FDA Approves First OTC Acetaminophen–Naproxen Combination for 12-Hour Pain Relief

The FDA has approved Tylenol with Naproxen (acetaminophen and naproxen sodium; Kenvue Brands LLC), the first nonprescription fixed-dose combination to pair acetaminophen with naproxen sodium in a single product. The combination is intended to provide up to 12 hours of relief from minor aches and pains.¹

The product is indicated for the temporary relief of minor pain associated with headache, backache, muscular aches, toothache, menstrual cramps, and minor arthritis pain in adults and children age 12 years and older.¹

Each tablet contains acetaminophen 325 mg and naproxen sodium 110 mg. A single dose consists of 2 tablets, providing a total of acetaminophen 650 mg and naproxen sodium 220 mg. The product is taken every 12 hours and will be available without a prescription. According to Kenvue, Tylenol with Naproxen will be coming soon to major retailers across the United States.¹˒²

Although nonprescription products combining acetaminophen with other nonsteroidal anti-inflammatory drugs (NSAIDs) are currently available, Tylenol with Naproxen is the first FDA-approved OTC product to combine acetaminophen specifically with naproxen sodium.¹

Evidence Supporting the Fixed-Dose Combination

The approval was supported by evidence demonstrating the safety and effectiveness of the fixed-dose combination, as well as the contribution of each active ingredient to the product’s overall analgesic effect.¹

According to Kenvue, the clinical development program included 8 studies evaluating the fixed-dose combination. Across these studies, Tylenol with Naproxen demonstrated superior pain relief compared with acetaminophen alone and naproxen sodium 220 mg alone. The combination began providing pain relief in less than 30 minutes and maintained relief for up to 12 hours following a single dose.²

The 2 active ingredients have complementary pharmacologic properties. Acetaminophen acts as an analgesic and antipyretic, whereas naproxen sodium is an NSAID that provides longer-lasting pain relief by targeting inflammation. Combining the agents in a single fixed dose may simplify pain management for patients who would otherwise need to coordinate separate OTC products and dosing schedules.²

The approval expands the range of nonopioid OTC options available to individuals seeking relief from minor aches and pains. However, because the product contains 2 commonly used active ingredients, pharmacists should help patients review their prescription and OTC medications to avoid unintentional duplicate therapy.

Safety and Counseling Considerations

The Drug Facts labeling contains warnings associated with both acetaminophen- and NSAID-containing products. Patients should not use Tylenol with Naproxen concurrently with other medications containing acetaminophen because excessive cumulative exposure can cause severe liver damage. Acetaminophen is found in hundreds of prescription and OTC medications, including many cough, cold, sleep, and combination pain products.¹˒³

FDA guidance advises adults and children 12 years and older not to exceed a total of 4000 mg of acetaminophen from all medications within 24 hours. Patients with liver disease should consult a health care professional before using acetaminophen. Severe liver damage may also occur in individuals who consume 3 or more alcoholic beverages per day while using an acetaminophen-containing product.³

Because naproxen sodium is an NSAID, the labeling includes warnings regarding gastrointestinal bleeding and an increased risk of myocardial infarction, heart failure, and stroke. These risks may increase when NSAIDs are taken at higher-than-recommended doses or for longer than directed.¹˒⁴

Patients should avoid taking Tylenol with Naproxen with other naproxen-containing medications or additional NSAIDs unless directed by a health care professional. Additional assessment may be appropriate for patients with a history of gastrointestinal ulcers or bleeding, cardiovascular disease, hypertension, kidney disease, or allergic reactions to aspirin or other NSAIDs.⁴

Individuals who are pregnant or breastfeeding should ask a health care professional before using the product. The Drug Facts label advises against using naproxen sodium at 20 weeks of pregnancy or later unless specifically directed by a physician. The FDA has warned that NSAID exposure beginning at approximately 20 weeks’ gestation may cause fetal renal dysfunction, potentially resulting in low amniotic fluid levels and related complications. NSAIDs should generally be avoided beginning at approximately 30 weeks because of the additional risk of premature closure of the fetal ductus arteriosus.¹˒⁵

Pharmacists play a crucial role in helping patients identify duplicate acetaminophen or NSAID ingredients, understand the 12-hour dosing interval, and recognize when the severity or duration of pain warrants further medical evaluation.

REFERENCES

1. US Food and Drug Administration. FDA approves first nonprescription fixed-dose combination of acetaminophen and naproxen sodium for 12-hour pain relief. FDA email communication. Accessed July 24, 2026.

2. Kenvue Inc. FDA approves Tylenol with Naproxen, the first and only over-the-counter fixed-dose combination of acetaminophen (650 mg) and naproxen sodium (220 mg). News release. Published July 24, 2026. Accessed July 24, 2026. https://www.kenvue.com/media/fda-approves-tylenol-with-naproxen

3. US Food and Drug Administration. Acetaminophen. Accessed July 24, 2026. https://www.fda.gov/drugs/safe-use-over-counter-pain-relievers-and-fever-reducers/acetaminophen

4. US Food and Drug Administration. Medication guide for nonsteroidal anti-inflammatory drugs. Accessed July 24, 2026. https://www.fda.gov/media/72932/download

5. US Food and Drug Administration. Nonsteroidal anti-inflammatory drugs (NSAIDs): Drug Safety Communication—avoid use of NSAIDs in pregnancy at 20 weeks or later. Updated September 1, 2022. Accessed July 24, 2026. https://www.fda.gov/safety/medical-product-safety-information/nonsteroidal-anti-inflammatory-drugs-nsaids-drug-safety-communication-avoid-use-nsaids-pregnancy-20