Pharmacodynamic interactions: Anti-hypertensive drugs: Ritalin may decrease the effectiveness of drugs used to treat hypertension.
Use with drugs that elevate blood pressure: Ritalin should be used with caution in patients being treated with drugs that elevate blood pressure (see also Cerebrovascular conditions in PRECAUTIONS).
Because of possible hypertensive crisis, Ritalin is contraindicated in patients being treated (currently or within the preceding 2 weeks) with MAO inhibitors (see CONTRAINDICATIONS).
Use with alcohol: Alcohol may exacerbate the adverse CNS effects of psychoactive drugs, including Ritalin. It is therefore advisable for patients to abstain from alcohol during treatment.
Use with anesthetics: There is a risk of sudden blood pressure and heart rate increase during surgery. If surgery is planned, Ritalin should not be taken 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, although no causality for the combination has been established.
Use with serotonergic drugs: The concomitant use of methylphenidate and serotonergic drugs is not recommended as this may lead to the development of serotonin syndrome (see PRECAUTIONS). Methylphenidate has been shown to increase extracellular serotonin and norepinephrine and appears to have weak potency in binding serotonin transporter.
Use with dopaminergic drugs: As an inhibitor of dopamine reuptake, Ritalin may be associated with pharmacodynamic interactions when co-administered with direct and indirect dopamine agonists (including DOPA and tricyclic antidepressants) as well as dopamine antagonists (antipsychotics, e.g. haloperidol). The co-administration of Ritalin with antipsychotics is not recommended because of the counteracting mechanism of action.
Pharmacokinetic interactions: Ritalin is not metabolized by cytochrome P450 to a clinically relevant extent. Inducers or inhibitors of cytochrome P450 are not expected to have any relevant impact on Ritalin pharmacokinetics. Conversely, the d- and l- enantiomers of methylphenidate in Ritalin did not relevantly inhibit cytochrome P450 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A.
Ritalin co-administration did not increase plasma concentrations of the CYP2D6 substrate desipramine.
Case reports suggested a potential interaction of Ritalin with coumarin anticoagulants, some anticonvulsants (e.g. phenobarbital, phenytoin, primidone), phenylbutazone, and tricyclic antidepressants but pharmacokinetic interactions were not confirmed when explored at larger sample sizes. The dosage of these drugs might have to be reduced.
An interaction with the anticoagulant ethylbiscoumacetate in 4 subjects was not confirmed in a subsequent study with a larger sample size (n=12).
Other specific drug-drug interaction studies with Ritalin have not been performed in vivo.
Drug/Laboratory test: Methylphenidate may induce false positive laboratory tests for amphetamines, particularly with immunoassays screen test.