General:As with other ergot derivatives, Cabaser should be given with caution to patients with severe cardiovascular disease, Raynaud's syndrome, peptic ulcer or gastrointestinal bleeding, or with a history of serious, particularly psychotic, mental disorders. 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 Cabaser 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 Cabaser, particularly during the first days of administration of Cabaser. Care should be exercised when administering Cabaser concomitantly with other drugs known to lower blood pressure.
Fibrosis and Cardiac Valvulopathy and Possibly Related Clinical PhenomenaFibrotic 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 Cabaser. In some cases, symptoms or manifestations of cardiac valvulopathy improved after discontinuation of Cabaser. 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 creatinine 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 Cabaser has been reported to result in improvement of signs and symptoms. (See section 4.3 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 Cabaser treatment for the patient should be reassessed to determine the suitability of continued treatment with Cabaser.Before initiating long-term treatment:All patients must 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 Cabaser treatment might worsen the underlying disease. If fibrotic valvular disease is detected, the patient should not be treated with Cabaser (See Section 4.3 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: Pleuropulmonary disease, such as dyspnoea, 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 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 fibrotic disorders, 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 least every 6 to 12 months.Cabaser should be discontinued if an echocardiogram reveals new or worsened valvular regurgitation, valvular restriction or valve leaflet thickening. (See Section 4.3 Contraindications). The need for other clinical monitoring (e.g. physical examination including, 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 a fibrotic disorder.
Somnolence/Sudden Sleep Onset:Cabaser has been associated with somnolence and episodes of sudden sleep onset in patients with Parkinson's disease. Sudden onset of sleep during activities, in some cases without awareness or warning signs, has been reported. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with cabergoline. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. A reduction of dosage or termination of therapy may be considered. (See section 4.7 Effects on ability to drive and use machines)The effects of alcohol on overall tolerability of Cabaser are currently unknown.
Impulse control disorders:Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including Cabaser. Dose reduction/tapered discontinuation should be considered if such symptoms develop.