Pharmacokinetic interactions: Coadministration of the anticholinergic drug trihexyphenidyl with standard Madopar reduces the rate, but not the extent, of levodopa absorption. Trihexyphenidyl given concomitantly with Madopar HBS does not affect the pharmacokinetic of levodopa.
Coadministration of antacids with Madopar HBS reduces the extent of levodopa absorption by 32%.
Ferrous sulphate decreases the maximum plasma concentration and the AUC of levodopa by 30-50%. The pharmacokinetic changes observed during co-treatment with ferrous sulphate appear to be clinically significant in some but not all patients.
Metoclopramide increases the rate of levodopa absorption.
Domperidone may increase the bioavailability of levodopa as a result of increased absorption of levodopa in the intestine.
Pharmacodynamic interactions: Neuroleptics, opioids and antihypertensive medications containing reserpine inhibit the action of Madopar.
If Madopar is to be administered to patients receiving irreversible non-selective MAO inhibitors, an interval of at least 2 weeks should be allowed between cessation of the MAO inhibitor and the start of Madopar therapy. Otherwise unwanted effects such as hypertensive crises are likely to occur (see Contraindications). Selective MAO-B inhibitors, such as selegiline and rasagiline and selective MAO-A inhibitors, such as moclobemide, can be prescribed to patients on Madopar therapy; it is recommended to readjust the levodopa dose to the individual patient's need, in terms of both efficacy and tolerability. Combination of MAO-A and MAO-B inhibitors is equivalent to non-selective MAO inhibition and hence this combination should not be given concomitantly with Madopar (see Contraindications).
Madopar should not be administered concomitantly with sympathomimetics (agents such as epinephrine, norepinephrine, isoproterenol or amphetamine which stimulate the sympathetic nervous system) as levodopa may potentiate their effects. Should concomitant administration prove necessary, close surveillance of the cardiovascular system is essential, and the dose of the sympathomimetic agents may need to be reduced.
Combination with other agents such as anticholinergics, amantadine, selegiline, bromocriptine and dopamine agonists is permissible, though both the desired and the undesired effects of treatment may be intensified. It may be necessary to reduce the dosage of Madopar or the other substance.
When initiating an adjuvant treatment with a COMT inhibitor, a reduction of the dosage of Madopar may be necessary.
Anticholinergics should not be withdrawn abruptly when Madopar therapy is instituted, as levodopa does not begin to take effect for some time.
Concomitant administration of antipsychotics with dopamine-receptor blocking properties, particularly D2-receptor antagonists might antagonize the antiparkinsonian effects of levodopa-benserazide. Levodopa may reduce antipsychotic effects of these drugs. These drugs should be co-administered with caution.
General anaesthesia with halothane: Madopar should be discontinued 12-48 hours before surgical intervention requiring general anaesthesia with halothane as fluctuations in blood pressure and/or arrhythmias may occur.
For general anaesthesia with other anaesthetics see General under Precautions.
Laboratory test interactions: Levodopa may affect the results of laboratory test for catecholamines, creatinine, uric acid and glycosuria. The urine test results can be false positive for ketone bodies.
Coombs' test may give a false-positive result in patients taking Madopar.
Food interactions: A diminution of effect is observed when the drug is taken with a protein-rich meal.
Levodopa is a large neutral amino acid (LNAA) and it competes with LNAAs from dietary protein for transport across the gastric mucosa and blood-brain barrier.