danazol
Regulatory sources consulted
Approved indications
- Treatment of symptoms and reduction of endometriosis lesions, alone or with surgery when other options have not worked.
- Prevention of hereditary angioedema attacks.
Contraindications
Absolute
- Pregnancy or breastfeeding; marked cardiac, renal, or liver dysfunction; porphyria; androgen-dependent tumor; undiagnosed genital bleeding.
- Active or prior thrombosis or thromboembolic disease; hypersensitivity; concomitant simvastatin use.
Clinical warnings
- Major warning · Stop for virilization, papilledema or intracranial hypertension, jaundice or liver dysfunction, thrombosis, or thromboembolism. — CIMA/AEMPS, ficha técnica 56256
- Major warning · Long-term use is associated with peliosis, hepatic adenoma, and hepatic carcinoma; monitor liver function and blood counts and consider liver ultrasound with prolonged or repeated treatment. — CIMA/AEMPS, ficha técnica 56256
- Major warning · Danazol may cause insulin resistance; people with diabetes may need reassessment of glycemic control and antidiabetic treatment. — CIMA/AEMPS, ficha técnica 56256
Drug interactions
- HighSimvastatin and other CYP3A4 statins
Mechanism: It increases the risk of myopathy and rhabdomyolysis; simvastatin is contraindicated.
Recommendation: Do not combine with simvastatin; review other CYP3A4-metabolized statins.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- HighWarfarin
Mechanism: It may potentiate the anticoagulant effect.
Recommendation: Closely monitor coagulation and adjust anticoagulation.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- ModerateCarbamazepine, phenytoin, or phenobarbital
Mechanism: Danazol may increase carbamazepine and alter response to other anticonvulsants.
Recommendation: Monitor concentrations or clinical response and adjust as appropriate.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- ModerateInsulin and other antidiabetic treatments
Mechanism: Danazol-induced insulin resistance may alter glycemic control and treatment requirements.
Recommendation: Monitor blood glucose and reassess antidiabetic treatment dosing according to clinical response.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- ModerateAntihypertensive drugs
Mechanism: Danazol may reduce antihypertensive effectiveness, possibly by promoting fluid retention.
Recommendation: Monitor blood pressure and fluid retention and adjust antihypertensive treatment if needed.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- HighCyclosporine or tacrolimus
Mechanism: Danazol may increase their plasma concentrations and renal toxicity.
Recommendation: Monitor concentrations, renal function, and toxicity; adjust the immunosuppressant as appropriate.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- ModerateAlfacalcidol
Mechanism: In primary hypoparathyroidism, danazol may increase the calcemic response to alfacalcidol.
Recommendation: Monitor calcium and adjust alfacalcidol if the calcemic response increases.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
Adverse events
Common (≥1%)
Weight or appetite gain · Acne, seborrhea, or hirsutism · Voice changes · Headache · Nausea · Hot flushes · Mood changes
Rare but serious
Thrombosis or stroke · Peliosis, hepatic adenoma, or hepatic carcinoma · Intracranial hypertension · Pancreatitis
Pregnancy and lactation
Contraindicated in pregnancy because of the risk of virilizing a female fetus; exclude pregnancy, start during menses, and use nonhormonal contraception. Discontinue the drug or breastfeeding.
Recent literature (PubMed)
Endometriosis is an inflammatory condition caused by the presence of endometrial tissue in extra-uterine locations and can involve bowel, bladder, and all peritoneal structures. It is one of the most common gynecologic disorders, affecting up to 10% of people of reproductive age. Presentation of endometriosis can vary widely, from infertility in asymptomatic people to debilitating pelvic pain, dysmenorrhea, and period-related gastrointestinal or urinary symptoms. Diagnosis of endometriosis in the primary care setting is clinical and often challenging, frequently resulting in delayed diagnosis and treatment. Although transvaginal ultrasonography is used to evaluate endometriosis of deep pelvic sites to rule out other causes of pelvic pain, magnetic resonance imaging is preferred if deep infiltrating endometriosis is suspected. Laparoscopy with biopsy remains the definitive method for diagnosis, although several gynecologic organizations recommend empiric therapy without immediate surgical diagnosis. Combined hormonal contraceptives with or without nonsteroidal anti-inflammatory drugs are first-line options in managing symptoms and have a tolerable adverse effect profile. Second-line treatments include gonadotropin-releasing hormone (GnRH) receptor agonists with add-back therapy, GnRH receptor antagonists, and danazol. Aromatase inhibitors are reserved for severe disease. All of these treatments are effective but may cause additional adverse effects. Referral to gynecology for surgical management is indicated if empiric therapy is ineffective, immediate diagnosis and treatment are necessary, or patients desire pregnancy. Alternative treatments have limited benefit in alleviating pain symptoms but may warrant further investigation.
Janus kinase (JAK) inhibitors approved for myelofibrosis provide spleen and symptom improvements but do not meaningfully improve anaemia. Momelotinib, a first-in-class inhibitor of activin A receptor type 1 as well as JAK1 and JAK2, has shown symptom, spleen, and anaemia benefits in myelofibrosis. We aimed to confirm the differentiated clinical benefits of momelotinib versus the active comparator danazol in JAK-inhibitor-exposed, symptomatic patients with anaemia and intermediate-risk or high-risk myelofibrosis. MOMENTUM is an international, double-blind, randomised, controlled, phase 3 study that enrolled patients at 107 sites across 21 countries worldwide. Eligible patients were 18 years or older with a confirmed diagnosis of primary myelofibrosis or post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis. Patients were randomly assigned (2:1) to receive momelotinib (200 mg orally once per day) plus danazol placebo (ie, the momelotinib group) or danazol (300 mg orally twice per day) plus momelotinib placebo (ie, the danazol group), stratified by total symptom score (TSS; <22 vs ≥22), spleen size (<12 cm vs ≥12 cm), red blood cell or whole blood units transfused in the 8 weeks before randomisation (0 units vs 1-4 units vs ≥5 units), and study site. The primary endpoint was the Myelofibrosis Symptom Assessment Form (MFSAF) TSS response rate at week 24 (defined as ≥50% reduction in mean MFSAF TSS over the 28 days immediately before the end of week 24 compared with baseline). MOMENTUM is registered with ClinicalTrials.gov, number NCT04173494, and is active but not recruiting. 195 patients were randomly assigned to either the momelotinib group (130 [67%]) or danazol group (65 [33%]) and received study treatment in the 24-week randomised treatment period between April 24, 2020, and Dec 3, 2021. A significantly greater proportion of patients in the momelotinib group reported a 50% or more reduction in TSS than in the danazol group (32 [25%] of 130 vs six
Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.
Breast pain is a common symptom in most women during their lifetime, and many times is self-limited. Mastalgia is categorized into 3 main groups: cyclic, noncyclic and extramammary. A good history, examination and targeted imaging can help to delineate the underlying cause of mastalgia and therefore guide treatment options. Diet, medications, stress, hormonal fluctuations, and an ill-fitting bra can be contributing factors for physiologic causes of mastalgia. Breast cancer is rarely a cause but should be excluded. Reassurance, support, dietary changes, nonsteroidal anti-inflammatory drugs and occasionally hormonal medications are options to help with improving breast pain. No information is available on the use of danazol during breastfeeding, and it is considered to be contraindicated during breastfeeding.[1-4] An alternate drug is preferred.