Megestrol Acetate

Progestin Hormonal agent / Synthetic progestogen

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO Estrus suppression: 2.2 mg/kg/day for 8 days, then 0.55 mg/kg/day for 14 days; or 1.1 mg/kg/day for 8 days, then 0.55 mg/kg/day for 14 days. For false pregnancy: 0.55-1.1 mg/kg/day for 5-8 days. For appetite stimulation: 0.25-0.5 mg/kg/day for 5-7 days. Once daily Duration: Variable depending on indication; estrus suppression: 22 days; false pregnancy: 5-8 days; appetite stimulation: 5-7 days.
Notes: Administer with food to reduce GI upset. Do not use in intact males or pregnant animals. For estrus suppression, start treatment during anestrus or early proestrus.
Cat PO Estrus suppression: 5 mg/cat/day for 3 days, then 2.5-5 mg/cat once weekly for up to 4 months. For dermatologic conditions: 2.5-5 mg/cat every other day to twice weekly. For appetite stimulation: 2.5-5 mg/cat every 2-3 days. Variable; daily initially, then weekly or as needed Duration: Estrus suppression: up to 4 months; dermatologic: 2-4 weeks; appetite: as needed.
Notes: Use lowest effective dose. Monitor for signs of diabetes mellitus or adrenal suppression with long-term use.
Horse PO Estrus suppression: 0.5-1 mg/kg/day (extra-label). Once daily Duration: Variable; often used for 7-10 days before expected estrus.
Notes: Not approved for use in horses; use with caution. May cause prolonged estrus suppression and endometrial changes.
Ferret PO For adrenal disease: 5 mg/ferret/day (extra-label). Once daily Duration: Long-term, as needed.
Notes: Use with caution; monitor for signs of hyperadrenocorticism.

Clinical Indications & Species Uses

General Indications
  • Synthetic progestin used for estrus suppression and various dermatologic and behavioral conditions in companion animals
Dog (Canine)
  • Control of estrus (heat) in female dogs
  • Treatment of false pregnancy (pseudopregnancy)
  • Management of behavioral disorders (e.g., aggression, urine marking) in some cases
  • Appetite stimulation in cachectic dogs
Cat (Feline)
  • Control of estrus in female cats
  • Treatment of feline acne
  • Treatment of eosinophilic granuloma complex
  • Treatment of psychogenic alopecia
  • Appetite stimulation in chronic illness
Exotic & Other Species
  • Occasionally used in ferrets for adrenal disease (extra-label) and in small mammals for reproductive control

Pharmacology & Mechanism of Action

Drug Class: Progestin | Pharmacological Group: Hormonal agent / Synthetic progestogen

Mechanism of Action: Megestrol acetate is a synthetic progestogen that exerts its effects by binding to progesterone receptors in target tissues. It inhibits the release of gonadotropins (LH and FSH) from the anterior pituitary, thereby suppressing ovarian function and estrus. It also has anti-inflammatory and anti-androgenic effects, and can stimulate appetite by affecting appetite centers in the hypothalamus. In some species, it may have glucocorticoid-like activity, leading to increased appetite and weight gain.

Pharmacodynamics: Megestrol acetate suppresses estrus in female dogs and cats by inhibiting the LH surge and preventing ovulation. It also causes endometrial proliferation and mucification of the vaginal epithelium. In cats, it is used to treat feline acne, eosinophilic granuloma complex, and psychogenic alopecia due to its anti-inflammatory and immunosuppressive properties. It can also be used as an appetite stimulant in cachectic animals. Its effects are dose-dependent and reversible upon discontinuation.

⚡ Pharmacokinetics Summary

Absorption: Megestrol acetate is well absorbed after oral administration. Peak plasma concentrations are reached within 1-4 hours in dogs and cats. Food may enhance absorption.
Distribution: It is lipophilic and distributes widely into tissues, including adipose tissue. It crosses the placenta and is excreted in milk. Volume of distribution is not well characterized in veterinary species.
Metabolism: It is extensively metabolized in the liver via hydroxylation and conjugation. Metabolites are excreted in urine and feces.
Excretion: Excretion is primarily via urine (about 50-60%) and feces (about 30-40%). Enterohepatic recirculation may occur.
Half-Life: Dog: approximately 4-8 hours; Cat: approximately 8-12 hours; Horse: approximately 1-2 days (based on limited data).
Bioavailability: Oral bioavailability is high, estimated at 80-100% in dogs and cats.
Protein Binding: Approximately 90% bound to plasma proteins, mainly albumin.

Available Formulations & Strengths

Oral Tablet 5 mg, 20 mg, 40 mg (PO)
Oral Suspension 40 mg/mL (compounded) (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Pregnancy (may cause masculinization of female fetuses and other developmental abnormalities)
  • Lactation (excreted in milk, may affect nursing offspring)
  • Known hypersensitivity to progestins
  • Uterine disease (e.g., pyometra, endometritis)
  • Mammary neoplasia (progestins may stimulate growth)
  • Diabetes mellitus (may worsen glycemic control)
  • Pancreatitis (may increase risk)
  • Use in intact males for behavioral problems (not effective and may cause prostatic disease)
Warnings & Clinical Precautions:
  • Use with caution in animals with a history of seizures, cardiac disease, or hepatic dysfunction.
  • Long-term use may increase risk of mammary tumors, uterine infections, and diabetes mellitus in cats and dogs.
  • May cause adrenal suppression; avoid abrupt withdrawal after prolonged therapy.
  • In cats, high doses may cause transient diabetes mellitus; monitor blood glucose.
  • Do not use in animals intended for breeding.
  • In food animals, extra-label use is prohibited in the US; withdrawal times must be observed if used in accordance with regulations.
  • Use in horses may cause sweating, laminitis, and altered behavior.

Adverse Effects & Reactions

Common:

  • Increased appetite and weight gain
  • Lethargy
  • Mild depression
  • Mammary gland enlargement
  • Changes in hair coat (e.g., thinning, alopecia)

Serious / Severe:

  • Diabetes mellitus (especially in cats)
  • Pyometra (uterine infection)
  • Mammary hyperplasia or neoplasia
  • Adrenal suppression
  • Iatrogenic Cushing's syndrome (with high doses)
  • Hepatotoxicity (rare)

Rare:

  • Thromboembolism
  • Pancreatitis
  • Skin reactions (e.g., injection site reactions if injectable form used)
  • Behavioral changes (e.g., aggression, increased vocalization)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Corticosteroids Additive immunosuppressive and hyperglycemic effects; may increase risk of adrenal suppression. Moderate
Insulin or oral hypoglycemic agents May antagonize the effects of these drugs, leading to poor glycemic control. Moderate
Phenobarbital or other hepatic enzyme inducers May increase metabolism of megestrol acetate, reducing its efficacy. Mild
Cyclosporine Potential for increased cyclosporine levels due to competition for CYP450 metabolism. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Diarrhea
  • Lethargy
  • Depression
  • Polyuria and polydipsia (due to hyperglycemia)
  • In severe cases, signs of adrenal suppression or diabetes mellitus

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is stable. Administer activated charcoal to reduce absorption. Monitor blood glucose and electrolytes. Provide fluid therapy if needed. In cases of prolonged overdose, taper the drug to avoid adrenal crisis.

Food Animal Withdrawal Times

Megestrol acetate is not approved for use in food-producing animals. Extra-label use in food animals is prohibited in the US under AMDUCA. If used in non-approved species, a prolonged withdrawal period (e.g., 30 days for meat, 7 days for milk) may be considered, but it is not recommended.

Storage, Handling & Regulatory Information

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

Handling & Special Conditions: Protect from moisture. Keep container tightly closed. Keep out of reach of children and animals.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use (e.g., for appetite stimulation in cancer patients).

Extra-Label (Off-Label) Use: In the US, megestrol acetate is not FDA-approved for veterinary use, but it is legally used in companion animals under the Animal Medicinal Drug Use Clarification Act (AMDUCA) when prescribed by a veterinarian. Extra-label use in food animals is prohibited. In the EU, it may be used under cascade regulations for non-food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Megestrol acetate is a valuable tool for managing estrus in dogs and cats, but its use requires careful consideration of risks, especially with long-term therapy. It is also effective for certain dermatologic conditions in cats and as an appetite stimulant. However, the potential for serious adverse effects, including diabetes mellitus and adrenal suppression, necessitates regular monitoring (e.g., blood glucose, cortisol levels) and using the lowest effective dose for the shortest duration. In dogs, it is generally reserved for short-term estrus postponement or for specific medical conditions. In cats, it is often used for behavioral dermatoses, but alternative treatments should be considered first. Always inform owners of the risks and monitor for signs of pyometra, mammary changes, or metabolic disturbances. For appetite stimulation, it can be useful in palliative care, but other appetite stimulants (e.g., mirtazapine) may be safer. Due to its progestogenic effects, it should not be used in breeding animals or those with reproductive tract disease.

References & Literature

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