Tenofovir Label Extended to Pediatric Indication

On 18 January 2012, the FDA extended the product indication for tenofovir disoproxil fumarate (Viread) to include dosing information in paediatric patients 2 to less than 18 years of age.

An oral powder (40 mg per 1 gram of oral powder) formulation and 150 mg, 200 mg and 250 mg tablets were also approved to support dosing in paediatric patients.

The major changes to the product labeling include information on dosing plus efficacy and safety concerns based on clinical studies.

These include:

Dosing

• Recommended dose in paediatric patients 2 years of age and older is 8 mg of tenofovir DF per kilogram of body weight (up to a maximum of 300 mg) once daily administered as oral powder or tablets. Tables 1 and 2 of the product labeling contain dosing recommendations for tenofovir oral powder and tablets based on body weight. Weight should be monitored periodically and the tenofovir dose adjusted accordingly.
• Tenofovir oral powder should be measured only with the supplied dosing scoop. One level scoop delivers 1 g of powder, which contains 40 mg of tenofovir DF. Tenofovir oral powder should be mixed in a container with 2 to 4 ounces of soft food not requiring chewing (e.g., applesauce, baby food, yogurt). The entire mixture should be ingested immediately to avoid a bitter taste. Do not administer tenofovir oral powder in a liquid as the powder may float on top of the liquid even after stirring. Further patient instructions on how to administer tenofovir oral powder with the supplied dosing scoop are provided in the FDA-approved patient labeling.
• Tenofovir is also available as tablets in 150, 200, 250 and 300 mg strengths for paediatric patients who weigh >/=17 kg and who are able to reliably swallow intact tablets. The dose is one tablet once daily taken orally, without regard to food.
• There are no data to recommend use of tenofovir tablets 150, 200 or 250 mg or tenofovir oral powder in patients with renal impairment.

Safety and Efficacy

The safety and efficacy data of tenofovir in paediatric patients is supported by data from two randomised trials (Studies 352 and 321). This involved only 184 treatment-experienced children (aged 2 to <18 years), only half of who received tenofovir and half received d4T or AZT. Tenofovir was later provided to these children.

Bone Mineral Density (BMD)

Bone effects were similar to those observed in adult subjects. Under normal circumstances BMD increases rapidly in paediatric patients. In Study 352 (2 to less than 12 years), the mean rate of BMD gain in lumbar spine at Week 48 was similar between the tenofovir and the d4T or AZT treatment groups. Total body BMD gain was less in the tenofovir compared to the d4T or AZT treatment group. One tenofovir-treated subject and none of the d4T or AZT-treated subjects experienced significant (greater than 4%) lumbar spine BMD loss at Week 48. Changes from baseline in BMD Z-scores were -0.012 for lumbar spine and -0.338 for total body in the 64 subjects who were treated with tenofovir for 96 weeks. In Study 321 (12 to less than 18 years), the mean rate of BMD gain at Week 48 was less in the tenofovir compared to the placebo treatment group. Six tenofovir treated subjects and one placebo treated subject had significant (greater than 4%) lumbar spine BMD loss at Week 48. Changes from baseline BMD Z-scores were -0.341 for lumbar spine and -0.458 for total body in the 28 subjects who were treated with tenofovir for 96 weeks. In both trials, skeletal growth (height) appeared to be unaffected. Markers of bone turnover in tenofovir-treated paediatric subjects suggest increased bone turnover, consistent with the effects observed in adults.

Eighty-nine paediatric subjects received tenofovir in Study 352 (48 who were initially randomised to tenofovir and 41 who were initially randomised to continue stavudine or zidovudine and then received tenofovir in the extension phase) for a median exposure of 104 weeks. Of these, 4 subjects discontinued from the trial due to adverse reactions consistent with proximal renal tubulopathy. Three of these four subjects presented with hypophosphatemia and also had decreases in total body or spine BMD Z score.

For full details please refer to the new label:

www.accessdata.fda.gov/scripts/cder/drugsatfda

Links to external websites are current at time of posting but not maintained.