Key takeaways
Combination pain relief medicines contain more than one active ingredient in one product.
Different ingredients may work through different mechanisms to help manage pain.[1,5]
TYLENOL® with Naproxen is the first and only FDA-approved OTC fixed-dose combination of acetaminophen and naproxen sodium.
Consumers should always follow label directions and talk with a healthcare provider if they have questions about pain relief options.
Why Are Combination Pain Relief Medicines Being Developed?
Many over-the-counter medicines are available to help relieve pain and reduce fever. At the same time, healthcare professionals may use a variety of approaches to help manage pain, including non-opioid medicines and non-drug therapies tailored to an individual's condition and needs.[3] One example of ongoing innovation in OTC pain relief is the development of combination pain medicines, which bring together complementary active ingredients in a single dose. Rather than relying on a single active ingredient, these products bring together complementary ingredients that may work in different ways. For consumers, this means more OTC pain relief options.
How Do Combination Pain Relievers Work?
Combination pain relievers contain more than one active ingredient that work differently in the body. Active ingredients can target pain in various ways; for example, some ingredients may help target pain at the source of inflammation.[1,5] Since the ingredients work through different mechanisms, researchers and healthcare professionals have explored whether combining them may provide benefits compared with a single ingredient alone.
Common OTC pain-relief ingredients include:
Acetaminophen
Ibuprofen
Naproxen sodium
Aspirin
Each ingredient has a different mechanism of action and safety profile.[1,5]
How Have Combination OTC Pain Relievers Evolved?
Combination OTC pain relief is not entirely new. Consumers may already be familiar with products that combine more than one pain-relief ingredient in a single dose.
Some examples of combination OTC pain relievers:
MOTRIN® Dual Action with TYLENOL®, which combines acetaminophen and ibuprofen.
TYLENOL® with Naproxen, which combines acetaminophen and naproxen sodium.
These products bring together ingredients with complementary mechanisms of action. The continued evolution of combination products is helping expand the range of OTC pain relief choices available to consumers.
What Is Multimodal Pain Management?
Multimodal pain management is an approach that combines different pain relief methods rather than relying on a single medication, therapy or mechanism.[3,6,7]
A multimodal recovery plan may include:[3,4,6]
Acetaminophen
NSAIDs
Ice therapy
Elevation
Physical therapy
Early movement when appropriate
Other techniques recommended by a healthcare provider
The goal is to support pain relief by addressing pain through multiple pathways.[3,6]
How does TYLENOL® with Naproxen Fit Into the Evolution of OTC Pain Relief?
TYLENOL® with Naproxen is the first and only FDA-approved over-the-counter pain reliever that combines 650 mg of acetaminophen and 220 mg of naproxen sodium in a single fixed-dose. It is indicated for the temporary relief of minor aches and pain in adults and children 12 years and over and is available without a prescription. For children under 12, consult a healthcare provider.
TYLENOL® with Naproxen contains the following active ingredients in each dose:
650 mg acetaminophen
220 mg naproxen sodium
Following rigorous testing, clinical studies, and partnerships with HCPs, TYLENOL® with Naproxen is redefining what’s possible in the OTC pain category and in doctors’ offices, with a simplified multimodal pain management option that aims to help drive increased adherence and patient relief.
Why Was TYLENOL® with Naproxen Developed?
Millions of Americans experience persistent pain, and until now, OTC options have been limited on both duration and strength, leaving 75% of sufferers dissatisfied with their relief. [8] It’s more important than ever to expand safe, effective non-opioid options for both consumers and healthcare providers. TYLENOL® with Naproxen provides a stronger* solution that lasts 12 hours and is available without a prescription or opioid risk.
TYLENOL® with Naproxen expands the range of available OTC pain relief options by combining acetaminophen and naproxen sodium in a single fixed-dose product.
Why Does TYLENOL® With Naproxen Contain Two Active Ingredients?
Acetaminophen and naproxen sodium work differently in the body. Acetaminophen is a pain reliever. Naproxen sodium is also a pain reliever and belongs to a class of medicines known as nonsteroidal anti-inflammatory drugs (NSAIDs). By combining both ingredients into a single dose, TYLENOL® with Naproxen provides a multimodal approach to pain relief while maintaining the convenience of one OTC product.
What Safety Information Should Consumers Know About TYLENOL® with Naproxen?
Consumers should always read and follow the Drug Facts label.
Acetaminophen and naproxen sodium have different safety considerations:
Taking too much acetaminophen may cause serious liver damage.[1,2]
NSAIDs can increase the risk of stomach bleeding in some individuals.[5]
NSAIDs, except aspirin, can increase the risk of heart attack, heart failure, and stroke.
NSAIDs may not be appropriate for everyone.[5]
If you have questions about pain relief options, medications you take, or whether a product is right for you, talk with your healthcare provider.
FAQs
*Compared to Aleve 220 mg or naproxen sodium 220 mg.
- Acetaminophen Tablets or Capsules, Cleveland Clinic, (Accessed 10/20/2026), https://my.clevelandclinic.org/health/drugs/18829-acetaminophen-capsules-or-tablets
- Pain Relievers, MedlinePlus (Accessed on 10/20/2026), https://medlineplus.gov/painrelievers.html
