What are nonsteroidal anti-inflammatory drugs (NSAIDs)?
In this article
MEDICINE GUIDE • UPDATED: 8 SEPTEMBER 2026
Why can an effect that reduces pain affect other organs?
NSAIDs are effective medicines for the right patient. Safe use depends on understanding the cause of pain, choosing an appropriate medicine and considering the stomach, kidneys, heart and other treatments together.
A tablet for headache, a gel after a sprain or a prescription for joint pain may involve the same medicine family: nonsteroidal anti-inflammatory drugs, or NSAIDs. In English, they are called non-steroidal anti-inflammatory drugs, abbreviated NSAIDs. They reduce pain, fever and inflammation, but are not equally effective for all pain.
Frequent use does not mean these medicines are risk-free for everyone. The same drug may suit short-term use in a healthy young person but cause major problems in someone with kidney disease taking multiple medicines. The right question is therefore not simply “Which painkiller is stronger?” but “Which is appropriate for my pain and health?” . [1], [3]
How do NSAIDs work? Two sides of the same mechanism
In the body, cyclooxygenase (COX) enzymes produce substances such as prostaglandins. Some increase pain sensitivity, fever and inflammation. Others help protect the stomach lining, maintain kidney blood flow and support vascular–platelet balance.
NSAIDs reduce COX activity. Alongside the desired pain relief, protective functions may therefore be affected. Distinguishing COX-1 from COX-2 is useful, but one is not entirely harmful and the other entirely beneficial. Both have physiological roles, particularly in the kidney. [2]
Pain, fever, swelling and movement-related symptoms may ease.
Gastrointestinal damage, impaired kidney function, fluid retention and vascular risk become concerns.
The diagram explains the biological mechanism; it does not show that every user will develop these effects.
Which medicines belong to this group?
Before looking at the brand on the box, check the active ingredient . The same ingredient may be sold under different brands; cold remedies or combination pain products may also contain NSAIDs. These examples are neither a prescription nor a ranking of superiority. [1], [3]
| Medicine / subgroup | Examples | The distinction to understand |
|---|---|---|
| Conventional nonselective NSAIDs | Ibuprofen, naproxen, diclofenac, dexketoprofen, ketoprofen, flurbiprofen, indomethacin | Their COX effects and durations differ. Adding one to another may lead to duplicate NSAID use. |
| Those relatively more directed toward COX-2 | Meloxicam, etodolac | Relative selectivity depends on dose; it does not fully protect the stomach, kidneys or heart. |
| Selective COX-2 inhibitors | Celecoxib, etoricoxib | Some gastrointestinal events may be less frequent. Cardiovascular and kidney risks must still be assessed. |
| Aspirin | Acetylsalicylic acid | It belongs to the NSAID family; low-dose use for platelet effects differs from pain and inflammation treatment. |
| Nimesulide | Systemic nimesulide products | Liver safety is particularly important. EMA introduced short-term-use restrictions; it should not be regarded as a routine option for long-term joint pain. |
EMA restrictions for systemic nimesulide include limiting treatment to a maximum of 15 days . This is not a shared duration limit for all NSAIDs; current prescribing information for the country and product must be considered separately. [6]
Why discuss paracetamol and metamizole separately?
| Medicine | Basic characteristic | Main caution |
|---|---|---|
| Paracetamol / acetaminophen | A painkiller and fever reducer; not a conventional NSAID because it lacks a pronounced peripheral anti-inflammatory effect. | Taking it simultaneously from different packages may exceed the total dose. Overdose can cause serious liver damage. |
| Metamizole / dipyrone | A pyrazolone derivative primarily used for pain and fever. Although included under NSAIDs in some broad classifications, it should not be presented within the same safety framework as conventional anti-inflammatory drugs. | There is a rare but severe risk of agranulocytosis, a serious reduction in particular infection-fighting white blood cells. |
If fever, chills, sore throat or mouth sores develop during metamizole use, stop it and seek urgent assessment and a blood count. This reaction is not dose-dependent; previous trouble-free use offers no assurance. It matters especially in patients with impaired bone marrow function. Switching to paracetamol or metamizole does not automatically mean switching to risk-free pain treatment. [4], [5]
For which pain may they help?
In appropriate patients, NSAIDs may be used for musculoskeletal injuries, toothache, menstrual cramps, acute gout and inflammatory joint symptoms. They also help some headaches. By contrast, for neuropathic pain felt as numbness, electric shocks or burning, they are not expected to suffice alone. Recurrent pain requires reassessing the cause, not merely seeking a stronger NSAID. [3], [16]
In osteoarthritis the aim is to reduce pain and facilitate movement; NSAIDs do not rebuild cartilage. NICE recommends topical NSAIDs for knee osteoarthritis. Medicines support exercise, muscle strengthening and weight management where appropriate. In rheumatoid arthritis, symptom relief does not replace disease-modifying treatments. [7], [3]
Side effects: why considering only the stomach is insufficient
1. Stomach and intestines: burning and bleeding are different
Indigestion, stomach pain or nausea may occur; more serious effects include ulcers, bleeding and perforation. Bleeding may occur without preceding significant stomach pain. Older age, previous ulcers or bleeding and other medicines increasing bleeding raise the risk. [8]
Taking the medicine with food may reduce some stomach symptoms but does not reliably prevent ulcers or bleeding. Protective treatment such as a proton pump inhibitor (PPI) may be used when needed to reduce upper gastrointestinal risk. A stomach-protective medicine does not protect the kidneys and heart; it does not make NSAID use indefinitely safe. [7], [25]
2. Heart and vessels: dose, duration and baseline risk matter
Systemic NSAIDs other than aspirin may increase heart attack and stroke risk, which can begin early in treatment. Fluid retention, raised blood pressure and worsening heart failure also matter. Absolute risk in someone with heart disease differs from that in a healthy person. [8]
Although naproxen had a relatively more favorable vascular risk profile in the same meta-analysis, this does not make it safe for the stomach, kidneys or heart failure. A one-dimensional ranking such as “safest for the heart” obscures other risks. [9]
In 24.081 arthritis patients over a mean follow-up of 34,1 months, cardiovascular death, nonfatal heart attack or stroke; intention-to-treat analysis. Mean daily doses were respectively 209, 852 and 2.045 mg. These are study doses, not usage recommendations. Celecoxib was not worse than the other two drugs at the compared doses (noninferiority). Numerical differences do not prove superiority or the “safest medicine”. There was no placebo arm, and discontinuation was frequent. [10]
3. Kidneys: dehydration and drug combinations can change risk
Particularly with kidney disease, heart failure or fluid loss, NSAIDs may impair kidney blood flow. Vomiting, diarrhea, insufficient fluids and dehydration in hot weather may make a previously tolerated drug riskier. Creatinine or potassium may rise, and reduced urination and edema may develop. [28]
A risky triple combination for the kidneys
In a BMJ observational study, this triple combination, compared with the corresponding two-drug treatment without an NSAID, was associated with an acute kidney injury rate approximately %31 higher in relative terms . In the first 30 days, the increase was approximately %82 . This does not mean kidney injury occurred in %31 or %82 of users. [11]
Other important effects
Dizziness or drowsiness may occur, so “does not cause grogginess” is incorrect. Some people may develop asthma attacks, hives or serious allergic reactions. Rare liver damage is possible. NSAIDs do not have opioids’ addiction mechanism, but uncontrolled continuous use is still not harmless. [25], [24]
Gel, tablet or injection: does the route really matter?
For localized knee or superficial soft tissue pain, an appropriate topical NSAID may reduce systemic drug exposure. The same effect is not expected in deep joints or widespread pain. Use over large areas, above recommended amounts or for prolonged periods, and alongside oral NSAIDs requires separate assessment. [7], [12]
Label data compare %1 diclofenac gel, 4 g to one knee four times daily, with oral 50 mg three times daily. Total bloodstream drug exposure (AUC) is approximately %6 of the oral regimen. This value is not the likelihood of side effects or the absorption rate of all gels. The doses describe only the research comparison. [12]
Injection or suppository does not eliminate gastrointestinal bleeding risk. Harm does not arise only from a tablet touching the stomach; biological effects of the circulating drug also matter. Thus “my stomach is sensitive, so I will get an injection” is not a general safety solution. [8]
Which drug combinations require particular caution?
| Concomitant medicine | Main problem / practical meaning |
|---|---|
| Another NSAID | Combinations such as ibuprofen + naproxen or diclofenac + dexketoprofen are generally not recommended; toxicity may increase. |
| Blood thinners / antiplatelet medicines | Bleeding risk must be assessed with warfarin, apixaban, rivaroxaban, clopidogrel or aspirin. |
| Corticosteroids and some antidepressants | Cortisone, SSRI and SNRI medicines require caution, particularly for gastrointestinal bleeding. |
| ACE inhibitor / ARB and diuretic | Risks include kidney injury and impaired blood pressure and fluid control. |
| Lithium or methotrexate | Drug levels or toxicity may increase, particularly important with high-dose methotrexate. |
| Low-dose aspirin + ibuprofen | Ibuprofen may reduce aspirin’s platelet-inhibiting effect. A universal timing interval is not the solution; the product and regimen must be assessed. |
This list is incomplete. Showing your current medicine list, including nonprescription products, cold remedies and supplements, to a pharmacist or physician also prevents duplicate active ingredients. [26], [27], [15]
How does the approach change in older age, pregnancy and children?
In older age, decisions are not based solely on birth year. Kidney function, previous bleeding, heart failure, frailty and medicine count are decisive. People with ulcer history, active bleeding, advanced kidney disease, severe heart failure or serious NSAID allergy should not self-treat. NSAIDs are not prohibited for everyone with asthma; previous breathing difficulty after aspirin/NSAIDs is crucial information. [3]
During pregnancy, NSAIDs should not be viewed as routine painkillers. FDA advises avoiding use without medical advice from approximately week 20 because of fetal kidney problems and reduced amniotic fluid. After approximately week 30, premature fetal ductus arteriosus closure also matters. Physician-prescribed low-dose aspirin for obstetric purposes is a separately considered exception and should not be stopped independently. [13]
In children, the medicine, age, weight and hydration are assessed together. Adult tablets or schedules are not directly adapted. Aspirin should not be used for fever in children and adolescents because of Reye syndrome, particularly with viral illnesses; NHS advises against giving it below age 16 without a prescription. Specialist-supervised aspirin for particular childhood diseases is different. [14]
NSAIDs in cancer patients: pain treatment is part of the plan
NSAIDs may contribute to pain control in selected cancer patients, especially inflammatory or bone-related pain, and are sometimes added to opioids. They are not tumor treatments and should not delay other necessary treatments for severe cancer pain. Undertreating cancer pain to avoid “strong medicines” is also inappropriate. [16]
| Treatment context | Why does it matter for NSAIDs? |
|---|---|
| Low platelets or active bleeding | Bleeding risk may increase; treatment-team approval is needed. |
| Vomiting, diarrhea, fluid loss or treatments affecting the kidneys | Kidney reserve may decrease; previously used NSAIDs require reassessment. |
| Steroid or anticoagulant treatment | Bleeding and other organ risks of combined use are assessed. |
| Pemetrexed treatment | Specific interaction and timing rules apply to ibuprofen at certain kidney-function levels; the chemotherapy team should plan this. |
For example, the pemetrexed label advises patients with creatinine clearance of 45–79 mL/minute to avoid ibuprofen during the two days before pemetrexed, the treatment day and the two days after. This rule cannot automatically be generalized to all chemotherapy or NSAIDs. [18]
Why discuss aspirin separately? Heart and cancer prevention are different
Aspirin irreversibly inhibits platelet COX-1, reducing clot formation. This is not a shared “heart-protective” property for which other NSAIDs can be substituted. You can read about its origins as a painkiller in the history of aspirin’s development . [2]
| Purpose of use | How should the evidence be framed? |
|---|---|
| Secondary prevention after cardiovascular disease | Aspirin prescribed after a heart attack or stent, for example, is part of a particular plan. Do not stop it independently after reading about painkiller risks. |
| Preventing a first heart attack / stroke in a healthy person | Not routinely recommended for everyone. USPSTF recommends against starting it for primary prevention at age 60 or older; for ages 40–59 with sufficiently high risk, the decision is individual. |
| Colorectal cancer prevention in the general population | This does not mean everyone should take aspirin. Bleeding risk exists; it does not replace screening, lifestyle or individual risk assessment. |
| Lynch syndrome | NICE recommends considering daily aspirin for longer than two years. Dose and suitability are decided with a specialist. |
| Selected surgically treated colorectal cancer | Data show benefits according to tumor characteristics such as PI3K pathway alterations; they cannot be generalized to all patients or NSAIDs. |
Primary-prevention age recommendations do not cover treatment in people with previous cardiovascular events. Starting aspirin for cancer prevention or recurrence reduction also requires a separate clinical decision. [19], [20]
The ALASCCA trialis an important example in surgically treated colorectal cancers with selected PI3K pathway alterations. In the main group with PIK3CA exon 9/20 alterations, three-year recurrence was, with daily 160 mg aspirin, %7,7 versus %14,1 with placebo: an absolute difference of 6,4 percentage points. This research dose is not a personal-use recommendation. For details, see aspirin data in colorectal cancer with PI3K alterations . [21]
In contrast, in a group not selected by molecular characteristics, ASCOLT did not show significant superiority in disease-free survival. Thus, the old statement “aspirin has been proven to prevent colorectal cancer” is too broad alone. An accurate explanation must specify which patient group received treatment, for what purpose and for how long. [22]
Practical decision tree: what to do before taking an NSAID?
This flow does not select a drug for an individual; it shows which questions should come first in discussion with a physician or pharmacist.
Identify its cause and duration and all medicines you take.
If chest pain, sudden weakness, bloody vomiting, black stools, severe allergy or fever during cancer treatment occurs: seek assessment without waiting to try a medicine.
With bleeding/ulcer, kidney/heart disease, pregnancy, allergy, blood thinners or multiple medicines: discuss suitability before starting independently.
For localized superficial pain, a topical option may be considered. If systemic treatment is needed, plan one NSAID at an appropriate dose and duration, adding exercise and cause-directed treatment.
If there is no benefit, frequent recurrence or side effects, do not increase the dose and add another NSAID. Review diagnosis and treatment; monitor blood pressure and laboratory results if needed.
What monitoring is needed during use?
Short use in a healthy person does not require the same monitoring as prolonged use in older age. For at-risk people, assess baseline blood pressure, kidney function and blood count, with liver tests as appropriate. NHS Specialist Pharmacy Service suggests considering kidney function and blood count checks within approximately two weeks after starting or changing dose, and blood pressure within about four weeks. Timing depends on the drug and patient.
During long-term treatment, regularly review whether the medicine remains necessary, its daily functional benefit and lower-risk options. Risk-based monitoring is needed rather than identical testing intervals for everyone. [23]
Frequently asked questions
Can I take painkillers from two different brands?
Both may be NSAIDs despite different brands. Check ingredients and avoid duplicate NSAIDs. Paracetamol may be planned alongside an NSAID in some cases, but liver status, total paracetamol intake and combination products must be considered. [4]
Is a serious side effect impossible after just one use?
No. Although many people face less risk with short use than with prolonged high doses, allergy or kidney problems in susceptible individuals may occur early. Previous trouble-free use does not guarantee safety in every circumstance. [3]
Can I stop when pain resolves, or must I finish the box like an antibiotic?
There is no universal “finish the box” rule for NSAIDs. Duration is planned according to the indication; the basic pain-treatment principle is the lowest effective dose for the shortest necessary time. Do not independently stop special uses such as aspirin prescribed as part of regular treatment. [3], [19]
How do alcohol and stomach-protective medicines affect risk?
Excess alcohol may increase risk, particularly gastrointestinal risk. A stomach-protective medicine does not eliminate this or NSAIDs’ effects on other organs. Do not increase the dose because “I took it with food” or “I also have a stomach medicine”. [25], [7]
The most useful approach in daily life
NSAIDs’ value is measured not only by lower pain scores but by improved walking, sleep and return to daily activities. They benefit the right patients but should be avoided in some. Knowing the active ingredient, avoiding two medicines from the same group, considering coexisting diseases and investigating recurrent painare fundamental to safe use. Particularly in older age and cancer treatment, painkiller selection must consider the entire treatment plan.
References
This text provides patient information. Study doses are not prescribing recommendations; regulatory decisions in different countries do not have the same meaning as product licenses or reimbursement conditions in Türkiye. Sources checked: 8 September 2026.
- NHS: NSAIDs — uses, side effects and interactions
- NCBI Bookshelf: COX Inhibitors — mechanism of action
- NICE BNF: Non-steroidal anti-inflammatory drugs
- American Cancer Society: Non-opioid medicines for cancer pain
- EMA: Metamizole-containing medicinal products — agranulocytosis precautions
- EMA: Restrictions on systemic nimesulide use
- NICE NG226: Osteoarthritis in over 16s — recommendations
- FDA: CALDOLOR (intravenous ibuprofen), January 2026 prescribing information
- CNT Collaboration, Lancet 2013: Vascular and upper gastrointestinal effects of NSAIDs
- Nissen et al., NEJM 2016: Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen — PRECISION
- Lapi et al., BMJ 2013: NSAIDs, diuretics and ACE inhibitor/ARB-associated acute kidney injury
- DailyMed: Diclofenac sodium %1 gel — pharmacokinetics and safety
- FDA: NSAIDs from week 20 of pregnancy and low amniotic fluid risk
- NHS: Reye’s syndrome — aspirin in children
- FDA: Concomitant ibuprofen and aspirin use
- NCI: Cancer Pain — PDQ for health professionals
- NCI: Infection and Neutropenia during Cancer Treatment
- DailyMed: Pemetrexed — ibuprofen interaction
- USPSTF 2022: Aspirin Use to Prevent Cardiovascular Disease
- NICE NG151: Aspirin prevention in Lynch syndrome
- Martling et al., NEJM 2025: Low-Dose Aspirin for PI3K-Altered Localized Colorectal Cancer — ALASCCA
- Chia et al., Lancet Gastroenterology & Hepatology 2025: ASCOLT
- NHS Specialist Pharmacy Service: NSAIDs monitoring
- NCBI Bookshelf: Nonsteroidal Anti-Inflammatory Drugs — LiverTox
- MedlinePlus: Ibuprofen — patient drug information
- MedlinePlus: Naproxen — patient drug information
- MedlinePlus: Diclofenac — patient drug information
- National Kidney Foundation: Pain Medicines and Kidney Disease
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