Safety Profile of Naproxen

Gastrointestinal Risks

Approximately 10–20 % of patients taking naproxen experience dyspepsia, although these symptoms do not reliably indicate ulcer formation. 1
The annual incidence of serious gastrointestinal bleeding with naproxen ranges from 1 in 2,100 in adults younger than 45 years to 1 in 110 in adults older than 75 years. 1
In the United States, naproxen‑related gastrointestinal bleeding accounts for roughly 32,000 hospital admissions and 3,200 deaths each year. 2
Concomitant use of anticoagulant therapy increases the risk of naproxen‑associated gastrointestinal bleeding by 5–6 fold. 1

The ADAPT trial was halted because naproxen use was associated with a higher rate of cardiovascular events compared with placebo, indicating a potential increase in cardiovascular risk. 3
All non‑steroidal anti‑inflammatory drugs, including naproxen, carry cardiovascular warnings following the market withdrawal of selective COX‑2 inhibitors. 3

Patients with an estimated creatinine clearance below 30 mL/min should avoid naproxen therapy. (Guideline recommendation based on renal safety considerations.) 2
Serum creatinine should be monitored after initiating naproxen in individuals at risk for renal impairment, especially those concurrently receiving ACE inhibitors or ARBs. 2

Up to 15 % of naproxen users exhibit mild, transient elevations in liver enzymes, while about 1 % develop clinically significant ALT/AST elevations (≥ 3 × upper limit of normal). (Observational data.)

Naproxen is considered compatible with breastfeeding, similar to ibuprofen and indomethacin, and may be used by lactating individuals without expected adverse effects on the infant. 2