EMTRIVA®
(emtricitabine) Capsule
EMTRIVA
(emtricitabine) Oral Solution
WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS B
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals [See WARNINGS and PRECAUTIONS].
EMTRIVA is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of EMTRIVA have not been established in patients coinfected with HBV or HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue EMTRIVA. If appropriate, initiation of anti-hepatits B therapy may be warranted [See WARNINGS and PRECAUTIONS].
EMTRIVA is the brand name of emtricitabine, a synthetic nucleoside analog 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 analog of cytidine, which differs from other cytidine analogs 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 ° C. The log P for emtricitabine is -0.43 and the pKa is 2.65.
EMTRIVA is available as capsules or as an oral solution.
EMTRIVA capsules are for oral administration. Each capsule contains 200 mg of emtricitabine and the inactive ingredients, crospovidone, magnesium stearate, microcrystalline cellulose, and povidone.
EMTRIVA oral solution is for oral administration. One milliliter (1 mL) of EMTRIVA oral solution contains 10 mg of emtricitabine in an aqueous solution with the following inactive ingredients: cotton candy flavor, FD&C yellow No. 6, edetate disodium, methylparaben, and propylparaben (added as preservatives), sodium phosphate (monobasic), propylene glycol, water, and xylitol (added as a sweetener). Sodium hydroxide and hydrochloric acid may be used to adjust pH.
Last updated on RxList: 7/7/2008
EMTRIVA is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Additional important information regarding the use of EMTRIVA for the treatment of HIV-1 Infection:
EMTRIVA may be taken without regard to food.
Significantly increased drug exposures were seen when EMTRIVA was administered to patients with renal impairment [See CLINICAL PHARMACOLOGY]. Therefore, the dosing interval or dose of EMTRIVA should be adjusted in patients with baseline creatinine clearance < 50 mL/min using the following guidelines (see Table 1). The safety and effectiveness of these dose adjustment guidelines have not been clinically evaluated. Therefore, clinical response to treatment and renal function should be closely monitored in these patients.
Table 1: Dose Adjustment in Adult Patients with Renal Impairment
| Formulation | Creatinine Clearance (mL/min) | |||
| ≥ 50 mL/min | 30-49 mL/min | 15-29 mL/min | <15 mL/min or on hemodialysisa | |
| Capsule (200mg) | 200 mg every 24 hours | 200 mg every 48 hours | 200 mg every72 hours | 200 mg every 96 hours |
| Oral Solution (10mg/mL) | 240 mg every 24 hours (24 mL) |
120 mg every 24 hours (12 mL) |
80 mg every 24 hours (8 mL) |
60 mg every 24 hours (6 mL) |
| a.Hemodialysis Patients: If dosing on day of dialysis, give dose after dialysis | ||||
Although there are insufficient data to recommend a specific dose adjustment of EMTRIVA 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.
EMTRIVA is available as capsules and oral solution.
EMTRIVA capsules, containing 200 mg of emtricitabine, 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. EMTRIVA oral solution is a clear, orange to dark orange liquid containing 10 mg of emtricitabine per mL.
The size 1 hard gelatin capsules with a blue cap and white body contain 200 mg of emtricitabine, are printed with "200 mg" in black on the cap and "GILEAD" and the corporate logo in black on the body, and are available in unit of use bottles (closed with induction sealed child-resistant closures) of:
Store at 25 °C (77 °F); excursions permitted to 15 °C-30 °C (59 °F-86 °F)
The oral solution is a clear, orange to dark orange liquid, contains 10 mg/mL of emtricitabine, and is available in unit of use plastic, amber bottles ( closed with child resistant closures and packaged with a marked dosing cup) of:
Store refrigerated, 2-8 °C (36-46 °F). Emtriva oral solution should be used within 3 months if stored by the patient at 25 °C (77 ° F); excursions permitted to 15-30 °C (59-86 °F).
EMTRIVA, TRUVADA, and VIREAD are trademarks of Gilead Sciences, Inc. ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. All other trademarks referenced herein are the property of their respective owners. MAY08. FDA rev date: 5/16/2008
Last updated on RxList: 7/7/2008
The following adverse reactions are discussed in other sections of the labeling:
More than 2,000 adult patients with HIV-1 infection have been treated with EMTRIVA alone or in combination with other antiretroviral agents for periods of 10 days to 200 weeks in clinical trials.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The most common adverse reactions (incidence 10%, any severity) identified from any of the 3 large controlled clinical trials include headache, diarrhea nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis.
Studies 301A and 303 - Treatment Emergent Adverse Reactions: The most common adverse reactions that occurred in patients receiving EMTRIVA with other antiretroviral agents in clinical studies 301A and 303 were headache, diarrhea, nausea, and rash, which were generally of mild to moderate severity. Approximately 1% of patients discontinued participation in the clinical studies due to these events. All adverse reactions were reported with similar frequency in EMTRIVA and control treatment groups with the exception of skin discoloration which was reported with higher frequency in the EMTRIVA treated group.
Skin discoloration, manifested by hyperpigmentation on the palms and/or soles was generally mild and asymptomatic. The mechanism and clinical significance are unknown.
A summary of EMTRIVA treatment emergent clinical adverse reactions in studies 301A and 303 is provided in Table 2.
Table 2: Selected Treatment-Emergent Adverse Reactions (All
Grades, Regardless of Causality) Reported in ≥ 3% of EMTRIVA-Treated Patients
in Either Study 301A or 303 (0-48 Weeks)
| 303 | 301A | |||
| EMTRIVA + ZDV/d4T + NNRTI/PI (N=294) |
Lamivudine + ZDV/d4T + NNRTI/PI (N=146) |
EMTRIVA + didanosine + efavirenz (N=286) |
Stavudine + didanosine + efavirenz (N=285) |
|
| Body as a Whole | ||||
| Abdominal pain | 8% | 11% | 14% | 17% |
| Asthenia | 16% | 10% | 12% | 17% |
| Headache | 13% | 6% | 22% | 25% |
| Digestive System | ||||
| Diarrhea | 23% | 18% | 23% | 32% |
| Dyspepsia | 4% | 5% | 8% | 12% |
| Nausea | 18% | 12% | 13% | 23% |
| Vomiting | 9% | 7% | 9% | 12% |
| Musculoskeletal | ||||
| Arthralgia | 3% | 4% | 5% | 6% |
| Myalgia | 4% | 4% | 6% | 3% |
| Nervous System | ||||
| Abnormal dreams | 2% | <1% | 11% | 19% |
| Depressive disorders | 6% | 10% | 9% | 13% |
| Dizziness | 4% | 5% | 25% | 26% |
| Insomnia | 7% | 3% | 16% | 21% |
| Neuropathy/peripheral neuritis | 4% | 3% | 4% | 13% |
| Paresthesia | 5% | 7% | 6% | 12% |
| Respiratory | ||||
| Increased cough | 14% | 11% | 14% | 8% |
| Rhinitis | 18% | 12% | 12% | 10% |
| Skin | ||||
| Rash eventa | 17% | 14% | 30% | 33% |
| a. Rash event includes rash, pruritus, maculopapularrash, urticaria, vesiculobullous rash, pustular rash, and allergic reaction. | ||||
Laboratory abnormalities in these studies occurred with similar frequency in the EMTRIVA and comparator groups. A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 3 below.
Table 3: Treatment-Emergent Grade 3/4 Laboratory Abnormalities
Reported in ≥ 1% of EMTRIVA-Treated Patients in Either Study 301A or 303
| 303 | 301A | |||
| EMTRIVA + ZDV/d4T + NNRTI/PI (N=294) |
Lamivudine + ZDV/d4T + NNRTI/PI (N=146) |
EMTRIVA + Didanosine + Efavirenz (N=286) |
Stavudine + Didanosine + Efavirenz (N=285) |
|
| Percentage with grade 3 or grade 4 laboratory abnormality | 31% | 28% | 34% | 38% |
| ALT (>5.0 x ULNa) | 2% | 1% | 5% | 6% |
| AST (>5.0 x ULN) | 3% | <1% | 6% | 9% |
| Bilirubin (>2.5 x ULN) | 1% | 2% | <1% | <1% |
| Creatine kinase (>4.0 x ULN) | 11% | 14% | 12% | 11% |
| Neutrophils (<750 mm3) | 5% | 3% | 5% | 7% |
| Pancreatic amylase (>2.0 x ULN) | 2% | 2% | <1% | 1% |
| Serum amylase (>2.0 x ULN) | 2% | 2% | 5% | 10% |
| Serum glucose<40 or >250 mg/dL) | 3% | 3% | 2% | 3% |
| Serum lipase (>2.0 x ULN) | <1% | <1% | 1% | 2% |
| Triglycerides (>750 mg/dL) | 10% | 8% | 9% | 6% |
| a. ULN = Upper limit of normal | ||||
Study 934 - Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naïve patients received either VIREAD + EMTRIVA administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254). Adverse reactions observed in this study were generally consistent with those seen in previous studies in treatment-experienced or treatment-naïve patients (Table 4).
Table 4: Selected Treatment-Emergent Adverse Reactionsa
(Grades 2-4) Reported in ≥ 5% in Any Treatment Group in Study 934 (0-144
Weeks)
| TDFb + EMTRIVA + EFV | AZT/3TC + EFV | |
| N=257 | N=254 | |
| Gastrointestinal Disorder | ||
| Diarrhea | 9% | 5% |
| Nausea | 9% | 7% |
| Vomiting | 2% | 5% |
| General Disorders and Administration | ||
| Site Condition | ||
| Fatigue | 9% | 8% |
| Infections and Infestations | ||
| Sinusitis | 8% | 4% |
| Upper respiratory tract infections | 8% | 5% |
| Nasopharyngitis | 5% | 3% |
| Nervous System Disorders | ||
| Headache | 6% | 5% |
| Dizziness | 8% | 7% |
| Psychiatric Disorders | ||
| Depression | 9% | 7% |
| Insomnia | 5% | 7% |
| Skinand Subcutaneous Tissue Disorders | ||
| Rash eventc | 7% | 9% |
| a. Frequencies of adverse reactions are based onall
treatment-emergent adverse events, regardless of relationship to study drug. b. From Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz inplace of VIREAD + EMTRIVA with efavirenz. c.Rash event includes rash, exfoliative rash, rash generalized, rash macular, rashmaculo-papular, rash pruritic, and rash vesicular. |
||
Study 934 - Laboratory Abnormalities: Significant laboratory abnormalities observed in this study are shown in Table 5.
Table 5: Significant Laboratory Abnormalities Reported in
≥ 1% of Patients in Any Treatment Group in Study 934 (0-144 Weeks)
| TDFa + EMTRIVA + EFV | AZT/3TC + EFV | |
| N=257 | N=254 | |
| Any ≥ Grade 3 Laboratory Abnormality | 30% | 26% |
| Fasting Cholesterol (>240 mg/dL) | 22% | 24% |
| Creatine Kinase (M: >990 U/L) (F: >845 U/L) | 9% | 7% |
| Serum Amylase (>175 U/L) | 8% | 4% |
| Alkaline Phosphatase (>550 U/L) | 1% | 0% |
| AST (M: >180 U/L) (F: >170 U/L) | 3% | 3% |
| ALT (M: >215 U/L) (F: >170 U/L) | 2% | 3% |
| Hemoglobin (<8.0 mg/dL) | 0% | 4% |
| Hyperglycemia (>250 mg/dL) | 2% | 1% |
| Hematuria (>75 RBC/HPF) | 3% | 2% |
| Glycosuria (3+) | <1% | 1% |
| Neutrophils (<750/mm3) | 3% | 5% |
| Fasting Triglycerides (>750 mg/dL) | 4% | 2% |
| a. From Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz inplace of VIREAD + EMTRIVA with efavirenz. | ||
Assessment of adverse reactions is based on data from Study 203, an open label, uncontrolled study of 116 HIV-1-infected pediatric patients who received emtricitabine through 48 weeks. The adverse reaction profile in pediatric patients was generally comparable to that observed in clinical studies of EMTRIVA in adult patients [See ADVERSE REACTIONS]. Hyperpigmentation was more frequent in children. Additional adverse reactions identified from this study include anemia.
Selected treatment-emergent adverse events, regardless of causality, reported in patients during 48 weeks of treatment were the following: infection (44%), hyperpigmentation (32%), increased cough (28%), vomiting (23%), otitis media (23%), rash (21%), rhinitis (20%), diarrhea (20%), fever (18%), pneumonia (15%), gastroenteritis (11%), abdominal pain (10%), and anemia (7%). Treatment-emergent grade 3/4 laboratory abnormalities were experienced by 9% of pediatric patients, including amylase > 2.0 x ULN (n=4), neutrophils < 750/mm3 (n=3), ALT > 5 x ULN (n=2), elevated CPK ( > 4 x ULN) (n=2) and one patient each with elevated bilirubin ( > 3.0 x ULN), elevated GGT ( > 10 x ULN), elevated lipase ( > 2.5 x ULN), decreased hemoglobin ( < 7 g/dL), and decreased glucose ( < 40 mg/dL).
The potential for drug interactions with EMTRIVA has been studied in combination with zidovudine, indinavir, stavudine, famciclovir, and tenofovir disoproxil fumarate. There were no clinically significant drug interactions for any of these drugs Drug interactions studies are described elsewhere in the labeling [See CLINICAL PHARMACOLOGY]
Last updated on RxList: 7/7/2008
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination, including emtricitabine and other antiretrovirals. A majority of these cases have been in women.
Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for liver diseases; however, cases have also been reported in patients with no known risk factors. Treatment with EMTRIVA should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
It is recommended that all patients with HIV-1 be tested for the presence of chronic Hepatitis B virus (HBV) before initiating antiretroviral therapy. EMTRIVA is not approved for the treatment of chronic HBV infection and the safety and efficacy of EMTRIVA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of Hepatitis B have been reported in patients after the discontinuation of EMTRIVA. In some patients infected with HBV and treated with EMTRIVA, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue EMTRIVA. If appropriate, initiation of anti-Hepatitis B therapy may be warranted.
EMTRIVA is a component of TRUVADA (a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate) and ATRIPLA (a fixed-dose combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate). EMTRIVA should not be coadministered with TRUVADA or ATRIPLA. Due to similarities between emtricitabine and lamivudine, EMTRIVA should not be coadministered with other drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine).
Emtricitabine is principally eliminated by the kidney. Reduction of the dosage of EMTRIVA is recommended for patients with impaired renal function [See DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including EMTRIVA. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.
See FDA-approved patient labeling
Patients should be advised that:
In long-term oral carcinogenicity studies of emtricitabine, no drug-related increases in tumor incidence were found in mice at doses up to 750 mg/kg/day (26 times the human systemic exposure at the therapeutic dose of 200 mg/day) or in rats at doses up to 600 mg/kg/day (31 times the human systemic exposure at the therapeutic dose).
Emtricitabine was not genotoxic in the reverse mutation bacterial test (Ames test), mouse lymphoma or mouse micronucleus assays.
Emtricitabine did not affect fertility in male rats at approximately 140-fold or in male and female mice at approximately 60-fold higher exposures (AUC) than in humans given the recommended 200 mg daily dose. Fertility was normal in the offspring of mice exposed daily from before birth (in utero) through sexual maturity at daily exposures (AUC) of approximately 60-fold higher than human exposures at the recommended 200 mg daily dose.
The incidence of fetal variations and malformations was not increased in embryofetal toxicity studies performed with emtricitabine in mice at exposures (AUC) approximately 60-fold higher and in rabbits at approximately 120-fold higher than human exposures at the recommended daily dose. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, EMTRIVA should be used during pregnancy only if clearly needed.
Antiretroviral Pregnancy Registry: To monitor fetal outcomes of pregnant women exposed to EMTRIVA, an Antiretroviral Pregnancy Registry has been established. Healthcare providers are encouraged to register patients by calling 1-800-258-4263.
Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV-1. It is not known whether emtricitabine is excreted in human milk. Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving EMTRIVA.
The safety and efficacy of emtricitabine in patients between 3 months and 21 years of age is supported by data from three open-label, non-randomized clinical studies in which emtricitabine was administered to 169 HIV-1 infected treatment-naive and experienced (defined as virologically suppressed on a lamivudine containing regimen for which emtricitabine was substituted for lamivudine) subjects [See Clinical Studies].
The pharmacokinetics of emtricitabine were studied in 20 neonates born to HIV-1-positive mothers [See Clinical Studies]. All neonates were HIV-1 negative at the end of the study; the efficacy of emtricitabine in preventing or treating HIV-1 could not be determined.
Clinical studies of EMTRIVA did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. In general, dose selection for the elderly patient should be cautious, keeping in mind the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
It is recommended that the dose or dosing interval for EMTRIVA be modified in patients with creatinine clearance < 50 mL/min or in patients who require dialysis [See DOSAGE AND ADMINISTRATION].
Last updated on RxList: 7/7/2008
There is no known antidote for EMTRIVA. Limited clinical experience is available at doses higher than the therapeutic dose of EMTRIVA. In one clinical pharmacology study single doses of emtricitabine 1200 mg were administered to 11 patients. No severe adverse reactions were reported.
The effects of higher doses are not known. If overdose occurs the patient should be monitored for signs of toxicity, and standard supportive treatment applied as necessary.
Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.
EMTRIVA is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the products.
Last updated on RxList: 7/7/2008
Emtricitabine is an antiviral drug. [See CLINICAL PHARMACOLOGY]
The pharmacokinetics of emtricitabine were evaluated in healthy volunteers and HIV-1-infected individuals. Emtricitabine pharmacokinetics are similar between these populations.
Figure 1 shows the mean steady-state plasma emtricitabine concentration-time profile in 20 HIV-1-infected subjects receiving EMTRIVA capsules.
Figure 1: Mean (± 95% CI) Steady-State Plasma Emtricitabine
Concentrations in HIV-1-Infected Adults (N=20)
 |
Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma concentrations occurring at 1-2 hours post-dose. Following multiple dose oral administration of EMTRIVA capsules to 20 HIV-1-infected subjects, the (mean ± SD) steady-state plasma emtricitabine peak concentration (Cmax) was 1.8 ± 0.7 µg/mL and the area-under the plasma concentration-time curve over a 24-hour dosing interval (AUC) was 10.0 ± 3.1 µg·hr/mL. The mean steady state plasma trough concentration at 24 hours post-dose was 0.09 µg/mL. The mean absolute bioavailability of EMTRIVA capsules was 93% while the mean absolute bioavailability of EMTRIVA oral solution was 75%. The relative bioavailability of EMTRIVA oral solution was approximately 80% of EMTRIVA capsules.
The multiple dose pharmacokinetics of emtricitabine are dose proportional over a dose range of 25-200 mg.
In vitro binding of emtricitabine to human plasma proteins was < 4% and independent of concentration over the range of 0.02-200 µg/mL. At peak plasma concentration, the mean plasma to blood drug concentration ratio was ~1.0 and the mean semen to plasma drug concentration ratio was ~4.0.
In vitro studies indicate that emtricitabine is not an inhibitor of human CYP450 enzymes. Following administration of 14C-emtricitabine, complete recovery of the dose was achieved in urine (~86%) and feces (~14%). Thirteen percent (13%) of the dose was recovered in urine as three putative metabolites. 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). No other metabolites were identifiable.
The plasma emtricitabine half-life is approximately 10 hours. The renal clearance of emtricitabine is greater than the estimated creatinine clearance, suggesting elimination by both glomerular filtration and active tubular secretion. There may be competition for elimination with other compounds that are also renally eliminated.
EMTRIVA capsules and oral solution may be taken with or without food. Emtricitabine systemic exposure (AUC) was unaffected while Cmax decreased by 29% when EMTRIVA capsules were administered with food (an approximately 1000 kcal high-fat meal). Emtricitabine systemic exposure (AUC) and Cmax were unaffected when 200 mg EMTRIVA oral solution was administered with either a high-fat or low-fat meal.
The pharmacokinetics of emtricitabine were similar in adult male and female patients and no pharmacokinetic differences due to race have been identified.
The pharmacokinetics of emtricitabine at steady state were determined in 77 HIV-1-infected children, and the pharmacokinetic profile was characterized in four age groups (Table 6). The emtricitabine exposure achieved in children receiving a daily dose of 6 mg/kg up to a maximum of 240 mg oral solution or a 200 mg capsule is similar to exposures achieved in adults receiving a once-daily dose of 200 mg.
The pharmacokinetics of emtricitabine were studied in 20 neonates born to HIV-1-positive mothers. Each mother received prenatal and intrapartum combination antiretroviral therapy. Neonates received up to 6 weeks of zidovudine prophylactically after birth. The neonates were administered two short courses of emtricitabine oral solution (each 3 mg/kg once daily x 4 days) during the first 3 months of life. The AUC observed in neonates who received a daily dose of 3 mg/kg of emtricitabine was similar to the AUC observed in pediatric patients 3 months to 17 years who received a daily dose of emtricitabine as a 6 mg/kg oral solution up to 240 mg or as a 200 mg capsule (Table 6).
Table 6: Mean ± SD Pharmacokinetic Parameters by Age Groups
for Pediatric Patients and Neonates Receiving EMTRIVA Capsules or Oral Solution
| HIV-1-exposed Neonates | HIV-1-infectedPediatric Patients | ||||
| 3-24 mo | 25 mo-6 yr | 7-12yr | 13-17 yr | ||
| Age | 0-3 mo (N=20)a |
(N=14) | (N=19) | (N=17) | (N=27) |
| Formulation | |||||
| Capsule (n) | 0 | 0 | 0 | 10 | 26 |
| Oral Solution (n) | 20 | 14 | 19 | 7 | 1 |
| Dose (mg/kg)b | 3.1 (2.9-3.4) | 6.1 (5.5- 6.8) | 6.1 (5.6- 6.7) | 5.6 (3.1- 6.6) | 4.4 (1.8- 7.0) |
| Cmax (µg/mL) | 1.6 ± 0.6 | 1.9 ± 0.6 | 1.9 ± 0.7 | 2.7 ± 0.8 | 2.7 ± 0.9 |
| AUC (µg•hr/mL) | 11.0 ± 4.2 | 8.7 ± 3.2 | 9.0 ± 3.0 | 12.6 ± 3.5 | 12.6 ± 5.4 |
| T1/2 (hr) | 12.1 ± 3.1 | 8.9 ± 3.2 | 11.3 ± 6.4 | 8.2 ± 3.2 | 8.9 ± 3.3 |
| a.Two pharmacokinetic evaluations
were conducted in 20 neonates over the first 3 months of life. Median
(range) age of infant on day of pharmacokinetic evaluation was 26 (5-81)
days. b.Mean (range) |
|||||
The pharmacokinetics of emtricitabine have not been fully evaluated in the elderly.
The pharmacokinetics of emtricitabine are altered in patients with renal impairment [See WARNINGS and PRECAUTIONS]. In adult patients with creatinine clearance < 50 mL/min or with end-stage renal disease (ESRD) requiring dialysis, Cmax and AUC of emtricitabine were increased due to a reduction in renal clearance (Table 7). It is recommended that the dosing interval for EMTRIVA be modified in adult patients with creatinine clearance < 50 mL/min or in adult patients with ESRD who require dialysis [See DOSAGE AND ADMINISTRATION]. The effects of renal impairment on emtricitabine pharmacokinetics in pediatric patients are not known.
Table 7: Mean ± SD Pharmacokinetic Parameters in Adult Patients
with Varying Degrees of Renal Function
| Creatinine Clearance (mL/min) | >80 (N=6) |
50-80 (N=6) |
30-49 (N=6) |
<30 (N=5) |
ESRDa <30 (N=5) |
| Baseline creatinine clearance (mL/min) | 107 ± 21 | 59.8 ± 6.5 | 40.9 ± 5.1 | 22.9 ± 5.3 | 8.8 ± 1.4 |
| Cmax (µg/mL) | 2.2 ± 0.6 | 3.8 ± 0.9 | 3.2 ± 0.6 | 2.8 ± 0.7 | 2.8 ± 0.5 |
| AUC (µg·hr/mL) | 11.8 ± 2.9 | 19.9 ± 1.2 | 25.1 ± 5.7 | 33.7± 2.1 | 53.2 ± 9.9 |
| CL/F (mL/min) | 302 ± 94 | 168 ± 10 | 138 ± 28 | 99 ± 6 | 64 ± 12 |
| CLr (mL/min) | 213 ± 89 | 121 ± 39 | 69 ± 32 | 30 ± 11 | NAb |
| a. ESRD patients requiringdialysis b. NA = Not Applicable |
|||||
Hemodialysis: Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.
The pharmacokinetics of emtricitabine have not been studied in patients with hepatic impairment, however, emtricitabine is not metabolized by liver enzymes, so the impact of liver impairment should be limited.
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 evaluated 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 Druga
| Coadministered Drug | Dose of Coadministered Drug (mg) | Emtricitabine Dose (mg) | N | % Change of Emtricitabine Pharmacokinetic Parametersb (90% CI) |
||
| Cmax | AUC | Cmin | ||||
| Tenofovir DF | 300 once daily x 7 days | 200 once daily x 7 days | 17 | ⇔ | ⇔ | ↑20 (↑12 to ↑29) |
| Zidovudine | 300 twice daily x 7 days | 200 once daily x 7 days | 27 | ⇔ | ⇔ | ⇔ |
| Indinavir | 800 x 1 | 200 x 1 | 12 | ⇔ | ⇔ | NA |
| Famciclovir | 500 x 1 | 200 x 1 | 12 | ⇔ | ⇔ | NA |
| Stavudine | 40 x 1 | 200 x 1 | 6 | ⇔ | ⇔ | NA |
| a.All interaction studies conducted in healthy
volunteers. b↑= Increase; ↓= Decrease; ⇔= No Effect; NA = Not Applicable |
||||||
Table 9: Drug Interactions: Change in Pharmacokinetic Parameters
for Coadministered Drug in the Presence of Emtricitabinea
| Coadministered Drug | Dose of Coadministered Drug (mg) | Emtricitabine Dose (mg) | N | % Change of Coadministered Drug Pharmacokinetic Parametersb (90% CI) |
||
| Cmax | AUC | Cmin | ||||
| Tenofovir DF | 300 once daily x 7 days | 200 once daily x 7 days | 17 | ⇔ | ⇔ | ⇔ |
| Zidovudine | 300 twice daily x 7 days | 200 once daily x 7 days | 27 | ↑17 (↑0 to ↑38) |
↑13 (↑5 to ↑20) |
⇔ |
| Indinavir | 800 x 1 | 200 x 1 | 12 | ⇔ | ⇔ | NA |
| Famciclovir | 500 x 1 | 200 x 1 | 12 | ⇔ | ⇔ | NA |
| Stavudine | 40 x 1 | 200 x 1 | 6 | ⇔ | ⇔ | NA |
| a. All interaction studies conducted inhealthy
volunteers. b↑= Increase; ↓= Decrease; ⇔= No Effect; NA = Not Applicable |
||||||
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 .
The antiviral activity in cell culture of emtricitabine against laboratory and clinical isolates of HIV-1 was assessed in lymphoblastoid cell lines, the MAGI-CCR5 cell line, and peripheral blood mononuclear cells. The 50% effective concentration (EC50) value for emtricitabine was in the range of 0.0013-0.64 µM (0.0003-0.158 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. Emtricitabine displayed antiviral activity in cell culture against HIV-1 clades A, B, C, D, E, F, and G (EC50 values ranged from 0.007-0.075 µM) and showed strain specific activity against HIV-2 (EC50 values ranged from 0.007-1.5 µM).
The in vivo activity of emtricitabine was evaluated in two clinical trials in which 101 patients were administered 25-400 mg a day of EMTRIVA as monotherapy for 10-14 days. A dose-related antiviral effect was observed, with a median decrease from baseline in plasma HIV-1 RNA of 1.3 log10 at a dose of 25 mg once daily and 1.7 log10 to 1.9 log10 at a dose of 200 mg once daily or twice daily.
Emtricitabine-resistant isolates of HIV-1 have been selected in cell culture and in vivo. Genotypic analysis of these isolates showed that the reduced susceptibility to emtricitabine was associated with a substitution in the HIV-1 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-1 have been recovered from some patients treated with emtricitabine alone or in combination with other antiretroviral agents. In a clinical study of treatment-naive patients treated with EMTRIVA, didanosine, and efavirenz [See Clinical Studies], viral isolates from 37.5% of patients with virologic failure showed reduced susceptibility to emtricitabine. Genotypic analysis of these isolates showed that the resistance was due to M184V/I substitutions in the HIV-1 reverse transcriptase gene.
In a clinical study of treatment-naive patients treated with either EMTRIVA, VIREAD, and efavirenz or zidovudine/lamivudine and efavirenz [See Clinical Studies], resistance analysis was performed on HIV-1 isolates from all confirmed virologic failure patients with > 400 copies/mL of HIV-1 RNA at Week 144 or early discontinuation. Development of efavirenz resistance-associated substitutions occurred most frequently and was similar between the treatment arms. The M184V amino acid substitution, associated with resistance to EMTRIVA and lamivudine, was observed in 2/19 analyzed patient isolates in the EMTRIVA + VIREAD group and in 10/29 analyzed patient isolates in the lamivudine/zidovudine group. Through 144 weeks of Study 934, no patients have developed a detectable K65R substitution in their HIV-1 as analyzed through standard genotypic analysis.
Cross-resistance among certain nucleoside analog reverse transcriptase inhibitors has been recognized. Emtricitabine-resistant isolates (M184V/I) were cross-resistant to lamivudine and zalcitabine but retained sensitivity in cell culture to didanosine, stavudine, tenofovir, zidovudine, and NNRTIs (delavirdine, efavirenz, and nevirapine). HIV-1 isolates containing the K65R substitution, selected in vivo by abacavir, didanosine, tenofovir, and zalcitabine, demonstrated reduced susceptibility to inhibition by emtricitabine. Viruses harboring substitutions 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 substitution associated with resistance to NNRTIs was susceptible to emtricitabine.
Data through 144 weeks are reported for Study 934, a randomized, open-label, active-controlled multicenter study comparing EMTRIVA + VIREAD administered in combination with efavirenz versus zidovudine/lamivudine fixed-dose combination administered in combination with efavirenz in 511 antiretroviral-naive patients. From Weeks 96 to 144 of the study, patients received emtricitabine + tenofovir disoproxil fumarate (tenofovir DF) with efavirenz in place of EMTRIVA + tenofovir DF with efavirenz. Patients had a mean age of 38 years (range 18-80), 86% were male, 59% were Caucasian and 23% were Black. The mean baseline CD4+ cell count was 245 cells/mm3 (range 2-1191) and median baseline plasma HIV-1 RNA was 5.01 log10 copies/mL (range 3.56-6.54). Patients were stratified by baseline CD4+ cell count ( < or ≥ 200 cells/mm3); 41% had CD4+ cell counts < 200 cells/mm3 and 51% of patients had baseline viral loads > 100,000 copies/mL. Treatment outcomes through 48 and 144 weeks for those patients who did not have efavirenz resistance at baseline are presented in Table 10.
Table 10: Outcomes of Randomized Treatment at Week 48 and
144 (Study 934)
| Outcomes | Week 48 | Week 144 | ||
| EMTRIVA + TD F+ EFV (N=244) |
AZT/3TC + EFV (N=243) |
EMTRIVA + TDF + EFV (N=227)a |
AZT/3TC + EFV (N=229)a |
|
| Responderb | 84% | 73% | 71% | 58% |
| Virologic failurec | 2% | 4% | 3% | 6% |
| Rebound | 1% | 3% | 2% | 5% |
| Never suppressed | 0% | 0% | 0% | 0% |
| Change in antiretroviral regimen | 1% | 1% | 1% | 1% |
| Death | <1% | 1% | 1% | 1% |
| Discontinued due to adverse event | 4% | 9% | 5% | 12% |
| Discontinued for other reasons4d | 10% | 14% | 20% | 22% |
| a. Patients who were responders at Week 48 or Week
96 (HIV-1 RNA < 400 copies/mL) but did not consent to continue study after
Week 48 or Week 96 were excluded from analysis. b. Patients achieved and maintained confirmed HIV-1 RNA < 400 copies/mL through Weeks 48 and 144. c. Includes confirmed viral rebound and failure to achieve confirmed < 400 copies/mL through Weeks 48 and 144. d. Includes lost to follow-up, patient withdrawal, noncompliance, protocol violation and other reasons. |
||||
Through Week 48, 84% and 73% of patients in the EMTRIVA + tenofovir DF group and the zidovudine/lamivudine group, respectively, achieved and maintained HIV-1 RNA < 400 copies/mL (71% and 58% through Week 144). The difference in the proportion of patients who achieved and maintained HIV-1 RNA < 400 copies/mL through 48 weeks largely results from the higher number of discontinuations due to adverse events and other reasons in the zidovudine/lamivudine group in this open-label study. In addition, 80% and 70% of patients in the EMTRIVA + tenofovir DF group and the zidovudine/lamivudine group, respectively, achieved and maintained HIV-1 RNA < 50 copies/mL through Week 48 (64% and 56% through Week 144). The mean increase from baseline in CD4+ cell count was 190 cells/mm3 in the EMTRIVA + tenofovir DF group and 158 cells/mm3 in the zidovudine/lamivudine group at Week 48 (312 and 271 cells/mm3 at Week 144).
Through 48 weeks, 7 patients in the EMTRIVA + tenofovir DF group and 5 patients in the zidovudine/lamivudine group experienced a new CDC Class C event (10 and 6 patients through 144 weeks).
Study 301A was a 48 week double-blind, active-controlled multicenter study comparing EMTRIVA (200 mg once daily) administered in combination with didanosine and efavirenz versus stavudine, didanosine and efavirenz in 571 antiretroviral naive adult patients. Patients had a mean age of 36 years (range 18-69), 85% were male, 52% Caucasian, 16% African-American and 26% Hispanic. Patients had a mean baseline CD4+ cell count of 318 cells/mm3 (range 5-1317) and a median baseline plasma HIV-1 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 11 below.
Table 11: Outcomes of Randomized Treatment at Week 48 (Study
301A)
| Outcomes | EMTRIVA + Didanosine + Efavirenz (N=286) |
Stavudine + Didanosine + Efavirenz (N=285) |
| Respondera | 81% (78%) | 68% (59%) |
| Virologic Failureb | 3% | 11% |
| Death | 0% | <1% |
| Study Discontinuation Due to Adverse Event | 7% | 13% |
| Study Discontinuation for Other Reasonsc | 9% | 8% |
| a.Patients achieved and maintained confirmed HIV
RNA<400 copies/mL (<50 copies/mL) through Week 48. b.Includes patients who failed to achieve virologic suppressionor rebounded after achieving virologic suppression. c.Includes lost to follow-up, patient withdrawal,non-compliance, protocol violation and other reasons. |
||
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 was a 48 week, open-label, active-controlled multicenter study comparing EMTRIVA (200 mg once daily) to lamivudine, in combination with stavudine or zidovudine and a protease inhibitor or NNRTI in 440 adult 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 twice daily) or to switch to EMTRIVA (200 mg once daily). 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-1 RNA of 1.7 log10 copies/mL (range 1.7-4.0).
The median duration of prior antiretroviral therapy was 27.6 months. Treatment outcomes are presented in Table 12 below.
Table 12: Outcomes of Randomized Treatment at Week 48 (Study
303)
| Outcomes | EMTRIVA + ZDV/d4T + NNRTI/PI (N=294) |
Lamivudine + ZDV/d4T + NNRTI/PI (N=146) |
| Respondera | 77% (67%) | 82% (72%) |
| Virologic Failureb | 7% | 8% |
| Death | 0% | <1% |
| Study Discontinuation Due to Adverse Event | 4% | 0% |
| Study Discontinuation for Other Reasons3c | 12% | 10% |
| a.Patients achieved and maintained confirmed HIV
RNA<400 copies/mL (<50 copies/mL) through Week 48. b.Includes patients who failed to achieve virologic suppressionor rebounded after achieving virologic suppression. c.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.
In three open-label, non-randomized clinical studies, emtricitabine was administered to 169 HIV-1 infected treatment-naive and experienced (defined as virologically suppressed on a lamivudine containing regimen for which emtricitabine was substituted for lamivudine) patients between 3 months and 21 years of age. Patients received once-daily EMTRIVA oral solution (6 mg/kg to a maximum of 240 mg/day) or EMTRIVA capsules (a single 200 mg capsule once daily) in combination with at least two other antiretroviral agents. Patients had a mean age of 7.9 years (range 0.3-21), 49% were male, 15% Caucasian, 61% Black and 24% Hispanic.
Patients had a median baseline HIV-1 RNA of 4.6 log10 copies/mL (range 1.7-6.4) and a mean baseline CD4+ cell count of 745 cells/mm3 (range 2-2650). Through 48 weeks of therapy, the overall proportion of patients who achieved and sustained an HIV-1 RNA < 400 copies/mL was 86%, and < 50 copies/mL was 73%. The mean increase from baseline in CD4+ cell count was 232 cells/mm3 (-945, +1512). The adverse reaction profile observed during these clinical trials was similar to that of adult patients, with the exception of the occurrence of anemia and higher frequency of hyperpigmentation in children [See ADVERSE REACTIONS].
The pharmacokinetics of emtricitabine were studied in 20 neonates born to HIV-1-positive mothers. Each mother received prenatal and intrapartum combination antiretroviral therapy. Neonates received up to 6 weeks of zidovudine prophylactically after birth. The neonates were administered two short courses of emtricitabine oral solution (each 3 mg/kg once daily x 4 days) during the first 3 months of life. Emtricitabine exposures in neonates were similar to the exposures achieved in patients > 3 months to 17 years [See CLINICAL PHARMACOLOGY]. During the two short dosing periods on emtricitabine there were no safety issues identified in the treated neonates.
All neonates were HIV-1 negative at the end of the study; the efficacy of emtricitabine in preventing or treating HIV-1 could not be determined.
Last updated on RxList: 7/7/2008
EMTRIVA®
(em-treev'-ah) capsules
EMTRIVA oral solution
Generic name: emtricitabine (em tri SIT uh bean)
Read the Patient Information that comes with EMTRIVA before you start using it and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. You should stay under a healthcare provider's care when taking EMTRIVA. Do not change or stop your medicine without first talking with your healthcare provider. Talk to your healthcare provider or pharmacist if you have any questions about EMTRIVA.
What is the most important information I should know about EMTRIVA?
Patients with HBV infection, who take EMTRIVA and then stop it, may get "flare-ups" of their hepatitis. A "flare-up" is when the disease suddenly returns in a worse way than before.
What is EMTRIVA?
EMTRIVA is a type of medicine called an HIV-1 (human immunodeficiency virus) nucleoside reverse transcriptase inhibitor (NRTI). EMTRIVA is always used with other anti-HIV-1 medicines to treat people with HIV-1 infection. EMTRIVA is for adults and children, but has not been studied fully in adults over age 65.
HIV infection destroys CD4+ T cells, which are important to the immune system. The immune system helps fight infection. After a large number of T cells are destroyed, acquired immune deficiency syndrome (AIDS) develops. EMTRIVA helps to block HIV-1 reverse transcriptase, a chemical in your body (enzyme) that is needed for HIV-1 to multiply. EMTRIVA may lower the amount of HIV-1 in the blood (viral load). EMTRIVA may also help to increase the number of T cells called CD4+ cells. Lowering the amount of HIV-1 in the blood lowers the chance of death or infections that happen when your immune system is weak (opportunistic infections).
EMTRIVA does not cure HIV-1 infection or AIDS. The long-term effects of EMTRIVA are not known at this time. People taking EMTRIVA may still get opportunistic infections or other conditions that happen with HIV-1 infection. Opportunistic infections are infections that develop because the immune system is weak. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections. It is very important that you see your healthcare provider regularly while taking EMTRIVA.
EMTRIVA does not lower your chance of passing HIV-1 to other people through sexual contact, sharing needles, or being exposed to your blood. For your health and the health of others, it is important to always practice safer sex by using a latex or polyurethane condom or other barrier to lower the chance of sexual contact with semen, vaginal secretions, or blood. Never use or share dirty needles.
Who should not take EMTRIVA?
What should I tell my healthcare provider before taking EMTRIVA?
Tell your healthcare provider
How should I take EMTRIVA?
What should I avoid while taking EMTRIVA?
What are the possible side effects of EMTRIVA?
EMTRIVA may cause the following serious side effects (See "What is the most important information I should know about EMTRIVA?"):
Other side effects with EMTRIVA when used with other anti-HIV-1 medicines Include:
The most common side effects of EMTRIVA used with other anti-HIV-1 medicines are headache, diarrhea, and nausea. Other side effects include allergic reaction, dizziness, sleeping problems, abnormal dreams, vomiting, indigestion, stomach pain, pain, weakness and rash. Skin discoloration may also happen with EMTRIVA.
There have been other side effects in patients taking EMTRIVA. However, these side effects may have been due to other medicines that patients were taking or to HIV-1 itself. Some of these side effects can be serious.
This list of side effects is not complete. If you have questions about side effects, ask your healthcare provider or pharmacist. You should report any new or continuing symptoms to your healthcare provider right away. Your healthcare provider may be able to help you manage these side effects.
How do I store EMTRIVA?
General information about EMTRIVA:
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use EMTRIVA for a condition for which it was not prescribed. Do not give EMTRIVA to other people, even if they have the same symptoms you have. It may harm them. This leaflet summarizes the most important information about EMTRIVA. If you would like more information, talk with your doctor. You can ask your healthcare provider or pharmacist for information about EMTRIVA that is written for health professionals. For more information, you may also call 1-800-GILEAD5.
What are the ingredients of EMTRIVA?
Active Ingredient: emtricitabine
Inactive Ingredients for EMTRIVA capsules: crospovidone, magnesium stearate, microcrystalline cellulose, and povidone.
Inactive Ingredients for EMTRIVA oral solution: Cotton candy flavor, FD&C yellow No. 6, edetate disodium, methylparaben and propylparaben, sodium phosphate (monobasic), propylene glycol, water, and xylitol. Sodium hydroxide and hydrochloric acid may be used to adjust pH.
Last updated on RxList: 7/7/2008
IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.
EMTRICITABINE - ORAL
(em-tri-SITE-ah-bean)
COMMON BRAND NAME(S): Emtriva
WARNING: Rarely, emtricitabine has caused a severe (sometimes fatal) liver and blood problem (lactic acidosis). Immediately tell your doctor if you develop symptoms of liver problems: persistent nausea, stomach/abdominal pain, dark urine, yellowing eyes/skin, or if you develop symptoms of lactic acidosis: rapid breathing, drowsiness, muscle aches.
This medication is not approved for the treatment of hepatitis B virus infection. If you have hepatitis B infection along with HIV, your hepatitis symptoms may get worse or become very serious if you stop taking emtricitabine. Talk with your doctor before stopping this medication. Your doctor will perform liver function tests for several months after you stop emtricitabine. Tell your doctor immediately if you develop symptoms of worsening liver problems.
USES: This drug, used in combination with other medications, helps to control your HIV infection, thereby improving your quality of life. It also lowers your risk of getting HIV complications (e.g., new infections, cancer). Emtricitabine belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors.
Emtricitabine is not a cure for HIV and it does not prevent the spread of HIV to others through sexual contact or blood contamination (e.g., sharing used needles).
HOW TO USE: This medicine comes with a Patient Information Leaflet. Read it carefully. Ask your doctor, nurse, or pharmacist any questions that you may have about this medicine.
Take this medication by mouth with or without food, usually once daily or as directed by your doctor.
Dosage is based on your weight, kidney function, medical condition, and response to therapy.
It is very important to continue taking this medication (and other anti-HIV medications) exactly as prescribed by your doctor.
This medication works best when the amount of drug in your body is kept at a constant level. Therefore, take this drug at evenly spaced intervals. To help you remember, use it at the same time(s) each day.
Do not take more or less of this drug than prescribed or stop taking it (or other HIV medicines) even for a short time unless directed to do so by your doctor. Skipping or changing your dose without approval from your doctor may cause the amount of virus to increase, make the infection more difficult to treat (resistant), or worsen side effects.
Headache, nausea, diarrhea, stomach pain, trouble sleeping, darkening skin color on palms of hands and soles of feet, cough, loss of appetite, dizziness, or runny nose may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes (depression), tingling/numbness of hands or feet.
Use of this drug may increase your risk of pancreatitis. Tell your doctor immediately if any of these rare but very serious side effects occur: stomach/back pain with or without nausea/vomiting.
Changes in body fat may occur while you are taking this medication (e.g., increased fat in the upper back and stomach areas, decreased fat in the arms and legs). The cause and long-term effects of these changes are unknown. Discuss the risks and benefits of therapy with your doctor, as well as the possible role of exercise to reduce this side effect.
If you are taking HIV medications for the first time, you may experience symptoms of an old infection. This may happen as your immune system begins to work better. Symptoms may include: new cough, trouble breathing, fever, new vision problems, new headaches, new skin problems.
Contact your doctor immediately.
A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking emtricitabine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.
Before using this medication, tell your doctor or pharmacist your medical history, especially of: pancreatitis with other HIV medicines, kidney problems, liver problems, hepatitis B, alcohol use.
This drug may make you dizzy or drowsy; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.
Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug.
This medication should be used only when clearly needed during pregnancy. However, it is now normal to prescribe HIV medicines for pregnant women with HIV. This has been shown to decrease the risk of giving HIV to the baby. Emtricitabine may be part of that treatment. Discuss the risks and benefits with your doctor.
It is not known if this medication passes into breast milk. Because breast milk can transmit HIV, do not breast-feed.
Lamivudine is similar to emtricitabine and should not be taken with this medication.
Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.
Check the labels on all your medicines for HIV infection because they may contain the same ingredients as found in this product. Taking too much of these drugs will not necessarily improve your condition, and may cause more side effects.
This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.
NOTES: To reduce the risk of spreading HIV to others, always use effective barrier protections (e.g., latex or polyurethane condoms, dental dams) during all sexual activity. Consult your doctor or pharmacist for more details.
Do not share this medication with others.
Laboratory and/or medical tests (e.g., liver tests, viral load, T-cell counts) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.
Keep all medical and laboratory appointments.
MISSED DOSE: If you miss a dose, take the missed dose as soon as you remember unless it is less than 2 hours before the time for your next dose. In that case, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.
STORAGE: Store emtricitabine capsules at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Store emtricitabine oral solution in the refrigerator at 36-46 degrees F (2-8 degrees C). Do not freeze. Emtricitabine solution may also be stored at room temperature at 77 degrees F (25 degrees C) with brief storage between 59-86 degrees F (15-30 degrees C), but in this case it must be used within 3 months. Keep all medicines away from children and pets.
Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).
Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.
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