Nonsteroidal anti-inflammatory drug (NSAID)
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used to relieve pain, fever and inflammation. Available without prescription, it can raise the risk of bleeding and of stomach or kidney problems, especially with long-term use or when combined with other medicines.
Also known as: Brufen
NSAIDs (Ibuprofen) with aminoglycosides (Streptomycin) raise the risk of renal injury, especially in the elderly or dehydrated.
Streptomycin is an aminoglycoside with well-known nephrotoxicity and ototoxicity; ibuprofen, by inhibiting renal prostaglandins, reduces renal blood flow and can potentiate tubular injury. The combination increases the risk of acute kidney injury, especially in the elderly, in dehydrated patients or in those with pre-existing renal disease. Monitor creatinine during treatment, maintain adequate hydration and use the NSAID only if strictly necessary and at the lowest effective dose.
Streptomycin + ibuprofen: additive risk of nephrotoxicity. Monitor renal function and maintain adequate hydration.
Reduced renal blood flow from NSAIDs and aminoglycoside tubular toxicity.
Renal function (creatinine, urine output).
Oliguria, oedema, rising creatinine.
Avoid NSAIDs during treatment; ensure hydration.
DailyMed/FDA (NIH/NLM) — approved Streptomycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=abd1f64e-4283-4370-aae8-3666316aa36e ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e
Bisphosphonate + NSAID: additive gastrointestinal risk.
Alendronate, like oral bisphosphonates, can irritate the esophageal and gastric mucosa, while ibuprofen inhibits gastroprotective prostaglandins (COX-1), increasing the risk of ulcer and bleeding. The combination potentiates the risk of upper gastrointestinal injury: esophagitis, peptic ulcer and bleeding, particularly in the elderly, in patients with a history of ulcer or with high NSAID doses. Take alendronate on an empty stomach with water (as per the dosing instructions), consider gastroprotection in at-risk patients and use the lowest effective ibuprofen dose for the shortest time, watching for symptoms such as epigastric pain, dysphagia and melaena.
Alendronate + ibuprofen: additive risk of upper gastrointestinal irritation and injury (esophagitis/ulcer). Use with caution, especially in the elderly and in patients with a history of ulcer.
Both may irritate the oesophagogastric mucosa.
GI symptoms (dyspepsia, pain, dysphagia).
Epigastric pain, dysphagia, melena.
Watch for GI symptoms; consider gastroprotection if risk factors exist.
DailyMed (FDA) — approved Alendronate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7e470d6-508e-466e-a78d-060bbbc9745c ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ibuprofen increases the risk of bleeding in patients treated with apixaban.
Apixaban inhibits factor Xa, reducing coagulation, and ibuprofen adds reversible platelet inhibition and gastrointestinal mucosal injury — two independent mechanisms that increase the risk of bleeding, including upper gastrointestinal and intracranial haemorrhage. The risk is higher in the elderly (over 75 years), in patients with reduced renal function, with a history of ulcer or bleeding, or with concomitant use of other antiplatelet agents. Whenever possible, avoid the combination; if unavoidable, use the lowest effective ibuprofen dose for the shortest time, consider gastroprotection and instruct the patient about alarm signs (blood in the stool, haematuria, extensive bruising, sudden headache).
Apixaban + ibuprofen: additive bleeding risk (platelet inhibition + gastrointestinal mucosal injury). Avoid or use with extreme caution and monitor for signs of bleeding.
Ibuprofen inhibits platelet aggregation and irritates the GI mucosa, adding to the anticoagulant effect.
Monitor dyspepsia, melaena and blood count.
GI bleeding, acute iron-deficiency anaemia.
Prefer paracetamol or a COX-2 selective NSAID where possible; limit NSAID duration.
DailyMed (FDA) — approved Apixaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a454cd24-0c6d-46e8-b1e4-197388606175 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Two NSAIDs (coxib + classical): no benefit and added GI/renal/cardiovascular risk.
Combining two NSAIDs — celecoxib, a selective COX-2 inhibitor, with ibuprofen, a non-selective one — adds no analgesic efficacy but increases toxicity: gastrointestinal risk (dyspepsia, ulcer, bleeding), renal risk (sodium retention, acute kidney injury in at-risk patients) and cardiovascular risk (hypertension, thrombotic events). Coxibs keep the cardiovascular and renal risk even with the relative gastrointestinal sparing. A single NSAID at the lowest effective dose should be chosen; chronic combination of two NSAIDs should be avoided, especially in the elderly and in patients with renal or cardiovascular disease or a history of ulcer.
Celecoxib + ibuprofen (two NSAIDs): no additional analgesic benefit and increased risk of gastrointestinal, renal and cardiovascular effects. Do not combine.
Additive adverse effects on gastric mucosa, renal function and cardiovascular balance.
Renal function, blood pressure and GI symptoms.
Dyspepsia, oedema, raised blood pressure.
Do not combine NSAIDs; use a single NSAID at the lowest effective dose.
DailyMed (FDA) — approved Celecoxib label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b06ced10-81c6-4f48-a205-1e0db228cb8b ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ibuprofen increases the bleeding risk with dabigatran.
Dabigatran is a direct thrombin inhibitor; ibuprofen reversibly inhibits platelet COX-1 and injures the gastric mucosa. The sum of these effects increases the risk of gastrointestinal and other bleeding. Aggravating factors: advanced age, renal impairment (dabigatran is eliminated renally), low body weight, history of bleeding or ulcer. Prefer, when needed, an analgesic without antiplatelet effect (paracetamol) and, if the NSAID is unavoidable, use the lowest dose for the shortest possible time, with monitoring of bleeding and renal function.
Dabigatran + ibuprofen: additive bleeding risk (antiplatelet effect + gastrointestinal injury). Avoid in high-risk patients and monitor for signs of bleeding.
Dabigatran and ibuprofen have additive anti-haemostatic effects; the NSAID also damages the gastric mucosa.
Monitor blood count and GI symptoms.
GI bleeding, acute anaemia.
Prefer alternative analgesia; if an NSAID is unavoidable, monitor closely.
DailyMed (FDA) — approved Dabigatran label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7ea7e2c-ca54-4ecc-9fc7-bd3571b0ebc2 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Not recommended to use two NSAIDs at once: increases the risk of bleeding, ulceration and renal injury without adding efficacy.
Combining two non-selective NSAIDs does not improve analgesia and adds up the adverse effects: gastrointestinal injury (dyspepsia, ulcer, bleeding), sodium retention and renal injury (especially in the elderly, in hypovolaemic patients or in those with pre-existing renal disease) and cardiovascular risk. Both inhibit COX-1, so the antiplatelet and gastric effect is additive. A single NSAID should be used at the lowest effective dose, preferring non-pharmacological alternatives or paracetamol when appropriate. Chronic combination should be avoided.
Diclofenac + ibuprofen (two NSAIDs): no analgesic benefit and increased risk of gastrointestinal, renal and cardiovascular toxicity. Do not combine.
Additive COX inhibition and reduced protective gastric and renal prostaglandins.
Gastrointestinal signs (dyspepsia, melaena) and renal function in prolonged use.
Abdominal pain, melaena, haematemesis, oedema, rising blood pressure.
Avoid the combination; use only one NSAID at the lowest effective dose, with gastric protection if unavoidable.
DailyMed/FDA (NIH/NLM) — approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e ; approved Diclofenac label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ddd2278b-70be-41ca-8a84-e3fe0f1a1561
Reduced antihypertensive effect and risk of renal injury. NSAIDs blunt the ACE inhibitor and increase the risk of renal impairment, especially in elderly or dehydrated patients.
NSAIDs inhibit the synthesis of renal prostaglandins, which are essential to maintain afferent arteriolar vasodilation in patients with reduced renal blood flow; ACE inhibitors block angiotensin II, which constricts the efferent arteriole. The combination can cause acute kidney injury (especially in the elderly, dehydration, heart failure or diuretic use), reduce the antihypertensive and nephroprotective effect of enalapril and cause sodium retention and possible hyperkalaemia. Monitor blood pressure, creatinine and potassium after starting or adjusting the NSAID, ensure adequate hydration and consider an analgesic alternative (paracetamol).
Enalapril + ibuprofen: the NSAID reduces the antihypertensive and nephroprotective effect of the ACE inhibitor and can worsen renal function. Monitor blood pressure, creatinine and potassium.
NSAIDs inhibit renal prostaglandins and retain sodium/water, opposing the ACE inhibitor mechanism.
BP and creatinine after 2 weeks of regular NSAID use.
Oedema, reduced urine output, rising BP.
Prefer Paracetamol as analgesic. If an NSAID is needed, use the lowest dose for the shortest time, with renal function monitoring.
DailyMed/FDA (NIH/NLM) — approved Enalapril label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b31372f7-cda3-4ead-a481-4cde62e843fd ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e
NSAID + methotrexate: reduced renal clearance and increased MTX toxicity.
Methotrexate is eliminated mainly by renal tubular secretion; NSAIDs reduce this excretion (by competition and by reducing renal blood flow) and can raise methotrexate concentrations and the risk of myelosuppression, mucositis, hepatotoxicity and nephrotoxicity. With high-dose methotrexate (chemotherapy) the combination is contraindicated; with low doses (rheumatoid arthritis, psoriasis) it should be used with caution, monitoring blood count, renal function and mucositis, especially in the elderly.
Ibuprofen + methotrexate: the NSAID reduces renal methotrexate clearance, with a risk of myelosuppression and severe toxicity. Avoid with high doses; monitor closely with low doses.
NSAIDs inhibit renal excretion of methotrexate, raising serum concentrations.
Full blood count and renal function; clinical signs of MTX toxicity.
Oral ulcers, marrow suppression, hepatotoxicity.
Avoid NSAIDs in patients on methotrexate; if needed, prefer paracetamol and monitor.
DailyMed (FDA) — approved Methotrexate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=757d6cef-6696-7a1c-8074-01258aaa8bdd ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Two NSAIDs together: no added benefit and increased GI/renal risk.
As with other combinations of two NSAIDs, ibuprofen + naproxen does not increase analgesic efficacy but adds up the risks: gastrointestinal bleeding and ulcer, sodium retention and renal deterioration, and cardiovascular events. Both inhibit platelet and gastric COX-1, so the antiplatelet and mucosal-injury effect is additive. Use a single NSAID at the lowest effective dose, alternating with paracetamol if needed, and avoid chronic simultaneous use.
Ibuprofen + naproxen (two NSAIDs): additive risk of gastrointestinal, renal and cardiovascular toxicity, without analgesic benefit. Do not combine.
Additive effects on gastric mucosa, renal function and platelet aggregation.
Renal function and GI intolerance signs in at-risk patients.
Dyspepsia, epigastric pain, oliguria, oedema.
Do not combine NSAIDs; use a single NSAID at the lowest effective dose.
DailyMed (FDA) — approved Naproxen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=24d44eb6-921e-4150-a6b2-81f42ced32ab ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining Levofloxacin with Ibuprofen (NSAID) increases the risk of seizures by lowering the seizure threshold.
Fluoroquinolones, such as levofloxacin, antagonise GABA receptors, lowering the seizure threshold; NSAIDs (ibuprofen) can potentiate this effect, increasing the risk of seizures, especially in patients with epilepsy, brain injury or renal impairment. The levofloxacin label and the Portuguese Prontuário Terapêutico advise against the combination in predisposed patients. If the antibiotic is needed, prefer an alternative analgesic or monitor closely; warn the patient about neurological symptoms (dizziness, confusion, tremor) and stop at any sign.
Levofloxacin + ibuprofen: increased risk of CNS stimulation and seizures. Avoid in patients with epilepsy or a history of seizures.
NSAIDs and quinolones may lower the seizure threshold (central interference, notably with GABA); combined use adds these effects and increases the seizure risk, especially in patients with epilepsy or predisposition.
Watch for neurological symptoms (dizziness, tremor, behavioral changes) and prodromal seizure signs.
Any seizure or suspicion thereof requires discontinuation and urgent neurological evaluation.
Prefer an alternative antibiotic in patients with epilepsy/a history of seizures; if the combination is necessary, monitor very closely.
DailyMed/FDA (NIH/NLM) — approved Levofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5c6c117c-9d91-48f4-9aaa-ee70b99218c2 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Increased risk of renal injury and gastrointestinal symptoms with prolonged use or high doses of both analgesics. At usual short-term doses it is generally well tolerated.
Paracetamol and ibuprofen have different mechanisms, but chronic use of both at high doses increases the risk of nephrotoxicity (papillary necrosis, renal failure) and, according to some studies, the risk of gastrointestinal bleeding and cardiovascular events compared with each drug alone. For occasional analgesia the combination is acceptable (additive effect), but prolonged unsupervised use should be avoided, daily limits should be respected (paracetamol up to 3–4 g/day; ibuprofen per presentation) and renal function should be monitored in at-risk patients.
Ibuprofen + paracetamol: prolonged combined use at high doses increases the risk of renal injury and gastrointestinal bleeding. Respect daily limits and monitor renal function.
Additive effects: Ibuprofen inhibits renal prostaglandin synthesis and chronic use adds renal load. At therapeutic doses the combination does not potentiate paracetamol hepatotoxicity.
Renal function and signs of toxicity in at-risk patients or prolonged use. Avoid the combination in children without weight-adjusted dosing.
New flank pain, oedema, reduced urine output, rising blood pressure.
Use the lowest effective doses for the shortest time. Prefer a single analgesic. In patients with renal disease, hypertension or older age, reinforce monitoring.
DailyMed/FDA (NIH/NLM) — approved Paracetamol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c737cd6-fe56-4cef-887c-cd6cf83b254c ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e
Increased gastrointestinal bleeding risk with corticosteroid plus NSAID.
Prednisolone, like systemic corticosteroids, inhibits mucosal repair and can mask signs of perforation; ibuprofen reduces gastroprotective prostaglandins and inhibits platelet aggregation. Together, the risk of ulcer, bleeding and digestive perforation increases, especially in the elderly, at high doses and in prolonged therapy. Whenever possible, use the lowest corticosteroid dose for the shortest time, consider gastroprotection (proton pump inhibitor) in at-risk patients and monitor digestive symptoms and signs of anaemia.
Prednisolone + ibuprofen: additive risk of peptic ulcer and gastrointestinal bleeding. Consider gastroprotection, especially in the elderly.
Additive gastric mucosal injury (reduced protective prostaglandins).
Watch for dyspepsia and occult blood in stool.
Severe abdominal pain, melaena, haematemesis.
Consider gastric protection (PPI) if the combination is unavoidable; use the lowest effective doses.
DailyMed/FDA (NIH/NLM) — approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e ; approved Prednisolone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e6e21d-94b8-41a0-8d13-371c0e66bcee
Ibuprofen increases the bleeding risk with rivaroxaban.
Rivaroxaban inhibits factor Xa and ibuprofen adds platelet inhibition and gastrointestinal mucosal injury, increasing the risk of bleeding, particularly digestive. Risk factors: advanced age, renal or hepatic impairment, history of bleeding or ulcer and use of other antiplatelet agents. Prefer paracetamol for analgesia; if the NSAID is needed, use the lowest effective dose for the shortest time, consider gastroprotection and instruct the patient about bleeding signs (dark stools, haematuria, bruising, sudden headache).
Rivaroxaban + ibuprofen: additive bleeding risk. Avoid if possible; if unavoidable, use the lowest dose, shortest time and monitor for signs of bleeding.
Ibuprofen's antiplatelet and gastro-irritative effect adds to rivaroxaban.
Monitor for GI bleeding signs.
Melaena, haematemesis, abdominal pain with anaemia.
Avoid long-term NSAIDs; use the lowest dose for the shortest duration.
DailyMed (FDA) — approved Rivaroxaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=481b7802-5093-43e7-bbd9-1532197eb6e6 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining Lithium with Ibuprofen increases serum Lithium concentrations, with a risk of toxicity.
NSAIDs, by inhibiting the synthesis of renal prostaglandins, reduce renal blood flow and lithium excretion, potentially raising serum lithium and precipitating toxicity (nausea, coarse tremor, confusion, ataxia, seizures) within days. The effect is particularly relevant in the elderly and in patients with reduced renal function. The lithium label and the Portuguese Prontuário Terapêutico recommend monitoring serum lithium and signs of toxicity when starting, adjusting or stopping the NSAID, and preferring paracetamol as the analgesic.
Ibuprofen + lithium: the NSAID reduces renal lithium clearance, with a risk of raised serum lithium and toxicity (tremor, confusion, seizures). Monitor lithium levels.
Non-steroidal anti-inflammatory drugs such as Ibuprofen reduce the renal excretion of Lithium, raising its levels.
Lithium levels after starting or adjusting the NSAID.
Confusion, coarse tremor, ataxia, vomiting, diarrhoea or seizures suggest Lithium toxicity and require urgent evaluation.
Avoid NSAIDs in patients taking Lithium; if unavoidable, use the lowest dose and monitor Lithium levels.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Ibuprofen may reduce the cardioprotective effect of low-dose Aspirin.
Ibuprofen, when taken before low-dose (antiplatelet) aspirin, can reversibly occupy the platelet COX-1 active site and prevent the irreversible acetylation by aspirin, reducing the antiplatelet effect and cardiovascular protection. The risk is higher with regular over-the-counter ibuprofen. Take ibuprofen at least 30–60 minutes after aspirin (or 8 hours before, as a single dose), or prefer paracetamol for occasional analgesia. In patients at high cardiovascular risk, this interaction should be avoided.
Ibuprofen may reduce the cardioprotective effect of low-dose aspirin. Take ibuprofen 30–60 min after aspirin or use paracetamol.
Ibuprofen occupies the COX-1 binding site, blocking Aspirin's irreversible inhibition.
No laboratory monitoring; consider an alternative analgesic in high-risk patients.
Signs of a new cardiovascular event — chest pain, sudden shortness of breath.
If both are needed, take Ibuprofen 2 hours after immediate-release Aspirin.
DailyMed/FDA (NIH/NLM) — approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e
Corticosteroid + NSAID: additive gastrointestinal risk (ulcer/bleeding).
Both corticosteroids and NSAIDs can injure the gastrointestinal mucosa; the combination increases the risk of peptic ulcer, perforation and digestive bleeding, especially in the elderly, at high doses and in prolonged treatment. Dexamethasone can also mask signs of infection and alter metabolism, while ibuprofen adds platelet inhibition. Use the lowest corticosteroid dose for the shortest time, consider gastroprotection (proton pump inhibitor) in at-risk patients and monitor digestive symptoms.
Dexamethasone + ibuprofen: additive risk of peptic ulcer and gastrointestinal bleeding. Consider gastroprotection in at-risk patients.
Both weaken gastric mucosal protection.
GI symptoms and full blood count if bleeding.
Epigastric pain, melena, haematemesis.
Avoid the combination when possible; if needed, use gastroprotection.
DailyMed (FDA) — approved Dexamethasone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7cbd9005-7df2-47ee-adb3-7244c1c69bc3 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=291602fa-8ebe-4200-bba7-9798c90f8a50 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ibuprofen can increase the effect of glyburide and lower blood sugar too much. Monitor blood glucose if you take both.
The glimepiride SmPC (EMC-UK) includes non-steroidal anti-inflammatory drugs among the drugs that potentiate the hypoglycaemic effect of sulfonylureas. The mechanism involves displacement from protein binding and inhibition of metabolism. In diabetic patients, NSAID use should be accompanied by blood glucose monitoring, especially in prolonged courses.
NSAIDs potentiate the hypoglycaemic effect of sulfonylureas. Monitor blood glucose during ibuprofen use, especially at high doses or with prolonged use.
Displacement from protein binding and inhibition of sulfonylurea metabolism by NSAIDs.
Capillary glucose; hypoglycaemia symptoms.
Hypoglycaemia — sweating, tremor, confusion.
Monitor blood glucose during NSAID use; use the lowest dose and shortest duration possible.
EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Severe bleeding risk. NSAIDs (Ibuprofen) increase gastrointestinal bleeding and potentiate the anticoagulant effect of Warfarin.
Ibuprofen increases the bleeding risk in anticoagulated patients through two mechanisms: direct injury to the gastrointestinal mucosa and reversible COX-1 inhibition, which reduces thromboxane A2 and impairs platelet aggregation. The effect on the INR is variable, but the increase in bleeding risk — particularly upper gastrointestinal bleeding — is well documented even with occasional NSAID doses. In patients taking warfarin, paracetamol is the first-line analgesic; if an NSAID is indispensable, use the lowest effective dose for the shortest time, consider gastric protection with a proton pump inhibitor, and remain vigilant for bleeding signs (dark stools, spontaneous bruising, bleeding).
NSAID + coumarin: markedly increased bleeding risk (gastrointestinal bleeding and variable INR increase). Prefer paracetamol; if the NSAID is unavoidable, minimal dose, short course and gastric protection; watch for bleeding signs.
Gastric mucosal injury + platelet inhibition + displacement of Warfarin from albumin.
INR and bleeding surveillance; FBC if occult loss is suspected.
Haematemesis, melaena, blood in stool, extensive bruising.
Avoid the combination. Use Paracetamol; if an NSAID is essential, consider gastric protection and strict INR.
DailyMed/FDA (NIH/NLM) — approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 ; approved Ibuprofen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14515409-736f-4119-b6a0-cb19ee2e948e
Taking with food reduces gastric irritation.
Take with food or milk if stomach discomfort occurs.
EMC-UK (MHRA) — approved Ibuprofen SmPC: https://www.medicines.org.uk/emc/product/6713/smpc
Alcohol worsens the NSAID-related gastric bleeding risk.
Limit or avoid alcohol.
EMC-UK (MHRA) — approved Ibuprofen SmPC: https://www.medicines.org.uk/emc/product/6713/smpc
NSAIDs may increase cardiovascular risk.
Use with caution in cardiovascular disease.
EMC-UK (MHRA) — approved Ibuprofen SmPC: https://www.medicines.org.uk/emc/product/6713/smpc
NSAIDs may worsen renal function.
Avoid or use the lowest dose with creatinine monitoring.
EMC-UK (MHRA) — approved Ibuprofen SmPC: https://www.medicines.org.uk/emc/product/6713/smpc
Risk of bronchospasm in NSAID-sensitive patients.
Avoid in aspirin-sensitive asthma; use with caution.
EMC-UK (MHRA) — approved Ibuprofen SmPC: https://www.medicines.org.uk/emc/product/6713/smpc
NSAIDs may worsen or perforate an active ulcer.
Contraindicated; seek an alternative (paracetamol).
EMC-UK (MHRA) — approved Ibuprofen SmPC: https://www.medicines.org.uk/emc/product/6713/smpc
Avoid in the 3rd trimester (ductus arteriosus closure, oligohydramnios). Occasional use in 1st/2nd trimester with caution.
Avoid in the 3rd trimester; use the lowest dose for the shortest time.
Low milk levels; occasional use is compatible.
Use paracetamol in pregnancy; no specific contraception.
EMC-UK (MHRA) — approved Ibuprofen SmPC: https://www.medicines.org.uk/emc/product/6713/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Non-selective NSAID with analgesic, anti-inflammatory and antipyretic activity. At low doses it reversibly inhibits platelet aggregation. In chronic conditions a therapeutic response appears within days to weeks (usually by two weeks); for mild to moderate pain, 400 mg every 4 to 6 hours, with no proven added benefit above 400 mg.
Non-selectively inhibits the cyclo-oxygenases COX-1 and COX-2, reducing the synthesis of prostaglandins (mediators of inflammation, pain and fever). COX-1 inhibition accounts for the gastrointestinal and platelet effects; COX-2 inhibition underlies the anti-inflammatory and analgesic effects.
Oral absorption is rapid and almost complete; peak plasma concentrations are reached 1 to 2 hours after dosing. Food slows absorption, although the extent of absorption is not significantly changed.
Metabolised in the liver, mainly by CYP2C9-mediated hydroxylation and carboxylation (with a minor contribution from CYP2C19 and CYP3A4), yielding inactive metabolites, and by glucuronic acid conjugation. The metabolites are eliminated mainly by the kidneys.
The elimination half-life is about 2 hours (1.8 to 3.5 h), allowing dosing every 4 to 6 hours in acute pain.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
