Dacarbazine

dah-kar′bah-zeen

Functional classification: Anticancer agent

Pharmacology and Mechanism of Action

Anticancer agent. Dacarbazine (DTIC) is a monofunctional alkylating agent; thus it effectively blocks RNA synthesis. Its action is cell-cycle nonspecific.

Indications and Clinical Uses

DTIC has been primarily used for malignant melanoma and lymphoreticular neoplasms.

Precautionary Information

Adverse Reactions and Side Effects

Most common adverse effects are leukopenia, nausea, vomiting, and diarrhea.

Contraindications and Precautions

Do not use in cats.

Drug Interactions

There are no drug interactions reported for small animals.

Instructions for Use

Consult anticancer protocol for specific regimens.

Patient Monitoring and Laboratory Tests

Monitor CBC during treatment.

Formulations

DTIC is available in 200-mg vial for injection.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated.

Small Animal Dosage

Dogs

• 200 mg/m² for 5 days q3wks IV or 800-1000 mg/m² q3wks IV.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

Withdrawal times are not established for animals that produce food. This drug should not be used in animals intended for food because it is an anticancer agent.

Dalteparin

dahl′tah-pare-in

Trade and other names: Fragmin and LMWH

Functional classification: Anticoagulant

Pharmacology and Mechanism of Action

Low-molecular-weight heparin (LMWH), also known as fragmented heparin. LMWH is characterized by a molecular weight of approximately 5000, compared to conventional heparin (unfractionated, or UFH) with a molecular weight of approximately 15,000. Subsequently, the absorption, clearance, and activity of LMWH differ from UFH. LMWHs produce their effect by binding to antithrombin (AT) and increasing antithrombin III–mediated inhibition of synthesis and activity of coagulation factor Xa. However, LMWH, unlike conventional heparin, produces less inhibition of thrombin (factor IIa). LMWH’s activity is described by the Anti-factor Xa/Anti-factor IIa ratio. For dalteparin, the ratio is 2.7 : 1 (conventional unfractionated heparin ratio is 1 : 1). In people, LMWHs have several advantages compared to UFH and include greater anti-Xa/IIa activity, more complete and predictable absorption from injection, longer duration, less frequent administration, reduced risk of bleeding, and a more predictable anticoagulant response. However, in dogs and cats, the half-life of LMWH is much shorter than in humans, reducing some of this advantage. In dogs the half-life of dalteparin is approximately 2 hours; in cats it is estimated to be 1.5 hours, which requires much more frequent administration in either species to maintain anti-Xa activity compared to humans. LMWHs used in veterinary medicine include tinzaparin (Innohep), enoxaparin (Lovenox), and dalteparin (Fragmin).

Indications and Clinical Uses

Dalteparin, like other LMWHs, is used to treat hypercoagulability disorders and prevent coagulation disorders such as thromboembolism, venous thrombosis, disseminated intravascular coagulopathy (DIC), and pulmonary thromboembolism. Clinical indications are derived from uses of conventional heparin or extrapolated from human medicine. There have been few clinical studies to examine efficacy of LMWH in animals. Previously published doses extrapolated from humans (100 units/kg q12h, SQ) have been shown not to produce adequate and consistent anti-Xa activity in dogs and cats and the doses listed in this entry are needed for therapy.

Precautionary Information

Adverse Reactions and Side Effects

Although better tolerated than regular heparin, bleeding is a risk. LMWHs are associated with a lower incidence of heparin-induced thrombocytopenia in people, but heparin-induced thrombocytopenia from any form of heparin has not been a clinical problem in animals. If excessive anticoagulation and bleeding occur as a result of an overdose, protamine sulfate should be administered to reverse heparin therapy. Protamine dose is 1.0 mg protamine for every 100 U dalteparin administered by slow IV infusion. Protamine complexes with heparin to form a stable, inactive compound.

Contraindications and Precautions

Do not administer IM to prevent hematoma; administer SQ only. LMWH is excreted by renal clearance in animals; therefore, if renal disease is present, the elimination will be prolonged. Rebound hypercoagulability may occur after discontinuation of heparin treatment; therefore, it may be advised to taper the dose slowly when discontinuing treatment.

Drug Interactions

Do not mix with other injectable drugs. Use cautiously in animals that are already receiving other drugs that can interfere with coagulation, such as aspirin and warfarin. Although a specific interaction has not been identified, use cautiously in animals that may be receiving certain chondroprotective compounds such as glycosaminoglycans for treatment of arthritis. Some antibiotics, suchs as cephalosporins, may inhibit coagulation.

Instructions for Use

Dosing recommendations extrapolated from human medicine are not appropriate for animals. Animal owners should be warned that LMWHs are expensive compared to conventional heparin. When dosing, do not interchange doses on a unit-for-unit basis with other heparins.

Patient Monitoring and Laboratory Tests

Monitoring patients for clinical signs of bleeding problems. When administering LMWH, aPTT and PT clotting times are not reliable indicators of therapy, although prolonged aPTT is a sign of overdosing. Anti-Xa activity is considered the preferred laboratory measure of LMWH activity. Peak anti-Xa activity occurs 2 hours after dosing, and the target range for anti-Xa activity should be 0.5-1.0 U/mL for cats and 0.4-0.8 U/mL for dogs.

Formulations

Dalteparin is available in 2500 units anti-factor Xa (16 mg dalteparin sodium) per 0.2 mL in a single-dose syringe; 5000 units anti-factor Xa (32 mg dalteparin sodium) per 0.2 mL in a single-dose syringe; and 10,000 units anti-factor Xa (64 mg dalteparin sodium) per mL in a 9.5 mL multiple-dose vial.

Stability and Storage

Use multiple-dose vial within 2 weeks of initial penetration. Store in a tightly sealed container protected from light.

Large Animal Dosage

Horses

• 50 units/kg/day SQ. High-risk patients should receive 100 units/kg/day.

Regulatory Information

Extralabel withdrawal times are not established. However, 24-hour withdrawal times are suggested because this drug has little risk from residues.

Danazol

dan′ah-zole

Trade and other names: Danocrine

Functional classification: Hormone

Pharmacology and Mechanism of Action

Gonadotropin inhibitor. Danazol suppresses luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and estrogen synthesis. Danazol has been used as adjunctive treatment for immune-mediated blood disorders. Its mechanism of action for treating immune-mediated diseases is not understood, but it may interfere with antibody production or the binding of complement or antibody to the platelet or red blood cell. It may also reduce receptors on monocytes for antibodies bound to platelets or red blood cells.

Indications and Clinical Uses

Danazol has hormone effects (antiestrogen) that are used for endometriosis in women. Danazol (Danocrine) also has been used for treating refractory patients with immune-mediated thrombocytopenia and immune-mediated hemolytic anemia. However, available evidence does not show a benefit in dogs when it has been used to treat immune-mediated hemolytic anemia.

Precautionary Information

Adverse Reactions and Side Effects

Danazol’s androgenic effects should be considered in treated animals. However, adverse effects have not been reported in animals.

Contraindications and Precautions

It is absolutely contraindicated in pregnancy.

Drug Interactions

It has been used with other drugs in the treatment of immune-mediated diseases without reported interactions.

Instructions for Use

When used to treat autoimmune disease, it is usually used in conjunction with other drugs (e.g., corticosteroids).

Patient Monitoring and Laboratory Tests

Monitor CBC if used for treatment of immune-mediated diseases.

Formulations

Danazol is available in 50-, 100-, and 200-mg capsules.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated.

Small Animal Dosage

Dogs and Cats

• 5-10 mg/kg q12h PO.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

Danazol is an anabolic agent and should not be administered to animals intended for food.

RCI Classification: 4

Danofloxacin Mesylate

dan-oh-floks′ah-sin mess′ih-late

Trade and other names: A180

Functional classification: Antibacterial

Pharmacology and Mechanism of Action

Danofloxacin like other fluoroquinolones has activity against a broad spectrum of bacteria, including gram-negative bacilli, especially Enterobacteriaceae (Escherichia coli, Klebsiella, Salmonella) and some gram-positive cocci, such as Staphylococcus. In particular it has good activity against pathogens in cattle, such as Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni (formerly Haemophilus somnus). In cattle, subcutaneous absorption is high. Half-life is 3-6 hours.

When used to treat bovine respiratory disease (BRD) in cattle at a dose of 6 mg/kg danofloxacin had a half-life of 4.2 hours, a peak concentration of 1.7 mcg/mL, and produced area under the curve (AUC):minimum inhibitory concentration (MIC) ratio >125.

Indications and Clinical Uses

Danofloxacin is indicated for the treatment of BRD caused by P. multocida, M. haemolytica, and H. somni (formerly H. somnus). As a fluoroquinolone with a broad spectrum of activity, other organisms are susceptible. However, extralabel use for other diseases in animals intended for food is prohibited. There are no published reports of danofloxacin use in other animals.

Precautionary Information

Adverse Reactions and Side Effects

All fluoroquinolones at high concentrations may cause CNS toxicity. In safety studies in cattle when high doses were administered it caused lameness, articular cartilage lesions, and CNS problems (tremors, nystagmus, etc.). Subcutaneous injections may cause tissue irritation. All of the fluoroquinolones have a potential to produce arthropathy in young animals. In field trials, danofloxacin was associated with lameness in some calves. Fluoroquinolones have caused blindness in cats, but this has not been reported in any species from danofloxacin.

Contraindications and Precautions

Do not inject more than 15 mL in one site. Do not use extralabel. Do not use in other species for which safety information is not available. Do not use in animals prone to seizures.

Drug Interactions

Fluoroquinolones may increase concentrations of theophylline if used concurrently. Do not mix in solutions or in vials with aluminum, calcium, iron, or zinc because chelation may occur.

Instructions for Use

Inject SQ in neck of cattle.

Patient Monitoring and Laboratory Tests

No specific monitoring is necessary. CLSI break points for sensitive organisms are ≤0.25 mcg/mL for cattle respiratory pathogens. Most organisms have minimum inhibitory concentration (MIC) values ≤0.06 mcg/mL.

Formulations

Danofloxacin is available in an injectable solution of 180 mg/mL (with 2-pyrrolidone and polyvinyl alcohol).

Stability and Storage

Store below 30°C, protected from light, and protected from freezing. A slight yellow or amber color is acceptable.

Small Animal Dosage

Dogs and Cats

No small animal dose has been reported.

Large Animal Dosage

Cattle

• 6 mg/kg (1.5 mL per 100 pounds), once per 48 hours, SQ.

Equine and Swine

No dose has been reported.

Regulatory Information

Do not use in calves intended for veal.

Cattle withdrawal time (for meat): 4 days. Not established for milk because it cannot be used in lactating cattle. It is prohibited to use extralabel.

Dantrolene Sodium

dan′troe-leen soe′dee-um

Trade and other names: Dantrium

Functional classification: Muscle relaxant

Pharmacology and Mechanism of Action

Muscle relaxant. Dantrolene inhibits calcium leakage from sarcoplasmic reticulum. By inhibiting calcium initiation of muscle contraction, it relaxes muscle.

Indications and Clinical Uses

Dantrolene is used as a muscle relaxant. However, in addition to muscle relaxation, it has been used for malignant hyperthermia and it also has been used to relax urethral muscle in cats.

In horses, it has improved clinical signs associated with exertional rhabdomyolysis (“tying up”).

Precautionary Information

Adverse Reactions and Side Effects

Muscle relaxants can cause weakness in some animals. Use of dantrolene in people has caused hepatitis in some cases.

Contraindications and Precautions

Do not use in animals with hepatic disease. Use with caution in weak or debilitated animals.

Drug Interactions

Do not mix or reconstitute the intravenous solution with acidic solutions because they are incompatible.

Instructions for Use

Give oral doses on an empty stomach. Doses have been primarily extrapolated from experimental studies or extrapolation of human studies. No clinical trials are available in veterinary medicine. To relax the urethra in cats, the most effective dose is 1 mg/kg IV. When administering dantrolene for treatment of malignant hyperthermia in large animals several vials may be needed because of dilute solution in vial.

Patient Monitoring and Laboratory Tests

When used for treatment of malignant hyperthermia, monitor body temperature, acid–base balance, and electrolytes. In people, dantrolene may cause hepatitis and tests of liver injury (e.g., liver enzymes) and/or function are monitored.

Formulations

Dantrolene is available in 100-mg capsules, and 20-mg vial for injection when reconstituted is equal to 0.33 mg/mL injection.

Stability and Storage

When intravenous solution is prepared, it is stable for a short time (6 hours). It may be mixed with solutions such as 5% dextrose and 0.9% sodium chloride. Do not use intravenous solution if cloudiness or precipitation is present in vial. Compounded oral suspensions are stable for 150 days if mixed with acid solutions (e.g., citric acid). Store in a tightly sealed container, protected from light, and at room temperature.

Large Animal Dosage

Horses

• 4 mg/kg PO.

Pigs

• Malignant hyperthermia: 1-3 mg/kg IV once.

• Prophylaxis: 5 mg/kg PO.

Regulatory Information

No regulatory information is available. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

RCI Classification: 4

Dapsone

dap′sone

Trade and other names: Generic brands

Functional classification: Antibacterial

Pharmacology and Mechanism of Action

Antimicrobial drug used for treatment of mycobacterium. It may also have some immunosuppressive properties or inhibit function of inflammatory cells.

Indications and Clinical Uses

Although originally used as an antibacterial drug, in veterinary medicine it is used primarily for dermatologic diseases in dogs, especially subcorneal pustular dermatosis and dermatitis herpetiformis. It also has been used for canine pemphigus.

Precautionary Information

Adverse Reactions and Side Effects

Hepatitis and blood dyscrasias may occur. Because it shares similar properties as a sulfonamide, the same reactions seen with sulfonamides can be seen with dapsone and include anemia, neutropenia, thrombocytopenia, hepatotoxicosis, and skin–drug eruptions. It is toxic to cats and will cause neurotoxicosis and anemia.

Contraindications and Precautions

Do not administer to cats. Do not administer to animals that are sensitive to sulfonamides.

Drug Interactions

Use caution when administering dapsone with trimethoprim/sulfonamide combinations. Trimethoprim may increase blood concentrations of dapsone because it inhibits excretion and potentiates dapsone adverse effects.

Instructions for Use

Doses are derived from extrapolation of human doses or empiricism. No well-controlled clinical studies have been performed in veterinary medicine.

Patient Monitoring and Laboratory Tests

Monitor for signs of hepatic reactions. Monitor CBC occasionally because bone marrow toxicity has occurred in some animals.

Formulations

Dapsone is available in 25- and 100-mg tablets.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Dapsone may discolor without change in potency. Compounded suspension formulations have been stable for 21 days when mixed with citric acid.

Small Animal Dosage

Dogs

• 1.1 mg/kg q8-12h PO.

Cats

Do not use.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

No regulatory information is available. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

Deferoxamine Mesylate

deh-fer-oks′ah-meen mess′ih-late

Trade and other names: Desferal

Functional classification: Antidote

Pharmacology and Mechanism of Action

Chelating agent with strong affinity for trivalent cations. Because of its ability to bind to and chelate cations, it is used to treat acute iron toxicosis.

Indications and Clinical Uses

Deferoxamine is indicated in cases of severe poisoning, especially iron toxicosis. Deferoxamine also has been used to chelate aluminum and facilitate removal.

Precautionary Information

Adverse Reactions and Side Effects

Adverse effects have not been reported in animals. Allergic reactions and hearing problems have occurred in people.

Contraindications and Precautions

No contraindications reported for animals.

Drug Interactions

Deferoxamine will chelate with cations; avoid mixing with cations prior to administration.

Instructions for Use

100 mg of deferoxamine binds 8.5 mg of ferric iron. Contact local poison control center for guidance on dosing after an overdose.

Patient Monitoring and Laboratory Tests

Monitor serum iron concentrations to determine severity of intoxication and success of therapy. Successful therapy is indicated by monitoring urine color (orange-rose color change to urine indicates chelated iron is being eliminated).

Formulations

Deferoxamine is available in a 500-mg vial for injection.

Stability and Storage

Deferoxamine is soluble in water. Stable when stored in solution for 14 days. Store in a tightly sealed container, protected from light, and at room temperature. Do not refrigerate and do not mix solutions with other medications.

Small Animal Dosage

Dogs and Cats

• 10 mg/kg q2h for 2 doses IV or IM, then 10 mg/kg q8h for 24 hours.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

No regulatory information is available. There are no anticipated problems from levels of residues in animals. However, for extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

Deracoxib

dare-ah-koks′ib

Trade and other names: Deramaxx

Functional classification: Anti-inflammatory

Pharmacology and Mechanism of Action

Deracoxib is a nonsteroidal anti-inflammatory drug (NSAID). Like other drugs in this class, deracoxib produces analgesic and anti-inflammatory effects by inhibiting the synthesis of prostaglandins. The enzyme inhibited by NSAID is the cyclo-oxygenase (COX) enzyme. The COX enzyme exists in two isoforms called COX-1 and COX-2. COX-1 is primarily responsible for synthesis of prostaglandins important for maintaining a healthy GI tract, renal function, platelet function, and other normal functions. COX-2 is induced and responsible for synthesizing prostaglandins that are important mediators of pain, inflammation, and fever. However, it is known that there is some crossover of COX-1 and COX-2 effects in some situations and COX-2 activity is important for some biological effects. Deracoxib, using in vitro assays, is more COX-1 sparing compared to older NSAIDs and is a selective inhibitor of COX-2. The COX-1/COX-2 ratio is high compared to some other drugs registered for dogs. It also is a selective COX-2 inhibitor in cats. It has not been established if the specificity for COX-1 or COX-2 is related to efficacy or safety. Deracoxib has a half-life of 3 hours in dogs at 2-3 mg/kg and 19 hours at 20 mg/kg. It is highly protein bound. Oral absorption is 90% in dogs. Feeding delays absorption but does not diminish overall absorption. In cats the half-life is approximately 8 hours.

Indications and Clinical Uses

Deracoxib is used to decrease pain, inflammation, and fever. It has been used for the acute and chronic treatment of pain and inflammation in dogs. One of the most common uses is osteoarthritis but also has been used for pain associated with surgery. There has been only limited use of deracoxib in horses, and administration to other large animals has not been reported.

Precautionary Information

Adverse Reactions and Side Effects

GI problems are the most often adverse effects associated with NSAIDs and can include vomiting, diarrhea, nausea, ulcers, and erosions of the GI tract. Gastric and duodenal ulcers have been reported from use of deracoxib in dogs. In field trials with deracoxib, vomiting was the most often reported adverse effect. Renal toxicity, especially in dehydrated animals or animals with preexisting renal disease, has been shown for some NSAIDs. In studies performed in dogs, higher doses (five times the dose) caused azotemia in normal dogs.

Contraindications and Precautions

Dogs and cats with preexisting GI or renal problems may be at a greater risk of adverse effects from NSAIDs. Safety in pregnancy is not known, but adverse effects have not been reported. Safety studies are not available for dogs <4 months of age, pregnant animals, or lactating animals. In cats, use only as a single dose.

Drug Interactions

Do not administer with other NSAIDs or with corticosteroids. Corticosteroids have been shown to exacerbate the GI adverse effects. Some NSAIDs may interfere with the action of diuretic drugs and angiotensin-converting enzyme (ACE) inhibitors.

Instructions for Use

Chewable tablets can be administered with or without food. Long-term studies have not been completed in cats, only single-dose studies have been reported.

Patient Monitoring and Laboratory Tests

Monitor GI signs for evidence of diarrhea, GI bleeding, or ulcers. Because of risk of renal injury, monitor renal parameters (water consumption, BUN, creatinine, and urine-specific gravity) periodically during treatment. Deracoxib does not appear to affect thyroid hormone assays in dogs.

Formulations

Deracoxib is available in 25-, 75-, and 100-mg chewable tablets.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Deracoxib has been mixed in a liquid suspension in water. However, stability of compounded formulations has not been evaluated.

Small Animal Dosage

Dogs

• Postoperative pain: 3-4 mg/kg once daily as needed for up to 7 days. Chronic use: 1-2 mg/kg once daily PO.

Cats

• 1 mg/kg single dose, PO.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

Do not administer to animals that produce food.

RCI Classification: 4

Desmopressin Acetate

dess-moe-press′in ass′ih-tate

Trade and other names: DDAVP

Functional classification: Hormone

Pharmacology and Mechanism of Action

Synthetic peptide similar to antidiuretic hormone (ADH). It produces similar effects as natural ADH and is used to treat diabetes insipidus (DI) in animals. This action is related to stimulation of permeability to water to increase water reabsorption in the distal renal tubule. The difference between DDAVP and natural ADH is that DDAVP is longer acting and produces fewer vasoconstriction effects. In addition to the hormone effects, in humans administration of DDAVP results in a twofold to fivefold increase in the plasma von Willebrand factor. It may induce a 50% increase in von Willebrand factor in some animals but not as consistently as when administered to people.

Indications and Clinical Uses

Desmopressin is used as replacement therapy for patients with DI and also has been used for treatment of patients with mild to moderate von Willebrand’s disease prior to surgery or other procedure that may cause bleeding. However, the response in von Willebrand–deficient dogs is not as consistent or as great as in people.

Precautionary Information

Adverse Reactions and Side Effects

No side effects reported. In people, it has rarely caused thrombotic events.

Contraindications and Precautions

There are no specific contraindications.

Drug Interactions

Administration of urea and fludrocortisone will increase the antidiuretic effects.

Instructions for Use

Desmopressin is used only for central forms of DI. Duration of effect is variable (8-20 hours) but typically has a duration of 8-12 hours. It is ineffective for treatment of nephrogenic diabetes insipidus or polyuria from other causes. Intranasal product has been administered as eye drops in dogs. Onset of effect is within 1 hour. Oral tablets are available for humans, but the effects in dogs have not been reported.

Patient Monitoring and Laboratory Tests

Monitor water intake and urinalysis to assess therapy. Desmopressin may be used as a test for DI in animals. To perform this test, administer 2 mcg/kg SQ or IV or 20 mcg intranasally or in the eye. This should be followed by monitoring of urine concentration and the animal’s body weight. Increase in urine concentrating ability may indicate a diagnosis of DI.

Formulations

Desmopressin is available in a 4-mcg/mL injection, acetate nasal solution 100-mcg/mL (0.01%) metered spray, and 0.1- and 0.2-mg tablets (scored).

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

Withdrawal times are not established. However, this drug has rapid clearance, with little risk from residues; therefore, a short withdrawal time is suggested for food animals.

Desoxycorticosterone Pivalate

dess-oks-ih-kor-tik-oh-steer′one piv′ah-late

Trade and other names: Percorten-V, DOCP, and DOCA pivalate

Functional classification: Corticosteroid

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