Version July 2025
Ketorolac is indicated for the short-term (up to 5 days in adults) management of moderately severe acute pain that requires analgesia at the opioid level. Oral ketorolac is only indicated as continuation treatment following IV or IM dosing of ketorolac, if necessary. The total combined duration of use of ketorolac tablets and injection should not exceed 5 days. The recommended total daily dose of ketorolac tablets (maximum 40 mg) is significantly lower than for ketorolac injection (maximum 120 mg).
Ketorolac is not indicated for use in pediatric patients and is not indicated for minor or chronic painful conditions. Increasing the dose of ketorolac beyond labeled recommendations will not provide better efficacy but will increase the risk of developing serious adverse events.
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction 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 surgery.
Ketorolac can cause peptic ulcers, GI bleeding, and/or perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Therefore, ketorolac is contraindicated in patients with active peptic ulcer disease, recent GI bleeding or perforation, and a history of peptic ulcer disease or GI bleeding. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.
Ketorolac is contraindicated for intrathecal or epidural administration due to its alcohol content.
Hypersensitivity reactions, ranging from bronchospasm to anaphylactic shock, have occurred and appropriate counteractive measures must be available when administering the first dose of ketorolac injection. Ketorolac is contraindicated in patients with previously demonstrated hypersensitivity to ketorolac or allergic manifestations to aspirin or other NSAIDs.
Ketorolac is contraindicated in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion.
Ketorolac inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, and those at high risk of bleeding.
Ketorolac is contraindicated as a prophylactic analgesic before any major surgery.
The use of ketorolac in labor and delivery is contraindicated because it may adversely affect fetal circulation and inhibit uterine contractions.
Ketorolac is contraindicated in patients currently receiving aspirin or NSAIDs because of the cumulative risks of inducing serious NSAID-related adverse events.
Dosage should be adjusted for patients ≥65 years of age, for patients <50 kg (110 lbs) of body weight, and for patients with moderately elevated serum creatinine. Doses of ketorolac injection are not to exceed 60 mg (total dose per day) in these patients.
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; do not shorten dosing interval of 4 to 6 hours. 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. Oral formulation should not be given as initial therapy; other better tolerated oral NSAIDs are generally preferred.
Weight ≥50 kg and <65 years of age:
IV: 30 mg as a single dose or 15 to 30 mg every 6 hours as needed; maximum daily dose: 120 mg/day; maximum duration: 5 days combined (parenteral, oral, and nasal) (Ref).
IM: 30 to 60 mg as a single dose or 15 to 30 mg every 6 hours as needed; alternatively, may administer 10 to 30 mg every 4 to 6 hours as needed; maximum daily dose: 120 mg/day; maximum duration: 5 days combined (parenteral, oral, and nasal) (Ref).
Oral (only as continuation of IM or IV therapy, not for initial therapy): 20 mg once, followed by 10 mg every 4 to 6 hours as needed; maximum daily dose: 40 mg/day; maximum duration: 5 days combined (parenteral, oral, and nasal) (Ref).
Weight <50 kg or ≥65 years of age:
IV: 15 mg as a single dose or 15 mg every 6 hours as needed; maximum daily dose: 60 mg/day; maximum duration: 5 days combined (parenteral, oral, and nasal) (Ref).
IM: 30 mg as a single dose or 15 mg every 6 hours as needed; alternatively, may administer 10 mg every 4 to 6 hours as needed; maximum daily dose: 60 mg/day; maximum duration: 5 days combined (parenteral, oral, and nasal) (Ref).
Oral (only as continuation of IM or IV therapy, not for initial therapy): 10 mg every 4 to 6 hours as needed; maximum daily dose: 40 mg/day; maximum duration: 5 days combined (parenteral, oral, and nasal) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
eGFR ≥60 mL/minute/1.73 m2: IM, IV, Oral: No dosage adjustment necessary (Ref).
eGFR >30 to <60 mL/minute/1.73 m2:
IM, IV: Use of analgesics other than nonsteroidal anti-inflammatory drugs may be preferred. If necessary, consider 7.5 to 15 mg every 6 hours (Ref); use the lowest effective dose for the shortest duration possible. Avoid use in patients at high risk for acute kidney injury (ie, volume depleted, hypotensive, elderly, or taking concurrent nephrotoxic medications) (Ref).
Oral: 10 mg every 4 to 6 hours as needed; maximum: 40 mg/day; oral dosing is intended to be a continuation of IM or IV therapy (Ref).
eGFR ≤30 mL/minute/1.73 m2: IM, IV, Oral: Avoid use due to increased risk of acute kidney injury (Ref). The manufacturer’s labeling states use is contraindicated in advanced kidney impairment.
Hemodialysis, intermittent (thrice weekly): Not dialyzable: IM, IV, Oral: Avoid use, as patients with end-stage kidney disease may be at increased risk for bleeding (eg, GI), cardiovascular adverse effects, and loss of residual kidney function (Ref). The manufacturer’s labeling states use is contraindicated in advanced kidney impairment.
Peritoneal dialysis: Unlikely to be significantly dialyzed given very high protein binding (Ref): IM, IV, Oral: Avoid use, as patients with end-stage kidney disease may be at increased risk for bleeding (eg, GI), cardiovascular adverse effects, and loss of residual kidney function (Ref). The manufacturer’s labeling states use is contraindicated in advanced kidney impairment.
CRRT: Avoid use (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Avoid use (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution to avoid adverse effects and discontinue if hepatic function worsens.
Avoid use (Ref).
(For additional information see "Ketorolac (systemic): Pediatric drug information")
Dosage guidance:
Dosing: To reduce the risk of adverse cardiovascular and GI effects, use the lowest effective dose for the shortest period of time. The total duration of ketorolac (combined IV/IM and oral) should not exceed 5 days (Ref).
Pain management (acute; moderately severe):
Infants and Children <2 years: Limited data available: IV: 0.5 mg/kg/dose every 6 to 8 hours, not to exceed 48 to 72 hours of treatment; has been used postoperatively primarily following cardiac and abdominal surgery; maximum dose: 15 mg/dose (Ref). A lower dose of 0.25 mg/kg/dose every 6 to 8 hours has also been recommended (Ref). Note: IM administration has been described in patients ≥6 months of age (Ref).
Children ≥2 years and Adolescents ≤16 years: Limited data available:
IM, IV: 0.5 mg/kg/dose every 6 to 8 hours; maximum dose: 30 mg/dose, usual reported duration: 48 to 72 hours; not to exceed 5 days of treatment (Ref).
Oral: 1 mg/kg/dose every 4 to 6 hours; maximum dose: 10 mg/dose; maximum daily dose: 40 mg/day (Ref). Note: Oral formulation should only be used as continuation of IV or IM therapy; do not use as initial therapy (Ref).
Adolescents ≥17 years: Note: The maximum combined duration of treatment (for parenteral and oral) is 5 days; do not increase dose or frequency; supplement with low-dose opioids if needed for breakthrough pain.
<50 kg:
IM: 30 mg as a single dose or 15 mg every 6 hours; maximum daily dose: 60 mg/day.
IV: 15 mg as a single dose or 15 mg every 6 hours; maximum daily dose: 60 mg/day.
Oral: Initial: 10 mg, then 10 mg every 4 to 6 hours; maximum daily dose: 40 mg/day.
≥50 kg:
IM: 60 mg as a single dose or 30 mg every 6 hours; maximum daily dose: 120 mg/day.
IV: 30 mg as a single dose or 30 mg every 6 hours; maximum daily dose: 120 mg/day.
Oral: Initial: 20 mg, then 10 mg every 4 to 6 hours; maximum daily dose: 40 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustments are recommended for adult patients. The specific degree of renal impairment where use is permitted is not defined in the product labeling; however, use is contraindicated in patients with advanced renal impairment or those at risk for renal failure due to volume depletion; some experts have suggested the following:
Infants, Children, and Adolescents:
Aronoff 2007 recommendations: Note: Renally adjusted dose recommendations are based on doses of IV, IM: 0.25 to 1 mg/kg/dose every 6 hours (Ref).
GFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 29 mL/minute/1.73 m2: Administer 50% of dose.
GFR <10 mL/minute/1.73 m2: Administer 25% to 50% of dose.
Intermittent hemodialysis: Avoid use.
Peritoneal dialysis: Avoid use.
KDIGO guidelines provide the following recommendations for NSAIDs (Ref):
eGFR 30 to <60 mL/minute/1.73 m2: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.
eGFR <30 mL/minute/1.73 m2: Avoid use.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution, may cause elevation of liver enzymes; discontinue if clinical signs and symptoms of liver disease develop.
Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of serious adverse cardiovascular (CV) events, including acute myocardial infarction (MI), cerebrovascular accident, and CV death. New-onset hypertension or exacerbation of hypertension may occur with NSAID use, which may also contribute to an increased risk of CV events; this effect was documented following use of celecoxib, ibuprofen, or naproxen in the PRECISION-ABPM trial (Ref). NSAIDS should be avoided in patients hospitalized for acute coronary syndromes due to the risk of adverse cardiac events (Ref). New-onset or exacerbation of heart failure may also occur with cyclooxygenase (COX)-2 selective NSAIDs (ie, coxibs) and nonselective NSAIDs, including ketorolac, resulting in an increased risk of hospitalizations for heart failure and death in patients with heart failure (Ref).
Data collected by the Coxib and traditional NSAID Trialists’ Collaborative have shown that high-dose naproxen may have the most favorable CV risk profile among NSAIDs analyzed (Ref); however, data from the PRECISION trial showed no difference with regards to risk between naproxen, ibuprofen, or celecoxib after a treatment duration of therapy of ~3 years (Ref).
CV risk associated with use of ketorolac was not evaluated in long-term studies as treatment with ketorolac is limited to short-term use (ie, 5 days). Additionally, several retrospective studies evaluating the use of ketorolac in patients with cardiovascular disease (CVD) undergoing coronary artery bypass graft (CABG) surgery have failed to find an increased risk of adverse effects including mortality, MI, and bleeding events in this patient population (Ref); clinicians should note that these studies cannot confirm mortality benefit and/or increased graft patency. The FDA states that there are insufficient data to determine if the risk of MI or stroke is definitely higher or lower for any particular NSAID as compared to another (Ref).
Mechanism: Dose- and time-related; inhibition of COX-2 by NSAIDs results in a reduction in the production of prostaglandin I2 (prostacyclin), a potent vasodilator and anticoagulant present in the vascular endothelium (Ref). Animal studies have shown that reduced prostacyclin activity may result in a predisposition to vascular injury (Ref). In addition, prostaglandins inhibit sodium resorption in the thick ascending loop of Henle and collecting tubule; therefore, a reduction in prostaglandin synthesis by NSAIDs may cause sodium and fluid retention and result in hypertension and decreased efficacy of diuretics (Ref).
Onset: Varied; increased risk is associated with both short- and long-term use and may be apparent within the first weeks following initiation of treatment (Ref); longer duration of therapy may further increase risk (Ref). Treatment with ketorolac is limited to short-term use (ie, 5 days).
Risk factors:
• ≥65 years of age
• Higher doses (especially with regards to CV thrombotic risk [(Ref)]
• Longer duration of use and frequent use (eg, ≥22 days per month (Ref)
- Note: Treatment with ketorolac is limited to short-term use (ie, 5 days).
• Preexisting CVD, including heart failure, or presence of risk factors for CVD (Ref)
- Note: Relative risk appears to be similar in those with and without known CVD or risk factors for CVD; however, absolute incidence of serious CV thrombotic events appears to be higher in patients with known CVD or risk factors for CVD due to an increased baseline risk (Ref).
- Note: The use of NSAIDs is contraindicated in the setting of CABG surgery due to an increased risk of MI and stroke in this patient population. Yet, retrospective studies specific to ketorolac have not shown an increased risk of death, MI, or bleeding events following use in postoperative CABG patients (Ref).
Use of nonsteroidal anti-inflammatory drugs (NSAIDs), especially nonselective NSAIDs, such as ketorolac, is associated with an increased risk of serious gastrointestinal (GI) adverse events, including gastrointestinal inflammation, gastrointestinal hemorrhage, gastrointestinal ulcer, and gastrointestinal perforation; severity may range from asymptomatic to fatal (Ref). The risk of upper GI hemorrhage and/or perforation has been reported to be higher with ketorolac as compared to other nonselective NSAIDs (Ref).
Mechanism: Dose- and time-related; inhibition of cyclooxygenase (COX)-1 by NSAIDs results in a reduction in the production of mucosal-protective prostaglandin E2 (Ref).
Onset: Varied; GI events can occur at any time during use and without warning symptoms. A longer duration of use (eg, ≥7 days (Ref)) is associated with a greater risk. Treatment with ketorolac is limited to short-term use (ie, 5 days).
Risk factors:
• Older age (eg, ≥65 years of age (Ref))
• Longer duration of use (eg, ≥5 days (Ref))
- Note: Treatment with ketorolac is limited to short-term use (ie, 5 days).
• Higher doses
• Prior history of peptic ulcer disease and/or GI bleeding (Ref)
• Concomitant use of agents known to increase the risk of GI bleeding (eg, aspirin (Ref), anticoagulants, corticosteroids (Ref), selective serotonin reuptake inhibitors (Ref))
• Comorbid Helicobacter pylori infection (Ref)
• Advanced liver disease/cirrhosis
• Coagulopathy
• Smoking
• Consumption of alcohol
• People with poor general health status
• Small intestine damage: Small intestine bacterial overgrowth (SIBO), including SIBO induced by proton pump inhibitor therapy, may be associated with an increased risk of small intestine damage (Ref)
Use of nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, is associated with prolonged bleeding time and an increased risk for hemorrhage, particularly gastrointestinal bleeding (Ref). Some studies have suggested that ketorolac is not associated with increased bleeding in the perioperative period (Ref).
In addition, drug-induced hemolytic anemia may occur with the use of NSAIDs (Ref). Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, aplastic anemia, neutropenia, thrombocytopenia) (Ref).
Mechanism:
Prolonged bleeding time: Inhibition of cyclooxygenase (COX)-1 by nonselective NSAIDs causes a decrease in the production of prostaglandins, prostacyclins, and thromboxanes, including thromboxane A2 (TxA2) (Ref). As a result, patients may exhibit a decrease in platelet adhesion and aggregation and subsequent prolonged bleeding time (Ref).
Blood dyscrasias: Not clearly established; anemia may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. May also be attributed to a drug-dependent immune mechanism (Ref).
Onset: Prolonged bleeding time: Rapid; suppression of platelet COX-1 activity occurs within hours of administration of an NSAID (Ref). Bleeding time was prolonged within hours of administration of a single dose of ketorolac in healthy volunteers (Ref); postoperatively, bleeding has been reported after a single dose of ketorolac (Ref).
Risk factors:
• Bleeding events:
- Preexisting coagulation disorders
- Concomitant use of agents known to increase the risk of bleeding (eg, anticoagulants (Ref), antithrombotics (Ref), antiplatelet agents [eg, aspirin, P2Y12 inhibitors], selective serotonin reuptake inhibitors (Ref), or serotonin norepinephrine reuptake inhibitors)
- Use during and immediately following surgical procedures (Ref)
• Note: Some studies have suggested that ketorolac is not associated with increased bleeding in the perioperative period (Ref)
- Age <21 days and <37 weeks corrected gestational age (Ref)
Nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, may cause mild transaminase elevations, especially with higher doses; one study found no association between use of parenteral ketorolac and hepatoxic effects (Ref). Rarely, serious liver injury may occur following use of NSAIDs (Ref). Cholestatic and mixed patterns of injury have been reported with the use of NSAIDs. NSAID-induced hepatic effects may occur following severe hypersensitivity reactions (eg, toxic epidermal necrosis, Stevens-Johnson syndrome) and are characterized by immune-mediated symptoms (eg, fever rash, eosinophilia, lymphadenopathy) (Ref). Severe liver injury requiring liver transplantation has also been reported following use of NSAIDs (Ref). Most cases of liver injury are likely reversible following discontinuation; full recovery may take several months (Ref). However, chronic vanishing bile duct syndrome with chronic liver failure has been reported following cholestatic liver injury secondary to ibuprofen (Ref).
Mechanism: Not clearly established; dose-related has been suggested (Ref). Proposed mechanisms include a toxic metabolite or a hypersensitivity reaction (Ref).
Onset: Varied; onset of NSAID-induced hepatotoxicity is generally classified as moderate (30 to 90 days) to long (>90 days) (Ref). For ibuprofen, a mean time of 12 days (range: 1 to 42 days) was reported in one study (Ref). Treatment with ketorolac is limited to short-term use (ie, 5 days).
Risk factors:
• Higher doses (Ref)
• Prior NSAID-related liver injury (Ref)
- Note: Cross-reactivity may occur between groups of NSAIDs (eg, cross-reactivity between propionic acid derivatives [ibuprofen, naproxen, ketoprofen]) (Ref). Ketorolac is a member of the pyrrolo-pyrrole group of NSAIDs.
Hypersensitivity reactions (immediate and delayed) involving the skin (eg, angioedema, urticaria), airways (eg, dyspnea, rhinorrhea), and/or other organs have been reported (Ref). Clinical phenotypes of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity reactions include NSAID-exacerbated respiratory disease (NERD), NSAID-induced urticaria/angioedema (NIUA), NSAID-exacerbated cutaneous disease (NECD), and single NSAID-induced urticaria/angioedema or anaphylaxis (Ref). Delayed hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have also been associated with ketorolac.
Mechanism:
Immediate reactions: Non–dose-related; most reactions (ie, NERD, NECD, NIUA) are nonimmunologic related to inhibition of cyclooxygenase (COX)-1 with subsequent activation of mast cells and eosinophils causing release of inflammatory mediators including cysteinyl-leukotrienes (Ref). Some immediate reactions may be IgE mediated (Ref).
Delayed reactions: Delayed hypersensitivity reactions are T-cell mediated (Ref).
Onset:
Immediate reactions: Rapid; generally occurs within 1 hour of administration but may occur several hours after exposure (Ref).
Delayed reactions (including DRESS and SJS/TEN): Varied; generally occurs after 1 to 8 weeks after initiation (Ref).
Risk factors:
• Presence of chronic rhinosinusitis with nasal polyps, family history of NERD, and/or severe asthma may increase the risk of NERD (Ref). The prevalence of NERD in adult patients with asthma is ~10% to 20% (Ref).
• Chronic urticaria increases the risk of NECD (Ref). NSAID-induced reactions are less frequent and less intense when chronic urticaria is in remission or under control (Ref). Approximately 12% to 30% of patients with chronic idiopathic urticaria develop exacerbations of their disease with use of ketorolac and other COX-1 inhibitors (Ref).
• Cross-reactivity between aspirin and NSAIDs, including ketorolac (with predominant COX-1 inhibition) have been described in patients with a history of NERD, NECD, and NIUA (Ref). Cross-reactivity between aspirin/NSAID and acetaminophen, a weak COX inhibitor, and between aspirin/NSAID and nonselective COX-2 inhibitors (eg, meloxicam, nimesulide) may occur (Ref). Although selective COX-2 inhibitors (eg, celecoxib, etoricoxib) are generally tolerated in patients with NERD (Ref), cross-reactions may occur, especially in patients with histories of urticaria/angioedema (Ref).
Hemodynamically mediated acute kidney injury (AKI) may occur following use of either cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) (ie, coxibs) or nonselective NSAIDs, including ketorolac (Ref); the risk may be greater with nonselective NSAIDs (Ref). The risk of developing AKI is decreased upon discontinuation (Ref). In patients who develop AKI, kidney function is likely to return to baseline following prompt discontinuation of the offending NSAID and supportive care (Ref); however, the mechanism of the damage and other concurrent factors can contribute to irreversibility.
Mechanism: Dose- and time-related; inhibition of COX-1 and COX-2 by NSAIDs results in a reduced production of nephroprotective prostaglandins and subsequent attenuation of renal vasodilation (Ref). In addition, an increase in vasoconstriction of the afferent arteriole and impaired renal blood flow causes a reduction in the glomerular capillary pressure and filtration (Ref).
Onset: Rapid; may occur within hour to days of treatment initiation (Ref).
Risk factors:
• AKI:
- Preexisting kidney impairment
- Chronic kidney disease
- ≥65 years of age (Ref)
• Note: NSAID-associated AKI may also occur in pediatric patients, even at therapeutic doses (Ref).
• Hemodynamically mediated AKI:
- Preexisting conditions that result in decreased effective arterial circulation (ie, conditions where renal blood flow/renal perfusion may be dependent on prostaglandin-mediated vasodilation) (Ref):
• Volume depletion (eg, due to concomitant diuretic use, vomiting)
• Heart failure (Ref)
• Cirrhosis and ascites (Ref)
• Nephrotic syndrome
- Concomitant use of diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or calcineurin inhibitors (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Some reactions listed are based on reports for other agents in this same pharmacologic class and may not be specifically reported for ketorolac.
>10%:
Gastrointestinal: Abdominal pain, dyspepsia, nausea
Hepatic: Increased liver enzymes (≤15%)
Nervous system: Headache
1% to 10%:
Cardiovascular: Edema, hypertension
Dermatologic: Diaphoresis, pruritus, skin rash
Gastrointestinal: Constipation, diarrhea, flatulence, gastrointestinal fullness, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, heartburn, stomatitis, vomiting
Hematologic & oncologic: Anemia, prolonged bleeding time, purpuric disease
Local: Pain at injection site (IM, IV)
Nervous system: Dizziness, drowsiness
Otic: Tinnitus
Renal: Altered kidney function
<1%:
Cardiovascular: Heart failure, palpitations, syncope, tachycardia
Dermatologic: Alopecia, ecchymoses, pallor, skin photosensitivity, urticaria
Endocrine & metabolic: Increased thirst, weight changes
Gastrointestinal: Anorexia, dysgeusia, eructation, esophagitis, gastritis, glossitis, hematemesis, increased appetite, melena, rectal hemorrhage, xerostomia
Genitourinary: Cystitis, dysuria, exacerbation of urinary frequency, hematuria, infertility, oliguria, proteinuria, urinary retention
Hematologic & oncologic: Eosinophilia, leukopenia, thrombocytopenia
Hepatic: Hepatitis, jaundice
Infection: Infection, sepsis
Nervous system: Abnormal dreams, anxiety, asthenia, changes in thinking, confusion, depression, euphoria, extrapyramidal reaction, hallucination, insomnia, lack of concentration, malaise, nervousness, paresthesia, stupor, tremor, vertigo
Neuromuscular & skeletal: Hyperkinetic muscle activity
Ophthalmic: Blurred vision, visual disturbance
Otic: Hearing loss
Renal: Interstitial nephritis, kidney failure, polyuria
Respiratory: Asthma, cough, dyspnea, epistaxis, pulmonary edema, rhinitis
Miscellaneous: Fever
Frequency not defined:
Cardiovascular: Coronary thrombosis
Gastrointestinal: Peptic ulcer
Nervous system: Cerebrovascular accident
Postmarketing:
Cardiovascular: Acute myocardial infarction, bradycardia, cardiac arrhythmia, chest pain, flushing, hypotension, vasculitis
Dermatologic: Bullous skin disease, erythema multiforme, exfoliative dermatitis, fixed drug eruption, Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Hyperglycemia, hyperkalemia (Haragsim 1994), hyponatremia
Gastrointestinal: Acute pancreatitis (Famularo 2002), aphthous stomatitis, exacerbation of Crohn disease, exacerbation of ulcerative colitis
Genitourinary: Azotemia
Hematologic: Agranulocytosis, aplastic anemia, hemolytic anemia, hemolytic-uremic syndrome (Randi 1993), lymphadenopathy, pancytopenia, postoperative hematoma, postoperative wound bleeding
Hepatic: Hepatic failure, hepatotoxicity (idiosyncratic) (Chalasani 2021)
Hypersensitivity: Anaphylaxis (Yousefi 2020), angioedema (Shapiro 1994), drug reaction with eosinophilia and systemic symptoms, hypersensitivity reaction, nonimmune anaphylaxis (Goetz 1992), tongue edema
Nervous system: Aseptic meningitis (Shahin 2024), coma, psychosis, seizure
Neuromuscular & skeletal: Myalgia
Ophthalmic: Conjunctivitis
Renal: Acute kidney injury (Haragsim 1994), flank pain, nephrotic syndrome, renal papillary necrosis (Witting 1996)
Respiratory: Bronchospasm (Chen 1994), laryngeal edema, pneumonia, respiratory depression
Hypersensitivity to ketorolac, aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), or any component of the formulation; active or history of peptic ulcer disease; recent or history of GI bleeding or perforation; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; advanced renal disease or patients at risk for renal failure due to volume depletion; prophylactic analgesic before any major surgery; suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or high risk of bleeding; concurrent use with aspirin, other NSAIDs, probenecid, or pentoxifylline; epidural or intrathecal administration (injection only); use in the setting of coronary artery bypass graft surgery; labor and delivery.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Intraoperative use; coagulation disorders; active GI bleeding; postoperative patients with high-bleeding risk; severe uncontrolled heart failure; inflammatory bowel disease; severe hepatic impairment or active hepatic disease; moderate to severe renal impairment (serum creatinine >442 micromol/L and/or creatinine clearance <30 mL/minute) or deteriorating renal disease; known hyperkalemia; third trimester of pregnancy; breast-feeding; use in children and adolescents <18 years of age
Concerns related to adverse effects:
• 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.
Disease-related concerns:
• Aseptic meningitis: May increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders.
• Bariatric surgery: Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may occur (Bhangu 2014; Mechanick 2020). Short-term use of celecoxib or IV ketorolac are recommended as part of a multimodal pain management strategy for postoperative pain (Chou 2016; Horsley 2019; Thorell 2016).
• Hepatic impairment: Use with caution in patients with hepatic impairment or a history of hepatic disease; patients with advanced hepatic disease are at an increased risk of GI bleeding and kidney failure with NSAIDs (AASLD [Biggins 2021]; AASLD [Runyon 2013]).
Special populations:
• Older adult: Patients ≥65 years of age are at greater risk for serious GI, cardiovascular, and/or renal adverse events; use with caution.
Other warnings/precautions:
• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.
In neonates, bleeding events have been reported; in a retrospective analysis of 57 postsurgical neonates and infants (age range: 0 to 3 months), 17.2% of patients experienced a bleeding event, most were PNA <21 days and those with PNA <14 days had a significantly higher risk than older neonates (Aldrink 2011). Acute kidney injury (AKI) has been observed in pediatric patients; with ketorolac use following cardiothoracic surgery, an increased risk of AKI was observed in neonates and infants who underwent a bidirectional Glenn procedure and were receiving concomitant aspirin therapy (Moffett 2013).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as tromethamine:
Generic: 15 mg/mL (1 mL); 30 mg/mL (1 mL)
Solution, Injection, as tromethamine [preservative free]:
Generic: 15 mg/mL (1 mL); 30 mg/mL (1 mL)
Solution, Intramuscular, as tromethamine:
Generic: 60 mg/2 mL (2 mL)
Solution, Intramuscular, as tromethamine [preservative free]:
Generic: 60 mg/2 mL (2 mL)
Tablet, Oral, as tromethamine:
Generic: 10 mg
Yes
Solution (Ketorolac Tromethamine Injection)
15 mg/mL (per mL): $0.84 - $4.50
30 mg/mL (per mL): $0.84 - $7.84
Solution (Ketorolac Tromethamine Intramuscular)
60 mg/2 mL (per mL): $0.54 - $4.92
Tablets (Ketorolac Tromethamine Oral)
10 mg (per each): $1.10 - $2.27
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intramuscular:
Toradol: 10 mg/mL (1 mL) [contains alcohol, usp]
Solution, Intramuscular, as tromethamine:
Generic: 30 mg/mL (1 mL)
Tablet, Oral, as tromethamine:
Toradol: 10 mg
Generic: 10 mg
Oral: May administer with food to reduce GI upset.
IM: Administer slowly and deeply into the muscle.
IV: Administer IV bolus over a minimum of 15 seconds.
Oral: May administer with food or milk to decrease GI upset.
Parenteral:
IM: Administer slowly and deeply into muscle; 60 mg per 2 mL vial is for IM use only.
IV bolus: Administer undiluted over at least 15 seconds; in children, ketorolac has been infused over 1 to 5 minutes (Ref).
An FDA-approved patient medication guide, which is available with the product information and at NSAIDs Class Medication Guide, must be dispensed with this medication.
Pain management, acute: Short-term (≤5 days) management of acute pain.
Migraine, severe, acute treatment
Ketorolac may be confused with Ketalar, ketamine, methadone
Toradol may be confused with Foradil, Inderal, Tegretol, traMADol, tromethamine
Beers Criteria: Ketorolac is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to an increased risk of GI bleeding, peptic ulcer disease, and acute kidney injury (Beers Criteria [AGS 2023]).
NSAIDs are identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as potentially inappropriate medications in older adults (≥65 years of age) for long-term use in the treatment of gout or osteoarthritis where other agents have not been tried (eg, acetaminophen for osteoarthritis, xanthine-oxidase inhibitors for gout). In addition, some disease states of concern include heart failure, renal impairment, peptic ulcer disease, gastrointestinal bleeding, severe hypertension, and coronary, cerebral or peripheral vascular disease (O’Mahony 2023).
Toradol [Canada and multiple international markets] may be confused with Theradol brand name for tramadol [Netherlands]
Substrate of OAT1/3;
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 (Systemic) may increase adverse/toxic effects of Aspirin. An increased risk of bleeding may be associated with use of this combination. Ketorolac (Systemic) may decrease cardioprotective effects of Aspirin. Risk X: Avoid
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
Fexinidazole: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider Therapy Modification
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 (Nasal): May increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid
Leflunomide: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
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 (Systemic) 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
Nitisinone: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). 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: May increase adverse/toxic effects of Ketorolac (Systemic). 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 (Systemic) may increase adverse/toxic effects of Pentoxifylline. Specifically, the risk of bleeding may be increased with this combination. 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
Pretomanid: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Probenecid: May increase serum concentration of Ketorolac (Systemic). 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
Taurursodiol: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid
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
Teriflunomide: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
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
Vaborbactam: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor
Vadadustat: May increase serum concentration of OAT1/3 Substrates (Clinically Relevant). 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
High-fat meals may delay time to peak (by ~1 hour) and decrease peak concentrations. Management: Administer tablet with food or milk to decrease gastrointestinal distress.
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. Consider discontinuing use in patients having difficulty conceiving or those undergoing investigation of fertility.
Ketorolac crosses the placenta (Walker 1988).
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) close to conception may be associated with an increased risk of miscarriage due to cyclooxygenase-2 inhibition interfering with implantation (Bermas 2014; Bloor 2013).
Birth defects have been observed following in utero NSAID exposure in some studies; however, data are conflicting (Bloor 2013). Nonteratogenic effects, including prenatal constriction of the ductus arteriosus, persistent pulmonary hypertension of the newborn, oligohydramnios, necrotizing enterocolitis, renal dysfunction or failure, and intracranial hemorrhage, have been observed in the fetus/neonate following in utero NSAID exposure (Bermas 2014; Bloor 2013). Maternal NSAID use may cause fetal renal dysfunction leading to oligohydramnios. Although rare, this may occur as early as 20 weeks' gestation and is more likely to occur with prolonged maternal use. Oligohydramnios may be reversible following discontinuation of the NSAID (Dathe 2019; FDA 2020). In addition, nonclosure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013).
Maternal use of NSAIDs should be avoided beginning at ~20 weeks' gestation. If NSAID use is necessary between 20 and 30 weeks' gestation, limit use to the lowest effective dose and shortest duration possible; consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found (FDA 2020). Because NSAIDs may cause premature closure of the ductus arteriosus, prescribing information for ketorolac specifically states use should be avoided starting at ~30 weeks' gestation
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of ketorolac may be altered. Ketorolac has S and R enantiomers; pharmacologic activity is associated with S-ketorolac enantiomer. The clearance of S-ketorolac was found to increase at delivery compared to postpartum values; the peak serum concentration was decreased (Kulo 2017; Välitalo 2017).
The use of ketorolac in labor and delivery is contraindicated because it may adversely affect fetal circulation and inhibit uterine contractions. The risk of uterine hemorrhage may be increased. NSAIDs may be used as part of multimodal pain management following cesarean delivery (ACOG 2019; Hostage 2023; Murdoch 2023).
Ketorolac is present in breast milk (Wischnik 1989).
The distribution of ketorolac into breast milk was studied in 10 women who were 2 to 6 days postpartum. Patients were given ketorolac 10 mg orally 4 times/day for 2 days. Simultaneous breast milk and maternal serum samples were drawn 4 times over the dosing period and the following day (day 3). Ketorolac concentrations were below the limit of quantification (5 ng/mL) in 4 patients at every sampling time, in all patients when measured prior to and 6 hours after the morning dose on days 1 and 2, and in all patients on day 3. When measurable, breast milk concentrations of ketorolac ranged from 5.2 to 7.9 ng/mL. The M/P ratio, when able to be calculated, ranged from 0.015 to 0.037. Using a breast milk concentration of 7.9 ng/mL, an infant weight of 3 kg, infant intake of 1 L of milk/day, and a maternal weight of 60 kg, the authors of the study estimated the exposure of ketorolac to the breastfeeding infant to be 0.16% to 0.40% of the maternal dose (Wischnik 1989). In general, breastfeeding is considered acceptable when the relevant infant dose is <10% (Anderson 2016; Ito 2000).
Data related to breastfeeding are available from 3 studies that evaluated use of ketorolac as part of a multimodal protocol for pain following cesarean delivery. In 1 study, women were given a single dose of ketorolac. There were no differences observed between neonates exposed to the protocol containing ketorolac compared to routine standard care without ketorolac in relation to breastfeeding, neonatal growth, sedation and respiratory depression (Hadley 2019). In a second study, ketorolac was used as needed or as a scheduled dose every 6 hours for 24 hours. More mothers who received the scheduled doses exclusively breastfed their newborns; the duration of breastfeeding was also increased (Teigen 2020). In a third study, the maternal dose of ketorolac (15 or 30 mg) was not found to influence the incidence of breastfeeding when used for up to 24 hours postpartum (Yurashevich 2020).
Nonopioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs), are preferred for breastfeeding patients who require pain control peripartum or for surgery outside of the postpartum period (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]).
The manufacturer recommends that caution be used if administered to patients who are breastfeeding. Maternal use of NSAIDs should be avoided if the breastfeeding infant has platelet dysfunction, thrombocytopenia, or a ductal-dependent cardiac lesion (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; Bloor 2013). Agents other than ketorolac are preferred in breastfeeding patients at risk of hemorrhage (ABM [Reece-Stremtan 2017]),
Administer tablet with food or milk to decrease gastrointestinal distress.
Monitor response (pain, range of motion, grip strength, mobility, ADL function), inflammation; observe for weight gain, edema; renal function (serum creatinine, BUN, urine output); CBC and platelets, liver function; chemistry profile; blood pressure; observe for bleeding, bruising; evaluate GI effects (abdominal pain, bleeding, dyspepsia); mental confusion, disorientation; signs and symptoms of hypersensitivity (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis).
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 action: Analgesic: ~30 minutes.
Peak effect: Analgesic: ~2 to 3 hours.
Duration: Analgesic: 4 to 6 hours.
Absorption: Oral: Well absorbed (100%), administration after a high-fat meal decreased peak and delayed time to peak concentrations by ~1 hour; IM: Rapid and complete.
Distribution: Poor penetration into cerebrospinal fluid.
Infants: Vdss: ~0.2 L/kg (McLay 2018).
Children and Adolescents <16 years: Vdss: 0.18 L/kg (McLay 2018).
Adults: Vd beta: Oral, IM: 0.17 ± 0.04 L/kg; IV: 0.21 ± 0.04 L/kg.
Protein binding: 99%.
Metabolism: Hepatic; undergoes hydroxylation and glucuronide conjugation.
Bioavailability: Oral, IM: 100%.
Half-life elimination:
Infants ≥6 months: S-enantiomer: 0.83 ± 0.7 hours; R-enantiomer: 4 ± 0.8 hours (Lynn 2007).
Children and Adolescents ≤16 years: 3 ± 1.1 hours (Dsida 2002).
Adults:
Mean: ~5 hours; Range: 2 to 9 hours [S-enantiomer ~2.5 hours (biologically active); R-enantiomer ~5 hours]; Prolonged 30% to 50% in elderly.
With renal impairment: Scr 1.9 to 5 mg/dL: Mean: ~11 hours; Range: 4 to 19 hours.
Renal dialysis patients: Mean: ~14 hours; Range: 8 to 40 hours.
Time to peak, serum: Oral: ~45 minutes; IM: ~30 to 45 minutes; IV: 1 to 3 minutes.
Excretion: Urine (92%, ~60% as unchanged drug); feces ~6%.
Altered kidney function: Clearance is reduced and half-life is increased in renal impairment. AUC is increased by ~100% and volume of distribution increases.
Pediatric: Vd and clearance are higher in pediatric patients compared to adults.
Older adult: Half-life is longer in patients ≥65 years of age.
