Applying multimodal pain management in primary care

Looking beyond a single analgesic

Family physicians help patients navigate acute pain management, including the selection and safe use of over-the-counter (OTC) medicines. Nonopioid therapies have an important role, with treatment selection guided by the pain condition, patient preferences, concurrent medications, and individual risks.^1,2

Multimodal analgesia involves using treatments that work in different ways to manage pain. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) may be used individually or together in selected settings.^1–3 Their complementary mechanisms of action provide the rationale for combination treatment, and evidence for specific fixed-dose regimens can help inform how they're used in practice.⁴

Evaluating an OTC fixed-dose combination

Acetaminophen is believed to work quickly to reduce pain signals. Naproxen sodium, an NSAID, provides longer-lasting relief by targeting pain caused by inflammation. Combining them in a single dose delivers both fast onset and extended duration of pain relief.^5,6

Tylenol^® with Naproxen, which was FDA approved in July 2026, is an opioid-free pain reliever that brings these two complementary analgesics in an OTC fixed-dose formulation. Each tablet contains acetaminophen 325 mg and naproxen sodium 110 mg; the labeled two-tablet dose provides 650 mg and 220 mg, respectively.⁵

A fixed-dose combination combines two ingredients in a single product, providing a simple approach for clinicians to consider for appropriate patients. One product provides one set of labeled directions and warnings and one dosing schedule.⁵

Clinical evidence can also inform treatment selection. In a randomized, double-blind Phase III trial involving patients with post-operative dental pain, the fixed-dose combination demonstrated greater pain relief than acetaminophen 650 mg, naproxen sodium 220 mg, or placebo, as measured by mean time-weighted sum of pain intensity difference over 12 hours (SPID 0–12).⁴

Putting the evidence into practice

For family physicians, applying a multimodal approach means matching treatment to the patient and the level of pain. When considering an OTC fixed-dose combination, this includes assessing the suitability of both ingredients, reviewing other medicines for overlapping ingredients, and discussing labeled directions and warnings.⁵

Understanding the evidence for a combination and the role of each ingredient can help physicians guide patients toward informed OTC pain management decisions. The launch of Tylenol^® with Naproxen expands and enhances pain relief options for both patients and their physicians to further meet evolving and complex pain needs. 

For further information, visit Tylenol Professional​, which offers a library of resources for healthcare professionals.

Tylenol^® with Naproxen is a multimodal, nonopioid option that broadens OTC analgesic choice, delivering effective analgesia when used as directed. Always read and follow the drug facts label for complete information.⁵