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Cytochrome P450 3A4 Interaction The concomitant use of DEMEROL Injection with all cytochrome P450 3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.

Monitor patients receiving DEMEROL Injection and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.5) , Drug Interactions (7) ] .

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

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of DEMEROL Injection with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of meperidine and prolong opioid…

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 with Midazolam : Noxafil can prolong hypnotic/sedative effects.

Increased plasma midazolam concentrations could potentiate and prolong hypnotic and sedative effects.

Benzodiazepines that are CYP3A4 Substrates Mechanism and Clinical Effect(s) Concomitant use of posaconazole with midazolam increased midazolam plasma concentrations which could potentiate and prolong hypnotic and sedative effects [see Clinical Pharmacology (12.3) ] .