Version July 2025
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.
Ketorolac is contraindicated during the perioperative setting of coronary artery bypass graft (CABG) surgery.
NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.
Dosage guidance:
Safety: Consider proton pump inhibitor coadministration in patients at risk for GI bleeding (eg, taking dual antiplatelet therapy or an anticoagulant, ≥60 years of age) (Ref). May increase cardiovascular risk (eg, thrombotic events), particularly in patients with established cardiovascular disease.
Dosing: Use the lowest effective dose for the shortest duration of time. Patients weighing <50 kg or ≥65 years of age may be at increased risk for adverse effects; lower doses are recommended.
Pain management, acute:
Note: Do not exceed recommended doses or administer with another nonsteroidal anti-inflammatory drug (NSAID). May supplement with analgesic(s) from another therapeutic class for breakthrough pain.
Weight ≥50 kg and <65 years of age:
Intranasal: One spray (15.75 mg) in each nostril (total dose: 2 sprays [31.5 mg]) every 6 to 8 hours as needed; maximum daily dose: 4 doses (8 sprays [126 mg])/day; maximum duration: 5 days combined (parenteral, oral, and nasal) (Ref).
Weight <50 kg or ≥65 years of age:
Intranasal: One spray (15.75 mg) in only 1 nostril (total dose: 1 spray [15.75 mg]) every 6 to 8 hours as needed; maximum daily dose: 4 doses (4 sprays [63 mg])/day; maximum duration: 5 days combined (parenteral, oral, and nasal) (Ref).
Migraine, severe, acute (off-label use):
Weight ≥50 kg and <65 years of age:
Intranasal: One spray (15.75 mg) in each nostril (total dose: 2 sprays [31.5 mg]) as a single dose (Ref).
Weight <50 kg or ≥65 years of age:
Intranasal: One spray (15.75 mg) in only 1 nostril (total dose: 1 spray [15.75 mg]) as a single dose (reduced dose based on general recommendations in manufacturer's labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal insufficiency: Intranasal: One spray (15.75 mg) in 1 nostril (total dose: 15.75 mg) every 6 to 8 hours; maximum dose: 4 doses (63 mg)/day
Advanced renal impairment (or at risk for renal failure due to volume depletion): Use is contraindicated
Use with caution with hepatic impairment or history of hepatic disease; use may cause elevation of liver enzymes; discontinue if clinical signs and symptoms of liver disease develop.
Note: Unless alternative agents are ineffective and a gastroprotective agent can be administered, avoid short-term scheduled use in combination with corticosteroids, anticoagulants, or antiplatelet agents or chronic use with or without medications that increase risk for bleeding (Ref).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%: Respiratory: Nasal discomfort (15%), nasal cavity pain (13%)
1% to 10%:
Cardiovascular: Bradycardia (2%), hypertension (2%)
Dermatologic: Skin rash (3%)
Genitourinary: Decreased urine output (2%), oliguria (3%)
Hepatic: Increased serum alanine aminotransferase (≤2%), increased serum aspartate aminotransferase (≤2%)
Ophthalmic: Increased lacrimation (5%)
Respiratory: Rhinitis (2%), throat irritation (4%)
<1%: Hematologic & oncologic: Hemorrhage
Frequency not defined:
Cardiovascular: Acute myocardial infarction
Gastrointestinal: Gastrointestinal hemorrhage, gastrointestinal inflammation, gastrointestinal perforation, gastrointestinal ulcer
Nervous system: Cerebrovascular accident
Hypersensitivity (eg, anaphylactic reactions, serious skin reactions) to ketorolac or any component of the formulation; active peptic ulcer disease; recent GI bleeding or perforation; patients with advanced renal disease or at risk for renal failure (due to volume depletion); history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs; prophylactic analgesic before major surgery; in the setting of coronary artery bypass graft surgery; labor and delivery; suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or those for whom hemostasis is critical; concomitant use with probenecid or pentoxifylline.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Bleeding: Inhibits platelet function; contraindicated in patients with cerebrovascular bleeding (suspected or confirmed), hemorrhagic diathesis, incomplete hemostasis and patients at high risk for bleeding. Effects on platelet adhesion and aggregation may prolong bleeding time. Anemia may occur; patients on long-term nonsteroidal anti-inflammatory drug (NSAID) therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).
• Cardiovascular events: Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of cardiovascular events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention, use with caution in patients with edema. Avoid use in patients with heart failure when possible (Heidenreich 2022). Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.
• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.
• Gastrointestinal events: Avoid use in patients with active GI bleeding. Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), smoking, use of alcohol, or in the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (ACC/ACG/AHA [Bhatt 2008]).
• Hepatic effects: Rare (sometimes fatal) severe hepatic reactions (eg, fatal fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue if signs or symptoms of liver disease develop, if systemic manifestations (eg, eosinophilia, rash) occur, or with persistent or worsening abnormal hepatic function tests.
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in patients ≥65 years of age, in patients with diabetes or renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE inhibitors). Monitor potassium closely.
• Hypersensitivity: Even in patients without prior exposure, hypersensitivity including bronchospasm and anaphylactic shock, may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy. Ketorolac nasal spray is contraindicated in patients with prior hypersensitivity reaction to aspirin or NSAIDs.
• Renal effects: Acute renal failure, interstitial nephritis, and nephrotic syndrome have been reported with ketorolac use; papillary necrosis and renal injury have been reported with the use of NSAIDs.
• Skin reactions: NSAIDs may cause serious skin adverse events (sometimes fatal), including exfoliative dermatitis, fixed drug eruption (including generalized bullous fixed drug eruption), Stevens-Johnson syndrome, and toxic epidermal necrolysis; may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).
Disease-related concerns:
• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur (may be fatal). Use caution in patients with other forms of asthma.
• Coronary artery bypass graft surgery/major surgery: Risk of MI and stroke may be increased with use following CABG surgery. Use is also contraindicated as prophylactic analgesic before any major surgery. Wound bleeding and postoperative hematomas have been associated with ketorolac use in the perioperative setting.
• Hepatic impairment: Use with caution in patients with hepatic impairment or a history of liver disease. Closely monitor patients with any abnormal LFT.
• Hypertension: Use with caution; may cause new-onset hypertension or worsening of existing hypertension.
• Renal impairment: Use is contraindicated in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion. NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation. Patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Dosage adjustment is required in patients with moderate elevation in serum creatinine.
Special populations:
• Older adult: Dosage adjustment is required for patients ≥65 years of age. Ketorolac is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients ≥65 years of age (independent of diagnosis or condition) due to an increased risk of GI bleeding, peptic ulcer disease, and acute kidney injury (Beers Criteria [AGS 2019]).
• Low body weight: Dosage adjustment is required for patients weighing <50 kg (<110 pounds).
Dosage form specific issues:
• Nasal spray: Avoid contact with the eyes. If eye exposure occurs, wash eye with water or saline; consult health care provider if irritation continues >1 hour.
Other warnings/precautions:
• Limitations of use: Ketorolac nasal spray is indicated for short-term (≤5 days) use in adults for treatment of moderate- to moderately-severe pain requiring opioid-level analgesia. The combined therapy duration (nasal and other ketorolac formulations) should not exceed 5 days. Therapy is not appropriate for minor or chronic pain therapy.
• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.
Each nasal spray bottle delivers 8 sprays for a total of ketorolac 126 mg.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Nasal, as tromethamine:
Generic: 15.75 mg/spray (1 ea [DSC])
Solution, Nasal, as tromethamine [preservative free]:
Sprix: 15.75 mg/spray (1 ea) [contains edetate (edta) disodium]
Yes
Solution (Sprix Nasal)
15.75 mg/spray (per each): $633.26
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Intranasal: For intranasal use only; do not inhale ketorolac nasal spray. Each nasal spray bottle contains medication for 1 day of therapy. Before first use of nasal spray, prime by holding the bottle upright and pressing pump 5 times. There is no need to prime again if more doses are administered during the next 24 hours using the same nasal spray bottle. Repeat priming each day prior to first use of each new nasal spray bottle. Blow nose to clear nostrils before using nasal spray.
Sit up straight or stand; tilt head slightly forward. Insert tip of container into nostril, keeping bottle upright, and point bottle toward the back and away from center of the nose. Hold breath and spray once, pressing down evenly on both sides of container. Immediately after administration, resume breathing through mouth to expel the product; pinch nose to help retain spray if dripping begins. Repeat in the opposite nostril if 2 sprays are prescribed per dose.
Discard bottle within 24 hours of priming even if there is unused medication.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/022382s022lbl.pdf#page=22, must be dispensed with this medication.
Pain management, acute: Short-term (up to 5 days) management of pain in adults that requires analgesia at the opioid level.
Migraine
Ketorolac may be confused with Ketalar, ketamine, methadone
Beers Criteria: Ketorolac is identified in the Beers Criteria as a potentially inappropriate medication to be avoided for chronic use in patients 65 years and older (unless alternative agents are ineffective and patient can receive concomitant gastroprotective agent) due to increased risk of GI bleeding and peptic ulcer disease in older adults in high-risk category (eg, older than 75 years of age or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents). In addition, avoid for short-term scheduled use in combination with oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents unless alternatives are ineffective and patient can receive concomitant gastroprotective agent (Beers Criteria [AGS 2023]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor
Abciximab: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Abrocitinib: Agents with Antiplatelet Effects may increase antiplatelet effects of Abrocitinib. Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Acemetacin: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Alcohol (Ethyl): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor
Aliskiren: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Aliskiren. Risk C: Monitor
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor
Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid
Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor
Anagrelide: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Angiotensin II Receptor Blockers: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Angiotensin II Receptor Blockers may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Anticoagulants (Miscellaneous Agents): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): Agents with Antiplatelet Effects may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Aspirin: Ketorolac (Nasal) may increase adverse/toxic effects of Aspirin. An increased risk of bleeding may be associated with use of this combination. Ketorolac (Nasal) may decrease cardioprotective effects of Aspirin. Management: Concurrent use of nasal ketorolac with analgesic doses of aspirin is generally not recommended. If using low-dose, cardioprotective aspirin with nasal ketorolac, monitor the patient closely for evidence of adverse GI effects. Risk D: Consider Therapy Modification
Bemiparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Bemiparin. Management: Avoid this combination if possible, due to an increased risk of bleeding. If coadministration cannot be avoided, monitor patients closely for clinical and laboratory evidence of bleeding. Risk D: Consider Therapy Modification
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Beta-Blockers. Risk C: Monitor
Bile Acid Sequestrants: May decrease absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor
Caplacizumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Caplacizumab. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Cardiac Glycosides: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Cardiac Glycosides. Risk C: Monitor
Collagenase (Systemic): Agents with Antiplatelet Effects may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
Corticosteroids (Systemic): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor
CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. Risk D: Consider Therapy Modification
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deferasirox: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Desirudin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Desirudin. Risk C: Monitor
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Direct Oral Anticoagulants (DOACs): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Drospirenone-Containing Products: May increase hyperkalemic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Enoxaparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Enoxaparin. Management: Discontinue nonselective NSAIDs prior to initiation of enoxaparin whenever possible. If coadministration cannot be avoided, monitor patients closely for clinical and laboratory evidence of bleeding. Risk D: Consider Therapy Modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Eplerenone. Risk C: Monitor
Fondaparinux: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Fondaparinux. Management: Discontinue nonselective nonsteroidal anti-inflammatory agents prior to the initiation of fondaparinux, if possible. If coadministration is required, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Heparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Heparin. Risk C: Monitor
Heparins (Low Molecular Weight): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of HydrALAZINE. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Ketorolac (Systemic). Risk X: Avoid
Limaprost: May increase adverse/toxic effects of Agents with Antiplatelet Effects. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider Therapy Modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may decrease diuretic effects of Loop Diuretics. Loop Diuretics may increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider Therapy Modification
Macimorelin: Coadministration of Nonsteroidal Anti-Inflammatory Agents and Macimorelin may alter diagnostic results. Risk X: Avoid
MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of MetFORMIN. Risk C: Monitor
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Methotrexate. Management: Avoid coadministration of higher dose methotrexate (such as that used for the treatment of oncologic conditions) and NSAIDs. Use caution if coadministering lower dose methotrexate and NSAIDs. Risk D: Consider Therapy Modification
Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor
Methoxyflurane: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Methoxyflurane. Risk X: Avoid
Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Mifamurtide. Risk X: Avoid
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Nadroparin: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Nadroparin. Management: Coadministration of NSAIDs and nadroparin is not recommended due to an increased risk of bleeding. If coadministration is required, monitor patients closely for clinical and laboratory signs of bleeding. Risk D: Consider Therapy Modification
Naftazone: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Neuromuscular-Blocking Agents (Nondepolarizing): Ketorolac (Nasal) may increase adverse/toxic effects of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): Nonsteroidal Anti-Inflammatory Agents (Topical) may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider Therapy Modification
Nonsteroidal Anti-Inflammatory Agents: Ketorolac (Nasal) may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Obinutuzumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and agents with antiplatelet effects, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor
Pentosan Polysulfate Sodium: Agents with Antiplatelet Effects may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Pentoxifylline: Ketorolac (Nasal) may increase adverse/toxic effects of Pentoxifylline. Specifically, the risk of bleeding may be increased. Risk X: Avoid
Phenylbutazone: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor
Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid
Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Potassium Salts. Risk C: Monitor
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may increase hyperkalemic effects of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may decrease antihypertensive effects of Potassium-Sparing Diuretics. Risk C: Monitor
PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Avoid coadministration of pralatrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). If coadministration cannot be avoided, closely monitor for increased pralatrexate serum levels or toxicity. Risk D: Consider Therapy Modification
Probenecid: May increase serum concentration of Ketorolac (Nasal). Risk X: Avoid
Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor
Quinolones: Nonsteroidal Anti-Inflammatory Agents may increase neuroexcitatory and/or seizure-potentiating effects of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Quinolones. Risk C: Monitor
Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase adverse/toxic effects of Salicylates. An increased risk of bleeding may be associated with use of this combination. Risk X: Avoid
Selective Serotonin Reuptake Inhibitor: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider Therapy Modification
Selumetinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification
Sodium Phosphates: May increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
Sulprostone: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Sulprostone. Risk X: Avoid
Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Tacrolimus (Systemic). Risk C: Monitor
Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may increase nephrotoxic effects of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider Therapy Modification
Tenoxicam: May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Nonsteroidal Anti-Inflammatory Agents may decrease therapeutic effects of Thiazide and Thiazide-Like Diuretics. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Thrombolytic Agents: Agents with Antiplatelet Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Tolperisone: Nonsteroidal Anti-Inflammatory Agents may increase adverse/toxic effects of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may increase therapeutic effects of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor
Tricyclic Antidepressants: May increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents. Tricyclic Antidepressants may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Risk C: Monitor
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase serum concentration of Vancomycin. Risk C: Monitor
Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may increase anticoagulant effects of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider Therapy Modification
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Nonsteroidal anti-inflammatory drugs may delay or prevent rupture of ovarian follicles. This may be associated with infertility that is reversible upon discontinuation of the medication.
Refer to the Ketorolac (Systemic) monograph for additional information.
Maternal use of nonsteroidal anti-inflammatory drugs may be associated with adverse pregnancy outcomes. Use of ketorolac nasal during labor and delivery is contraindicated.
Refer to the Ketorolac (Systemic) monograph for additional information.
Ketorolac is present in breast milk following oral administration.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Refer to the Ketorolac (Systemic) monograph for additional information.
Monitor for weight gain/edema; renal function (serum creatinine, BUN, urine output); observe for bleeding, bruising; evaluate gastrointestinal effects (abdominal pain, bleeding, dyspepsia); CBC and platelets, liver function tests
Serum concentration: Therapeutic: 0.3 to 5 mcg/mL; Toxic: >5 mcg/mL
Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties
Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.
Onset of analgesia: Within 20 minutes (Singla 2010)
Absorption: Rapid and well absorbed; Cmax, Tmax, and AUC values were similar following multiple administrations for 5 days compared to the single-dose study in healthy volunteers.
Distribution: ~13 L following complete distribution; following intranasal administration, ketorolac is deposited primarily in the nasal cavity and pharynx; <20% deposited in the esophagus and stomach; <0.5% in the lungs
Protein binding: 99%
Metabolism: Hepatic to hydroxylated and conjugated forms
Bioavailability: ~60% relative to IM administration
Half-life elimination: ~5 to 6 hours (similar to IM administration)
Time to peak: 0.75 hours
Excretion: Urine (~92%, ~60% as unchanged drug); feces ~6%
Altered kidney function: Cl is reduced, half-life is increased up to 19 h, AUC is increased by approximately 100%, and Vd increases.
Older adult: Half-life is longer and exposure is increased by 23% in patients ≥65 years of age.
