danazol

REMS

Treatment of moderate endometriosis that is unresponsive to conventional therapy.
Palliative therapy of fibrocystic breast disease.
Prophylaxis of hereditary angioedema.

Action ⬆ ⬇

Inhibits pituitary output of gonadotropins, resulting in suppression of ovarian function. Has weak androgenic-anabolic activity.

Therapeutic effects:

Atrophy of ectopic endometrial tissue in endometriosis.
Decreased pain and nodularity in fibrocystic breast disease.
Correction of biochemical abnormalities in hereditary angioedema.

Pharmacokinetics ⬆ ⬇

Absorption: Absorbed from the GI tract.

Distribution: Unknown.

Metabolism/Excretion: Metabolized by the liver.

Half-Life: 4.5 hr.

Time/Action Profile ⬆ ⬇

(disease response)

ROUTE	ONSET	PEAK	DURATION
PO (endometriosis)	unknown	6–8 wk	60–90 days
PO (fibrocystic disease)	1 mo	2–6 mo	1 yr
PO (angioedema)	unknown	1–3 mo	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Male patients with breast or prostate cancer;
Hypercalcemia;
Severe hepatic, renal, or cardiac disease;
OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Previous history of liver disease;
History of porphyria;
Coronary artery disease;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema

Derm: acne, hirsutism, oiliness

EENT: deepening of voice

Endo: ↓breast size (women), amenorrhea, anovulation, ↓libido

GI: hepatitis (cholestatic jaundice)

GU: amenorrhea, clitoral enlargement, testicular atrophy

Metab: weight gain

Neuro: emotional lability

Interactions ⬆ ⬇

Drug-drug:

May potentiate warfarin, oral hypoglycemic agents, insulins, or corticosteroids.
May ↑ cyclosporine or carbamazepine levels and risk of toxicity.
May ↑ the requirement for insulin in patients with diabetes.
↑risk of myopathy or rhabdomyolysis with HMG Co-A reductase inhibitors.

Route/Dosage ⬆ ⬇

Endometriosis

PO (Adults ): 400 mg twice daily (for milder cases may initiate therapy with 100–200 mg twice daily).

Fibrocystic Breast Disease

PO (Adults ): 50–200 mg twice daily.

Hereditary Angioedema

PO (Adults ): 200 mg 2–3 times daily. Attempt to ↓ dosage by 50% or less every 1–3 mo. If acute attack occurs, ↑ dose by up to 200 mg/day.

Availability ⬆ ⬇

(Generic available)

Capsules: 50 mg; 100 mg; 200 mg

Assessment ⬆ ⬇

Endometriosis: Assess endometrial pain before and periodically during therapy.
Fibrocystic Breast Disease: Assess breast pain, tenderness, and nodules before and monthly during therapy. To rule out carcinoma, mammography or cyst biopsy is recommended before and during treatment if nodules persist or enlarge.
Hereditary Angioedema: Monitor for edematous attacks during therapy, especially during dose adjustments.

Lab Test Considerations:

Monitor liver function tests periodically during therapy.
- Semen volume and viscosity, sperm count, and motility determinations are recommended every 3–4 mo during treatment for hereditary angioedema, especially in adolescents.
- May alter results of glucose tolerance or thyroid function tests. May also cause ↑ serum glucose and low-density lipoprotein concentrations and ↓ high-density lipoprotein concentrations.

Implementation ⬆ ⬇

In patients with endometriosis or fibrocystic breast disease, therapy should be started during menstruation or preceded by a pregnancy test.
PO: Medication may be administered with meals to minimize GI irritation.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication exactly as directed. Take missed doses as soon as remembered, if not almost time for next dose; do not double doses.
- Advise patient to notify health care professional if masculinizing effects occur (abnormal growth of facial hair or other body hair, deepening of the voice).
- Advise patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
- Advise patient to use a nonhormonal form of contraception and avoid breastfeeding during therapy. Inform patient that amenorrhea is expected with higher doses. Instruct patient to notify health care professional if regular menstruation does not occur within 60–90 days after discontinuation of therapy or if pregnancy is suspected.
- Emphasize the importance of routine visits to health care professional to check progress during therapy.
Fibrocystic Breast Disease: Teach patient the correct technique for monthly breast self-exam. Instruct patient to report increase in size of nodules to health care professional promptly.

Evaluation/Desired Outcomes ⬆ ⬇

Decrease in symptoms of endometriosis. Therapy for endometriosis usually requires 3–6 mo and may extend to 9 mo to decrease symptoms.
Relief of pain and tenderness in fibrocystic breast disease, which is usually relieved by the first mo and eliminated in 2–3 mo. Elimination of nodularity usually requires 4–6 mo.
Resolution of signs and symptoms of hereditary angioedema. Initial response in hereditary angioedema may require 1–3 mo of therapy; efforts should be made to decrease dose at 1–3-mo intervals.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇