What it is
Naproxen is an NSAID from the propionic acid group (the same family as ibuprofen) with a much longer half-life: 12–17 hours compared with about 2 hours for ibuprofen. That allows dosing every 12 hours, which helps adherence.
It stands out because, of the commonly used NSAIDs, it has shown the lowest thrombotic risk. Even so, in a patient with cardiovascular risk the first step is to avoid the NSAID or use it for as short a time as possible.
Non-selective inhibition of COX-1 and COX-2
Naproxen shares ibuprofen's mechanism, with some clinically relevant differences:
- It inhibits COX-1 and COX-2 non-selectively, like ibuprofen.
- It has a stronger effect on platelet COX-1 than other NSAIDs → some antiplatelet effect (but reversible, unlike aspirin).
- That reversible antiplatelet effect may contribute to its lower cardiovascular risk.
- Analgesic, anti-inflammatory and antipyretic effect similar to ibuprofen.
- Greater anti-inflammatory potency than ibuprofen at equivalent doses.
At the counter
When to recommend it
- Pain with inflammation lasting days to weeks: arthritis, osteoarthritis, low back pain, periarthritis
- Primary dysmenorrhoea: as effective as ibuprofen with fewer doses
- Chronic musculoskeletal pain where convenient dosing (every 12 h) improves adherence
- Patients with moderate cardiovascular risk in whom the doctor considers an NSAID necessary: it has shown the lowest risk
- Migraine: effective in the acute phase, especially combined with triptans
When not to
- Severe kidney or liver failure
- Pregnancy (avoid from week 20; contraindicated in the third trimester)
- Active peptic ulcer without gastric protection
- Allergy to NSAIDs
- Do not combine with other NSAIDs
- In patients who need a real antiplatelet effect: naproxen does not replace aspirin
Warnings
- Caution GASTRIC RISK: similar to ibuprofen. Always advise taking it with food and offer gastric protection if there are risk factors (older age, previous ulcer, corticosteroids).
- Caution OLDER PEOPLE: the longer half-life in older people can lead to accumulation. Start with low doses and monitor kidney function.
- Caution INTERACTION WITH ASPIRIN: naproxen can block the antiplatelet effect of low-dose aspirin (the same interaction as ibuprofen). If the patient takes antiplatelet aspirin, take that first.
- Worth knowing BETTER CARDIOVASCULAR PROFILE: consistent epidemiological studies show that naproxen has a lower risk of cardiovascular events than diclofenac, celecoxib and high-dose ibuprofen. If an NSAID is needed in a patient with cardiovascular risk, it is the lowest-risk option —but the first question is whether it is needed.
Pharmacokinetics
- Absorption
- Oral: rapid and almost complete absorption (95%). Peak plasma level at 2–4 hours. Food delays absorption but does not reduce it.
- Distribution
- High plasma protein binding (99%). Good penetration into synovial fluid: especially useful in arthritis.
- Metabolism
- Hepatic, via CYP2C9. It produces inactive metabolites. Caution with CYP2C9 inhibitors.
- Elimination
- Renal (95%). Half-life: 12–17 hours → dosing every 12 hours. In older people the half-life may be longer.
Naproxen vs ibuprofen
| Aspect | Naproxen | Ibuprofen |
|---|---|---|
| Half-life | 12–17 hours | 1.8–2 hours |
| Dosing | Every 12 hours | Every 6–8 hours |
| Onset of action | Slower (2–4 hours) | Faster (1–1.5 hours) |
| Cardiovascular risk | The lowest of the common NSAIDs | Low to moderate (higher at high doses) |
| Gastric risk | Similar to ibuprofen | Similar |
| Best for | Chronic pain, adherence, moderate cardiovascular risk | One-off acute pain, fast effect |
Naproxen when prolonged cover is needed or there is moderate cardiovascular risk. Ibuprofen when a fast effect is wanted for one-off pain. Both need gastric protection in at-risk patients.
Self-assessment
Three questions. When you check your answers you will see the explanation for each one.
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Dosing frequency depends on the half-life. With a half-life of 12–17 hours, naproxen keeps therapeutic levels throughout the day with only 1–2 doses. Ibuprofen, with a half-life of about 2 hours, has to be repeated every 6–8 hours to keep its effect.
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Epidemiological studies and meta-analyses place naproxen as the NSAID with the lowest cardiovascular risk in long-term use; even so, the lowest dose for the shortest time remains the rule. Diclofenac has the worst cardiovascular profile. Celecoxib also carries increased cardiovascular risk, although lower than diclofenac.
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Ibuprofen reaches its peak plasma level at 60–90 minutes, compared with 2–4 hours for naproxen. For one-off acute pain where quick relief is wanted, ibuprofen is better. Naproxen shines where prolonged cover is the priority.
Training content. It does not replace the summary of product characteristics or clinical judgement.