q6-12h or 0. 1-1 mg/kg PO q12-24h (Otto 2005) e) As an antiemetic for adjunctive treatment of uremia: 0. 6-1 mg/kg PO or IV q12h; usually combined with metoclopr-amide. (Polzin 2005a)	pppbs.pdf
670 ORBIFLOXACIN TT ! CATS: a) For intractable vomiting when other less expensive drugs are ineffective: 0. 22 mg/kg (route not identiﬁed) 2-3 times a day (Willard 1999) b) As an anti-emetic for intractable vomiting: 0. 1-0. 15 mg/kg slow IV push q6-12h as needed (Scherk 2003c) c) As an antiemetic for adjunctive treatment of severe pancrea-titis: 0. 1-1 mg/kg PO or IV q12-24h (Armstrong 2007) Monitoring T ! Clinical efﬁcacy Client Information T ! his medication is generally used in inpatient settings for treat-ment of serious vomiting. Chemistry/Synonyms A selective inhibitor of serotonin type 3 (5-HT 3), ondansetron HCl dihydrate occurs as a white to off-white powder that is soluble in water. Ondansetron HCl may also be known as: GR-38032F or on-dansetroni hydrochloridum, and Zofran®. Storage/Stability Unless otherwise labeled, store oral products in tight, light-resis-tant containers between 2-30°C. The injection should be stored between 2-30°C and protected from light. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Ondansetron HCl Tablets: 4 mg, 8 mg and 24 mg; Zofran® (Glaxo S-mith Kline), generic; (Rx) Ondansetron Orally Disintegrating Tablets: 4 mg & 8 mg (as base); Zofran® ODT (Glaxo Smith Kline), generic; (Rx) Ondansetron HCl Oral Solution: 4 mg/5 m L (5 mg as the HCl) in 50 m L bottles; Zofran® (Glaxo Smith Kline), generic; (Rx) Ondansetron HCl Injection: 2 mg/m L in 2 m L single-dose and 20 m L multi-dose vials, and 32 mg/50 m L (premixed; preservative free) in 50 m L single-dose containers; Zofran® (Glaxo Smith Kline); generic; (Rx) o,p-DDD—see Mitotane Opiate Antidiarrheals-See Separate Monographs for Diphenoxylate/Atropine, Loperamide, or Paregoric ORBIFLOXACIN (or-bi-ﬂox-a-sin) Orbax® FLUOROQUINOLONE ANTIBIOTIC Prescriber Highlights TT Fluoroquinolone antibiotic labeled for dogs & cats TT Contraindications: Immature dogs during the rapid growth phase; known hypersensitivity to this class of drugs. Caution: Known or suspected CNS disorders TT Adverse Effects: GI effects most likely TT Drug Interactions Uses/Indications Orbiﬂoxacin is indicated for treatment in dogs and cats for bacte-rial infections susceptible to it. Orbiﬂoxacin may also be of beneﬁt in treating susceptible gram-negative infections in horses. Pharmacology/Actions Orbiﬂoxacin is a concentration-dependent bactericidal agent. It acts by inhibiting bacterial DNA-gyrase (a type-II topoisomerase), thereby preventing DNA supercoiling and DNA synthesis. The net result is disruption of bacterial cell replication. Orbiﬂoxacin has good activity against many gram-negative and gram-positive bacilli and cocci, including most species and strains of Klebsiella spp., Staphylococcus intermedius or aureus, E. coli, Enterobacter, Campylobacter, Shigella, Proteus, Pasturella species. Some strains of Pseudomonas aeruginosa and Pseudomonas spp. are resistant to orbiﬂoxacin and most Enterococcus spp. are resistant. Like other ﬂuoroquinolones, orbiﬂoxacin has weak activity against most anaerobes and is not a good choice when treating known or suspected anaerobic infections. Pharmacokinetics After oral administration in dogs or cats, orbiﬂoxacin is apparently nearly completely absorbed. The drug is distributed well (V d=1. 5 L/kg in dogs and 1. 4 L/kg in cats) and only bound slightly to plasma proteins (8% dogs; 15% cats). Orbiﬂoxacin is eliminated primar-ily via the kidneys. Approximately 50% of the drug is excreted un-changed. Serum half-life is about 6 hours in both dogs and cats. Urine levels remain well above MIC's for susceptible organisms for at least 24 hours after dosing. In horses, orbiﬂoxacin is well absorbed after oral administration (bioavailability is about 70%) and distributes in many body ﬂu-ids and endometrial tissue. Elimination half-life is approximately 9 hours. Contraindications/Precautions/Warnings Orbiﬂoxacin, like other ﬂuoroquinolones, can cause arthropathies in immature, growing animals. Because dogs appear to be more sensitive to this effect, the manufacturer states that the drug is con-traindicated in immature dogs during the rapid growth phase (be-tween 2-8 months in small and medium-sized breeds and up to 18 months in large and giant breeds). The drug is also contraindicated in dogs and cats known to be hypersensitive to orbiﬂoxacin or other drugs in its class (quinolones). The manufacturer states that orbiﬂoxacin should be used with caution in animals with known or suspected CNS disorders (e. g., seizure disorders) as, rarely, drugs in this class have been associated with CNS stimulation. Adverse Effects While the manufacturer reports that no adverse effects were re-ported during clinical studies (at 2. 5. mg/kg dosing) in adult ani-mals, higher doses or additional experience with use of the drug may demonstrate additional adverse effects. Gastrointestinal effects (anorexia, vomiting, diarrhea) would most likely be the ﬁrst adverse effects noted. Ophthalmic adverse effects are not likely in cats, but the FDA 's Adverse Drug Reaction database has received 10 reports (as of July 3, 2007) of blindness associated with orbiﬂoxacin. Causal effect cannot be proven, but use higher dosages carefully. Reproductive/Nursing Safety Safety in breeding or pregnant dogs or cats has not been established. It is not known whether orbiﬂoxacin enters maternal milk.	pppbs.pdf
OSELTAMIVIR PHOSPATE 671 Overdosage/Acute Toxicity Dogs and cats receiving up to 5X (37. 5mg/kg) for 30 days did not result in any signiﬁcant adverse effects. Cats receiving the higher dosages exhibited soft feces and decreased body weight gains. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving orbiﬂoxacin or re-lated ﬂuoroquinolones and may be of signiﬁcance in veterinary patients: Al+++T ! ANTACIDS/DAIRY PRODUCTS : Containing cations (Mg++,, Ca++) may bind to orbiﬂoxacin and prevent its absorption; sepa-rate doses of these products by at least 2 hours T ! ANTIBIOTICS, OTHER (aminoglycosides, 3 rd-generation cephalosporins, penicillins—extended-spectrum : Synergism may occur, but is not predictable, against some bacteria (particularly Pseudomonas aeruginosa) with these compounds. Although orbiﬂoxacin has minimal activity against anaerobes, in vitro synergy has been re-ported when used with clindamycin against strains of Peptostrep-tococcus, Lactobacillus and Bacteroides fragilis. T ! CYCLOSPORINE : Fluoroquinolones may exacerbate the neph-rotoxicity, and reduce the metabolism of, cyclosporine (used systemically) T ! FLUNIXIN : Has been shown in dogs to increase the AUC and elimi-nation half-life of enroﬂoxacin and enroﬂoxacin increases the AUC and elimination half-life of ﬂunixin; it is unknown if orbi-ﬂoxacin also causes this effect or if other NSAIDs interact with orbiﬂoxacin in dogs T ! GLYBURIDE : Severe hypoglycemia possible T ! IRON, ZINC (oral): Decreased orbiﬂoxacin absorption; separate doses by at least two hours T ! METHOTREXATE : Increased MTX levels possible with resultant toxicity T ! NITROFURANTOIN : May antagonize the antimicrobial activ-ity of the ﬂuoroquinolones and their concomitant use is not recommended T ! PHENYTOIN : Orbiﬂoxacin may alter phenytoin levels T ! PROBENECID : Blocks tubular secretion of ciproﬂoxacin and may also increase the blood level and half-life of orbiﬂoxacin T ! SUCRALFATE : May inhibit absorption of orbiﬂoxacin; separate doses of these drugs by at least 2 hours T ! THEOPHYLLINE : Orbiﬂoxacin may increase theophylline blood levels T ! WARFARIN : Potential for increased warfarin effects Doses T ! DOGS & CAT S: For susceptible infections: a) 2. 5 mg/kg-7. 5 mg/kg, once daily PO. Higher end of the dos-ing range may be necessary in hospitalized patients, those with underlying disease (e. g., malignancy) or structural al-terations (e. g., burns, complicated urinary tract infections, foreign body infections), infections associated with vascular compromise and infections caused by “problem” pathogens. (Package Insert; Orbax®) T ! HORSES: For susceptible infections: a) 5 mg/kg, once daily PO (Davis, Papich et al. 2006) b) 7. 5 mg/kg PO once daily (Haines, Brown et al. 2001) Monitoring/Client Information T ! Efﬁcacy is the most important monitoring parameter T ! Clients should be instructed on the importance of giving the medication as instructed and not to discontinue it on their own. Chemistry/Synonyms A 4-ﬂuoroquinolone antibiotic, orbiﬂoxacin is slightly soluble in water at neutral p H. Solubility increases in either an acidic or basic medium. Orbiﬂoxacin may also be known as maruﬂoxacin or Orbax®. Storage/Stability/Compatibility The commercially available tablets should be stored between 2-30°C (36-86°F) and protected from excessive moisture. An orbiﬂoxacin 22. 7 mg tablet crushed and mixed with mollas-es, dark corn syrup, water from canned tuna, Kame ﬁsh sauce, Ora-Plus, Syrplata, or simple syrup was relatively stable (>85% expected value) for up to 7 days when stored unrefrigerated, but protected from light. Mixing with oral supplements that contain calcium or magnesium (e. g., Lixotinic) showed signiﬁcant inactivation of orbi-ﬂoxacin by 4 days (Kukanich and Papich 2003). Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Orbiﬂoxacin Oral Tablets: 5. 7 mg (yellow) in btls of 250; 22. 7 mg (green; E-Z Break) in btls of 250; 68 mg (blue; E-Z Break) in btls of 100; Orbax® (Schering-Plough Animal Health); (Rx). Approved for use in dogs and cats. Federal law prohibits the use of the drug in food-producing animals. HUMAN-LABELED PRODUCTS: None Ormetoprim—see Sulfadimethoxine/Ormetoprim OSELTAMIVIR PHOSPHATE (oh-sell-tam-ih-vir) Tamiﬂu® NEURAMINIDASE INHIBITOR ANTIVIRAL Prescriber Highlights TT Neuraminidase inhibitor antiviral for inﬂuenza A & B viruses; anecdotally, may be effective for parvovirus infec-tions in dogs or other mixed bacterial/viral infections TT Very limited information on efﬁcacy & safety in animals TT Due to public health issues, use in veterinary medicine is controversial TT Expense an issue, especially for treating horses Uses/Indications Although, there is no research published (at the time of writing— January 2007) documenting oseltamivir safety or efﬁcacy in dogs or cats, there is much interest and discussion regarding its poten-tial for the adjunctive treatment of parvovirus infections in dogs. It may be of beneﬁt for adjunctive treatment of other viral infec-tions, particularly those with associated secondary bacterial com-ponents, but research or experience is lacking. A recent study per-formed in horses, experimentally infected with equine inﬂuenza A (H3N8), documented some efﬁcacy in the attenuation of clinical signs (pyrexia), viral shedding, and secondary bacterial pneumo-nias (Y amanaka, Tsujimura et al. 2006).	pppbs.pdf
672 OSELTAMIVIR PHOSPATE Because oseltamivir is the primary antiviral agent proposed for treatment or prophylaxis for an H5N1 inﬂuenza (“bird ﬂu”) pan-demic in humans, its use in veterinary patients is controversial, par-ticularly due to concerns of adequate drug supply for the human population and the potential for inﬂuenza virus resistance develop-ment. In 2006, the FDA banned the extra-label use of oseltamivir and other inﬂuenza antivirals in chickens, turkeys and ducks. At the time of writing, its use is still allowed in mammal veterinary patients, but veterinarians should use the drug prudently and be cognizant of these public health concerns. Pharmacology/Actions Oseltamivir phosphate is a prodrug that is converted after ab-sorption into oseltamivir carboxylate, the active form of the drug. Oseltamivir carboxylate competitively inhibits inﬂuenza virus neuraminidase, an enzyme that is required for viral replication, re-lease of virus from infected cells and the prevention of formation of viral aggregates after release from cells. Resistance to oseltamivir has been induced in the laboratory and from post-treatment iso-lates from infected humans. Oseltamivir or oseltamivir carboxylate do not act as substrates or inhibitors for any CYP-450 isoenzymes. It has been postulated that oseltamivir may limit the ability of canine parvovirus to pass through intestinal mucosa and infect in-testinal crypt cells. There is evidence that oseltamivir has this ef-fect (increased mucous inactivation) on inﬂuenza viruses in the respiratory tract of humans. Additionally, it may reduce GI bacteria colonization, translocation and toxin production. Pharmacokinetics No information was located for the pharmacokinetic proﬁles of oseltamivir in dogs, cats or horses. In humans, oseltamivir phos-phate is readily absorbed and converted into the carboxylate (ac-tive) form predominantly via liver esterases. The bioavailability of oseltamivir carboxylate is about 75%; it is minimally bound to plasma proteins. Elimination of oseltamivir carboxylate is primar-ily via renal mechanisms, both glomerular ﬁltration and tubular secretion. Elimination half-life is about 6-10 hours in patients with normal renal function. Up to 20% of a dose may be eliminated in the feces. Contraindications/Precautions/Warnings Oseltamivir should not be used in patients with documented hy-persensitivity to it. For efﬁcacy, treatment must begin as early as possible. Delay in treatment beyond 40 hours after the onset of clinical signs in humans with inﬂuenza is associated with minimal efﬁcacy. Dosages may need adjustment in patients with severe renal insufﬁciency. Studies where neonatal rats were administered 1 g/kg levels of the prodrug in the brain were 1500X greater and the active metabo-lite was 3 times higher than those found in adult rats. Potentially, newborn puppies could exhibit similar ﬁndings; neurotoxicity is a possibility. In 2006, the FDA banned the extra-label use of oseltamivir and other inﬂuenza antivirals in chickens, turkeys and ducks. Adverse Effects Adverse effect proﬁle in animals is not known. In the study men-tioned above performed in horses, no adverse effects were noted. In humans, oseltamivir can cause gastrointestinal effects (nausea, vom-iting), insomnia and vertigo. Bronchitis has been reported, but may be an artifact associated with inﬂuenza infection. Gastrointestinal effects are usually transient and may be alleviated by giving the medication with food. Reproductive/Nursing Safety Oseltamivir appears to be relatively safe during pregnancy. In rab-bits, doses of 150 and 500 mg/kg (13X, 100X) caused dose-depen-dent increases of minor skeletal abnormalities. In humans, the FDA categorizes oseltamivir 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. ) Oseltamivir and oseltamivir carboxylate have been detected in the milk of lactating rats. Safety during nursing cannot be guaran-teed, but it is unlikely to pose signiﬁcant risk in nursing veterinary patients. Overdosage/Acute Toxicity Oseltamivir has relatively low toxic potential. In humans, overdoses of up to 1000 mg have caused only nausea and vomiting. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oseltamivir and may be of signiﬁcance in veterinary patients: !TPROBENECID : May increase 2-fold the exposure to oseltamivir car-boxylate (active metabolite) by reducing tubular secretion. This could potentially be useful in reducing drug dosages or dosing frequency, or increasing serum concentrations at the usual dos-age, however, supporting data is not readily available. Because of the implications associated with treating H5N1inﬂuenza in humans, expect more information to be published on this in-teraction in the future. See the Probenecid monograph for more information. !TVACCINES, INFLUENZA (live): Oseltamivir may potentially reduce the immune response to live inﬂuenza virus vaccines. There does not appear to be any effect on inactivated (killed) vaccines. Laboratory Considerations No concerns noted Doses !TDOGS: For adjunctive treatment of canine parvovirus enteritis: a) 2. 2 mg/kg PO q12h. Should be administered as early as possi-ble in the course of the disease. More data is needed to prove efﬁcacy. (Macintire 2006f) !THORSES: For treatment of equine Inﬂuenza A: a) 2 mg/kg PO twice daily for 5 days. Must be given early in the course of the disease to obtain satisfactory outcome. Dose used in this experimental study was based upon human pe-diatric dosage; not equine pharmacokinetic or pharmacody-namic data. This study also showed efﬁcacy in reducing the clinical effects of inﬂuenza when used prophylactically. Dos-age used was 2 mg/kg PO once daily for 5 days, but the au-thors concluded that this dosage may need to be given longer or changed for better prophylaxis. (Y amanaka, Tsujimura et al. 2006) Monitoring !TEfﬁcacy Client Information !TIf used in veterinary patients, clients should understand the ex-perimental nature of using this treatment	pppbs.pdf
OXACILLIN SODIUM 673 Chemistry/Synonyms Oseltamivir phosphate occurs as a white crystalline solid. Molecular weights are 312. 4 for the free base and 410. 4 for the phosphate salt. Oseltamivir phosphate may also be known as GS-4104/002, or Ro-64-0796/002 and Tamiﬂu®. Storage/Stability Oseltamivir capsules should be stored at 25°C, excursions are per-mitted to 15-30°C. The oral powder for reconstitution should be stored between 15-30°C. Once reconstituted with 23 m L of water, it should be stored at room temperature (15-30°C) or in the refrig-erator (2-8°C) and protected from freezing. After reconstitution, it is stable for 10 days. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None In 2006, the FDA banned the extra-label use of oseltamivir and other inﬂuenza antivirals in chickens, turkeys and ducks. HUMAN-LABELED PRODUCTS: Oseltamivir Phosphate Oral Capsules: 30, 45, & 75 mg (as base); Tamiﬂu® (Roche); (Rx) Oseltamivir Phosphate Powder for Oral Suspension: 12 mg/m L (as base) after reconstitution in 25 m L bottles; Tutti-frutti ﬂavor, con-tains sorbitol, and saccharin; Tamiﬂu® (Roche); (Rx) OXACILLIN SODIUM (ox-a-sill-in) ANTI-STA PHYLOCOCCAL PENICILLIN Prescriber Highlights TT Oral & intramammary isoxazolyl (anti-staphylococcal) penicillin TT Contraindications: Hypersensitivity to penicillins; do not use oral medications in critically ill patients TT Predominant adverse effects are GI in nature TT Must dose orally quite often (6-8h); owner compliance may be an issue Uses/Indications The veterinary use of these agents has been primarily in the treat-ment of bone, skin, and other soft tissue infections in small animals when penicillinase-producing Staphylococcus species have been isolated. Because of its rapid elimination and required frequent dosing, it is infrequently used. Pharmacology/Actions Cloxacillin, dicloxacillin and oxacillin have nearly identical spec-trums of activity and can be considered therapeutically equivalent when comparing in vitro activity. These penicillinase-resistant penicillins have a narrower spectrum of activity than the natural penicillins. Their antimicrobial efﬁcacy is aimed directly against penicillinase-producing strains of gram-positive cocci, particularly staphylococcal species. They are sometimes called anti-staphylo-coccal penicillins. There are documented strains of Staphylococcus that are resistant to these drugs (so-called methicillin-resistant or oxacillin-resistant Staph), but these strains have only begun to be a signiﬁcant problem in veterinary 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-resis-tant penicillins are inactive against Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses. Pharmacokinetics Oxacillin sodium is resistant to acid inactivation in the gut, but is only partially absorbed after oral administration. The bioavailabil-ity after oral administration in humans has been reported to range from 30-35%, and, if given with food, both the rate and extent of absorption is decreased. After IM administration, oxacillin is rap-idly absorbed and peak levels generally occur within 30 minutes. The drug is distributed to the lungs, kidneys, bone, bile, pleural ﬂuid, synovial ﬂuid, and ascitic ﬂuid. The volume of distribution is reportedly 0. 4 L/kg in human adults and 0. 3 L/kg in dogs. As with the other penicillins, only minimal amounts are distributed into the CSF, but levels are increased with meningeal inﬂammation. In humans, approximately 89-94% of the drug is bound to plasma proteins. Oxacillin is partially metabolized to both active and inactive me-tabolites. These metabolites and the parent compound are rapidly 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 18-48 minutes. In dogs, the elimination half-life has been reported as 20-30 minutes. Contraindications/Precautions/Warnings Penicillins are contraindicated in patients with a history of hyper-sensitivity to them. Because there may be cross-reactivity, use peni-cillins cautiously in patients who are documented hypersensitive to other beta-lactam antibiotics (e. g., cephalosporins, cefamycins, carbapenems). Do not administer systemic antibiotics orally in patients with septicemia, shock, or other grave illnesses as absorption of the medi-cation from the GI tract may be signiﬁcantly delayed or diminished. Parenteral (preferably IV) routes should be used for these cases. 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 hypersensitive to cephalosporins will also be hypersensitive to penicillins. The incidence of cross-reactivity in veterinary patients is unknown. When given orally, penicillins may cause GI effects (anorexia, vomiting, diarrhea). Because the penicillins may also alter gut ﬂora, antibiotic-associated diarrhea can occur and allow the proliferation of resistant bacteria in the colon (superinfections). Neurotoxicity (e. g., ataxia in dogs) has been associated with very high doses or very prolonged use. Although the penicillins are not considered hepatotoxic, elevated liver enzymes have been reported. Other effects reported in dogs include tachypnea, dyspnea, edema, and tachycardia. 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	pppbs.pdf
674 OXACILLIN SODIUM 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 class: A (Probably safe. Although speciﬁc studies may not have proved he safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women. ) Penicillins are excreted in maternal milk in low concentrations; use may cause diarrhea, candidiasis, or allergic response in nursing offspring. Overdosage/Acute Toxicity Acute oral penicillin overdoses are unlikely to cause signiﬁcant problems other than GI distress, but other effects are possible (see Adverse effects). In humans, very high dosages of parenteral peni-cillins, especially in patients with renal disease, have induced CNS effects. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oxacillin and may be of signiﬁcance in veterinary patients: !TAMINOGLYCOSIDES : In vitro evidence of synergism with oxacillin against S. aureus strains !TCYCLOSPORINE : Oxacillin may reduce levels !TPROBENECID : Competitively blocks the tubular secretion of oxa-cillin, thereby increasing serum levels and serum half-lives !TTETRACYCLINES : Theoretical antagonism; use together usually not recommended !TWARFARIN : Oxacillin may cause decreased warfarin efﬁcacy Laboratory Considerations !TAs penicillins and other beta-lactams can inactivate aminogly-cosides in vitro (and in vivo in patients in renal failure), serum concentrations of aminoglycosides may be falsely decreased if the patient is also receiving beta-lactam antibiotics and the serum is stored prior to analysis. It is recommended that if the assay is delayed, samples be frozen and, if possible, drawn at times when the beta-lactam antibiotic is at a trough. Doses Note : Oxacillin is only available commercially in the USA for use as a parenteral injection and an oral suspension. For oral therapy, dicloxacillin capsules may be substituted for oxacillin. !TDOGS: For susceptible infections: a) 22-40 mg/kg PO, SC, IM, or IV q8h (Lappin 2003a) b) For non-superﬁcial pyoderma: 25-30 mg/kg PO three times daily for 3-6 weeks. Maximum dose is 1 gram three times daily. Increase dose if no response in one week. If no response by second week, discontinue. (Aucoin 2002a) c) For Staph. acute osteomyelitis: 22 mg/kg IV, IM, SC or PO three to four times daily (Harari 2003) d) For penicillinase-producing Staph. Endocarditis: 50-60 mg/ kg three times daily for 4-6 weeks (route not indicated) (Sis-son and Thomas 1986) e) For systemic therapy for Staph. blepharitis: 22 mg/kg PO three times daily (Laratta 1986) !TCATS: For susceptible infections: a) 22-40 mg/kg PO, SC, IM, or IV q8h (Lappin 2003a) !THORSES: For susceptible infections: a) Foals: 20-30 mg/kg IV q6-8h (Dose extrapolated from adult horse data; use lower dose or longer interval in prema-ture foals or those less than 7 days old. ) (Caprile and Short 1987); (Brumbaugh 1999) b) 25-50 mg/kg IM, IV twice daily (Robinson 1987) Monitoring !TBecause penicillins usually have minimal toxicity associated with their use, monitoring for efﬁcacy is usually all that is required un-less toxic signs develop. Serum levels and therapeutic drug moni-toring are not routinely done with these agents. Client Information !TUnless otherwise instructed by the veterinarian, this drug should be given to an animal with an empty stomach, at least 1 hour before feeding or 2 hours after. !TKeep oral solution in the refrigerator and discard any unused sus-pension after 14 days. Chemistry/Synonyms An isoxazolyl-penicillin, oxacillin sodium is a semi-synthetic pen-icillinase-resistant penicillin. It is available commercially as the monohydrate sodium salt, which occurs as a ﬁne, white, crystalline powder that is odorless or has a slight odor. It is freely soluble in water and has a p K a of about 2. 8. One mg of oxacillin sodium con-tains not less than 815-950 micrograms of oxacillin. Each gram of the commercially available powder for injection contains 2. 8-3. 1 m Eq of sodium. Oxacillin sodium may also be known as: sodium oxacillin, meth-ylphenyl isoxazolyl penicillin (5-methyl-3-phenyl-4-isoxazolyl) penicillin sodium, oxacillinum natricum, oxacillinum natrium, P-12, or SQ-16423. Storage/Stability/Compatibility Oxacillin sodium powder for oral solution, and powder for injec-tion should be stored at room temperature (15-30°C) in tight con-tainers. After reconstituting with water, refrigerate and discard any remaining oral solution after 14 days. If kept at room temperature, the oral solution is stable for 3 days. After reconstituting the sterile powder for injection with sterile water for injection or sterile sodium chloride 0. 9%, the resultant solution with a concentration of 167 mg/m L is stable for 3 days at room temperature or 7 days if refrigerated. The manufacturer recommends using different quantities of diluent depending on whether the drug is to be administered IM, IV directly, or IV (pig-gyback). Refer to the package insert for speciﬁc instructions. Oxacillin sodium injection is reportedly physically compatible with the following ﬂuids/drugs: dextrose 5% and 10% in water, dextrose 5% and 10% in sodium chloride 0. 9%, lactated Ringer's injection, sodium chloride 0. 9% amikacin sulfate, cephapirin sodi-um, chloramphenicol sodium succinate, dopamine HCl, potassium chloride, sodium bicarbonate, and verapamil. Oxacillin sodium injection is reportedly physically incompatible with the following ﬂuids/drugs: oxytetracycline HCl and tetracy-cline HCl. Compatibility is dependent upon factors such as p H, concentration, temperature, and diluent used; consult specialized references or a hospital pharmacist for more speciﬁc information.	pppbs.pdf
OXAZEPAM 675 Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Oxacillin Sodium Powder for Oral Solution: 250 mg/5 m L when re-constituted in 100 m L; generic; (Rx) Oxacillin Sodium Powder for Injection: 500 mg, 1 g & 2 g in vials, Add-Vantage vials, and piggyback vials; 10 g bulk vials; generic; (Rx) OXAZEPAM (ox-a-ze-pam) Serax® BENZODIAZEPINE Prescriber Highlights TT Benzodiazepine used primarily as an appetite stimulant in cats, but may also be useful to treat behavior prob-lems in dogs or cats TT Contraindications: Known benzodiazepine hypersensitiv-ity, acute narrow angle glaucoma. Caution: Myasthenia gravis, hepatic dysfunction, seizure disorders. TT Adverse Effects: Primarily sedation & occasionally, ataxia. TT Possibly teratogenic TT C-IV Controlled substance Uses/Indications Oxazepam is used most frequently in small animal medicine as an appetite stimulant in cats and dogs. It may also be useful as an oral anxiolytic agent for adjunctive therapy of behavior-related disor-ders for both dogs and cats. Pharmacology/Actions The subcortical levels (primarily limbic, thalamic, and hypotha-lamic) of the CNS are depressed by oxazepam 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: antago-nism of serotonin, increased release of gamma-aminobutyric acid (GABA) and/or facilitation of GABA activity, and diminished re-lease or turnover of acetylcholine in the CNS. Benzodiazepine spe-ciﬁc 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 Oxazepam is absorbed from the GI tract, but it is one of the more slowly absorbed oral benzodiazepines. Oxazepam, like other benzo-diazepines is widely distributed; it is highly bound to plasma pro-teins (97% in humans). While not conﬁrmed, oxazepam may cross the placenta and enter maternal milk. Oxazepam is principally con-jugated in the liver via glucuronidation to an inactive metabolite. Serum half-life in humans ranges from 3-21 hours. Contraindications/Precautions/Warnings Oxazepam is contraindicated in patients who are hypersensitive to it or other benzodiazepines or have acute narrow angle glaucoma. Benzodiazepines have been reported to exacerbate myasthenia gravis. While oxazepam is less susceptible to accumulation than many other benzodiazepines in patients with hepatic dysfunction, it should be used with caution nonetheless. Adverse Effects The most prevalent adverse effects seen with oxazepam in small animals is sedation and occasionally, ataxia. These may be transient and dosage adjustment may be required to alleviate. Paradoxical effects such as excitability, vocalization or aggression are possible. When used to treat negative behaviors, a rebound effect can occur, particularly if the drug is not withdrawn slowly. Rarely, oxazepam has reportedly precipitated tonic-clonic sei-zures; use with caution in susceptible patients. Potentially, oxazepam could cause hepatic toxicity in cats, but this occurs very rarely. Reproductive/Nursing Safety Safe use during pregnancy has not been established; teratogenic effects of similar benzodiazepines have been noted 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. ) Benzodiazepines are excreted in maternal milk. Since neonates metabolize benzodiazepines more slowly than adults do, accumu-lation of the drug and its metabolites to toxic levels is possible. Chronic diazepam use in nursing mothers reportedly caused hu-man infants to be lethargic and lose weight; avoid the use of benzo-diazepines in nursing patients. Overdosage/Acute Toxicity When used alone, oxazepam overdoses are generally limited to sig-niﬁcant CNS depression (confusion, coma, decreased reﬂexes, etc. ). Treatment of signiﬁcant overdoses consists of standard protocols for removing and/or binding the drug (if taken orally) in the gut, and supportive systemic measures. The use of analeptic agents, (CNS stimulants such as caffeine, amphetamines, etc. ) are gener-ally not recommended. Flumazenil could potentially be used in life-threatening overdoses. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oxazepam and may be of signiﬁcance in veterinary patients: T ! CNS DEPRESSANT DRUGS : If oxazepam administered with other CNS depressant agents ( barbiturates, narcotics, anesthetics, etc. ) additive effects may occur T ! PHENYTOIN : May decrease oxazepam concentrations T ! PROBENECID : May impair glucuronide conjugation (in dogs) and prolong effects T ! RIFAMPIN : May induce hepatic microsomal enzymes and decrease the pharmacologic effects of benzodiazepines T ! ST. JOHN'S WORT : May decrease oxazepam effectiveness T ! THEOPHYLLINES : May decrease oxazepam effectiveness Laboratory Considerations T ! Benzodiazepines may decrease the thyroidal uptake of I123 or I131. Doses T ! DOGS: For treating fears and phobias: a) 0. 2-0. 5 mg/kg PO q12-24h (Siebert 2003c) b) 0. 2-1 mg/kg PO q12-24h (Virga 2002) c) 0. 2-1 mg/kg one to two times a day (Landsberg 2005b) T ! CATS: As an appetite stimulant: a) 2 mg per cat (total dose) every 12 hours (Hartke, Rojko et al. 1992), (Hodgkins and Franks 1991)	pppbs.pdf
676 OXFENDAZOLE b) In cats with hepatic lipidosis, if cat has a small interest in eat-ing: 0. 1-0. 3 mg/kg PO q12-24h (Twedt 2005c) c) 0. 25-0. 5 mg/kg PO one to two times daily. (Sparkes 2005) For behavior-related conditions: a) For treating fears and phobias: 1-2. 5 mg per cat (total dose) PO every 12 hours (Siebert 2003c) b) For treating fears and phobias 0. 2-0. 5 mg/kg PO q12-24h (Virga 2002) c) For feline urine marking: 0. 2-0. 5 mg/kg PO once to twice a day. (Landsberg 2007) d) For spraying or overgrooming: 0. 2-0. 5 mg/kg PO q12-24h (Seksel 2006) Monitoring T ! Efﬁcacy T ! Adverse effects Client Information T ! Caution clients not to discontinue medication or adjust dosage without ﬁrst checking with veterinarian. T ! Efﬁcacy for anorexia may be improved if given just prior to feed-ing as effects are generally seen within 30 minutes. Chemistry/Synonyms A benzodiazepine, oxazepam occurs as a creamy white to pale yel-low powder. It is practically insoluble in water. Oxazepam may also be known as: oxazepamum, Wy-3498, and Serax®. Storage/Stability/Compatibility Store oxazepam capsules and tablets at room temperature in well-closed containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Oxazepam Capsules: 10 mg, 15 mg & 30 mg; Serax® (Alpharma); ge-neric; (Rx; C-IV) Oxazepam Tablets: 15 mg; Serax® (Alpharma); (Rx; C-IV) OXFENDAZOLE (ox-fen-da-zole) Synanthic® ANTIPARASITIC AGENT (ANTHELMINTIC) Prescriber Highlights TT Benzimidazole anthelmintic used primarily in cattle TT Contraindications: Not for use in female dairy cattle of breeding age TT Caution: Debilitated or sick horses; 7 day slaughter with-drawal in cattle TT Adverse Effects: Unlikely; hypersensitivity possible Uses/Indications Oxfendazole (Synanthic®) is indicated in cattle for the removal and control of lungworms, roundworms (including inhibited forms of Ostertagia ostertagi) and tapeworms. Oxfendazole as Benzelmin® was indicated (no longer marketed in the USA) for the removal of the following parasites in horses: large roundworms (Parascaris equorum), large strongyles (S. eden-tatus, S. equinus, S. vulgaris), small strongyles, and pinworms (Oxyuris equi). Oxfendazole has also been used extra-label in sheep, goats, and swine; see Dosage section for more information. Pharmacology/Actions Benzimidazole antiparasitic agents have a broad spectrum of activ-ity against a variety of pathogenic internal parasites. In susceptible parasites, their mechanism of action is believed due to disrupting intracellular microtubular transport systems by binding selectively and damaging tubulin, preventing tubulin polymerization, and in-hibiting microtubule formation. Benzimidazoles also act at higher concentrations to disrupt metabolic pathways within the helminth, and inhibit metabolic enzymes, including malate dehydrogenase and fumarate reductase. Pharmacokinetics Limited information is available regarding this compound's phar-macokinetics. Unlike most of the other benzimidazole compounds, oxfendazole is absorbed more readily from the GI tract. The elimi-nation half-life has been reported to be about 7. 5 hours in sheep and 5. 25 hours in goats. Absorbed oxfendazole is metabolized (and vice-versa) to the active compound, fenbendazole (sulfoxide) and the sulfone. Contraindications/Precautions/Warnings Not for use in female dairy cattle of breeding age. A 7 day slaughter withdrawal is required when using at labeled doses. There are no contraindications to using this drug in horses, but it is recommended to use oxfendazole cautiously in debilitated or sick horses. Adverse Effects When used as labeled, it is unlikely any adverse effects will be noted. Hypersensitivity reactions secondary to antigen release by dying parasites are theoretically possible, particularly at high dosages. Reproductive/Nursing Safety Oxfendazole may be safely used in pregnant mares and foals. Overdosage/Acute Toxicity Doses of 10 times those recommended elicited no adverse reactions in horses tested. It is unlikely that this compound would cause seri-ous toxicity when given alone. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oxfendazole and may be of signiﬁcance in veterinary patients: T ! BROMSALAN FLUKICIDES (dibromsalan, tribromsalan ): Oxfendazole should not be given concurrently with these agents; abortions in cattle and death in sheep have been reported after using these compounds together	pppbs.pdf
OXIBENDAZOLE 677 Doses T ! DOGS: a) For Oslerus osleri: 10 mg/kg PO once daily for 28 days. (Bow-man 2006a) T ! HORSES: a) For susceptible parasites: 10 mg/kg PO (Roberson 1988b), (Package insert; Benzelmin®—Fort Dodge) T ! CATTLE: a) For susceptible parasites: 4. 5 mg/kg either PO or via intrar-uminal injection (22. 5% only). May repeat in 4-6 weeks. Dose of the 9. 06% suspension is 2. 5 m L per 100 lb (50 kg) of body weight PO. Dose of the 22. 5% suspension is 1 m L per 100 lb (50 kg) of body weight either PO or intraruminal injection. See package label for speciﬁc directions if giving by intraruminal injection. (Package inserts; Synanthic® 9. 06% and 22. 5%—Fort Dodge) T ! SWINE: a) For susceptible parasites: 3-4. 5 mg/kg PO (Roberson 1988b) T ! SHEEP: a) For susceptible parasites: 5 mg/kg PO (Roberson 1988b), (Brander, Pugh, and Bywater 1982) T ! GOATS: a) For susceptible parasites: 7. 5 mg/kg PO (Roberson 1988b) Monitoring T ! Efﬁcacy Client Information T ! Not to be used in horses intended for food purposes T ! Shake suspension well T ! Slaughter withdrawal in cattle is 7 days; not approved for lactat-ing dairy cattle Chemistry/Synonyms A benzimidazole anthelmintic, oxfendazole occurs as white or al-most white powder possessing a characteristic odor. It is practically insoluble in water. Oxfendazole is the sulfoxide metabolite of fen-bendazole. Oxfendazole may also be known as RS 8858; there are many in-ternational trade names. Storage/Stability Unless otherwise directed by the manufacturer, oxfendazole prod-ucts should be stored at room temperature and protected from light. The manufacturer recommends discarding any unused sus-pension 24 hours after it has been reconstituted. Dosage Forms/Preparations/Regulatory Status VETERINARY-LABELED PRODUCTS: Oxfendazole Oral Suspension: 9. 06% in 1 liter and 4 liter. Synanthic® (Fort Dodge); (OTC). Approved for use in beef cattle and in female dairy cattle not of breeding age. At recommended dosages, slaughter withdrawal is 7 days. Oxfendazole Oral Suspension: 22. 5% in 500 m L and 1 liter. Synan-thic® (Fort Dodge); (Rx). Approved for use in beef cattle and in female dairy cattle not of breeding age. At recommended dosages, slaughter withdrawal is 7 days. HUMAN-LABELED PRODUCTS: None OXIBENDAZOLE (ox-i-ben-da-zole) Anthelcide EQ® ANTIPARASITIC AGENT (ANTHELMINTIC) Prescriber Highlights TT Benzimidazole anthelmintic used primarily in horses TT Contraindications: Severely debilitated horses or in hors-es suffering from colic, toxemia or infectious disease. TT Adverse Effects: Unlikely; hypersensitivity possible Uses/Indications Oxibendazole is indicated (labeled) for the removal of the following parasites in horses: large roundworms (Parascaris equorum), large strongyles (S. edentatus, S. equinus, S. vulgaris), small strongyles, threadworms, and pinworms (Oxyuris equi). Oxibendazole has also been used in cattle, sheep, and swine; see Dosage section for more information. Pharmacology/Actions Benzimidazole antiparasitic agents have a broad spectrum of activ-ity against a variety of pathogenic internal parasites. In susceptible parasites, their mechanism of action is believed due to disrupting intracellular microtubular transport systems by binding selectively and damaging tubulin, preventing tubulin polymerization, and in-hibiting microtubule formation. Benzimidazoles also act at higher concentrations to disrupt metabolic pathways within the helminth, and inhibit metabolic enzymes, including malate dehydrogenase and fumarate reductase. Pharmacokinetics No information was located. Contraindications/Precautions/Warnings Oxibendazole is stated by the manufacturer to be contraindicated in severely debilitated horses or in horses suffering from colic, tox-emia, or infectious disease. Adverse Effects When used in horses at recommended doses, it is unlikely any ad-verse effects would be seen. Hypersensitivity reactions secondary to antigen release by dying parasites are theoretically possible, particu-larly at high dosages. Oxibendazole in combination with diethylcarbamazine (Filaribits Plus®) was implicated in causing periportal hepatitis in dogs when it was marketed (1980's). Reproductive/Nursing Safety Oxibendazole is considered safe to use in pregnant mares. Overdosage/Acute Toxicity Doses of 60 times those recommended elicited no adverse reactions in horses tested. It is unlikely that this compound would cause seri-ous toxicity when given alone to horses. Drug Interactions No signiﬁcant interactions have been reported	pppbs.pdf
678 OXYBUTYNIN CHLORIDE Doses T ! HORSES: For susceptible parasites: a) 10 mg/kg PO; 15 mg/kg PO for strongyloides; horses main-tained on premises where reinfection is likely to occur should be retreated in 6-8 weeks. (Package insert; Anthelcide EQ®— Pﬁzer) b) 10 mg/kg, PO (Robinson 1987), (Roberson 1988b) T ! CATTLE: For susceptible parasites: a) 10-20 mg/kg PO (Brander, Pugh, and Bywater 1982) T ! SWINE: For susceptible parasites: a) 15 mg/kg, PO (Roberson 1988b) T ! SHEEP: For susceptible parasites: a) 10-20 mg/kg PO (Brander, Pugh, and Bywater 1982) Monitoring T ! Efﬁcacy Client Information T ! Protect suspension from freezing T ! Shake suspension well before using T ! Not for use in horses intended for food Chemistry/Synonyms A benzimidazole anthelmintic, oxibendazole occurs as a white pow-der that is practically insoluble in water. Oxibendazole may also be known as SKF-30310 and Anthelcide EQ® and in the U. K. by the proprietary names: Dio® (Alan Hitchings), Equidin® (Univet), Equitac® (SKF) or Loditac® (SKF). Storage/Stability Unless otherwise directed by the manufacturer, oxibendazole prod-ucts should be stored at room temperature; protect from freezing. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Oxibendazole Suspension: 100 mg/m L (10%) in gallons. Anthelcide EQ® Suspension (Pﬁzer); (Rx). Approved for use in horses not used for food. Oxibendazole Oral Paste: 227 mg/gram (22. 7%) in 24-gram syringes. Anthelcide EQ® Paste (Pﬁzer); (OTC). Approved for use in horses not used for food. HUMAN-LABELED PRODUCTS: None OXYBUTYNIN CHLORIDE (ox-i-byoo-tin-in) Ditropan®, Oxytrol® GENITOURINARY SMOOTH MUSCLE RELAXANT Prescriber Highlights TT Urinary antispasmodic potentially useful in dogs or cats TT Cautions (risk vs. beneﬁt): Obstructive GI tract disease or intestinal atony/paralytic ileus, angle closure glaucoma, hiatal hernia, cardiac disease (particularly associated with mitral stenosis, associated arrhythmias, tachycardia, CHF, etc. ), myasthenia gravis, hyperthyroidism, prostatic hypertrophy, severe ulcerative colitis, urinary retention, or other obstructive uropathies TT Adverse Effects: Diarrhea, constipation, urinary retention, hypersalivation, & sedation Uses/Indications Oxybutynin may be useful for the adjunctive therapy of detrusor hyperreﬂexia in dogs and in cats with Fe LV-associated detrusor instability. Pharmacology/Actions Considered a urinary antispasmodic, oxybutynin has direct anti-muscarinic (atropine-like) and spasmolytic (papaverine-like) ef-fects on smooth muscle. Spasmolytic effects appear to be most pre-dominant on the detrusor muscle of the bladder and small and large intestine. It does not have appreciable effects on vascular smooth muscle. Studies done in patients with neurogenic bladders showed that oxybutynin increased bladder capacity, reduced the frequency of uninhibited contractions of the detrusor muscle and delayed ini-tial desire to void. Effects were more pronounced in patients with uninhibited neurogenic bladders than in patients with reﬂex neu-rogenic bladders. Other effects noted in lab animal studies include moderate antihistaminic, local anesthetic, mild analgesic, very low mydriatic, and antisialagogue effects. Pharmacokinetics Oxybutynin is apparently rapidly and well absorbed from the GI tract. Studies done in rats show the drug distributed into the brain, lungs, kidneys, and liver. While elimination characteristics have not been well documented, oxybutynin apparently is metabolized in the liver and excreted in the urine. In humans, the duration of ac-tion is from 6-10 hours after a dose. Contraindications/Precautions/Warnings Because of the drug's pharmacologic actions, oxybutynin should be used when its beneﬁts outweigh its risks if the following conditions are present: obstructive GI tract disease or intestinal atony/para-lytic ileus, angle closure glaucoma, hiatal hernia, cardiac disease (particularly associated with mitral stenosis, associated arrhyth-mias, tachycardia, CHF, etc. ), myasthenia gravis, hyperthyroidism, prostatic hypertrophy, severe ulcerative colitis, urinary retention or other obstructive uropathies. Adverse Effects While use in small animals is limited, diarrhea, constipation, uri-nary retention, hypersalivation, and sedation have been reported. Other adverse effects reported in humans, and potentially seen in animals, primarily result from the drug's pharmacologic effects, in-cluding: dry mouth or eyes, tachycardia, anorexia, vomiting, weak-ness, or mydriasis.	pppbs.pdf
OXYMORPHONE HCL 679 Reproductive/Nursing Safety While safety during pregnancy has not been ﬁrmly established, studies in a variety of lab animals have demonstrated no teratogen-ic effect associated with the drug. 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 demonstrat-ed a risk to the fetus in the ﬁrst trimester of pregnancy, and there is no evidence of risk in later trimesters. ) It is not known whether this drug is excreted in maternal milk. While oxybutynin may inhibit lactation, no documented problems associated with its use in nursing offspring have been noted. Overdosage/Acute Toxicity Overdosage may cause CNS effects (e. g., restlessness, excitement, seizures), cardiovascular effects (e. g., hyper-or hypotension, tachy-cardia, circulatory failure), fever, nausea or vomiting. Massive over-doses may lead to paralysis, coma, respiratory failure and death. Treatment of overdoses should consist of general techniques to limit absorption of the drug from the GI tract and supportive care as re-quired; intravenous physostigmine may be useful. See the atropine monograph for more information on the use of physostigmine. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oxybutynin and may be of signiﬁcance in veterinary patients: T ! ANTICHOLINERGIC AGENTS (e. g., atropine, propantheline, scopolamine, isopropamide, glycopyrrolate, hyoscyamine, tricyclic antidepressants, disopyramide, procainamide, antihistamines, etc. ): May intensify oxybutynin's anticholinergic effects T ! AZOLE ANTIFUNGALS (ketoconazole, etc. ): May increase oxybutynin levels T ! CNS DEPRESSANTS : Other sedating drugs may exacerbate the se-dating effects of oxybutynin T ! MACROLIDE ANTIBIOTICS (erythromycin, clarithromycin ): May increase oxybutynin levels Doses T ! DOGS: T o decrease bladder contractility (detrusor hyperreﬂexia): a) 0. 2 mg/kg PO q8-12h; most dogs are dosed at 1. 25-3. 75 mg (total dose) q12h. Juvenile animals may require a prolonged dosing interval. (Lane 2000) b) 1. 25-5 mg (total dose) PO q8-12h (Bartges 2003a) c) 2-5 mg (total dose) PO q8-12h (Vernau 2006) T ! CATS: T o decrease bladder contractility (detrusor hyperreﬂexia): a) 0. 5-1 mg (total dose) PO q8-12h. Juvenile animals may re-quire a prolonged dosing interval. (Lane 2000) b) 0. 5-1. 25 mg per cat PO q8-12h (Osborne, Kruger et al. 2000), (Bartges 2003a), (Polzin 2005c) Monitoring T ! Efﬁcacy T ! Adverse effects Chemistry/Synonyms A synthetic tertiary amine, oxybutynin chloride occurs as white to off-white crystals. It is freely soluble in water. Oxybutynin chloride may also be known as: oxybutinyn HCl, 5058, MJ-4309-1, oxybutynini hydrochloridum, Ditropan ® and Oxytrol ®. Storage/Stability Tablets and oral solution should be stored at room temperature in tight containers. Protect oral solution from light. Tablets have an expiration date of 4 years after manufacture. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Oxybutynin Chloride Tablets: 5 mg; Ditropan® (ALZA); (Rx); ge-neric; (Rx) Oxybutynin Chloride Extended release tablets: 5 mg, 10 mg and 15 mg; Ditropan® XL (ALZA); (Rx) Oxybutynin Chloride Syrup: 1 mg/m L in 473 m L; Ditropan® (ALZA); (Rx) Oxybutynin Chloride Transdermal System: 36 mg of oxybutynin delivering 3. 9 mg oxybutynin per day in 39 cm2 system; Oxytrol® (Watson); (Rx) OXYMORPHONE HCL (ox-ee-mor-fone) Numorphan® OPIATE A GONIST Prescriber Highlights TT Injectable opiate sedative/restraining agent, analgesic, & preanesthetic TT Contraindications: Hypersensitivity to it, diarrhea caused by a toxic ingestion. Extreme Caution: Respiratory dis-ease or acute respiratory dysfunction. Caution: Hypothy-roidism, severe renal insufﬁciency (acute uremia), adre-nocortical insufﬁciency, geriatric or severely debilitated patients, head injuries or increased intracranial pressure & acute abdominal conditions (e. g., colic). TT Adverse Effects: Respiratory depression & bradycardia. Decreased GI motility with resultant constipation pos-sible. Cats (high dosages): ataxia, hyperesthesia, & be-havioral changes (without concomitant tranquilization) TT Availability & expense are issues TT C-II controlled substance Uses/Indications Oxymorphone is used in dogs and cats as a sedative/restraining agent, analgesic, and preanesthetic; occasionally in horses as an analgesic and anesthesia induction agent. It may also be used in swine as an adjunctive analgesic with ketamine/xylazine anesthe-sia and small rodents as an analgesic/anesthetic for minor surgical procedures. Pharmacology/Actions Receptors for opiate analgesics are found in high concentrations in the limbic system, spinal cord, thalamus, hypothalamus, striatum, and midbrain. They are also found in tissues such as the gastroin-testinal tract, urinary tract, and other smooth muscle. The morphine-like agonists (morphine, meperidine, oxymor-phone) have primary activity at the mu receptors, with some activ-ity possible at the delta receptor. The primary pharmacologic effects of these agents include: analgesia, antitussive activity, respiratory depression, sedation, emesis, physical dependence, and intestinal	pppbs.pdf
680 OXYMORPHONE HCL effects (constipation/defecation). Secondary pharmacologic effects include: CNS: euphoria, sedation, and confusion. Cardiovascular: bradycardia due to central vagal stimulation, alpha-adrenergic receptors may be depressed resulting in peripheral vasodilation, decreased peripheral resistance, and baroreceptor inhibition. Orthostatic hypotension and syncope may occur. Urinary: Increased bladder sphincter tone can induce urinary retention. Various species may exhibit contradictory effects from these agents. For example, horses, cattle, swine, and cats may develop excitement after morphine injections and dogs may defecate after morphine. These effects are in contrast to the expected effects of sedation and constipation. Dogs and humans may develop mio-sis, while other species (especially cats) may develop mydriasis. For more information, see the individual monographs for each agent. Oxymorphone is approximately 10 times more potent an an-algesic on a per weight basis when compared to morphine. It has less antitussive activity than morphine. In humans, it has more of a tendency to cause increased nausea and vomiting than does mor-phine, while in dogs the opposite appears to be true. At the usual doses employed, oxymorphone alone has good sedative qualities in the dog. Respiratory depression can occur especially in debilitated, neonatal or geriatric patients. Bradycardia, as well as a slight de-crease in cardiac contractility and blood pressure, may also be seen. Like morphine, oxymorphone does initially increase the respira-tory rate (panting in dogs) while actual oxygenation may be de-creased and blood CO 2 levels may increase by 10 mm Hg or more. Oxymorphone may cause more panting in dogs than morphine. Gut motility is decreased with resultant increases in stomach emp-tying times. Unlike either morphine or meperidine, oxymorphone does not appear to cause histamine release when administered IV and may cause less excitement than morphine. Pharmacokinetics Oxymorphone is absorbed when given by IV, IM, SC, and rectal routes. Although absorbed when given orally, bioavailability is re-duced, probably from a high ﬁrst-pass effect. After IV administra-tion, analgesic efﬁcacy usually occurs within 3-5 minutes. Like morphine, oxymorphone concentrates in the kidney, liver, and lungs; lower levels are found in the CNS. Oxymorphone cross-es the placenta and narcotized newborns can result if mothers are given the drug before giving birth, but these effects can be rapidly reversed with naloxone. The drug is metabolized in the liver; primarily by glucuronida-tion. Because cats are deﬁcient in this metabolic pathway, half-lives in cats are probably prolonged. The kidneys excrete the glucuroni-dated metabolite. Contraindications/Precautions/Warnings All opiates should be used with caution in patients with hypo-thyroidism, severe renal insufﬁciency, adrenocortical insufﬁcien-cy (Addison's), and in geriatric or severely debilitated patients. Oxymorphone is contraindicated in patients hypersensitive to narcotic analgesics, those receiving monamine oxidase inhibitors (MAOIs), or with diarrhea caused by a toxic ingestion until the toxin is eliminated from the GI tract. Oxymorphone should be used with extreme caution in patients with head injuries, increased intracranial pressure or acute abdomi-nal conditions (e. g., colic) as it may obscure the diagnosis or clinical course of these conditions, and suffering from respiratory disease or from acute respiratory dysfunction (e. g., pulmonary edema sec-ondary to smoke inhalation). Oxymorphone can cause bradycardia and, therefore, should be used cautiously in patients with preexisting bradyarrhythmias. Neonatal, debilitated, or geriatric patients may be more suscep-tible to the effects of oxymorphone and may require lower dosages. Patients with severe hepatic disease may have prolonged duration's of action of the drug. If used in cats at high dosages, it is recommended the drug be given along with a tranquilizing agent as oxymorphone can produce bizarre behavioral changes in this species. This also is true in cats for the other opiate agents, such as morphine. Opiate analgesics are also contraindicated in patients who have been stung by the scorpion species Centruroides sculpturatus Ewing and C. gertschi Stahnke as it may potentiate these venoms. Adverse Effects Oxymorphone may cause respiratory depression and bradycardia (see above). When used in cats at high dosages, oxymorphone may cause ataxia, hyperesthesia, and behavioral changes (without con-comitant tranquilization). Decreased GI motility with resultant constipation has been described. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category C for use dur-ing pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as 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. ) Most opioids appear in maternal milk, but effects on offspring may not be signiﬁcant. Withdrawal symptoms have occurred in breastfeeding human infants when maternal administration of an opioid-analgesic is stopped. Overdosage/Acute Toxicity Massive overdoses may produce profound respiratory and/or CNS depression in most species. Other effects may include cardiovascu-lar collapse, hypothermia, and skeletal muscle hypotonia. Naloxone is the agent of choice in treating respiratory depression. In massive overdoses, naloxone doses may need to be repeated, and animals should be closely observed as naloxone's effects sometimes dimin-ish before sub-toxic levels of oxymorphone are attained. Mechanical respiratory support should be considered in cases of severe respira-tory depression. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oxymorphone and may be of signiﬁcance in veterinary patients: !TBUTORPHANOL, NALBUPHINE : Potentially could antagonize opiate effects !TCNS DEPRESSANTS, OTHER : Additive CNS effects possible !TDIURETICS : Opiates may decrease efﬁcacy in CHF patients !TMONOAMINE OXIDASE INHIBITORS (e. g., amitraz, possibly selegiline ): Use MAOI's with oxymorphone with extreme caution as meperi-dine (a related opiate) is contraindicated in human patients re-ceiving monamine oxidase (MAO) inhibitors for at least 14 days after receiving MAO inhibitors. Some human patients have ex-hibited signs of opiate overdose after receiving therapeutic doses of meperidine while taking MAOIs. !TMUSCLE RELAXANTS, SKELETAL : Oxymorphone may enhance effects !TPHENOTHIAZINES : Some phenothiazines may antagonize analgesic effects and increase risk for hypotension	pppbs.pdf
OXYMORPHONE HCL 681 !TTRICYCLIC ANTIDEPRESSANTS (clomipramine, amitriptyline, etc. ): Oxy-morphone may exacerbate the effects of tricyclic antidepressants !TWARFARIN : Opiates may potentiate anticoagulant activity Laboratory Considerations !TAs they may increase biliary tract pressure, opiates can increase plasma amylase and lipase values up to 24 hours following their administration. Doses !TDOGS: For sedation for minor procedures: a) Up to 0. 2 mg/kg IM or IV; initially a maximum of 5 mg total dose (Combine with acepromazine 0. 05-0. 1 mg/kg IM or IV) (Shaw et al. 1986) b) 0. 05-0. 1 mg/kg IV or 0. 1-0. 2 mg/kg IM, SC (Morgan 1988) For analgesia (acute pain): a) 0. 1-0. 2 mg/kg IM, IV, or SC q1-3h (Hendrix and Hansen 2000) b) For animals with cardiovascular disease: 0. 05-0. 1 mg/kg IV, IM or SC q2-4h (Hansen 2003a) c) Epidural administration: 0. 05 mg/kg. Dilution may be neces-sary for accurate measurement. T otal volume administered is not to exceed 0. 3 m L/kg. (Mathews 1999) d) 0. 1-0. 2 mg/kg IM or SC q3-4h for acute pain. (Gaynor 2007) e) 0. 05-0. 4 mg/kg IV, IM, or SC q2-4h (Wagner 2002) For premedication to anesthesia in healthy dogs: a) 0. 1-0. 2 mg/kg IM or IV (used with acepromazine and at-ropine or glycopyrrolate unless contraindicated. Thiopental/ thiamylal dose may be reduced to 2-4 mg/kg when using high end of oxymorphone dose). (Shaw et al. 1986) Induction of anesthesia in geriatric or sick dogs: a) 0. 1-0. 2 mg/kg IM or IV; give incrementally to effect (admin-istered alternately with diazepam at 0. 2-0. 5 mg/kg; use with atropine or glycopyrrolate unless contraindicated; follow with halothane, methoxyﬂurane or isoﬂurane) (Shaw et al. 1986) Facilitation of inhalation anesthesia without thiobarbiturates or ketamine in sight hounds: a) Up to 0. 2 mg/kg IV or IM (Combine with acepromazine; use with atropine or glycopyrrolate unless contraindicated) (Shaw et al. 1986) !TCATS: For restraint/sedation for minor procedures: a) 0. 05 mg/kg IV, SC or IM; may cause dysphoria in cats with-out pain or with excessive dose (Carroll 1999) b) 0. 025-0. 1 mg/kg IV (must be given with tranquilizer; e. g., acepromazine 0. 1 mg/kg) (Shaw et al. 1986) c) 0. 02-0. 03 mg/kg IV or IM with or without another tranquil-izer (Mandsager 1988) As a preanesthetic/analgesic: a) 0. 1-0. 4 mg/kg IV (Shaw et al. 1986) As an analgesic (acute pain): a) 0. 05-0. 1 mg/kg IM, SC or IV q1-3h; concomitant tranquil-ization recommended (Hendrix and Hansen 2000) b) For animals with cardiovascular disease: 0. 05-0. 1 mg/kg IV, IM or SC q2-4h (Hansen 2003a) c) 0. 025-0. 1 mg/kg IV (IM or SC) q2-6h (Scherk 2003a) d) 0. 02-0. 1 mg/kg IV, IM, or SC q3-4h (Wagner 2002) !TFERRETS: a) 0. 05-0. 2 mg/kg IV or IM 2-4 times daily (Williams 2000) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 0. 2 mg/kg IM q2-4h (Ivey and Morrisey 2000) b) Anesthetic/analgesic for minor surgical procedures: 0. 15 mg/ kg IM (for a hamster-sized animal) (Shaw et al. 1986) c) Hamsters, Gerbils, Mice, Rats, Guinea pigs: 0. 2-0. 5 mg/kg SC, IM q6-12h for analgesia (Adamcak and Otten 2000) !THORSES: (Note : ARCI UCGFS Class 1 Drug) As an analgesic: a) 0. 01-0. 02 mg/kg IV (Muir 1987) b) 0. 01-0. 022 mg/kg IV; up to 15 mg total (divide dose into 3-4 increments and give several minutes apart (Shaw et al. 1986) c) 0. 02-0. 03 mg/kg IM (Robinson 1987) d) 0. 015-0. 03 mg/kg IV (Thurmon and Benson 1987) Anesthetic induction in severely compromised horses: a) 0. 01-0. 022 mg/kg IV (after approx. 45 minutes, may be necessary to “top off ” with another 1/3 of the original dose) (Shaw et al. 1986) Note : Narcotics (oxymorphone included) may cause CNS excite-ment in the horse. Some clinicians recommend pretreatment with acepromazine (0. 02-0. 04 mg/kg IV), or xylazine (0. 3-0. 5 mg/kg IV) to reduce the behavioral changes these drugs can cause. Warning : Narcotic analgesics can mask the behavioral and cardio-vascular clinical signs associated with mild colic. !TSWINE: a) T o increase analgesia when used with ketamine (2 mg/kg)/ xylazine (2 mg/kg): 0. 075 mg/kg IV (duration of anesthesia and recumbency: 20-30 minutes) (Shaw et al. 1986) Monitoring !TRespiratory rate/depth !TCNS level of depression/excitation !TBlood pressure (especially with IV use) !TAnalgesic activity !TCardiac rate Client Information !TWhen given parenterally, this agent should be used in an inpa-tient setting or with direct professional supervision. Chemistry/Synonyms A semi-synthetic phenanthrene narcotic agonist, oxymorphone HCl occurs as odorless white crystals or white to off-white powder. It will darken in color with prolonged exposure to light. One gram of oxymorphone HCl is soluble in 4 m L of water; it is sparingly soluble in alcohol or ether. The commercially available injection has a p H of 2. 7-4. 5. Oxymorphone HCl may also be known as: 7,8-Dihydro-14-hy-droxymorphinone hydrochloride, or oximorphone hydrochloride, Numorphan® and Opana®. Storage/Stability/Compatibility The injection should be stored protected from light and at room temperature (15-30°C); avoid freezing. The commercially available suppositories should be stored at temperatures between 2-15°C. Oxymorphone has been reported to be physically compatible when mixed with acepromazine, atropine, and glycopyrrolate. It is physi-cally incompatible when mixed with barbiturates or diazepam.	pppbs.pdf
682 OXYTETRACYCLINE Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 1 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Oxymorphone HCl Tablets: 5 mg & 10 mg; Opana® (Endo Pharma-ceuticals); (Rx, C-II) Oxymorphone HCl Extended-Release Tablets: 5 mg, 10 mg, 20 mg & 40 mg; Opana® ER (Endo Pharmaceuticals); (Rx, C-II) Oxymorphone HCl for Injection: 1 mg/m L in 1 m L amps; Numor-phan® (Endo Laboratories); (Rx, C-II) Note : Oxymorphone is a Class-II controlled substance. Very accurate record keeping is required as to use and disposition of stock. OXYTETRACYCLINE OXYTETRACYCLINE HCL (ox-it-tet-ra-sye-kleen) Terramycin® TETRACYCLINE ANTIBIOTIC Prescriber Highlights TT Tetracycline antibiotic; while many bacteria are now re-sistant, it still may be very useful to treat mycoplasma, rickettsia, spirochetes, & Chlamydia TT Contraindications: Hypersensitivity. Extreme Caution: Pregnancy. Caution: Liver, renal insufﬁciency TT Adverse Effects: GI distress, staining of developing teeth & bones, superinfections, photosensitivity; long-term use may cause uroliths. CATS do not tolerate very well. HORSES: if stressed may break with diarrheas (oral use). RUMINANTS: high oral doses can cause ruminal microﬂora depression & ruminoreticular stasis. Rapid IV of undiluted propylene glycol-based products can cause intravascular hemolysis & cardiodepressant effects. IM: local reactions, yellow staining & necrosis may be seen at the injection site. Uses/Indications Oxytetracycline products are approved for use in dogs and cats (no known products are being marketed, however), calves, non-lactat-ing dairy cattle, beef cattle, swine, ﬁsh, and poultry. For more infor-mation, refer to the Doses section, below. Pharmacology/Actions T etracyclines generally act as bacteriostatic antibiotics and inhibit protein synthesis by reversibly binding to 30S ribosomal subunits of susceptible organisms, preventing binding to those ribosomes of aminoacyl transfer-RNA. T etracyclines also are believed to re-versibly bind to 50S ribosomes and additionally alter cytoplasmic membrane permeability in susceptible organisms. In high concen-trations, tetracyclines can also inhibit protein synthesis by mam-malian 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 tetracyclines have activity against some strains of staphylococci 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 activity 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 Pseudomonas aeruginosa show in vitro resistance to tetracyclines, those compounds attaining high urine levels (e. g., tetracycline, oxytetracycline) have been associated with clinical cures in dogs with UTI secondary to this organism. Oxytetracycline and tetracycline share nearly identical spec-trums of activity and patterns of cross-resistance. A tetracycline susceptibility disk is usually used for in vitro testing for oxytetracy-cline susceptibility. Pharmacokinetics Both oxytetracycline and tetracycline are readily absorbed after oral administration to fasting animals. Bioavailabilities are approximate-ly 60-80%. The presence of food or dairy products can signiﬁcant-ly reduce the amount of tetracycline absorbed, with reductions of 50% or more possible. After IM administration of oxytetracycline (not long-acting), peak levels may occur in 30 minutes to several hours, depending on the volume and site of injection. The long-acting product (LA-200®) has signiﬁcantly slower absorption after IM injection. T etracyclines as a class are widely distributed in the body, in-cluding to the heart, kidney, lungs, muscle, pleural ﬂuid, bronchial secretions, sputum, bile, saliva, urine, synovial ﬂuid, ascitic ﬂuid, and aqueous and vitreous humor. Only small quantities of tetracy-cline and oxytetracycline are distributed to the CSF and therapeutic levels may not be attainable. While all tetracyclines distribute to the prostate and eye, doxycycline or minocycline penetrate better into these and most other tissues. T etracyclines cross the placenta, en-ter fetal circulation and are distributed into milk. The volume of distribution of oxytetracycline is approximately 2. 1 L/kg in small animals, 1. 4 L/kg in horses, and 0. 8 L/kg in cattle. The amount of plasma protein binding is about 10-40% for oxytetracycline. Both oxytetracycline and tetracycline are eliminated unchanged primarily via glomerular ﬁltration. Patients with impaired renal function can have prolonged elimination half-lives and may accu-mulate the drug with repeated dosing. These drugs apparently are not metabolized, but are excreted into the GI tract via both biliary and nonbiliary routes and may become inactive after chelation with fecal materials. The elimination half-life of oxytetracycline is ap-proximately 4-6 hours in dogs and cats, 4. 3-9. 7 hours in cattle, 10. 5 hours in horses, 6. 7 hours in swine, and 3. 6 hours in sheep. Contraindications/Precautions/Warnings Oxytetracycline is contraindicated in patients hypersensitive to it or other tetracyclines. Because tetracyclines can retard fetal skeletal de-velopment and discolor deciduous teeth, they should only be used in the last half of pregnancy when the beneﬁts outweigh the fetal risks. Oxytetracycline and tetracycline are considered more likely to cause these abnormalities than either doxycycline or minocycline. In patients with renal insufﬁciency or hepatic impairment, oxytetracycline and tetracycline must be used cautiously. Lower than normal dosages are recommended with enhanced monitor-ing of renal and hepatic function. Avoid concurrent administra-tion of other nephrotoxic or hepatotoxic drugs with tetracyclines. Monitoring of serum levels should be considered if long-term ther-apy is required.	pppbs.pdf
OXYTETRACYCLINE 683 T TAdverse Effects Oxytetracycline and tetracycline given to young animals can cause a yellow, brown, or gray discoloration of bones and teeth. High dosages or chronic administration may delay bone growth and healing. T etracyclines in high levels can exert an antianabolic effect, which can cause an increase in BUN and/or hepatotoxicity, par-ticularly in patients with preexisting renal dysfunction. As renal function deteriorates secondary to drug accumulation, this effect may be exacerbated. In ruminants, high oral doses can cause ruminal microﬂora de-pression and ruminoreticular stasis. Rapid intravenous injection of undiluted propylene glycol-based products can cause intravascular hemolysis with resultant hemoglobinuria. Propylene glycol based products have also caused cardiodepressant effects when admin-istered to calves. When administered IM, local reactions, yellow staining, and necrosis may be seen at the injection site. In small animals, tetracyclines can cause nausea, vomiting, an-orexia, and diarrhea. Cats do not tolerate oral tetracycline or oxytet-racycline very well, and may present with clinical signs of colic, fever, hair loss, and depression. There are reports that long-term tetracycline use may cause urolith formation in dogs. Horses, who 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-susceptible bacteria or fungi. T etracyclines have also been associated with photosensitivity re-actions and, rarely, hepatotoxicity or blood dyscrasias. Reproductive/Nursing Safety In humans, the FDA categorizes this drug as category D for use dur-ing pregnancy (There is evidence of human fetal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: D (Contraindicated. These drugs have been shown to cause congenital malformations or embryotoxicity. ) T etracyclines are excreted in maternal milk. Milk to plasma ra-tios varies between 0. 25 to 1. 5. Because of the potential for serious adverse reactions, decide whether to discontinue nursing or discon-tinue the drug. Overdosage/Acute Toxicity T etracyclines are generally well tolerated after acute overdoses. Dogs given more than 400 mg/kg/day orally or 100 mg/kg/day IM of oxytetracycline did not demonstrate any toxicity. Oral overdoses would most likely be associated with GI disturbances (vomiting, anorexia, and/or diarrhea). Should the patient develop severe em-esis or diarrhea, ﬂuids and electrolytes should be monitored and replaced if necessary. Chronic overdoses may lead to drug accumu-lation and nephrotoxicity. High oral doses given to ruminants, can cause ruminal micro-ﬂora depression and ruminoreticular stasis. Rapid intravenous injection of undiluted propylene glycol-based products can cause intravascular hemolysis with resultant hemoglobinuria. Rapid intravenous injection of tetracyclines has induced tran-sient collapse and cardiac arrhythmias in several species, presum-ably due to chelation with intravascular calcium ions. Overdose quantities of drug could exacerbate this effect if given too rapidly IV. If the drug must be given rapidly IV (less than 5 minutes), some clinicians recommend pre-treating the animal with intravenous calcium gluconate. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oxytetracycline and may be of signiﬁcance in veterinary patients: !TATOVAQUONE : T etracyclines have caused decreased atovaquone levels !TBETA-LACTAM or AMINOGLYCOSIDE ANTIBIOTICS : Bacteriostatic drugs, like the tetracyclines, may interfere with bactericidal activity of the penicillins, cephalosporins, and aminoglycosides; there is some controversy regarding the actual clinical signiﬁcance of this interaction, however. !TDIGOXIN : T etracyclines may increase the bioavailability of digoxin in a small percentage of human patients and lead to digoxin tox-icity. These effects may persist for months after discontinuation of the tetracycline. !TDIVALENT OR TRIVALENT CATIONS (oral antacids, saline cathartics or other GI products containing aluminum, calcium, iron, magnesium, zinc, or bismuth cations ): When orally administered, tetracyclines can chelate divalent or trivalent cations that can decrease the ab-sorption of the tetracycline or the other drug if it contains these cations; it is recommended that all oral tetracyclines be given at least 1-2 hours before or after the cation-containing products. !TMETHOXYFLURANE : Fatal nephrotoxicity has occurred in humans when used with tetracycline; concomitant use with oxytetracy-cline is not recommended !TWARFARIN : T etracyclines may depress plasma prothrombin activ-ity and patients on anticoagulant) therapy may need dosage ad-justment Laboratory Considerations !Tetracyclines (not minocycline) may cause falsely elevated val-ues of urine catecholamines when using ﬂuorometric methods of determination. !Tetracyclines reportedly can cause false-positive urine glucose re-sults if using the cupric sulfate method of determination (Bene-dict's reagent, Clinitest®), but this may be the result of ascorbic acid, which is found in some parenteral formulations of tetra-cyclines. T etracyclines have also reportedly caused false-negative results in determining urine glucose when using the glucose oxi-dase method (Clinistix®, Tes-Tape®). Doses !TDOGS: For susceptible infections: a) For systemic infections: 22 mg/kg PO q8h for 7-14 days or 20 mg/kg IM (using repositol form) every 7 days as needed. (Greene, Hartmannn et al. 2006) b) 20 mg/kg PO q8-12h; (may give with food if GI upset oc-curs; avoid or reduce dose in animals with renal or severe liver failure; avoid in young, pregnant or breeding animals) (Vaden and Papich 1995) !TCATS: For susceptible infections: a) For hemotropic mycoplasmosis: 10-25 mg/kg PO, IV q8h for 5-7 days (Greene, Hartmannn et al. 2006) b) 20 mg/kg PO q8-12h; (may give with food if GI upset oc-curs; avoid or reduce dose in animals with renal or severe liver failure; avoid in young, pregnant or breeding animals) (Vaden and Papich 1995) c) For haemobartonellosis: 16-20 mg/kg PO three times daily for 3 weeks (Lissman 1988)	pppbs.pdf
684 OXYTETRACYCLINE !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 15 mg/kg SC, IM q8h; 15-50 mg/kg PO once daily; 1 mg/m L in drinking water (Ivey and Morrisey 2000) b) Chinchillas: 50 mg/kg PO q12h (Hayes 2000); (Adamcak and Otten 2000) c) Gerbils: 10 mg/kg PO q8h or 20 mg/kg SC q24h; Guinea Pigs: 50 mg/kg, PO q12h; Hamsters: 16 mg/kg, SC q24h; Mice : 10-20 mg/kg PO q8h; Rats: 10-20 mg/kg PO q8h or 6-10 mg/kg IM q12h (Adamcak and Otten 2000) !TCATTLE: For susceptible infections: a) 5-10 mg/kg IM q24h or 20 mg/kg q48-72h IM if depot form (LA ®-200); 2. 5-5 mg/kg, IV q24h; 10-20 mg/kg, PO q12h (Jenkins 1986) b) For respiratory tract infections: Using 50 mg/m L product: 11 mg/kg IM or SC q24h or IV q12-24h; Using 100 mg/m L, product: 20 mg/kg IM q24h; Using 200 mg/m L, product (LA-200®): 20 mg/kg IM q3-4 days; IM or SC doses should be injected into the neck and not more than 10 m L per site. IM route may lead to myositis and abscesses. Rapid IV injection may cause collapse. Phlebitis is possible with IV dosing. (Beech 1987b) c) For anthrax: 4. 4 mg/kg IM or IV daily. Do not use in healthy animals recently vaccinated against anthrax as the protective effect of the vaccine may be negated. (Kaufmann 1986) d) For bovine anaplasmosis: For control: At start of vector season give 6. 6-11 mg/kg (if using 50 mg/m L or 100 mg/m L product) or 20 mg/kg (if us-ing depot form —LA ®-200) every 21-28 days and extending 1-2 months after vector season ends. T o eliminate carrier state: If using 50 mg/m L or 100 mg/m L product: 22 mg/kg IM (not over 10 m L per injection site) or IV (diluted in saline) daily for 5 days; or 11 mg/kg as above for 10 days. If using depot form (LA ®-200): Give 20 mg/kg for 4 treatments deep IM in two separate injection sites at 3-day intervals. For treatment of sick animals: Preferably using depot form (LA®-200): Give 20 mg/kg one time. For temporary/prolonged protection for rest of herd: If using 50 mg/m L or 100 mg/m L product: 6. 6-11 mg/kg IM (not over 10 m L per injection site) repeat at 21-28 day intervals throughout vector season for prolonged protection. If us-ing depot form (LA ®-200): Give 20 mg/kg IM as above and repeat at 28-day intervals for prolonged protection. (Richey 1986) e) For pneumonia: If using 50 mg/m L or 100 mg/m L product: 11 mg/kg SC once daily. If using depot form (LA ®-200): Give 20 mg/kg IM q48h (Hjerpe 1986) !THORSES: For susceptible infections: a) Foals: 5-10 mg/kg IV q12h diluted and given slowly, or 10-20 mg/kg IV q24h diluted and given slowly. Monitor creatinine and UA. (Bentz 2007) b) Drug of choice for equine monocytic or granulocytic ehrli-chiosis: 6. 6 mg/kg IV q24h; to safeguard against adverse ef-fects (muscle tremors, agitation or acute collapse) dilute at least in a 1:1 ratio and give IV slowly, or deliver it as an infu-sion in 500 m L or 1 liter of ﬂuids. (Bentz 2007) c) For Lyme disease: 6. 6 mg/kg IV once to twice daily (Divers 1999) d) For Potomac Horse Fever (Ehrlichia risticii) early in the clini-cal course of the disease: 6. 6 mg/kg IV twice a day. Usually no more than 5 days treatment is necessary. For Equine Granulocytic Ehrlichiosis: 7 mg/kg once daily for 5-7 days (Madigan and Pusterla 2000) e) For intrauterine infusion: 1-5 grams; use povidone based products only. Little science is available for recommending doses, volume infused, frequency, diluents, etc. Most intra-uterine treatments are commonly performed every day or every other day for 3-7 days. (Perkins 1999) !TSWINE: For susceptible infections: a) For anthrax: 4. 4 mg/kg IM or IV daily. Do not use in healthy animals recently vaccinated against anthrax as the protective effect of the vaccine may be negated. (Kaufmann 1986) b) 6-11 mg/kg IV or IM; 10-20 mg/kg PO q6h (Howard 1986) c) If using 50 mg/m L or 100 mg/m L product: 10 mg/kg IM ini-tially, then 7. 5 mg/kg IM once daily (Baggot 1983) !TSHEEP & GOATS: For susceptible infections: a) For anthrax: 4. 4 mg/kg IM or IV daily. Do not use in healthy animals recently vaccinated against anthrax as the protective effect of the vaccine may be negated. (Kaufmann 1986) b) 6-11 mg/kg IV or IM; 10-20 mg/kg PO q6h (Howard 1986) !TBIRDS: For chlamydiosis (Psittacosis): a) Using 200 mg/m L product (LA-200®): 50 mg/kg IM once ev-ery 3-5 days in birds suspected or conﬁrmed of having dis-ease. Used in conjunction with other forms of tetracyclines. IM injections may cause severe local tissue reactions. (Mc-Donald 1989) b) Using 200 mg/m L, product (LA-200®): 200 mg/kg IM once daily for 3-5 days. Has worked well in treating breeding birds to control outbreak and while getting birds to eat oral forms doxycycline or chlortetracycline. (Clubb 1986) !TREPTILES: For susceptible infections: a) For turtles and tortoises: 10 mg/kg PO once daily for 7 days (useful in ulcerative stomatitis caused by Vibrio) (Gauvin 1993) Monitoring !TAdverse effects !TClinical efﬁcacy !TLong-term use or in susceptible patients: periodic renal, hepatic, hematologic evaluations Client Information !TAvoid giving this drug orally within 1-2 hours of feeding, milk, or other dairy products Chemistry/Synonyms A tetracycline derivative obtained from Streptomyces rimosus, oxytetracycline base occurs as a pale yellow to tan, crystalline pow-der that is very slightly soluble in water and sparingly soluble in alcohol. Oxytetracycline HCl occurs as a bitter-tasting, hygroscopic, yellow, crystalline powder that is freely soluble in water and spar-ingly soluble in alcohol. Commercially available 50 mg/m L and 100 mg/m L oxytetracycline HCl injections are usually available in ei-ther propylene glycol or povidone-based products.	pppbs.pdf
OXYTOCIN 685 Oxytetracycline may also be known as: glomycin, hydroxytet-racycline, oxytetracyclinum, riomitsin, terrafungine, Biomycin®, Liquamycin®, Medamycin®, Oxyject®, Oxytet®, and Terramycin®. Storage/Stability/Compatibility Unless otherwise directed by the manufacturer, oxytetracycline HCl and oxytetracycline products should be stored in tight, light-resistant containers at temperatures of less than 40°C (104°F) and preferably at room temperature (15-30°C); avoid freezing. Oxytetracycline HCl is generally considered to be physically com-patible with most commonly used IV infusion solutions, including D5W, sodium chloride 0. 9%, and lactated Ringer's, but can become relatively unstable in solutions with a p H >6, particularly in those containing calcium. This is apparently more of a problem with the veterinary injections that are propylene glycol based, rather than those that are povidone based. Other drugs that are reported to be physically compatible with oxytetracycline for injection include: colistimethate sodium, corticotropin, dimenhydrinate, insulin (regular), isoproterenol HCl, methyldopate HCl, norepinephrine bitartrate, polymyxin B sulfate, potassium chloride, tetracycline HCl, and vitamin B-complex with C. Drugs that are reportedly physically incompatible with oxytet-racycline, data conﬂicts, or compatibility is concentration/time dependent, include: amikacin sulfate, aminophylline, amphoteri-cin B, calcium chloride/gluconate, carbenicillin disodium, cepha-lothin sodium, cephapirin sodium, chloramphenicol sodium suc-cinate, erythromycin gluceptate, heparin sodium, hydrocortisone sodium succinate, iron dextran, methicillin sodium, methohexital sodium, oxacillin sodium, penicillin G potassium/sodium, pento-barbital sodium, phenobarbital sodium, and sodium bicarbonate. 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 information. Dosage Forms/Regulatory Status/Withdrawal Times VETERINARY-LABELED PRODUCTS: Oxytetracycline HCl 50 mg/m L, 100 mg/m L Injection: There are many approved oxytetracycline products marketed in these concen-trations. Some trade names for these products include: Terramycin®, Liquamycin®, Biomycin® (Bio-Ceutic), Medamycin® (T ech America), Biocyl® (Anthony), Oxyject® (Fermenta), and Oxytet® (BI). Some are labeled for Rx (prescription) use only, while some are over-the-coun-ter (OTC). Depending on the actual product, this drug may be ap-proved for use in swine, cattle, beef cattle, chickens or turkeys. Prod-ucts may also be labeled for IV, IM, or SC use. Withdrawal times vary with regard to individual products; when used as labeled, slaughter withdrawal times vary in cattle from 15-22 days, swine 20-26 days, and 5 days for chickens and turkeys. Refer to the actual labeled infor-mation for the product used for more information. Oxytetracycline base 200 mg/m L Injection in 100, 250, and 500 m L bottles; Liquamycin® LA-200 (Pﬁzer); (OTC or Rx). Approved for use in swine and cattle. When used as labeled, slaughter withdrawal = 28 days for swine and cattle; Milk withdrawal = 96 hours Oxytetracycline Oral Tablets (Boluses) 250 mg tablet; Terramycin ® Scours T ablets (Pﬁzer); (OTC). Approved for use in non-lactating dairy and beef cattle. Slaughter withdrawal (at labeled doses) = 7 days. Oxytetracycline is also available in feed additive, premix, ophthalmic, and intramammary products. Established residue tolerances: Uncooked edible tissues of swine, cattle, salmonids, catﬁsh and lobsters: 0. 10 ppm. Uncooked kidneys of chickens or turkeys: 3 ppm. Uncooked muscle, liver, fat or skin of chickens or turkeys: 1 ppm. HUMAN-LABELED PRODUCTS: Oxytetracycline For Injection: 50 mg/m L or 125 mg/m L (both with 2% lidocaine) in 2 m L amps and 10 m L multidose vials (125 mg/m L only); Terramycin® (Roerig/Pﬁzer); (Rx) OXYTOCIN (ox-i-toe-sin) Pitocin® HORMONAL AGENT Prescriber Highlights TT Hypothalamic hormone used for induction or enhance-ment of uterine contractions at parturition, postpar-tum retained placenta & metritis, uterine involution after manual correction of prolapsed uterus in dogs, & agalactia. TT Contraindications: Known hypersensitivity, dystocia due to abnormal presentation of fetus(es) unless correction is made. When used prepartum, oxytocin should be used only when the cervix is relaxed naturally or by the prior administration of estrogens. TT Treat hypoglycemia or hypocalcemia before using TT Adverse Effects: Usually occur only when used in inappro-priate patients or at too high a dosage. TT Drug Interactions Uses/Indications In veterinary medicine, oxytocin has been used for induction or enhancement of uterine contractions at parturition, treatment of postpartum retained placenta and metritis, uterine involution af-ter manual correction of prolapsed uterus in dogs, and in treating agalactia. Pharmacology/Actions By increasing the sodium permeability of uterine myoﬁbrils, oxy-tocin stimulates uterine contraction. The threshold for oxytocin-induced uterine contraction is reduced with pregnancy duration, in the presence of high estrogen levels and in patients already in labor. Oxytocin can facilitate milk ejection, but does not have any ga-lactopoietic properties. While oxytocin only has minimal antidi-uretic properties, water intoxication can occur if it is administered at too rapid a rate and/or if excessively large volumes of electrolyte-free intravenous ﬂuids are administered. Pharmacokinetics Oxytocin is destroyed in the GI tract and, therefore, must be admin-istered parenterally. After IV administration, uterine response oc-curs almost immediately. Following IM administration, the uterus responds generally within 3-5 minutes. The duration of effect in dogs after IV or IM/SC administration has been reported to be 13 minutes and 20 minutes, respectively. While oxytocin can be admin-istered intranasally, absorption can be erratic. Oxytocin is distribut-ed throughout the extracellular ﬂuid. It is believed that small quanti-ties of the drug cross the placenta and enter the fetal circulation.	pppbs.pdf
686 OXYTOCIN In humans, plasma half-life of oxytocin is about 3-5 minutes. In goats, this value has been reported to be about 22 minutes. Oxytocin is metabolized rapidly in the liver and kidneys and a cir-culating enzyme, oxytocinase can also destroy the hormone. Very small amounts of oxytocin are excreted in the urine unchanged. Contraindications/Precautions/Warnings Oxytocin is considered contraindicated in animals with dystocia due to abnormal presentation of fetus(es), unless correction is made. When used prepartum, oxytocin should be used only when the cervix is relaxed naturally or by the prior administration of es-trogens ( Note : Most clinicians avoid the use of estrogens, as natu-ral relaxation is a better indicator for the proper time to induce contractions. ) Oxytocin is also contraindicated in patients who are hypersensitive to it. Before using oxytocin, treat hypoglycemia or hypocalcemia if present. In humans, oxytocin is contraindicated in patients with signiﬁ-cant cephalopelvic disproportion, unfavorable fetal positions, in obstetrical emergencies when surgical intervention is warranted, severe toxemia, or when vaginal delivery is contraindicated. Nasally administered oxytocin is contraindicated in pregnancy. Adverse Effects When used appropriately at reasonable dosages, oxytocin rarely causes signiﬁcant adverse reactions. Most adverse effects are a result of using the drug in inappropriate individuals (adequate physical exam and monitoring of patient are essential) or at too high doses (see Overdosage below). Most of the older dosage recommenda-tions for dogs or cats are obsolete as mini doses have been found to improve the frequency of uterine contractility, and are less haz-ardous to the bitch (uterine rupture) and to the fetuses (placental compromise). Hypersensitivity reactions are a possibility in non-synthetically produced products. Repeated bolus injections of oxy-tocin may cause uterine cramping and discomfort. Overdosage/Acute Toxicity Effects of overdosage on the uterus depend on the stage of the uter-us and the position of the fetus(es). Hypertonic or tetanic contrac-tions can occur leading to tumultuous labor, uterine rupture, fetal injury, or death. Water intoxication can occur if large doses are infused for a long period, especially if large volumes of electrolyte-free intra-venous ﬂuids are concomitantly being administered. Early clinical signs can include listlessness or depression. More severe intoxica-tion clinical signs can include coma, seizures and eventually death. Treatment for mild water intoxication is stopping oxytocin therapy and restricting water access until resolved. Severe intoxication may require the use of osmotic diuretics (mannitol, urea, dextrose) with or without furosemide. Reproductive/Nursing Safety In humans, oxytocin is contraindicated in patients with signiﬁcant cephalopelvic disproportion, unfavorable fetal positions, in obstet-rical emergencies when surgical intervention is warranted, severe toxemia, or when vaginal delivery is contraindicated. Nasally ad-ministered oxytocin is contraindicated in pregnancy. No known indications for use in the ﬁrst trimester exist other than in relation to spontaneous or induced abortion. Oxytocin is not expected to present a risk of fetal abnormalities when use as indicated. Oxytocin may be found in small quantities in maternal milk but is unlikely to have signiﬁcant effects. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving oxytocin and may be of signiﬁcance in veterinary patients: !TTHIOPENTAL : One case in humans has been reported where thio-pental anesthesia was delayed when oxytocin was being admin-istered. The clinical signiﬁcance of this interaction has not been ﬁrmly established. !TVASOCONSTRICTORS : If sympathomimetic agents or other vaso-constrictors are used concurrently with oxytocin post-partum hypertension may result. Monitor and treat if necessary. Doses !TDOGS: T o augment uterine contractions during parturition: a) 0. 5-3 Units SC or IM every 30-60 minutes, best based upon the results of tokodynamometry. (Davidson 2004b) For uterine inertia if no fetuses in birth canal, cervix is dilated, and fetal and maternal obstruction have been ruled out: a) Oxytocin at 5-20 Units (depending on size of animal) IM or as an IV drip (10 Units/liter) beginning as a slow drip and gradually increasing until effective contractions are ob-served. If no response to IM injection in 30 minutes, may re-peat along with 10% dextrose IV slowly. If no response again in 30 minutes, repeat IM again. Some texts recommend giv-ing calcium gluconate (2-10 m L slowly IV while monitoring ECG for bradycardia or arrhythmias). If no response to this medical management, perform Caesarian section. (Macintire 2006e) T o induce milk let-down in bitches with adequate milk produc-tion and who tolerate nursing: a) Oxytocin nasal spray (Syntocinon®): 5-10 minutes prior to nursing three times daily (Loar 1988) For adjunctive treatment of acute metritis: a) T o promote uterine involution and evacuation: 0. 5-1 Unit/ kg IM; may repeat in 1-2 hours. It's less effective if parturi-tion occurred several days ago. (Magne 1986) T o promote uterine involution after uterine prolapse manual reduction: a) 5-20 Units IM (Nelson 1988) !TCATS: T o promote uterine involution after uterine prolapse manual reduction: a) 5 Units IM once (Morgan 1988) T o treat primary uterine inertia: a) 0. 25-1 unit SC or IM every 30-60 minutes, best based upon the results of tokodynamometry (Davidson 2004b) !TRABBITS, RODENTS, SMALL MAMMALS: a) Mice, Rats, Gerbils, Hamsters, Guinea pigs, Chinchillas: 0. 2-3 IU/kg IV, IM or SC (Adamcak and Otten 2000) !TCATTLE: For retained placenta in patients a) 40-60 Units oxytocin q2h (often used in conjunction with intravenous calcium therapy) as necessary. Of limited value after 48 hours postpartum as uterine sensitivity is reduced. (Mc Clary 1986) b) T o reduce incidence of retained placenta: 20 Units IM im-mediately following calving and repeated 2-4 hours later (Hameida, Gustafsson, and Whitmore 1986) For mild to moderate cases of acute post-partum metritis: a) 20 Units IM 3-4 times a day for 2-3 days (Hameida, Gustafs-son, and Whitmore 1986)	pppbs.pdf
OXYTOCIN 687 T o augment uterine contractions during parturition: a) 30 Units IM; repeat no sooner than 30 minutes if necessary (Wheaton 1989) b) For obstetrical use in cows: 100 Units IV, IM or SC (Package Insert; Oxytocin Injection—Anthony Products) For milk let-down in cows: a) 10-20 Units IV (Package Insert; Oxytocin Injection—An-thony Products) !THORSES: T o augment or initiate uterine contractions during parturition in properly evaluated mares: a) For induction: 2. 5-5 IU IV, every 15-20 minutes until foal is born (Mc Cue 2003a) For evacuation of uterine ﬂuid: a) 20 IU IV or IM one to three times a day (Mc Cue 2003a) T o aid in removal of retained fetal membranes: a) Oxytocin: 30-100 Units in 1 liter of normal saline IV over 30-60 minutes or 10-120 IU IM or 10-40 IU by IV bolus ( Note : large dose IV boluses are not recommended as they may cause uterine spasm and abdominal discomfort) (Per-kins 1999) b) Oxytocin: 20 IU IV or IM given every hour beginning 2-3 hours after foaling. Repeat as needed. (Mc Cue 2003a) For mild to moderate cases of acute post-partum metritis: a) 20 Units IM 3-4 times a day for 2-3 days (Hameida, Gustafs-son, and Whitmore 1986) !TSWINE: For adjunctive treatment of agalactia syndrome (MMA) in sows: a) 30-40 Units per sow at 3-4 hours (Powe 1986) b) 20-50 Units IM or 5-10 Units IV (Einarsson 1986) For retained placenta in patients with uterine atony: a) 20-30 Units oxytocin q2-3h as necessary (with broad-spec-trum antibiotics) (Mc Clary 1986) T o augment uterine contractions during parturition: a) 10 Units IM; repeat no sooner than 30 minutes if necessary (Wheaton 1989) b) For obstetrical use in sows: 30-50 Units IV, IM or SC (Pack-age Insert; Oxytocin Injection—Anthony Products) For mild to moderate cases of acute post-partum metritis: a) 5-10 Units IM 3-4 times a day for 2-3 days (Hameida, Gustafsson, and Whitmore 1986) b) 5 Units IM; may need to be repeated as effect may be as short as 30 minutes (Meredith 1986) For milk let-down in sows: a) 5-20 Units IV (Package Insert; Oxytocin Injection—Antho-ny Products) !TSHEEP & GOATS: For retained placenta in patients with uterine atony: a) 10-20 Units oxytocin. Of limited value after 48 hours post-partum as uterine sensitivity is reduced. If signs of metritis develop, treat with antibiotics. (Mc Clary 1986) For mild to moderate cases of acute post-partum metritis: a) 5-10 Units IM 3-4 times a day for 2-3 days (Hameida, Gustafsson, and Whitmore 1986) T o control post-extraction cervical and uterine bleeding after in-ternal manipulations (e. g., fetotomy, etc. ): a) Goats: 10-20 Units IV, may repeat SC in 2 hours (Franklin 1986a) !TBIRDS: As a uterotonic agent: a) 0. 5 IU/kg IM; may repeat in 60 minutes (Pollock 2007b) For egg expulsion: a) 0. 01-0. 1 m L once IM. Should be administered with Vitamin A and calcium (injectable) (Clubb 1986) !TREPTILES: For egg binding in combination with calcium (Calcium glubionate: a) Calcium glubionate (10-50 mg/kg IM as needed until cal-cium levels back to normal or egg binding is resolved); oxy-tocin: 1-10 IU/kg IM. Use care when giving multiple injec-tions. Not as effective in lizards as in other species. (Gauvin 1993) T o induce oviposition: a) Doses range from 1-30 IU/kg. A dose of 10 IU/kg appears to be effective in many chelonians. May have to repeat in sev-eral hours, but there is a risk of oviduct rupture if cloaca is obstructed or eggs cannot pass for other reasons. (Lewbart 2001) Monitoring !TUterine contractions, status of cervix !TFetal monitoring if available and indicated Client Information !TOxytocin should only be used by individuals able to adequately monitor its effects. Chemistry/Synonyms A nonapeptide hypothalamic hormone stored in the posterior pituitary (in mammals), oxytocin occurs as a white powder that is soluble in water. The commercially available preparations are highly puriﬁed and have virtually no antidiuretic or vasopressor activity when administered at usual doses. Oxytocin potency is standardized according to its vasopressor activity in chickens and is expressed in USP Posterior Pituitary Units. One unit is equivalent of approximately 2-2. 2 micrograms of pure hormone. Commercial preparations of oxytocin injection have their p H adjusted with acetic acid to 2. 5-4. 5 and multi-dose vials generally contain chlorobutanol 0. 5% as a preservative. Oxytocin may also be known as: alpha-hypophamine, or oxy-tocinum and Pitocin®. Storage/Stability/Compatibility Oxytocin injection should be stored at temperatures of less than 25°C, but should not be frozen. Some manufacturers recommend storing the product under refrigeration (2-8°C), but some prod-ucts have been demonstrated to be stable for up to 5 years if stored at less than 26°C. Oxytocin is reportedly physically compatible with most com-monly used intravenous ﬂuids and the following drugs: chloram-phenicol sodium succinate, metaraminol bitartrate, netilmicin sul-fate, sodium bicarbonate, tetracycline HCl, thiopental sodium, and verapamil HCl. Oxytocin is reportedly physically incompatible with the following drugs: ﬁbrinolysin, norepinephrine bitartrate, prochlorperazine edisylate, and warfarin sodium. 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.	pppbs.pdf
688 PAMIDRONATE DISODIUM Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Oxytocin for Injection: 20 USP Units/m L in 10 m L, 30 m L, and 100 m L vials; available labeled generically from several manufacturers; (Rx). Oxytocin products are labeled for several species, including horses, dairy cattle, beef cattle, sheep, swine, cats, and dogs. There are no milk or meat withdrawal times speciﬁed for oxytocin. HUMAN-LABELED PRODUCTS: Oxytocin for Injection: 10 Units/m L in 1 m L amps, 3 m L and 10 m L vials; 1 m L Steri-Dose syringes and 1 m L Steri-Vials; Pitocin® (Mon-arch); generic; (Rx) PAMIDRONATE DISODIUM (pah-mih-dro-nate) Aredia® BISPHOSPHONATE Prescriber Highlights TT Bisphosphonate used IV for treating hypercalcemia as-sociated with Vitamin D-analog toxicity or hypercalcemia of malignancy; being investigated for adjuvant treatment of osteosarcomas TT Must be given IV in saline over several hours TT Potentially can cause electrolyte abnormalities, anemias, or renal toxicity TT Expense may be an issue Uses/Indications Pamidronate may be useful in treating hypercalcemia associated with vitamin D-related toxicoses or hypercalcemia of malignancy. There is ongoing research on the use of this drug to determine if it has clinical usefulness in directly treating “micro-metastases” in osteosarcomas. Pharmacology/Actions Bisphosphonates at therapeutic levels inhibit bone resorption and do not inhibit bone mineralization via binding to hydroxyapatite crystals. They impede osteoclast activity, and induce osteoclast apoptosis. Pamidronate has approximately 100 times greater rela-tive antiresorptive potency when compared to etidronate. Bisphosphonates in vitro have direct cytotoxic or cytostatic ef-fects on human osteosarcoma cell lines. They may also have antian-giogenic effects and inhibit cell migration in certain cancers. Pharmacokinetics After intravenous infusion in rats, 50-60% of the dose is rapidly absorbed by bone. Bone uptake is highest in areas of rapid bone turnover. The kidneys very slowly eliminate the drug. T erminal half-life is on the order of 300 days in rats. Contraindications/Precautions/Warnings Pamidronate is contraindicated in patients hypersensitive to it or any of the bisphosphonate drugs. It should be used with caution in patients with impaired renal function; the drug has been associated with renal toxicity. In humans, it has not been tested in patients with serum creatinine levels greater than 5 mg/dl. Adverse Effects Electrolyte abnormalities may occur with pamidronate therapy. One case of a dog developing hypomagnesemia and arrhythmias after pamidronate has been reported (Kadar, Rush et al. 2004). Pamidronate may cause renal toxicity in dogs, but it is thought this can be minimized or avoided by infusing the drug over at least 2 hours. Anemia, thrombocytopenia and granulocytosis have been reported in humans. Reproductive/Nursing Safety In pregnant humans, the FDA as a category D drug (There is evi-dence of human fetal risk, but the potential beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Pamidronate has produced both maternal and embryo/fetal toxicity in laboratory animals when given at dosages therapeutically used in human patients. If it is used in pregnant veterinary patients, informed consent by the owner accepting the risks to both mother and offspring is recommended. It is unknown if pamidronate is excreted into milk. Use with caution in nursing mothers. Overdosage/Acute Toxicity Overdosage of pamidronate may cause hypocalcemia, including tet-any. Should this occur, treat with short-term, intravenous calcium. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pamidronate and may be of signiﬁcance in veterinary patients: T ! CALCIUM-AFFECTING D RUGS (e. g., furosemide, corticosteroids ): Pamidronate must be used carefully (with monitoring) when used in conjunction with other drugs that can affect calcium T ! NEPHROTOXIC DRUGS (e. g., cisplatin, aminoglycosides ): Use with caution, potential for increased risk for nephrotoxicity Laboratory Considerations No speciﬁc laboratory interactions or considerations noted. Doses T ! DOGS: a) For refractory hypercalc emia: 1 mg/kg IV given over 2 hours in 250 m L of normal saline every 4 weeks. (Chun 2007c) b) For control of hypercalcemia: Treat each patient individually and if possible remove the underlying cause. If parenteral sa-line, furosemide and corticosteroids do not resolve the issue then bisphosphonates can be considered for more chronic control of hypercalcemia. Pamidronate 1. 3-2 mg/kg in 150 m L of 0. 9% saline with a 2 hour IV infusion; can repeat in 1-3 weeks. (Chew, Schenck et al. 2003) c) For treatment of cholecalciferol-induced toxicosis: 0. 65-2 mg/kg in 0. 9% Na Cl on days 1 and 4 post-ingestion (Rum-beiha, Fitzgerald et al. 2000) d) For attempting to reduce bone pain associated with osteosar-coma in combination with an NSAID: 1-2 mg/kg; diluted into 250 m L of 0. 9% sodium chloride and administered as a CRI over 2 hours every 28 days. (Fan and de Lorimier 2003), (Fan, de Lorimier et al. 2007) e) For calcipotriene toxicosis: 1. 3-2 mg/kg slow IV infusion. In most cases, a single dose will lower calcium levels back to normal levels. Recommended to monitor calcium levels daily for at least 10 days after they have returned to normal. (Gwaltney-Brant 2003) T ! CATS: a) For control of hypercalcemia: 1. 5-2 mg/kg IV (from a retro-spective study of 2 cats). (Hostutler, Chew et al. 2005)	pppbs.pdf
PANCRELIPASE 689 TMonitoring T ! Renal function (serum creatinine, etc. ) and hydration status should be monitored before treating and prior to each dose T ! Serum calcium, phosphate, magnesium, potassium T ! CBC; baseline and continued if ongoing treatment T ! Urinalysis Client Information T ! he medication must be given in an inpatient setting. T ! Clients should understand the costs for the medication, care, and monitoring associated with its use. Chemistry/Synonyms Pamidronate disodium a bisphosphonate inhibitor of bone resorp-tion occurs as a white, crystalline powder that is soluble in water and practically insoluble in organic solvents. Pamidronate may also be known as: ADP sodium, AHPr BP so-dium, GCP-23339A, Aminomux®, Aredia®, Aredronet®, Ostepam®, or Pamidran®. Storage/Stability/Compatibility Do not store at temperatures greater than 30°C (86°F). Once the lyophilized powder for injection is reconstituted (10 m L) with sterile water for injection, it may be stored in the refrig-erator for 24 hours. Be sure drug is completely dissolved before withdrawing into syringe. Do not mix pamidronate with any intravenous ﬂuid containing calcium (e. g., Ringer's). It is recommended to use a dedicated IV solution (0. 45% or 0. 9% Na Cl, or D 5W) and intravenous line. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Pamidronate Disodium (IV infusion) Lyophilized Powder for Injec-tion: 30 mg & 90 mg with 470 mg mannitol in vials; Aredia® (Novar-tis); generic (Sandoz); (Rx) Pamidronate Disodium Injection: 3 mg/m L, 6 mg/m L & 9 mg/m L (may contain mannitol) in 10 m L vials; generic; (Rx) PANCRELIPASE (pan-kree-lih-pase) Viokase® PANCREATIC ENZYMES Prescriber Highlights TT Pancreatic enzymes used to treat exocrine pancreatic enzyme deﬁciency or to test for pancreatic insufﬁciency secondary to chronic pancreatitis TT Contraindications: Hypersensitivity to pork products TT Adverse Effects: High doses may cause GI distress TT Avoid inhalation of powder; may cause skin irritation; wash off if gets on hands Uses/Indications Pancrelipase is used to treat patients with exocrine pancreatic en-zyme deﬁciency. It may also be used in the attempt to test for pan-creatic insufﬁciency secondary to chronic pancreatitis. Pharmacology/Actions The enzymes found in pancrelipase help to digest and absorb fats, proteins, and carbohydrates. Contraindications/Precautions/Warnings Pancrelipase products are contraindicated in animals that are hy-persensitive to pork proteins. Do not inhale the powder or bronchial/lung irritation can occur. Avoid contact with mucous membranes or skin. Adverse Effects High doses may cause GI distress (diarrhea, cramping, nausea). Concentrated pancreatic enzymes can cause oral or esophageal ul-cers; follow dosing with food or water. 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. ) These enzymes are unlikely to be excreted in maternal milk or pose risk to offspring. Overdosage/Acute Toxicity Overdosage may cause diarrhea or other intestinal upset. The ef-fects should be temporary; treat by reducing dosage and support-ively if diarrhea is severe. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pancrelipase and may be of signiﬁcance in veterinary patients: T ! ANTACIDS (magnesium hydroxide, calcium carbonate ): May diminish the effectiveness of pancrelipase T ! CIMETIDINE (or other H 2 antagonists) : May increase the amount of pancrelipase that reaches the duodenum Doses T ! DOGS: For pancreatic exocrine insufﬁciency: a) 1-1. 5 teaspoonsful with each meal mixed with food. Mix with food thoroughly and allow to stand for 15-20 minutes before feeding. Dosage should be adjusted as necessary. Best results are usually obtained by feeding small meals frequently (at least 3 times per day). (Package Insert; Viokase®-V Pow-der—Fort Dodge) b) 1/2-2 teaspoonsful PO with each meal. (Williams 2000) c) 1-2 teaspoonsful of powder or ﬁnely crushed nonenteric-coated tablets to each of two meals of balanced canine ration. It is not necessary to incubate the enzyme preparation before feeding. Tailor regimen to maintain optimal body weight. (Bunch 2003) d) Maintenance dose is usually 1 teaspoonful per meal. (Wester-marck, Wiberg et al. 2005) T ! CATS: Note : Cats reportedly “hate” the taste of the powder and may be more easily dosed using solid dosage forms (enteric-coated tab-lets or compounded capsules made from powder or crushed tab-lets). If using these products, be certain that the cat follows the tablets with water or food to reduce the risk for esophageal dam-age. It has also been reported that some cats will eat food mixed with one brand of veterinary powder and refuse another.	pppbs.pdf
690 PANCURONIUM BROMIDE For pancreatic exocrine insufﬁciency: a) 0. 5-0. 75 teaspoonsful with each meal mixed with food. Mix with food thoroughly and allow it to stand for 15-20 min-utes before feeding. Dosage should be adjusted as necessary. Best results are usually obtained by feeding small meals fre-quently (at least 3 times per day). (Package Insert; Viokase®-V Powder—Fort Dodge) b) 1 teaspoonful of powder or ﬁnely crushed nonenteric-coated tablets to each of two meals of balanced feline ration. Cats that refuse to eat food treated with powder may be dosed with capsules ﬁlled with powder or crushed non-enteric coated tablets. It is not necessary to incubate the enzyme preparation before feeding. Tailor regimen to maintain op-timal body weight. (Bunch 2003) c) 0. 5 teaspoonsful of powder per meal. (Westermarck, Wiberg et al. 2005) T ! RABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: For gastric trichobezoars: 1 teaspoonful (5 m L) pan-crelipase powder plus 3 teaspoonsful (15 m L) of yogurt; let stand for 15 minutes, then give 2-3 m L PO q12h. Question-able efﬁcacy for removing “hairballs”, but might help dissolve the protein matrix surrounding hair. (Ivey and Morrisey 2000) T ! BIRDS: For pancreatic exocrine insufﬁciency (used in birds that are polyphagic “going light”, passing whole seeds, and slow in emp-tying crops): a) 1/8 tsp per kg. Mix with moistened feed or administer by gavage. Incubate with food for 15 minutes prior to gavage. (Clubb 1986) Monitoring T ! Animal's weight T ! Stool consistency, frequency Client Information T ! Powder spilled on hands should be washed off or skin irritation may develop; do not allow powder to contact eyes T ! Avoid inhaling powder; causes mucous membrane irritation and may trigger asthma attacks in susceptible individuals. Chemistry/Synonyms Pancrelipase contains pancreatic enzymes, primarily lipase but also amylase and protease, and is obtained from the pancreas of hogs. Each mg of pancrelipase contains not less than 24 USP Units of lipase activity, not less than 100 USP Units of protease activity, and not less than 100 USP Units of amylase activity. When compared on a per weight basis, pancrelipase has at least 4 times the trypsin and amylase content of pancreatin, and at least 12 times the lipolytic activity of pancreatin. Pancrelipase may also be known as pancrelipasa, Epizyme®, Panakare®, Pancrepowder Plus®, Pancreved®, Pancrezyme®, and Viokase®. Storage/Stability Unless otherwise recommended by the manufacturer, store at room temperature in a dry place in tight containers. When present in quantities greater than trace amounts, acids will inactivate pancre-lipase. Dosage Forms/Regulatory Status Note : There are several dosage forms (both human and veterinary-label) available containing pancrelipase, including oral capsules, oral delayed-release capsules, tablets, and delayed-released tablets. Most small animal practitioners feel that the oral powder is most effective in dogs. VETERINARY-LABELED PRODUCTS: Pancrelipase Powder containing (approximately) per teaspoonful (2. 8 grams): 71,400 Units lipase; 388,000 Units protease; 460,000 Units amylase; in 8 oz bottle; Viokase®-V Powder (Fort Dodge), Pan-crezyme® Powder (Virbac); Pancrepowder Plus® (Butler), Pancreved® Powder (Vedco), Epizyme® Powder (V. E. T. ), Panakare® Plus Powder (Neogen), (Rx). Labeled for use in dogs and cats. HUMAN-LABELED PRODUCTS: There are capsules, tablets, and powders available containing lipase, protease, and amylase in varying units available for human consump-tion from many distributors. PANCURONIUM BROMIDE (pan-kue-roe-nee-um) Pavulon® NON-DEPOLARIZING NEUROMUSCULAR BLOCKER Prescriber Highlights TT Non-depolarizing neuromuscular blocker used as an ad-junct to general anesthesia TT Contraindications: Known hypersensitivity. Extreme Cau-tion: Myasthenia gravis TT Caution: Renal dysfunction, hepatic or biliary disease; patients where tachycardias may be deleterious TT No analgesic or sedative/anesthetic actions TT Adverse Effects: Slight elevations in cardiac rate & blood pressure, hypersalivation (if not pretreated with an an-ticholinergic agent), prolonged or profound muscular weakness, & respiratory depression. Very Rarely: Hista-mine release with resultant hypersensitivity reaction TT Drug Interactions Uses/Indications Pancuronium is indicated as an adjunct to general anesthesia to produce muscle relaxation during surgical procedures or mechani-cal ventilation and to facilitate endotracheal intubation. Pharmacology/Actions Pancuronium is a nondepolarizing neuromuscular blocking agent and acts by competitively binding at cholinergic receptor sites at the motor endplate, inhibiting the effects of acetylcholine. It is considered 5 times as potent as d-tubocurarine and 1/3 as potent as vecuronium (some sources say that pancuronium is equipotent with vecuronium in animals). It has little effect on the cardiovascu-lar system other than increasing heart rate slightly, and only rarely does it cause histamine release.	pppbs.pdf
PANCURONIUM BROMIDE 691 TPharmacokinetics After intravenous administration, muscle relaxation sufﬁcient for endotracheal intubation occurs generally within 2-3 minutes, but is dependent on the actual dose administered. Duration of action may persist 30-45 minutes, but this again is dependent on the dose. Additional doses may slightly increase the magnitude of the block-ade and will signiﬁcantly increase the duration of action. In humans, pancuronium is approximately 87% bound to plasma proteins, but it may be used in hypoalbuminemic patients. Activity is non-affected substantially by either plasma p H or carbon dioxide levels. The half-life in humans ranges from 90-161 minutes. Approximately 40% of the drug is excreted unchanged by the kid-neys. The remainder is excreted in the bile (11%) or metabolized by the liver. In patients with renal failure, plasma half-lives are dou-bled; atracurium may be a better choice for these patients. Contraindications/Precautions/Warnings Pancuronium is contraindicated in patients hypersensitive to it. It should be used with caution in patients with renal dysfunction, or where tachycardias may be deleterious. Lower doses may be neces-sary in patients with hepatic or biliary disease. Pancuronium has no analgesic or sedative/anesthetic actions. In patients with myas-thenia gravis, neuromuscular blocking agents should be used with extreme caution, if at all. Adverse Effects Adverse reactions seen with pancuronium include: slight elevations in cardiac rate and blood pressure, hypersalivation (if not pretreat-ed with an anticholinergic agent), occasional rash (humans), and prolonged or profound muscular weakness and respiratory depres-sion. Very rarely, pancuronium will cause substantial histamine re-lease with resultant hypersensitivity 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. ) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: B (Safe for use if used cautiously. Studies in laboratory animals may have un-covered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term. ) It is not known whether these drugs are excreted in maternal milk. Overdosage/Acute Toxicity Monitoring muscle twitch response to peripheral nerve stimula-tion can minimize overdosage possibilities. Increased risks of hy-potension and histamine release occur with overdoses, as well as prolonged duration of muscle blockade. Besides treating conservatively (mechanical ventilation, O 2, ﬂu-ids, etc. ), reversal of blockade may be accomplished by administer-ing an anticholinesterase agent (edrophonium, physostigmine, or neostigmine) with an anticholinergic (atropine or glycopyrrolate). A suggested dose for neostigmine is 0. 06 mg/kg IV after atropine 0. 02 mg/kg IV. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pancuronium and may be of signiﬁcance in veterinary patients: !TAZATHIOPRINE : May reverse pancuronium's neuromuscular block-ing effects !TAMINOGLYCOSIDES (gentamicin, etc. ): May enhance the neuromus-cular blocking activity of pancuronium !TLINCOSAMIDES : (clindamycin, etc. ): May enhance the neuromuscu-lar blocking activity of pancuronium !TMAGNESIUM SULFATE or HCl: May enhance the neuromuscular blocking activity of pancuronium !TQUINIDINE : May enhance the neuromuscular blocking activity of pancuronium !TSUCCINYLCHOLINE : Other muscle relaxant drugs may cause a syn-ergistic or antagonistic effect. Succinylcholine may speed the on-set of action and enhance the neuromuscular blocking actions of pancuronium. Do not give pancuronium until succinylcholine effects have subsided. !TTHEOPHYLLINE : May inhibit or reverse the neuromuscular block-ing action of pancuronium and possibly induce arrhythmias !TTRICYCLIC ANTIDEPRESSANTS (e. g., clomipramine, amitriptyline ): In-creased risk for cardiac arrhythmias when used with halothane anesthesia Doses !TDOGS: a) As a paralytic during mechanical ventilation: 0. 05-0. 1 mg/ kg IV; lasts about an hour, must give sedation as well (Carr 2003) b) 0. 044-0. 11 mg/kg IV; higher dose used initially; lower doses required if repeated doses are necessary (Mandsager 1988) c) On occasions when anesthesia maintenance with IV or re-gional techniques are not adequate to prevent spontaneous movement and the addition of inhalational agents results in severe hypotension (not corrected with ﬂuid therapy): 0. 02-0. 04 mg/kg IV provides 30-45 minutes of muscle re-laxation. (Day 2005) !TCATS: a) 0. 044-0. 11 mg/kg IV; higher dose used initially; lower doses required if repeated doses are necessary (Mandsager 1988) !TRABBITS, RODENTS, SMALL MAMMALS: a) Rabbits: 0. 1 mg/kg IV (Ivey and Morrisey 2000) !TSWINE: a) 0. 11 mg/kg IV (Muir) Monitoring !TLevel of neuromuscular blockade !TCardiac rate Client Information !This drug should only be used by professionals familiar with us-ing neuromuscular blocking agents in a supervised setting with adequate ventilatory support Chemistry/Synonyms A synthetic, non-depolarizing neuromuscular blocker, pancuro-nium bromide occurs as a white, odorless, bitter-tasting, hygro-scopic, ﬁne powder. It has a melting point of 215°C and one gram is soluble in 100 m L of water; it is very soluble in alcohol. Acetic acid is used to adjust the commercially available injection to a p H of approximately 4. Pancuronium bromide may also be known as: NA-97, Org-NA-97, or pancuronii bromidum.	pppbs.pdf
692 PANTOPRAZOLE Storage/Stability/Compatibility Pancuronium injection should be stored under refrigeration (2-8°C), but, according to the manufacturer, it is stable for 6 months at room temperature. Do not store pancuronium in plastic syringes or containers as it may be adsorbed to plastic surfaces. It may be administered in plastic syringes, however. It is recommended that pancuronium not be mixed with barbi-turates, as a precipitate may form, although data conﬂicts on this point. No precipitate was seen when pancuronium was mixed with succinylcholine, meperidine, neostigmine, gallamine, tubocurarine, or promethazine. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Pancuronium Bromide for Injection: 1 mg/m L in 10 m L vials; 2 mg/ m L in 2 m L and 5 m L amps; generic; (Rx) PANTOPRAZOLE (pan-toe-prah-zohl) Protonix®, Pantoloc® PROTON PUMP INHIBITOR Prescriber Highlights TT Proton pump inhibitor similar to omeprazole; also avail-able in IV dosage form TT May be useful in treating or preventing gastric acid-relat-ed pathologies in dogs, cats, foals & camelids TT Relatively limited research & experience in veterinary medicine, particularly when compared with omeprazole TT Appears well tolerated Uses/Indications Pantoprazole may be useful in treating or preventing gastric acid-related pathologies in dogs, cats, foals and camelids, particularly when the intravenous route is preferred. Pantoprazole is available in both intravenous and oral tablet (delayed-release) formulations. One study (Bersenas, Mathews et al. 2005) performed in dogs, com-paring the gastric p H effects of intravenous pantoprazole with oral omeprazole, intravenous ranitidine, and intravenous famotidine, found at the dosages used, that pantoprazole was more effective than ranitidine, but similar to famotidine, and that oral omeprazole was more effective in maintaining intragastric p H >3 for a longer period than pantoprazole. Pantoprazole has been shown to directly reduce in vitro counts of H. pylori and is used in some H. pylori treatment protocols for humans. Pharmacology/Actions Pantoprazole is a substituted benzimidazole, similar to omeprazole and the other proton pump inhibitors (PPIs). At the secretory sur-face of gastric parietal cells, pantoprazole forms a covalent bond at two sites of the H +/K+ ATPase (proton pump) enzyme system. There it inhibits the transport of hydrogen ions into the stomach. Pantoprazole reduces acid secretion during both basal and stimu-lated conditions. Pharmacokinetics No speciﬁc information was located for pantoprazole pharmacoki-netics in dogs or cats. In neonatal foals, intragastric (IG) adminis-tered pantoprazole bioavailability was 41% and drug was detected in plasma within 5 minutes of administration. Mean hourly gastric p H was increased for 2-24 hours versus untreated foals after either IV or IG administration, but IV administration increased p H sig-niﬁcantly greater than IG administration, presumably due to low GI bioavailability (Ryan, Sanchez et al. 2005). In humans, it is rapidly absorbed after oral administration with an oral bioavailability of 77%. Food can reduce the rate of absorp-tion, but does not appear to affect the extent of absorption. On av-erage, 51% of gastric acid secretion is inhibited at 2. 5 hours after a single dose and 85% is inhibited after the seventh day of daily administration. Protein binding is 98%, primarily to albumin. The drug is metabolized in the liver, primarily by CYP2C19 isoenzymes. CYP3A4, 2D6, 2C9, or 1A2 are minor components of pantoprazole biotransformation; pantoprazole does not appear to clinically affect (either induce or inhibit) the metabolism of other drugs using these isoenzymes for biotransformation. Metabolites of pantoprazole do not appear to have pharmacologic activity. Elimination half-life for both oral and IV administration is only about an hour, but the drug's pharmacologic action can persist for 24 hours or more, pre-sumably due to irreversible binding at the receptor site. About 71% of a dose is excreted as metabolites in the urine, with the remainder in the feces as metabolites and unabsorbed drug. Contraindications/Precautions/Warnings Pantoprazole is contraindicated in patients known to be hypersen-sitive to it or other substituted benzimidazole PPIs. Parenteral pantoprazole must be administered IV; do not give IM or SQ. Reconstituted injection (4 mg/m L) must be adminis-tered intravenously over not less than 2 minutes. Adverse Effects Use has been limited in small animals and an adverse effect proﬁle is not well established; however, the drug appears to be tolerated well. In humans, the most commonly reported adverse effects are di-arrhea and headache. Hyperglycemia has been reported in about 1% of patients. Proton pump inhibitors have been associated with an increased risk of developing community-acquired pneumonia in humans. Injection site reactions (thrombophlebitis, abscess) have occurred with IV administration. Reproductive/Nursing Safety When pantoprazole was dosed in rats (98X human dose) and rab-bits (16X), no affects on fertility or teratogenic effects were noted. In humans, the FDA categorizes pantoprazole 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. ) Pantoprazole and its metabolites have been detected in milk, but it should be relatively safe to use in nursing veterinary patients. Overdosage/Acute Toxicity There is limited information available. A single oral dose of 887 mg/kg was lethal in dogs. Acute toxic signs included ataxia, hypo-activity, and tremor. In humans, single oral overdoses of up to 600 mg have been reported without adversity. In the event of a large overdose, it is recommended to contact an animal poison control center for guidance.	pppbs.pdf
PARAPOX OVIS VIRUS IMMUNOMODULATOR 693 TDrug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving pantoprazole and may be of signiﬁcance in veterinary patients: T ! DRUGS REQUIRING DECREASED GASTRIC PH FOR OPTIMAL ABSORPTION (e. g., ketoconazole, itraconazole, iron, ampicillin esters ): Pantopra-zole may decrease drug absorption T ! SUCRALFATE : May decrease bioavailability of orally administered pantoprazole T ! WARFARIN : Pantoprazole may increase anticoagulant effect Laboratory Considerations T ! Although not likely to be important for veterinary patients, pan-toprazole may cause false-positive results for urine screening tests for THC (tetrahydrocannabinol) Doses T ! DOGS/CAT S: a) Dogs: For intravenous treatment of stress-related mucosal disease: 0. 7-1 mg/kg IV once daily. (Bateman 2003) T ! HORSES: a) For gastric acid suppression in neonatal foals: 1. 5 mg/kg IV once daily. Note : From an experimental study evaluating the pharmacokinetics and pharmacodynamics in normal neona-tal foals. Further studies are required to investigate the use of this drug in critically ill patients. (Ryan, Sanchez et al. 2005) Monitoring T ! Efﬁcacy T ! Adverse effects (vomiting, diarrhea, injection site reactions if used IV) Client Information T ! ablets must be given whole; do not split or crush T ! If patient develops bloody diarrhea, tarry-black stools, or vomits blood, contact veterinarian immediately T ! Contact veterinarian if vomiting or diarrhea persist or are severe Chemistry/Synonyms Pantoprazole sodium sesquihydrate occurs as a white to off-white crystalline powder and is racemic. It is freely soluble in water and very slightly soluble in phosphate buffer at a p H of 7. 4. Stability of aqueous solutions is p H dependent. At room temperature, solutions of p H 5 are stable for about 3 hours; at a p H of 7. 8, 220 hours. Pantoprazole may also be known as BY-1023, or SKF-96022. International trade names include: Controloc®, Pantoloc®, Zurcal, Pantozol®, Pantop®, Protonix®, Protium®, Somac-MA®, and many others. Storage/Stability/Compatibility Delayed-release tablets should be stored between 15-30°C. The powder for injection should be stored protected from light at 20-25°C; excursions are permitted to 15-30°C. For a 2-min-ute IV infusion; reconstitute with 10 m L of 0. 9% sodium chloride injection. T o prepare the injection for a 15-minute IV infusion, re-constitute with 10 m L of 0. 9% sodium chloride injection, then di-lute further with 100 m L of D5W, 0. 9% sodium chloride or lactated Ringer's injection to a ﬁnal concentration of approximately 0. 4 mg/ m L. Reconstituted solutions (10 m L) are stable for up to 2 hours at room temperature. If further diluted (per 15 minute infusion), it is stable for up to 22 hours at room temperature. Reconstituted solu-tions do not need to be protected from light. Do not freeze. Do not use the IV solution if discoloration or precipitates are seen; should these be observed during the infusion, stop immediately. Pantoprazole injection is not compatible with midazolam and may not be compatible with solutions containing zinc. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 5 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Pantoprazole Sodium Delayed-Release Tablets: 20 mg (as base) & 40 mg (as base); Protonix® (Wyeth-Ayerst); (Rx) Pantoprazole Powder (freeze-dried) for Injection: 40 mg (as base)/ vial; Protonix I. V. ® (Wyeth-Ayerst); (Rx) PARAPOX OVIS VIRUS IMMUNOMODULATOR (pair-ah-poks oh-vis) Zylexis® IMMUNOSTIMULANT Prescriber Highlights TT Biologic immunostimulant labeled for use in healthy horses of 4 months of age & older as an aid in reducing upper respiratory disease caused by equine herpesvirus types 1 & 4 TT Limited published information available on safety & efﬁcacy Uses/Indications Parapox ovis virus immunomodulator is commercially available in the USA labeled for “use in healthy horses of 4 months of age and older as an aid in reducing upper respiratory disease caused by equine herpesvirus types 1 and 4. ” A parapoxvirus product (Baypamun®) is reportedly available in some European countries for use in small animals. Pharmacology/Actions Parapox ovis is the virus responsible for “orf ” in sheep, a contagious pustular dermatitis. The virus is inactivated in the commercial product. Parapoxvirus products are so-called “paramunity induc-ers” and are believed to prevent viral infection by pathogenic vi-ruses via viral interference. By “infecting” host cells with a defective (non-replicating) virus, interference with infection by the patho-genic virus can occur. Postulated mechanisms of action include induction of interferons, cytokines and colony-stimulating factors, and activation of natural killer cells. Pharmacokinetics Effects on the immune system are reported to occur 4-6 hours af-ter treating; effects persist for 1-2 weeks. Contraindications/Precautions/Warnings Do not be use in patients with prior hypersensitivity to the agent. The manufacturer warns that in the case of an anaphylactic reac-tion, administer epinephrine or equivalent. Reproductive/Nursing Safety No information was located.	pppbs.pdf
694 PAREGORIC Adverse Effects No adverse effects are listed in the package insert, but anaphylaxis is possible. Overdosage/Acute Toxicity No information was located. Drug Interactions None noted Laboratory Considerations None identiﬁed Doses T ! HORSES: a) For an aid in reducing upper airway disease caused by her-pesvirus types 1 and 4: After reconstituting with the sterile diluent provided, administer 2 m L IM. Repeat doses on days 2 and 9 following the initial dose. Retreatment is recom-mended during subsequent disease episodes or prior to stress inducing situations. (Label information; Zylexis®—Pﬁzer) Monitoring T ! Clinical Efﬁcacy (respiratory infection improvement) Chemistry/Synonyms Zylexis® is provided commercially as a freeze-dried inactivated (killed) virus component with separate 2 m L vial of sterile diluent. Parapox ovis virus immunomodulator may also be known as: PPOV, PIND-ORF, or Baypamune® and Zylexis®. Storage/Stability Zylexis® should be stored refrigerated (2-8°C), but not be frozen. After reconstituting, entire contents should be used. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: Parapox Ovis Virus Immunomodulator Injection in boxes of 5-sin-gle dose vials for reconstitution with 5-2m L vials of sterile diluent; Zylexis® (Pﬁzer); Labeled for use in horses. Note : This product is a USDA-licensed biologic and is not approved by the FDA. The label for Zylexis® states that it should not be admin-istered to horses within 21 days of slaughter. HUMAN-LABELED PRODUCTS: None PAREGORIC (par-eh-gore-ik); Camphorated Tincture of Opium OPIATE ANTIDIARRHEAL Prescriber Highlights TT Opiate GI motility modiﬁer for diarrhea TT Contraindications: Known hypersensitivity to narcotic analgesics, patients receiving monoamine oxidase inhibi-tors (MAOIs), diarrhea caused by a toxic ingestion until the toxin is eliminated from the GI tract TT Caution: Respiratory disease, hepatic encephalopathy, hypothyroidism, severe renal insufﬁciency, adrenocorti-cal insufﬁciency (Addison's), head injuries, or increased intracranial pressure, acute abdominal conditions (e. g., colic), & in geriatric or severely debilitated patients TT Adverse Effects: DOGS: Constipation, bloat, & sedation. Potential for: paralytic ileus, toxic megacolon, pancreati-tis, & CNS effects. CATS: Use is controversial, may exhibit excitatory behavior. HORSES: With GI bacterial infection, may delay the disappearance of the microbe from the feces & prolong the febrile state TT Dose carefully in small animals; do not confuse with opium tincture TT Paregoric is a C-III controlled substance Uses/Indications Paregoric is occasionally used as a motility modiﬁers for animals diarrhea. Opiates as antidiarrheal treatments in cats is controversial and many clinicians do not recommend their use in this species. Pharmacology/Actions Among their other actions, opiates inhibit GI motility and exces-sive GI propulsion. They also decrease intestinal secretion induced by cholera toxin, prostaglandin E 2 and diarrheas caused by factors in which calcium is the second messenger (non-cyclic AMP/GMP mediated). Opiates may also enhance mucosal absorption. Pharmacokinetics The morphine in paregoric is absorbed in a variable fashion from the GI tract. It is rapidly metabolized in the liver and serum mor-phine levels are considerably less than when morphine is adminis-tered parenterally. Contraindications/Precautions/Warnings All opiates should be used with caution in patients with hypothy-roidism, severe renal insufﬁciency, adrenocortical insufﬁciency, (Addison's), in geriatric or those severely debilitated. Opiate an-tidiarrheals are contraindicated in cases where the patient is hyper-sensitive to narcotic analgesics, those receiving monoamine oxidase inhibitors (MAOIs), and with diarrhea caused by a toxic ingestion until the toxin is eliminated from the GI tract. Opiate antidiarrheals should be used with caution in patients with head injuries or increased intracranial pressure and acute ab-dominal conditions (e. g., colic), as it may obscure the diagnosis or clinical course of these conditions. It should be used with extreme caution in patients suffering from respiratory disease or acute re-spiratory dysfunction (e. g., pulmonary edema secondary to smoke inhalation). Opiate antidiarrheals should be used with extreme	pppbs.pdf
PAROMOMYCIN SULFATE 695 caution in patients with hepatic disease with CNS clinical signs of hepatic encephalopathy; hepatic coma may result. Adverse Effects In dogs, constipation, bloat, and sedation are the most likely ad-verse reactions encountered when usual doses are used. Potentially, paralytic ileus, toxic megacolon, pancreatitis, and CNS effects could be seen. Use of antidiarrheal opiates in cats is controversial; this species may react with excitatory behavior. Opiates used in horses with acute diarrhea (or in any animal with a potentially bacterial-induced diarrhea) may have a detri-mental effect. Opiates may enhance bacterial proliferation, delay the disappearance of the microbe from the feces, and prolong the febrile state. Reproductive/Nursing Safety Opium tincture is classiﬁed 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. ) Safe use of paregoric during breastfeeding in women has not been established; use with caution in nursing animals. Overdosage/Acute Toxicity Acute overdosage of the opiate antidiarrheals could result in CNS, cardiovascular, GI, or respiratory toxicity. Because the opiates may signiﬁcantly reduce GI motility, absorption from the GI may be de-layed and prolonged. For more information, refer to the meperidine and morphine monographs found in the CNS section. Naloxone may be necessary to reverse the opiate effects. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving opiate antidiarrheals and may be of signiﬁcance in veterinary patients: T ! CNS DEPRESSANT DRUGS (e. g., anesthetic agents, antihistamines, phenothiazines, barbiturates, tranquilizers, alcohol, etc. ): May cause increased CNS or respiratory depression when used with opiate antidiarrheal agents T ! MONOAMINE OXIDASE INHIBITORS (including amitraz, and possibly selegiline ): Opiate antidiarrheal agents are contraindicated in hu-man patients receiving monoamine oxidase (MAO) inhibitors for at least 14 days after receiving MAO inhibitors Laboratory Considerations T ! Plasma amylase and lipase values may be increased for up to 24 hours following administration of opiates. Doses T ! DOGS: a) For acute colitis: 0. 06 mg/kg, PO three times daily (De Novo 1988) b) For maldigestion; malabsorption; antidiarrheal: 0. 05-0. 06 mg/kg PO two to three times daily (Chiapella 1988), (John-son 1984) c) As an antidiarrheal: 0. 05-0. 06 mg/kg PO q12h (Willard 2003a) T ! CATS: Note : Use of antidiarrheal opiates in cats is controversial; this species may react with excitatory behavior. For maldigestion, malabsorption, anti-diarrheal: a) 0. 05-0. 06 mg/kg PO two to three times daily (Chiapella 1988), (Johnson 1984) T ! CATTLE: a) Calves: 15-30 m L PO (Cornell 1985) T ! HORSES: a) Foals: 15-30 m L PO; Adults: 15-60 m L PO (Cornell 1985) Monitoring T ! Clinical efﬁcacy T ! Fluid and electrolyte status in severe diarrhea T ! CNS effects if using high dosages Client Information T ! If diarrhea persists or animal appears listless or develops a high fever, contact veterinarian. Chemistry/Synonyms Paregoric contains 2 mg of the equivalent of anhydrous morphine (usually as powdered opium or opium tincture) per 5 m L. Also included (per 5 m L) is 0. 02 m L anise oil, 0. 2 m L glycerin, 20 mg benzoic acid, 20 mg camphor, and a sufﬁcient quantity of diluted alcohol to make a total of 5 m L. Paregoric should not be confused with opium tincture (tincture of opium) which contains 50 mg of anhydrous morphine equivalent per 5 m L. Paregoric is also known as camphorated tincture of opium. Storage/Stability Paregoric should be stored in tight, light-resistant containers. Avoid exposure to excessive heat or direct exposure to sunlight. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Paregoric (camphorated tincture of opium): 2 mg of morphine equiv. per 5 m L; 45% alcohol in 473 m L; generic; (Rx; C-III) Note : Do not confuse with opium tincture which contains 25 times more morphine per m L than paregoric. PAROMOMYCIN SULFATE (pair-oh-moe-my-sin) Humatin® ORAL AMINOGLYCOSIDE ANTIPARASITIC Prescriber Highlights TT Aminoglycoside used primarily as an alternative for PO treatment of cryptosporidiosis in small animals TT Not appreciably absorbed when dosed orally in humans & dogs TT Some state that the drug is contraindicated in cats sec-ondary to toxicity TT Adverse effects are usually limited to GI effects (N,V,D); cats may be susceptible to renal & ophthalmic toxicity TT Use with caution in patients with intestinal ulceration Uses/Indications Paromomycin may be useful as a secondary treatment for cryp-tosporidiosis in dogs and cats. It has also been used topically to treat cutaneous Leishmaniasis. In humans, it has been used as an alternative treatment for giardiasis, Dientamoeba fragilis, and he-patic coma.	pppbs.pdf
696 PAROXETINE HCL Pharmacology/Actions Paromomycin has an antimicrobial spectrum of activity similar to neomycin, but its primary therapeutic uses are for the treatment of protozoa, including Leishmania spp., Entamoeba histolytica, and Cryptosporidium spp. It also has activity against a variety of tape-worms, but there are better choices available for clinical use. Pharmacokinetics Like neomycin, paromomycin is very poorly absorbed when given orally. Potentially systemic toxicity (nephrotoxicity, ototoxicity, pancreatitis) could occur if used in patients with signiﬁcant ulcer-ative intestinal lesions or for a prolonged period at high dosages. Contraindications/Precautions/Warnings Paromomycin is contraindicated in patients with known hy-persensitivity to the drug, ileus or intestinal obstruction, and GI ulceration. Use with caution in cats. Because of potential toxicity, some cli-nicians recommend not using the drug in this species. Do not use in animals with blood in the stool as this may signal that the drug could be absorbed and cause nephrotoxicity. Adverse Effects Gastrointestinal effects (nausea, inappetence, vomiting, diarrhea) are the most likely adverse effects to be noted with therapy. Because paromomycin can affect gut ﬂora, nonsusceptible bacterial or fun-gal overgrowths are a possibility. In patients with signiﬁcant gut ulceration, paromomycin may be absorbed systemically with resul-tant nephrotoxicity, ototoxicity, or pancreatitis. Use in cats has been associated with renal dysfunction and blindness. Reproductive/Nursing Safety Because minimal amounts are absorbed when administered orally, paromomycin should be safe to use during pregnancy. It should not be used parenterally during pregnancy. When used orally, paromomycin should be safe to use during lactation. Overdosage/Acute Toxicity Because paromomycin is not absorbed orally, acute overdose ad-verse effects should be limited to gastrointestinal distress in patients with an intact GI system. Chronic overdoses may lead to systemic toxicity. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving paromomycin and may be of signiﬁcance in veterinary patients: T ! DIGOXIN : Paromomycin may reduce digoxin absorption T ! METHOTREXATE : Paromomycin may reduce methotrexate absorption Laboratory Considerations None were noted. Doses T ! DOGS: For treatment of cryptosporidiosis: a) 125-165 mg/kg PO twice daily for 5 days (Blagburn 2003a) b) 150 mg/kg PO once a day for 5 days (Tams 2003c) T ! CATS: For treatment of cryptosporidiosis: Note : Higher dosages of paromomycin have caused renal toxicity and/or blindness in some treated cats. Consider using an alternate treatment ﬁrst (e. g., azithromycin) or paromomycin at an initially reduced dos-age level. a) 125-165 mg/kg PO twice daily for 5 days. (Blagburn 2003a) b) 150 mg/kg PO once a day for 5 days. (Tams 2003c) T ! REPTILES: For treatment of cryptosporidiosis: 300-800 mg/kg PO q24-48h for 7-14 days or as needed (de la Navarre 2003b) Monitoring T ! Efﬁcacy T ! GI adverse effects T ! If used in cats, monitor renal function Client Information T ! Unless otherwise instructed, give with food. Chemistry/Synonyms An aminoglycoside antibiotic, paromomycin sulfate occurs as an odorless, creamy white to light yellow, hygroscopic, amorphous powder having a saline taste. Paromomycin is very soluble in water (>1 g/m L). Paromomycin may also be known as: aminosidin sulphate, aminosidine sulphate, catenulin sulphate, crestomycin sulphate; estomycin sulphate, hydroxymycin sulphate, monomycin A sul-phate, neomycin E sulphate, paucimycin sulphate, Gabbromicina®, Gabbroral®, Gabroral®, Humagel®, Humatin®, Kaman®, and Sinosid®. Storage/Stability Paromomycin capsules should be stored at room temperature (15-30°C; 59-86°F) in tight containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Paromomycin Sulfate Capsules: 250 mg (of paromomycin); Huma-tin® (Parke-Davis); (Rx) PAROXETINE HCL (pah-rox-a-teen) Paxil® SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI) ANTIDEPRESSANT Prescriber Highlights TT Selective serotonin reuptake inhibitor antidepressant related to ﬂuoxetine used in dogs & cats for variety of behavior disorders TT Contraindications: Patients with known hypersensitivity or receiving monoamine oxidase inhibitors TT Caution: Patients with severe cardiac, renal or hepatic disease. Dosages may need to be reduced in patients with severe renal, or hepatic impairment TT Adverse effect proﬁle is not well established; potentially in DOGS: Anorexia, lethargy, GI effects, anxiety, irritability, insomnia/hyperactivity, or panting. Aggressive behavior in previously unaggressive dogs possible. CATS: May exhibit behavior changes (anxiety, irritability, sleep disturbances), anorexia, constipation & changes in elimination patterns	pppbs.pdf
PAROXETINE HCL 697 Uses/Indications Paroxetine may be beneﬁcial for the treatment of canine aggres-sion, and stereotypic or other obsessive-compulsive behaviors. It has been used occasionally in cats as well. Pharmacology/Actions Paroxetine is a highly selective inhibitor of the reuptake of sero-tonin in the CNS, thus potentiating the pharmacologic activity of serotonin. Paroxetine apparently has little effect on other neu-rotransmitters (e. g., dopamine or norepinephrine). Pharmacokinetics No veterinary data was located. In humans, paroxetine is slowly, but nearly completely, absorbed from the GI tract. Because of a relative-ly high ﬁrst pass-effect, relatively small amounts reach the systemic circulation unchanged. Food does not impair absorption. The drug is about 95% bound to plasma proteins. Paroxetine is extensively metabolized, probably in the liver. Half-life in humans ranges from 7-65 hours and averages about 24 hours. Contraindications/Precautions/Warnings Paroxetine is contraindicated in patients with known hypersensitiv-ity to it or those receiving monoamine oxidase inhibitors (see Drug Interactions below). Use with caution in patients with seizure dis-orders, severe cardiac, hepatic, or renal disease. Dosages may need to be reduced in patients with severe hepatic or renal impairment. Adverse Effects In dogs, paroxetine can cause lethargy, GI effects, anxiety, irritabil-ity, insomnia/hyperactivity, or panting. Anorexia is a common side effect in dogs (usually transient and may be negated by temporar-ily increasing the palatability of food and/or hand feeding). Some dogs have persistent anorexia that precludes further treatment. Aggressive behavior in previously unaggressive dogs has been re-ported. SSRIs may also cause changes in blood glucose levels and potentially, reduce seizure threshold. Paroxetine in cats can cause behavior changes (anxiety, irrita-bility, sleep disturbances), anorexia, constipation and changes in elimination patterns. Reproductive/Nursing Safety Paroxetine's safety during pregnancy has not been established. Preliminary studies done in rats demonstrated no overt terato-genic effects. 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. ) The drug is excreted into milk but at low levels; caution is ad-vised in nursing patients. Overdosage/Acute Toxicity There is limited information available. Experience with overdoses in humans yields a mixed picture. While not as toxic as the tricyclic antidepressants, fatalities and signiﬁcant morbidity have occurred after paroxetine overdoses. There were 214 exposures to paroxetine reported to the ASPCA Animal Poison Control Center (APCC; www. apcc. aspca. org ) dur-ing 2005-2006. In these cases 187 were dogs with 19 showing clini-cal signs, 22 were cats with 4 showing clinical signs and the remain-ing 5 cases were birds of which 1 showed clinical signs. Common ﬁndings in dogs recorded in decreasing frequency included lethar-gy, ataxia, agitation, depression and hyperthermia. Common ﬁnd-ings in cats recorded in decreasing frequency included anorexia, lethargy, adipsia, anuria and hypersalivation. Common ﬁndings in birds recorded in decreasing frequency included anorexia, erratic behavior, head bobbing, lethargy and regurgitation. In overdoses with small animals, it is recommended to err on the safe side and employ gut evacuation (if not contraindicated) and then treat supportively. 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 paroxetine and may be of signiﬁcance in veterinary patients: !TBUSPIRONE : Increased risk for serotonin syndrome !TCIMETIDINE : May increase paroxetine levels !TCYPROHEPTA DINE: May decrease or reverse the effects of SSRIs !TDIGOXIN : Paroxetine (in humans) can decrease digoxin AUC by 15% !TINSULIN : May alter insulin requirements !TISONIAZID : Increased risk for serotonin syndrome !TMAO INHIBITORS (including amitraz and potentially, selegiline ): High risk for serotonin syndrome; use contraindicated; in hu-mans, a 5 week washout period is required after discontinuing paroxetine and a 2 week washout period if ﬁrst discontinuing the MAO inhibitor !TPENTAZOCINE : Serotonin syndrome-like adverse effects possible !TPHENOBARBITAL : May decrease paroxetine levels !TPHENYTOIN : Increased plasma levels of phenytoin possible; may decrease paroxetine levels !TPROPRANOLOL, METOPROLOL : Paroxetine may increase these beta-blockers' plasma levels and cause hypotension; atenolol may be safer to use if paroxetine required !TTRICYCLIC ANTIDEPRESSANTS (e. g., clomipramine, amitriptyline ): Par-oxetine may increase TCA blood levels and may increase the risk for serotonin syndrome !TTHEOPHYLLINE : Increased plasma levels of theophylline possible !TWARFARIN : Paroxetine may increase the risk for bleeding Doses !TDOGS: For SSRI responsive behavior problems: a) For compulsive disorders: 1 mg/kg (up to 3 mg/kg) PO once daily (q24h) (Landsberg 2004) b) For storm phobias: 1 mg/kg PO once daily for 3-5 months, then taper (Crowell-Davis 2003c) c) For adjunctive treatment of phobias, fears, and anxieties: 0. 5-1 mg/kg PO once daily (Moffat 2007a) !TCATS: For SSRI responsive behavior problems: a) 2. 5-5 mg (total dose) per cat PO once daily (Reisner and Houpt 2000) b) For compulsive disorders: 0. 5-1 mg/kg PO once daily (q24h) (Landsberg 2004) c) For interspecies aggression: 0. 5-1 mg/kg PO once daily (Crowell-Davis 2003b) d) For marking: 0. 5-1 mg/kg PO once daily (Landsberg 2007), (Neilson 2007) e) For intercat aggression: 0. 5-1 mg/kg PO once daily (Moffat 2007b) Monitoring !TEfﬁcacy !TAdverse effects; including appetite (weight)	pppbs.pdf
698 PENICILLAMINE Client Information T ! Keep medication out of reach of children and pets T ! May cause GI effects (especially lack of appetite, constipation), behavior and sleep changes; if these become issues, contact vet-erinarian Chemistry/Synonyms A selective serotonin reuptake inhibitor (SSRI) antidepressant, par-oxetine HCl occurs as an off-white, odorless powder. It has a solu-bility in water of 5. 4 mg/m L and a p Ka of 9. 9. Paroxetine may also be known as: BRL-29060, FG-7051, and Paxil®. Storage/Stability Paroxetine oral tablets should be stored at 15-30°C. The oral sus-pension should be stored below 25°C. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None The ARCI (Racing Commissioners International) has designated this drug as a class 2 substance. See the appendix for more information. HUMAN-LABELED PRODUCTS: Paroxetine Tablets: 10 mg, 20 mg, 30 mg & 40 mg; Paxil® (Glaxo S-mith Kline); generic; (Rx) Paroxetine Tablets Controlled-release: 12. 5 mg, 25 mg and 37. 5 mg; Paxil® CR (Glaxo Smith Kline); (Rx) Paroxetine Oral Suspension: 2 mg/m L in 250 m L btls (orange ﬂa-vored); Paxil® (Glaxo Smith Kline); (Rx) PEG 3550 Products—see Saline Cathartics PENICILLAMINE (pen-i-sill-a-meen) Depen®, Cuprimine® ANTIDOTE; CHELATING AGENT Prescriber Highlights TT Chelating agent used primarily for copper-storage he-patopathies (dogs). May be considered for lead poisoning or cystine urolithiasis TT Contraindications: History of penicillamine-related blood dyscrasias TT Adverse Effects: Nausea, vomiting, & depression. Rarely: Fever, lymphadenopathy, skin hypersensitivity reactions, or immune-complex glomerulonephropathy TT Potentially teratogenic TT Preferably given on an empty stomach Uses/Indications Penicillamine is used primarily for its chelating ability in veterinary medicine. It is the drug of choice for Copper storage-associated he-patopathies in dogs, and may be used for the long-term oral treat-ment of lead poisoning or in cystine urolithiasis. Although the drug may be of beneﬁt in chronic hepatitis, doses necessary for effective treatment may be too high to be tolerated. Pharmacology/Actions Penicillamine chelates a variety of metals, including copper, lead, iron, and mercury, forming stable water soluble complexes that are excreted by the kidneys. Penicillamine combines chemically with cystine to form a stable, soluble complex that can be readily excreted. Penicillamine has antirheumatic activity. The exact mechanisms for this action are not understood, but the drug apparently im-proves lymphocyte function, decreases Ig M rheumatoid factor and immune complexes in serum and synovial ﬂuid. Penicillamine possesses antiﬁbrotic activity via inhibition of col-lagen crosslinking thereby causing collagen to be more susceptible to degradation. Although penicillamine is a degradation product of penicillins, it has no antimicrobial activity. Pharmacokinetics In humans, penicillamine is well absorbed after oral administration and peak serum levels occur about one hour after dosing. The drug apparently crosses the placenta but, otherwise, little information is known about its distribution. Penicillamine that is not complexed with either a metal or cystine is thought to be metabolized by the liver and excreted in the urine and feces. Contraindications/Precautions/Warnings Penicillamine is contraindicated in patients with a history of pen-icillamine-related blood dyscrasias. Adverse Effects In dogs, the most prevalent adverse effects associated with pen-icillamine are nausea, vomiting, and depression. If vomiting is a problem, attempt to alleviate by giving smaller doses of the drug on a more frequent basis. Although food probably decreases the bioavailability of the drug, many clinicians recommend mixing the drug with food or giving at mealtimes if vomiting persists. Although thought infrequent or rare, fever, lymphadenopathy, skin hypersen-sitivity reactions, or immune-complex glomerulonephropathy may occur. Reproductive/Nursing Safety Penicillamine has been associated with the development of birth defects in offspring of rats given 10 times the recommended dose. There are also some reports of human teratogenicity. 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 beneﬁts from the use of the drug in pregnant women may be acceptable despite its potential risks. ) Lactation safety has not been established. Overdosage/Acute Toxicity No speciﬁc acute toxic dose has been established for penicillamine and toxic effects generally occur in patients taking the drug chroni-cally. Any relationship of toxicity to dose is unclear; patients on small doses may develop toxicity. Drug Interactions The following drug interactions have either been reported or are theoretical in humans or animals receiving penicillamine and may be of signiﬁcance in veterinary patients: T ! 4-AMINOQUINOLINE DRUGS (e. g., chloroquine, quinacrine ): Concomi-tant administration with these agents may increase the risks for severe dermatologic adverse effects T ! CATIONS, ORAL INCLUDING ZINC, IRON, CALCIUM, MAGNESIUM : May de-crease the effectiveness of penicillamine if given orally together	pppbs.pdf
PENICILLIN 699 !TFOOD, ANTACIDS : The amount of penicillamine absorbed from the GI tract may be reduced by the concurrent administration of food or antacids !TGOLD COMPOUNDS : May increase the risk of hematologic and/or renal adverse reactions !TIMMUNOSUPPRESSANT DRUGS (e. g., cyclophosphamide, azathioprine, but not corticosteroids ): May increase the risk of hematologic and/or renal adverse reactions !TPHENYLBUTAZONE : May increase the risk of hematologic and/or renal adverse reactions Laboratory Considerations !TWhen using technetium Tc 99m gluceptate to visualize the kidneys, penicillamine may chelate this agent and form a compound that is excreted via the hepatobiliary system resulting in gallbladder visualization that could confuse the results. Doses !TDOGS: For copper-associated hepatopathy: a) 10-15 mg/kg PO q12h on an empty stomach. Do not give concurrently with any medication, including zinc or a vita-min-mineral supplement. (Jergens and Willard 2000) b) 10-15 mg/kg PO two times a day. If vomiting ensues the dose is split and given at mealtime or with a small portion of meat. (Center 2002) c) 10-15 mg/kg PO two times a day 30 minutes prior to food. Start low and increase. (Webb 2007b) For cystine urolithiasis: a) 15 mg/kg: PO twice daily. If nausea and vomiting occur, mix with food or give at mealtime. Some dogs may need to have the dosage slowly increased to full dose in order to tolerate the drug. (Osborne, Hoppe, and O'Brien 1989) b) 15 mg/kg: PO twice daily with food (Lage, Polzin, and Ze-noble 1988) For lead poisoning: a) After initial therapy regimen with Ca EDTA and if continued therapy is desired at home, may give penicillamine at 110 mg/kg/day, PO divided q6-8h for 1-2 weeks. If vomiting, depression, and anorexia occur, may reduce dose to 33-55 mg/kg/day divided q6-8h, which should be better tolerated. (Mount 1989) b) As an alternate or adjunct to Ca EDTA: 110 mg/kg/day di-vided q6-8h PO 30 minutes before feeding for 1-2 weeks. If vomiting a problem may premedicate with dimenhydrinate (2-4 mg/kg PO). Alternatively, may give 33-55 mg/kg/day divided as above. Dissolving medication in juice may facili-tate administration. (Nicholson 2000) !TCATS: For lead poisoning: a) After initial therapy with Ca EDTA and if blood lead is greater than 0. 2 ppm at 3-4 weeks post-treatment, may repeat Ca E-DTA or give penicillamine at 125 mg q12h PO for 5 days. (Reid and Oehme 1989) !TSMALL RUMINANTS: Note : When used in food animals, FARAD recommends a mini-mum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal. (Haskell, Payne et al. 2005) For copper toxicity: a) 52 mg/kg daily for 6 days is sometimes successful (Reilly 2004) !TBIRDS: For adjunctive treatment of lead poisoning: a) 55 mg/kg PO q12h for 1-2 weeks. It has been suggested that combining Ca EDTA and penicillamine for several days until symptoms dissipate followed by a 3-6 week treatment with penicillamine as the best regimen for lead toxicity. (Jones 2007a) Monitoring !TMonitoring of penicillamine therapy is dependent upon the rea-son for its use; refer to the references in the Dose section above for further discussion on the diseases and associated monitoring of therapy. Client Information !This drug should preferably be given on an empty stomach, at least 30 minutes before feeding. If the animal develops problems with vomiting or anorexia, three remedies have been suggested: 1) Give the same total daily dose, but divide into smaller indi-vidual doses and give more frequently 2) T emporarily reduce the daily dose and gradually increase to recommended dosage, or 3) Give with meals (will probably reduce amount of drug ab-sorbed). Chemistry/Synonyms A monothiol chelating agent that is a degradation product of peni-cillins, penicillamine occurs as a white or practically white, crys-talline powder with a characteristic odor. Penicillamine is freely soluble in water and slightly soluble in alcohol with p K a values of 1. 83, 8. 03, and 10. 83. Penicillamine may also be known as: D-Penicillamine, beta,beta-Dimethylcysteine, D-3-Mercaptovaline, penicillaminum, Depen ® and Cuprimine®. Storage/Stability Penicillamine should be stored at room temperature (15-30°C). The capsules should be stored in tight containers; tablets in well-closed containers. Dosage Forms/Regulatory Status VETERINARY-LABELED PRODUCTS: None HUMAN-LABELED PRODUCTS: Penicillamine Titratable Tablets: 250 mg (scored); Depen ® (Wallace); (Rx) Penicillamine Capsules: 125 mg & 250 mg; Cuprimine® (Merck); (Rx) PENICILLINS, GENERAL INFORMATION (pen-i-sill-in) Uses/Indications Penicillins have been used for a wide range of infections in various species. FDA-approved indications/species, as well as non-approved uses, are listed in the Uses/Indications and Dosage section for each drug. T	pppbs.pdf
700 PENICILLIN Pharmacology/Actions Penicillins are usually bactericidal against susceptible bacteria and act by inhibiting mucopeptide synthesis in the cell wall resulting in a defective barrier and an osmotically unstable spheroplast. The ex-act mechanism for this effect has not been deﬁnitively determined, but beta-lactam antibiotics have been shown to bind to several en-zymes (carboxypeptidases, transpeptidases, endopeptidases) within the bacterial cytoplasmic membrane that are involved with cell wall synthesis. The different afﬁnities that various beta-lactam antibiot-ics have for these enzymes (also known as penicillin-binding pro-teins; PBPs) help explain the differences in spectrums of activity the drugs have that are not explained by the inﬂuence of beta-lacta-mases. Like other beta-lactam antibiotics, penicillins are generally considered more effective against actively growing bacteria. The clinically available penicillins encompass several distinct classes of compounds with varying spectrums of activity: The so-called natural penicillins including penicillin G and V; the peni-cillinase-resistant penicillins including cloxacillin, dicloxacillin, oxacillin, nafcillin, and methicillin; the aminopenicillins including ampicillin, amoxicillin, cyclacillin, hetacillin, and bacampicillin; extended-spectrum penicillins including carbenicillin, ticarcillin, piperacillin, azlocillin, and mezlocillin; and the potentiated peni-cillins including amoxicillin-potassium clavulanate, ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin-potassium cla-vulanate. The natural penicillins (G and K) have similar spectrums of ac-tivity, but penicillin G is slightly more active in vitro on a weight basis against many organisms. This class of penicillin has in vitro activity against most spirochetes and gram-positive and gram-neg-ative aerobic cocci, but not penicillinase-producing strains. They have activity against some aerobic and anaerobic gram-positive bacilli such as Bacillus anthracis, Clostridium spp. (not C. difﬁcile), Fusobacterium, and Actinomyces. The natural penicillins are cus-tomarily inactive against most gram-negative aerobic and anaero-bic bacilli, and all Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses. The penicillinase-resistant penicillins have a narrower spec-trum of activity than the natural penicillins. Their antimicrobial efﬁcacy is aimed directly against penicillinase-producing strains of gram-positive cocci, particularly staphylococcal species; these drugs are sometimes called anti-staphylococcal penicillins. There are documented strains of Staphylococcus that are resistant to these drugs (so-called methicillin-resistant or oxacillin-resistant Staph), but these strains have only begun to be a signiﬁcant problem in veterinary species. While this class of penicillins does have activity against some other gram-positive and gram-negative aerobes and anaerobes, other antibiotics are usually better choices. The penicil-linase-resistant penicillins are inactive against Rickettsia, mycobac-teria, fungi, Mycoplasma, and viruses. The aminopenicillins, also called the “broad-spectrum” or am-picillin penicillins, have increased activity against many strains of gram-negative aerobes not covered by either the natural penicillins or penicillinase-resistant penicillins, including some strains of E. coli, Klebsiella, and Haemophilus. Like the natural penicillins, they are susceptible to inactivation by beta-lactamase-producing bacteria (e. g., Staph aureus). Although not as active as the natural penicil-lins, they do have activity against many anaerobic bacteria, includ-ing Clostridial organisms. Organisms that are generally not sus-ceptible include Pseudomonas aeruginosa, Serratia, Indole-positive Proteus ( Proteus mirabilis is susceptible), Enterobacter, Citrobacter, and Acinetobacter. The aminopenicillins also are inactive against Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses. The extended-spectrum penicillins, sometimes called anti-pseudomonal penicillins, include both alpha-carboxypenicillins (carbenicillin and ticarcillin) and acylaminopenicillins (piperacillin, azlocillin, and mezlocillin). These agents have similar spectrums of activity as the aminopenicillins but with additional activity against several gram-negative organisms of the family Enterobacteriaceae, including many strains of Pseudomonas aeruginosa. Like the amin-openicillins, these agents are susceptible to inactivation by beta-lactamases. In order to reduce the inactivation of penicillins by beta-lacta-mases, potassium clavulanate and sulbactam have been developed to inactivate these enzymes and extend the spectrum of those peni-cillins. When used with penicillin, these combinations are often ef-fective against many beta-lactamase-producing strains of otherwise resistant E. coli, Pasturella spp., Staphylococcus spp., Klebsiella, and Proteus. Type I beta-lactamases are often associated with E. coli, Enterobacter, and Pseudomonas, and not generally inhibited by clavulanic acid. Pharmacokinetics (General) The oral absorption characteristics of the penicillins are dependent upon its class. Penicillin G is the only available oral penicillin that is substantially affected by gastric p H and can be completely in-activated at a p H of less than 2. The other orally available peni-cillins are resistant to acid degradation but bioavailability can be decreased (not amoxicillin) by the presence of food. Of the orally administered penicillins, penicillin V and amoxicillin tend to have the greatest bioavailability in their respective classes. Penicillins are generally distributed widely throughout the body. Most drugs attain therapeutic levels in the kidneys, liver, heart, skin, lungs, intestines, bile, bone, prostate, and peritoneal, pleural, and synovial ﬂuids. Penetration into the CSF and eye only occur with inﬂammation and may not reach therapeutic levels. Penicillins are bound in varying degrees to plasma proteins and cross the placenta. Most penicillin's are rapidly excreted largely unchanged by the kidneys into the urine via glomerular ﬁltration and tubular secre-tion. Probenecid can prolong half-lives and increase serum levels by blocking the tubular secretion of penicillins. Except for nafcillin and oxacillin, hepatic inactivation and biliary secretion is a minor route of excretion. Contraindications/Precautions/Warnings Penicillins are contraindicated in patients with a history of hyper-sensitivity to them. Because there may be cross-reactivity, use peni-cillins cautiously in patients who are documented hypersensitive to other beta-lactam antibiotics (e. g., cephalosporins, cefamycins, carbapenems). Do not administer systemic antibiotics orally in patients with septicemia, shock, or other grave illnesses, as absorption of the medication from the GI tract may be signiﬁcantly delayed or di-minished. Parenteral (preferably IV) routes should be used for these cases. Certain species (snakes, birds, turtles, Guinea pigs, and chinchillas) are reportedly sensitive to procaine penicillin G. High doses of penicillin G sodium or potassium, particularly in small animals with a preexisting electrolyte abnormality, renal dis-ease, or congestive heart failure may cause electrolyte imbalances. Other injectable penicillins, such as ticarcillin, carbenicillin, and ampicillin, have signiﬁcant quantities of sodium per gram and may cause electrolyte imbalances when used in large dosages in suscep-tible patients. Adverse Effects Adverse effects with the penicillins are usually not serious and have a relatively low frequency of occurrence. Hypersensitivity reactions unrelated to dose can occur with these agents and can manifest as rashes, fever, eosinophilia, neu-	pppbs.pdf