23

24

25

Table 8 Drug Interactions: Changes in Pharmacokinetic Parameters for Coadministered Drug in the Presence of Tenofovir Disoproxil Fumarate*,†  Coadministered Drug Dose of Coadministered Drug (mg) N Mean % Change of Coadministered Drug Pharmacokinetic Parameters‡
(90% CI)
Cmax AUC Cmin
Atazanavir§ 400 once daily × 14 days 34 ↓ 21
(↓ 27 to ↓ 14) ↓ 25
(↓ 30 to ↓ 19) ↓ 40
(↓ 48 to ↓ 32)
 Atazanavir/ritonavir 300/100 once daily × 42 days 10 ↓ 28
(↓ 50 to ↑ 5) ↓ 25¶
(↓ 42 to ↓ 3) ↓ 2330
(↓ 46 to ↑ 10)
Lopinavir Lopinavir/ritonavir 400/100 twice daily × 14 days 24 ↔ ↔ ↔
Ritonavir Lopinavir/ritonavir 400/100 twice daily × 14 days 24 ↔ ↔ ↔
26

27

28

29

30

Coadministration of tenofovir DF with didanosine results in changes in the pharmacokinetics of didanosine that may be of clinical significance. Table 9 summarizes the effects of tenofovir DF on the pharmacokinetics of didanosine. Concomitant dosing of tenofovir DF with didanosine buffered tablets or enteric-coated capsules significantly increases the Cmax and AUC of didanosine. When didanosine 250 mg enteric-coated capsules were administered with tenofovir DF, systemic exposures of didanosine were similar to those seen with the 400 mg enteric-coated capsules alone under fasted conditions. The mechanism of this interaction is unknown [for didanosine dosing adjustment recommendations see Drug Interactions (7.3), Table 4].
Table 9 Drug Interactions: Changes in Pharmacokinetic Parameters for Didanosine in the Presence of Tenofovir Disoproxil Fumarate*,†  Didanosine Dose (mg)/Method of Administration‡ Tenofovir DF Method of Administration32,33 N Mean % Change (90% CI) vs. Didanosine 400 mg Alone, Fasted§
Cmax AUC
Buffered tablets
400 once daily¶ × 7 days Fasted 1 hour after didanosine 14 ↑ 28
(↑ 11 to ↑ 48) ↑ 44
(↑ 31 to ↑ 59)
Enteric coated capsules
400 once, fasted With food, 2 hr after didanosine 26 ↑ 48
(↑ 25 to ↑ 76) ↑ 48
(↑ 31 to ↑ 67)
400 once, with food Simultaneously with didanosine 26 ↑ 64
(↑ 41 to ↑ 89) ↑ 60
(↑ 44 to ↑ 79)
250 once, fasted With food, 2 hr after didanosine 28 ↓ 10
(↓ 22 to ↑ 3) ↔
250 once, fasted Simultaneously with didanosine 28 ↔ ↑ 14
(0 to ↑ 31)
250 once, with food Simultaneously with didanosine 28 ↓ 29
(↓ 39 to ↓ 18) ↓ 11
(↓ 23 to ↑ 2)
31
32

33

34

35
Mechanism of Action
Efavirenz: Efavirenz is a non-nucleoside reverse transcriptase (RT) inhibitor of HIV-1. Efavirenz activity is mediated predominantly by noncompetitive inhibition of HIV-1 reverse transcriptase (RT). HIV-2 RT and human cellular DNA polymer