Adult: For the reduction of breast pain, tenderness, and nodularity in mastalgia and fibrocystic breast disease: 100-400 mg daily given in 2 divided doses, may be adjusted according to response. Initiate therapy during menstruation (preferably on the 1st day) and ensure that pregnancy has been excluded. Treatment duration: 3-6 months. Dosage and treatment recommendations may vary among individual products or between countries (refer to local detailed product guidelines).
Oral Endometriosis
Adult: 200-800 mg daily given in 2-4 divided doses, may be adjusted depending on the severity of the condition and patient's response. Initiate therapy during menstruation (preferably on the 1st day) and ensure that pregnancy has been excluded. Continue uninterrupted treatment for 3-6 months, may be extended for up to 9 months as necessary. Dosage and treatment recommendations may vary among individual products or between countries (refer to local detailed product guidelines).
Oral Prevention of recurrent attacks of hereditary angioedema
Adult: Initially, 200 mg bid or tid. After a favourable initial response is achieved, reduce the dose by ≤50% at intervals of 1-3 months or longer depending on the frequency of attacks prior to treatment. If an attack occurs, dose may be increased by up to 200 mg daily. Use the lowest effective dose. Dosage and treatment recommendations may vary among individual products or between countries (refer to local detailed product guidelines).
Renal Impairment
Markedly impaired: Contraindicated.
Hepatic Impairment
Markedly impaired: Contraindicated.
Administration
May be taken with or without food. Take consistently either always w/ or always w/o meals.
Contraindications
Active or history of thromboembolic disease or thrombosis; markedly impaired cardiac function, porphyria, undiagnosed abnormal genital bleeding, androgen-dependent tumour. Marked renal and hepatic impairment. Pregnancy and lactation. Concomitant use with simvastatin.
Special Precautions
Patient with diabetes mellitus, hypertension, CV disease, migraine, epilepsy, polycythaemia, and lipoprotein disorder. Patients who have shown persistent or marked androgenic reaction to previous gonadal steroid treatment. Renal and hepatic impairment.
Adverse Reactions
Significant: Peliosis hepatis and benign hepatic adenoma (particularly with long-term use); benign intracranial hypertension, androgenic effects (e.g. acne, weight gain, seborrhoea, hirsutism, hair loss, voice changes, fluid retention, hypertrophy of clitoris), changes in blood lipids (e.g. decreased HDL, increased LDL), exacerbation of acute intermittent porphyria. Blood and lymphatic system disorders: Eosinophilia, leucopenia, polycythaemia. Cardiac disorders: Palpitation, tachycardia. Eye disorders: Blurred vision. Gastrointestinal disorders: Nausea, epigastric pain, vomiting, constipation. General disorders and administration site conditions: Fatigue. Hepatobiliary disorders: Jaundice, hepatocellular injury. Investigations: Increased serum transaminase levels, increased creatine phosphokinase. Metabolism and nutrition disorders: Changes in appetite, impaired glucose tolerance, increased insulin resistance. Musculoskeletal and connective tissue disorders: Back pain, muscle cramps, joint pain or swelling. Nervous system disorders: Dizziness, headache, tremor. Psychiatric disorders: Emotional lability, anxiety, depressed mood, nervousness, changes in libido. Reproductive system and breast disorders: Amenorrhoea, menstrual spotting, vaginal dryness and irritation, reduction in breast size. Respiratory, thoracic and mediastinal disorders: Pleuritic pain, interstitial pneumonitis. Skin and subcutaneous tissue disorders: Rash, diaphoresis, photosensitivity, Stevens-Johnson syndrome, erythema multiforme. Vascular disorders: Flushing, hypertension. Potentially Fatal: Thromboembolism, thrombotic and thrombophlebitic events, including sagittal sinus thrombosis and stroke.
Women of childbearing potential must use effective non-hormonal birth control methods during treatment.
Monitoring Parameters
Evaluate pregnancy status before treatment initiation in women of childbearing potential. Exclude the presence of hormone-dependent carcinoma, including persisting or enlarged breast nodules prior to starting the therapy. Monitor liver and renal function tests periodically; lipid profile, CBC, blood pressure, and blood sugar levels (particularly in diabetic patients). For long-term therapy or repeated treatment courses, obtain liver ultrasound at baseline and annually. Assess for signs and symptoms of intracranial hypertension, fluid retention, and androgenic changes.
Drug Interactions
Increased risk of myopathy and rhabdomyolysis with statins (e.g. simvastatin, atorvastatin, lovastatin). May increase the serum concentrations of ciclosporin, tacrolimus, and carbamazepine. May result in prolonged prothrombin time with warfarin. May increase the calcaemic response to synthetic vitamin D analogues in primary hypoparathyroidism. Danazol may diminish the therapeutic effect of antidiabetic drugs, including insulin.
Food Interaction
Increased plasma concentration and extent of availability with high-fat meals. Additionally, the time to peak plasma levels may be delayed with food.
Lab Interference
May interfere with laboratory determinations of testosterone, plasma proteins, androstenedione, and dehydroepiandrosterone.
Action
Description: Mechanism of Action: Danazol is a synthetic derivative of ethisterone (ethinyl testosterone) with a weak androgenic activity. It suppresses the pituitary-ovarian axis by inhibiting the pituitary output of FSH and LH, leading to the regression and atrophy of normal and ectopic endometrial tissue. It also decreases the growth rate of abnormal breast tissues. In hereditary angioedema, danazol reduces attacks by increasing the levels of the deficient C1 esterase inhibitor (C1EI) and consequently increasing the C4 component of the complement system. Pharmacokinetics: Absorption: Absorbed from the gastrointestinal tract. Increased plasma concentration and extent of availability with high-fat meals; time to peak plasma levels may also be delayed with food. Time to peak plasma concentration: 4 hours (range: 2-8 hours). Metabolism: Extensively metabolised in the liver to form 2-hydroxymethyl danazol and ethisterone. Excretion: Via urine and faeces. Elimination half-life: 9.7 hours ± 3.29 hours.
Chemical Structure
Danazol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 28417, Danazol. https://pubchem.ncbi.nlm.nih.gov/compound/Danazol. Accessed Mar. 22, 2024.
Storage
Store between 20-25°C. Protect from light and moisture.
G03XA01 - danazol ; Belongs to the class of antigonadotropins and similar agents.
References
Anargil 100 mg and 200 mg Capsules, Hard (Komedic Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 28/02/2024.Anon. Danazol. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 28/02/2024.Anon. Danazol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 28/02/2024.Buckingham R (ed). Danazol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/02/2024.Danazol Capsule (Chartwell RX, LLC.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 28/02/2024.Danazol Capsules 100 mg (Generics [UK] Ltd t/a Mylan). MHRA. https://products.mhra.gov.uk. Accessed 28/02/2024.Danazol. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 14/03/2024.Preston CL (ed). Danazol + Insulin. Stockley’s Drug Interactions [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/03/2024.
Sign Out
