Learn how to prepare for Severe Allergy Attacks.

Class: Androgens
ATC Class: G03XA01
VA Class: HS100
CAS Number: 17230-88-5

Warning(s)

  • Fetotoxicity
  • May cause fetal harm; contraindicated in pregnant women.b f Pregnancy must be excluded before the start of treatment and prevented thereafter by use of a nonhormonal method of contraception during therapy.b f (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Thrombotic Events
  • Serious and potentially life-threatening thromboembolic events reported.b f (See Cardiovascular Effects under Cautions.)

  • Hepatic Effects
  • Serious and potentially life-threatening hepatic effects (e.g., peliosis hepatis and benign hepatic adenoma resulting in intra-abdominal hemorrhage) reported with long-term therapy.b f (See Hepatic Effects under Cautions.)

  • Administer lowest effective dosage.b f

  • If therapy initiated at time of exacerbation of hereditary angioedema due to trauma, stress, or other causes, periodically attempt to decrease dosage or withdraw therapy.b f

  • Pseudotumor Cerebri
  • Risk of pseudotumor cerebri (benign intracranial hypertension); manifested by papilledema, headache, nausea and vomiting, and/or visual disturbances.b f

  • If signs and symptoms of pseudotumor cerebri occur, examine for the presence of papilledema; if present, discontinue danazol immediately and refer patient to a neurologist for further evaluation and care.b f

Introduction

A synthetic androgenic anabolic steroid hormone.a

Uses for Danazol

Endometriosis

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

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).a b f

Slideshow: Vaccination Safety: Your Questions Answered

Hereditary Angioedema

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

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

Other Uses

Should not be used to produce regression of secondary sexual characteristics in children with precocious puberty; does not halt the progression of bone age.a

Danazol Dosage and Administration

General

  • Individualize dosage carefully according to individual requirements and response.a b f

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

Endometriosis

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

Fibrocystic Breast Disease

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

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

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

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

Hereditary Angioedema

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

Administration

Oral Administration

Administer orally 2 or 3 times daily.b f

Dosage

Adults

Endometriosis
Mild Endometriosis
Oral

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

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

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.a b f

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

Fibrocystic Breast Disease
Oral

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

If symptoms recur after discontinuance, reinstitute therapy.b f

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.b f

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

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

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

Prescribing Limits

Adults

Hereditary Angioedema
Oral

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

Special Populations

Hepatic Impairment

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

Renal Impairment

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

Cautions for Danazol

Contraindications

  • Undiagnosed abnormal genital bleeding.b f

  • Markedly impaired hepatic, renal, or cardiac function.b f

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

  • Nursing women.b f

  • Porphyria.b f (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.a b f

Exclude pregnancy immediately prior to initiation of therapy.b f

Use nonhormonal method of contraception during therapy.b f

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

Cardiovascular Effects

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

Hepatic Effects

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

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

Periodic liver function evaluation recommended.a b f

Pseudotumor Cerebri

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

Lipid Abnormalities

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

Breast Cancer

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

Androgenic Effects

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

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).b f

Porphyria

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

Specific Populations

Pregnancy

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

Lactation

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

Pediatric Use

Safety and efficacy not established.b f

Hepatic Impairment

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

Renal Impairment

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

Interactions for Danazol

Specific Drugs and Laboratory Tests

Drug

Interaction

Comments

Anticoagulants, oral

Increased PT b f

Monitor closely when danazol is initiated or discontinued; adjust warfarin dosage as neededb f

Carbamazepine

Potential increased carbamazepine concentrationsb f

Tests for androgens (testosterone, androstenedione, dehydroepiandrosterone)

Possible interference with laboratory determinations of androgensb f

Danazol Pharmacokinetics

Absorption

Food

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

Elimination

Metabolism

Metabolized to 2-hydroxymethylethisterone.a

Half-life

4.5–9 hours.d e

Stability

Storage

Oral

Capsules

20–25°C.b f

Actions

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

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

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

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

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

  • May decrease plasma testosterone and dihydroepiandrosterone concentrations.a

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

  • Produces changes in vaginal cytology and cervical mucus.b f

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

Advice to Patients

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

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

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

  • Importance of women using nonhormonal contraceptive measures.b f

  • 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.b f

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

Preparations

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

Danazol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

50 mg

Danazol Capsules

Barr

100 mg

Danazol Capsules

Barr

200 mg

Danazol Capsules

Barr, Lannett

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Danazol 100MG Capsules (TEVA PHARMACEUTICALS USA): 30/$69.99 or 90/$199.98

Danazol 200MG Capsules (TEVA PHARMACEUTICALS USA): 30/$110.76 or 90/$322.63

Danazol 50MG Capsules (TEVA PHARMACEUTICALS USA): 30/$55.99 or 90/$155.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

a. AHFS drug information 2006. McEvoy GK, ed. Danazol. Bethesda, MD: American Society of Health-System Pharmacists; 3009-3011.

b. Barr Laboratories, Inc. Danazol capsules, USP prescribing information. Pomona, NY; 1999 Feb.

c. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation, 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:421.

d. Hooper WD, Eadie MJ, Dickinson RG. Single oral dose pharmacokinetics and comparative bioavailability of danazol in humans. Biopharm Drug Dispos. 1991; 12:577-582. [PubMed 1801964]

e. Davison C, Banks W, Fritz A. The absorption, distribution and metabolic fate of danazol in rats, monkeys and human volunteers. Arch Int Pharmacodyn Ther. 1976; 221:294-310. [PubMed 822792]

f. Lannett Company, Inc. Danazol capsules, prescribing information. Philadelphia, PA; 2006 Nov.

Hide
(web5)