be expected based on NRTIs elimination pathways.
Efavirenz has been shown in vivo to cause hepatic enzyme induction, thus increasing the biotransformation of some drugs metabolized by CYP3A and CYP2B6. In vitro studies have shown that efavirenz inhibited CYP isozymes 2C9, 2C19, and 3A4 with Ki values (8.5–17 µM) in the range of observed efavirenz plasma concentrations. In in vitro studies, efavirenz did not inhibit CYP2E1 and inhibited CYP2D6 and CYP1A2 (Ki values 82–160 µM) only at concentrations well above those achieved clinically. Coadministration of efavirenz with drugs primarily metabolized by 2C9, 2C19, and 3A4 isozymes may result in altered plasma concentrations of the coadministered drug. Drugs which induce CYP3A activity would be expected to increase the clearance of efavirenz resulting in lowered plasma concentrations.
Drug interaction trials were performed with efavirenz and other drugs likely to be coadministered or drugs commonly used as probes for pharmacokinetic interaction. There was no clinically significant interaction observed between efavirenz and zidovudine, lamivudine, azithromycin, fluconazole, lorazepam, cetirizine, or paroxetine. Single doses of famotidine or an aluminum and magnesium antacid with simethicone had no effects on efavirenz exposures. The effects of coadministration of efavirenz on Cmax, AUC, and Cmin are summarized in Table 5 (effect of other drugs on efavirenz) and Table 6 (effect of efavirenz on other drugs). For information regarding clinical recommendations see Drug Interactions (7).
Table 5 Drug Interactions: Changes in Pharmacokinetic Parameters for Efavirenz in the Presence of the Coadministered Drug Mean % Change of Efavirenz Pharmacokinetic Parameters* (90% CI)
Coadministered Drug Dose of Coadministered Drug (mg) Efavirenz Dose (mg) N Cmax AUC Cmin
Indinavir 800 mg q8h × 14 days 200 mg qd × 14 days 11 ↔ ↔ ↔
Lopinavir/
ritonavir 400/100 mg q12h × 9 days 600 mg qd × 9 days 11, 12† ↔ ↓ 16
(↓ 38 to
↑ 15) ↓ 16
(↓ 42 to
↑ 20)
Nelfinavir 750 mg q8h × 7 days 600 mg qd × 7 days 10 ↓ 12
(↓ 32 to ↑ 13)‡ ↓ 12
(↓ 35 to
↑ 18)8 ↓ 21
(↓ 53 to
↑ 33)
Ritonavir 500 mg q12h × 8 days 600 mg qd × 10 days 9 ↑ 14
(↑ 4 to
↑ 26) ↑ 21
(↑ 10 to
↑ 34) ↑ 25
(↑ 7 to
↑ 46)8
Saquinavir SGC§ 1200 mg q8h × 10 days 600 mg qd × 10 days 13 ↓ 13
(↓ 5 to
↓ 20) ↓ 12
(↓ 4 to
↓ 19) ↓ 14
(↓ 2 to
↓ 24)8
Clarithromycin 500 mg q12h × 7 days 400 mg qd × 7 days 12 ↑ 11
(↑ 3 to
↑ 19) ↔ ↔
Itraconazole 200 mg q12h × 14 days 600 mg qd × 28 days 16 ↔ ↔ ↔
Rifabutin 300 mg qd × 14 days 600 mg qd × 14 days 11 ↔ ↔ ↓ 12
(↓ 24 to
↑ 1)
Rifampin 600 mg × 7 days 600 mg qd × 7 days 12 ↓ 20
(↓ 11 to ↓ 28) ↓ 26
(↓ 15 to
↓ 36) ↓ 32
(↓ 15 to
↓ 46)
Atorvastatin 10 mg qd × 4 days 600 mg qd × 15 days 14 ↔ ↔ ↔
Pravastatin 40 mg qd × 4 days 600 mg qd × 15 days 11 ↔ ↔ ↔
Simvastatin 40 mg qd × 4 days 600 mg qd × 15 days 14 ↓ 12
(↓ 28 to
↑ 8) ↔ ↓ 12
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