DANAZOL

Chemistry - A synthetic derivative of ethisterone (ethinyl testosterone), danazol occurs as a whiteto pale yellow, crystalline powder. It is practically insoluble in water and sparingly soluble inalcohol.

Storage, Stability, Compatibility

Danazol capsules should be stored in well-closed containersat room temperature.

Pharmacology - DANAZOL

Danazol is a synthetic androgen with weak androgenic effects. It suppresses thepituitary-ovarian axis. Danazol probably directly inhibits the synthesis of sex steroids and binds tosex steroid receptors in tissues, where it may express anabolic, weak androgenic, and antiestrogeniceffects.
Uses, Indications - In veterinary medicine, danazol is primarily used as adjunctive therapy (with corticosteroids) in the treatment of canine immune-mediated thrombocytopenia and hemolytic anemia. There is apparently synergism when danazol is combined with corticosteroids for these indications. Once remission is attained, some dogs may have their dosage reduced or other medications may be eliminated and be controlled with danazol alone. In humans, danazol has been used for the treatment of endometriosis, fibrocystic breast disease, idiopathic thrombocytopenic purpura and a variety of other conditions.

Pharmacokinetics - DANAZOL

There is very limited data available. Danazol is absorbed from the GI tract, but appears to be a rate limited process as increasing the dosage does not yield a corresponding increase in serum level. Distribution information is practically nonexistent; the drug apparently crosses the placenta. Danazol is believed to be principally metabolized in the liver. In humans, half-lives average about 4-5 hours.

Contraindications, Precautions, Reproductive Safety

Danazol should be used in patients withsevere cardiac, renal or hepatic function impairment, or undiagnosed abnormal vaginal bleeding onlywhen its benefits outweigh its risks.
Because of documented teratogenic effects, danazol is considered contraindicated during pregnancy. While it is unknown if danazol enters maternal milk, the potential adverse effects associatedwith androgens in young animals warrants that caution be used.

Adverse Effects, Warnings

Hepatotoxicity (incidence rare) is the most significant of the adverseeffects that have been reported thus far in dogs. Otherwise virilization in females is the most likelyother effect that may be seen. Rarely, danazol may cause weight gain, or lethargy. Human patientshave developed vaginitis. Other potential adverse effects include edema, testicular atrophy, hirsutismor alopecia.

Overdosage, Acute Toxicity

No information was located. Significant overdoses should initiallybe handled by contacting an animal poison control center and initiate gut emptying protocols whenapplicable.

Drug Interactions

Concomitant use of danazol with anticoagulants may enhance the anticoagulant effect because danazol may decrease the synthesis of procoagulant factors in the liver. Indiabetics, danazol may affect insulin requirements (doses may need to be increased) by affectingcarbohydrate metabolism.
Laboratory Considerations - Danazol may decrease total serum thyroxine (T4) and increase
T3 uptake; because thyroid-binding globulin is decreased free T4 and TSH remain normal. ALT(SGPT) and AST (SGOT) may increase early in therapy but decrease towards baseline later intherapy. After discontinuation of danazol, levels usually return to baseline.