Based on NIH | Is it true that naproxen increases the risk of gastrointestinal bleeding and kidney injury compared with ibuprofen?

Naproxen vs. Ibuprofen: What we know about GI bleeding and kidney injury risks

Both naproxen and ibuprofen are non-steroidal anti-inflammatory drugs (NSAIDs) that can cause gastrointestinal (GI) bleeding and kidney injury, especially at higher doses, with longer use, or in people with certain risk factors. Based on regulatory labeling and comparative research, neither naproxen nor ibuprofen is universally “safer” across all outcomes; risks are broadly similar, with some differences by outcome, dose, and patient factors. ^{[1] [2] [3]}

Bottom line

• GI bleeding/ulcers: All NSAIDs, including naproxen and ibuprofen, can cause stomach and intestinal ulcers and bleeding, which can occur without warning and may be serious or fatal. Regulatory warnings apply to both drugs, and the chance increases with higher doses, longer use, older age, alcohol use, smoking, and certain medications (like corticosteroids, anticoagulants, SSRIs/SNRIs). There is no consistent high‑quality evidence that naproxen has a meaningfully higher GI bleeding risk than ibuprofen at comparable doses in the general population; the risk appears comparable and driven by dose and patient risk factors. ^{[1] [2] [3] [4]}
• Kidney injury (acute kidney injury, AKI): NSAIDs as a class increase AKI risk. Comparative analyses suggest the AKI risk is elevated and fairly similar across individual traditional NSAIDs, including naproxen and ibuprofen, without statistically significant differences between them in pooled estimates. ^[5] A large VA cohort found AKI risk varied by agent, with adjusted odds ratios higher for ibuprofen than naproxen; however, absolute differences were modest and confounded by dose and patient factors. ^[6]

In practice, clinicians usually choose the lowest effective dose for the shortest time, consider user‑specific risk factors, and add stomach protection (like a proton pump inhibitor) for high‑risk users rather than favoring one of these two NSAIDs solely on presumed safety. If you have prior ulcers, GI bleeding, chronic kidney disease, heart failure, are older, or take interacting drugs, NSAIDs may warrant extra caution or alternatives. ^{[1] [2] [3]}

---

What official safety information says

• Serious GI risks with all NSAIDs: Ulcers and bleeding in the stomach or intestines can occur at any time, often without warning, and can be fatal. Risk rises with higher doses, longer use, older age, alcohol, smoking, poor health, corticosteroids, anticoagulants, SSRIs/SNRIs, or a history of ulcers/GI bleeding. ^{[1] [2] [4]}
• Serious kidney risks with all NSAIDs: Long‑term administration can cause renal papillary necrosis and other kidney injury, especially in people relying on kidney prostaglandins to maintain blood flow (e.g., those with dehydration, heart failure, liver disease, diuretic or ACE inhibitor use). Labels for both ibuprofen and naproxen carry the same kidney warnings. ^{[3] [7]}

These warnings emphasize class effects rather than a clear safety advantage of one drug over another. They recommend the lowest effective dose for the shortest possible duration and considering non‑NSAID alternatives in high‑risk users. ^{[1] [2]}

---

Comparative evidence at a glance

Kidney injury (AKI)

• Systematic review/meta‑analysis of observational studies: A pooled analysis of cohort data showed a statistically significant increase in AKI risk with most traditional NSAIDs. Pooled risk ratios among individual NSAIDs including ibuprofen and naproxen were consistent (approximately 1.6–2.1) and differences between drugs did not reach statistical significance. ^[5]
• Large VA nested case‑control cohort (laboratory‑defined AKI): Among new NSAID users, AKI risk increased compared with non‑users; agent‑specific adjusted odds ratios suggested ibuprofen (2.25) and naproxen (1.72) were both associated with higher AKI risk, with ibuprofen numerically higher than naproxen in this dataset. Risk tended to be lower with more COX‑2 selective agents and higher with multiple NSAIDs. ^[6]

Takeaway: AKI risk rises with any NSAID; comparative signals vary by dataset and are influenced by dose, exposure, and patient characteristics. The best pooled evidence does not show a statistically significant difference between naproxen and ibuprofen overall, while a large cohort suggests numerically higher AKI odds with ibuprofen than naproxen. ^{[5] [6]}

Gastrointestinal bleeding/ulcers

• Regulatory labeling for NSAIDs uniformly warns of ulcers and GI bleeding for both naproxen and ibuprofen. The chance increases with dose, duration, age, alcohol, smoking, interacting drugs, and prior ulcer/bleed history. Short‑term use is not risk‑free. ^{[1] [2] [4]}
• Randomized trial meta‑analyses and safety reviews across NSAIDs have shown GI risk is a class effect and varies with dose and COX‑2 selectivity; however, direct head‑to‑head differences between naproxen and ibuprofen at over‑the‑counter doses are not consistently significant. In high‑risk users, adding gastroprotection (e.g., a PPI) or choosing a COX‑2 selective agent may be considered to reduce GI events. ^[8]

Takeaway: At comparable doses, naproxen and ibuprofen both carry meaningful GI risks, and consistent, definitive evidence that naproxen is worse than ibuprofen for GI bleeding across typical use is lacking. Risk mitigation (dose, duration, and PPIs in high‑risk users) matters more than choosing one of these two in most cases. ^{[1] [2] [8]}

---

Practical guidance for safer use

• Use the lowest effective dose, for the shortest time. This is emphasized across NSAID labeling to reduce both GI and kidney risks. ^{[1] [2]}
• Avoid combining NSAIDs (e.g., ibuprofen plus naproxen), and be cautious with other bleeding‑risk medicines (anticoagulants, antiplatelets, SSRIs/SNRIs, corticosteroids). ^{[1] [2]}
• Protect the stomach if you are high‑risk (older age, prior ulcer or GI bleed, or on interacting drugs) by discussing a proton pump inhibitor with your clinician. ^[2]
• Stay hydrated and avoid NSAIDs during illnesses that cause dehydration (vomiting/diarrhea) to lower kidney stress, and monitor kidney function if you have CKD, heart failure, cirrhosis, or take diuretics/ACE inhibitors/ARBs. ^{[3] [7]}
• Watch for warning signs: black or bloody stools, vomiting blood, severe stomach pain (GI bleed), reduced urination, swelling, sudden weight gain, or rising creatinine if monitored (kidney injury). Stop the NSAID and seek care if these occur. ^{[1] [3]}

---

Summary table

Question	Naproxen	Ibuprofen	What this means
GI ulcers/bleeding	Class warning; risk increases with dose/duration and patient factors. [1] [2] [4]	Class warning; risk increases with dose/duration and patient factors. [1] [2] [3]	No consistent evidence that one is uniformly safer for GI bleeding at comparable doses; manage risk factors and consider PPIs if high‑risk.
Acute kidney injury	Elevated AKI risk; pooled estimates similar to other NSAIDs; not significantly different from ibuprofen in meta‑analysis. [5]	Elevated AKI risk; pooled estimates similar to other NSAIDs; not significantly different from naproxen in meta‑analysis. [5]	Meta‑analysis: similar AKI risk across traditional NSAIDs; one large cohort showed ibuprofen with numerically higher odds than naproxen. [6]

---

Key takeaways

• It would be an oversimplification to say naproxen “increases” GI bleeding or kidney injury risk compared with ibuprofen across the board. Both carry these risks as class effects, and differences are small, dose‑dependent, and influenced by who is taking them and for how long. ^{[1] [2] [5]}
• For many users, choosing between naproxen and ibuprofen should focus on the lowest effective dose, shortest duration, and personal risk profile, with stomach protection or alternative pain strategies if risk is high. ^{[1] [2]}

If you’re unsure which option fits your health conditions or other medications, speaking with your clinician or pharmacist can help tailor a safer plan. 😊 ^{[1] [2]}