PIC QUESTION OF THE WEEK: 02/05/07 Q: Please describe recent FDA action related to the discontinuation of “unapproved” drugs. A: During the past few years, a number of high-profile cases, especially those involving COX-2 inhibitors such as Vioxx, have prompted the FDA to expand its efforts to maximize drug quality and patient safety. Continued monitoring of drug safety and efficacy are also supported by the long-standing DESI (Drug Efficacy Study Implementation) legislation that requires manufacturers to provide clinical efficacy data for all drugs marketed prior to 1962. The FDA is now requesting drug manufacturers to submit safety and efficacy data for several compounds that have been used for decades but never formally received an approved New Drug Application. Most noteworthy are the antihistamine carbinoxamine and quinine sulfate. Carbinoxamine has been linked to the deaths of several children less than two years of age. This prompted the FDA to issue a notice that all carbinoxamine-containing products be removed from the market by June, 2006 unless the manufacturer submitted evidence supporting its safety and efficacy. Many products that contained carbinoxamine now substitute chlorpheniramine as the antihistamine. One manufacturer, Mikart, did submit supportive data and is currently the only distributor of carbinoxamine. More recently, quinine sulfate has undergone close scrutiny and now faces restrictions similar to those for carbinoxamine. The only approved quinine product currently available is manufactured by Mutual Pharmaceutical Company, Inc. It is specifically labeled only for the treatment of malaria. The FDA estimates that over 99.5% of prescriptions for quinine had been for off-label uses, primarily leg cramps. Because of concern over frequently severe adverse reactions and questionable efficacy, this product is specifically labeled as contraindicated for leg cramps. Unless additional data is presented by manufacturers prior to February 13th, 2007, all other prescription and OTC quinine-containing products must be removed from the market. Other widely prescribed drugs now undergoing similar FDA evaluation include the antihistamines pheniramine and dexbrompheniramine, single-ingredient opiate analgesics such as oxycodone (plain 5mg tablet) and codeine phosphate, and the sedative/hypnotics phenobarbital and chloral hydrate. It is estimated that 2% of prescription drugs have never undergone formal FDA evaluation and approval. The agency is expected to vigorously continue its assessment program of old, unapproved drugs. References: • • •
FDA. Drugs marketed in the United States that do not have required FDA approval. http://www.fda.gov (accessed 2007 Jan 31) All quinine products except qualaquin will soon disappear. Pharmacist’s Letter/Prescriber’s Letter 2007;23(1):23010. Young D. FDA orders firms to stop selling unapproved quinine. http://www.ashp.org (accessed 2007 Jan 31)
Renee R. Tis and Michael R. Schmitt, Pharmacy Clerkship Students The PIC Question of the Week is a publication of the Pharmaceutical Information Center, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA 15282