Medroxyprogesterone Acetate

Progestin Hormonal / Progestogen

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 5-10 mg/kg q24h Duration: Up to 4 months for estrus suppression; shorter for other indications
Notes: For estrus suppression, start during anestrus. For pseudopregnancy, use 2-5 mg/kg/day for 5-7 days.
Dog SC 10-20 mg/kg (depot) Every 3-6 months Duration: As needed
Notes: Depot injection for long-term estrus suppression; monitor for pyometra.
Cat PO 2.5-5 mg/cat q24h Duration: Up to 4 months
Notes: For estrus suppression; use lowest effective dose.
Cat SC 50-100 mg/cat (depot) Every 3-6 months Duration: As needed
Notes: Depot injection; risk of mammary neoplasia and diabetes mellitus with long-term use.
Horse IM 1-2 mg/kg q24h Duration: 5-7 days
Notes: Off-label; altrenogest is preferred for estrus suppression.

Clinical Indications & Species Uses

General Indications
  • Temporary suppression of estrus in female dogs and cats
  • Management of certain hormone-responsive dermatoses
  • Behavioral modification in some species
Dog (Canine)
  • Estrus suppression (temporary)
  • Treatment of false pregnancy (pseudopregnancy)
  • Management of behavioral disorders (e.g., aggression, urine marking)
  • Adjunct in treatment of prostatic hyperplasia
  • Treatment of some dermatological conditions (e.g., eosinophilic granuloma complex)
Cat (Feline)
  • Estrus suppression (temporary)
  • Treatment of feline acne
  • Management of behavioral problems (e.g., urine spraying, aggression)
  • Adjunct in treatment of eosinophilic granuloma complex
Horse (Equine)
  • Treatment of some reproductive disorders (off-label)
Cattle (Bovine)
  • May be used for estrus synchronization in some countries (off-label)

Pharmacology & Mechanism of Action

Drug Class: Progestin | Pharmacological Group: Hormonal / Progestogen

Mechanism of Action: Medroxyprogesterone acetate (MPA) is a synthetic progestogen that binds to progesterone receptors in target tissues, mimicking the effects of endogenous progesterone. It inhibits the secretion of gonadotropins (LH and FSH) from the anterior pituitary, thereby suppressing ovulation and estrus. It also induces endometrial glandular proliferation and maintains pregnancy, but in non-pregnant animals it causes endometrial hyperplasia and mucification of the vaginal epithelium. Additionally, MPA has anti-androgenic and mild glucocorticoid-like effects, which contribute to its use in certain dermatological and behavioral conditions.

Pharmacodynamics: MPA exerts its effects by altering the hypothalamic-pituitary-gonadal axis, leading to suppression of follicular development and ovulation. It also reduces the secretion of testosterone in males by inhibiting LH. In females, it causes a prolonged diestrus-like state, with endometrial changes that may predispose to cystic endometrial hyperplasia and pyometra if used long-term. Its glucocorticoid activity can cause mild adrenal suppression and increased appetite. The drug also has anti-inflammatory and antipruritic effects in some dermatological conditions.

⚡ Pharmacokinetics Summary

Absorption: MPA is well absorbed after oral administration, but bioavailability is variable due to first-pass metabolism. Injectable formulations (depot) provide sustained release over weeks to months. In dogs, oral bioavailability is approximately 50-70%.
Distribution: MPA is highly lipophilic and distributes widely into tissues, with high concentrations in adipose tissue, liver, and reproductive organs. It crosses the placenta and is excreted in milk. Protein binding is approximately 90%.
Metabolism: MPA is extensively metabolized in the liver via hydroxylation and conjugation. Metabolites are excreted in urine and bile. Some metabolites retain progestogenic activity.
Excretion: Excretion occurs primarily via urine and feces. The elimination half-life is prolonged due to accumulation in adipose tissue and slow release from depot injections.
Half-Life: Dogs: ~12-24 hours (oral), but depot injection can last 2-4 months. Cats: ~8-12 days (depot).
Bioavailability: Oral: ~50-70% in dogs; injectable depot provides complete bioavailability over time.
Protein Binding: Approximately 90% bound to plasma proteins, mainly albumin and corticosteroid-binding globulin.

Available Formulations & Strengths

Oral Tablet 2.5 mg, 5 mg, 10 mg (PO)
Injectable Suspension (Depot) 100 mg/mL, 150 mg/mL (SC, IM)

Contraindications & Clinical Warnings

Contraindications:
  • Pregnancy (especially during first trimester; may cause masculinization of female fetuses)
  • Known hypersensitivity to medroxyprogesterone acetate
  • Existing mammary tumors or history of mammary neoplasia
  • Uterine disease (e.g., pyometra, metritis)
  • Diabetes mellitus (may worsen glycemic control)
  • Liver dysfunction
  • Use in growing animals (may affect bone growth)
Warnings & Clinical Precautions:
  • Use with caution in animals with a history of seizures or epilepsy.
  • May cause transient increase in appetite and weight gain.
  • Long-term use may increase risk of mammary tumors, especially in cats.
  • In dogs, prolonged use may lead to cystic endometrial hyperplasia and pyometra.
  • May cause adrenal suppression; avoid concurrent use with corticosteroids.
  • Do not use in animals intended for breeding unless specifically indicated.
  • In food animals, extra-label use is prohibited in the US; withdrawal times must be observed if used off-label.

Adverse Effects & Reactions

Common:

  • Increased appetite and weight gain
  • Lethargy
  • Mild depression
  • Mammary gland enlargement
  • Changes in hair coat (alopecia or hirsutism)

Serious / Severe:

  • Pyometra (in dogs and cats)
  • Cystic endometrial hyperplasia
  • Mammary neoplasia (especially in cats)
  • Diabetes mellitus (with long-term use)
  • Adrenal suppression
  • Hepatotoxicity (rare)

Rare:

  • Thromboembolism
  • Iatrogenic Cushing's syndrome
  • Injection site reactions (sterile abscesses)
  • Behavioral changes (increased aggression)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Corticosteroids Additive immunosuppressive and adrenal suppressive effects. High
Insulin or oral hypoglycemic agents May reduce glucose tolerance, requiring dose adjustments of antidiabetic medications. Moderate
Hepatic enzyme inducers (e.g., phenobarbital, rifampin) May increase metabolism of MPA, reducing its efficacy. Moderate
Cyclosporine Potential for increased cyclosporine levels due to competitive metabolism. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Lethargy
  • Increased thirst and urination
  • Weight gain
  • In severe cases, signs of adrenal suppression or hepatotoxicity

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent oral ingestion and animal is stable. Administer activated charcoal to reduce absorption. Monitor for electrolyte imbalances and adrenal function. No specific antidote; provide supportive care including fluid therapy and monitoring of blood glucose and liver enzymes.

Food Animal Withdrawal Times

Not approved for use in food animals in the US. Extra-label use is prohibited in food animals. If used off-label in non-US countries, consult local regulations; typical withdrawal times may be 30 days for meat and 7 days for milk, but must be based on legal requirements.

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).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light. Keep container tightly closed. Do not freeze.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats for estrus suppression and certain dermatological conditions. Not approved for food animals.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is prohibited by AMDUCA. In dogs and cats, extra-label use is permitted under veterinary supervision. In horses, use is off-label but allowed under certain conditions; must follow withdrawal times for horses intended for slaughter.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Medroxyprogesterone acetate is a potent progestin used primarily for temporary estrus suppression in dogs and cats. It is also used off-label for behavioral issues and some dermatoses. Due to significant adverse effects, especially with long-term use, it should be used with caution and only when alternative therapies are not suitable. In dogs, the risk of pyometra and mammary tumors increases with repeated administration. In cats, long-term use is associated with a high risk of mammary adenocarcinoma and diabetes mellitus. Therefore, it is recommended to use the lowest effective dose for the shortest duration. For estrus suppression, consider surgical sterilization as a permanent and safer alternative. In horses, altrenogest is preferred. Always monitor animals for signs of uterine infection, metabolic changes, and endocrine disturbances during therapy. Client education is essential regarding the risks and benefits.

References & Literature

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