Tramadol (Ultram®) versus Ketorolac (Toradol®)
Based on "Essential Pain Pharmacology"
written by Howard S. Smith, MD; Marco Pappagallo, MD
Difference between Tramadol and Ketorolac
Table 1. Comparison of tramadol vs ketorolac
|Ultram ®||Toradol ®|
|Synthetic opioid analgesic||Non-steroidal anti-inflammatory drug, non-selective COX inhibitor|
|Synthetic 4-phenylpiperidine analogue of codeine||Carboxylic acid derivative, structurally related to indomethacin|
• capsules, extended release
• solution for injection or infusion
• solution for injection
• nasal spray
• ophthalmic solution
|• Rx only
• Controlled substance Schedule IV
|• Rx only
• Not a controlled drug
|• Moderate to moderately severe pain
• Moderate to moderately severe chronic pain (extended-release formulation)
|• Short-term (≤5 days) management of moderately severe acute pain that requires analgesia at the opioid level.
Maximum duration of ketorolac therapy should not exceed 5 days for tablets, or 2 days for continuous daily dosing with parenteral formulations
• Neuropathic pain
|• Athletic injuries
• Injection administration into the intra-articular space
• Subcutaneous administration when no other route of administration is available
• Anti-inflammatory (weak)
|Mechanism of action|
|• Tramadol is centrally acting analgesic
• Weak µ-opioid receptor agonism
• Weak norepinephrine and serotonin reuptake inhibition
|• Peripherally acting analgesic
• Inhibition of prostaglandin synthesis through blocking cyclooxygenase enzymes COX-1 and COX-2
|Onset of action|
|1 hour||30-60 min|
|Duration of action|
|4-6 hours||4-6 hours|
|6.3 hours||5-6 hours|
|• Undergoes CYP3A4- and CYP2D6 metabolism in the liver.
• Excreted primarily through liver metabolism and the metabolites are eliminated primarily by the kidneys.
|• Ketorolac undergoes hepatic metabolism. The metabolic products and unchanged drug are excreted in the urine.|
|• Hypersensitivity to tramadol or other opioids
• Acute intoxication with alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or psychotropic drugs
|• Hypersensitivity to ketorolac
• Active peptic ulcer disease
• Recent gastrointestinal bleeding
• History of peptic ulcer disease or gastrointestinal bleeding.
• Ketorolac should not be used as prophylactic analgesic before any major surgery
• Advanced renal impairment or in patients at risk for renal failure due to volume depletion
• Labor and delivery patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding
• Concomitant use with other NSAIDs, probenecid, or pentoxifylline
• Risk of physical and psychological dependence
• Fluid retention
• Elevations of ALT or AST
• Gastrointestinal damage - ketorolac makes stomach lining susceptible to damage, promotes ulcers in the stomach and bleeding.
• Renal injury (including renal failure, interstitial nephritis and nephrotic syndrome)
|• CYP2D6 and CYP3A4 inhibitors
• Carbamazepine significantly increases tramadol metabolism
• Serotonergic medications - serotonin syndrome risk
|• Diuretics - reduced the natriuretic effect of furosemide and thiazides
• Probenecid - concomitant use is contraindicated
• ACE inhibitors, angiotensin II receptor antagonists - increased risk of renal impairment
• NSAIDs - concomitant use is contraindicated because of the cumulative risk of inducing serious NSAIDs toxic effects
Ketorolac advantages over Tramadol:
- Ketorolac does not bind to opioid receptors and accordingly lacks many of the side effects typically associated with opioids.
- Ketorolac produces pain control comparable to opioids without respiratory depression, constipation, and tolerance.
- Ketorolac is free of the potential for abuse and addiction.
- Absence of any psychomotor effects and withdrawal symptoms.
- Ketorolac has an opioid sparing. The drug reduces narcotic consumption by 25-45% and indirectly lowers opioid side effects such as constipation, nausea, and vomiting.
Tramadol advantages over Ketorolac:
- Tramadol does not inhibit COX enzymes (inhibits prostaglandin synthesis) and accordingly lacks gastrointestinal, cardiovascular and renal toxicities typically associated with ketorolac.
- Tramadol is not nephrotoxic.
- Tramadol does not damage gastrointestinal tract.
- Can be used in aspirin-sensitive and ulcer-prone patients.
- No analgesic ceiling effect.
- Unlike ketorolac does not increase surgical blood loss.
- Suitable for chronic pain control.
- Tramadol is available in extended-release tablets which are approved for use for an extended period of time to provide around-the-clock pain control.
Head-to-head comparative studies
Tramadol provides better pain control for pain following surgery, and is better tolerated than ketorolac.
Ketorolac caused a higher incidence of both gastrointestinal and surgical site bleeding than did opioids.
Dental extraction pain
Oral tramadol and oral ketorolac are equally effective in relieving pain in the first 6 hours after molar extraction 9. However, postoperative tramadol has been found to be more effective than preoperative in relieving the pain, whereas the preoperative ketorolac has been found to be better than postoperative.
Oral ketorolac taken 30 min before the third molar surgery provides longer time of analgesia and less postoperative pain when compared with intramuscular tramadol administrated 30 min before surgery6.
Both ketorolac (30 mg intramuscular) and tramadol (1 mg/kg subcutaneous) are effective in renal colic. Both have an efficacy greater than 80% when used separately and almost 100% when used in combination. Pain relieving effect of ketorolac is achieved earlier than that of tramadol 8.
Tramadol is a better analgesic compared to ketorolac for patients undergoing day care gynecologic laparoscopy 7.
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Published: October 16, 2017
Last updated: August 14, 2018