New Drug Approvals and Extended Indications for Infants, Children, and Adolescents

Marcia L. Buck, PharmD, FCCP, FPPAG


Pediatr Pharm. 2015;21(11) 

In This Article

New Pediatric Indications

Abacavir and Lamivudine

The FDA approval for the combination of abacavir and lamivudine (Epzicom®) was extended on September 17, 2015 to include use in children with HIV-1 infection weighing 25 kg or more.[18] The weight limit is the result of the need for the patient to receive the currently available tablet containing 600 mg abacavir and 300 mg lamivudine. The FDA waived the requirement for pediatric studies in patients weighing less than 25 kg and the development of an oral liquid formulation because of the availability of similar products for that population.

The efficacy and safety of the abacavir and lamivudine combination were evaluated in the ARROW trial, a 5-year multicenter randomized trial which included 23 children with HIV-1 infection who were treatment-naïve and between the ages of 3 months and 17 years of age.[19] The initial phase consisted of abacavir and lamivudine dosed twice daily according to current World Health Organization recommendations. After 36 weeks, patients could be enrolled in a second phase comparing once-daily and twice-daily dosing of the combination, given along with a third antiretroviral drug, for an additional 96 weeks. A total of 669 of the original 1,206 patients in the ARROW trial were included. The percentage of subjects with an HIV-1 RNA less than 80 copies/mL at week 96 were not significantly different: 70% in the twice-daily dosing group and 67% in the once-daily group. There were no differences in the frequency of adverse effects between the groups. Based on this study and others, once-daily administration of Epzicom® has been approved by the FDA.


On August 2, 2015, the FDA indication for aprepitant (Emend®) was amended to include adolescents 12 years of age and older and children less than 12 years who weigh at least 30 kg.[20] Aprepitant is an antiemetic that serves as an antagonist at substance P/neurokinin 1 (NK1) receptors. It is used in combination with other antiemetics in the prevention of acute or delayed nausea and vomiting associated with moderately or highly emetogenic chemotherapy. The expanded indication was based on the results of a randomized, double-blind active-comparator study comparing aprepitant and ondansetron to ondansetron alone in 132 children and adolescents. There was a significantly greater percentage of subjects with a complete response (0–24 hours after chemotherapy) in the combination group (34.9%) compared to the group given ondansetron alone (13%). Results were also significant for comparisons of response in the acute and delayed phases when assessed independently.


The approved age range for atazanavir (Reyataz®) oral powder for suspension was extended by the FDA on September 24, 2015 to include treatment of HIV-1 infection in children 3 months of age or older who weigh at least 5 kg.[21] The age extension was based on two pharmacokinetic, safety, and efficacy studies: PRINCE 1, conducted in children 3 months to 6 years of age, and PRINCE II, conducted in children 3 months to 11 years of age.[22] A total of 155 children were studied. The percentages of antiretroviral-experienced and antiretroviral-naïve patients with HIV-1 RNA counts less than 400 copies/mL at week 48 were 79% and 62%, respectively. The percentages with HIV-1 RNA counts less than 50 copies/mL were 54% and 50%. The median increase in absolute CD4 count at week 48 for the two groups were 215 cells/mm3 and 133 cells/mm3, respectively.

Mesalamine Delayed-release Capsules

On September 9, 2015, the FDA granted an extension of the approval for mesalamine delayed-release 400 mg capsules (Delzicol®) to include children 5 years of age and older.[23,24] The product was previously approved for adults and children 12 years of age and older. Mesalamine, an aminosalicylate, blocks the mucosal production of arachidonic acid metabolites that are increased in patients with chronic ulcerative colitis. The delayed-release form provides effective topical anti-inflammatory activity in the colon. The effectiveness of delayed-release mesalamine was studied in 82 children between 5 and 17 years of age with mild to moderately-active ulcerative colitis. In a 6-week randomized, double-blind, parallel-group study, patients were divided into groups (17–32 kg, 33–53 kg, and 54–90 kg) and randomly assigned to a low-dose (1.2, 2.0, or 2.4 g/day) or high-dose (2.0, 3.6, or 4.8 g/day) regimen. At week 6, 73.2% of patients in the low-dose group and 70.0% in the high-dose group experienced successful treatment. Of those patients, 34.1% in the low-dose group and 42.5% in the high-dose group had a complete resolution of symptoms. Based on the similar degree of benefit between the two dosing strategies, the low-dose regimen was chosen for approval.


On August 26, 2015, the FDA extended the approval for rilpivirine (Edurant®) to include HIV-1 treatment-naïve pediatric patients 12 years of age and older who weigh at least 35 kg.[25,26] Rilpivirine is indicated for the treatment of patients with an HIV-1 RNA < 100,000 copies/mL and is given as one 25 mg tablet once daily with a meal. The pharmacokinetics, safety, and efficacy of rilpivirine were evaluated in a 48-week phase 2 open-label trial in 36 treatment-naïve children with HIV-1 infection between 12 and 18 years of age. In patients with an HIV-1 RNA ≥ 100,000 copies/mL at baseline, 50% had level < 50 copies/mL at week 48. Of the patients with a baseline HIV-1 RNA < 100,000 copies/mL, 79% had an HIV-1 RNA < 50 copies/mL. The mean increase in CD4 count from baseline was 201.2 cells/mm3.


The FDA extended approval of tiotropium (Spiriva® Respimat®) to include the treatment of asthma in adults and children 12 years of age and older on September 15, 2015.[27,28] Tiotropium had previously been approved only as a maintenance treatment for patients with chronic obstructive pulmonary disease. Efficacy and safety data for its use in asthma was obtained from 12 clinical trials of nearly 5,000 adolescents and adults with asthma. In placebo-controlled trials, the addition of tiotropium to standard therapy significantly improved lung function and reduced asthma exacerbations. The recommended dose is 2.5 mcg (2 puffs) once daily.