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Drug Details

CABASER

• Drug Class Description
  Dopamine agonists (dopaminergics) .
• Generic Name
  Cabergoline
• Presentation
  Cabaser 1 mg tablets are white, oval, 3.8 x 7.4mm and concave with one side scored and engraved '7' on the left and '01' on the right Cabaser 2 mg tablets are white, oval, 5.1 x 10mm and concave with one side scored and engraved '7' on the left and '02' on the right
• Description
  Cabaser® Tablets 1 mg Cabaser® Tablets 2 mg
• Indications
  

  Treatment of Parkinson's disease If treatment with a dopamine agonist is being considered, cabergoline is indicated as second line therapy in patients who are intolerant or fail treatment with a non-ergot compound, as monotherapy, or as adjunctive treatment to levodopa plus dopa-decarboxylase inhibitor, in the management of the signs and symptoms of Parkinson's disease.

  Treatment should be initiated under specialist supervision. The benefit of continued treatment should be regularly reassessed taking into account the risk of fibrotic reactions and valvulopathy

• Adult Dosage
  

  The tablets are for oral administration.

  Since the tolerability of dopaminergic agents is improved when administered with food, it is recommended that Cabaser be taken with meals.

  Cabaser is intended for chronic, long term treatment.

  As expected for dopamine agonists, dose response for both efficacy and side effects appears to be linked to individual sensitivity. Optimization of dose should be obtained through slow initial dose titration, from starting doses of 1 mg daily. The dosage of concurrent levodopa may be gradually decreased, while the dosage of Cabaser is increased, until the optimum balance is determined. In view of the long half-life of the compound, increments of the daily dose of 0.5-1 mg should be done at weekly (initial weeks) or bi-weekly intervals, up to optimal doses.

  The recommended therapeutic dosage is 2 to 3 mg/day for patients with signs and symptoms of Parkinson's disease. Cabaser should be given as a single daily dose.

• Child Dosage
  

  The safety and efficacy of Cabaser have not been investigated in children as Parkinson's disease does not affect this population.

• Contra Indications
  

  Hypersensitivity to cabergoline, other ergot alkaloids or to any of the excipients.

  History of pulmonary, pericardial and retroperitoneal fibrotic disorders.

  For long-term treatment: Evidence of cardiac valvulopathy as determined by pre-treatment echocardiography

• Special Precautions
  

  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 5HT_2B 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.

  Valvulopathy has been associated with cumulative doses, therefore patients should be treated with thelowest 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 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 ESR 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.

  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 valvular disease or fibrosis, as appropriate, is essential. Following treatment initiation, the first echocardiogram should 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.

  Cabergoline should be discontinued if an echocardiogram reveals new or worsened valvular regurgitation, valvular restriction or valve leaflet thickening. 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.

  While renal insufficiency has been shown not to modify cabergoline kinetics, hepatic insufficiency of severe degree (> 10 Child-Pugh score, maximum score 12) has been shown to be associated with an increase of AUC, thus indicating that dose regimens in Parkinsonian patients with severe hepatic insufficiency should be modified accordingly.

  In addition, by analogy with other ergot derivatives, Cabaser should be given with caution to patients suffering from severe cardiovascular disease, Raynaud's syndrome, peptic ulcer, gastrointestinal bleeding or a history of serious, particularly psychotic mental disease. Symptomatic hypotension can occur following adminstration of Cabaser: particular attention should be paid when administering Cabaser concomitantly with other drugs known to lower blood pressure.

  Cabergoline has been associated with somnolence and episodes of sudden sleep onset, particularly in Patients with Parkinson's disease. Sudden onset of sleep during 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 of dosage or termination of therapy may be considered.

  The effects of alcohol on overall tolerability of Cabaser are currently unknown.

  Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson's disease, including Cabergoline/Cabaser.

• Interactions
  

  No pharmacokinetic interaction with L-Dopa or selegiline was observed in the studies carried out in parkinsonian patients. The concomitant use of other drugs, particularly other antiparkinsonian non-dopamine-agonist agents, was not associated with detectable interactions modifying the efficacy and safety of Cabaser.

  No other information is available about possible interaction between Cabaser and other ergot alkaloids: therefore the concomitant use of these medications during long term treatment with Cabaser is not recommended.

  Since Cabaser exerts its therapeutic effect by direct stimulation of dopamine receptors, it should not be concurrently administered with drugs which have dopamine antagonist activity (such as phenothiazines, butyrophenones, thioxanthenes, metoclopramide) since these might reduce the therapeutic effect of Cabaser.

  By analogy with other ergot derivatives, Cabaser should not be used in association with macrolide antibiotics (e.g erythromycin) since the systemic bioavailability of Cabaser and adverse effects could increase.

• Adverse Drug Reactions
  

  About 1070 parkinsonian patients have received Cabaser as adjuvant therapy to L-dopa in clinical studies; of these 74% had at least one adverse event, mainly of mild to moderate severity and transient in nature, and requiring discontinuation in a small proportion of cases.

  In the majority of cases (51%), events were related to the nervous system: most frequently reported events were dyskinesia, hyperkinesia, hallucinations or confusion. The gastrointestinal system was involved in 33% of cases: events most frequently reported were nausea, vomiting, dyspepsia and gastritis. The cardiovascular system was involved in 27% of cases, most frequently reported events being dizziness and hypotension.

  There have been reports of fibrotic and serosal inflammatory conditions, such as pleuritis, pleural effusion, pleural fibrosis, pulmonary fibrosis, pericarditis, pericardial effusion, cardiac valvulopathy and retroperitoneal fibrosis, in patients taking cabergoline (see 'Special warnings and special precautions for use'). The incidence of cardiac valvulopathy (including regurgitation) and related disorders (pericarditis and pericardial effusion) is considered to be very common.

  There is limited information available on the reversibility of these reactions.

  Other adverse events expected for the pharmacological class, in view of the vasoconstrictive properties, include angina (reported in about 1% of the patients on cabergoline) and erythromelalgia (observed in 0.4% of the patients). Similarly expected for the pharmacological class, peripheral oedema occurred in 6% of patients.

  Gastric upset was more frequent in female than in male patients, while CNS events were more frequent in the elderly.

  A blood pressure decrease of clinical relevance was observed mainly on standing in a minority of patients. The effect was mainly evident in the first weeks of therapy. Neither modification of heart rate nor consistent changes of ECG tracing were observed during Cabaser treatment.

  Cabergoline is associated with somnolence and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes.

  Alterations in standard laboratory tests are uncommon during long term therapy with Cabaser.

  Patients treated with dopamine agonists for treatment of Parkinson's disease, including Cabergoline/Cabaser, especially at high doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose or treatment discontinuation.