Assessment of Drug Interactions

At concentrations up to 14-fold higher than those observed in vivo, emtricitabine did not inhibit in vitro drug metabolism mediated by any of the following human CYP isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Emtricitabine did not inhibit the enzyme responsible for glucuronidation (uridine-5'-disphosphoglucuronyl transferase). Based on the results of these in vitro experiments and the known elimination pathways of emtricitabine, the potential for CYP mediated interactions involving emtricitabine with other medicinal products is low.

Emtriva has been eva luated in healthy volunteers in combination with tenofovir disoproxil fumarate (DF), zidovudine, indinavir, famciclovir, and stavudine. Tables 8 and 9 summarize the pharmacokinetic effects of coadministered drug on emtricitabine pharmacokinetics and effects of emtricitabine on the pharmacokinetics of coadministered drug.

Table 8 Drug Interactions: Change in Pharmacokinetic Parameters for Emtricitabine in the Presence of the Coadministered Drug* Coadministered Drug Dose of Coadministered Drug (mg) Emtricitabine Dose (mg) N % Change of Emtricitabine Pharmacokinetic Parameters† (90% CI)
Cmax AUC Cmin
*
All interaction trials conducted in healthy volunteers.
†
↑ = Increase; ↓ = Decrease;  = No Effect; NA = Not Applicable
 
Tenofovir DF 300 once daily x 7 days 200 once daily × 7 days 17   ↑ 20
(↑ 12 to ↑ 29)
Zidovudine 300 twice daily × 7 days 200 once daily × 7 days 27   
Indinavir 800 × 1 200 × 1 12   NA
Famciclovir 500 × 1 200 × 1 12   NA
Stavudine 40 × 1 200 × 1 6   NA
Table 9 Drug Interactions: Change in Pharmacokinetic Parameters for Coadministered Drug in the Presence of Emtricitabine* Coadministered Drug Dose of Coadministered Drug (mg) Emtricitabine Dose (mg) N % Change of Coadministered Drug Pharmacokinetic Parameters† (90% CI)
Cmax AUC Cmin
*
All interaction trials conducted in healthy volunteers.
†
↑ = Increase; ↓ = Decrease;  = No Effect; NA = Not Applicable
 
Tenofovir DF 300 once daily × 7 days 200 once daily × 7 days 17   
Zidovudine 300 twice daily × 7 days 200 once daily × 7 days 27 ↑ 17
(↑ 0 to ↑ 38) ↑ 13
(↑ 5 to↑ 20) 
Indinavir 800 × 1 200 × 1 12   NA
Famciclovir 500 × 1 200 × 1 12   NA
Stavudine 40 × 1 200 × 1 6   NA
Microbiology
Mechanism of Action

Emtricitabine, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase α, β, ε, and mitochondrial DNA polymerase γ.

Antiviral Activity

The antiviral activity in cell culture of emtricitab