cabergoline
Sources réglementaires consultées
Indications approuvées
- Inhibition ou suppression de la lactation physiologique post-partum lorsqu’elle est cliniquement indiquée.
- Troubles hyperprolactinémiques, notamment adénome hypophysaire sécrétant de la prolactine, hyperprolactinémie idiopathique ou associée à une selle turcique vide.
Contre-indications
Absolues
- Hypersensibilité à la cabergoline, aux autres alcaloïdes de l’ergot ou aux excipients.
- Antécédent de fibrose pulmonaire, péricardique ou rétropéritonéale ; pour un traitement prolongé, valvulopathie cardiaque démontrée par échocardiographie.
- Insuffisance hépatique sévère, toxémie gravidique, traitement antipsychotique concomitant ou antécédent de psychose puerpérale.
Mises en garde cliniques
- Mise en garde majeure · Elle peut provoquer une hypotension orthostatique. En cas d’utilisation prolongée, rechercher avant et pendant le traitement une valvulopathie et une fibrose pleuropulmonaire, péricardique ou rétropéritonéale. — CIMA/AEMPS, ficha técnica 60867
- Mise en garde majeure · Surveiller la somnolence ou l’endormissement soudain et les troubles du contrôle des impulsions ; réduire ou arrêter après évaluation s’ils surviennent. — CIMA/AEMPS, ficha técnica 60867
Interactions médicamenteuses
- SévèreAntagonistes dopaminergiques, notamment antipsychotiques, métoclopramide et dompéridone
Mécanisme: Ils peuvent réduire l’effet de la cabergoline ; les antipsychotiques concomitants sont contre-indiqués dans cette notice.
Recommandation: Éviter l’association et envisager une alternative.
CIMA/AEMPS, ficha técnica 60867https://cima.aemps.es/cima/dochtml/ft/60867/FT_60867.html
- SévèreMacrolides et autres inhibiteurs puissants du CYP3A4
Mécanisme: Ils peuvent augmenter l’exposition systémique à la cabergoline.
Recommandation: Éviter ou surveiller étroitement la toxicité et l’hypotension.
CIMA/AEMPS, ficha técnica 60867https://cima.aemps.es/cima/dochtml/ft/60867/FT_60867.html
Effets indésirables
Communs (≥1%)
Nausées et dyspepsie · Céphalées ou vertiges · Douleur abdominale · Asthénie ou fatigue
Rares mais graves
Valvulopathie ou fibrose cardiopulmonaire · Épanchement péricardique · Psychose ou trouble sévère du contrôle des impulsions
Grossesse et allaitement
Elle peut rétablir la fertilité. Exclure une grossesse avant l’instauration ; si une conception est prévue, arrêter la cabergoline un mois auparavant en raison de sa longue demi-vie et des données limitées sur l’exposition intra-utérine. Si la conception survient pendant le traitement, arrêter dès la confirmation de la grossesse afin de limiter l’exposition fœtale, sauf décision contraire de l’équipe soignante. Ne pas utiliser si l’allaitement doit être maintenu, car elle inhibe la production lactée.
Bibliographie récente (PubMed)
Pituitary adenomas are neoplasms of the pituitary adenohypophyseal cell lineage and include functioning tumors, characterized by the secretion of pituitary hormones, and nonfunctioning tumors. Clinically evident pituitary adenomas occur in approximately 1 in 1100 persons. Pituitary adenomas are classified as either macroadenomas (≥10 mm) (48% of tumors) or microadenomas (<10 mm). Macroadenomas may cause mass effect, such as visual field defects, headache, and/or hypopituitarism, which occur in about 18% to 78%, 17% to 75%, and 34% to 89% of patients, respectively. Thirty percent of pituitary adenomas are nonfunctioning adenomas, which do not produce hormones. Functioning tumors are those that produce an excess of normally produced hormones and include prolactinomas, somatotropinomas, corticotropinomas, and thyrotropinomas, which produce prolactin, growth hormone, corticotropin, and thyrotropin, respectively. Approximately 53% of pituitary adenomas are prolactinomas, which can cause hypogonadism, infertility, and/or galactorrhea. Twelve percent are somatotropinomas, which cause acromegaly in adults and gigantism in children, and 4% are corticotropinomas, which secrete corticotropin autonomously, resulting in hypercortisolemia and Cushing disease. All patients with pituitary tumors require endocrine evaluation for hormone hypersecretion. Patients with macroadenomas additionally require evaluation for hypopituitarism, and patients with tumors compressing the optic chiasm should be referred to an ophthalmologist for formal visual field testing. For those requiring treatment, first-line therapy is usually transsphenoidal pituitary surgery, except for prolactinomas, for which medical therapy, either bromocriptine or cabergoline, is usually first line. Clinically manifest pituitary adenomas affect approximately 1 in 1100 people and can be complicated by syndromes of hormone excess as well as visual field defects and hypopituitarism from mass effect in larger tumors. First-
Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the "hook effect" and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations.
Hyperprolactinaemia can result from physiological causes, pharmacological agents, or pathological conditions such as prolactin-secreting pituitary adenomas and other pituitary stalk-compressing masses. Sporadic prolactinomas are the most common functioning pituitary adenomas, with a female predominance during reproductive years. In men, these adenomas are usually larger and more aggressive. Prolactinomas are characterised by positive immunostaining for prolactin, pituitary-specific positive transcription factor 1, and oestrogen receptor α. Dopamine agonists, particularly cabergoline, are typically used as primary therapy. Treatment with up to 2·0 mg per week of cabergoline for at least 6 months normalises prolactin concentrations, achieves adenoma shrinkage of at least 30%, and restores gonadal function in most patients. Transsphenoidal surgery is increasingly used as primary therapy for small prolactinomas given a high chance of remission; transsphenoidal surgery is also indicated for patients with dopamine agonist intolerance or resistance. Radiotherapy is reserved for treatment-refractory prolactinomas. Multidisciplinary management and an individualised approach are key to maximising therapeutic responsiveness and optimising outcomes. In this Review, we assess evidence relating to pathogenesis, diagnosis, and management of prolactinomas, and highlight opportunities for future research.
Acromegaly is typically caused by a growth hormone-secreting pituitary adenoma, driving excess secretion of insulin-like growth factor 1. Acromegaly may result in a variety of cardiovascular, respiratory, endocrine, metabolic, musculoskeletal, and neoplastic comorbidities. Early diagnosis and adequate treatment are essential to mitigate excess mortality associated with acromegaly. PubMed searches were conducted using the keywords growth hormone, acromegaly, pituitary adenoma, diagnosis, treatment, pituitary surgery, medical therapy, and radiation therapy (between 1981 and 2021). The diagnosis of acromegaly is confirmed on biochemical grounds, including elevated serum insulin-like growth factor 1 and lack of growth hormone suppression after glucose administration. Pituitary magnetic resonance imaging is advised in patients with acromegaly to identify an underlying pituitary adenoma. Transsphenoidal pituitary surgery is generally first-line therapy for patients with acromegaly. However, patients with larger and invasive tumors (macroadenomas) are often not in remission postoperatively. Medical therapies, including somatostatin receptor ligands, cabergoline, and pegvisomant, can be recommended to patients with persistent disease after surgery. Select patients may also be candidates for preoperative medical therapy. In addition, primary medical therapy has a role for patients without mass effect on the optic chiasm who are unlikely to be cured by surgery. Clinical, endocrine, imaging, histologic, and molecular markers may help predict the response to medical therapy; however, confirmation in prospective studies is needed. Radiation therapy is usually a third-line option and is increasingly administered by a variety of stereotactic techniques. An improved understanding of the pathogenesis of acromegaly may ultimately lead to the design of novel, efficacious therapies for this serious condition.
Pyometra is a common disease in intact bitches and queens and occurs, although less frequently, in most other female pets. In bitches and queens, the illness is generally diagnosed within 4 months after estrus, in middle-aged to older individuals. Complications such as peritonitis, endotoxemia, and systemic inflammatory response syndrome are not uncommon and associated with more severe illness. Ovary-sparing surgical options such as hysterectomy could be considered in individuals with high-risk for detrimental side effects of spaying or without infection of the uterus but has not yet been evaluated for safety in pyometra.