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Pramipexole dihydrochloride monohydrate is bound to plasma proteins to a very low (< 20%) extent and little biotransformation is seen in man. Therefore, interactions with other medication affecting plasma protein binding or elimination by biotransformation are unlikely.
Medication that inhibit the active renal tubular secretion of basic (cationic) drugs, such as cimetidine, or are themselves eliminated by active renal tubular secretion, may interact with SIFROL resulting in reduced clearance of either or both medication. In case of concomitant treatment with these kinds of drugs (incl. amantadine) attention should be paid to signs of dopamine over stimulation, such as dyskinesias, agitation or hallucinations. In such cases a dose reduction is necessary.
Selegiline and levodopa do not influence the pharmacokinetics of pramipexole dihydrochloride monohydrate. The overall extent of absorption or elimination of levodopa is not changed by pramipexole dihydrochloride monohydrate. The interaction with anticholinergics and amantadine has not been examined.
As anticholinergics are mainly eliminated by hepatic metabolism, pharmacokinetic drug-drug interactions with pramipexole dihydrochloride monohydrate are rather unlikely. With amantadine, an interaction is possible via the same system of excretion in the kidney.
While increasing the dose of SIFROL in Parkinson's disease patients it is recommended that the dosage of levodopa is reduced and the dosage of other antiparkinsonian medication kept constant.
Because of possible additive effects, caution should be advised when patients are taking other sedating medication or alcohol in combination with SIFROL and when taking concomitant medication that increase plasma levels of pramipexole dihydrochloride monohydrate (e.g. cimetidine).
Antipsychotic medicinal products: Co-administration of antipsychotic medicinal products with pramipexole dihydrochloride monohydrate should be avoided, e.g. if dopamine-antagonistic effects can be expected. (see Precautions).
