A Staple in the Medicine Cabinet
For decades, Alka-Seltzer has been a trusted brand for relieving everything from heartburn to headaches [1.4.2]. Its sister product, Alka-Seltzer Plus, was specifically formulated to tackle the miserable symptoms of the common cold and flu, such as nasal and sinus congestion [1.5.6]. A key component in these cold formulas was a nasal decongestant that was effective and widely available. However, in the early 2000s, a significant change was made to the formulation of many over-the-counter (OTC) cold remedies, including Alka-Seltzer Plus. A primary active ingredient was completely removed due to serious safety concerns raised by the U.S. Food and Drug Administration (FDA).
What Ingredient Was Removed from Alka-Seltzer Plus?
The ingredient removed from Alka-Seltzer Plus was Phenylpropanolamine (PPA) [1.2.8]. It is a sympathomimetic amine that functions as a nasal decongestant by causing vasoconstriction (narrowing of blood vessels) in the nasal passages [1.6.4]. This action reduces swelling and inflammation, providing relief from a stuffy nose. PPA was also a common ingredient in OTC appetite suppressants [1.2.2]. For years, it was a staple in hundreds of cold, cough, and diet products found on pharmacy shelves across the country [1.2.2].
The FDA's Bombshell Announcement
In November 2000, the FDA issued a public health advisory warning consumers to stop using any drug products containing PPA [1.2.4]. This unprecedented move came after the agency reviewed the results of a multi-year study conducted by researchers at Yale University School of Medicine [1.6.1]. The study, known as the Hemorrhagic Stroke Project, investigated the association between PPA use and the risk of hemorrhagic stroke, a type of stroke where a blood vessel in the brain ruptures [1.2.1, 1.6.7].
The study's findings were alarming. It revealed a significant association between PPA use and an increased risk of hemorrhagic stroke, particularly in women aged 18 to 49 [1.6.7]. The risk was most pronounced for those using PPA in appetite suppressants, but an increased risk was also found with the first-time use of PPA in cold and cough remedies [1.6.6]. While the overall risk was low, the FDA concluded that the seriousness of a stroke did not justify the use of PPA for its intended purposes, such as temporary relief from nasal congestion [1.6.5]. The agency estimated that PPA could be responsible for 200 to 500 strokes per year in the 18-to-49 age group alone [1.3.6]. In response, the FDA requested that all drug companies voluntarily discontinue marketing products containing PPA [1.6.5].
The Industry Responds: Reformulation
Following the FDA's advisory, manufacturers, including Bayer, acted swiftly. Bayer confirmed it removed PPA from its Alka-Seltzer Plus formulations in 2000 [1.2.8]. Across the industry, companies began pulling products containing PPA from store shelves and scrambling to reformulate their popular cold and diet medications [1.2.2, 1.2.7].
The replacement for PPA in most decongestant products, including the new versions of Alka-Seltzer Plus, was primarily phenylephrine or, in some cases, pseudoephedrine [1.5.6, 1.2.7]. Phenylephrine is also a vasoconstrictor that works similarly to PPA to relieve nasal congestion [1.5.3]. Today, various formulations of Alka-Seltzer Plus Severe Cold & Flu contain phenylephrine hydrochloride as the nasal decongestant, combined with other ingredients like acetaminophen (pain reliever/fever reducer), dextromethorphan (cough suppressant), and chlorpheniramine maleate (antihistamine) [1.5.1, 1.5.5].
Interestingly, the effectiveness of oral phenylephrine has since come under scrutiny. In 2023, an FDA advisory committee concluded that oral phenylephrine as a sole active ingredient is not effective as a nasal decongestant [1.2.5]. However, it remains in many combination cold products on the market.
Comparison: Old vs. New Decongestants
| Feature | Phenylpropanolamine (PPA) | Phenylephrine (PE) |
|---|---|---|
| Primary Use | Nasal Decongestant, Appetite Suppressant [1.2.2] | Nasal Decongestant [1.5.6] |
| Mechanism | Vasoconstriction of nasal blood vessels [1.6.4] | Vasoconstriction of nasal blood vessels [1.5.3] |
| Reason for Removal | Linked to increased risk of hemorrhagic stroke [1.6.1] | N/A (Still in use) |
| FDA Status | No longer considered Generally Recognized As Safe and Effective (GRASE) [1.6.5] | Oral form deemed ineffective by an FDA advisory panel in 2023 [1.2.5] |
| Availability | Banned from OTC sale [1.2.2] | Widely available in OTC cold medications [1.5.1] |
Conclusion
The removal of Phenylpropanolamine from Alka-Seltzer Plus and hundreds of other products marked a major shift in the regulation and formulation of over-the-counter medications. Driven by scientific evidence from the Hemorrhagic Stroke Project, the FDA's decisive action aimed to protect public health by eliminating an ingredient that, while effective for minor ailments, carried a rare but devastating risk [1.6.5]. Consumers today will find that Alka-Seltzer Plus products now contain alternative decongestants like phenylephrine to provide cold and flu symptom relief, a direct result of this critical regulatory change from over two decades ago [1.5.6].
For more information on drug safety, you can visit the U.S. Food and Drug Administration's website.
