Emtricitabine dosing

Tenofovir in its prodrug form tenofovir, disoproxil fumarate (TDF), is indicated in the treatment of HIV infections (AIDS). It is administered as a single oral dose of 300 mg per day. When combined with emtricitabine and efavirenz, TDF has proven to be more efhcacious than the standard combination therapy of combivir (azidothymidine plus lamivudine) and efavirenz (Gallant et al. 2006) and less prone to cause adverse side effects (Pozniak et al. 2006 De Clercq 2007b). 

The dose of emtricitabine/tenofovir disoproxil fumarate is 1 tablet taken orally once daily with or without food. 

Renal function impairment Significantly increased drug exposures occurred when emtricitabine or tenofovir disoproxil fumarate were administered to patients with moderate to severe renal impairment. Because the safety and efficacy of the dosing... 

Pharmacokinetics One emtricitabine/tenofovir disoproxil fumarate tablet was bioequivalent to 1 emthcitabine capsule (200 mg) plus 1 tenofovir disoproxil fumarate tablet (300 mg) following single-dose administration to fasting healthy subjects. 

Single Dose Pharmacokinetic Parameters for Emtricitabine and Tenofovir in... 

Fixed dose combination This combination contains fixed doses of 2 nucleoside analogs emtricitabine and tenofovir disoproxil fumarate. Do not administer concomitantly with emtricitabine or tenofovir disoproxil fumarate. 

Renal function impairment Emtricitabine and tenofovir disoproxil fumarate are principally eliminated by the kidney. Dosing interval adjustment is recommended in all patients with Ccr 30 to 49 mL/min do not administer the combination to patients with Ccr less than 30 mL/min or patients requiring hemodialysis. 

Although there are insufficient data to recommend a specific dose adjustment of emtricitabine in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval similar to adjustments for adults should be considered. 

Metabolism/Excretion - Emtricitabine is not an inhibitor of human CYP450 enzymes. Following administration of emtricitabine, complete recovery of the dose was achieved in urine (approximately 86%) and feces (approximately 14%). The plasma emtricitabine half-life is approximately 10 hours. The renal... 

Emtricitabine (FTC) is a fluorinated analog of lamivudine with a long intracellular half-life (> 24 hours), allowing for once-daily dosing (Figure 49-2). Oral bioavailability of the capsules is 93% and is unaffected by food, but penetration into the cerebrospinal fluid is low. Elimination is by both glomerular filtration and active tubular secretion. 

After oral administration, emtricitabine is rapidly absorbed with a bioavailability of 93%, and it could be administered with or without food. The peak plasma concentration occurs 1-2 h after the oral dose. It does not significantly bind to plasma proteins, and its elimination half-life is 8-10 h. Following glomerular filtration and active tubular secretion, it is primarily excreted unmetabolized in urine. In combination with other antiretroviral agents, emtricitabine is recommended for the treatment of HIV infection. 

In 2001, tenofovir disoproxil fumarate 61, a prodrug of tenofovir was approved for treatment of HIV, subsequently being preregistered in the USA for treatment of hepatitis B. Emtricitabine 62, a reverse transcriptase inhibitor, was approved in 2003 for HIV. What is of import is that these compounds are now part of fixed dose combination therapies for treatment of HIV, either two drug (tenofovir disoproxil fumarate/emtricitabine) or three drug Atripla (tenofovir disoproxil fumarate/emtricitabine/efavirenz) formulations. Thus, even 50 + years after Bergmann s discovery of bioactive arabinose nucleosides, small molecules synthesised as result of his discoveries are still in clinical use and others are in clinical trials for treatment of viral diseases. 

Preferred Pl-based regimens are lopinavir/ritonavir plus lamivudine or emtricitabine plus another NRTI, usually zidovudine, stavudine or abacavir. Alternative combinations include other Pis with or without ritonavir, and two NRTIs. The combination of a protease inhibitor with ritonavir provides inhibition of cytochrome p450 enzymes and permits less frequent dosing of amprenavir, indinavir, lopinavir and saquinavir. Use of ritonavir in this setting is also known as boosting. ... 

In a study in 12 healthy subjects there was no important pharmacokinetic interaction between single doses of emtricitabine 200 mg and famciclovir 500 mg. ... 

In a single-dose study in 6 healthy subjects the AUC and maximum level of zidovudine 300 mg were increased by 26% and 66%, respectively, by emtricitabine 200 mg. The pharmacokinetics of emtricitabine were not al-tered. The authors suggest that these increases in zidovudine levels are unlikely to be clinically relevant based on experience of using the two drugs together for 48 weeks in a phase HI clinical study Further experience is needed. 

EUon R, Cohen C, Gathe J, ShaUt P, Hawkins T, Liu HC, et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection. AIDS 2011 25(15) 1881-6. 

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