No clinically significant pharmacokinetic interactions are expected between enfuvirtide and concomitantly given medicinal products metabolised by CYP450 enzymes. In an in vivo human metabolism study enfuvirtide, at the recommended dose of 90 mg twice daily, did not inhibit the metabolism of substrates by CYP3A4 (dapsone), CYP2D6 (debrisoquine), CYP1A2 (caffeine), CYP2C19 (mephenytoin), and CYP2E1 (chlorzoxazone). In separate pharmacokinetic interaction studies, co-administration of ritonavir (potent CYP3A4 inhibitor) or saquinavir in combination with a booster dose of ritonavir or rifampicin (potent CYP34A inducer) did not result in clinically significant changes of the pharmacokinetics of enfuvirtide.
Fuzeon Summary of Product Characteristics, Roche Products Ltd, July 2008.

Results from in vitro and in vivo studies suggest that enfuvirtide is unlikely to have significant drug interactions with concomitantly administered drugs metabolised by CYP450 enzymes. No drug interactions with other antiretroviral medications have been identified that would warrant alteration of either the enfuvirtide dose or the dose of the other antiretroviral medication. Coadministration of ritonavir (200 mg twice daily for 4 days) and enfuvirtide (90 mg twice daily) to 12 HIV+ subjects results in increases in enfuvirtide Cmax, AUC and Cmin of 24%, 22% and 14% respectively. Coadministration of ritonavir (100 mg twice daily for 4 days with 1000 mg saquinavir) and enfuvirtide (90 mg twice daily) to 12 HIV+ subjects results in no change in enfuvirtide Cmax, and increases in enfuvirtide AUC and Cmin of 14% and 26% respectively.
Fuzeon Prescribing Information, Roche Laboratories Inc, June 2007.

The coadministration of enfuvirtide (90 mg twice daily, sc) with either ritonavir (200 mg twice daily, n=12) or saquinavir/ritonavir (1000/100 mg twice daily, n=12) was investigated in HIV+ patients. Although bioequivalence criteria were not met for coadministration of enfuvirtide with and without ritonavir, the increase in enfuvirtide AUC, Cmax and Cmin were small (22, 24 and 14%, respectively) and not clinically relevant. When administered with ritonavir-boosted saquinavir there was a 14, 7 and 25% increase in AUC, Cmax and Cmin, respectively and bioequivalence criteria were met for AUC and Cmax. Thus, no dosage adjustments are warranted when enfuvirtide is coadministered with low-dose ritonavir or low-dose ritonavir-boosted saquinavir.
Lack of interaction between enfuvirtide and ritonavir or ritonavir-boosted saquinavir in HIV-infected patients. Ruxrungtham K, Boyd M, Eralp Bellibas S et al. J Clin Pharmacol, 2004, 44: 793-802.