Osaterone

Overview

Osaterone (Ypozane®) is an antiandrogenic drug with progestational activity used in intact male dogs for the treatment of benign prostatic hypertrophy (BPH). Although treatment is administered for only 7 days, clinical improvement may persist for several months after therapy.

Osaterone is approved for use in dogs in some countries but is not commercially available in the United States. In addition to its use for BPH, it is also being investigated as a potential treatment for alopecia X in dogs.

Mechanism of Action (MOA): Osaterone acetate is structurally related to progesterone and exerts antiandrogenic effects through multiple mechanisms. It decreases testosterone transport into the prostate, inhibits 5-alpha reductase, competitively inhibits androgen receptor binding within the prostate, and reduces androgen nuclear receptors. Its active metabolite (PB-4) also possesses antiandrogenic activity. Osaterone has progestational activity but lacks mineralocorticoid activity.

Indications

Osaterone is used in intact male dogs for the management of benign prostatic hypertrophy (BPH).

• Benign prostatic hypertrophy (BPH): Treatment of benign enlargement of the prostate in intact male dogs, including dogs not fit for surgical castration and stud dogs, without loss of fertility.
• Alopecia X (investigational use): Currently being investigated as a potential treatment option in dogs.

Dosage (Reference)

Dog

Osaterone is used as a short-course oral treatment for benign prostatic hypertrophy (BPH) in intact male dogs. Although treatment lasts only 7 days, clinical improvement may persist for several months.

Warnings & Precautions

Osaterone should be used carefully in selected patients because of its hormonal effects and potential impact on adrenal function.

• Female animals: Contraindicated in female dogs.
• Hypersensitivity: Contraindicated in patients with known hypersensitivity to osaterone.
• Hepatic dysfunction: Use cautiously in dogs with liver disease; safety in dogs with a history of liver disease has not been thoroughly investigated; reversible increases in ALT and ALP have occurred in some treated dogs with liver disease; monitor liver enzymes (ALT, ALP) in dogs with a history or signs of hepatic dysfunction.
• Adrenosuppression: Osaterone and its active metabolite may reduce cortisol concentrations. Effects can persist for several weeks after treatment, and treated dogs should be monitored for clinical signs related to hypoadrenocorticism.
• Hypoadrenocorticism or physiologic stress: Dogs with hypoadrenocorticism or those undergoing physiologic stress (e.g., post-surgery or post-trauma) may require additional monitoring and glucocorticoid support if needed.
• ACTH stimulation testing: Plasma cortisol concentrations may decrease after treatment, and ACTH stimulation test results may be suppressed.
• Human exposure: Wash hands after handling osaterone tablets.
• Women of child-bearing age: Should avoid contact with osaterone whenever possible or wear disposable gloves during administration; the stricter advice is that people who are or may become pregnant should not handle it at all.

Drug Interactions

No clinically significant drug interactions have been reported for osaterone. Concurrent administration with antimicrobial agents has been reported without known interaction concerns.

• Antimicrobials: Osaterone may be administered concurrently with antimicrobial medications.
• Known interactions: No specific drug interactions have been identified in the available literature.

Side Effects & Overdose

Side Effects

The most commonly reported adverse effects of osaterone are transient increases in appetite and temporary behavioral changes. Most effects are generally mild and reversible.

• Increased appetite: The most commonly reported adverse effect and is usually temporary.
• Behavioral changes: Transient changes in activity level and sociability may occur.
• Polyuria and polydipsia: Increased urination and water consumption have been reported.
• Gastrointestinal effects: Vomiting and diarrhea may occur.
• Mammary gland hyperplasia: Reported rarely.
• Hair coat changes: Reported rarely.
• Decreased plasma cortisol concentrations: Commonly occurs early in treatment and may persist for several weeks.

Overdose

Information regarding osaterone overdose is limited. Doses greater than 10 mg/kg may cause neurologic signs (ataxia and tremors); dogs given 1.25 mg/kg for 10 days showed only a decrease in plasma cortisol.

• Ataxia: May occur at doses greater than 10 mg/kg.
• Tremors: May occur at doses greater than 10 mg/kg.
• Decreased cortisol concentrations: Observed in dogs receiving 1.25 mg/kg (approximately 2.5 times the labeled dose) for 10 days.
• Management: Monitor the patient closely and provide supportive care as needed.

Key Notes

Practical clinical points that may help optimize the use of osaterone in dogs:

• Rapid absorption: Peak plasma concentrations occur approximately 2 hours after oral administration.
• Long elimination half-life: The reported elimination half-life is approximately 80 hours.
• Protein binding: Osaterone and its active metabolite are highly protein bound in plasma.
• Primary elimination route: The drug is eliminated mainly through biliary excretion into the feces, with a smaller proportion excreted in urine.
• Prolonged detection: Osaterone and its metabolites may be detectable in urine and feces for up to 14 days after a single dose.
• Semen quality: Transient abnormalities in semen quality have been reported, including in an early study in beagles, although other studies report no adverse effects on semen quality.