NSAIDs · Pain & inflammation
Naproxen
Naprosyn® · Aleve®(brand names vary by market)
The long-acting NSAID with the least cardiovascular signal.
Also: modified release, oral liquid, suppository
Mechanism
Non-selective COX inhibition: less prostaglandin, so less inflammation and pain, and less protection for the gastric mucosa and the renal afferent arteriole.
Indications
- Inflammatory arthritis and osteoarthritis
- Acute gout
- Musculoskeletal pain
- Dysmenorrhoea
Formulations
Dosing concepts
Duration
Used at the lowest effective dose for the shortest period. Most NSAID harm is a function of duration and of the patient rather than of the dose.
Gastroprotection
A proton pump inhibitor is added for anyone over 65, with prior ulceration, or on an anticoagulant, antiplatelet, steroid or SSRI.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- ~95%
- Half-life
- 12 to 17 h
- Elimination
- hepatic: Glucuronidation and CYP2C9; long half-life allows twice-daily dosing
- Protein binding
- >99%
Adverse effects
- Gastrointestinal ulceration and bleedingcommon & serious
- Acute kidney injuryseriousEspecially with an ACE inhibitor and a diuretic, the triple whammy.
- Fluid retention and worsening heart failureserious
- Raised blood pressurecommon
- Bronchospasm in aspirin-exacerbated respiratory diseaseserious
Contraindications & precautions
Contraindications
- Active peptic ulceration or gastrointestinal bleeding
- Severe heart failure
- eGFR below about 30
- Third trimester of pregnancy
- Coronary artery bypass grafting, peri-operatively
Precautions
- Older adults
- CKD
- Concurrent RAAS blockade or diuretics
- Concurrent anticoagulants, antiplatelets, steroids or SSRIs
- Hypertension
Interactions
- ACE inhibitor / ARB + diuretic + NSAID (the 'triple whammy')avoidAcute kidney injury, classically in a dehydrated older adult who bought ibuprofen for a sore knee.
- Warfarin + NSAIDs (e.g. ibuprofen, naproxen)avoidMajor GI bleeding risk multiplies while the INR looks reassuring.
- SSRIs + NSAIDs / anticoagulantsmonitorUpper GI bleeding risk roughly doubles versus either alone.
- NSAIDs + LithiumcautionLithium rise within days of regular NSAID use.
- NSAIDs + Methotrexate (especially high-dose)cautionMethotrexate toxicity: mucositis, cytopenias, renal injury (chiefly with high-dose oncology regimens).
Monitoring
Renal function and blood pressure
Both move, and both move silently · Within a week or two of starting in anyone at risk
Gastrointestinal symptoms and hemoglobin
Bleeding is often occult
Whether it is still needed
NSAIDs bought over the counter are the invisible half of most NSAID harm
Counselling points
- Take it with food.
- Do not take other anti-inflammatories at the same time, including ones you buy yourself.
- Stop and contact us if you get stomach pain, black stools, or notice you are passing much less urine.
- Tell us if you have kidney problems, heart failure, or take blood pressure or blood thinning medicines.
Clinical pearls
- Of the non-selective NSAIDs, naproxen carries the smallest cardiovascular signal, which is why it is often the choice when an NSAID is needed in someone with cardiac risk.
- The triple whammy of NSAID, ACE inhibitor and diuretic is one of the most reliable ways to produce an acute kidney injury, and the NSAID is usually the one the patient bought themselves.
References & review
- Naproxen product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.