Dilantin and Ritonavir

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Talk to your doctor before using ritonavir together with phenytoin. Combining these medications may reduce the blood levels and effects of both medications. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Let your doctor know if your conditions worsen during treatment with these medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

MONITOR: Coadministration of ritonavir and phenytoin may result in decreased plasma concentrations of both drugs. The proposed mechanism involves ritonavir induction of phenytoin metabolism via CYP450 2C9 and, conversely, phenytoin induction of ritonavir metabolism via CYP450 3A4. Data are limited. In one case report, serum phenytoin levels in a patient receiving carbamazepine (1200 mg/day), phenytoin (500 mg/day), and phenobarbital (250 mg/day) declined 30% following initiation of antiretroviral therapy containing ritonavir (300 mg twice a day). In another case, a patient receiving carbamazepine (600 mg/day) and phenytoin (400 mg/day) was started on ritonavir (600 mg twice daily) with no apparent change in serum phenytoin levels. In a pharmacokinetic study of 8 healthy volunteers, administration of phenytoin (300 mg once daily for 22 days) in combination with lopinavir-ritonavir (400 mg-100 mg twice a day on days 12 thru 22) decreased phenytoin peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 28%, 31% and 34%, respectively, compared to administration of phenytoin alone. In a different arm of the same study, Cmax, AUC and Cmin of lopinavir decreased by 24%, 33% and 46%, respectively, when lopinavir-ritonavir (400 mg-100 mg twice a day for 22 days) was coadministered with phenytoin (300 mg once daily on days 11 through 22) in 12 healthy subjects. Ritonavir Cmax, AUC and Cmin were also reduced by 20%, 28% and 47%, respectively, although only the change in Cmin was statistically significant.

MANAGEMENT: The potential for reduced therapeutic effects of phenytoin should be considered during coadministration with ritonavir. Phenytoin serum levels and pharmacologic effects should be closely monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of ritonavir in patients who are stabilized on their anticonvulsant regimen. In addition, it may be necessary to monitor patients for potentially reduced antiretroviral response due to decreased plasma levels of ritonavir and other antiretroviral agents induced by phenytoin.

Dilantin

Generic Name: phenytoin

Brand name: Dilantin, Phenytek, Dilantin Infatabs, Phenytoin Sodium, Prompt

Synonyms: n.a.

What is Dilantin?

Ritonavir

Generic Name: ritonavir

Brand name: Norvir, Norvir Soft Gelatin

Synonyms: n.a.

What is Ritonavir?