Capromorelin — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO (oral)	3 mg/kg (range 2-5 mg/kg)	Once daily (q24h)	Duration: Typically 3-14 days; may be used longer if needed Notes: Administer on an empty stomach (at least 1 hour before or 2 hours after feeding) for optimal absorption. If no response after 3 days, reassess the patient.
Cat	PO (oral)	2-3 mg/kg (extrapolated from dog dose)	Once daily (q24h)	Duration: Short-term use; monitor for efficacy Notes: Not FDA-approved for cats; use with caution and under veterinary supervision.

Clinical Indications & Species Uses

General Indications

Appetite stimulation in dogs

Dog (Canine)

Management of decreased appetite (anorexia) in dogs
Weight loss management in dogs

Cat (Feline)

May be used off-label for appetite stimulation in some cases

Pharmacology & Mechanism of Action

Drug Class: Ghrelin receptor agonist | Pharmacological Group: Appetite stimulant

Mechanism of Action: Capromorelin is a selective agonist of the ghrelin receptor (growth hormone secretagogue receptor type 1a, GHS-R1a). It mimics the action of the endogenous hormone ghrelin, which is known as the 'hunger hormone'. Activation of GHS-R1a in the hypothalamus stimulates the release of growth hormone (GH) from the pituitary gland and also activates neurons in the arcuate nucleus that produce neuropeptide Y (NPY) and agouti-related peptide (AgRP), which are potent orexigenic signals. This leads to increased appetite and food intake. Additionally, capromorelin may enhance gastric motility and gastric emptying, contributing to its appetite-stimulating effects.

Pharmacodynamics: Capromorelin produces a dose-dependent increase in food intake and body weight in animals. It also stimulates the release of growth hormone, which may have anabolic effects. The appetite-stimulating effect is typically observed within 1-2 hours after oral administration and can last for up to 24 hours. In dogs, capromorelin has been shown to increase food intake and improve body condition in animals with reduced appetite due to various causes. It does not appear to have significant effects on other hormones such as cortisol or ACTH at therapeutic doses.

⚡ Pharmacokinetics Summary

Absorption: Capromorelin is rapidly absorbed after oral administration. In dogs, peak plasma concentrations are reached within 1-2 hours. The oral bioavailability is approximately 50-60% in dogs, but it is significantly reduced when administered with food (by about 50%). Therefore, it is recommended to administer on an empty stomach for optimal absorption.

Distribution: Capromorelin is widely distributed in the body. The volume of distribution is approximately 1-2 L/kg in dogs. It is moderately bound to plasma proteins (about 60-70%). It crosses the blood-brain barrier to exert its central effects.

Metabolism: Capromorelin is extensively metabolized in the liver, primarily by cytochrome P450 enzymes (CYP3A4 in humans, but in dogs likely CYP3A12). The major metabolic pathways include oxidation and glucuronidation. The metabolites are less active than the parent compound.

Excretion: The metabolites are primarily excreted in the feces (about 60-70%) and to a lesser extent in the urine (about 20-30%). The elimination half-life in dogs is approximately 2-4 hours, but the pharmacodynamic effect on appetite lasts longer than the plasma half-life.

Half-Life: Dogs: ~2-4 hours; Cats: ~2-3 hours (estimated)

Bioavailability: Dogs: ~50-60% (oral, fasted); reduced when given with food

Protein Binding: Approximately 60-70% in dogs

Available Formulations & Strengths

Oral Solution 30 mg/mL (PO)

Tablet 15 mg, 30 mg, 60 mg (PO)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to capromorelin or any component of the formulation
Use in animals with known or suspected growth hormone-secreting tumors (e.g., pituitary tumors)
Use in animals with severe hepatic or renal impairment (caution)
Use in pregnant or lactating animals (safety not established)

Warnings & Clinical Precautions:

Use with caution in animals with diabetes mellitus, as capromorelin may affect glucose metabolism.
Use with caution in animals with cardiovascular disease, as ghrelin receptor agonists may have cardiovascular effects.
Do not use in animals with a history of seizures.
Safety in breeding, pregnant, or lactating dogs has not been established.
Administer on an empty stomach to maximize absorption; if given with food, the dose may need to be adjusted.
Monitor for signs of vomiting or diarrhea, especially in the first few days of treatment.
Not for use in humans; keep out of reach of children.

Adverse Effects & Reactions

Common:

Vomiting
Diarrhea
Lethargy
Increased salivation
Decreased appetite (paradoxical)

Serious / Severe:

Hypersensitivity reactions (angioedema, urticaria)
Seizures (rare)
Hepatotoxicity (rare)

Rare:

Cardiac arrhythmias
Behavioral changes (aggression, restlessness)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
CYP3A inhibitors (e.g., ketoconazole, itraconazole)	May increase capromorelin plasma concentrations, leading to increased risk of adverse effects.	Moderate
CYP3A inducers (e.g., phenobarbital, rifampin)	May decrease capromorelin plasma concentrations, reducing efficacy.	Moderate
Corticosteroids	May antagonize the appetite-stimulating effects of capromorelin.	Mild
Anticholinergic drugs	May reduce gastric motility, potentially affecting absorption of capromorelin.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Vomiting
Diarrhea
Lethargy
Tremors
Seizures (in severe cases)
Hypersalivation

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce vomiting if ingestion is recent and the animal is conscious. Administer activated charcoal to reduce absorption. Provide fluid therapy to correct dehydration and electrolyte imbalances. Monitor vital signs and neurological status. In cases of seizures, administer anticonvulsants (e.g., diazepam).

Food Animal Withdrawal Times

Not approved for use in food-producing animals. Withdrawal times are not established.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

Handling & Special Conditions: Keep the container tightly closed. Protect from moisture. Do not freeze the oral solution.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved by the FDA for use in dogs (as Entyce®) for the management of decreased appetite.

Extra-Label (Off-Label) Use: In the US, capromorelin is FDA-approved for use in dogs only. Extra-label use in other species (e.g., cats) is permitted under the Animal Medicinal Drug Use Clarification Act (AMDUCA) if a valid veterinarian-client-patient relationship exists, and if there is no approved animal drug for the condition, or the approved drug is ineffective. However, withdrawal times for food animals must be considered, but since capromorelin is not approved for food animals, its use is generally prohibited in food-producing animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Capromorelin is a valuable tool for managing anorexia in dogs, particularly in cases of chronic kidney disease, cancer, or post-operative recovery. It is generally well-tolerated, with vomiting being the most common adverse effect. It is important to administer the drug on an empty stomach to ensure adequate absorption. Clinical response should be assessed within 3 days; if no improvement in appetite is observed, the diagnosis and treatment plan should be reevaluated. Capromorelin should not be used as a sole therapy for underlying diseases; it is intended to stimulate appetite while the primary condition is being treated. In cats, its use is off-label and efficacy is less well-documented; alternative appetite stimulants such as mirtazapine may be preferred. Always monitor for potential drug interactions and adverse effects, especially in animals with hepatic or renal impairment.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)