New REMS for Prescription Oral Sodium Phosphate Products Raises Questions on Application of REMS To Active Ingredients Available Both As Prescription and OTC

December 21, 2008

By Jamie K. Wolszon

FDA’s recent decision to require a Risk Evaluation and Mitigation Strategy (“REMS”) for two prescription oral sodium phosphate (“OSP”) products raises questions regarding the impact the agency’s evolving application of its new REMS authority will have in instances where both prescription and OTC products are available that contain the same active ingredient.

On Thursday December 11, FDA issued a press release announcing that it was adding a Black Box warning to two prescription OSP products, Visicol and OsmoPrep, to address the kidney injury, acute phosphate nephropathy.  FDA directed the companies to develop a REMS.  The Agency also required the firms to distribute a Medication Guide and to conduct a clinical trial to further assess the risk.   

FDA also observed that the Agency had similar concerns regarding OTC products used at higher dosages for bowel cleansing, but that “the available data show no risk of acute kidney injury when OTC products are used at the lower dosages as laxatives.”  FDA recommended “that consumers not use OTC OSP products for bowel cleansing,” and promised to amend the labeling conditions for OTC OSP products. The press release specifically mentioned Fleet Phospho-soda’s OSP product.      

Consistent with the press release, FDA also issued two responses on the same day to citizen petitions related to OSP products.  The agency denied C.B. Fleet of Lynchburg, Virginia’s (“Fleet”) 2003 petition requesting professional labeling for OTC sodium phosphates oral solution for bowel cleansing.  In the wake of FDA’s statement, Fleet announced that it would voluntarily cease marketing its product.

FDA also responded to a citizen petition submitted by food and drug attorney Natasha Leskovsek on behalf of an unnamed client.  FDA denied the petitioner’s request to remove all prescription OSP drugs from the market; however, the Agency granted the petition’s request to apply a black box warning to the prescription OSP products; and granted the petition’s request to amend the Tentative Final Monograph to remove the professional labeling for OSP products. 

Although not mentioned in the press release, along with the Black Box warning and Medication guide, the REMS requires the two makers of Visicol and OsmoPrep to develop a communication plan targeted at gastroenterologists, surgeons, primary care physicians, and other healthcare providers who are likely to prescribe or dispense OSP products or perform follow-up assessments of patients following bowel cleansing. 

In order to invoke its REMS authority, FDA must determine that, without a strategy, the benefit of the drug would not outweigh its risk.  Meanwhile, a product cannot be marketed OTC if the drug “because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such a drug.”  An OTC drug also must be safe and effective for use in self-medication. 

FDA’s new statutory REMS authority applies to new drugs that the agency approves under the new drug or abbreviated new drug approval provisions and that require a prescription.  FDA thus cannot impose REMS on OTC monograph drugs, but the agency has the means to address specific risks for OTC monograph drugs through labeling warnings or restrictions. 

There are multiple other examples of active ingredients that are marketed, albeit at different dosages or indications, both as a prescription and OTC product.  For instance, aspirin, while marketed OTC, also has professional labeling for the cardiovascular and rheumatologic indications. The professional labeling allows the maker of an aspirin product to detail the professional labeling to health care providers.  Prilosec OTC (omeprazole magnesium) is marketed with a shorter course of treatment than the prescription version and unlike the prescription version is solely marketed for treatment of heartburn. 

Categories: Drug Development