General:The safety and efficacy of DOSTINEX have not yet been established in patients with renal and hepatic disease. As with other ergot derivatives, DOSTINEX should be given with caution to patients with severe cardiovascular disease, Raynaud's syndrome, renal insufficiency, peptic ulcer or gastrointestinal bleeding, or with a history of serious, particularly psychotic, mental disorders. Particular care should be taken when patients are taking concomitant psychoactive medication.Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.Symptomatic hypotension can occur with DOSTINEX administration for any indication. Care should be exercised when administering DOSTINEX concomitantly with other drugs known to lower blood pressure.The effects of alcohol on overall tolerability of DOSTINEX are currently unknown.Before DOSTINEX administration, pregnancy should be excluded and after treatment pregnancy should be prevented for at least one month.Hepatic Insufficiency:Lower doses should be considered in patients with severe hepatic insufficiency who receive prolonged treatment with DOSTINEX. 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 DOSTINEX. Care should be exercised when administering DOSTINEX concomitantly with other drugs known to lower blood pressure.Somnolence/Sudden Sleep Onset:DOSTINEX has been associated with somnolence. Dopamine agonists can be associated with sudden sleep onset episodes in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly. 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. Furthermore a reduction in dosage or termination of therapy may be considered. (See section 4.7 Effects on ability to drive and use machines)
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 DOSTINEX. Dose reduction/tapered discontinuation should be considered if such symptoms develop.
Inhibition/suppression of physiological lactation:As with other ergot derivatives, DOSTINEX should not be used in women with pregnancy-induced hypertension, for example, preeclampsia or post-partum hypertension, unless the potential benefit is judged to outweigh the possible risk.In post-partum studies with DOSTINEX, blood pressure decreases were mostly asymptomatic and were frequently observed on a single occasion 2 to 4 days after treatment. Since decreases in blood pressure are frequently noted during the puerperium, independently of drug therapy, it is likely that many of the observed decreases in blood pressure after DOSTINEX administration were not drug-induced. However, periodic monitoring of blood pressure, particularly during the first few days after DOSTINEX administration, is advised.A single dose of 0.25 mg of DOSTINEX should not be exceeded in nursing women treated for suppression of established lactation to avoid potential postural hypotension. A clinical study exploring the efficacy and tolerability of 0.5 mg of DOSTINEX given as a single dose for suppression of lactation has shown that the risk of side effects is approximately doubled in this indication if the drug is administered as a single dose of 0.5 mg.
Treatment of hyperprolactinaemic disorders:Because hyperprolactinaemia accompanied with amenorrhoea/galactorrhoea and infertility may be associated with pituitary tumour, a complete evaluation of the pituitary is indicated before treatment with DOSTINEX is initiated.DOSTINEX restores ovulation and fertility in women with hyperprolactinaemic hypogonadism.Because pregnancy might occur prior to reinitiation of menses, a pregnancy test is recommended at least every four weeks during the amenorrhoeic period and, once menses are reinitiated, every time a menstrual period is delayed by more than three days. Women who wish to avoid pregnancy should be advised to use mechanical contraception during treatment with DOSTINEX and after discontinuation of DOSTINEX until recurrence of anovulation. As a precautionary measure, women who become pregnant should be monitored to detect signs of pituitary enlargement since expansion of pre-existing pituitary tumours may occur during gestation.Before administration of DOSTINEX, pregnancy should be excluded. Because clinical experience is still limited and the product has a long half-life, as a precautionary measure it is recommended that once regular ovulatory cycles have been achieved women seeking pregnancy discontinue DOSTINEX one month before intended conception. Should pregnancy occur during treatment, DOSTINEX is to be discontinued. As a precautionary measure, women who become pregnant should be monitored to detect signs of pituitary enlargement since expansion of pre-existing pituitary tumours may occur during gestation.Regular gynaecological assessment, including cervical and endometrial cytology, is recommended for patients taking DOSTINEX for extensive periods.
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 DOSTINEX. In some cases, symptoms or manifestations of cardiac valvulopathy improved after discontinuation of DOSTINEX.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.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 DOSTINEX treatment for the patient should be reassessed to determine the suitability of continued treatment with DOSTINEX.
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 cabergoline treatment might worsen the underlying disease. If fibrotic valvular disease is detected, the patient should not be treated with DOSTINEX (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:• Pleuro-pulmonary 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.DOSTINEX 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.