| Indication |
Indicated, in combination with other antiretroviral agents, for
the treatment of HIV-1 infection in adults and for postexposure
prophylaxis of HIV infection in health care workers and others exposed
occupationally or nonoccupationally via percutaneous injury or mucous
membrane or nonintact skin contact with blood, tissues, or other body
fluids associated with risk for transmission of the virus. |
| Pharmacodynamics |
Emtricitabine is a nucleoside reverse transcriptase inhibitor
(NRTI) with activity against Human Immunodeficiency Virus Type 1
(HIV-1). Emtricitabine helps to block HIV reverse transcriptase, a
chemical in your body (enzyme) that is needed for HIV to multiply.
Emtricitabine is always used with other anti-HIV medicines to treat
people with HIV infection. Emtricitabine may lower the amount of HIV in
the blood (viral load). Emtricitabine may also help to increase the
number of T cells called CD4 cells. Lowering the amount of HIV in the
blood lowers the chance of death or infections that happen when your
immune system is weak (opportunistic infections). People taking
emtricitabine may still get opportunistic infections or other conditions
that happen with HIV infection. |
| Mechanism of action |
Emtricitabine works by inhibiting reverse transcriptase, the
enzyme that copies HIV RNA into new viral DNA. Emtricitabine is a
synthetic nucleoside analogue of cytidine. It is phosphorylated by
cellular enzymes to form emtricitabine 5'-triphosphate, which is
responsible for the inhibition of HIV-1 reverse transcriptase. It
competes with the natural substrate deoxycytidine 5'-triphosphate and
incorporates into nascent viral DNA, resulting in early chain
termination. Therefore emtricitabine inhibits the activity of HIV-1
reverse transcriptase (RT) both by competing with the natural substrate
deoxycytidine 5'-triphosphate and by its incorporation into viral DNA.
By inhibiting HIV-1 reverse transcriptase, emtricitabine can help to
lower the amount of HIV, or "viral load", in a patient's body and can
indirectly increase the number of immune system cells (called T cells or
CD4+ T-cells). Both of these changes are associated with healthier
immune systems and decreased likelihood of serious illness. |
| Absorption |
Rapidly absorbed (mean absolute bioavailability of 93% for capsules, and 75% for solution). Food does not effect absorption. |
| Volume of distribution |
Not Available |
| Protein binding |
Very low (less than 4%) |
| Metabolism |
Minimally transformed (13%), most appears unchanged in urine
(86%). The biotransformation of emtricitabine includes oxidation of the
thiol moiety to form the 3′-sulfoxide diastereomers (~ 9% of dose) and
conjugation with glucuronic acid to form 2′-O-glucuronide (~ 4% of
dose). In vitro studies indicate emtricitabine is not an inhibitor or
cytochrome P450 enzymes. |
| Route of elimination |
The renal clearance of emtricitabine is greater than the estimated
creatinine clearance, suggesting elimination by both glomerular
filtration and active tubular secretion. |
| Half life |
10 hours |
| Clearance |
- 302 +/- 94 mL/min [Renal Function Creatinine Clearance>80 ml/min]
- 168 +/- 10 mL/min [Renal Function Creatinine Clearance 50-80 ml/min]
- 138 +/- 28 mL/min [Renal Function Creatinine Clearance 30-49 ml/min]
- 99 +/- 6 mL/min [Renal Function Creatinine Clearance<30 ml/min]
- 64 +/- 12 mL/min [ESRD patients requiring dialysis]
|
| Toxicity |
Symptoms of overdose include serious liver problems
(hepatotoxicity, with liver enlargement and fat in the liver called
steatosis) or a lactic acidosis (buildup of an acid in the blood). |
