Advisory committee calls for further clarification of true pediatric drug indications

The Pediatric Advisory Committee of the FDA met Tuesday to review data for numerous drugs to determine their safety for pediatric populations.

Based on data that showed no new pediatric safety concerns as of September 2014, the committee agreed that the FDA should continue to conduct standard safety monitoring for the following drugs:

Dymista (azelastine hydrochloride-fluticasone propionate, Meda Pharmaceuticals) for seasonal allergic rhinitis in patients aged 12 years and older;
QNASL (beclomethasone dipropionate, Teva) for treatment of nasal symptoms associated with perennial and seasonal allergic rhinitis among patients aged 4 to 11 years and older than 12 years;
Venofer (iron sucrose, Luitpold Pharmaceuticals) to maintain iron levels among patients aged 2 years and older with hemodialysis-dependent chronic kidney disease or nondialysis-dependent or peritoneal dialysis-dependent chronic kidney disease;
Invirase (saquinavir mesylate, Genentech) as an HIV protease inhibitor indicated for patients aged 0 to 16 years;
Risperdal (risperidone, Janssen Pharmaceuticals) for treatment of schizophrenia in patients aged 13 years and older, manic or mixed episodes with Bipolar I disorder in patients aged 10 years and older and irritability associated with autism in patients aged 5 years and older;
Oxtellar XR (oxcarbazepine, Supernus Pharmaceuticals) for treatment of partial seizures in patients aged 6 years and older;
FluMist Quadrivalent (influenza vaccine live intranasal, MedImmune); and
Fluarix Quadrivalent (inactivated influenza vaccine, GlaxoSmithKline).

A few drugs prompted discussions that highlighted significant discrepancies between drug utilization and indications.

Some committee members expressed concerns after viewing data that indicated Cymbalta (duloxetine hydrochloride, Eli Lilly), which is indicated for treatment of generalized anxiety disorder in patients aged 7 to 17 years, was prescribed to patients aged younger than 7 years. Specifically, data showed that of patients prescribed duloxetine between August 2013 and September 2014, 0.4% were aged 0 to 1 years and 0.6% were aged 2 to 5 years. Committee members suggested that efforts be made to clarify the true indications of the drug to health care professionals. Ultimately, all committee members agreed that the FDA should continue to routinely monitor duloxetine.

“I was somewhat disappointed to see that 31% of prescriptions that were in the 6- to 11-year-old population were for depressive disorder, which we know from the randomized trials was not demonstrated to be effective, and similarly for the 12- to 16-year-olds that depressive disorder not elsewhere classified was the largest use,” Kenneth E. Towbin, MD, chair of the Pediatrics Advisory Committee, said during the meeting. “It might be on us to get the word out to people since it appears that this drug is still being used when there hasn’t been any demonstration of efficacy.”

Quillivant XR (methylphenidate hydrochloride, NextWave Pharmaceuticals) brought up similar concerns, as data showed that 14.8% of patients who received a prescription for it between September 2012 and June 2014 were aged 2 to 5 years, despite only having evidence of safety and efficacy in patients aged 6 years and older.

“It is a bit bemusing to me that psychiatry accounts for the largest prescriber group in children and adolescents [for oxcarbazepine]. It appears that the use for this drug, if the diagnoses that go along with it are accurate, still appears to be in bipolar and bipolar spectrum disorders for which there is no demonstrated efficacy for this drug,” Towbin said. “Again, it is one of those things where there is a downward extension perhaps from adult studies or suggestions, but really the evidence in children is quite lacking. It is unfortunate that we still continue to see such high use in children and adolescents when there really hasn’t been any demonstrated efficacy of this drug in this population for that indication.”

Data for risperidone and oxcarbazepine also highlighted inconsistencies between drug utilization and indication, but the committee ultimately agreed the FDA should move forward with standard safety monitoring for these drugs.

Because the safety and efficacy of Lunesta (eszopiclone, Sunovion Pharmaceuticals) has yet to be determined for treatment of ADHD-related insomnia in children, the committee agreed the FDA should return to ongoing surveillance of the drug.

Although Revatio (sildenafil, Pfizer) is indicated for treatment of pulmonary arterial hypertension in adults only, pediatric use has significantly increased from 2005 to 2014, according to data presented at the meeting.

One committee member attested to sildenafil’s efficacy in children and cited that the study design did not yield valuable information from which the committee could make a recommendation. The FDA acknowledged that it was difficult to determine if there were new safety concerns regarding sildenafil, as many of the nonfatal serious adverse events reported were likely related to underlying disease.

Finally, the committee agreed the FDA should continue post-market monitoring of Advair HFA (fluticasone propionate/salmeterol xinafoate, GlaxoSmithKline) for the treatment of asthma among children aged 4 to 12 years. – by Amanda Oldt