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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Danazol may be confused with Dantrium®
Danocrine may be confused with Dacriose®
Pronunciation
(DA na zole)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of endometriosis, fibrocystic breast disease, and hereditary angioedema
Pregnancy Risk Factor
X
Pregnancy Considerations
[U.S. Boxed Warning]: Pregnancy should be ruled out prior to treatment using a sensitive test (beta subunit test, if available). Nonhormonal contraception should be used during therapy. May cause androgenic effects to the female fetus; clitoral hypertrophy, labial fusion, urogenital sinus defect, vaginal atresia, and ambiguous genitalia have been reported.
Lactation
Enters breast milk/contraindicated
Contraindications
Hypersensitivity to danazol or any component of the formulation; undiagnosed genital bleeding; pregnancy; breast-feeding; porphyria; markedly impaired hepatic, renal, or cardiac function
Warnings/Precautions
Boxed warnings:
• Hepatic effects: See “Concerns related to adverse effects” below.
• Intracranial hypertension: See “Concerns related to adverse effects” below.
• Pregnancy: See “Special populations” below.
• Thromboembolic events: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Androgenic effects: May cause nonreversible androgenic effects.
• Blood lipid changes: Anabolic steroids may cause blood lipid changes with increased risk of arteriosclerosis.
• Hepatic effects: [U.S. Boxed Warning]: Peliosis hepatis and benign hepatic adenoma have been reported with long-term use (may be complicated by acute intra-abdominal hemorrhage).
• Intracranial hypertension: [U.S. Boxed Warning]: May cause benign intracranial hypertension (pseudotumor cerebri); monitor for headache, nausea/vomiting, visual disturbances and/or papilledema.
• Thromboembolic events: [U.S. Boxed Warning]: Thromboembolism, thrombotic, and thrombophlebitic events have been reported (including life-threatening or fatal strokes).
Disease-related concerns:
• Diabetes: Use with caution in patients with diabetes mellitus; monitor carefully.
• Edematous conditions: Use with caution in patients with conditions influenced by edema (eg, cardiovascular disease, migraine, seizure disorder, renal impairment); may cause fluid retention.
• Fibrocystic disease: Breast cancer should be ruled out prior to treatment for fibrocystic breast disease.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Porphyria: Use with caution in patients with a history of porphyria.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
• Pregnancy: [U.S. Boxed Warning]: Pregnancy must be ruled out prior to treatment; a nonhormonal method of contraception should be used during therapy.
Adverse Reactions
Frequency not defined.
Cardiovascular: Benign intracranial hypertension (rare), edema, flushing, hypertension
Central nervous system: Anxiety (rare), chills (rare), convulsions (rare), depression, dizziness, emotional lability, fainting, fever (rare), Guillain-Barré syndrome, headache, nervousness, sleep disorders, tremor
Dermatologic: Acne, hair loss, mild hirsutism, maculopapular rash, papular rash, petechial rash, pruritus, purpuric rash, seborrhea, Stevens-Johnson syndrome (rare), photosensitivity (rare), urticaria, vesicular rash
Endocrine & metabolic: Amenorrhea (which may continue post therapy), breast size reduction, clitoris hypertrophy, glucose intolerance, HDL decreased, LDL increased, libido changes, nipple discharge, menstrual disturbances (spotting, altered timing of cycle), semen abnormalities (changes in volume, viscosity, sperm count/motility), spermatogenesis reduction
Gastrointestinal: Appetite changes (rare), bleeding gums (rare), constipation, gastroenteritis, nausea, pancreatitis (rare), vomiting, weight gain
Genitourinary: Vaginal dryness, vaginal irritation, pelvic pain
Hematologic: Eosinophilia, erythrocytosis (reversible), leukocytosis, leukopenia, platelet count increased, polycythemia, RBC increased, thrombocytopenia
Hepatic: Cholestatic jaundice, hepatic adenoma, jaundice, liver enzymes increased, malignant tumors (after prolonged use), peliosis hepatis
Neuromuscular & skeletal: Back pain, carpal tunnel syndrome (rare), extremity pain, joint lockup, joint pain, joint swelling, muscle cramps, neck pain, paresthesia, spasms, weakness
Ocular: Cataracts (rare), visual disturbances
Renal: Hematuria
Respiratory: Nasal congestion (rare)
Miscellaneous: Diaphoresis, voice change (hoarseness, sore throat, instability, deepening of pitch)
Metabolism/Transport Effects
Inhibits CYP3A4 (weak)
Drug Interactions
CarBAMazepine: Danazol may decrease the metabolism of CarBAMazepine. Risk D: Consider therapy modification
CycloSPORINE: Androgens may enhance the hepatotoxic effect of CycloSPORINE. Androgens may increase the serum concentration of CycloSPORINE. Risk D: Consider therapy modification
HMG-CoA Reductase Inhibitors: Danazol may decrease the metabolism of HMG-CoA Reductase Inhibitors. Exceptions: Fluvastatin; Pravastatin; Rosuvastatin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Androgens may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Delays time to peak; high-fat meal increases plasma concentration
Storage
Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Suppresses pituitary output of follicle-stimulating hormone and luteinizing hormone that causes regression and atrophy of normal and ectopic endometrial tissue; decreases rate of growth of abnormal breast tissue; reduces attacks associated with hereditary angioedema by increasing levels of C4 component of complement
Pharmacodynamics/Kinetics
Onset of action: Therapeutic: ?4 weeks
Metabolism: Extensively hepatic, primarily to 2-hydroxymethylethisterone
Half-life elimination: 4.5 hours (variable)
Time to peak, serum: Within 2 hours
Excretion: Urine
Dosage
Adults: Oral:
Females: Endometriosis: Initial: 200-400 mg/day in 2 divided doses for mild disease; individualize dosage. Usual maintenance dose: 800 mg/day in 2 divided doses to achieve amenorrhea and rapid response to painful symptoms. Continue therapy uninterrupted for 3-6 months (up to 9 months).
Females: Fibrocystic breast disease: Range: 100-400 mg/day in 2 divided doses
Males/Females: Hereditary angioedema: Initial: 200 mg 2-3 times/day; after favorable response, decrease the dosage by 50% or less at intervals of 1-3 months or longer if the frequency of attacks dictates. If an attack occurs, increase the dosage by up to 200 mg/day.
Monitoring Parameters
Signs and symptoms of intracranial hypertension (papilledema, headache, nausea, vomiting), lipoproteins, androgenic changes, hepatic function
Test Interactions
Testosterone, androstenedione, dehydroepiandrosterone
Patient Education
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed; do not discontinue without consulting prescriber. Therapy may take up to several months depending on purpose for therapy. If you have diabetes, monitor serum glucose closely and notify prescriber of changes; this medication can alter hypoglycemic requirements. Consult prescriber for appropriate self-breast-exam technique. May cause headache, sleeplessness, anxiety (use caution when driving or engaging in potentially hazardous tasks until response to drug is known); acne, growth of body hair, deepening of voice, loss of libido, impotence, or menstrual irregularity (usually reversible). Report changes in menstrual pattern; deepening of voice or unusual growth of body hair; persistent penile erections; fluid retention (eg, swelling of ankles, feet, or hands, respiratory difficulty, or sudden weight gain); change in color of urine or stool; yellowing of eyes or skin; unusual bruising or bleeding; or other adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. This drug should not be used in the 2nd or 3rd trimester of pregnancy. Consult prescriber for appropriate contraceptive measures if necessary or if you suspect you might be pregnant. This drug may cause severe fetal defects. Do not donate blood during or for 1 month following therapy. Do not breast-feed.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess other pharmacological or herbal products patient may be taking for potential interactions (eg, anticoagulants and hypoglycemic agents). Assess results of laboratory tests, therapeutic effectiveness (according to purpose for use), and adverse response (eg, hypertension, increased LDL, CNS changes, jaundice, hematuria). Caution patients with diabetes to monitor glucose levels closely (may enhance the glucose-lowering effect of hypoglycemic agents). Teach patient proper use, possible side effects/appropriate interventions (eg, good self-breast-exam technique), and adverse symptoms to report. Pregnancy risk factor X: Determine that patient is not pregnant before starting therapy. Do not give to female patients of childbearing age unless capable of complying with barrier contraceptive use. Instruct patient in appropriate contraceptive measures.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: 50 mg, 100 mg, 200 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Danazol)
50 mg (30): $52.99
100 mg (30): $68.60
200 mg (30): $110.76
References
Gately LE 3d and Andes WA, “Danazol and Erythema Multiforme,” Ann Intern Med, 1988, 109(1):85.
Makdisi WJ, Cherian R, Vanveldhuizen PJ, et al, “Fatal Peliosis of the Liver and Spleen in a Patient With Agnogenic Myeloid Metaplasia Treated With Danazol,” Am J Gastroenterol, 1995, 90(2):317-8.
Saenger P, “Abnormal Sex Differentiation,” J Pediatr, 1984, 104(1):1-17.
Weinblatt ME, Kochen J, and Ortega J, “Danazol for Children With Immune Thrombocytopenic Purpura,” Am J Dis Child, 1988, 142(12):1317-9.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2009
Content last modified March 2009
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