VIREAD (tenofovir disoproxil fumarate) Tablets
WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including VIREAD, in combination with other antiretrovirals (See Warnings and Precautions).
- Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including VIREAD. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VIREAD. If appropriate, resumption of anti-hepatitis B therapy may be warranted (See Warnings and Precautions).
INDICATIONS AND USAGE: VIREAD is indicated for the treatment of chronic hepatitis B in adults. The following points should be considered when initiating therapy with VIREAD for the treatment of HBV infection:
- This indication is based primarily on data from treatment of nucleoside-treatment-na’i’ve subjects and a smaller number of subjects who had previously received lamivudine or adefovir. Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease.
- The numbers of subjects in clinical trials who had lamivudine- or adefovir-associated substitutions at baseline were too small to reach conclusions of efficacy.
- VIREAD has not been evaluated in patients with decompensated liver disease.
DOSAGE AND ADMINISTRATION: For the treatment of chronic hepatitis B, the dose of VIREAD is 300 mg once daily taken orally, without regard to food. The optimal duration of treatment is unknown. Dose Adjustment for Renal Impairment: Significantly increased drug exposures occurred when VIREAD was administered to subjects with moderate to severe renal impairment. Therefore, the dosing interval of VIREAD should be adjusted in patients with baseline creatinine clearance <50 mL/min using the recommendations in Table 1. These dosing interval recommendations are based on modeling of single-dose pharmacokinetic data in non-HIV and non-HBV infected subjects with varying degrees of renal impairment, including end-stage renal disease requiring hemodialysis. The safety and effectiveness of these dosing interval adjustment recommendations have not been clinically evaluated in patients with moderate or severe renal impairment, therefore clinical response to treatment and renal function should be closely monitored in these patients (See Warnings and Precautions). No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50-80 mL/min). Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in patients with mild renal impairment (See Warnings and Precautions).
The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance <10 mL/min; therefore, no dosing recommendation is available for these patients.
Table 1 Dosage Adjustment for Patients with Altered Creatinine Clearance
|Creatinine Clearance (mL/min)a||
|Recommended 300 mg Dosing Interval||Every 24 hours||Every 48 hours||Every 72 to 96 hours||Every 7 days or after a total of approximately 12 hours of dialysisb|