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The Body Covers: The 36th Annual Meeting of the Infectious Diseases Society of America

Abstract 460: Summary of Pharmacokinetic Drug Interaction Studies with Efavirenz

Coverage provided by Frederick L. Altice, M.D.

November 14, 1998

Efavirenz, the most recently FDA-approved antiretroviral, induces the CYP3A4 isoenzyme of P450 and in vitro, may also inhibit CYP3A4, CYP2C9 and CYP2C19. This presentation explored several of the completed drug interaction studies of efavirenz with other antiretrovirals as well as with antimicrobial agents used for the prevention or treatment of opportunistic infections. These findings will continue to provide clinicians and patients with useful drug interaction information.

For the following drugs, there was no significant interaction with efavirenz or the agent itself that would require a modification in dose: zidovudine, lamivudine, nelfinavir, ritonavir, fluconazole, mylanta, famotidine or ethinyl estradiol. Dose adjustments were suggested for each of the following:

  1. Efavirenz decreased the AUC of amprenavir by 36%. There are insufficient data to suggest the extent to which the dose of amprenavir should increased.

  2. Efavirenz decreased the AUC of indinavir by 31%, however indinavir had no effect on efavirenz. Therefore, the recommended dose increase for indinavir is 1,000 mg Q 8h.

  3. Efavirenz decreased the AUC and Cmax of Saquinavir by 62% and 50%, respectively. The effect of SQV on EFV was minimal with a decrease of 13% and 12%, respectively. The degree to which SQV levels were diminished suggests that SQV should not be used as the sole protease inhibitor with EFV. No data of dual protease combinations (e.g. RTV+SQV) with EFV were presented.

  4. Efavirenz decreased the AUC of clarithromycin by 39%, however it increased the AUC of the active 14-OH metabolite of clarithromycin by 34%. Clarithromicin had a minimal effect on EFV. The paradoxical response of levels by the induction of P450 leading to the increased degradation of the parent compound led the authors to suggest an alternative antimicrobial agent if possible.

  5. Rifampin, a very potent inducer of P450, led to a reduction of 26% AUC of efavirenz in patients stabilized on EFV. In this group of patients, rifampin and its metabolites did not have a reduction in levels. Patients on rifampin were not co-administered efavirenz to determine if efavirenz had a likewise reduction in rifampin levels. No dose adjustments were recommended for either drug in patients stabilized on EFV, but needing the addition of rifampin. Further studies will be needed to determine if EFV can safely be added to patients receiving rifampin.

  6. Efavirenz reduced the AUC and Cmax of rifabutin by 38% and 32%, respectively. Rifabutin, however, had no effect on EFV levels. A 50% increase in rifabutin dosing is recommended for patients co-administered both agents. [Data presented in Abstract 461].
These data assist physicians in the co-administration of EFV with a multitude of other common antivirals and antimicrobials, commonly prescribed in the management of HIV. Unfortunately, information with combinations of medications (e.g. RTV + SQV) was not provided where one drug is markedly reduced by EFV and when the other may block the effects of EFV in inducing P450.

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