warnings
WARNINGS Pregnancy: Dopamine agonists in general should not be used in patients with pregnancy-induced hypertension, for example, preeclampsia eclampsia, and post partum hypertension, unless the potential benefit is judged to outweigh the possible risk. Fibrotic Complications: a. Cardiac Valvulopathy: All patients should undergo a cardiovascular evaluation, including echocardiogram to assess the potential presence of valvular disease. If valvular disease is detected, the patient should not be treated with cabergoline (See Contraindications ). Post marketing cases of cardiac valvulopathy have been reported in patients receiving cabergoline. These cases have generally occurred during administration of high doses of cabergoline (>2 mg/day) for the treatment of Parkinson's disease. Cases of cardiac valvulopathy have also been reported in patients receiving lower doses of cabergoline for the treatment of hyperprolactinemic disorders. A multi-country, retrospective cohort study using general practice records and record linkage systems in the UK, Italy and the Netherlands was conducted to assess the association between new use of dopamine agonists including cabergoline (n=27,812) for Parkinson's disease and hyperprolactinemia and cardiac valvular regurgitation (CVR), other fibroses, and other cardiopulmonary events over a maximum of 12 years of follow up. In this study, the use of cabergoline among persons with Parkinson's disease was associated with an increased risk of CVR when compared to non-ergot-derived dopamine agonists (DAs) and levodopa [Incidence Rate (IR) per 10,000 person years of 68.1 (95% confidence interval (CI): 37.2 - 115.3) for cabergoline vs. 10.0 (95% CI: 5.2 - 19.4) for non-ergot DAs and 11.3 (95% CI: 7.2 - 17.0) for levodopa]. In the study analysis confined to persons with dopamine agonist-treated hyperprolactinemia (n=8,386), when compared to non-use (n=15,147), persons exposed to cabergoline did not have an elevated risk of CVR. The findings with respect to the risk of CVR associated with cabergoline treatment for persons with Parkinson's disease (increased risk) and those with hyperprolactinemia (no increased risk) are consistent with the findings in other published studies. Physicians should use the lowest effective dose of cabergoline for the treatment of hyperprolactinemic disorders and should periodically reassess the need for continuing therapy with cabergoline. Following treatment initiation, clinical and diagnostic monitoring (for example, chest x-ray, CT scan and cardiac echocardiogram) should be conducted to assess the risk of cardiac valvulopathy. The recommended frequency of routine echocardiographic monitoring is every 6 to 12 months or as clinically indicated with the presence of signs and symptoms such as edema, new cardiac murmer, dyspnea or congestive heart failure. Cabergoline should be discontinued if an echocardiogram reveals new valvular regurgitation, valvular restriction or valve leaflet thickening. Cabergoline should be used with caution in patients exposed to other medications associated with valvulopathy. b. Extracardiac Fibrotic Reactions: Postmarketing cases of pleural, pericardial and retroperitoneal fibrosis have been following administration of cabergoline. Some reports were in patients previously treated with other ergotinic dopamine agonists. Cabergoline should not be used in patients with a history of cardiac or extracardiac fibrotic disorders. Fibrotic disorders can have an insidious onset and patients should be monitored for manifestations of progressive fibrosis. Therefore, during treatment, attention should be paid to the signs and symptoms of: Pleuro-pulmonary disease such as dyspnea, shortness of breath, persistent cough or chest pain Renal insufficiency or ureteral/abdominal vascular obstruction that may occur with pain in the loin/flank and lower limb edema 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 and diagnostic monitoring such as erythrocyte sedimentation rate, chest x-ray, serum creatinine measurements, and other investigations should be considered at baseline and as necessary while patients are treated with cabergoline. Following diagnosis of pleural effusion or pulmonary fibrosis, the discontinuance of cabergoline was reported to result in improvement of signs and symptoms.