Aspirin (acetylsalicylic acid) is used for pain, fever and inflammation at regular doses, and at low doses to prevent heart attacks and stroke. It is one of the most used medicines, but increases the risk of bleeding and stomach irritation.
Also known as: Aspirina
Combining apixaban with aspirin increases the risk of bleeding, particularly gastrointestinal, although it may be beneficial in specific indications.
Aspirin irreversibly inhibits platelet COX-1 and injures the gastrointestinal mucosa; apixaban inhibits factor Xa. Together, the risk of bleeding — particularly digestive — increases in an additive and clinically relevant way, especially in the elderly, with reduced renal function, a history of ulcer or bleeding, or with other antiplatelet agents. Dual therapy with an anticoagulant and an antiplatelet is reserved for specific indications (for example, AF with recent coronary disease). Outside these situations, avoid the combination; if unavoidable, use the lowest aspirin dose, consider gastroprotection and instruct the patient about bleeding signs.
Apixaban + aspirin: additive bleeding risk (antiplatelet + anticoagulant + gastrointestinal injury). Assess the indication carefully.
Apixaban inhibits factor Xa and aspirin inhibits platelet COX-1; the anti-haemostatic effects are additive with no relevant pharmacokinetic interaction.
Monitor for bleeding signs, haemoglobin and gastrointestinal symptoms.
Uncontrolled bleeding, melaena, haematemesis, haematuria.
Assess bleeding risk; when indicated (e.g. AF with arterial disease), use the lowest effective dose and a gastroprotectant.
DailyMed (FDA) — approved Apixaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a454cd24-0c6d-46e8-b1e4-197388606175 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Very high bleeding risk. Combined anticoagulation + antiplatelet therapy almost doubles major bleeding rates.
Aspirin irreversibly inhibits platelet COX-1 and warfarin reduces the vitamin K-dependent clotting factors: the two mechanisms add up and the risk of major bleeding — including intracranial and gastrointestinal bleeding — nearly doubles compared with each drug alone. The combination is only indicated in specific situations (e.g. acute coronary syndrome requiring anticoagulation, mechanical valve prosthesis with atherosclerotic disease), always keeping the INR at the lower end of the target range and with gastric protection when indicated. Outside these situations, dual therapy should be avoided, always weighing the individual bleeding risk.
Coumarin + antiplatelet agent: the risk of major bleeding nearly doubles (intracranial and gastrointestinal bleeding). Reserve the combination for specific cardiology indications; otherwise avoid.
Aspirin's irreversible antiplatelet effect added to Warfarin anticoagulation.
Strict INR and regular bleeding surveillance.
GI bleeding; intracranial haemorrhage (sudden severe headache).
Avoid except for specific indications (e.g. mechanical valves) under specialist supervision.
DailyMed/FDA (NIH/NLM) — approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366
Dabigatran with aspirin increases bleeding risk, especially gastrointestinal.
Aspirin inhibits platelets and injures the gastric mucosa, and dabigatran directly inhibits thrombin; the combination increases the risk of gastrointestinal and other bleeding in an additive way. The risk is higher in the elderly (over 75 years), renal impairment (dabigatran is eliminated renally), low body weight and a history of bleeding or ulcer. Anticoagulant plus antiplatelet combinations are reserved for specific indications (AF + recent coronary disease); outside them, avoid. If unavoidable, consider the lowest dabigatran dose, gastroprotection and monitoring for bleeding signs.
Aspirin + dabigatran: additive bleeding risk (antiplatelet + antithrombin + gastrointestinal injury). Assess the indication and dose.
Dabigatran inhibits thrombin and aspirin inhibits platelet COX-1; additive bleeding effect.
Monitor bleeding and dyspeptic symptoms.
GI bleeding, anaemia, haematuria.
Assess risk-benefit; the combination is used in selected AF + coronary artery disease.
DailyMed (FDA) — approved Dabigatran label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f7ea7e2c-ca54-4ecc-9fc7-bd3571b0ebc2 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Metamizole may reduce the antiplatelet effect of low-dose acetylsalicylic acid.
Metamizole, like some NSAIDs, can interfere with the irreversible acetylation of platelet COX-1 by aspirin and reduce its antiplatelet effect, especially when taken before aspirin; additionally, metamizole is associated with agranulocytosis, although rare. The combination should be weighed: prefer paracetamol for occasional analgesia in patients taking low-dose aspirin, separate administration when possible and instruct the patient about bleeding signs or signs of infection (fever, pharyngitis) that may indicate agranulocytosis.
Aspirin + metamizole: metamizole can interfere with the antiplatelet effect of aspirin and adds haematological risk (agranulocytosis). Monitor.
Metamizole interferes with aspirin COX-1 platelet inhibition, which may reduce cardioprotection.
Patient cardiovascular risk and adherence to antiplatelet therapy.
New ischaemic event while on aspirin requires review of the antithrombotic strategy.
Avoid coadministration when aspirin is used for cardiovascular prevention.
EMA (Article 31 referral) — Metamizole: https://www.ema.europa.eu/en/medicines/human/referrals/metamizole-containing-medicinal-products ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — with additional references: Prontuário Terapêutico do INFARMED (11th ed., 2012) and national Analgin 500 mg SmPC (HALMED)
Aspirin + methotrexate: possible increased methotrexate toxicity (renal clearance).
Methotrexate is eliminated mainly by renal tubular secretion, and salicylates (aspirin) and other NSAIDs reduce that excretion by tubular competition, potentially raising 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), use with caution, monitoring blood count, renal function and mucositis, especially in the elderly. In patients with an antiplatelet indication, the risk should be weighed with the rheumatologist.
Aspirin + methotrexate: aspirin reduces renal methotrexate clearance and increases toxicity. Avoid with high doses; monitor closely with low doses.
Aspirin (especially at NSAID doses) may reduce methotrexate renal clearance.
Full blood count and renal function on long-term therapy.
Oral ulcers, signs of marrow suppression.
Prefer paracetamol when possible; monitor full blood count if the combination is needed.
DailyMed (FDA) — approved Methotrexate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=757d6cef-6696-7a1c-8074-01258aaa8bdd ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
NSAID + low-dose aspirin: may reduce aspirin cardioprotection and increase GI risk.
Combining aspirin with another NSAID (naproxen) adds up gastrointestinal toxicity (ulcer, bleeding) and renal toxicity, with no additional analgesic benefit. Regarding the antiplatelet effect, interference with the irreversible acetylation of platelet COX-1 by aspirin is well documented with ibuprofen; with naproxen the data are less consistent, but the precaution applies out of prudence in patients on low-dose aspirin. Avoid simultaneous administration: use a single NSAID, consider paracetamol for analgesia and, if antiplatelet aspirin is needed, separate naproxen administration (at least 2 hours, ideally more) or use an NSAID with less interference.
Aspirin + naproxen: additive gastrointestinal risk and possible interference of naproxen with the antiplatelet effect of aspirin. Avoid simultaneous administration.
NSAIDs may occupy the same COX active site and interfere with aspirin irreversible antiplatelet inhibition.
Periodically reassess the need for the combination and gastroprotection.
Signs of thrombotic event or GI bleeding.
Take aspirin at least 2 h before the NSAID when possible; consider paracetamol for analgesia.
DailyMed (FDA) — approved Naproxen label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=24d44eb6-921e-4150-a6b2-81f42ced32ab ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining rivaroxaban with aspirin increases the risk of bleeding, particularly gastrointestinal.
Aspirin inhibits platelets and injures the gastric mucosa, and rivaroxaban inhibits factor Xa; the combination increases the risk of bleeding, particularly digestive, in an additive way. Risk factors: advanced age, renal or hepatic impairment, history of ulcer or bleeding and use of other antiplatelet agents. Anticoagulant + antiplatelet combinations are reserved for specific indications (for example, AF + recent coronary disease, or peripheral artery disease in which rivaroxaban 2.5 mg is intentionally used with aspirin). Outside these indications, avoid; if used, respect the approved regimen and monitor for bleeding signs.
Aspirin + rivaroxaban: additive bleeding risk (antiplatelet + anti-Xa + gastrointestinal injury). Assess the indication and dose.
Rivaroxaban inhibits factor Xa; aspirin blocks the platelet thromboxane pathway, with an additive bleeding effect.
Monitor haemoglobin, haematocrit and signs of bleeding.
GI bleeding, acute anaemia, dizziness from blood loss.
Weigh cardiovascular benefit against bleeding risk; use the lowest effective dose.
DailyMed (FDA) — approved Rivaroxaban label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=481b7802-5093-43e7-bbd9-1532197eb6e6 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Dual antiplatelet therapy: increases bleeding risk. This association is frequently indicated (e.g. after acute coronary syndrome), but requires bleeding risk assessment.
Aspirin and clopidogrel inhibit platelet aggregation by complementary mechanisms (COX-1 and the P2Y12 receptor), and dual antiplatelet therapy is the standard treatment after acute coronary syndrome and coronary stents, reducing thrombotic events. However, the benefit is accompanied by an increased bleeding risk, particularly digestive, especially in the elderly, with a history of ulcer or bleeding, or with anticoagulants. The duration of dual therapy should be defined by the ischaemic vs bleeding risk (usually 1–12 months depending on the scenario), with gastroprotection (PPI) in at-risk patients and periodic reassessment.
Aspirin + clopidogrel: dual antiplatelet therapy with additive bleeding risk. Use only in approved indications (ACS, stents) and assess the duration.
Aspirin irreversibly inhibits COX-1 and Clopidogrel blocks the P2Y12 receptor — additive platelet inhibition.
Watch for signs of bleeding throughout therapy.
Prolonged bleeding, haematuria, melaena, severe abdominal pain.
Use only under medical prescription within approved indications; assess treatment duration and individual bleeding risk.
DailyMed/FDA (NIH/NLM) — approved Clopidogrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9928956-bb7b-4ec2-bc38-d3c9c4199cae ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366
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
Enoxaparin with aspirin increases bleeding risk.
Aspirin and enoxaparin (low-molecular-weight heparin) act on complementary haemostatic pathways — platelet antiaggregation and anti-Xa/antithrombin — and the combination is used intentionally in acute coronary syndrome. The bleeding risk (particularly digestive and at puncture sites) is additive, especially in the elderly, renal impairment, low body weight or with other antiplatelet/anticoagulant agents. Monitor signs of bleeding, renal function and platelet count (risk of heparin-induced thrombocytopenia, especially with enoxaparin), and consider gastroprotection.
Aspirin + enoxaparin: additive bleeding risk. Use only with a clear indication (ACS) and monitor bleeding, renal function and thrombocytopenia.
LMWH potentiates antithrombin and aspirin blocks thromboxane; additive bleeding risk.
Monitor injection-site bleeding, bruising and blood count.
Large haematoma, melaena, prolonged bleeding.
Use the combination only when indicated (e.g. ACS); monitor for bleeding.
DailyMed (FDA) — approved Enoxaparin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5017a927-2a24-4f27-89f9-27c805bf7d59 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Hydroxychloroquine + aspirin: additive gastrointestinal risk.
Aspirin, especially at anti-inflammatory doses or with prolonged use, can irritate the gastric mucosa; hydroxychloroquine is also associated with gastrointestinal symptoms (nausea, diarrhoea, abdominal discomfort). The combination can add these effects and increase the risk of dyspepsia or, more rarely, mucosal injury. In patients with a history of ulcer, consider gastroprotection, use the lowest effective aspirin dose and monitor digestive symptoms; taking with food can reduce discomfort.
Hydroxychloroquine + aspirin: additive gastrointestinal risk. Use with caution and monitor digestive symptoms.
Both may irritate the gastric mucosa.
GI symptoms after the combination.
Dyspepsia, epigastric pain, melena.
Watch for dyspeptic symptoms; consider gastroprotection in at-risk patients.
DailyMed (FDA) — approved Hydroxychloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=da435181-0c5a-4188-8d59-51234116b005 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Corticosteroid + aspirin: additive gastrointestinal risk (ulcer/bleeding).
Aspirin (especially at anti-inflammatory doses or with prolonged use) inhibits gastroprotective prostaglandins and can injure the mucosa; systemic corticosteroids such as dexamethasone inhibit mucosal repair and can mask signs of perforation. Together, the risk of ulcer, bleeding and digestive perforation increases, particularly in the elderly, at high doses and in prolonged treatment. Consider gastroprotection with a proton pump inhibitor in at-risk patients, use the lowest effective dose of each drug and monitor digestive symptoms.
Aspirin + dexamethasone: additive risk of peptic ulcer and gastrointestinal bleeding. Consider gastroprotection in at-risk patients.
Both weaken gastric mucosal protection.
GI symptoms and signs of bleeding.
Melena, haematemesis, abdominal pain.
Consider gastroprotection (PPI) in at-risk patients.
DailyMed (FDA) — approved Dexamethasone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7cbd9005-7df2-47ee-adb3-7244c1c69bc3 ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
High-dose aspirin can increase the effect of glyburide and lower blood sugar too much. Monitor blood glucose.
The glimepiride SmPC (EMC-UK) and the glyburide label list salicylates among the drugs that potentiate the hypoglycaemic effect of sulfonylureas, through displacement from protein binding and an intrinsic hypoglycaemic effect at high doses. Antiplatelet-dose aspirin (75–100 mg) has a limited impact, but analgesic/anti-inflammatory doses require blood glucose monitoring.
High-dose salicylates potentiate the hypoglycaemic effect of sulfonylureas (protein displacement and an intrinsic hypoglycaemic effect). Monitor blood glucose; low-dose antiplatelet aspirin has a minimal effect.
Displacement from protein binding and an intrinsic hypoglycaemic effect of salicylates at high doses.
Capillary glucose; hypoglycaemia symptoms.
Hypoglycaemia — sweating, tremor, confusion.
Monitor blood glucose if high aspirin doses are used; prefer a low antiplatelet dose when possible.
DailyMed/FDA (NIH/NLM) — approved Glyburide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=524eec41-37ee-419a-b7a1-d23e888ae6ab ; approved Aspirin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ba0a9f2-062a-401e-82eb-54383a822366 ; EMC-UK (MHRA) — approved Glimepiride SmPC: https://www.medicines.org.uk/emc/product/10742/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol increases the risk of gastric irritation and bleeding.
Avoid alcohol, especially at anti-inflammatory doses or in at-risk patients.
EMC-UK (MHRA) — approved Aspirin SmPC: https://www.medicines.org.uk/emc/product/8627/smpc
Aspirin may trigger severe bronchospasm in patients with NSAID-induced asthma.
Do not use aspirin in patients with a history of NSAID-induced asthma/urticaria.
EMC-UK (MHRA) — approved Aspirin SmPC: https://www.medicines.org.uk/emc/product/102206/smpc
Aspirin is contraindicated in active peptic ulcer and active GI bleeding because of the risk of worsening.
Do not use in active ulcer; consider an alternative antiplatelet after assessment.
EMC-UK (MHRA) — approved Aspirin SmPC: https://www.medicines.org.uk/emc/product/102206/smpc
Aspirin (at NSAID dose) may reduce renal function.
Use the lowest effective dose and monitor creatinine in renal impairment.
EMC-UK (MHRA) — approved Aspirin SmPC: https://www.medicines.org.uk/emc/product/8627/smpc
Low-dose aspirin can be used in pregnancy when indicated (e.g. pre-eclampsia); high doses should be avoided.
Low dose (75-150 mg/day) under medical guidance; avoid high analgesic doses in the 3rd trimester.
Aspirin passes into milk in small amounts; occasional use is acceptable, high doses should be avoided.
No specific additional contraception.
EMC-UK (MHRA) — approved Aspirin SmPC: https://www.medicines.org.uk/emc/product/102206/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
NSAID with irreversible, dose-dependent antiplatelet effect: at low dose (75–100 mg/day) it inhibits platelet thromboxane A2 production, preventing thrombotic events; at higher doses it has analgesic, antipyretic and anti-inflammatory effects. It binds to serum albumin (aspirin and salicylic acid) and distributes into the synovial cavity, CNS and saliva.
Irreversibly acetylates cyclo-oxygenase (COX-1 and COX-2), inhibiting the synthesis of prostaglandins and thromboxane A2. Since platelets have no nucleus and cannot synthesise new enzyme, the antiplatelet effect lasts for the life of the platelet (7–10 days).
In aqueous solution aspirin is rapidly absorbed in the stomach (low pH); with tablets absorption is limited by disintegration. Absorption follows first-order kinetics with an absorption half-life of 5 to 16 minutes; only about 68% of a dose reaches the systemic circulation as aspirin.
Aspirin is extensively hydrolysed to salicylic acid by non-specific esterases in the liver and, to a lesser extent, the stomach. Salicylic acid is conjugated (salicyluric acid via glycine; glucuronides), oxidised to gentisic acid and partly excreted unchanged by the kidneys; renal elimination depends on urinary pH, urine flow and the presence of organic acids.
The serum half-life of aspirin is about 20 minutes; that of salicylic acid is dose-dependent — about 2 to 3 hours at low doses, extending to 15 to 30 hours at high anti-inflammatory doses (saturation of metabolic pathways).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
