Danazol
Danazol is a **synthetic androgen** derived from ethisterone. In veterinary medicine, it is primarily utilized as an adjunctive immunomodulatory agent for the treatment of **immune-mediated hemolytic anemia (IMHA)** and **immune-mediated thrombocytopenia (ITP)** in dogs and cats. * **Clinical Pearl**: Due to its high cost, unpredictable efficacy, and slow onset of action, danazol is typically reserved as a salvage or third-line therapy when patients become refractory to standard immunosuppressants like glucocorticoids, cyclosporine, or mycophenolate. * It exhibits synergism when combined with corticosteroids, potentially allowing for a reduction in the glucocorticoid dose once remission is achieved. * In human medicine, it is also used for endometriosis, fibrocystic breast disease, and idiopathic thrombocytopenic purpura.
Mechanism: Danazol possesses weak androgenic, anabolic, and antiestrogenic properties. Its immunomodulatory effects are achieved through several mechanisms: * **Fc Receptor Modulation**: Reduces the affinity of autoantibodies for the **mononuclear phagocytic system Fc receptors** → decreases the macrophage-mediated destruction of antibody-coated red blood cells and platelets. * **Steroid-Binding Globulin Competition**: Competes with glucocorticoids for binding sites on **corticosteroid-binding globulin (CBG)** → increases the fraction of free, pharmacologically active glucocorticoids in circulation, enhancing their efficacy. * **Pituitary-Ovarian Axis Suppression**: Inhibits the synthesis of sex steroids and binds directly to sex steroid receptors in target tissues.
Dosing by species
- Adjunctive treatment of immune-mediated hemolytic anemia · 5 mg/kg PO twice daily · PO · q12h
- Adjunctive treatment of immune-mediated hemolytic anemia (non-regenerative forms) · 5 mg/kg PO three times daily. · PO · q8h · Used to reduce the dose of glucocorticoids needed for long-term therapy.
- Adjunctive treatment of immune-mediated hemolytic anemia or thrombocytopenia · 5 mg/kg PO 2-3 times per day · PO · q8-12h · Rarely helpful. Costly and has limited effectiveness.
- Adjunctive treatment of immune-mediated hemolytic anemia or thrombocytopenia · 10 mg/kg/day PO. Once anemia improves, corticosteroids may be slowly tapered and eventually DC'd. When remission maintained by danazol alone, may lower to 5 mg/kg/day. Slowly taper after 2-3 months of normal hemograms with frequent monitoring of hemograms. · PO · q24h · Long-term · Initially given in addition to prednis(ol)one.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Pregnancy (Teratogenic - FDA Category X)
- Nursing/breastfeeding
- Severe cardiac function impairment
- Severe renal function impairment
- Severe hepatic function impairment
- Undiagnosed abnormal vaginal bleeding
Adverse effects
- Hepatotoxicity (rare but significant in dogs)
- Virilization in females
- Weight gain
- Lethargy
- Edema
- Testicular atrophy
- Hirsutism
- Alopecia
- Vaginitis (reported in humans)
Drug interactions
- Cyclosporine · May significantly increase cyclosporine levels
- Insulin · By affecting carbohydrate metabolism, danazol may affect insulin requirements (doses may need to be increased) in diabetic patients
- Warfarin · Concomitant use may enhance the anticoagulant effect as danazol may decrease the synthesis of procoagulant factors in the liver
Monitoring
- Efficacy (CBC, platelets, reticulocyte count)
- Hepatic function (baseline and at regular intervals while on therapy)
Overdose
No specific information was located regarding acute toxicity in animals. Significant overdoses should initially be handled by contacting an animal poison control center and initiating gut emptying protocols (emesis or gastric lavage, followed by activated charcoal) when applicable.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.