Danamet200 mg

Danamet is a synthetic androgen derivative (attenuated androgen) used in the following clinical settings:

Established / FDA-approved uses

• Endometriosis: Danamet is indicated for the management of pelvic pain and other symptoms of endometriosis in patients who cannot tolerate, or have not responded to, other therapies, when the goal is symptomatic relief rather than cure.
• Prophylaxis of hereditary angioedema (HAE): Danamet is indicated to reduce the frequency and severity of attacks of angioedema (abdominal, facial, laryngeal, and limb) in males and females with this condition.

Guideline-supported / historically established use

• Fibrocystic breast disease: Danamet has established use for relief of pain, tenderness, and nodularity of moderate to severe fibrocystic breast disease; because of its androgenic and hepatic risks, it is now generally reserved for patients who have not responded adequately to other measures.

Danamet is not a first-line agent for endometriosis or fibrocystic breast disease in most current practice; it is generally used when other options have failed or are not suitable, and treatment is time-limited (see Duration of Treatment).

Each capsule of Danazol contains danazol as the active pharmaceutical ingredient, commonly available in strengths such as 50 mg, 100 mg, and 200 mg, along with standard pharmaceutical excipients (e.g., lactose, starch, magnesium stearate) used for capsule formulation. Exact strengths and excipients vary by manufacturer and market; refer to the specific product label for the marketed formulation of Danazol.

Danamet is a synthetic steroid derived from ethisterone, classified as an attenuated (mildly androgenic) androgen. It suppresses pituitary output of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby reducing ovarian estrogen production, and it also has direct effects on steroid hormone receptors and the complement system.

Danamet is administered orally in capsule form and is used for a limited number of specific gynecologic and immunologic conditions where its hormonal and anti-complement actions provide benefit, always under close medical supervision because of its androgenic and hepatic risk profile.

Danamet belongs to the class of synthetic androgens (attenuated androgens / gonadotropin inhibitors), structurally related to ethisterone.

Danazol is an isoxazole derivative of ethisterone (17α-ethinyl testosterone) with weak androgenic activity. Its principal mechanisms include:

• Suppression of the hypothalamic-pituitary-ovarian axis: Danazol inhibits the mid-cycle surge of LH and FSH, leading to anovulation and a hypoestrogenic state that causes atrophy of ectopic and eutopic endometrial tissue.
• Binding to steroid hormone receptors: Danazol binds to androgen, progesterone, and glucocorticoid receptors, contributing to its androgenic and other hormonal effects.
• Increase in C1-esterase inhibitor: In hereditary angioedema, Danazol increases hepatic synthesis of C1-esterase inhibitor and C4 complement levels, reducing the frequency and severity of angioedema attacks.

Following oral administration, Danazol is absorbed from the gastrointestinal tract, extensively metabolized in the liver, and excreted mainly via bile and urine as metabolites.

Danamet capsules should be taken orally, exactly as prescribed by the physician. Capsules may be taken with food if gastrointestinal upset occurs. Treatment with Danamet should generally begin during menstruation, and a negative pregnancy test should be confirmed immediately before starting therapy. Non-hormonal contraception (e.g., barrier methods) should be used throughout treatment. Do not stop, skip doses, change the dose, or share Danamet with another person without consulting the prescribing physician.

Danamet has several well-documented, clinically significant drug interactions:

• Warfarin and other oral anticoagulants: Danamet potentiates the anticoagulant effect, prolonging prothrombin time and increasing bleeding risk; anticoagulant dose reduction and closer INR monitoring are usually required when Danamet is started or stopped.
• Insulin and oral hypoglycemic agents: Danamet may alter glucose tolerance and insulin requirements; blood glucose should be monitored and antidiabetic doses adjusted as needed.
• Carbamazepine: Danamet may increase plasma carbamazepine levels, raising the risk of carbamazepine toxicity; clinical and/or laboratory monitoring is advised.
• Cyclosporine and tacrolimus: Danamet may increase plasma levels of these agents, increasing the risk of nephrotoxicity; monitoring of drug levels and renal function is recommended.
• Statins (HMG-CoA reductase inhibitors): concurrent use with Danamet has been associated with increased risk of myopathy/rhabdomyolysis; combined use should be approached cautiously.

Patients should inform their physician of all medicines being taken before starting Danamet.

Common and serious adverse effects associated with Danamet include:

• Androgenic effects: acne, oily skin/hair, hirsutism, weight gain, edema, voice deepening or hoarseness, and (rarely) clitoral enlargement; voice changes and other virilizing effects may be irreversible even after stopping Danamet and require prompt reporting to a physician.
• Menstrual changes: amenorrhea, spotting, or irregular bleeding.
• Hepatic effects: elevated liver enzymes, cholestatic jaundice; rarely, peliosis hepatis and benign or malignant hepatic tumors with long-term use (see Precautions and Warnings).
• Lipid changes: decreased HDL and increased LDL cholesterol.
• Nervous system: headache, dizziness, mood changes/depression, and rarely benign intracranial hypertension (pseudotumor cerebri).
• Other: hot flashes, muscle cramps, nausea, rash, and reduced sperm count in men.

Danamet is contraindicated in pregnancy. Androgenic effects on a female fetus (such as clitoral hypertrophy and labial fusion, i.e., ambiguous genitalia) have been reported with use during pregnancy. A sensitive pregnancy test should be performed to rule out pregnancy before starting therapy, treatment should begin during menstruation, and effective non-hormonal contraception must be used throughout treatment with Danamet. If pregnancy occurs during treatment, Danamet should be discontinued immediately and the patient counseled about potential fetal risk.

Danamet is also contraindicated during breast-feeding, as it may be excreted in breast milk and could cause virilizing effects in a nursing infant; breast-feeding should not be undertaken while taking Danamet.

Danamet carries several serious, well-established safety concerns that require careful monitoring:

• Hepatotoxicity: Danamet has been associated with serious liver injury, including cholestatic jaundice, peliosis hepatis (blood-filled cysts in the liver), and benign or malignant hepatic tumors, which can rupture and cause life-threatening intra-abdominal hemorrhage. Liver function should be assessed before and periodically during treatment; therapy should be stopped promptly if significant liver abnormalities or jaundice develop.
• Androgenic/virilizing effects: Voice deepening, hirsutism, and clitoral enlargement can occur and may not reverse even after Danamet is discontinued; patients should be advised to report any such changes immediately so the drug can be stopped early.
• Thromboembolism: Cases of thrombosis, thrombotic and thrombo-embolic events (including stroke and life-threatening or fatal events) have been reported with Danamet; use with caution in patients with risk factors for thrombosis.
• Benign intracranial hypertension (pseudotumor cerebri): Symptoms such as severe headache, visual disturbance, nausea, and vomiting require prompt evaluation and discontinuation of Danamet if confirmed.
• Lipid and metabolic effects: Danamet can adversely affect the lipid profile (decreased HDL, increased LDL) and glucose tolerance; use with caution in patients with cardiovascular risk factors or diabetes.
• Use with caution in patients with a seizure disorder, migraine, or cardiac/renal disease.

Specific data on acute overdosage with Danamet are limited. In the event of a suspected overdose of Danamet, seek immediate medical attention or contact a poison control center/emergency services. Management is supportive and symptomatic; there is no specific antidote. Do not attempt to treat an overdose at home without professional medical guidance.

Store at room temperature (below 30°C/86°F, ideally 20-25°C), away from light and moisture. Keep Danamet out of reach of children.

Pediatric use: The safety and efficacy of Danamet have not been established in pediatric patients. Use in children, when considered by a specialist for hereditary angioedema, requires careful weighing of androgenic and growth-related risks against benefit, with close monitoring.

Geriatric use: There is limited experience with Danamet in elderly patients; use with caution given the higher likelihood of hepatic, renal, or cardiovascular impairment in this age group, all of which may be contraindications.

Hepatic/renal/cardiac impairment: Danamet is contraindicated in patients with markedly impaired hepatic, renal, or cardiac function (see Contraindications).

Women of reproductive potential: Effective non-hormonal contraception is required during treatment with Danamet (see Pregnancy and Lactation).

Treatment duration with Danamet is indication-specific: endometriosis is typically treated for 3-6 months, extendable up to 9 months if needed; fibrocystic breast disease is typically treated for 3-6 months; hereditary angioedema prophylaxis may require longer-term therapy at the lowest effective dose, with periodic reassessment of the need for continued treatment and regular monitoring (including liver function tests) throughout use of Danamet.

Danazol is classified as a synthetic androgen (attenuated androgen), also referred to as a gonadotropin inhibitor.

Danazol acts primarily by suppressing pituitary gonadotropin (LH and FSH) secretion, producing a hypoestrogenic, anovulatory state that causes atrophy of endometrial tissue in endometriosis. It also binds directly to androgen and progesterone receptors and increases hepatic synthesis of C1-esterase inhibitor, which underlies its efficacy in preventing attacks of hereditary angioedema.

X (legacy FDA pregnancy category) - contraindicated in pregnancy

The safety and efficacy of Danamet have not been established in pediatric patients for endometriosis or fibrocystic breast disease. In hereditary angioedema, pediatric use of Danamet is occasionally considered by specialists when benefits are judged to outweigh risks, but androgenic effects (including effects on growth and puberty) and hepatic risks mean it should only be used under close specialist supervision, with the lowest effective dose and regular monitoring.