Tenofovir Disoproxil Fumarate

TENOFOVIR DISOPROXIL FUMARATE- tenofovir disoproxil fumarate tablet, coated
Apotex Corp.

WARNING: POSTTREATMENT EXACERBATION OF HEPATITIS

Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including tenofovir disoproxil fumarate tablets. 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 tenofovir disoproxil fumarate. If appropriate, resumption of anti-hepatitis B therapy may be warranted [See Warnings and Precautions (5.1)] .

1 INDICATIONS AND USAGE

1.1 HIV-1 Infection

Tenofovir disoproxil fumarate tablets are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older.

The following points should be considered when initiating therapy with tenofovir disoproxil fumarate tablets for the treatment of HIV-1 infection:

  • Tenofovir disoproxil fumarate tablets should not be used in combination with ATRIPLA ®, COMPLERA ®, DESCOVY ®, GENVOYA ®, ODEFSEY ®, STRIBILD ®, TRUVADA ®, or VEMLIDY ® [See Warnings and Precautions (5.4)] .Tenofovir disoproxil fumarate tablets should not be used in combination with ATRIPLA ®, COMPLERA ®, DESCOVY ®, GENVOYA ®, ODEFSEY ®, STRIBILD ®, TRUVADA ®, or VEMLIDY ® [See Warnings and Precautions (5.4)] .

1.2 Chronic Hepatitis B

Tenofovir disoproxil fumarate tablets are indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older .

The following points should be considered when initiating therapy with tenofovir disoproxil fumarate tablets for the treatment of HBV infection:

  • The indication in adults is based on safety and efficacy data from treatment of subjects who were nucleoside-treatment-naïve and subjects who were treatment-experienced with documented resistance to lamivudine. Subjects were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease [See Clinical Studies (14.2)].
  • Tenofovir disoproxil fumarate tablets were evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease [See Adverse Reactions (6.1), Clinical Studies (14.2)] .
  • The numbers of subjects in clinical trials who had adefovir resistance-associated substitutions at baseline were too small to reach conclusions of efficacy [See Microbiology (12.4), Clinical Studies (14.2)].

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose in Adults and Pediatric Patients 12 Years of Age and Older (35 kg or more)

For the treatment of HIV-1 or chronic hepatitis B: The dose is one 300 mg tenofovir disoproxil fumarate tablet once daily taken orally, without regard to food.

In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown. Safety and efficacy in pediatric patients with chronic hepatitis B weighing less than 35 kg have not been established.

2.2 Recommended Dose in Pediatric Patients 2 Years to Less than 12 Years of Age

HIV-1 Infection

For the treatment of HIV-1 in pediatric patients 2 years of age and older, the recommended oral dose of tenofovir disoproxil fumarate tablets is 8 mg of tenofovir disoproxil fumarate (tenofovir DF) per kilogram of body weight (up to a maximum of 300 mg) once daily administered as tablets.

Tenofovir disoproxil fumarate tablets are available as tablets in 300 mg strength for pediatric patients who weigh greater than or equal to 35 kg and who are able to reliably swallow intact tablets. The dose is one tablet once daily taken orally, without regard to food.

Table 2 contains dosing recommendations for tenofovir disoproxil fumarate tablets based on body weight. Weight should be monitored periodically and the tenofovir disoproxil fumarate tablets dose adjusted accordingly.

Table 2 Dosing Recommendations for Pediatric Patients ≥2 Years of Age and Weighing ≥35 kg Using tenofovir disoproxil fumarate tablets
Body Weight Kilogram (kg) Tablets Once Daily
≥35 300 mg

Chronic Hepatitis B

Safety and efficacy of tenofovir disoproxil fumarate tablets in patients younger than 12 years of age have not been established.

2.3 Dose Adjustment for Renal Impairment in Adults

Significantly increased drug exposures occurred when tenofovir disoproxil fumarate tablets were administered to subjects with moderate to severe renal impairment [See Clinical Pharmacology (12.3)] . Therefore, the dosing interval of tenofovir disoproxil fumarate tablets 300 mg should be adjusted in patients with baseline creatinine clearance below 50 mL/min using the recommendations in Table 3. 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 (5.2)] .

No dose adjustment of tenofovir disoproxil fumarate tablets 300 mg is necessary for patients with mild renal impairment (creatinine clearance 50-80 mL/min). Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in patients with mild renal impairment [See Warnings and Precautions (5.2)] .

Table 3 Dosage Adjustment for Patients with Altered Creatinine Clearance
Creatinine Clearance (mL/min) *
≥50 30-49 10-29 Hemodialysis Patients
*
Calculated using ideal (lean) body weight.
Generally once weekly assuming three hemodialysis sessions a week of approximately 4 hours’ duration. Tenofovir disoproxil fumarate tablets should be administered following completion of dialysis.
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 dialysis

The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance below 10 mL/min; therefore, no dosing recommendation is available for these patients.

No data are available to make dose recommendations in pediatric patients with renal impairment.

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