Triamcinolone Nasal Spray Can Go OTC, FDA Panel Says

Miriam E. Tucker

July 31, 2013

SILVER SPRING, Maryland — A federal advisory panel has voted to allow triamcinolone acetonide (TAA) nasal spray (Nasacort, sanofi-aventis) to be switched from prescription to over-the-counter (OTC), but with the proviso that the product label must clearly reflect the risk for slowing of growth in children, among other concerns.

In a 10-to-6 vote with 2 abstentions, the US Food and Drug Administration's (FDA) Nonprescription Drugs Advisory Committee supported sanofi-aventis' new drug application for the switch of TAA nasal spray to OTC status for the same indication it now has as a prescription product "for the treatment of seasonal and perennial allergic rhinitis for the temporary relief of hay fever and other respiratory allergies (nasal congestion, runny nose, sneezing, itchy nose)."

The age indication, 2 years and older, would also be the same as the current prescription indication, but several committee members said they wanted the FDA to include specific information in the label advising consumers to consult a physician regarding TAA use in children. The product is delivered as a metered-dose nasal spray.

If approved for the OTC indication by the FDA, TAA would be the first OTC intranasal steroid. Other currently available OTC allergy medications — antihistamines, decongestants, and mast cell stabilizers — are considered less effective than steroids and none address all the symptoms included in the indication for TAA.

Efficacy of TAA was not a major part of the deliberations, as it is already available by prescription and has been shown to be effective in reducing allergic rhinitis symptoms in both adults and children.

Most of the debate addressed safety in the OTC setting, with the known risk for diminished growth velocity and the variety of concerns regarding inappropriate use, including for colds, and among patients who are already using orally inhaled steroids to treat asthma or other inflammatory conditions. Several panel members expressed concern about a lack of information on the effects of long-term unmonitored use.

Nasacort is already approved for OTC use in 11 countries, with a variety of age restrictions. In the UK, for example, OTC use is restricted to ages 18 and above, while in New Zealand OTC use is extended down to age 6 years. The FDA had suggested that sanofi request the OTC indication down to 2 years of age to prevent inappropriate use, because the dosing for children is different, FDA reviewer Sofia Chaudhry explained.

Safety data provided by sanofi and reviewed by the FDA came from controlled clinical trials of 1389 adults and adolescents aged 12 years or older and 575 children aged 2 to 11 years, as well as from worldwide postmarketing data collected from April 2000 to March 2012. During that time, more than 120 million bottles of TAA were sold worldwide, including 50 million by prescription in the US.

Specific studies conducted by sanofi to look at effects of TAA on immune function and on suppression of the hypothalamic-adrenal-pituitary axis showed no increased risk compared with placebo. Studies in children aged 2 to 5 and 6 to 12 years showed no significant difference in 24-hour serum cortisol production in stimulation studies conducted at 4 to 6 weeks of use.

However, in a study conducted in 299 children aged 3 to 9 years who used TAA for 1 year, mean growth velocity rates were 5.65 cm/year in the TAA group compared with 6.09 cm/year in the placebo group, a statistically significant difference of -0.45 cm/year, with 95% confidence interval -0.78 -0.11. The difference was most pronounced during the first 2 months of treatment, Sharon Levy, MD, chief medical officer of Prosoft Clinical reported on behalf of sanofi.

Saul Shiffman, PhD, professor of psychology and pharmaceutical sciences at the University of Pittsburgh, Pennsylvania, presented sanofi's data on consumer comprehension of the proposed labeling in a total of 475 participants including 146 with low literacy. Overall comprehension of various aspects of the label — including indications, instructions for use of the device, and cautionary statements — ranged from 79% to 95%.

Panel Debate

However, panel members expressed concern that consumers might not read all the instructions, might not know exactly what a "steroid" medication is, and might use TAA for inappropriate indications.

There was considerable discussion about sanofi's proposed label advice for parents of patients aged 12 years and younger to "tell your child's doctor when he/she starts using this medication." Some panel members noted that such an instruction would be novel for an OTC product, which consumers generally perceive to be "safe."

Regardless of their vote, panel members all felt that the label would need to clearly reflect potential risks to growing children.

Judith M. Kramer, MD, professor of medicine at Duke University, Durham, North Carolina, voted yes but added, "I do think we should say something about patients under 12 shouldn't take it longer than a month without talking to a doctor, because of concerns about growth."

Committee chairman Richard A. Neill, MD, chief of the department of family medicine at Penn Presbyterian Medical Center, Philadelphia, Pennsylvania, said, "I voted no, out of concern for inadequate data and duration of data to inform the growth issues, and believe that the best way to address that is going to be through longer both actual uses studies and changes to the label."

Michael K. Paasche-Orlow, MD, from Boston University School of Medicine, Boston, Massachusetts, was one of the 2 abstainers. "I was torn, primarily because I wanted to vote yes for older people but no for younger people.… We don't have a mechanism of action and don't know other implications of this growth differential. It seems rather unsafe to have unmonitored use," he said.

But Ruth M. Parker, MD, professor of medicine and pediatrics, and a specialist in label comprehension and health literacy at Emory University School of Medicine, Atlanta, Georgia, voted "Yes, but I do look for the changes to the label that I think we're going to need."

Members of FDA advisory panels are vetted for conflicts of interest and are granted waivers for participation if necessary. No waivers were granted for this meeting.

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