Understanding Ketorolac and Its Potency
Ketorolac, often known by the brand name Toradol, is a powerful nonsteroidal anti-inflammatory drug (NSAID) prescribed for the short-term management of moderately severe pain, typically after surgery [1.3.2]. It is not a narcotic and is not habit-forming [1.3.2]. Its effectiveness comes from its ability to block the body's production of prostaglandins, natural substances that cause inflammation, pain, and fever [1.3.8]. However, this potency comes with significant risks, which is why its use is strictly limited to 5 days or less for combined injection and oral tablet use [1.3.6]. Using it for longer or at higher doses dramatically increases the chance of serious side effects, particularly gastrointestinal (GI) bleeding, kidney damage, and cardiovascular thrombotic events like heart attack and stroke [1.3.1, 1.3.6].
The Black Box Warning: A Critical Alert
Ketorolac carries an FDA "black box warning," the most serious type of warning, for several risks [1.3.5].
- Gastrointestinal Risk: Ketorolac can cause peptic ulcers, bleeding, and perforation of the stomach or intestines, which can be fatal. These events can happen at any time without warning symptoms, and the risk is higher in older adults [1.2.8]. For this reason, it is contraindicated in patients with active or a history of peptic ulcer disease or GI bleeding [1.2.8].
- Cardiovascular Risk: NSAIDs like ketorolac can increase the risk of serious and potentially fatal heart attack or stroke [1.3.6]. This risk can increase with the duration of use and is higher for individuals with existing heart disease or risk factors [1.3.5]. It should not be used right before or after coronary artery bypass graft (CABG) surgery [1.3.6].
- Bleeding Risk: Because it inhibits platelet function, ketorolac is contraindicated as a pre-operative analgesic before major surgery and in patients with suspected cerebrovascular bleeding or other high-risk bleeding conditions [1.3.5].
- Kidney Risk: The medication is contraindicated in patients with advanced renal impairment or those at risk for kidney failure due to volume depletion [1.3.5].
Absolute Contraindications: Medications You Must Not Mix
Certain medications are strictly contraindicated with ketorolac, meaning they should never be taken together due to the high probability of a severe, dangerous interaction.
- Other NSAIDs (Prescription or OTC): Taking ketorolac with other NSAIDs—such as ibuprofen (Advil, Motrin), naproxen (Aleve), aspirin, celecoxib (Celebrex), or diclofenac—is contraindicated [1.2.1, 1.3.3]. This combination leads to a cumulative risk, drastically increasing the chance of serious NSAID-related side effects like GI bleeding and kidney damage [1.3.3].
- Probenecid: This medication, used to treat gout, significantly increases the plasma levels and half-life of ketorolac, elevating the risk of toxicity. The concurrent use of probenecid and ketorolac is contraindicated [1.2.5, 1.3.5].
- Pentoxifylline: When taken with ketorolac, pentoxifylline leads to an increased tendency for bleeding and is therefore contraindicated [1.2.1, 1.3.5].
High-Risk Interactions: Medications Requiring Extreme Caution
Many other medications can interact with ketorolac, requiring close monitoring and potential dose adjustments by a healthcare provider. The primary risks of these combinations involve increased bleeding, kidney toxicity, and reduced efficacy of the interacting drug.
Drugs That Increase Bleeding Risk
Combining ketorolac with other drugs that affect blood clotting can lead to severe and sometimes fatal bleeding [1.4.2].
- Anticoagulants (Blood Thinners): Medications like warfarin (Coumadin, Jantoven), dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) significantly amplify the risk of serious GI bleeding when used with ketorolac [1.2.2, 1.4.2, 1.4.6]. The effects are synergistic, meaning the combined risk is greater than the sum of the individual risks [1.2.5].
- Antiplatelet Drugs: Drugs like clopidogrel (Plavix) and ticagrelor (Brilinta) also inhibit platelets. Using them with ketorolac heightens the risk of hemorrhagic complications [1.4.2, 1.4.3, 1.4.5].
- Selective Serotonin Reuptake Inhibitors (SSRIs): Antidepressants like fluoxetine, sertraline, and citalopram can increase the risk of gastrointestinal bleeding when combined with NSAIDs [1.2.5, 1.5.1].
- Corticosteroids: Oral steroids like prednisone, when taken with ketorolac, can also increase the risk of stomach ulceration and bleeding [1.2.2].
Drugs Affecting Kidney Function and Blood Pressure
Ketorolac can diminish the effectiveness of some blood pressure medications and increase the risk of kidney damage, especially when combined with other drugs that affect the kidneys [1.5.3, 1.5.4].
- Diuretics ("Water Pills"): Ketorolac can reduce the salt- and water-removing effects of loop diuretics (like furosemide) and thiazide diuretics. This interaction is due to the inhibition of renal prostaglandin synthesis [1.2.5]. Combining them also increases the risk of renal failure [1.5.4].
- ACE Inhibitors and Angiotensin II Receptor Blockers (ARBs): Medications like lisinopril, enalapril, losartan, and valsartan may have their blood-pressure-lowering effects diminished by ketorolac [1.2.5, 1.5.5]. More critically, this combination, especially in elderly or volume-depleted patients, can lead to a significant decline in kidney function or even acute renal failure [1.5.1, 1.5.7].
Other Significant Interactions
- Lithium: NSAIDs like ketorolac reduce the renal clearance of lithium, leading to elevated and potentially toxic levels of lithium in the blood [1.2.5, 1.5.1].
- Methotrexate: Caution is required when administering ketorolac with methotrexate, as NSAIDs can enhance its toxicity by reducing its renal clearance [1.2.5, 1.5.1].
- Alcohol: Drinking alcohol while taking ketorolac is strongly discouraged. Alcohol is a mucosal irritant that can worsen the gastrointestinal side effects of ketorolac, significantly increasing the risk of stomach bleeding [1.6.2, 1.6.8]. The combination can cause serious complications, including ulcers and major hemorrhage [1.6.3, 1.6.4].
Comparison of Major Ketorolac Interactions
| Interacting Drug Class | Primary Risk of Combination | Mechanism of Interaction |
|---|---|---|
| Other NSAIDs (e.g., Ibuprofen, Naproxen) | Severe GI bleeding, kidney toxicity | Additive inhibition of prostaglandin synthesis, cumulative side effects [1.3.3]. |
| Anticoagulants (e.g., Warfarin, Xarelto) | Major, potentially fatal bleeding | Ketorolac inhibits platelet function while anticoagulants inhibit clotting factors, creating a synergistic effect [1.2.5, 1.4.1]. |
| ACE Inhibitors/ARBs (e.g., Lisinopril, Losartan) | Acute kidney injury, reduced antihypertensive effect | NSAIDs inhibit prostaglandins that help maintain renal blood flow, counteracting the effects of these drugs [1.5.1, 1.5.7]. |
| Diuretics (e.g., Furosemide) | Reduced diuretic efficacy, kidney damage | Inhibition of renal prostaglandin synthesis reduces the drug's natriuretic effect and can impair renal function [1.2.5, 1.5.4]. |
| SSRIs (e.g., Sertraline, Fluoxetine) | Increased risk of GI bleeding | Both drug classes can independently increase bleeding risk; the combined effect is additive [1.2.5, 1.5.1]. |
| Alcohol | Severe stomach irritation and bleeding | Alcohol is a direct mucosal irritant, and when combined with NSAIDs that inhibit protective prostaglandins, the risk of ulcers and bleeding is magnified [1.6.1, 1.6.2]. |
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Conclusion
Ketorolac is a highly effective pain reliever but carries substantial risks that are magnified when mixed with other common medications and substances. The most dangerous interactions increase the risk of severe bleeding, kidney failure, and cardiovascular events. It is absolutely essential to provide your healthcare provider with a complete list of all medications, including over-the-counter drugs and supplements, before starting ketorolac [1.3.4]. Never combine ketorolac with other NSAIDs, and strictly avoid alcohol. Given the short-term nature of ketorolac therapy (5 days or less), careful management and communication with your doctor and pharmacist are paramount to using this medication safely and effectively [1.3.2].
