warnings and cautions
5 WARNINGS AND PRECAUTIONS • Cardiac Valvulopathy and Pericardial Fibrosis : Before initiating CABERGOLINE, perform a cardiovascular evaluation, including echocardiogram, to evaluate for valvular disease. During CABERGOLINE treatment, monitor for the development of valvulopathy with a cardiac echocardiogram at intervals of 6 to 12 months or as clinically indicated and monitor for chest pain and signs and symptoms of heart failure (if heart failure occurs, exclude valvular fibrosis and pericarditis). Consider additional clinical and diagnostic monitoring at baseline and as necessary during CABERGOLINE treatment. Use CABERGOLINE in patients treated with other drugs associated with valvulopathy only if the potential benefit of CABERGOLINE outweighs the risk. Discontinue CABERGOLINE if the patient has a new diagnosis of valvular regurgitation, valvular restriction, valve leaflet thickening, or pericarditis. ( 5.1 ) • Pleural, Pulmonary and Retroperitoneal Fibrosis : During CABERGOLINE treatment monitor for signs and symptoms of progressive fibrosis, (e.g., pleuro-pulmonary disease, renal impairment, ureteral/abdominal vascular obstruction). Consider clinical and diagnostic monitoring for pleural, pulmonary, and retroperitoneal fibrosis at baseline and as necessary during CABERGOLINE treatment. If pleural, pericardial, retroperitoneal, or pulmonary fibrosis occur, discontinue CABERGOLINE. ( 5.2 ) • Orthostatic Hypotension : Check blood pressure at baseline and during treatment with CABERGOLINE and monitor for orthostatic hypotension. ( 5.3 ) • Risks with Use of CABERGOLINE for Postpartum Lactation Inhibition or Suppression : Avoid use of CABERGOLINE for the inhibition or suppression of physiologic lactation. Use of bromocriptine, another dopamine agonist for this unapproved use has been associated with cases of hypertension, stroke, myocardial infarction, seizures, and death. ( 5.4 ) • Impulse Control Disorders and Compulsive Behaviors : Specifically ask patients about the development of new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated with CABERGOLINE. Consider dosage reduction or stopping CABERGOLINE if a patient develops such urges while taking CABERGOLINE. ( 5.5 ) 5.1 Cardiac Valvulopathy and Pericardial Fibrosis Before initiating CABERGOLINE, perform a cardiovascular evaluation, including with an echocardiogram, to evaluate for valvular disease. CABERGOLINE is contraindicated in the presence of valvular disease or pericardial fibrosis [see Contraindications (4) ] . Cases of valvular and pericardial fibrosis have often manifested as heart failure. Following CABERGOLINE treatment initiation, monitor for the development of valvulopathy with a cardiac echocardiogram at intervals of 6 to 12 months or as clinically indicated with new onset edema, cardiac murmur, dyspnea, or heart failure. During CABERGOLINE treatment, monitor for chest pain and signs and symptoms of heart failure and if heart failure occurs, valvular fibrosis and pericarditis should be excluded. Consider clinical and diagnostic monitoring such as erythrocyte sedimentation rate, serum creatinine measurements, chest-x- ray, and other investigations and cardiac imaging at baseline and as necessary while patients are treated with during CABERGOLINE treatment. Use CABERGOLINE in patients treated with other drugs associated with valvulopathy only if the potential benefit of CABERGOLINE outweighs the risk. Discontinue CABERGOLINE if the patient has a new diagnosis of valvular regurgitation, valvular restriction, valve leaflet thickening, or pericarditis. Postmarketing cases of cardiac valvulopathy have been reported in patients who received CABERGOLINE. These cases have generally occurred during administration of high doses of CABERGOLINE (>2 mg/day) for the treatment of Parkinson’s disease (PD) (CABERGOLINE is not approved for the treatment of PD). Cases of cardiac valvulopathy have also been reported in patients who received lower dosages of CABERGOLINE for the treatment of hyperprolactinemic disorders. In a 12-year, multi-country retrospective cohort study, the use of CABERGOLINE for PD was associated with an increased risk of cardiac valvular regurgitation (CVR). Compared to non-ergot-derived dopamine agonists and levodopa, CVR with CABERGOLINE use had an incidence rate per 10,000 person years of 68 (95% CI: 37, 115) versus 10 (95% CI: 5, 19) for non-ergot dopamine agonists and 11 (95% CI: 7, 17) for levodopa. 5.2 Pleural, Pulmonary and Retroperitoneal Fibrosis CABERGOLINE is contraindicated in patients with a history of pleural, pulmonary, or retroperitoneal fibrosis. During CABERGOLINE treatment monitor for signs and symptoms of progressive fibrosis, including: • Pleuro-pulmonary disease (e.g., dyspnea, shortness of breath, persistent cough, chest pain). • Renal impairment or ureteral/abdominal vascular obstruction (e.g., pain in the loin/flank, lower limb edema, abdominal masses or tenderness that may indicate retroperitoneal fibrosis). Consider clinical and diagnostic monitoring for pleural, pulmonary, and retroperitoneal fibrosis such as with erythrocyte sedimentation rate, serum creatinine measurements, chest-x-ray, and other investigations at baseline and as necessary during CABERGOLINE treatment. If pleural, pericardial, retroperitoneal, or pulmonary fibrosis occur, discontinue CABERGOLINE. Postmarketing cases of pleural, pulmonary, and retroperitoneal fibrosis have been reported following CABERGOLINE administration. Some reports were in patients previously treated with other ergotinic dopamine agonists. CABERGOLINE-treated patients who developed a pleural effusion or pulmonary fibrosis and subsequently discontinued CABERGOLINE had improvement of their pulmonary symptoms. 5.3 Orthostatic Hypotension Check blood pressure at baseline and during treatment with CABERGOLINE and monitor for orthostatic hypotension. Warn patients about the risk of orthostatic hypotension and precautions to take when rising from a supine or sitting position. Instruct patients to report dizziness or lightheadedness with changes in position to their healthcare provider. CABERGOLINE can cause orthostatic hypotension [see Adverse Reactions (6.1) ] . In a 4-week, placebo-controlled trial in patients with hyperprolactinemic disorders, the percentage of CABERGOLINE-treated patients and placebo-treated patients who developed orthostatic hypotension was 4% and 0%, respectively [see Adverse Reactions (6.1) ] . The risk of orthostatic hypotension is greater in CABERGOLINE-treated patients when taking concomitant drugs that lower blood pressure. 5.4 Risks with Use of CABERGOLINE for Postpartum Lactation Inhibition or Suppression Avoid use of CABERGOLINE for the inhibition or suppression of postpartum physiologic lactation because of the risk of serious adverse reactions. Use of bromocriptine, another dopamine agonist for this unapproved use has been associated with cases of hypertension, stroke, myocardial infarction seizures, and death. 5.5 Impulse Control Disorders and Compulsive Behaviors Because patients may not recognize impulse control and compulsive behaviors as abnormal, it is important for health care providers to specifically ask patients about the development of new or increased gambling urges, sexual urges, uncontrolled spending, or other urges while being treated with CABERGOLINE. Consider dosage reduction or stopping CABERGOLINE if a patient develops such urges while taking CABERGOLINE. Patients can experience intense urges to gamble or to spend money, increased sexual urges, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more drugs that increase central dopaminergic tone, including CABERGOLINE. In some cases, these urges were reported to have stopped when the dosage was reduced, or the drug was stopped.