Nucleoside Reverse Transcriptase Inhibitors

Dosage adjustment in hepatic impairment:
The recommended dose of abacavir tablets in patients with mild hepatic impairment (Child-Pugh score 5 to 6) is 200 mg twice daily. To enable dose reduction, abacavir sulfate oral solution (10 mL twice daily) should be used for the treatment of these patients. The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate to severe hepatic impairment; therefore, abacavir tablets are contraindicated in these patients.

SUPPLIED:
Solution, oral: 20 mg/mL (240 mL)
Tablet: 300 mg

Adults and pediatric patients 12 years of age and older with body weight at least 40 kg
(at least 88 lbs): The dose of ATRIPLA is one tablet once daily taken orally on an empty stomach. Dosing at bedtime may improve the tolerability of nervous system symptoms.

Renal Impairment: Because ATRIPLA is a fixed-dose combination, it should not be prescribed for patients requiring dosage adjustment such as those with moderate or severe renal impairment (estimated creatinine clearance below 50 mL/min).

Rifampin Coadministration: When ATRIPLA is administered with rifampin to patients weighing 50 kg or more, an additional 200 mg/day of efavirenz is recommended

DOSAGE FORMS AND STRENGTHS
ATRIPLA is available as tablets. Each tablet contains 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (tenofovir DF, which is equivalent to 245 mg of tenofovir disoproxil). The tablets are pink, capsule-shaped, film-coated, debossed with "123" on one side and plain-faced on the other side.

Adults and Adolescents Weighing ≥30 kg
The recommended oral dose of COMBIVIR in HIV-1-infected adults and adolescents weighing greater than or equal to 30 kg is 1 tablet (containing 150 mg of lamivudine and 300 mg of zidovudine) twice daily.

Pediatric Patients
The recommended oral dosage of scored COMBIVIR Tablets for pediatric patients who weigh greater than or equal to 30 kg and for whom a solid oral dosage form is appropriate is 1 tablet administered twice daily.

Before prescribing COMBIVIR Tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a COMBIVIR Tablet, the liquid oral formulations should be prescribed: EPIVIR® (lamivudine) Oral Solution and RETROVIR® (zidovudine) Syrup.

Patients Requiring Dosage Adjustment
Because COMBIVIR is a fixed-dose combination tablet, it should not be prescribed for pediatric patients weighing less than 30 kg or patients requiring dosage adjustment, such as those with reduced renal function (creatinine clearance less than 50 mL/min), patients with hepatic impairment, or patients experiencing dose-limiting adverse reactions. Liquid and solid oral formulations of the individual components of COMBIVIR are available for these populations.

DOSAGE FORMS AND STRENGTHS
COMBIVIR Tablets contain 150 mg of lamivudine and 300 mg of zidovudine. The tablets are white, scored, film-coated, modified capsule-shaped tablets, debossed on both tablet faces, such that when broken in half, the full “GX FC3” code is present on both halves of the tablet (“GX” on one face and “FC3” on the opposite face of the tablet).

Patient weight <60 kg: (Tablets): 125 mg orally twice daily or 250mg once daily or 167 mg (Buffered powder) twice daily. Patient weight > 60kg: (Tablets): 200mg orally twice daily or 400mg orally once daily. (Buffered Powder): 250mg orally twice daily.

Supplied: chewable tablet: (25, 50, 100, 150, and 200mg); Oral powder for solution (100, 167, and 200mg packets).

Renal Dosing:

DOSAGE AND ADMINISTRATION

Recommended Dose
EMTRIVA may be taken without regard to food.

Adult Patients (18 years of age and older)
EMTRIVA capsules: one 200 mg capsule administered once daily orally.
EMTRIVA oral solution: 240 mg (24 mL) administered once daily orally.

Pediatric Patients (0-3 months of age)
EMTRIVA oral solution: 3 mg per kg administered once daily orally.

Pediatric Patients (3 months through 17 years)
EMTRIVA oral solution: 6 mg per kg up to a maximum of 240 mg (24 mL) administered once daily orally.
EMTRIVA capsules: for children weighing more than 33 kg who can swallow an intact capsule, one 200 mg capsule administered once daily orally.

Dose Adjustment in Adult Patients with Renal Impairment
Significantly increased drug exposures were seen when EMTRIVA was administered to subjects with renal impairment [See package insert Clinical Pharmacology (12.3)]. Therefore, the dosing interval or dose of EMTRIVA should be adjusted in patients with baseline creatinine clearance less than 50 mL per 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 Creatinine Clearance (mL/min):

*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.

DOSAGE FORMS AND STRENGTHS
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.

CONTRAINDICATIONS
EMTRIVA is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the products.

Lamivudine is a synthetic nucleoside analogue. Intracellularly lamivudine is phosphorylated to its active 5'-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue. CBV-TP and 3TC-TP are weak inhibitors of cellular DNA polymerases α, β, and γ.

Dosing (Adults):  One tablet (abacavir 600 mg and lamivudine 300 mg) once daily.

Renal Dosing: crcl <50 ml/min: Use not recommended.
Hepatic Impairment: Use not recommended.

Supplied: Tablet: Abacavir 600 mg & lamivudine 300 mg

Dosing (Adults): 
Note: The formulation and dosage of Epivir-HBV® are not appropriate for patients infected with both HBV and HIV. Use with at least two other antiretroviral agents when treating HIV

Prevention of HIV following needlesticks (unlabeled use): 150 mg twice daily (with zidovudine with or without a protease inhibitor, depending on risk)

HIV: 150 mg twice daily or 300 mg once daily; <50 kg: 2 mg/kg twice daily

Treatment of hepatitis B (Epivir-HBV®): 100 mg/day

Dosing interval in renal impairment in patients >16 years for HIV:
Clcr 30-49 mL/minute: Administer 150 mg once daily
Clcr 15-29 mL/minute: Administer 150 mg first dose, then 100 mg once daily
Clcr 5-14 mL/minute: Administer 150 mg first dose, then 50 mg once daily
Clcr<5 mL/minute: Administer 50 mg first dose, then 25 mg once daily

Dosing interval in renal impairment in adult patients with hepatitis B:
Clcr 30-49: Administer 100 mg first dose then 50 mg once daily
Clcr 15-29: Administer 100 mg first dose then 25 mg once daily
Clcr 5-14: Administer 35 mg first dose then 15 mg once daily
Clcr<5: Administer 35 mg first dose then 10 mg once daily

Dialysis: Negligible amounts are removed by 4-hour hemodialysis or peritoneal dialysis. Supplemental dosing is not required.

SUPPLIED:
Solution, oral:
Epivir®: 10 mg/mL (240 mL) [strawberry-banana flavor]
Epivir-HBV®: 5 mg/mL (240 mL) [strawberry-banana flavor]

Tablet:
Epivir®: 150 mg, 300 mg
Epivir-HBV®: 100 mg

Supplied: [15, 20, 30, 40mg capsules; 1 mg/ml oral powder for solution].

Renal Dosing:

Renal Dosing:
crcl 30-49 ml/min: 300 mg every 48 hours
crcl 10-29 ml/min: 300 mg twice weekly
crcl <10 ml/min: No recommendation available.
Hemodialysis: 300 mg every 7 days or after a total of 12 hours of dialysis (usually once weekly assuming 3 dialysis sessions lasting about 4 hours each).

Supplied: Tablet: 300 mg

TRIZIVIR can be taken with or without food.

Adults and Adolescent Patients
The recommended oral dose of TRIZIVIR is one tablet twice daily.

TRIZIVIR is not recommended in adolescents who weigh less than 40 kg because it is a fixed-dose tablet and cannot be dose adjusted.

Dosage Adjustment
Because it is a fixed-dose combination, TRIZIVIR should not be prescribed for:

•patients requiring dosage adjustment such as those with creatinine clearance <50 mL/min.
•patients with hepatic impairment.

Supplied:
Tablet [film coated]: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg

Recommended Dose for Treatment of HIV-1 Infection
The recommended dose of TRUVADA in adults and in pediatric patients 12 years of age and older with body weight greater than or equal to 35 kg (greater than or equal to 77 lb) is one tablet (containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) once daily taken orally with or without food.

Recommended Dose for Pre-exposure Prophylaxis
The dose of TRUVADA in HIV-1 uninfected adults is one tablet (containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) once daily taken orally with or without food.

Dose Adjustment for Renal Impairment
Treatment of HIV-1 Infection

Significantly increased drug exposures occurred when EMTRIVA or VIREAD were administered to subjects with moderate to severe renal impairment [See EMTRIVA or VIREAD Package Insert]. Therefore, adjust the dosing interval of TRUVADA in HIV-1 infected adult patients with baseline creatinine clearance 30-49 mL/min using the recommendations in Table 1. These dosing interval recommendations are based on modeling of single-dose pharmacokinetic data in non-HIV infected subjects. The safety and effectiveness of these dosing interval adjustment recommendations have not been clinically evaluated in patients with moderate renal impairment, therefore clinical response to treatment and renal function should be closely monitored in these patients [See package insert Warnings and Precautions (5.3)].

No dose adjustment is necessary for HIV-1 infected patients with mild renal impairment (creatinine clearance 50–80 mL/min). No data are available to make dose recommendations in pediatric patients with renal impairment.

 Table 1 Dosage Adjustment for HIV-1 Infected Adult Patients with Altered Creatinine Clearance

*Calculated using ideal (lean) body weight

 Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in all individuals with mild renal impairment [See Warnings and Precautions (5.3)].

Pre-exposure Prophylaxis
Do not use TRUVADA for a PrEP indication in HIV-1 uninfected individuals with estimated creatinine clearance below 60 mL/min.

Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in all individuals with mild renal impairment. If a decrease in estimated creatinine clearance is observed in uninfected individuals while using TRUVADA for PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use.

DOSAGE FORMS AND STRENGTHS
TRUVADA is available as tablets. Each tablet contains 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil). The tablets are blue, capsule-shaped, film-coated, debossed with "GILEAD" on one side and with "701" on the other side.

Renal Dosing:
>40/ no change; 10-40/ 0.75 mg twice daily;
<10/ 0.75 mg once daily.

Supplied: [0.375mg , 0.75mg tablet]

During labor and delivery, administer zidovudine I.V. at 2 mg/kg over 1 hour followed by a continuous I.V. infusion of 1 mg/kg/hour until the umbilical cord is clamped

HIV infection:  (ADULTS):
Oral: 300 mg twice daily or 200 mg 3 times/day

I.V.: 1-2 mg/kg/dose (infused over 1 hour) administered every 4 hours around-the-clock (6 doses/day)

Prevention of HIV following needlesticks (unlabeled use): 200 mg 3 times/day plus lamivudine 150 mg twice daily; a protease inhibitor (eg, indinavir) may be added for high risk exposures; begin therapy within 2 hours of exposure if possible

Patients should receive I.V. therapy only until oral therapy can be administered

Dosing interval in renal impairment: Clcr<10 mL/minute: May require minor dose adjustment

Hemodialysis: At least partially removed by hemo- and peritoneal dialysis; administer dose after hemodialysis or administer 100 mg supplemental dose; during CAPD, dose as for Clcr<10 mL/minute

Continuous arteriovenous or venovenous hemodiafiltration effects: Administer 100 mg every 8 hours

Dosing adjustment in hepatic impairment: Reduce dose by 50% or double dosing interval in patients with cirrhosis

Supplied:
Capsule: 100 mg
Injection, solution: 10 mg/mL (20 mL)
Syrup: 50 mg/5 mL (240 mL)
Tablet: 300 mg