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 Indications, Dosage, Storage, Stability - Emtricitabine
Emtriva Indications, Dosage, Storage, Stability - Emtricitabine
INDICATION AND USAGE
EMTRIVA is indicated, in combination with other antiretroviral
agents, for the treatment of HIV-1 infection in adults.
This indication is based on analyses of plasma HIV-1 RNA levels
and CD4 cell counts from controlled studies of 48 weeks duration in antiretroviral-naïve
patients and antiretroviral-treatment-experienced patients who were virologically
suppressed on an HIV treatment regimen.
In antiretroviral-treatment-experienced patients, the use of
EMTRIVA may be considered for adults with HIV strains that are expected to be
susceptible to EMTRIVA as assessed by genotypic or phenotypic testing. (See
MICROBIOLOGY, Drug Resistance and Cross Resistance).
Description of Clinical Studies
Study 301A: EMTRIVA QD + didanosine QD + efavirenz QD compared
to stavudine BID + didanosine QD + efavirenz QD
Study 301A was a 48 week double-blind, active-controlled multicenter
study comparing EMTRIVA (200 mg QD) administered in combination with didanosine
and efavirenz versus stavudine, didanosine and efavirenz in 571 antiretroviral
naïve patients. Patients had a mean age of 36 years (range 18 to 69), 85%
were male, 52% Caucasian, 16% African-American and 26% Hispanics. Patients had
a mean baseline CD4 cell count of 318 cells/mm3 (range 5-1317) and
a median baseline plasma HIV RNA of 4.9 log10 copies/mL (range 2.6-7.0).
Thirty-eight percent of patients had baseline viral loads > 100,000 copies/mL
and 31% had CD4 cell counts < 200 cells/mL. Treatment outcomes are presented
in Table 4 below.
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Table 4. Outcomes of Randomized Treatment at Week 48 (Study
301A)
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Outcome at Week 48
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EMTRIVA+ didanosine+ efavirenz (N=286)
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Stavudine+ didanosine+ efavirenz (N=285)
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Responder1
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81% (78%)
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68% (59%)
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Virologic Failure2
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3%
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11%
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Death
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0%
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<1%
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Study Discontinuation Due to Adverse Event
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7%
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13%
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Study Discontinuation For Other Reasons3
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9%
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8%
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1. Patients achieved and maintained confirmed HIV RNA
< 400 copies/mL (<50 copies/mL) through Week 48.
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2. Includes patients who failed to achieve virologic
suppression or rebounded after achieving virologic suppression.
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3. Includes lost to follow-up, patient withdrawal, non-compliance,
protocol violation and other reasons.
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The mean increase from baseline in CD4 cell count was 168 cells/mm3
for the EMTRIVA arm and 134 cells/mm3 for the stavudine arm.
Through 48 weeks in the EMTRIVA group, 5 patients (1.7%) experienced
a new CDC Class C event, compared to 7 patients (2.5%) in the stavudine group.
Study 303: EMTRIVA QD + Stable Background Therapy (SBT) compared
to lamivudine BID + SBT
Study 303 was a 48 week, open-label, active-controlled multicenter
study comparing EMTRIVA (200 mg QD) to lamivudine, in combination with stavudine
or zidovudine and a protease inhibitor or NNRTI in 440 patients who were on
a lamivudine-containing triple-antiretroviral drug regimen for at least 12 weeks
prior to study entry and had HIV-1 RNA £ 400 copies/mL.
Patients were randomized 1:2 to continue therapy with lamivudine
(150 mg BID) or to switch to EMTRIVA (200 mg QD). All patients were maintained
on their stable background regimen. Patients had a mean age of 42 years (range
22-80), 86% were male, 64% Caucasian, 21% African-American and 13% Hispanic.
Patients had a mean baseline CD4 cell count of 527 cells/mm3 (range
37-1909), and a median baseline plasma HIV RNA of 1.7 log10 copies/mL
(range 1.7-4.0).
The median duration of prior antiretroviral therapy was 27.6
months.
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Table 5. Outcomes of Randomized Treatment at Week 48 (Study
303)
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Outcome at Week 48
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EMTRIVA + ZDV/d4T + NRTI/PI (N=294)
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Lamivudine + ZDV/d4T + NNRTI/PI (N=146)
|
|
Responder1
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77% (67%)
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82% (72%)
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Virologic Failure2
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7%
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8%
|
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Death
|
0%
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<1%
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Study Discontinuation Due to Adverse Event
|
4%
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0%
|
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Study Discontinuation For Other Reasons3
|
12%
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10%
|
|
1. Patients achieved and maintained confirmed HIV RNA
< 400 copies/mL (< 50/mL) through Week 48.
|
|
2. Includes patients who failed to achieve virologic
suppression or rebounded after achieving virologic suppression.
|
|
3. Includes lost to follow-up, patient withdrawal, non-compliance,
protocol violation and other reasons.
|
The mean increase from baseline in CD4 cell count was 29 cells/mm3
for the EMTRIVA arm and 61 cells/mm3 for the lamivudine arm.
Through 48 weeks, in the EMTRIVA group 2 patients (0.7%) experienced
a new CDC Class C event, compared to 2 patients (1.4%) in the lamivudine group.
DOSAGE AND ADMINISTRATION
For adults 18 years of age and older, the dose of EMTRIVA is
200 mg once daily taken orally with or without food.
Dose Adjustment in Patients with Renal Impairment:
Significantly increased drug exposures were seen when EMTRIVA
was administered to patients with renal impairment, (see CLINICAL
PHARMACOLOGY: Special Populations). Therefore, the dosing interval of
EMTRIVA should be adjusted in patients with baseline creatinine clearance <
50 mL/min using the following guidelines (see Table 8). The safety and effectiveness
of these dosing interval adjustment guidelines have not been clinically evaluated.
Therefore, clinical response to treatment and renal function should be closely
monitored in these patients.
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Table 8. Dosing Interval Adjustment in Patients with Renal
Impairment
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| |
Creatinine Clearance (mL/min)
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³ 50
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30 - 49
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15 - 29
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< 15 (including patients requiring hemodialysis)*
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|
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Recommended Dose and
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200 mg every
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200 mg every
|
200 mg every
|
200 mg every
|
|
Dosing Interval
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24 hours
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48 hours
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72 hours
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96 hours
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| |
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* Hemodialysis Patients: If dosing on day of dialysis,
give dose after dialysis.
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| |
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HOW SUPPLIED
EMTRIVA is available as capsules. EMTRIVA capsules, 200 mg,
are size 1 hard gelatin capsules with a blue cap and white body, printed with
"200 mg" in black on the cap and "GILEAD" and the corporate
logo in black on the body.
They are packaged in bottles of 30 capsules (NDC 61958-0601-1)
with induction sealed child-resistant closures.
Store at 25 C (77 ° F); excursions
permitted to 15 C – 30 C (59 F – 86 F) [see USP Controlled Room Temperature].
EMTRIVA is manufactured for Gilead Sciences,
Inc., Foster City, CA 94404. September 2004
EMTRIVA™ is a trademark of Gilead Sciences,
Inc. © 2003-2004 Gilead Sciences, Inc. GS-21-500-02
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