Pharmacokinetic interactions: It is not known how methylphenidate may affect plasma concentrations of concomitantly administered medicinal products. Therefore, caution is recommended at combining methylphenidate with other medicinal products, especially those with a narrow therapeutic window.
Methylphenidate is not metabolised by cytochrome P450 to a clinically relevant extent. Inducers or inhibitors of cytochrome P450 are not expected to have any relevant impact on methylphenidate pharmacokinetics. Conversely, the d- and l-enantiomers of methylphenidate do not relevantly inhibit cytochrome P450 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A.
However, there are reports indicating that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (e.g. phenobarbital, phenytoin, primidone) and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). When starting or stopping treatment with methylphenidate, it may be necessary to adjust the dosage of these medicinal products already being taken and establish drug plasma concentrations (or for coumarin, coagulation times).
Pharmacodynamic interactions: Anti-hypertensive medicinal products: Methylphenidate may decrease the effectiveness of active substances used to treat hypertension.
Use with medicinal products that elevate blood pressure: Caution is advised in patients being treated with methylphenidate with any other active substance that can also elevate blood pressure (see also Precautions for cardiovascular and cerebrovascular conditions).
Because of possible hypertensive crisis, methylphenidate is contraindicated in patients being treated (currently or within the preceding 2 weeks) with non-selective, irreversible MAO-inhibitors (see Contraindications).
Use with alcohol: Alcohol may exacerbate the adverse CNS effects of psychoactive active substances, including methylphenidate. In case of very high alcohol concentrations the kinetic profile may change towards a more immediate release-like pattern. It is therefore advisable for patients to abstain from alcohol during treatment.
Use with halogenated anaesthetics: There is a risk of sudden blood pressure increase during surgery. If surgery is planned, methylphenidate treatment should not be used on the day of surgery.
Use with centrally acting alpha-2 agonists (e.g. clonidine): Serious, adverse events, including sudden death, have been reported in concomitant use with clonidine. The safety of using methylphenidate in combination with clonidine or other centrally acting alpha-2 agonists has not been systematically evaluated.
Use with dopaminergic active substances: Caution is recommended when administering methylphenidate with dopaminergic active substances, including antipsychotics. Because a predominant action of methylphenidate is to increase extracellular dopamine levels, methylphenidate may be associated with pharmacodynamic interactions when co-administered with direct and indirect dopamine agonists (including DOPA and tricyclic antidepressants) or with dopamine antagonists including antipsychotics.
Use with other medicines: Medikinet CR must not be taken together with H2 receptor blockers or antacids, as this could lead to a faster release of the total amount of active substance.