cabergoline
Regulatory sources consulted
Approved indications
- Inhibition or suppression of physiological postpartum lactation when clinically indicated.
- Hyperprolactinemic disorders, including prolactin-secreting pituitary adenoma, idiopathic hyperprolactinemia, or hyperprolactinemia associated with empty sella syndrome.
Contraindications
Absolute
- Hypersensitivity to cabergoline, other ergot alkaloids, or excipients.
- History of pulmonary, pericardial, or retroperitoneal fibrosis; for long-term treatment, cardiac valvulopathy shown by echocardiography.
- Severe hepatic impairment, toxemia of pregnancy, concomitant antipsychotics, or history of puerperal psychosis.
Clinical warnings
- Major warning · It may cause postural hypotension. For long-term use, assess before and during treatment for valvulopathy and pleuropulmonary, pericardial, or retroperitoneal fibrosis. — CIMA/AEMPS, ficha técnica 60867
- Major warning · Monitor for somnolence or sudden sleep onset and impulse-control disorders; reduce or discontinue after assessment if they occur. — CIMA/AEMPS, ficha técnica 60867
Drug interactions
- HighDopamine antagonists, including antipsychotics, metoclopramide, and domperidone
Mechanism: They may reduce cabergoline effect; concomitant antipsychotics are contraindicated in this label.
Recommendation: Avoid the combination and review an alternative.
CIMA/AEMPS, ficha técnica 60867https://cima.aemps.es/cima/dochtml/ft/60867/FT_60867.html
- HighMacrolides and other strong CYP3A4 inhibitors
Mechanism: They may increase systemic cabergoline exposure.
Recommendation: Avoid or closely monitor toxicity and hypotension.
CIMA/AEMPS, ficha técnica 60867https://cima.aemps.es/cima/dochtml/ft/60867/FT_60867.html
Adverse events
Common (≥1%)
Nausea and dyspepsia · Headache or dizziness · Abdominal pain · Asthenia or fatigue
Rare but serious
Valvulopathy or cardiopulmonary fibrosis · Pericardial effusion · Psychosis or severe impulse-control disorder
Pregnancy and lactation
It may restore fertility. Exclude pregnancy before starting; if conception is planned, discontinue cabergoline one month beforehand because of its prolonged half-life and limited intrauterine exposure data. If conception occurs during treatment, discontinue as soon as pregnancy is confirmed to limit fetal exposure, unless the clinical team determines treatment should continue. Do not use when breastfeeding is to be maintained because it inhibits milk production.
Recent literature (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.