What are the risks associated with Toradol (Ketorolac) use?

Risks Associated with Toradol (Ketorolac)

Toradol carries significant risks of gastrointestinal bleeding and perforation, acute renal failure, cardiovascular thrombotic events, and bleeding complications—all of which can be fatal—and must be limited to a maximum of 5 days of use with careful patient selection to avoid these serious adverse events. 1, 2

Critical Time Limitation

• Treatment duration must not exceed 5 days (combined IV, IM, and oral routes), as risk of serious adverse events increases markedly with prolonged use, particularly in vulnerable populations. 3, 1, 2

Major Risk Categories

Gastrointestinal Complications

• Ketorolac has one of the highest risks of GI toxicity among all NSAIDs, including peptic ulcers, bleeding, and perforation of the stomach or intestines, which can occur at any time without warning symptoms and can be fatal. 3, 1, 2
• Only 1 in 5 patients who develop serious upper GI events will have warning symptoms, making this risk particularly dangerous. 2
• Risk factors that dramatically increase GI complications include: age >60 years, history of peptic ulcer disease or GI bleeding, concurrent corticosteroid use, anticoagulant therapy, significant alcohol use, and poor general health status. 3, 2

Renal Toxicity

• Ketorolac can cause acute renal failure, particularly in patients with compromised fluid status, pre-existing renal impairment, or volume depletion—though this is usually reversible upon discontinuation. 3, 1, 4
• Approximately 2% of patients stop NSAIDs due to renal complications. 3
• Hyperkalemia may develop alongside renal dysfunction. 4
• Baseline renal function testing (BUN and creatinine) is mandatory before initiating therapy, with ongoing monitoring required. 3, 5

Cardiovascular Risks

• NSAIDs including ketorolac increase the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal and may occur early in treatment. 1, 2
• Ketorolac can worsen hypertension, causing mean blood pressure increases of approximately 5 mm Hg. 3
• It is absolutely contraindicated in the setting of coronary artery bypass graft (CABG) surgery. 1

Bleeding and Hematologic Complications

• Ketorolac reversibly inhibits platelet function and thromboxane synthesis, increasing bleeding time and risk of hemorrhage. 1, 2, 6, 7
• Concurrent use with anticoagulants (warfarin, heparin), antiplatelet agents, SSRIs, or SNRIs significantly elevates bleeding risk. 3, 5, 2
• While bleeding time may remain within normal values in most patients, surgical site bleeding has been reported, particularly after tonsillectomy. 7

Absolute Contraindications

Ketorolac must be avoided in patients with: 3, 5, 1, 2

• Active peptic ulcer disease or history of GI bleeding/perforation
• Advanced renal impairment or risk of renal failure due to volume depletion
• Suspected or confirmed cerebrovascular bleeding
• Hemorrhagic diathesis or incomplete hemostasis
• Concurrent anticoagulant therapy or thrombocytopenia
• Aspirin/NSAID-induced asthma or prior hypersensitivity reactions to NSAIDs
• History of cardiovascular disease or high cardiovascular risk
• Coronary artery bypass graft surgery setting
• Labor and delivery (may adversely affect fetal circulation and inhibit uterine contractions)
• Concurrent use with other NSAIDs or aspirin

Special Population Considerations

Elderly Patients (≥60 years)

• Maximum daily dose must be reduced to 40 mg/day in patients ≥60 years due to significantly elevated risk for all toxicities. 5
• Elderly patients are at greatest risk for fatal GI events and require the most cautious approach. 3, 5, 2

Patients <50 kg (110 lbs)

• Dosage adjustment is required, with total daily dose not to exceed 60 mg. 1

Pediatric Patients

• Ketorolac is not indicated for use in pediatric patients according to FDA labeling, though research suggests efficacy in postoperative pain with appropriate dosing (0.5 mg/kg IV). 1, 7

Required Monitoring

Baseline and periodic monitoring must include: 3, 5

• Blood pressure measurement
• Renal function tests (BUN and creatinine)
• Liver function tests
• Complete blood count
• Fecal occult blood testing

Discontinue ketorolac immediately if: 3

• Liver function studies increase
• BUN or creatinine doubles
• Hypertension develops or worsens
• Signs of GI bleeding or perforation appear

Drug Interactions to Avoid

• Concurrent NSAIDs or aspirin (cumulative toxicity risk) 5, 1
• Anticoagulants including warfarin, heparin, or prophylactic low-dose heparin 5, 2
• SSRIs and SNRIs (elevated bleeding risk) 5
• Other nephrotoxic drugs (increased renal toxicity) 3

Common Pitfalls

• Using ketorolac beyond 5 days is the most common error and dramatically increases all serious adverse event risks. 3, 1, 8
• Failing to recognize that ketorolac is marketed primarily as an analgesic, leading practitioners to underestimate its potent prostaglandin synthesis inhibition and associated risks. 4
• Assuming parenteral administration avoids GI toxicity—ketorolac causes dose-related gastric ulcerations even when given IV or IM. 6
• Using ketorolac for minor or chronic pain conditions, when it is indicated only for moderately severe acute pain requiring opioid-level analgesia. 1