New Drug Approvals and New Pediatric Indications

An Update for Pediatric Healthcare Providers

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS


Pediatr Pharm. 2017;23(7) 

In This Article

Newly Approved Drug Products


The first biosimilar of infliximab was approved by the FDA on April 24, 2017. Infliximab-abda (Renflexis®) is an alternative to Remicade®.[1,2] Infliximab-abda is approved for the same indications, including use in patients 6 years of age and older with Crohn's disease, as well as ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis in adults. The recommended dose of infliximab is 5 mg/kg at 0, 2, and 6 weeks, followed by a dose every 8 weeks for pediatric Crohn's disease. Biosimilars, unlike generic products, are not identical to the originator, or reference, product. While not the same exact chemical entity, biosimilars have been found in premarketing testing to have no clinically meaningful differences from the reference product. Unlike generic drugs that have the same name as the original (brand) product, biosimilars have the name of the original drug followed by a suffix to designate the difference.

Methotrexate Oral Suspension

Until the approval of a commercial methotrexate oral solution (XatmepTM) in April, it was necessary for patients and families needing a liquid preparation to find a hospital or compounding pharmacy able to prepare it for outpatient use. This often limited patient access to the drug in rural or underserved areas and increased both cost and time to have the prescription filled. The alternative, splitting or cutting tablets, creates a risk for family members or healthcare personnel for exposure to the drug through the skin during handling or inhalation of aerosolized particles. Silvergate Pharmaceuticals created a 2.5 mg/mL methotrexate solution that requires no further manipulation.[3,4] It is recommended that it be refrigerated, but the solution is stable for 60 days at room temperature. Methotrexate oral solution is approved by the FDA for children with acute lymphoblastic leukemia or children with active polyarticular juvenile idiopathic arthritis who have had an insufficient response to non-steroidal anti-inflammatory agents.

Cerliponase alfa

The FDA has also approved cerliponase alfa (BrineuraTM) for use in pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also referred to as tripeptidyl peptidase-1 deficiency.[5–7] CLN2 is one of a group of disorders known as Batten disease. This rare inherited disease is typically diagnosed with the onset of symptoms at 2 to 4 years of age. The disease produces language delays, epilepsy, and ataxia, with progression to myoclonus and vision loss. Cerliponase alfa is a recombinant form of human tripeptidyl peptidase-1. It is administered into the CSF through a surgically-implanted intraventricular access device and reservoir. The recommended dose is 300 mg given every other week by an intraventricular infusion over 4 to 5 hours. The efficacy of cerliponase alfa was determined in an open-label dose escalation study in 22 symptomatic children.[8] Their motor and language skills were compared to a historical control group of 42 untreated children. Patients receiving treatment had significantly less decline in walking compared to the controls.

The most common adverse effects reported with the drug include bradycardia, hypotension, hypersensitivity, changes in CSF protein levels, vomiting, seizures, hematoma, headache, irritability, pleocytosis, jitteriness, and infection related to the intraventricular infusion device.[9] The FDA has required the manufacturer, BioMarin Pharmaceuticals, to conduct a 10-year safety study of the drug, as well as a study to evaluate the efficacy and safety in younger patients so that treatment may be initiated at a younger age.

Epinephrine Injection

In June, the FDA approved a new epinephrine 0.3 mg pre-filled syringe for IM or subcutaneous injection for the emergency treatment of anaphylaxis or other severe hypersensitivity reactions.[10,11] The new product, SymjepiTM (Adamis Pharmaceuticals) is an alternative to EpiPen®. It is supplied in a package of two syringes. An image of the syringe is available on the manufacturer's website at A lower dose pediatric version is currently being evaluated by the FDA. The manufacturer anticipates having the product available for purchase by fall. No price has been set yet, but the manufacturer has indicated that the price will be lower than the average retail price of $368 for a package of two EpiPens®.

Once-Daily ADHD Treatments

Two new products for the management of attention deficit/hyperactivity disorder (ADHD) were also approved by the FDA in June. A new once-daily capsule of amphetamine salts was approved for patients 13 years of age and older with ADHD.[12,13] Shire's mixed salts of a single-entity amphetamine product (MydayisTM) contains three different types of coated beads that release drug at separate intervals, producing up to 16 hours of symptom control. This is the longest duration of action from a single dose of any central nervous system stimulant currently on the market in the United States.

MydayisTM has undergone extensive testing in adolescents and adults, with 16 premarketing clinical trials enrolling more than 1,600 patients. The efficacy and safety of the drug was studied in a multicenter, randomized double-blind placebo-controlled study of 84 adolescents (13–17 years of age). This crossover study compared treatment with 12.5 or 25 mg capsules to placebo in a classroom-like setting. Active drug treatment resulted in statistically significant differences in testing performance at 2, 4, 8, 12, 14, and 16 hours post-dose, based on the ADHD Rating Scale IV and the Permanent Product Measure of Performance (PERMP). The adverse effect profile was similar to that seen with other once daily amphetamine products. There were no serious adverse effects, and none of the patients discontinued treatment as the result of an adverse effect.

A new extended-release orally disintegrating tablet (ODT) formulation of methylphenidate (Cotempla XR-ODT TM) was approved for use in children and adolescents from 6 to 17 years of age with ADHD.[14,15] Like most other once-daily products on the market, methylphenidate XR-ODT provides 12 hours of symptom control. It reflects continued expansion of ODT products from Neos Therapeutics. Their extended-release amphetamine ODT (Adzenys XR-ODTTM) was approved for the US market in June 2016. The studies supporting the safety and efficacy of methylphenidate XR-ODT will be reviewed in a subsequent issue of Pediatric Pharmacotherapy.