danazol
Cyclomen ◆, Danocrine

Available forms
Available by prescription only
Capsules: 50 mg, 100 mg, 200 mg

Indications and dosages
 Mild endometriosis. Adults: Initially, 100 to 200 mg P.O. b.i.d. uninterrupted for 3 to 6 months; may continue for 9 months. Subsequent dosage based on patient response.
 Moderate to severe endometriosis. Adults: 400 mg P.O. b.i.d. uninterrupted for 3 to 6 months; may continue for 9 months.
 Fibrocystic breast disease. Adults: 100 to 400 mg P.O. daily in two divided doses uninterrupted for 2 to 6 months.
 Prevention of hereditary angioedema. Adults: 200 mg P.O. b.i.d. or t.i.d., continued until favorable response is achieved. Then, decrease dosage by one-half at 1- to 3-month intervals. If attack occurs, increase dosage by no more than 200 mg/day. Monitor dosage adjustments carefully.

Pharmacodynamics
Antiestrogenic action: The antiestrogenic actions of danazol cause regression and atrophy of normal and ectopic endometrial tissue. Drug also decreases the growth and nodularity of abnormal breast tissue in fibrocystic breast disease.
Androgenic action: The androgenic effects of danazol increase levels of the C1 and C4 components of complement, which reduces the frequency and severity of attacks caused by hereditary angioedema.

Pharmacokinetics
Absorption: Amount absorbed isn’t proportional to dose; doubling the dose produces an increase of only 35% to 40% in absorption.
Distribution: Unknown.
Metabolism: Metabolized to 2-hydroxymethylethisterone.
Excretion: Unknown.

Contraindications and precautions
Contraindicated in pregnant and breast-feeding patients and in those with undiagnosed abnormal genital bleeding, porphyria, or impaired renal, cardiac, or hepatic function. Use cautiously in patients with seizure disorders or migraine headaches.

Interactions
Drug-drug. Carbamazepine: May increase plasma carbamazepine levels. Evaluate patient carefully.
Cyclosporine: Increases cyclosporine levels and increases risk of nephrotoxicity. Monitor patient closely.
Warfarin-type anticoagulants: Prolongs PT and INR. Monitor PT and INR.

Adverse reactions
CNS: dizziness, headache, sleep disorders, fatigue, tremor, irritability, excitation, lethargy, mental depression, chills, paresthesia.
CV: elevated blood pressure.
EENT: visual disturbances.
GI: gastric irritation, nausea, vomiting, diarrhea, constipation, change in appetite.
GU: hematuria; hypoestrogenic effects, such as flushing, diaphoresis, vaginitis (including itching, dryness, and burning), vaginal bleeding, nervousness, emotional lability, menstrual irregularities.
Hematologic: prolonged PT and INR (especially during anticoagulant therapy).
Hepatic: reversible jaundice, hepatic dysfunction.
Musculoskeletal: muscle cramps or spasms.
Other: androgenic effects in women, including weight gain, hirsutism, hoarseness, acne, clitoral enlargement, decreased breast size, edema, altered libido, oily skin or hair, voice deepening.

Effects on lab test results
• May cause elevated liver enzyme levels.
• May increase PT and INR.

Overdose and treatment
No information available.
 Empty stomach by induced emesis or gastric lavage; follow with activated charcoal to reduce absorption. Treatment is supportive.

Special considerations
• To treat endometriosis and fibrocystic breast disease, begin danazol therapy during menstruation or make sure patient isn’t pregnant.
• Danazol provides alternative therapy for patients who can’t tolerate or fail to respond to other therapy. (It isn’t indicated when surgery is the best choice.)
Breast-feeding patients
• Because of the risk of serious adverse reactions in the infant, a decision should be made to discontinue breast-feeding or drug, depending on the importance of drug to patient. Drug is contraindicated in breast-feeding women.
Pediatric patients
• Use cautiously because of possible androgenic effects.
• Use with extreme caution in children to avoid precocious puberty and premature closure of the epiphyses. Obtain X-ray examinations every 6 months to assess skeletal maturation.
Geriatric patients
• Use cautiously. Assess elderly men for the development of prostatic hypertrophy; symptomatic prostatic hypertrophy or prostatic carcinoma mandates discontinuation of danazol.

Patient education
• Advise patient taking danazol for fibrocystic disease to examine breasts regularly. Tell patient to immediately report a breast nodule that enlarges during treatment.
• Tell patient desiring birth control to use a nonhormonal contraceptive; during danazol treatment, ovulation may not be suppressed by hormonal contraceptives.
• Advise women to report voice changes or other signs of virilization promptly. Some androgenic effects such as deepening of the voice may not be reversed by stopping drug.
• Instruct patient to immediately report nausea, vomiting, headache, and visual disturbances, which may suggest pseudotumor cerebri.
• Advise women that amenorrhea usually occurs after 6 to 8 weeks of therapy.
• Advise men that periodic evaluation of semen may be indicated.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use