Danazol
Mechanism :
The drug has anti-gonadotropic and anti-estrogenic effects. It mainly acts by suppressing the anterior pituitary gland hence suppressing output of gonadotropins. Danazol also has some androgenic effects.
Indication :
- Treatment of endometriosis
- Treatment of fibrocystic breast disease
- Prophylaxis of angioedema in patients with hereditary angioedema
- Treatment of chronic immune thrombocytopenic purpura (ITP)
- Treatment of breast pain associated with pre-menstrual syndrome (PMS) or PMS-associated bloating, weight gain, anxiety, depression or global complaints.
- Emergency post-coital contraception
Contraindications :
Hypersensitivity to the drug or its components
Carcinoma which is androgen-dependent
Caution in polycythemia, diabetes mellitus, women of reproductive age
Active thrombosis or thromboembolice disease
Cardiac disease, migraine, hypertension, congestive heart failure, renal dysfunction and failure, seizure disorders:
Caution is advised in patients with the above conditions as the drug can exacerbate these conditions by increasing fluid retention. The drug is strictly contra-indicated in severe cardiac dysfunction and severe renal dysfunction (including renal failure).
Hepatic dysfunction, liver toxicity, jaundice, peliosis hepatis:
Strictly contraindicated in patients with severe liver dysfunction. If the drug has to be used, maintain caution while using in patients with mild liver dysfunction. The drug can lead to toxic effects on the liver like cholestatic jaundice, peliosis hepatis, and benign hepatic adenoma. Peliosis hepatis and adenoma may not present until the patient visits the ER with near-fatal intra-abdominal bleeds. Regular liver function panel (LFPs) must be done in all patients.
Porphyria:
The drug can increase ALA synthetase activity and porphyrin metabolism. Hence do not use danazol in patients with acute intermittent porphyria as it can result in an attack.
Vaginal bleeds:
The drug is known to result in irregular menstrual bleeding and breakthrough bleeding infemales that can increase/mask existing vaginal conditions. Hence, strictly contraindicated in un-diagnosed vaginal bleeds.
Breast carcinoma:
Do not use the drug for management of fibrocystic breast disease until the possibility of CA Breast has been ruled out. If there are persisting nodules or their enlargement during therapy, investigate the possibility of carcinoma.
Old age, prostatic hypertrophy
Old aged patients must be treated with the drug with caution as safety and efficacy have not been proven in patients =65 years during random trials. Old aged male patients may have a higher risk of developing clinical hypertrophy.
Dosing :
Endometriosis:
Mild cases: Oral dosing in adult women:
Administer 200-400 mg daily orally in 2 divided doses. Start treatment during menstruation to make sure the woman is not pregnant. Subsequently, doses can be adjusted based on the patient's response. Continue uninterrupted treatment for 3-6 months or up to 9 months as required. If clinical features continue to present post stopping treatment, re-start therapy.
Moderate-severe cases: Oral dosing in adult women:
Administer 800 mg daily orally in 2 divided doses. Start treatment during menstruation to make sure the woman is not pregnant. Subsequently, doses can be adjusted based on the patient's response. Continue uninterrupted treatment for 3-6 months or up to 9 months as required. If clinical features continue to present post stopping treatment, re-start therapy.
Fibrocystic breast disease:
Oral dosing in adults:
Administer 100-400 mg daily orally in 2 divided doses. Start treatment during menstruation to make sure the patient is not pregnant. Adjust dose based on the patient's requirement and response. Though clinical features may be relieved in 3 months, uninterrupted treatment up to 6 months may be necessary to cure nodularity. As ovulation may not be suppressed at this dose, an effective non-hormonal mode of contraception is advised during treatment.
Prophylaxis of angioedema in patients with hereditary angioedema:
Oral dosing in adults:
Start with administration of 200 mg orally twice or thrice a day. The dose can be decreased by 50% every 1-3 months if there is a beneficial response. If not, eg. An attack of angioedema during therapy,elevate the dose by up to 200 mg daily. However, if the drug was started during exacerbation of angioedema caused by stressors like trauma or other causes, attempts must be made from time to time to decrease or stop treatment.
Chronic immune thrombocytopenic purpura (ITP):
Oral dosing in adults:
Administer 200 mg orally 4 times a day. Danazol must be given for at least 6 months as there generally is a slow response.
Breast pain associated with premenstrual syndrome (PMS) or for PMS-associated bloating, elevated weight, anxiety, depression or global complaints:
Oral dosing in adults:
Administer 50-100 mg orally 2 times everyday. Individually adjust the dosing to get the desired effects. The drug has been found to reduce psychiatric features like anxiety, depression and global complaints. For weight gain and bloating, treatment should be limited to patients with pre-menstrual weight gain of >1.4 kilograms.
Emergency post-coital contraception:
Oral dosing in adults:
There are contrasting statements or data about danazol’s efficacy for emergency post-coital contraception. 800-1200 mg orally q12 for 2 doses and 800 mg orally q12 for 3 doses are recommendations that have been studied.
Adverse Effect :
Common side effects:
• Androgenic effects: Hirsutism, hoarseness, acne, sore throat, hair loss, oily skin/hair, reduced size of breast
• Menstrual irregularities
Others: Hypertension, psychiatric illness such as anxiety, depression, intracranial hypertension, thromboembolism, urticaria, diarrhea, nausea, emesis, increased AST, ALT, arthralgia, muscle spasm and dizziness.
Interaction :
Acarbose, acetaminophen, albendazole, amlodipine, amiodarone, apixaban, betamethasone, bisoprolol, cabergoline, carvedilol, canagliflozin, dapsone, dexamethasone, diclofenac, diltiazem are some drugs that can interact with this drug.
Lactation :
Contraindicated as the drug enters breast milk and can cause androgenic effects on the infant.
Pregnanacy :
Danazol is contraindicated in pregnant females, so prior to administering the treatment, it must be ensured that the patient is not pregnant and contraception should be advised so that she does not conceive during the course of treatment. Pregnancy tests like beta sub-unit test that are sensitive to detecting pregnancy early must be performed prior to start of therapy.
Its teratogenic effects occur due to androgens. Some of its effects are: Virilization of the external genitalia of the female fetus with features such as enlarged clitoris, abnormal vaginal development and fusion of genital folds. Extent of virilization depends on the drug dose given and fetal age. More commonly seen in female fetus when drug is given during the first trimester of pregnancy.
Contraception: Women of reproductive age must be advised about the need for contraception specifically non-hormonal methods during treatment. If the woman becomes pregnant during therapy, the drug should be discontinued immediately and the patient must undergo counselling about the possible hazards to the fetus.
Pregnancy Category: X