Drug class: Androgens
ATC class: G03XA01
VA class: HS100
CAS number: 17230-88-5

Medically reviewed by Drugs.com on Nov 17, 2023. Written by ASHP.

Introduction

A synthetic androgenic anabolic steroid hormone.

Uses for Danazol

Endometriosis

Palliative treatment of endometriosis (e.g., pain relief, reduction in endometrial lesions).

Fibrocystic Breast Disease

Palliative treatment of fibrocystic breast disease (e.g., decreasing pain, tenderness, and nodularity) in patients unresponsive to simple measures (e.g., the use of padded brassieres and/or analgesics).

Hereditary Angioedema

Prophylactic treatment of all types (i.e., abdominal, cutaneous, laryngeal) of hereditary angioedema in males and females.

Some clinicians believe fibrinolytic inhibitors (e.g., aminocaproic acid) may be preferable in children and pregnant women because of hazardous adverse effects. (See Hepatic Effects under Cautions.)

Other Uses

Should not be used to produce regression of secondary sexual characteristics in children with precocious puberty^{† [off-label]}; does not halt the progression of bone age.

Misuse, Abuse, and Dependence

Misuse and abuse of androgens reported in athletes, bodybuilders, weightlifters, and others to enhance athletic performance or physique^{† [off-label]}.

Based on review of data, FDA concluded that misuse and abuse of androgens associated with serious adverse cardiovascular, hepatic, endocrine, and mental health effects. (See Misuse, Abuse, and Dependence under Cautions.)

Evaluate serum testosterone concentrations if misuse or abuse of androgens suspected (e.g., patients experiencing serious adverse cardiovascular or psychiatric effects). Serum testosterone concentrations may be below or within the normal range in patients abusing synthetic derivatives of testosterone.

Danazol Dosage and Administration

General

• Individualize dosage carefully according to individual requirements and response.

• Administer lowest effective dosage to minimize risk and occurrence of adverse effects. (See Hepatic Effects under Cautions.)

Endometriosis

• Initiate therapy during menstruation; otherwise, perform appropriate laboratory tests to ensure that patient is not pregnant.

Fibrocystic Breast Disease

• Initiate therapy during menstruation; otherwise, perform appropriate laboratory tests to ensure that patient is not pregnant.

• Ovulation may not be suppressed at recommended dosage. Use of an effective nonhormonal method of contraception is essential.

• Regular menstrual patterns, irregular menstrual patterns, and amenorrhea each occur in approximately one-third of patients receiving 100 mg daily. Irregular menstrual patterns and amenorrhea occur more frequently at higher doses.

• Breast pain and tenderness substantially relieved during the first month of therapy and eliminated in 2–3 months. Elimination of nodularity usually requires 4–6 months of uninterrupted therapy.

Hereditary Angioedema

• Closely monitor patients during dosage adjustment phase, especially if history of airway involvement.

Administration

Oral Administration

Administer orally 2 or 3 times daily.

Dosage

Adults

Endometriosis

Mild Endometriosis

Oral

Initially, 200–400 mg daily in 2 divided doses. Adjust subsequent doses depending on patient tolerance and therapeutic response.

Continue therapy uninterrupted for 3–6 months; may extend to 9 months if necessary. If symptoms recur after discontinuance, reinstitute therapy.

Moderate to Severe Endometriosis or Infertility due to Endometriosis

Initially, 800 mg daily in 2 divided doses; gradually reduce dosage, depending on therapeutic response, to a level sufficient to maintain amenorrhea.

Continue therapy uninterrupted for 3–6 months; may extend to 9 months if necessary. If symptoms recur after discontinuance, reinstitute therapy.

Fibrocystic Breast Disease

Oral

Usual dose: 100–400 mg daily in 2 divided doses. Adjust therapy according to severity of disease and patient response.

If symptoms recur after discontinuance, reinstitute therapy.

Hereditary Angioedema

Oral

Initially, 200 mg given 2 or 3 times daily until a favorable response (i.e., prevention of episodes of edematous attacks) is attained.

Determine subsequent maintenance dosage by decreasing dosage by ≤50% at intervals of 1–3 months or longer, based on frequency of attacks before therapy.

Dosage may be increased by ≤200 mg daily if an attack occurs during therapy.

If danazol was initiated during exacerbation of angioedema resulting from trauma, stress, or other cause, periodically attempt to reduce dosage or withdraw therapy.

Prescribing Limits

Adults

Hereditary Angioedema

Oral

Dosage may be increased by maximum of 200 mg daily if an attack occurs during therapy.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time; contraindicated in patients with markedly impaired hepatic function. (See Contraindications under Cautions.)

Renal Impairment

No specific dosage recommendations at this time; contraindicated in patients with markedly impaired renal function. (See Contraindications under Cautions.)

Cautions for Danazol

Contraindications

• Undiagnosed abnormal genital bleeding.

• Markedly impaired hepatic, renal, or cardiac function.

• Known or suspected pregnancy. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

• Nursing women.

• Porphyria. (See Porphyria under Cautions.)

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; virilization of the external genitalia (e.g., clitoral hypertrophy, labial fusion of the external genital fold to form a scrotal-like structure, ambiguous genitalia, abnormal vaginal development, persistence of a urogenital sinus) of female fetus reported.

Exclude pregnancy immediately prior to initiation of therapy.

Use nonhormonal method of contraception during therapy.

Avoid pregnancy during therapy. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.

Cardiovascular Effects

Serious and potentially life-threatening thromboembolism, thrombotic and thrombophlebitic events (e.g., sagittal sinus thrombosis, stroke) reported.

Hepatic Effects

Peliosis hepatis and benign hepatic adenoma reported with prolonged use of high doses of androgens. Such hepatic effects may not be apparent until complicated by acute, potentially life-threatening intra-abdominal hemorrhage. Administer lowest effective dosage.

Elevated concentrations of hepatic enzymes (e.g., alkaline phosphatase, AST, ALT) and/or jaundice reported with dosages of ≥400 mg daily.

Periodic liver function evaluation recommended.

Pseudotumor Cerebri

Pseudotumor cerebri (benign intracranial hypertension), manifested by papilledema, headache, nausea and vomiting, and/or visual disturbances, reported. (See Pseudotumor Cerebri under Boxed Warnings.)

Lipid Abnormalities

May alter serum lipoprotein concentrations; decreased HDL and increased LDL reported. Consider the increased risk of cardiovascular disease (e.g., atherosclerosis and CAD) versus the possible benefits of therapy.

Breast Cancer

Exclude breast cancer before initiating therapy for fibrocystic breast disease; breast nodularity, pain, and tenderness may prevent recognition of underlying carcinoma. If any nodule persists or enlarges during treatment, consider and rule out carcinoma.

Androgenic Effects

Possible androgenic effects (e.g., weight gain, acne, seborrhea, hirsutism, edema, hair loss, voice change); may be irreversible. Monitor patient closely.

Misuse, Abuse, and Dependence

Serious adverse effects (e.g., increased aggression, antisocial behavior, manic episode, hostility, depression, changes in libido, increased risk of cardiovascular events, hepatotoxicity, testicular atrophy, sperm abnormalities) associated with misuse and abuse of androgens (see Misuse, Abuse, and Dependence under Uses).

Manifestations of withdrawal (e.g., depressed mood, major depression, fatigue, cravings, restlessness, irritability, anorexia, insomnia, decreased libido, hypogonadotropic hypogonadism) may occur if androgens discontinued abruptly or dosage substantially reduced in physically dependent patients or in those taking supratherapeutic dosages of such drugs; withdrawal symptoms may persist for weeks or months.

General Precautions

Fluid Retention

May cause fluid retention; use caution in conditions adversely affected by fluid retention (e.g., epilepsy, migraine, cardiac or renal dysfunction).

Porphyria

May induce 5-aminolevulinate synthetase activity and porphyrin; possible exacerbation of manifestations of acute intermittent porphyria. Contraindicated in patients with porphyria. (See Contraindications under Cautions.)

Specific Populations

Pregnancy

Category X. (See Contraindications and also Fetal/Neonatal Morbidity and Mortality, under Cautions.)

Lactation

Discontinue nursing because of potential risk to nursing infants. (See Contraindications under Cautions.)

Pediatric Use

Safety and efficacy not established.

Hepatic Impairment

Use not recommended in patients with severe hepatic impairment. (See Contraindications under Cautions.)

Renal Impairment

Use with caution in renal dysfunction. (See Fluid Retention under Cautions). Use not recommended in patients with severe renal impairment. (See Contraindications under Cautions.)

Common Adverse Effects

Mild hirsutism, decreased breast size, voice changes, sore throat, acne, increased oiliness of skin or hair, hair loss, weight gain, edema, flushing, sweating, nervousness, emotional lability, vaginitis, menstrual irregularities.

Drug Interactions

Specific Drugs and Laboratory Tests

Danazol Pharmacokinetics

Absorption

Food

Food delays time to peak plasma concentration by about 30 minutes. A high-fat meal (>30 grams of fat) increases bioavailability and peak plasma concentrations threefold to fourfold.

Elimination

Metabolism

Metabolized to 2-hydroxymethylethisterone.

Half-life

4.5–9 hours.

Stability

Storage

Oral

Capsules

20–25°C.

Actions

• Suppresses the pituitary-ovarian axis by inhibiting output of pituitary and hypothalamic gonadotropins.

• Directly inhibits the synthesis of sex steroids and binds to gonadal (sex) steroid receptors in the cytoplasm of target tissues.

• Possesses weak androgenic and anabolic properties but exerts no estrogenic or progestogenic activity; androgenic activity is dose related.

• In patients with endometriosis, suppresses ovarian steroidogenesis which produces atrophy and involution of normal and ectopic endometrial tissue. Also, substantially decreases IgG, IgM, and IgA concentrations as well as phospholipid and IgG isotope autoantibodies and associated elevations of autoantibodies.

• Does not suppress normal pituitary release of corticotropin or adrenocortical release of cortisol.

• May decrease plasma testosterone and dihydroepiandrosterone concentrations.

• May suppress the midcycle surge of FSH and LH and may decrease plasma estradiol and progesterone concentrations.

• Produces changes in vaginal cytology and cervical mucus.

• Increases serum levels of complement 1 (C1) esterase inhibitor, which results in increased serum levels of complement C4 in patients with hereditary angioedema.

Advice to Patients

• Importance of advising patients of the potential for serious adverse effects associated with misuse and abuse of androgens.

• Risk of virilization in females. Advise female patients to contact their clinician if they notice hoarseness, acne, or the growth of facial hair.

• Importance of informing clinicians of headache, nausea and vomiting, or visual disturbances.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

• Importance of women using nonhormonal contraceptive measures.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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