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Ketorolac (Nasal)

Pronunciation

Pronunciation

(KEE toe role ak)

Index Terms

  • Ketorolac Tromethamine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Nasal, as tromethamine [preservative free]:

Sprix: 15.75 mg/spray (1 ea) [contains edetate disodium]

Brand Names: U.S.

  • Sprix

Pharmacologic Category

  • Nonsteroidal Anti-inflammatory Drug (NSAID), Nasal

Pharmacology

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.

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

Metabolism

Hepatic to hydroxylated and conjugated forms

Excretion

Urine (~92%, ~60% as unchanged drug); feces ~6%

Onset of Action

Analgesia: Within 20 minutes (Singla 2010)

Time to Peak

0.75 hours

Half-Life Elimination

~5 to 6 hours (similar to IM administration)

Protein Binding

99%

Special Populations: Renal Function Impairment

Cl is reduced, half-life is increased up to 19 h, AUC is increased by approximately 100%, and Vd increases.

Special Populations: Elderly

Half-life is longer and exposure is increased by 23% in patients ≥65 years of age.

Use: Labeled Indications

Moderate to moderately severe pain: Short-term (up to 5 days) management of moderate to moderately severe pain in adults that requires analgesia at the opioid level.

Contraindications

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 NSAIDs; prophylactic analgesic before major surgery; in the setting of coronary artery bypass graft (CABG) 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

Dosing: Adult

Pain management (acute; moderate to moderately severe): Note: The maximum combined duration of treatment (for nasal spray or other ketorolac formulations) is 5 days.

Intranasal: Adults<65 years and ≥50 kg: One spray (15.75 mg) in each nostril (total dose: 31.5 mg) every 6-8 hours; maximum dose: 4 doses (126 mg)/day

Dosage adjustments in adults with low body weight (<50 kg): One spray (15.75 mg) in 1 nostril (total dose: 15.75 mg) every 6-8 hours; maximum dose: 4 doses (63 mg)/day

Dosing: Geriatric

Elderly (≥65 years): Intranasal: One spray (15.75 mg) in 1 nostril (total dose: 15.75 mg) every 6-8 hours; maximum dose: 4 doses (63 mg)/day

Dosing: Renal Impairment

Renal insufficiency: Intranasal: One spray (15.75 mg) in 1 nostril (total dose: 15.75 mg) every 6-8 hours; maximum dose: 4 doses (63 mg)/day

Advanced renal impairment (or at risk for renal failure due to volume depletion): Use is contraindicated

Dosing: Hepatic Impairment

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.

Administration

Do not inhale ketorolac nasal spray. Each nasal spray contains medication for 1 day of therapy. Before first use of a nasal spray container, prime by pressing pump 5 times. There is no need to prime the pump again if more doses are administered during the next 24 hours using the same nasal container. Repeat priming each day prior to first use of each new nasal spray. Blow nose to clear nostrils. Sit up straight or stand; tilt head slightly forward. Insert tip of container into nostril, keeping bottle upright, and point container away from the center of 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.

Discard container within 24 hours of priming even if there is unused medication.

Storage

Store unopened nasal spray between 2°C to 8°C (36°F to 46°F); protect from freezing and light. During use, store between 15°C to 30°C (59°F to 86°F) and out of direct sunlight. Discard each nasal spray bottle within 24 hours of priming.

Drug Interactions

5-ASA Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-ASA Derivatives. Monitor therapy

ACE 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 ACE Inhibitors. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. 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. 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. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. Monitor therapy

Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy

Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. 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. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy

Apixaban: NSAID (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. 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. Avoid combination

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Consider therapy modification

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. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. 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. Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of NSAID (Nonselective). 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. Specifically, elevated diclofenac concentrations have been reported. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (e.g., hypertension) during concomitant therapy with NSAIDs. Consider therapy modification

Dabigatran Etexilate: NSAID (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. Consider therapy modification

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. 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. 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. Monitor therapy

Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Monitor therapy

Drospirenone: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone. Monitor therapy

Edoxaban: NSAID (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. 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. Monitor therapy

Floctafenine: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. Consider therapy modification

HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Monitor therapy

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Ketorolac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. 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. Consider therapy modification

Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate. Consider therapy modification

Morniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. 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. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Ketorolac (Nasal) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. 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. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Pelubiprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

PEMEtrexed: NSAID (Nonselective) may increase the serum concentration of PEMEtrexed. Management: Patients with mild-to-moderate renal insufficiency (estimated creatinine clearance 45-79 mL/min) should avoid NSAIDs for 2-5 days prior to, the day of, and 2 days after pemetrexed. Consider therapy modification

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. Monitor therapy

Pentoxifylline: Ketorolac (Nasal) may enhance the adverse/toxic effect of Pentoxifylline. Specifically, the risk of bleeding may be increased. Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. 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. 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: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Monitor therapy

Probenecid: May increase the serum concentration of Ketorolac (Nasal). Avoid combination

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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). Monitor therapy

Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Monitor therapy

Rivaroxaban: NSAID (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. Consider therapy modification

Salicylates: NSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Choline Magnesium Trisalicylate. Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Consider therapy modification

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy

Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Consider therapy modification

Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Monitor therapy

Talniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Avoid combination

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. Consider therapy modification

Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. 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. Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Vitamin K Antagonists (eg, warfarin): NSAID (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification

Adverse Reactions

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% (Limited to important or life-threatening): Anemia, hematoma, hemorrhage

ALERT: U.S. Boxed Warning

Cardiovascular thrombotic events:

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.

Gastrointestinal bleeding, ulceration, and perforation:

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.

Warnings/Precautions

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 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 (ACCF/AHA [Yancy 2013]). 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.

• 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 (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 the elderly, diabetics, 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 (SJS), and toxic epidermal necrolysis (TEN); 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Dosage adjustment is required for patients ≥65 years of age.

• 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.

Monitoring Parameters

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

Pregnancy Risk Factor

C/D ≥30 weeks gestation

Pregnancy Considerations

Adverse events were not observed in the initial animal reproduction studies; therefore, the manufacturer classifies ketorolac (nasal) as pregnancy category C (category D: ≥30 weeks gestation).When administered IM, ketorolac crosses the placenta. The amount of ketorolac available systemically following intranasal administration is 60% to 70% in comparison to IM doses. Adverse fetal effects have been observed following maternal use of NSAIDs. Maternal use ≥30 weeks gestation increases the risk of premature closure of the ductus arteriosus. When used during labor and delivery, ketorolac may cause adverse effects on the fetal circulation, inhibit uterine contractions and increase the risk of uterine hemorrhage. Use during labor and delivery is contraindicated. Refer to the Ketorolac (Systemic) monograph for details.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nose pain, rhinitis or pharyngitis. Have patient report immediately to prescriber signs of abdominal ulcers (severe abdominal or back pain; black, tarry, or bloody stools; vomiting blood or vomit that looks like coffee grounds; or weight gain or abnormal swelling), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weak, shortness of breath, numbness or tingling feeling), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), severe headache, severe dizziness, passing out, vision changes, angina, shortness of breath, excessive weight gain, swelling of arms or legs, severe diarrhea, severe swelling or pain of hands or feet, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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