4. Method of administration Cabergoline is to be administered by the oral route. In order to reduce the risk of gastrointestinal undesirable effects it is recommended that cabergoline is taken with meals for all therapeutic indications.
3 Contraindications Pre-eclampsia, eclampsia Uncontrolled hypertension. 1. History of pulmonary, pericardial and retroperitoneal fibrotic disorders or adverse pulmonary reactions. 4 Special warnings and precautions for use – Fibrosis and cardiac valvulopathy and possibly related clinical phenomena).
4 Special warnings and precautions for use General As with other ergot derivatives, cabergoline should be given with caution to subjects with severe cardiovascular disease, hypotension, Raynaud's syndrome, peptic ulcer or gastrointestinal bleeding, or with a history of serious, particularly psychotic, mental disorders.
The effects of alcohol on overall tolerability of cabergoline are currently unknown. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Hepatic insufficiency:
Lower doses of cabergoline should be considered in patients with severe hepatic insufficiency. Compared to normal volunteers and those with lesser degrees of hepatic insufficiency, an increase in AUC has been seen in patients with severe hepatic insufficiency (Child-Pugh Class C) who received a single 1 mg dose.
Postural hypotension:
Postural hypotension can occur following administration of cabergoline, particularly during the first days of administration of cabergoline. Care should be exercised when administering cabergoline concomitantly with other drugs known to lower blood pressure.
Fibrosis and cardiac valvulopathy and possibly related clinical phenomena:
Fibrotic and serosal inflammatory disorders such as pleuritis, pleural effusion, pleural fibrosis, pulmonary fibrosis, pericarditis, pericardial effusion, cardiac valvulopathy involving one or more valves (aortic, mitral and tricuspid) or retroperitoneal fibrosis have occurred after prolonged usage of ergot derivatives with agonist activity at the serotonin 5HT2B receptor, such as cabergoline.
In some cases, symptoms or manifestations of cardiac valvulopathy improved after discontinuation of cabergoline. Erythrocyte sedimentation rate (ESR) has been found to be abnormally increased in association with pleural effusion/fibrosis.
Chest x-ray examination is recommended in cases of unexplained ESR increases to abnormal values. Serum creatine measurements can also be used to help in the diagnosis of fibrotic disorder. Following diagnosis of pleural effusion/pulmonary fibrosis or valvulopathy, the discontinuance of cabergoline has been reported to result in improvement of signs and symptoms.
3 Contraindications). Valvulopathy has been associated with cumulative doses, therefore, patients should be treated with the lowest effective dose. At each visit, the risk benefit profile of cabergoline treatment for the patient should be reassessed to determine the suitability of continued treatment with cabergoline.
Before initiating long-term treatment:
All patients should undergo a cardiovascular evaluation, including echocardiogram, to assess the potential presence of asymptomatic valvular disease. It is also appropriate to perform baseline investigations of erythrocyte sedimentation rate or other inflammatory markers, lung function/chest x-ray and renal function prior to initiation of therapy.
In patients with valvular regurgitation, it is not known whether cabergoline treatment might worsen the underlying disease. If fibrotic valvular disease is detected, the patient should not be treated with cabergoline. 3 Contraindications).
During long-term treatment:
Fibrotic disorders can have an insidious onset and patients should be regularly monitored for possible manifestations of progressive fibrosis. Therefore during treatment, attention should be paid to the signs and symptoms of: Pleuro-pulmonary disease, such as dyspnoea, shortness of breath, persistent cough, or chest pain.
Renal insufficiency or ureteral/abdominal vascular obstructions that may occur with pain in the loin/flank, and lower limb oedema, as well as any possible abdominal masses or tenderness that may indicate retroperitoneal fibrosis.
Cardiac failure; cases of valvular and pericardial fibrosis have often manifested as cardiac failure. Therefore, valvular fibrosis (and constrictive pericarditis) should be excluded if such symptoms occur. Clinical diagnostic monitoring for development of valvular disease or fibrotic disease as appropriate, is essential.
Following treatment initiation, the first echocardiogram must occur within 3-6 months, thereafter, the frequency of echocardiographic monitoring should be determined by appropriate individual clinical assessment with particular emphasis on the above-mentioned signs and symptoms, but must occur at a least every 6 to 12 months.
3 Contraindications). g. physical examination including careful cardiac auscultation, X-ray, CT scan) should be determined on an individual basis. Additional appropriate investigations such as erythrocyte sedimentation rate, and serum creatinine measurements should be performed if necessary to support a diagnosis of fibrotic disorder.
Somnolence/sudden sleep onset:
Cabergoline has been associated with somnolence and episodes of sudden sleep onsetin patients with Parkinson's disease. Sudden onset of sleep during activities, in […]