danazol
Sources réglementaires consultées
Indications approuvées
- Traitement des symptômes et réduction des lésions d’endométriose, seul ou associé à la chirurgie lorsque les autres options n’ont pas été efficaces.
- Prévention des crises d’angiœdème héréditaire.
Contre-indications
Absolues
- Grossesse ou allaitement ; dysfonction cardiaque, rénale ou hépatique importante ; porphyrie ; tumeur androgénodépendante ; saignement génital non diagnostiqué.
- Thrombose ou maladie thromboembolique active ou antérieure ; hypersensibilité ; utilisation concomitante de simvastatine.
Mises en garde cliniques
- Mise en garde majeure · Arrêter en cas de virilisation, d’œdème papillaire ou d’hypertension intracrânienne, d’ictère ou de dysfonction hépatique, de thrombose ou de thromboembolie. — CIMA/AEMPS, ficha técnica 56256
- Mise en garde majeure · L’utilisation prolongée est associée à une péliose, un adénome et un carcinome hépatiques ; surveiller la fonction hépatique et l’hémogramme et envisager une échographie hépatique lors de traitements prolongés ou répétés. — CIMA/AEMPS, ficha técnica 56256
- Mise en garde majeure · Le danazol peut provoquer une résistance à l’insuline ; chez les personnes diabétiques, le contrôle glycémique et le traitement antidiabétique peuvent devoir être réévalués. — CIMA/AEMPS, ficha técnica 56256
Interactions médicamenteuses
- SévèreSimvastatine et autres statines métabolisées par le CYP3A4
Mécanisme: Le risque de myopathie et de rhabdomyolyse augmente ; la simvastatine est contre-indiquée.
Recommandation: Ne pas associer à la simvastatine ; réévaluer les autres statines métabolisées par le CYP3A4.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- SévèreWarfarine
Mécanisme: Il peut potentialiser l’effet anticoagulant.
Recommandation: Surveiller étroitement la coagulation et ajuster l’anticoagulation.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- ModéréeCarbamazépine, phénytoïne ou phénobarbital
Mécanisme: Le danazol peut augmenter la carbamazépine et modifier la réponse aux autres anticonvulsivants.
Recommandation: Surveiller les concentrations ou la réponse clinique et ajuster si nécessaire.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- ModéréeInsuline et autres traitements antidiabétiques
Mécanisme: La résistance à l’insuline induite par le danazol peut modifier le contrôle glycémique et les besoins thérapeutiques.
Recommandation: Surveiller la glycémie et réévaluer la posologie du traitement antidiabétique selon la réponse clinique.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- ModéréeAntihypertenseurs
Mécanisme: Le danazol peut réduire l’efficacité des antihypertenseurs, probablement en favorisant la rétention hydrique.
Recommandation: Surveiller la pression artérielle et la rétention hydrique et ajuster le traitement antihypertenseur si nécessaire.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- SévèreCiclosporine ou tacrolimus
Mécanisme: Le danazol peut augmenter leurs concentrations plasmatiques et leur toxicité rénale.
Recommandation: Surveiller les concentrations, la fonction rénale et la toxicité ; ajuster l’immunosuppresseur si nécessaire.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
- ModéréeAlfacalcidol
Mécanisme: Dans l’hypoparathyroïdie primitive, le danazol peut augmenter la réponse calcémique à l’alfacalcidol.
Recommandation: Surveiller la calcémie et ajuster l’alfacalcidol si la réponse calcémique augmente.
CIMA/AEMPS, ficha técnica 56256https://cima.aemps.es/cima/dochtml/ft/56256/FT_56256.html
Effets indésirables
Communs (≥1%)
Prise de poids ou augmentation de l’appétit · Acné, séborrhée ou hirsutisme · Modification de la voix · Céphalées · Nausées · Bouffées de chaleur · Troubles de l’humeur
Rares mais graves
Thrombose ou accident vasculaire cérébral · Péliose, adénome ou carcinome hépatique · Hypertension intracrânienne · Pancréatite
Grossesse et allaitement
Contre-indiqué pendant la grossesse en raison du risque de virilisation d’un fœtus féminin ; exclure une grossesse, commencer pendant les règles et utiliser une contraception non hormonale. Arrêter le médicament ou l’allaitement.
Bibliographie récente (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.