Usage
Danazol is primarily prescribed for the treatment of endometriosis, a condition where tissue similar to the lining of the uterus grows outside the uterus. It is also used to treat fibrocystic breast disease (painful, lumpy breasts) and hereditary angioedema (swelling in various parts of the body). Danazol is classified as a synthetic androgen (a male hormone) and functions as an anti-gonadotropin. It works by suppressing the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, leading to a decrease in the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary gland. This, in turn, reduces estrogen production in the ovaries and creates a hypoestrogenic environment that helps to shrink endometrial tissue.
Alternate Names
Danazol is also known as Gonadan. Brand names for danazol include Danocrine, Cyclomen, and Danol.
How It Works
Pharmacodynamics: Danazol binds to various steroid hormone receptors, including androgen, progesterone, and glucocorticoid receptors, with varying affinities. Its primary effect is the suppression of the hypothalamic-pituitary-ovarian axis. This leads to reduced estrogen production and creates a high-androgen, low-estrogen environment in the body. It also increases the levels of C1 esterase inhibitor, a protein deficient in individuals with hereditary angioedema.
Pharmacokinetics: Danazol is administered orally and is well-absorbed from the gastrointestinal tract. It is extensively metabolized in the liver, primarily by CYP3A4 enzymes. The bioavailability of danazol is affected by food intake, with high-fat meals increasing its absorption. Elimination is primarily through hepatic metabolism and biliary excretion, with a small portion excreted in the urine.
Mode of Action: Danazol’s mode of action involves:
- Modulation of Steroid Hormone Receptors: Danazol binds to androgen, progesterone, and glucocorticoid receptors.
- Inhibition of Steroidogenesis Enzymes: It interferes with enzymes involved in the production of sex hormones.
- Antigonadotropic Activity: Danazol suppresses the release of GnRH, FSH, and LH.
Dosage
Standard Dosage
Adults:
- Endometriosis (Mild): 200-400 mg daily in two divided doses for 3-9 months.
- Endometriosis (Moderate to Severe): 800 mg daily in two divided doses for 3-9 months.
- Fibrocystic Breast Disease: 100-400 mg daily in two divided doses for 3-6 months.
- Hereditary Angioedema: Initially 200 mg two or three times a day. The dose may be adjusted based on the patient’s response.
Children:
The use and dosage in children must be determined by a doctor.
Special Cases:
- Elderly Patients: Dose adjustments may be needed based on renal or hepatic function.
- Patients with Renal Impairment: Dose reduction may be necessary.
- Patients with Hepatic Dysfunction: Danazol is contraindicated in patients with severe hepatic impairment. Dose adjustment is required in mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Close monitoring is needed for patients with diabetes, cardiovascular disease, or other conditions that may be affected by hormonal changes.
Clinical Use Cases
Danazol’s use in settings like intubation, surgical procedures, mechanical ventilation, ICU, and emergency situations is not standard practice. It is not indicated for these clinical scenarios.
Dosage Adjustments
Dosage adjustments may be needed based on individual patient characteristics, including renal or hepatic impairment, other medical conditions, and response to therapy.
Side Effects
Common Side Effects:
Acne, oily skin, weight gain, hirsutism, decreased breast size, voice deepening, menstrual irregularities, vaginal dryness, emotional lability, headache, and muscle cramps.
Rare but Serious Side Effects:
Liver dysfunction (jaundice, elevated liver enzymes), thromboembolic events (blood clots), and benign intracranial hypertension (increased pressure in the skull).
Long-Term Effects:
Chronic liver disease, virilization (development of male characteristics in women), and adverse cardiovascular effects.
Adverse Drug Reactions (ADR):
Hepatotoxicity, thromboembolism, and intracranial hypertension require immediate medical attention.
Contraindications
Pregnancy, undiagnosed abnormal genital bleeding, porphyria, androgen-dependent tumors, severe hepatic, renal, or cardiac disease, and hypersensitivity to danazol.
Drug Interactions
Danazol interacts with warfarin, carbamazepine, cyclosporine, tacrolimus, statins, and synthetic vitamin D analogs. It can also affect blood glucose control, requiring adjustment of antidiabetic medications.
Pregnancy and Breastfeeding
Danazol is contraindicated in pregnancy due to the risk of virilization of female fetuses. It is not recommended during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Suppresses the hypothalamic-pituitary-ovarian axis, reducing estrogen and increasing androgen levels.
- Side Effects: Acne, weight gain, hirsutism, voice deepening, liver dysfunction, thromboembolic events.
- Contraindications: Pregnancy, severe liver disease, androgen-dependent tumors.
- Drug Interactions: Warfarin, carbamazepine, statins.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Variable depending on condition and patient response.
- Monitoring Parameters: Liver function tests, lipid profile, blood glucose, blood pressure.
Popular Combinations
Danazol is not typically used in combination with other drugs for its primary indications.
Precautions
- General Precautions: Assess liver function, lipid profile, and blood glucose before and during treatment.
- Specific Populations: Contraindicated in pregnancy and breastfeeding. Use with caution in patients with hepatic or renal dysfunction.
- Lifestyle Considerations: Patients should be advised about the potential for androgenic side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Danazol?
A: The dosage varies depending on the condition being treated. For endometriosis, it ranges from 200-800 mg daily. For fibrocystic breast disease, the dosage is 100-400 mg daily. For hereditary angioedema, the initial dose is 200 mg two or three times daily.
Q2: What are the common side effects of Danazol?
A: Common side effects include acne, oily skin, weight gain, hirsutism, voice deepening, menstrual changes, and vaginal dryness.
Q3: Is Danazol safe during pregnancy?
A: No, Danazol is contraindicated during pregnancy as it can cause virilization of female fetuses.
Q4: How does Danazol work in endometriosis?
A: Danazol suppresses the hypothalamic-pituitary-ovarian axis, leading to a decrease in estrogen production, causing the endometrial tissue to shrink.
Q5: What are the serious side effects of Danazol?
A: Serious side effects include liver dysfunction, thromboembolic events, and benign intracranial hypertension.
Q6: Can Danazol interact with other medications?
A: Yes, Danazol can interact with several medications, including warfarin, carbamazepine, and statins.
Q7: What precautions should be taken before prescribing Danazol?
A: Assess liver and kidney function, lipid profile, and blood glucose. Rule out pregnancy and androgen-dependent tumors.
Q8: How long is the typical treatment duration for endometriosis with Danazol?
A: Treatment typically lasts for 3 to 9 months.
Q9: Can Danazol be used in children?
A: The safety and efficacy of Danazol in children have not been established. Use with caution and under the guidance of a specialist.
