A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Emtriva Online, Description, Chemistry, Ingredients - Emtricitabine
Emtriva Online, Description, Chemistry, Ingredients - Emtricitabine
Emtriva™ (emtricitabine) Capsules
WARNING
LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS,
INCLUDING FATAL CASES, HAVE BEEN REPORTED WITH THE USE OF NUCLEOSIDE ANALOGUES
ALONE OR IN COMBINATION WITH OTHER ANTIRETROVIRALS (SEE WARNINGS).
EMTRIVA IS NOT INDICATED FOR THE TREATMENT OF CHRONIC HEPATITIS B VIRUS (HBV) INFECTION AND THE SAFETY
AND EFFICACY OF EMTRIVA HAVE NOT BEEN ESTABLISHED IN PATIENTS CO-INFECTED WITH HBV AND HIV. SEVERE ACUTE
EXACERBATIONS OF HEPATITIS B HAVE BEEN REPORTED IN PATIENTS AFTER THE DISCONTINUATION OF EMTRIVA. HEPATIC
FUNCTION SHOULD BE MONITORED CLOSELY WITH BOTH CLINICAL AND LABORATORY FOLLOW-UP AT LEAST SEVERAL MONTHS
IN PATIENTS WHO DISCONTINUE EMTRIVA AND ARE CO-INFECTED WITH HIV AND HBV. IF APPROPRIATE, INITIATION OF ANTI-
HEPATITIS B THERAPY MAY BE WARRANTED (SEE WARNINGS).
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DESCRIPTION
EMTRIVA is the brand name of emtricitabine, a synthetic nucleoside
analogue with activity against human immunodeficiency virus type 1 (HIV-1) reverse
transcriptase.
The chemical name of emtricitabine is 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.
Emtricitabine is the (-) enantiomer of a thio analogue of cytidine, which differs
from other cytidine analogues in that it has a fluorine in the 5-position.
It has a molecular formula of C8H10FN3O3S
and a molecular weight of 247.24. It has the following structural formula:
Emtricitabine is a white to off-white powder with a solubility
of approximately 112 mg/mL in water at 25 oC. The log P for emtricitabine
is –0.43 and the pKa is 2.65.
EMTRIVA capsules are for oral administration. Each capsule
contains 200 mg of emtricitabine and the inactive ingredients, crospovidone,
magnesium stearate, microcrystalline cellulose and povidone.
MICROBIOLOGY
Mechanism of Action:
Emtricitabine, a synthetic nucleoside analog of cytosine, 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 a,
b, e and mitochondrial
DNA polymerase g.
Antiviral Activity In Vitro:
The in vitro antiviral activity of emtricitabine against laboratory
and clinical isolates of HIV was assessed in lymphoblastoid cell lines, the
MAGI-CCR5 cell line, and peripheral blood mononuclear cells. The 50% inhibitory
concentration (IC50) value for emtricitabine was in the range of
0.0013 to 0.64 µM (0.0003 to 0.158 µg/mL). In drug combination studies of emtricitabine
with nucleoside reverse transcriptase inhibitors (abacavir, lamivudine, stavudine,
tenofovir, zalcitabine, zidovudine), non-nucleoside reverse transcriptase inhibitors
(delavirdine, efavirenz, nevirapine), and protease inhibitors (amprenavir, nelfinavir,
ritonavir, saquinavir), additive to synergistic effects were observed. Most
of these drug combinations have not been studied in humans. Emtricitabine displayed
antiviral activity in vitro against HIV-1 clades A, C, D, E, F, and G (IC50
values ranged from 0.007 to 0.075 m M) and showed
strain specific activity against HIV-2 (IC50 values ranged from 0.007
to 1.5 m M).
Drug Resistance:
Emtricitabine-resistant isolates of HIV have been selected
in vitro. Genotypic analysis of these isolates showed that the reduced susceptibility
to emtricitabine was associated with a mutation in the HIV reverse transcriptase
gene at codon 184 which resulted in an amino acid substitution of methionine
by valine or isoleucine (M184V/I).
Emtricitabine-resistant isolates of HIV have been recovered
from some patients treated with emtricitabine alone or in combination with other
antiretroviral agents. In a clinical study, viral isolates from 37.5% of treatment-naïve
patients with virologic failure showed reduced susceptibility to emtricitabine.
Genotypic analysis of these isolates showed that the resistance was due to M184V/I
mutations in the HIV reverse transcriptase gene.
Cross Resistance:
Cross-resistance among certain nucleoside analogue reverse
transcriptase inhibitors has been recognized. Emtricitabine-resistant isolates
(M184V/I) were cross-resistant to lamivudine and zalcitabine but retained sensitivity
to abacavir, didanosine, stavudine, tenofovir, zidovudine, and NNRTIs (delavirdine,
efavirenz, and nevirapine). HIV-1 isolates containing the K65R mutation, selected
in vivo by abacavir, didanosine, tenofovir, and zalcitabine, demonstrated reduced
susceptibility to inhibition by emtricitabine. Viruses harboring mutations conferring
reduced susceptibility to stavudine and zidovudine (M41L, D67N, K70R, L210W,
T215Y/F, K219Q/E) or didanosine (L74V) remained sensitive to emtricitabine.
HIV-1 containing the K103N mutation associated with resistance to NNRTIs was
susceptible to emtricitabine.
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