Interaction Checker
Potential Interaction
Efavirenz (EFV)
Felbamate
Quality of Evidence: Very Low
Summary:
Coadministration has not been studied. Felbamate is excreted in urine as unchanged drug (~40%) and metabolized by CYP3A4 (<20%) with CYP2E1 having a minor role. Efavirenz is metabolized by CYP2B6 and CYP3A4. Felbamate is unlikely to affect CYP2B6. Felbamate is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on efavirenz as rifampicin (a strong inducer) had only a modest effect on efavirenz exposure. However, efavirenz is a moderate CYP3A4 inducer and may decrease felbamate exposure leading to a loss of efficacy. The relevance of this interaction is unknown. Caution is required with coadministration and patients should be monitored for felbamate efficacy. In addition, felbamate has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. Efavirenz was shown to prolong the QT interval above the regulatory threshold of concern in homozygous carriers of the CYP2B6*6/*6 allele (i.e. 516T variant in the gene encoding CYP2B6). The European product label for efavirenz contraindicates coadministration with a drug with a known risk of TdP. Whereas the American product label for efavirenz recommends that alternatives should be considered. As the potential risk of a QT interval prolongation relates specifically to homozygous carriers of CYP2B6*6/*6 and given the accumulated years of safety data with efavirenz and such drugs, the contraindication is not reflected in the colour coding of this interaction summary.
Description:
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