Publication

Article

Long-Lasting Pain Relief: A Pharmacist’s Guide to the Efficacy and Safety of Naproxen Sodium

This article is sponsored by Aleve®.

Aleve® (naproxen sodium) temporarily reduces fever and temporarily relieves minor aches and pains due to minor pain of arthritis, muscular aches, backache, menstrual cramps, headache, toothache, and the common cold. Use as directed.1

Pain management plays a crucial role in people’s lives, significantly impacting their physical well-being, emotional health, and overall quality of life.2 Acute pain, as defined by the International Association for the Study of Pain, is characterized by sudden onset of sharp or intense discomfort that serves as a protective mechanism signaling potential disease or injury.3 This type of pain commonly occurs with conditions such as injury, surgery, illness, trauma, or invasive medical procedures, and typically resolves within 6 months as the underlying cause is treated or heals.3 Data from the National Center for Health Statistics reveal the widespread nature of acute pain among US adults with 58.9% reporting some form of pain within a 3-month period.4 The most common manifestations were back pain (39.0%), lower limb pain (36.5%), and upper limb pain (30.7%).4

Patients can choose from multiple treatment approaches, ranging from over-the-counter (OTC) medications to prescription drugs and nonpharmacological methods. Aleve® has demonstrated both safety and efficacy for OTC pain relief when used as directed, along with several other treatment options.1,5 It is important for pharmacists to have a thorough understanding of treatment options for acute pain to effectively guide patients in managing their pain.

Acute Nonprescription Pain Management

Common OTC pain relievers include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) like ibu­profen and naproxen sodium.6,7

Acetaminophen, ibuprofen, andnaproxen sodium provide temporary relief for minor aches and pains including headaches, colds, backaches, toothaches, menstrual cramps, muscle aches, and minor arthritis pain. They can also be used as antipyretics.1,6,7

Mechanisms of Action

NSAIDs primarily work by inhibiting cyclooxygenase (COX) enzymes, reducing production of eicosanoids, which contribute to platelet adhesion, vasodilation, temperature regulation, and pain perception.8

Acetaminophen inhibits COX pathways centrally; it lacks peripheral anti-inflammatory activity or direct COX-1 and COX-2 binding.9 Its exact mechanism remains unclear, but it primarily acts in the central nervous system to provide analgesic and antipyretic effects.9

Dosing

It is crucial to use the lowest effective dose and not exceed the recommended amount on the label. Understanding the differences in duration of action and dosing among these OTC options is important. Depending on the strength and labeling, both acetaminophen and ibuprofen can be dosed every 4 to 6 hours for adults and children 12 years and older.6,7

Naproxen sodium 220 mg is also indicated for adults and children 12 years and older but has a longer duration of action of up to 12 hours, allowing for less frequent dosing intervals of 8 to 12 hours per dose.1

Opioid-Free Pain Management Strategies

The CDC guidelines recommend clinicians prescribe opioids only when the anticipated benefits in pain relief outweigh associated risks.10 When appropriate, clinicians are encouraged to consider alternative nonopioid pain management options such as NSAIDs.10

Clinical Efficacy of Aleve® (Naproxen Sodium)

Aleve® temporarily reduces fever and temporarily relieves minor aches and pains due to minor pain of arthritis, muscular aches, backache, menstrual cramps, headache, toothache, and the common cold.1

Dental Pain

Naproxen Sodium vs Hydrocodone Plus Acetaminophen

A single-center, randomized, double-blind, parallel, placebo-​controlled, single-dose study (NCT04307940) evaluated the efficacy and safety of naproxen sodium versus hydrocodone plus acetaminophen for dental pain relief.11 Patients experiencing moderate or severe pain (N=221) after surgical removal of impacted third molars were randomized to receive either naproxen sodium 440 mg (n=90), hydrocodone plus acetaminophen 650 mg/10 mg (n=87), or placebo (n=44) over a 12-hour study period.11 Naproxen sodium (440 mg) was as effective as hydrocodone plus acetaminophen in hours 0 to 4 at reducing pain intensity. It was also significantly more effective than hydrocodone plus acetaminophen in the secondary outcomes of total pain intensity (P=.01), total pain relief (0 to 6 and 0 to 12 hours, P<.05), time to rescue pain medication (P<.001), and the duration of pain at least half gone over 12 hours (P<.001).11 The incidence of adverse events (AE) ​was higher with hydrocodone plus acetaminophen (n=63) compared with naproxen sodium (n = 2) and placebo (n = 20).11

Osteoarthritis

Professional associations, like the American Academy of Orthopaedic Surgeons and the American College of Rheumatology strongly recommend NSAIDs such as naproxen sodium, the active ingredient in Aleve®, for the treatment of osteoarthritis (OA) pain.12,13

Aleve® vs Ibuprofen

In 2 identical multicenter, randomized, double-blind, placebo-​controlled, multidose, parallel-design studies, the efficacy and safety of Aleve® (< 65 years, 660 mg/day; age ≥ 65 years, 440 mg/day) was compared with those of ibuprofen (1200 mg/day) and placebo in individuals 25 years and older with osteo­arthritis of the knee.14 The study enrolled 461 participants; the results demonstrated that Aleve® and ibuprofen effectively relieved pain in participants with mild to moderate knee osteoarthritis over the 7-day study period.14 Additionally, Aleve® demonstrated significantly greater efficacy in managing symptoms of night pain on days 1, 2, 3, and 5 (P<.05 for nights 1 and 3; P < .01 for nights 2 and 5) compared to ibuprofen, which showed significantly greater efficacy on nights 1 and 2 (P < .05).14

Aleve® vs Placebo

In a post hoc pooled analysis of 4 randomized, double-blind, placebo-controlled studies (NCT03570554), the efficacy of Aleve® in osteoarthritis patients using age-based dosing (<65 years, 660 mg/day; ≥65 years, 440 mg/day) was evaluated over 7 days.15 Key outcomes including pain severity, stiffness, and physical function were assessed via 5-point rating scales and timed walking tests.15 Compared to placebo, Aleve® significantly improved both pain relief and physical function (P<.05) shown in the Figure.15

Dysmenorrhea

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well established initial therapy for dysmenorrhea, as they provide a direct analgesic effect through inhibition of prosta­glandin synthesis, the primary contributor to menstrual pain.16 Recommendations from the American Academy of Family Physicians support the use of NSAIDs as the first-line treatment for primary dysmenorrhea.17

Aleve® vs Acetaminophen

In a double-blind, randomized, crossover study (NCT03448536), the efficacy of Aleve® (440 mg) was compared with that of acetaminophen (1000 mg) in 201 healthy female participants aged 15 to 35 years with primary dysmenorrhea.18 From 0 to 6 hours after dosing, both pain intensity and total pain relief were mostly comparable between naproxen sodium and acetaminophen; significant differences in pain intensity and pain relief in favor of naproxen sodium became apparent after approximately hour 6 and were maintained over 12 hours through a single dose. Over the ​12-hour study period, Aleve® provided significantly greater total pain relief (P<.001) and lower pain intensity (P<.001) compared to acetaminophen through a single dose.18

Safety Profile

Naproxen sodium has been demonstrated to be safe when used as directed for various acute pain conditions.1,5 A retrospective analysis of pooled safety data revealed that the safety profile of naproxen sodium was comparable to that of placebo, with similar rates of adverse events observed across all treatment groups, including the active comparators.5 Most adverse events experienced by participants were considered mild to moderate and were often related to the gastrointestinal system; no significant differences were noted between placebo and Aleve® groups.5

Role of Pharmacist

Pharmacists play a crucial role in promoting safe and effective pain management options to consumers. In discussions about first-line OTC pain therapies, pharmacists can recommend the use of NSAIDs like Aleve® as a viable treatment option, especially when long-lasting pain relief is desired. Aleve® has been clinically proven to be a strong, long-lasting, nonopioid drug alternative approved for the temporary relief of headaches, minor pain of arthritis, toothaches, muscular aches, backaches, dysmenorrhea, minor aches and pains linked to the common cold, as well as for temporarily reducing fever.1 It offers advantages such as strong, effective pain relief with less frequent dosing compared to alternative treatments when pain persists.1, 6, 7

REFERENCES

  1. Aleve® professional information. Bayer HealthCare. 2021. Accessed October 22, 2024. https://www.bayer.com/sites/default/files/Aleve%20Professional%20Information%202021.pdf
  2. Pandelani FF, Nyalunga SLN, Mogotsi MM, Mkhatshwa VB. Chronic pain: its impact on the quality of life and gender. Front Pain Res (Lausanne). 2023;4:1253460. doi:10.3389/fpain.2023.1253460
  3. International Association for the Study of Pain. Acute pain. Published 2021. Accessed January 10, 2025. https://www.iasp-pain.org/resources/topics/acute-pain/
  4. Lucas J, Connor E, Bose J. Back, Lower Limb, and Upper Limb Pain Among U.S. Adults, 2019. Published online July 29, 2021. Accessed January 10, 2025. doi:https://doi.org/10.15620/cdc:107894
  5. Kyeremateng K, Troullos E, Paredes-Diaz A. Safety of naproxen compared with placebo, ibuprofen and acetaminophen: a pooled analysis of eight multiple-dose, short-term, randomized controlled studies. Curr Med Res Opin. 2019;35(10):1671-1676. doi:10.1080/03007995.2019.1612338
  6. Tylenol (acetaminophen tablet). Drug label. National Institutes of Health DailyMed. October 2024. Accessed October 22, 2024. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1622f694-4d63-4c56-8737-fae31f0ecfb7
  7. Advil (ibuprofen tablet). Drug label. National Institutes of Health DailyMed. July 2024. Accessed October 22,2024. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=772360bd-8631-4d24-b4db-5a7e6e1d9a13
  8. Ghlichloo I, Gerriets V. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. https://www.ncbi.nlm.nih.gov/books/NBK547742/
  9. Gerriets V, Anderson J, Patel P, et al. Acetaminophen. [Updated 2024 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. https://www.ncbi.nlm.nih.gov/books/NBK482369/
  10. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC clinical practice guideline for prescribing opioids for pain — United States, 2022. MMWR Recomm Rep. 2022;71(No. RR-3):1–95. doi:10.15585/mmwr.rr7103a1
  11. Cooper SA, Desjardins PJ, Bertoch T, et al. Analgesic efficacy of naproxen sodium versus hydrocodone/acetaminophen in acute postsurgical dental pain: a randomized, double-blind, placebo-controlled trial. Postgrad Med. 2022;134(5):463-470. doi:10.1080/00325481.2021.2008180
  12. Brophy RH, Fillingham YA. AAOS clinical practice guideline summary: management of osteoarthritis of the knee (nonarthroplasty), third edition. J Am Acad Orthop Surg. 2022;30(9):e721-e729. doi:10.5435/JAAOS-D-21-01233
  13. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheumatol. 2020;72(2): 220-233. doi:10.1002/art.41142
  14. Schiff M, Minic M. Comparison of the analgesic efficacy and safety of nonprescription doses of naproxen sodium and Ibuprofen in the treatment of osteoarthritis of the knee. J Rheumatol. 2004;31(7):1373-1383.
  15. Couto A, Troullos E, Moon J, Paredes-Diaz A, An R. Analgesic efficacy and safety of non-prescription doses of naproxen sodium in the management of moderate osteoarthritis of the knee or hip. Curr Med Res Opin. 2018;34(10):1747-1753. doi:10.1080/03007995.2018.1437029
  16. French L. Dysmenorrhea. Am Fam Physician. 2005;71(2):285-291.
  17. Osayande AS, Mehulic S. Diagnosis and initial management of dysmenorrhea. Am Fam Physician. 2014;89(5):341-346.
  18. Daniels SE, Paredes-Diaz A, An R, Centofanti R, Tajaddini A. Significant, long-lasting pain relief in primary dysmenorrhea with low-dose naproxen sodium compared with acetaminophen: a double-blind, randomized, single-dose, crossover study. Curr Med Res Opin. 2019;35(12):2139-2147. doi:10.1080/03007995.2019.1654987
Download PDF