Toradol - Drug Monograph

Introduction

Toradol (ketorolac tromethamine) is a nonsteroidal anti-inflammatory drug (NSAID) with potent analgesic properties. It is distinguished from other NSAIDs by its primarily analgesic rather than anti-inflammatory clinical application. Toradol is indicated for short-term management of moderate to severe acute pain and is particularly valuable in postoperative settings where opioid-sparing effects are desired.

Mechanism of Action

Ketorolac exerts its pharmacological effects through nonselective inhibition of cyclooxygenase enzymes (COX-1 and COX-2). This inhibition prevents the conversion of arachidonic acid to prostaglandin precursors, particularly prostaglandins E2 and I2, which are mediators of pain and inflammation at peripheral and central sites. Unlike opioids, ketorolac does not act on opioid receptors and does not produce respiratory depression or dependence.

Indications

• Short-term management of moderate to severe acute pain (maximum 5 days duration)
• Postoperative pain management
• Pain associated with musculoskeletal disorders
• Renal colic (off-label use)

Dosage and Administration

• IV/IM: 30 mg every 6 hours (max 120 mg/day)
• Oral: 20 mg initially, then 10 mg every 4-6 hours (max 40 mg/day)
• Conversion: Single dose IV/IM to oral is 1:1

• Elderly (≥65 years), renal impairment: Reduce dose by 50%
• Hepatic impairment: Use with caution
• Pediatrics: Not recommended under age 17

Pharmacokinetics

• Absorption: Rapid and complete (oral bioavailability ~100%)
• Distribution: Vd = 0.15-0.3 L/kg; 99% protein bound
• Metabolism: Hepatic via glucuronidation
• Elimination: Renal excretion (91%); half-life 2.5-9 hours
• Onset: IV - within 30 minutes; Peak effect: 1-2 hours

Contraindications

• Hypersensitivity to ketorolac, aspirin, or other NSAIDs
• Active peptic ulcer disease
• Recent gastrointestinal bleeding or perforation
• History of asthma, urticaria, or allergic reactions after NSAIDs
• Prophylactic analgesia before major surgery
• Advanced renal impairment or risk for renal failure
• Concomitant use with probenecid or pentoxifylline
• Labor and delivery
• Breastfeeding
• Third trimester of pregnancy

Warnings and Precautions

• Increased risk of serious cardiovascular thrombotic events, MI, and stroke
• Increased risk of serious GI adverse events including bleeding, ulceration, and perforation

• Renal toxicity: Monitor renal function, especially in elderly and volume-depleted patients
• Hepatotoxicity: Monitor LFTs periodically
• Hypertension and fluid retention
• Anaphylactoid reactions
• Hematologic effects: May inhibit platelet aggregation
• Avoid use in patients with coagulation disorders

Drug Interactions

• Anticoagulants: Increased risk of bleeding (warfarin, heparin, DOACs)
• SSRIs/SNRIs: Increased bleeding risk
• ACE inhibitors/ARBs: Reduced antihypertensive effect
• Diuretics: Reduced efficacy and increased nephrotoxicity
• Lithium: Increased lithium levels
• Methotrexate: Increased methotrexate toxicity
• Other NSAIDs: Avoid concomitant use
• Corticosteroids: Increased GI toxicity

Adverse Effects

• Gastrointestinal: nausea (12%), dyspepsia (12%), GI pain (13%)
• CNS: headache (17%), dizziness (7%)
• Local: injection site pain (2%)

• Gastrointestinal bleeding/perforation
• Acute renal failure
• Anaphylaxis
• Cardiovascular thrombotic events
• Severe skin reactions
• Platelet dysfunction

Monitoring Parameters

• Pain assessment (regular intervals)
• Renal function (BUN, creatinine) especially in at-risk patients
• Signs of GI bleeding (Hgb/Hct, guaiac testing)
• Blood pressure
• Hepatic function (with prolonged use)
• Signs of allergic reactions
• Injection sites for reactions

Patient Education

• Take with food to minimize GI upset
• Report any signs of bleeding (black stools, coffee-ground emesis)
• Report signs of allergic reaction (rash, swelling, difficulty breathing)
• Avoid alcohol during therapy
• Do not exceed prescribed dose or duration
• Not for chronic pain management
• May cause dizziness/drowsiness - use caution when driving
• Inform all healthcare providers of ketorolac use before any procedures

References

1. FDA Prescribing Information: Ketorolac Tromethamine (2022) 2. Lexicomp Online: Ketorolac Drug Monograph 3. Turturro MA, Paris PM, Yealy DM. Ketorolac: an update on its use in pain management. J Pain Symptom Manage. 1998;16(2):71-73. 4. Gillis JC, Brogden RN. Ketorolac: a reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management. Drugs. 1997;53(1):139-188. 5. American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain. 7th ed. 2016. 6. Strom BL, Berlin JA, Kinman JL, et al. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. JAMA. 1996;275(5):376-382.