Therapeutic doses of methylphenidate hydrochloride, given for the minimal cerebral dysfunction syndrome, were found to raise the serum levels of primidone, diphenylhydantoin sodium, and phenobarbital in a child. In this patient, diphenylhydantoin levels rose from therapeutic to toxic levels and ataxia was produced. To explain this apparent inhibition of drug metabolism, experiments in four adult male volunteers were performed. Methylphenidate slowed the rate of disappearance of ethyl biscoumacetate from the serum. This suggests that enhanced anticoagulant action may occur in the presence of methylphenidate.
Garrettson LK, Perel JM, Dayton PG. Methylphenidate Interaction With Both Anticonvulsants and Ethyl BiscoumacetateA New Action of Methylphenidate. JAMA. 1969;207(11):2053-2056. doi:10.1001/jama.1969.03150240073007