MADOPAR

What it is

Madopar is a medicine containing levodopa and benserazide hydrochloride. Levodopa is the metabolic precursor of dopamine, which is severely depleted in the striatum, pallidum and substantia nigra of Parkinsonian patients, and administration of levodopa raises the level of available dopamine in these centres. Benserazide is a decarboxylase inhibitor that does not cross the blood-brain barrier to any significant degree at recommended therapeutic doses, allowing inhibition of the peripheral decarboxylation of levodopa without significantly affecting its metabolism in the brain. Combined therapy with levodopa and benserazide reduces the amount of levodopa required for optimal therapeutic benefit and permits an earlier response to therapy.

Approved indications

— Parkinson's disease and parkinsonian symptoms including post-encephalitic and toxic forms, but excluding drug-induced parkinsonism. — Madopar HBS is indicated for patients presenting with all types of fluctuations in response (including peak dose dyskinesia and end of dose deterioration) and for better control of nocturnal symptoms.

Dosing overview

Madopar therapy must be individualised and dosage must be carefully titrated in the elderly, with titration and adjustment made in small steps, as combined therapy with Madopar has a narrower therapeutic range than levodopa alone. Initial dosage is one Madopar 125 capsule or tablet three times daily, increased by one capsule or tablet at weekly intervals until the individual therapeutic dosage is reached (or twice weekly if the patient can be monitored frequently), with effective dose potentially reached in as little as four days, and the effective dosage generally between 4 and 8 capsules or tablets daily, divided into three or four doses. The average maintenance dosage is one Madopar capsule or tablet three times daily, though dosage division must be adapted to individual requirements as improvement may fluctuate. Madopar Rapid 62.5 and Rapid 125 tablets are particularly suitable for patients with dysphagia or in situations where a more rapid onset of action is required, such as in patients suffering from early morning and afternoon akinesia, or in patients who exhibit delayed on or wearing off phenomenon. Switching to Madopar HBS is preferably made from one day to the next while keeping the same daily dose and frequency of intake, with dosage gradually increased by about 50 per cent after two to three days because of the lower bioavailability of this formulation.

Key safety warnings

All patients should be carefully observed for signs of depression with suicidal tendencies or other serious behavioural changes, and extreme caution should be used in treating patients with a history of psychotic disorders or who are receiving psychotherapeutic agents such as phenothiazines or tricyclic anti-depressants. Care should be exercised in administering Madopar to patients with a history of myocardial infarction or who have atrial, nodal or ventricular arrhythmias, and patients with cardiac abnormalities should have their treatment initiated in a facility with adequate monitoring equipment and provision for intensive care. Madopar has been associated with somnolence and episodes of sudden sleep onset, with sudden onset of sleep during daily activities reported very rarely without awareness or warning signs, and patients must be informed of this and advised to exercise caution while driving or operating machines during treatment. Madopar must not be withdrawn abruptly, as abrupt withdrawal may result in a neuroleptic malignant-like syndrome which may be life-threatening, requiring the patient to be kept under surveillance by a physician and rapid symptomatic treatment, which may include re-introduction of Madopar after appropriate evaluation.

Contraindications

Patients in whom sympathomimetic amines are contraindicated should not receive Madopar, and monoamine oxidase inhibitors should not be given concomitantly and should be withdrawn at least two weeks prior to initiating Madopar therapy. Madopar should not be administered to patients with clinical or laboratory evidence of uncompensated cardiovascular, endocrine, renal, hepatic, haematological or pulmonary disease, or in patients with narrow angle glaucoma, or with active psychosis or serious psychoneurosis. Because levodopa may activate a malignant melanoma, Madopar should not be used in patients with suspicious, undiagnosed lesions or a history of melanoma. Madopar must not be given to patients under 30 years of age. Madopar is contraindicated in those patients who may be hypersensitive to levodopa, benserazide or any of the excipients.

Regulatory history

Madopar was first approved on 23 August 1991. The initial ARTG registrations for Madopar 62.5, 125, 250 and HBS 125 capsules, and Madopar 250 tablets were listed on 1991-08-23, with Madopar 125 tablets first listed on 1993-09-28 and Madopar Rapid 62.5 and Rapid 125 dispersible tablets first listed on 1997-09-18.