HEARTBEARN, HEADACHES, AND HANGOVERS: THE DECISION TO REFORMULATE ANALGESIC COMBINATION PRODUCTS. HOW DOES THE FDA WEIGH-IN?

Posted by on October 6, 2017

On April 4th, the Nonprescription Drugs Advisory Committee (NDAC) discussed safety issues associated with over-the-counter (OTC) analgesic combination products used for indications such as upset stomach (i.e. heartburn, nausea, bloating, belching, gas, dyspepsia, and/or sour stomach) and hangover indications under the Internal Analgesic and Antacid OTC monograph.

Industry representatives from the Consumer Healthcare Products Association (CHPA), Bayer HealthCare LLC, and Rally Labs LLC were present to discuss the role of analgesic combination products, proposed product reformulations, and products specifically formulated to treat hangover. Below is a summary of these proceedings.

A typical OTC analgesic combination product is formulated with an analgesic product, such as aspirin (ASA), and antacid substance, such as sodium bicarbonate and citric acid. This formulation characterizes Bayer HealthCare’s three Alka-Seltzer® effervescent products: Alka-Seltzer® Original, Alka-Seltzer® Lemon Lime, and Alka-Seltzer® Extra Strength, this product line has distributed an estimated 1.4 billion doses from 2010-2016. The rationale for these product’s is to provide efficacious, rapid relief of the combined symptoms of headache/body pain accompanied with GI discomfort.

The safety profile of ASA-containing products, such as the three combination products listed above, are favorable. From 1982-2016 Bayer has continuously monitored the ASA/antacid products for any new safety information and when considering the usage of the product on a yearly bases year, the pharmacovigilance data continues to demonstrate the positive safety profile of these Alka-Seltzer® products. Specifically, Bayer’s position was that, when used according to the label, the benefit-risk profile of the Alka-Seltzer® products remains favorable. However, to reduce or eliminate any potential for consumer misuse of these combination products, Bayer has chosen to reformulate, removing the ASA component and eliminating thee analgesic-associated indications from the products.

Following the Bayer presentation, CHPA provided two researchers who devoted their careers to “hangover science” and supported the need for OTC products that treat the most common hangover symptoms such as headache, fatigue, and GI distress.

Rally Labs LLC, the other industry sponsor present at the meeting, followed-up CHPA’s presentation with an introduction to their product, Blowfish. Blowfish, marketed under the OTC Drug Monograph for the relief of hangover symptoms, is an effervescent tablet formulated with 500 mg/serving ASA and 60 mg/serving caffeine. The sponsor noted that millions of doses have been sold since 2011 and no serious adverse events (SAEs) have been reported, per their robust pharmacovigilance program. Moreover, the Rally Labs LLC presentation supported the use of the hangover indication in the OTC monograph and demonstrated the favorable safety profile of their Blowfish product.

The first question posed to panel members was to discuss the safety of OTC analgesic combination products for the relief of minor aches/pains and GI discomfort, such as heartburn, sour stomach, and dyspepsia. The panel largely agreed that erosive gastritis is a complication associated with NSAID use and that the most common AEs associated with ASA use were GI-related in nature. This suggests that the ASA component may reduce the efficacy of the antacid component of such combination products. Additional comments acknowledged that combination products do not represent the current best practice to treat the associated symptoms, but no significant safety concerns were apparent after review of the pharmacovigilance data presented.

A voting question was also posed to the panel: “Is the combination of an analgesic with antacids a rational combination for OTC use for the relief of minor aches and pains associated with heartburn, sour stomach, acid indigestion, fullness, belching, gas, or nausea?”  The vote resulted in 5 YES votes, 15 NO votes, and 0 abstentions. Much of the panel agreed that analgesic/antacid combination products are not rational for OTC use for the indications listed above. The post-vote discussion raised the issue of consumer confusion of active ingredients, which may result in misuse.

The meeting concluded with ad discussion as to whether the treatment of hangover is an appropriate indication for OTC drug products and what ingredients would be acceptable for use – FDA was specifically interested in ASA and acetaminophen. The panel had mixed opinions on the issue, stating that since hangover is a self-limiting condition, it is not clear if treatment is completely necessary and if current combination products have specifically demonstrated efficacy, relating to the indication. The committee agreed that acetaminophen is not an appropriate ingredient for hangover, due to a heightened risk of liver toxicity in the presence of alcohol, but agreed that the inclusion of ASA was less worrisome.

Innovative Science Solutions (ISS) was proud to assist in providing regulatory insight and knowledge to Bayer HealthCare throughout the FDA Advisory Committee Meeting process. ISS has almost two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact info@innovativescience.net.

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