Version May 2024
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 in the 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) (ACC/ACG/AHA [Abraham 2010]; ACC/ACG/AHA [Bhatt 2008]). 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) (manufacturer's labeling [US]).
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) (manufacturer's labeling [US]).
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 (Rao 2016).
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. Events reported with intranasal use; refer to Ketorolac (Systemic) monograph for other potential ketorolac-related adverse events.
>10%: Respiratory: Nasal discomfort (15%), sore nose (13%)
>1% to 10%:
Cardiovascular: Bradycardia (2%), hypertension (2%)
Dermatologic: Skin rash (3%)
Genitourinary: Oliguria (3%), decreased urine output (2%)
Hepatic: Increased serum ALT (≤2%), increased serum AST (≤2%)
Ophthalmic: Increased lacrimation (5%)
Respiratory: Throat irritation (4%), rhinitis (2%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Anemia, hematoma, hemorrhage
Hypersensitivity 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: [US Boxed Warning]: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. Risk may occur early during treatment and may increase with duration of use. 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 (FDA 2015). 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:[US Boxed Warning]: NSAIDs cause an increased risk of serious gastrointestinal inflammation, ulceration, bleeding, and perforation (may be fatal); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. These events may occur at any time during therapy and without warning. 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 including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; discontinue use at first sign of skin rash or 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: [US Boxed Warning]: Use is contraindicated in the setting of coronary artery bypass graft (CABG) 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): $592.39
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/2021/022382s021lbl.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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor therapy
Abrocitinib: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor therapy
Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Risk C: Monitor therapy
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Apixaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Aspirin: Ketorolac (Nasal) may enhance the adverse/toxic effect of Aspirin. An increased risk of bleeding may be associated with use of this combination. Ketorolac (Nasal) may diminish the cardioprotective effect 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 may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy
CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the 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
Dabigatran Etexilate: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Edoxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Enoxaparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Heparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required. Risk D: Consider therapy modification
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Ketorolac (Systemic). Risk X: Avoid combination
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the 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 diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect 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: Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of MetFORMIN. Risk C: Monitor therapy
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the 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 enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Ketorolac (Nasal) may enhance the adverse/toxic effect of Neuromuscular-Blocking Agents (Nondepolarizing). Specifically, episodes of apnea have been reported in patients using this combination. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Ketorolac (Nasal) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect 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
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: Ketorolac (Nasal) may enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased. Risk X: Avoid combination
Phenylbutazone: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the 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 the serum concentration of Ketorolac (Nasal). Risk X: Avoid combination
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor therapy
Quinolones: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy
Rivaroxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. 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 enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect 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 enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy
Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect 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 enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Tolperisone: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Tricyclic Antidepressants may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Risk C: Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect 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
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
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.
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