HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ISENTRESS safely and effectively. See full prescribing information for ISENTRESS. ATTENTION PHARMACIST: Detach “Patient’s Instructions for Use” from package insert and dispense with the product.
TRUVADA is a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate. TRUVADA- emtricitabine and tenofovir disoproxil fumarate tablet, film coated. HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use VIRAMUNE safely and effectively. See full prescribing information for VIRAMUNE. TRUVADA safely and effectively. See full prescribing information for TRUVADA. VIREAD Package Insert. Therefore, the dosing interval of TRUVADA should be. FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1Overview 2.2 Dosage of REYATAZ in Adult Patients 2.3 Dosage of REYATAZ Capsules in Pediatric Patients. The purpose of this site is to make the package inserts for South African medicines available to the public in electronic. NDC 0049-3420-41 Unit dose package of 100. DIFLUCAN 150 mg Tablets: Engraved with 'DIFLUCAN' and '150' on the front and 'ROERIG' on the back. NDC 0049-3500-79 Unit dose package of 1. Gilead Sciences, Inc: TRUVADA is a combination of EMTRIVA and VIREAD, both nucleoside analog HIV-1 reverse transcriptase inhibitors. TRUVADA is indicated in.
Daily. Med - TRUVADA - emtricitabine and tenofovir disoproxil fumarate tablet, film coated. For additional information on Mechanism of Action, Antiviral Activity, Resistance and Cross Resistance, please consult the EMTRIVA and VIREAD prescribing information. TRUVADA is a fixed- dose combination of antiviral drugs emtricitabine and tenofovir disoproxil fumarate . Following oral administration of EMTRIVA, emtricitabine is rapidly absorbed with peak plasma concentrations occurring at 1. Less than 4% of emtricitabine binds to human plasma proteins in vitro and the binding is independent of concentration over the range of 0.
Following administration of radiolabelled emtricitabine, approximately 8. The metabolites of emtricitabine include 3'- sulfoxide diastereomers and their glucuronic acid conjugate. Emtricitabine is eliminated by a combination of glomerular filtration and active tubular secretion. Following a single oral dose of EMTRIVA, the plasma emtricitabine half- life is approximately 1. Tenofovir Disoproxil Fumarate: The pharmacokinetic properties of tenofovir disoproxil fumarate are summarized in Table 6. Following oral administration of VIREAD, maximum tenofovir serum concentrations are achieved in 1.
Less than 0. 7% of tenofovir binds to human plasma proteins in vitro and the binding is independent of concentration over the range of 0. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. Following a single oral dose of VIREAD, the terminal elimination half- life of tenofovir is approximately 1.
Effects of Food on Oral Absorption. TRUVADA may be administered with or without food. Administration of TRUVADA following a high fat meal (7. Cmax by approximately 0. The mean increases in tenofovir AUC and Cmax were approximately 3.
In previous safety and efficacy trials, VIREAD (tenofovir) was taken under fed conditions. Emtricitabine systemic exposures (AUC and Cmax) were unaffected when TRUVADA was administered with either a high fat or a light meal. Special Populations. Race. Emtricitabine: No pharmacokinetic differences due to race have been identified following the administration of EMTRIVA. Tenofovir Disoproxil Fumarate: There were insufficient numbers from racial and ethnic groups other than Caucasian to adequately determine potential pharmacokinetic differences among these populations following the administration of VIREAD. Gender. Emtricitabine and Tenofovir Disoproxil Fumarate: Emtricitabine and tenofovir pharmacokinetics are similar in male and female subjects.
Pediatric Patients. TRUVADA should not be administered to HIV- 1 infected pediatric patients less than 1. Emtricitabine: The pharmacokinetics of emtricitabine at steady state were determined in 2.
HIV- 1- infected pediatric subjects 1. EMTRIVA capsule. Exposures achieved in pediatric subjects 1.
Tenofovir Disoproxil Fumarate: Steady- state pharmacokinetics of tenofovir were evaluated in 8 HIV- 1 infected pediatric subjects (1. Tenofovir exposure achieved in these pediatric subjects receiving oral daily doses of VIREAD 3. VIREAD 3. 00 mg. Geriatric Patients. Pharmacokinetics of emtricitabine and tenofovir have not been fully evaluated in the elderly (6.
Patients with Impaired Renal Function. The pharmacokinetics of emtricitabine and tenofovir are altered in subjects with renal impairment . In adult subjects with creatinine clearance below 5. L/min, Cmax, and AUC0. It is recommended that the dosing interval for TRUVADA be modified in HIV- infected adult patients with creatinine clearance 3. No data are available to make dose recommendations in pediatric patients with renal impairment. TRUVADA should not be used in patients with creatinine clearance below 3.
L/min and in patients with end- stage renal disease requiring dialysis . If a decrease in creatinine clearance is observed in uninfected individuals while using TRUVADA for Pr. EP, evaluate potential causes and re- assess potential risks and benefits of continued use . There were no substantial alterations in tenofovir pharmacokinetics in subjects with hepatic impairment compared with unimpaired subjects. The pharmacokinetics of TRUVADA or emtricitabine have not been studied in subjects with hepatic impairment; however, emtricitabine is not significantly metabolized by liver enzymes, so the impact of liver impairment should be limited.
Assessment of Drug Interactions. The steady state pharmacokinetics of emtricitabine and tenofovir were unaffected when emtricitabine and tenofovir disoproxil fumarate were administered together versus each agent dosed alone. In vitro studies and clinical pharmacokinetic drug- drug interaction trials have shown that the potential for CYP mediated interactions involving emtricitabine and tenofovir with other medicinal products is low.
No clinically significant drug interactions have been observed between emtricitabine and famciclovir, indinavir, stavudine, tenofovir disoproxil fumarate, and zidovudine (see Tables 7 and 8). Similarly, no clinically significant drug interactions have been observed between tenofovir disoproxil fumarate and abacavir, efavirenz, emtricitabine, entecavir, indinavir, lamivudine, lopinavir/ritonavir, methadone, nelfinavir, oral contraceptives, ribavirin, saquinavir/ritonavir, and tacrolimus in trials conducted in healthy volunteers (see Tables 9 and 1. Following multiple dosing to HIV- negative subjects receiving either chronic methadone maintenance therapy or oral contraceptives, or single doses of ribavirin, steady state tenofovir pharmacokinetics were similar to those observed in previous trials, indicating lack of clinically significant drug interactions between these agents and VIREAD. Coadministration of tenofovir disoproxil fumarate with didanosine results in changes in the pharmacokinetics of didanosine that may be of clinical significance. Table 1. 1 summarizes the effects of tenofovir disoproxil fumarate on the pharmacokinetics of didanosine. Concomitant dosing of tenofovir disoproxil fumarate with didanosine buffered tablets or enteric- coated capsules significantly increases the Cmax and AUC of didanosine.
When didanosine 2. The mechanism of this interaction is unknown. See Drug Interactions (7.
VIREAD. 1. 92. 02. Mechanism of Action.
Emtricitabine: 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 (RT) 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 . Tenofovir disoproxil fumarate requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate inhibits the activity of HIV- 1 RT by competing with the natural substrate deoxyadenosine 5'- triphosphate and, after incorporation into DNA, by DNA chain termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases . The 5. 0% effective concentration (EC5. In drug combination studies of emtricitabine with nucleoside reverse transcriptase inhibitors (abacavir, lamivudine, stavudine, 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 (EC5.
The EC5. 0 values for tenofovir were in the range of 0. In drug combination studies of tenofovir with nucleoside reverse transcriptase inhibitors (abacavir, didanosine, lamivudine, stavudine, zalcitabine, zidovudine), non- nucleoside reverse transcriptase inhibitors (delavirdine, efavirenz, nevirapine), and protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir, saquinavir), additive to synergistic effects were observed. Tenofovir displayed antiviral activity in cell culture against HIV- 1 clades A, B, C, D, E, F, G and O (EC5. Of the 1. 8 control animals, 1. In contrast, 4 of the 6 animals treated daily with oral FTC and TDF remained uninfected and the two infections that did occur were significantly delayed until 9 and 1. An M1. 84. I- expressing FTC- resistant variant emerged in 1 of the 2 macaques after 3 weeks of continued drug exposure. Resistance. Emtricitabine and Tenofovir Disoproxil Fumarate: HIV- 1 isolates with reduced susceptibility to the combination of emtricitabine and tenofovir have been selected in cell culture.
Genotypic analysis of these isolates identified the M1. V/I and/or K6. 5R amino acid substitutions in the viral RT. In a clinical trial of treatment- naive subjects . Development of efavirenz resistance- associated substitutions occurred most frequently and was similar between the treatment arms. The M1. 84. V amino acid substitution, associated with resistance to EMTRIVA and lamivudine, was observed in 2/1. EMTRIVA + VIREAD group and in 1.
Through 1. 44 weeks of Study 9. K6. 5R substitution in their HIV- 1 as analyzed through standard genotypic analysis. Emtricitabine: 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 RT gene at codon 1. M1. 84. V/I). Tenofovir Disoproxil Fumarate: HIV- 1 isolates with reduced susceptibility to tenofovir have been selected in cell culture. These viruses expressed a K6.
R substitution in RT and showed a 2. In treatment- experienced subjects, 1. VIREAD through Week 9.
Genotypic analysis of the resistant isolates showed a substitution in the HIV- 1 RT gene resulting in the K6. R amino acid substitution. Pr. Ex Trial: In a clinical study of HIV- 1 seronegative subjects .