Calcitriol

kal-sih-trye’ole

Trade and other names: Rocaltrol and Calcijex

Functional classification: Calcium supplement

Pharmacology and Mechanism of Action

Vitamin D analogue, also called 1,25-dihydroxycholecalciferol. Calcitriol is normally formed in the kidneys from 25-hydroxycholecalciferol. Action of calcitriol is to increase calcium absorption from the intestine and facilitate a parathyroid hormone (PTH) effect on bone. Low calcitriol levels in animals lead to decreased intestinal calcium absorption. Animals with chronic renal failure and hyperparathyroidism often have low calcitriol levels. Calcitriol can also inhibit synthesis and storage of PTH.

Indications and Clinical Uses

Calcitriol is used to treat calcium deficiency and diseases such as hypocalcemia associated with hyperparathyroidism. It is also used to increase calcium in cats that have had parathyroid glands removed. In this use, it is often administered with calcium supplements to the diet. It is used in dogs and cats to manage calcium and phosphorous balance with chronic kidney disease. Although used by veterinarians to reduce renal secondary PTH concentrations in animals with chronic renal disease, this benefit is more controversial and not supported by strong evidence. Calcitriol should not be used as a vitamin D supplement.

Precautionary Information

Adverse Reactions and Side Effects

Overdose can result in hypercalcemia.

Contraindications and Precautions

Do not use in patients that are at risk of hypercalcemia. Capsules made for humans may contain high overdoses for dogs and cats and should be reformulated.

Drug Interactions

Calcitriol may cause hypercalcemia if used with thiazide diuretics.

Instructions for Use

Doses should be adjusted in each patient according to response and monitoring calcium plasma concentration. Dose requirements may vary depending on the adjustment to calcium levels. For example, when used for treating dogs with chronic kidney disease, the dose was 2.5 ng/kg/day but ranged from 0.75 to 5 ng/kg/day based on adjustments from measuring calcium concentrations. When used in chronic renal failure, it is often used with intestinal phosphate binders (e.g., aluminum hydroxide) and dietary phosphorous restriction.

Patient Monitoring and Laboratory Tests

Monitor plasma ionized calcium concentration. Adjust doses as necessary to maintain normal calcium, phosphorous, and PTH concentrations. Monitor serum PTH concentrations (assays are available in many diagnostic laboratories). Monitor serum creatinine in animals when used to treat chronic kidney disease.

Formulations

Calcitriol is available as injection (Calcijex) in a 1- and 2-mcg/mL and in 0.25- and 0.5-mcg capsules and 1 mcg/mL oral solution (Rocaltrol).

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

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

Calcium Carbonate

Trade and other names: Titralac, Calci-mix, Tums, and generic brands

Functional classification: Calcium supplement

Pharmacology and Mechanism of Action

Calcium supplement. Calcium is essential for the functional integrity of several body systems. Calcium carbonate is equivalent to 400 mg of calcium ion per gram. Calcium carbonate neutralizes stomach acid for treating and preventing stomach ulcers.

Indications and Clinical Uses

Calcium carbonate is used as an oral calcium supplement for hypocalcemia, sometimes used with vitamin D supplements or calcitriol. It is used as antacid to treat gastric hyperacidity and GI ulcers and as an intestinal phosphate binder for hyperphosphatemia associated with renal failure.

Precautionary Information

Adverse Reactions and Side Effects

Few side effects. High calcium concentrations are possible. With any calcium supplements, constipation and intestinal bloating can occur.

Contraindications and Precautions

Do not administer to animals predisposed to forming calcium-containing renal or cystic calculi. When calcium carbonate or calcium citrate are used as a phosphate binder to prevent hyperphosphatemia, caution is advised to avoid hypercalcemia in patients with renal failure.

Drug Interactions

Oral administration of calcium supplements may interfere with absorption of other drugs such as fluoroquinolones (e.g., enrofloxacin, orbifloxacin, marbofloxacin), bisphosphonates, zinc, iron, and tetracyclines. Use cautiously with thiazide diuretics because this could cause a high increase in calcium concentrations.

Instructions for Use

Calcium carbonate is equivalent to 400 mg of calcium ion per gram. Doses are primarily derived from extrapolation of human doses. When used as a calcium supplement, doses should be adjusted according to serum calcium concentrations. Some tablets also contain vitamin D. Doses are based on calcium carbonate, not the ion concentration (e.g., a 650-mg tablet contains 260 mg of calcium ion).

Patient Monitoring and Laboratory Tests

Monitor serum calcium levels, particularly if patients have renal failure.

Formulations

Calcium carbonate is available in tablets or oral suspension, most of which are OTC. One gram of calcium carbonate is equivalent to 400 mg of calcium ion. Calci-mix is available in 1.25 g capsules. OTC tablets are available in 500, 600 mg and 1, 1.25, and 1.5 g. Oral suspension (Titralac) is 1.25 g per 5 mL.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated. Do not mix with other compounds that may chelate with calcium.

Small Animal Dosage

Dogs and Cats

• Calcium supplementation: 70-185 mg/kg/day given with food PO.

• Phosphate binder: 60-100 mg/kg/day in divided doses usually given with food PO.

Large Animal Dosage

No dose has been reported for large animals. Usually other calcium salts are used for supplementation in cattle.

Regulatory Information

No withdrawal times are available. Because this is a normal dietary supplement with little risk from residues, no withdrawal time is suggested for animals intended for food.

Calcium Chloride

Trade and other names: Generic brands

Functional classification: Calcium supplement

Pharmacology and Mechanism of Action

Calcium supplement. Calcium is essential for the functional integrity of several body systems. Injection is 27.2 mg of calcium ion (1.36 mEq) per mL. Calcium chloride increases ionized calcium in blood greater than other calcium salts.

Indications and Clinical Uses

Calcium chloride is used in acute situations to supplement as electrolyte replacement or as a cardiotonic. It is administered to cows for hypocalcemia (milk fever).

Precautionary Information

Adverse Reactions and Side Effects

Overdose with calcium is possible. Do not administer intravenous solution SQ or IM because it may cause tissue necrosis.

Contraindications and Precautions

Do not administer by IV injection at a rapid rate. Rapid intravenous administration to cows can cause cardiac arrhythmias and even death.

Drug Interactions

Calcium chloride will precipitate with sodium bicarbonate. Do not mix with compounds known to chelate with calcium.

Instructions for Use

Injection is 27.2 mg of calcium ion (1.36 mEq) per mL. It is usually used in emergency situations. Intracardiac administrations have been performed, but avoid injections into the myocardium.

Patient Monitoring and Laboratory Tests

Monitor serum calcium concentration. Monitor heart rhythm during administration.

Formulations

Calcium chloride is available in a 10% (100 mg/mL) solution. This supplies 1.36 mEq calcium ion per mL. Preparations for cattle usually contain 8.5-11.5 g calcium per 500 mL. Many formulations also contain magnesium.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated. Do not mix with other compounds that may chelate with calcium.

Small Animal Dosage

Dogs and Cats

• 0.1-0.3 mL/kg IV (slowly).

Large Animal Dosage

Cows

• 2 g/100 kg body weight, IV at a rate of 1 g/min.

Horses

• 1-2 g per adult horse IV slowly.

Regulatory Information

No withdrawal times are available. Because this is a normal supplement with little risk from residues, no withdrawal time is suggested for animals intended for food.

Calcium Citrate

Trade and other names: Citracal (OTC)

Functional classification: Calcium supplement

Pharmacology and Mechanism of Action

Calcium supplement. Calcium is essential for the functional integrity of several body systems. It is administered orally to supply calcium to the diet.

Indications and Clinical Uses

Calcium citrate is used in the treatment of hypocalcemia, such as with hypoparathyroidism. It also is used as an intestinal phosphate binder for hyperphosphatemia associated with renal failure.

Precautionary Information

Adverse Reactions and Side Effects

Hypercalcemia is possible with oversupplementation. With any calcium supplements, constipation and intestinal bloating can occur.

Contraindications and Precautions

When calcium carbonate or calcium citrate are used as a phosphate binder to prevent hyperphosphatemia, caution is advised to avoid hypercalcemia in patients with renal failure.

Drug Interactions

Oral administration of calcium supplements may interfere with absorption of other drugs such as fluoroquinolones (e.g., enrofloxacin, orbifloxacin, marbofloxacin), bisphosphonates, zinc, iron, and tetracyclines.

Instructions for Use

Doses should be adjusted according to serum calcium concentration.

Patient Monitoring and Laboratory Tests

Monitor serum calcium levels, particularly if patients have renal failure.

Formulations

Calcium citrate is available in 950-mg tablets (contains 200 mg of calcium ion).

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated. Do not mix with other compounds that may chelate with calcium.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

No withdrawal times are available. Because this is a normal dietary supplement with little risk from residues, no withdrawal time is suggested for animals intended for food.

Calcium Gluconate and Calcium Borogluconate

Trade and other names: Kalcinate, AmVet, Cal-Nate, and generic brands

Functional classification: Calcium supplement

Pharmacology and Mechanism of Action

Calcium supplement. Calcium is essential for the functional integrity of several body systems. It is administered orally to supply calcium to the diet, but injected for acute conditions in which a rapid increase in serum calcium is needed.

Indications and Clinical Uses

Calcium gluconate and calcium borogluconate are used in the treatment of hypocalcemia, such as with hypoparathyroidism. They are used in electrolyte deficiency. Calcium supplements are administered to cattle for treatment of hypocalcemia (milk fever).

Precautionary Information

Adverse Reactions and Side Effects

Hypercalcemia is possible with oversupplementation. Calcium supplements may cause constipation. SQ or IM injections of calcium salts may cause tissue injury and necrosis at the site of injection.

Contraindications and Precautions

Avoid rapid intravenous administration. Avoid use in patients that are prone to calcium-containing renal or cystic calculi. Avoid administration of intravenous solution IM or SQ because it will cause tissue necrosis.

Drug Interactions

Do not mix with any bicarbonate (sodium bicarbonate) phosphates, sulfates, and tartrates because it may precipitate. Specific drugs that can precipitate with calcium gluconate include oxytetracycline, promethazine, sulfamethazine, tetracycline, cephalothin, and amphotericin B. Calcium supplements may interfere with the oral absorption of iron, tetracyclines, and fluoroquinolones.

Instructions for Use

The 500-mg tablets contain 45 mg of calcium ion. The 10% injection contains 97 mg (9.3 mg of calcium ion [0.47 mEq]) per mL.

Patient Monitoring and Laboratory Tests

Monitor serum calcium concentration. Monitor heart rate during intravenous administration.

Formulations

Calcium gluconate is available as 10% (100 mg/mL) injection. Calcium gluconate 10% contains 9.3 mg of calcium ion per mL, or 0.465 mEq per mL. Calcium gluconate is available in tablets in sizes of 325, 500, 650, 975 mg, and 1 g. Each gram contains 90 mg of calcium ion. Chewable tablets intended for human use are available in 650-mg and 1-g tablets.

Calcium borogluconate is available as 230 mg/mL (AmVet Calcium Gluconate 23% and Cal Nate).

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Solutions should be clear. If crystals are present, warm vial up to 30-40°C (86-104°F) to dissolve crystals. Stability of compounded formulations has not been evaluated. Do not mix with other compounds that may chelate with calcium.

Small Animal Dosage

Dogs and Cats

• 75-500 mg IV, slowly.

Regulatory Information

No withdrawal times are available. Because this is a normal dietary supplement with little risk from residues, no withdrawal time is suggested for animals intended for food.

Calcium Lactate

Trade and other names: Generic brands

Functional classification: Calcium supplement

Pharmacology and Mechanism of Action

Calcium supplement. Calcium is essential for the functional integrity of several body systems. This oral supplement is used to provide animals with dietary calcium to prevent or treat a deficiency.

Indications and Clinical Uses

Calcium lactate is used in treatment of hypocalcemia, such as with hypoparathyroidism, and in electrolyte deficiency.

Precautionary Information

Adverse Reactions and Side Effects

Hypercalcemia possible with over supplementation.

Contraindications and Precautions

Avoid use in patients that are prone to calcium-containing renal or cystic calculi.

Drug Interactions

Calcium supplements may interfere with the oral absorption of iron, tetracyclines, and fluoroquinolones.

Instructions for Use

Calcium lactate contains 130 mg of calcium ion per gram.

Patient Monitoring and Laboratory Tests

Monitor serum calcium concentrations.

Formulations

Calcium lactate is available in 325-mg (42.25 mg of calcium ion) and 650-mg (84.5 mg of calcium ion) OTC tablets.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated. Do not mix with other compounds that may chelate with calcium.

Small Animal Dosage

Dogs

• 0.5 g/day (in divided doses) PO.

Cats

• 0.2-0.5 g/day (in divided doses) PO.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

No withdrawal times are available. Because this is a normal dietary supplement with little risk from residues, no withdrawal time is suggested for animals intended for food.

Captopril

kap’toe-pril

Trade and other names: Capoten

Functional classification: Vasodilator, angiotensin-converting enzyme (ACE) inhibitor

Pharmacology and Mechanism of Action

ACE inhibitor. Captopril inhibits conversion of angiotensin I to angiotensin II, leading to vasodilation. Angiotensin II is a potent vasoconstrictor and will stimulate sympathetic stimulation, renal hypertension, and synthesis of aldosterone. ACE inhibitors limit the ability of aldosterone to cause sodium and water retention that contribute to congestion. Captopril, like other ACE inhibitors, will cause vasodilation, but ACE inhibitors also contribute to vasodilation by increasing concentrations of some vasodilating kinins and prostaglandins.

Indications and Clinical Uses

Captopril, like other ACE inhibitors, is used to treat hypertension and CHF. It has been used primarily in dogs, but its use has declined. Captopril is the first ACE inhibitor available for clinical use but has been replaced by other ACE inhibitors such as enalapril, benazepril and lisinopril. Unlike benazepril and enalapril, it has not been studied for clinical use in dogs and cats.

Precautionary Information

Adverse Reactions and Side Effects

Hypotension is possible with excessive doses. Captopril may cause azotemia in some patients, especially when administered with potent diuretics (e.g., furosemide). GI side effects, predominantly anorexia, are common in dogs.

Contraindications and Precautions

Discontinue ACE inhibitors in pregnant animals; they cross the placenta and have caused fetal malformations and death of the fetus.

Drug Interactions

Use cautiously with diuretics and potassium supplements. Nonsteroidal anti-inflammatory drugs (NSAIDs) may diminish antihypertensive effect.

Instructions for Use

Use of captopril has been replaced by enalapril and benazepril in small animal practices, and most clinical experts recommend these other drugs instead of captopril.

Patient Monitoring and Laboratory Tests

Monitor patients carefully to avoid hypotension. With all ACE inhibitors, monitor electrolytes and renal function 3-7 days after initiating therapy and periodically thereafter.

Formulations

Captopril is available in 12.5-, 25-, 50-, and 100-mg tablets.

Stability and Storage

Store in a tightly sealed container at room temperature. More stable at acidic pH. Oral compounded solutions are stable for 30 days refrigerated. However, tap water should not be used; purified water is necessary to ensure stability.

Small Animal Dosage

Dogs

• 0.5-2 mg/kg q8-12h PO.

Cats

• 3.12-6.25 mg/cat q8h PO.

Large Animal Dosage

No dose has been reported for large animals.

Regulatory Information

Do not administer to animals intended for food.

RCI Classification: 3

Carbenicillin

kar-ben-ih-sill’in

Trade and other names: Geopen and Pyopen Carbenicillin indanyl sodium (Geocillin)

Functional classification: Antibacterial

Pharmacology and Mechanism of Action

Beta-lactam antibiotic. Carbenicillin has an action similar to ampicillin, which inhibits bacterial cell wall synthesis. Carbenicillin has a broad spectrum of activity that includes both gram-positive and gram-negative bacteria. However, resistance is possible, especially among beta-lactamase–positive strains. The difference between carbenicillin and ampicillin is that it is active against Pseudomonas aeruginosa and other gram-negative bacteria that are resistant to ampicillin and amoxicillin. Half-life is short and clearance is rapid in animals; therefore it requires frequent administration.

Indications and Clinical Uses

Carbenicillin is used to treat gram-negative infections in animals, including infections caused by Pseudomonas aeruginosa. The use of carbenicillin is uncommon in veterinary medicine and has been replaced by other drugs such as ticarcillin and cephalosporins. Indanyl sodium carbenicillin (Geocillin) is poorly absorbed orally and should not be used for systemic infections. However, this form may produce high enough urine concentrations for treating some infections of lower urinary tract.

Precautionary Information

Adverse Reactions and Side Effects

Carbenicillin, like other penicillin drugs, may cause allergy. Carbenicillin may cause bleeding problems in some animals by interfering with platelets.

Contraindications and Precautions

Use cautiously in patients sensitive to penicillins (e.g., allergy).

Drug Interactions

No drug interactions are reported in animals. Do not mix in vial with other drugs because inactivation may result.

Instructions for Use

Carbenicillin has a short half-life and should be administered frequently for optimum bactericidal effect. Carbenicillin injection often is administered with an aminoglycoside when treating Pseudomonas infections. Do not mix with aminoglycosides prior to administration or inactivation will result. Carbenicillin indanyl sodium is the oral formulation of carbenicillin but attains concentrations that are only sufficient for treating UTIs. Do not use for systemic infections.

Patient Monitoring and Laboratory Tests

Culture and sensitivity testing recommended to guide therapy. CLSI break points are ≤128 mcg/mL when testing for Pseudomonas-susceptible organisms and ≤16 mcg/mL for other gram-negative organisms.

Formulations

Carbenicillin has been unavailable because other drugs are used as a replacement. However, older formulations include 1-, 2-, 5-, 10-, and 30-g vials for injection and 500-mg tablets.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stable at pH of 6.5, but rate of degradation is greater at higher or lower pH. Use quickly after reconstitution of vials for injection.

Small Animal Dosage

Dogs and Cats

• Carbenicillin: 40-50 mg/kg and up to 100 mg/kg q6-8h IV, IM, or SQ.

• Carbenicillin indanyl sodium: 10 mg/kg q8h PO.

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).

Carbimazole

kar-bih’mah-zole

Trade and other names: Neomercazole, Vidalta

Functional classification: Antithyroid drug

Pharmacology and Mechanism of Action

Antithyroid drug similar to methimazole. It is a pro-drug converted to methimazole after administration. Like methimazole, the action is to serve as substrate for thyroid peroxidase (TPO) and inhibits it and decreases incorporation of iodide into tyrosine molecules. It also inhibits coupling of mono-iodinated and di-iodinated residues to form T4 and T3. Carbimazole has been preferred in some patients because, compared to methimazole, it may have fewer side effects, such as less frequent GI problems. Oral absorption (based on methimazole concentrations) is 88% in cats.

Indications and Clinical Uses

Carbimazole has been used for treating hyperthyroidism, primarily in cats. Carbimazole has been more readily available in Europe, where there is more clinical experience, than in the US. Experience in the US is limited because of lack of availability. Sustained-release formulation in Europe (Vidalta) administered to people as 15 mg once per day, followed by 10-25 mg once daily in people.

Precautionary Information

Adverse Reactions and Side Effects

In cats, lupus-like reactions are possible, such as vasculitis and bone marrow changes. In people, it has caused agranulocytosis and leukopenia. Other systemic effects reported for methimazole are expected to be similar for carbimazole (for example, bone marrow effects).

Contraindications and Precautions

Do not use in cats with bone marrow suppression or thrombocytopenia.

Drug Interactions

No drug interactions are reported in animals.

Instructions for Use

Carbimazole is used in Europe; clinical experience in US is limited. Otherwise, the clinical indications and use are similar as for methimazole.

Patient Monitoring and Laboratory Tests

Monitor thyroid concentrations to adjust dose. Monitor CBC periodically for evidence of bone marrow suppression.

Formulations

This drug has not been approved in the United States. This drug has been obtained in Europe.

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

Do not administer to animals intended for food.

Carboplatin

kar-boe-plat’ in

Trade and other names: Paraplatin

Functional classification: Anticancer agent

Pharmacology and Mechanism of Action

Anticancer agent. Carboplatin is a second-generation platinum compound and is related to cisplatin. Action is similar to cisplatin. Its action is a bifunctional alkylating agent, which interrupts replication of DNA in tumor cells. It induces a non-cell cycle–dependent tumor cell lysis. Major route of elimination is via the kidneys. It has replaced cisplatin in some anticancer protocols because it may not be as toxic.

Indications and Clinical Uses

Carboplatin has been used for squamous cell carcinoma and other carcinomas, melanoma, osteosarcomas, and other sarcomas. When used in dogs, myelosuppression has been the most dose-limiting factor. Compared to cisplatin, carboplatin is better tolerated in cats and is preferred. However, bone marrow suppression is the dose-limiting toxicity in cats.

Precautionary Information

Adverse Reactions and Side Effects

Compared to cisplatin, carboplatin is less emetogenic and less nephrotoxic. In dogs, the other most common adverse effects relate to GI system toxicity (gastroenteritis, vomiting, anorexia, and diarrhea). The dose limiting effect is myelosuppression, anemia, leukopenia, or thrombocytopenia. In dogs, nadir of myelosuppression occurs at 14 days, but recovery occurs by 21-28 days. In cats, the nadir is 21 days and recovery occurs by 28 days. Vomiting is not as much of a problem as for cisplatin, but GI toxicosis is still a problem, especially in smaller dogs. Because it is excreted by the kidneys, animals with decreased renal function may have a higher rate of GI toxicosis.

Contraindications and Precautions

In one study, small dogs were more prone than larger dogs to adverse effects.

Drug Interactions

Do not use with other nephrotoxic drugs.

Instructions for Use

Available for reconstitution for injection. It is stable for 1 month when reconstituted with 5% dextrose. It may be frozen at -4°C to prolong the stability of a reconstituted vial. Do not use with administration sets containing aluminum because of incompatibility. It is usually administered in specific anticancer protocols; consult oncology protocols for regimen. In dogs, it has been dosed on a milligram per square meter dose, which has produced a higher incidence of adverse effects in smaller dogs compared to larger dogs; however, smaller dogs also were more likely to respond. Carboplatin is excreted by the kidneys; therefore, the dose should be decreased in proportion to reduced GFR and creatinine clearance.

Patient Monitoring and Laboratory Tests

Monitoring of CBC and platelets is recommended during treatment.

Formulations

Carboplatin is available in 50- and 150-mg vials for injection.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stable for 1 month if reconstituted with 5% dextrose solution. It is stable if frozen at −4°C.

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.

Carprofen

car-proe’fen

Trade and other names: Rimadyl, Vetprofen, Zinecarp (Europe), and generic brands

Functional classification: NSAID

Pharmacology and Mechanism of Action

Carprofen is a nonsteroidal anti-inflammatory drug (NSAID). Like other drugs in this class, carprofen has analgesic and anti-inflammatory effects by inhibiting the synthesis of prostaglandins. The enzyme inhibited by an NSAID is the cyclo-oxygenase enzyme (COX). The COX enzyme exists in two isoforms: 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. (There may be crossover of COX-1 and COX-2 effects in some situations.) Carprofen is relatively COX-1 sparing compared to older NSAIDs, but it is not known if the specificity for COX-1 or COX-2 determines efficacy or safety. In horses, carprofen is not as COX-2 selective as it is in dogs. As an analgesic agent the mechanism of action may involve other mechanisms other than inhibition of prostaglandin synthesis.

Indications and Clinical Uses

Carprofen is used primarily for treatment of musculoskeletal pain and acute pain related to surgery or trauma. It is used primarily for treatment of dogs. Long-term safe use in cats has not been established. However, it is registered in Europe for one-time administration in cats at 4 mg/kg injection. Although use in large animals is uncommon, in cattle, carprofen has been shown to reduce inflammation in cows associated with Escherichia coli mastitis at a dose of 0.7 mg/kg IV. Although carprofen has been used in horses, it does not show the same COX-2 selectivity of inhibition as in dogs. In cattle, carprofen is registered in Europe for treatment of fever associated with mastitis and used to reduce inflammation associated with bovine respiratory disease.

Precautionary Information

Adverse Reactions and Side Effects

Safety of carprofen in dogs was determined by the sponsor during preclinical studies. The most common adverse effect in dogs has been in the GI tract (vomiting, anorexia, and diarrhea). GI ulcers, perforation, and bleeding are uncommon in dogs. In rare cases, carprofen has caused idiosyncratic acute hepatic toxicity in dogs. Signs of toxicity usually appear 2-3 weeks after exposure. There were no adverse effects on kidneys when carprofen was evaluated in anesthetized dogs. Carprofen may lower total thyroid (T4) concentrations in dogs but not free T4. Carprofen has produced toxicity in cats if administered at the same dose rates as for dogs.

Contraindications and Precautions

Do not use in cats at doses intended for dogs. Do not administer to animals prone to GI ulcers. Do not administer with ulcerogenic drugs such as corticosteroids. If a patient has had previous adverse effects from NSAIDs, carprofen should be used cautiously.

Drug Interactions

Use NSAIDs cautiously with other drugs known to cause GI injury (e.g., corticosteroids). The efficacy of angiotensin-converting enzyme (ACE) inhibitors and diuretics (e.g., furosemide) may be diminished when administered concurrently with NSAIDs.

Instructions for Use

Doses are based on clinical investigations in dogs with arthritis and for treatment of pain associated with surgery. Dogs may receive carprofen either once daily or twice daily with similar effectiveness. The only approved dose for cats is 4 mg/kg as a one-time injection for surgical pain. However, for long-term use, pharmacokinetic extrapolations suggest a long-term dose of 0.5 mg/kg q24h PO. Long-term safety at this dose has not been established.

Patient Monitoring and Laboratory Tests

After administration has begun, one should monitor hepatic enzymes for evidence of drug-induced hepatic toxicity approximately 7-14 days after treatment has started. If liver enzymes are elevated, discontinue the medication and contact the drug manufacturer.

Formulations

Carprofen is available in 25-, 75-, and 100-mg caplets; 25-, 75- and 100-mg chewable tablets; and injectable solution: 50 mg/mL.

(Zinecarp injection has also been available in Europe.)

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Carprofen has been compounded by mixing tablets with methylcellulose gel (1%), simple syrup, and a suspending and flavoring vehicle to make a 1.25-, 2.5- and 5-mg/mL suspension. This formulation was stable if stored in refrigerator or room temperature for 28 days.

Regulatory Information

Withdrawal times have not been established for carprofen in the US. It is suggested (based on European labeling) that the withdrawal time for meat is 21 days but zero days for milk. Caution is advised when considering carprofen for cattle because it has a longer half-life in cows compared to other animals (30-40 hours).

RCI Classification: 4

Carvedilol

kar-ved’ ih-lole

Trade and other names: Coreg

Functional classification: Antiarrhythmic

Pharmacology and Mechanism of Action

Antiarrhythmic. Nonselective beta-receptor blocker. Carvedilol is a third-generation adrenergic blocker. Carvedilol blocks both beta₁-receptors and beta₂-receptors in heart and other tissues. Carvedilol is unique because it also has alpha-receptor–blocking properties that will produce vasodilation. It also is reported to have antioxidant properties.

In dogs the half-life is short (1.2 hrs). Oral absorption is low and variable because of high systemic clearance and first-pass effects. Average oral absorption in one study was only 14% and highly variable, but in another study it was only 1.6% (range 0.4%-54%), making the oral use of carvedilol in dogs unpredictable. In people, it has been also shown to prolong survival in human patients with heart failure, but this effect has not been measured in animals.

Indications and Clinical Uses

Carvedilol has been used to treat arrhythmias in animals. It is also used to treat systemic hypertension and to block beta-cardiac receptors in animals with rapid heart rates. Efficacy has been based on anecdotal accounts, extrapolation from humans, and limited studies in healthy dogs. In healthy dogs, 0.2 mg/kg PO decreased heart rate and 0.4 mg/kg PO decreased heart rate and lowered blood pressure. At 0.4 mg/kg, the effects in healthy dogs persisted for 36 hours. In other studies, doses of 0.3 mg/kg were not effective. In clinical patients, the optimum dose is not known and long-term benefits have not been established. Because oral absorption is inconsistent in dogs (discussed in pharmacology section), the response may be variable. Elimination is rapid after oral administration to dogs, but clinical pharmacodynamic effects may persist for up to 12 hours, possibly from the metabolites.

< div class='tao-gold-member'>

Only gold members can continue reading. Log In or Register to continue

Fastest Veterinary Medicine Insight Engine

C