VIRAMUNE induces hepatic cytochrome P450 (CYP) metabolic isoenzymes 3A and 2B6. Co-administration of VIRAMUNE and drugs primarily metabolized by CYP3A or CYP2B6 may result in decreased plasma concentrations of these drugs and attenuate their therapeutic effects (see CLINICAL PHARMACOLOGY section in Full Prescribing Information). While primarily an inducer of cytochrome P450 3A and 2B6 enzymes, VIRAMUNE may also inhibit this system.
The effects of VIRAMUNE on the AUC, Cmax, and Cmin of co-administered drugs are summarized in Table 5 in Full Prescribing Information. To measure the full potential pharmacokinetic interaction effect following induction, patients on the concomitant drug at steady state were administered 28 days of VIRAMUNE (200 mg qd for 14 days followed by 200 mg bid for 14 days) followed by a steady-state reassessment of the concomitant drug.
In addition to established drug interactions, there may be potential pharmacokinetic interactions between nevirapine and other drug classes that are metabolized by the cytochrome P450 system. Additional clinical monitoring may be warranted when co-administering with these drugs. For a list of drugs which may require dosage adjustment, see Table 4 and Table 5 in Full Prescribing Information. For a list of established drug interactions, see Table 5 in Full Prescribing Information.
The data in Tables 4 and 5 are based on the results of drug interaction studies conducted in HIV-1 seropositive subjects unless otherwise indicated. In addition to established drug interactions, there may be potential pharmacokinetic interactions between nevirapine and other drug classes that are metabolized by the cytochrome P450 system. These potential drug interactions are also listed in Table 4. Although specific drug interaction studies in HIV-1 seropositive subjects have not been conducted for some classes of drugs listed in Table 4, additional clinical monitoring may be warranted when co-administering these drugs.
The in vitro interaction between nevirapine and the antithrombotic agent warfarin is complex. As a result, when giving these drugs concomitantly, plasma warfarin levels may change with the potential for increases in coagulation time. When warfarin is co-administered with nevirapine, anticoagulation levels should be monitored frequently.
Nevirapine and rifampin should not be administered concomitantly because decreases in nevirapine plasma concentrations may reduce the efficacy of the drug. Physicians needing to treat patients co-infected with tuberculosis and using a nevirapine-containing regimen may use rifabutin instead.
Oral contraceptives and other hormonal methods of birth control should not be used as the sole method of contraception in women taking VIRAMUNE, since nevirapine may lower the plasma levels of these medications. Additionally, when oral contraceptives are used for hormonal regulation during VIRAMUNE therapy, the therapeutic effect of the hormonal therapy should be monitored. Nevirapine may decrease plasma concentrations of methadone by increasing its hepatic metabolism. Narcotic withdrawal syndrome has been reported in patients treated with VIRAMUNE and methadone concomitantly. Methadone-maintained patients beginning nevirapine therapy should be monitored for evidence of withdrawal and methadone dose should be adjusted accordingly.
Concomitant use of St. John's wort and VIRAMUNE is not recommended.
Please consult Full Prescribing Information, including boxed WARNING, Medication Guide, and Important Safety Information for VIRAMUNE.
