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In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in meperidine plasma concentration.

• Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of meperidine.

Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in DEMEROL Injection treated patients may increase meperidine plasma concentrations and prolong opioid adverse reactions.

When using DEMEROL Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in DEMEROL Injection treated patients, monitor patients closely at frequent intervals and consider dosage reduction of DEMEROL Injection until stable drug effects are achieved [see Drug Interactions (7) ].

Concomitant use of DEMEROL Injection with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease meperidine plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to meperidine.