Non-steroidal anti-inflammatory drugs (NSAIDs)
ATC code: M01AB15 (Ketorolac)
Non-selective COX-1 and COX-2 inhibitor with predominantly analgesic (rather than anti-inflammatory) effect. Analgesic potency is comparable to morphine for certain pain syndromes. Rapid onset: 30-60 minutes orally, 10-15 minutes intramuscularly. One of the most potent non-opioid analgesics.
First line
First-line for acute moderate-to-severe pain when rapid non-opioid analgesia is needed. Oral dose is 10 mg every 4-6 hours, maximum 40 mg daily. Course is strictly limited to 5 days. Beyond 5 days, the risk of GI bleeding and renal injury rises sharply. Not indicated for chronic pain.
First line
Widely used in the early postoperative period. Reduces opioid requirements by 25-45%. Intramuscularly or intravenously – 30 mg loading dose, then 15-30 mg every 6 hours. In patients over 65, weighing under 50 kg, or with renal impairment – maximum 60 mg daily. Total parenteral and oral course duration must not exceed 5 days.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Ketorolac is a short-acting nonsteroidal anti-inflammatory drug (NSAID). It is prescribed for moderate-to-severe acute pain, primarily postoperative, for a maximum of 5 days (AEMPS Ficha Técnica). For unconfirmed migraine and any headache, ketorolac is not used as first-line ( NG150 2021, AHS 2021): for migraine, triptans and other proven options work; for tension-type headache, paracetamol or ibuprofen at usual doses. Ketorolac has serious risks: severe gastrointestinal bleeding and perforation, acute kidney injury, and cardiovascular events. These risks are not justified for ordinary headache. If ketorolac was prescribed for migraine or any headache, consider seeking a second opinion.
16 pairs found. Sorted from critical to minor.
Mechanism
Ketorolac is the most potent oral and parenteral NSAID. Aspirin irreversibly blocks platelet cyclooxygenase. Co-administration of two NSAIDs adds up the risks: gastrointestinal bleeding, acute kidney injury, sodium and fluid retention. Toradol Section 4.3 specifically lists aspirin and other NSAIDs as contraindications.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Acute kidney injury and a rise in blood pressure are also possible. Risk of bleeding multiplies in patients over 65 and with prior peptic ulcer disease.
Management
The combination is not prescribed. If aspirin is required for cardioprotection (75–100 mg/day), replace ketorolac with paracetamol, metamizole, or a short opioid course. Ketorolac courses are limited to 5 days under all circumstances.
Mechanism
Ketorolac and diclofenac are both NSAIDs. Co-administration adds up the risks: gastrointestinal bleeding, acute kidney injury, raised blood pressure. Toradol Section 4.3 specifically lists other NSAIDs as contraindications.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Acute kidney injury and a rise in blood pressure are also possible. Risk of bleeding multiplies in patients over 65 and with prior peptic ulcer disease.
Management
The combination is not prescribed. For adequate analgesia, choose one NSAID as monotherapy (diclofenac or ketorolac short course with PPI cover such as pantoprazole). Alternative: paracetamol plus an opioid if pain is insufficiently controlled.
Sources
Mechanism
Ketorolac and ibuprofen are both NSAIDs. Additive risk of gastrointestinal bleeding, acute kidney injury, and blood pressure dysregulation. Toradol Section 4.3 specifically lists other NSAIDs as contraindications.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Acute kidney injury and a rise in blood pressure are also possible. Risk of bleeding multiplies in patients over 65 and with prior peptic ulcer disease.
Management
The combination is not prescribed. One NSAID at a time. Ketorolac courses are limited to 5 days. If analgesia from one NSAID is insufficient, add paracetamol or a short opioid – not a second NSAID.
Sources
Mechanism
Ketorolac is a potent non-selective NSAID; nimesulide is a selective COX-2 inhibitor. Despite different selectivity, gastrointestinal and renal effects are additive. Toradol Section 4.3 specifically lists all NSAIDs as contraindications.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Acute kidney injury and a rise in blood pressure are also possible. Risk of bleeding multiplies in patients over 65 and with prior peptic ulcer disease.
Management
The combination is not prescribed. Use one NSAID at the minimum effective dose with PPI cover (pantoprazole). Alternative: paracetamol as baseline analgesia.
Mechanism
Apixaban inhibits factor Xa, while ketorolac is the most potent available NSAID. Ketorolac injures the gastric mucosa and inhibits platelet aggregation. Massive GI bleeding risk increases several-fold. Toradol Section 4.3 lists anticoagulants as contraindications.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
The combination is not prescribed. For analgesia in a patient on apixaban, use paracetamol (up to 3 g/day), metamizole, or a short opioid course. Ketorolac courses never exceed 5 days under any circumstances.
Mechanism
Dual NSAID therapy – additive GI bleeding, nephrotoxicity, and cardiovascular event risks. Ketorolac itself is limited to 5 days of use.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.
Management
The combination is not prescribed. One NSAID at a time. For enhanced analgesia, add paracetamol or a short opioid course, not a second NSAID.
Mechanism
Additive nephrotoxicity. Ketorolac (NSAID) suppresses prostaglandin-dependent renal blood flow; iodinated contrast (iopromide) adds osmotic load. High risk of acute kidney injury.
Symptoms
Reduced urine output, rising creatinine, proteinuria. Severe cases include oliguria and need for haemodialysis. Symptoms appear 1–3 days after contrast.
Management
Stop ketorolac 48 hours before planned contrast and resume 48 hours after with stable renal function. Alternative analgesics: paracetamol, metamizole, or a short opioid course. Provide contrast nephroprotection with adequate saline hydration.
Mechanism
Dual NSAID therapy – additive GI bleeding and nephrotoxicity risk. Despite meloxicam's preferential COX-2 selectivity, GI toxicity adds up when combined with ketorolac.
Symptoms
Black or tarry stools, vomiting blood, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.
Management
The combination is not prescribed. One NSAID at a time. Ketorolac courses no more than 5 days. For enhanced analgesia: paracetamol or a short opioid.
Mechanism
Ketorolac reduces renal methotrexate clearance and suppresses tubular secretion. At high oncologic methotrexate doses: risk of severe toxicity (pancytopenia, nephrotoxicity, mucositis).
Symptoms
Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases: fatal pancytopenia, nephrotoxicity.
Management
At oncologic methotrexate doses, the combination is not prescribed. At low rheumatologic doses, avoid ketorolac; use paracetamol or a short opioid course for analgesia. Ketorolac courses never exceed 5 days.
Mechanism
Dual NSAID therapy – sharp rise in GI bleeding risk (3- to 5-fold), acute kidney injury, and cardiovascular events.
Symptoms
Black or tarry stools, vomiting blood, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.
Management
The combination is not prescribed. One NSAID at a time. For enhanced analgesia: paracetamol or a short opioid course, not a second NSAID. Ketorolac courses never exceed 5 days.
Mechanism
Ketorolac inhibits platelet aggregation and strongly injures the gastric mucosa. Combined with rivaroxaban (direct factor Xa inhibitor): additive massive GI bleeding risk. Toradol Section 4.3 lists anticoagulants as contraindications.
Symptoms
Black or tarry stools (melena), vomiting blood or coffee-ground material, epigastric pain. Risk multiplies in older patients and with prior peptic ulcer disease.
Management
The combination is not prescribed. For analgesia on rivaroxaban, use paracetamol (up to 3 g/day), metamizole, or a short opioid course. Ketorolac courses never exceed 5 days under any circumstances.
Mechanism
Ketorolac is the most nephrotoxic NSAID, limited to 5 days of use. Tacrolimus is nephrotoxic in its own right. Additive acute kidney injury risk multiplies in transplant patients.
Symptoms
Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and chronic kidney disease.
Management
The combination is not prescribed. For post-transplant analgesia: paracetamol (up to 2 g/day), metamizole, or a short opioid course. For neuropathic pain: gabapentin or pregabalin.
Mechanism
Ketorolac is the most potent available NSAID. It inhibits platelet aggregation and strongly injures the gastric mucosa. On warfarin, massive GI bleeding risk multiplies. Toradol Section 4.3 lists anticoagulants as contraindications.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
The combination is not prescribed. For analgesia on warfarin, use paracetamol (up to 2 g/day), metamizole, or a short opioid course. Ketorolac courses never exceed 5 days under any circumstances.
Mechanism
Ketorolac suppresses vasodilator prostaglandins, weakening amlodipine's antihypertensive effect. Plus additive nephrotoxicity.
Symptoms
Gradual blood pressure rise 1–2 weeks after starting the NSAID. In chronic kidney disease: risk of fluid retention and oedema.
Management
Ketorolac courses are limited to 5 days. Monitor blood pressure and creatinine in the first days. In chronic kidney disease or reduced ejection fraction, avoid ketorolac; use paracetamol or a short opioid course for analgesia.
Mechanism
NSAIDs weaken the antihypertensive effect of beta-blockers via prostaglandin-dependent renal regulation (natriuresis). Ketorolac is the most potent NSAID.
Symptoms
Gradual blood pressure rise 1–2 weeks after starting the NSAID. In chronic kidney disease: risk of fluid retention and oedema.
Management
Ketorolac courses are limited to 5 days. Check blood pressure in the first days. In borderline hypertension, temporarily increase bisoprolol. For chronic analgesia: paracetamol or a short opioid course.
Mechanism
Glucocorticoid plus NSAID — additive risk of GI ulcers and bleeding. Systemic budesonide (Cortiment, Entocort) raises risk; inhaled budesonide does not.
Symptoms
Epigastric pain, heartburn, black or tarry stools, blood in vomit, bruising. Higher risk in older patients, prior peptic ulcer, and concurrent anticoagulants.
Management
Ketorolac is not prescribed with systemic budesonide — risk outweighs benefit. For acute pain: paracetamol up to 3 g/day or metamizole. If NSAIDs are necessary (short course in cancer or postoperative pain), add pantoprazole 20 mg/day and cap ketorolac at 5 days. Inhaled budesonide with NSAIDs is safe.
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Boxed warning
Ketorolac is contraindicated for chronic pain management. Total treatment duration must not exceed 5 days. Increased risk of serious GI adverse events – bleeding, ulceration, perforation. Increased risk of cardiovascular thrombotic events.
FDA category C in the first and second trimesters. Contraindicated in the third trimester (category D) – causes premature ductus arteriosus closure and oligohydramnios. Avoid after 20 weeks.
Passes into breast milk in small amounts. Short-term use (1-2 days) is acceptable during breastfeeding per LactMed.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Ketorolac is evaluated for the following indications with varying evidence strength: Acute moderate-to-severe pain (evidence tier A), Postoperative pain (evidence tier A), Memory and concentration enhancement (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Ketorolac (≥ 1 in 100): Dyspepsia, nausea, abdominal pain, Headache, dizziness, Drowsiness, Edema. See the Safety section for uncommon and serious reactions.
FDA category C. FDA category C in the first and second trimesters. Contraindicated in the third trimester (category D) – causes premature ductus arteriosus closure and oligohydramnios. Avoid after 20 weeks.
Passes into breast milk in small amounts. Short-term use (1-2 days) is acceptable during breastfeeding per LactMed.
Ketorolac is contraindicated in: Active peptic ulcer or history of GI bleeding; Severe renal impairment or risk of renal failure (hypovolemia, dehydration); Perioperative setting in CABG surgery; Hemostatic disorders or concurrent anticoagulant use; Third trimester of pregnancy. Full list in the Safety section.
Ketorolac is contraindicated for chronic pain management. Total treatment duration must not exceed 5 days. Increased risk of serious GI adverse events – bleeding, ulceration, perforation. Increased risk of cardiovascular thrombotic events.