KETOROLAC TROMETHAMINE
Clinical safety rating: avoid
Contraindicated (not allowed)
Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis, thereby decreasing pain and inflammation.
| Metabolism | Hepatic metabolism via conjugation (glucuronidation) and hydroxylation (involves CYP450 enzymes, primarily CYP2C9). Renal excretion of metabolites and unchanged drug (approximately 90% as glucuronide conjugates). |
| Excretion | Primarily renal excretion: ~92% of dose excreted in urine as parent drug (60%) and metabolites (p-hydroxyketorolac, conjugated forms). Fecal excretion accounts for ~6%. Biliary excretion is minimal. |
| Half-life | Terminal half-life is 5-6 hours in young adults, prolonged to 9-10 hours in elderly patients (≥65 years) and up to 12-15 hours in renal impairment (CrCl <30 mL/min). Context: q6h dosing interval recommended; accumulation risk in elderly/renal impairment. |
| Protein binding | 99% bound to plasma albumin. High binding limits distribution and may be affected by hypoalbuminemia. |
| Volume of Distribution | 0.15-0.3 L/kg (apparent Vd). Relatively low, indicating limited extravascular distribution; clinically correlates with low tissue penetration. |
| Bioavailability | Oral: 80-100%. Intramuscular: 100%. Ophthalmic: minimal systemic absorption (<0.5% of ocular dose). |
| Onset of Action | Intramuscular: ~10 minutes for analgesia. Intravenous: ~1 minute. Oral: 30-60 minutes. Ophthalmic: corneal anesthesia within 1-2 hours. |
| Duration of Action | Analgesic duration: 4-6 hours (IM/IV); 6-8 hours (oral). Ophthalmic: up to 8 hours. Note: For pain, continuous use limited to 5 days due to risk of adverse effects. |
10 mg orally every 4-6 hours, not to exceed 40 mg per day; or 15-30 mg intramuscularly or intravenously every 6 hours, not to exceed 120 mg per day (maximum 60 mg for single dose).
| Dosage form | INJECTABLE |
| Renal impairment | Contraindicated in patients with advanced renal impairment (CrCl <30 mL/min). For CrCl 30-60 mL/min: reduce dose by 50% and limit to 60 mg/day IM/IV or 20 mg/day oral. No adjustment for mild impairment. |
| Liver impairment | No specific dosing adjustment recommended for mild to moderate hepatic impairment (Child-Pugh A or B). Contraindicated in severe hepatic disease (Child-Pugh C). |
| Pediatric use | For patients <16 years: 0.5 mg/kg (maximum 15 mg) single dose IM/IV. Not recommended for repeated dosing or oral use in pediatric patients. |
| Geriatric use | For patients ≥65 years: reduce dose by 50% (maximum 60 mg/day IM/IV or 20 mg/day oral). Limit duration to 5 days total therapy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious bleeding and renal impairment.
| Breastfeeding | Excreted into breast milk; M/P ratio approximately 0.037. Avoid breastfeeding due to potential adverse effects in nursing infants (e.g., gastrointestinal bleeding, renal impairment). |
| Teratogenic Risk | Pregnancy Category C in first and second trimesters, Category D in third trimester and near term. Avoid in third trimester due to risk of premature closure of ductus arteriosus and oligohydramnios. First trimester: limited human data, animal studies show adverse effects. Second trimester: use only if clearly needed; may cause fetal renal impairment. |
■ FDA Black Box Warning
Cardiovascular risk: NSAIDs increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk may increase with duration of use and in patients with cardiovascular risk factors. Contraindicated for treatment of perioperative pain in coronary artery bypass graft (CABG) surgery. Gastrointestinal risk: NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time without warning symptoms. Elderly patients and those with a prior history of peptic ulcer disease or GI bleeding are at greater risk.
| Common Effects | Skin peeling Application site reactions burning irritation itching and redness Nausea Vomiting Abdominal pain Increased liver enzymes Application site redness Itching Diarrhea Abnormal liver function tests Adrenal insufficiency Application site burning |
| Serious Effects |
["Hypersensitivity to ketorolac or other NSAIDs","History of asthma, urticaria, or allergic-type reactions after taking aspirin or NSAIDs","Active peptic ulcer disease, recent GI bleeding, or perforation","History of peptic ulcer disease or GI bleeding","Advanced renal disease or patients at risk for renal failure","Patients with confirmed or suspected cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, or high risk of bleeding","Concurrent use of probenecid (increases ketorolac levels)","Concurrent use of aspirin or other NSAIDs (including selective COX-2 inhibitors)","Use in patients undergoing coronary artery bypass graft (CABG) surgery","Use as prophylactic analgesic before any major surgery","Use in labor and delivery (contraindicated due to antiplatelet effect and potential adverse effects on fetal circulation)","Use in breastfeeding (due to potential adverse effects on infant)","Use in pediatric patients (except ophthalmic drops)"]
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| Fetal Monitoring | Monitor maternal renal function, bleeding time, and signs of gastrointestinal bleeding. Fetal monitoring for oligohydramnios and ductus arteriosus constriction if used in third trimester. Monitor infant for adverse effects if breastfeeding. |
| Fertility Effects | May impair female fertility via inhibition of prostaglandin synthesis, affecting ovulation. Reversible upon discontinuation. |
| Precautions | ["Cardiovascular: Increased risk of thrombotic events, MI, stroke; avoid in patients with recent MI or established cardiovascular disease unless benefit outweighs risk","Gastrointestinal: Risk of GI bleeding, ulceration, perforation; use with caution in patients with history of peptic ulcer disease or GI bleeding","Renal: Can cause renal toxicity, especially in patients with impaired renal function, dehydration, or concurrent use of diuretics or ACE inhibitors","Hematologic: Inhibits platelet aggregation; may prolong bleeding time; use caution in patients with coagulation disorders or on anticoagulants","Hypersensitivity: Anaphylactoid reactions may occur; contraindicated in patients with aspirin/NSAID allergy","Hepatic: May cause elevations of liver enzymes; rarely, severe hepatic reactions","Fluid retention and edema","Use in elderly: Increased risk of GI and renal adverse effects","Not for use in pediatric patients (except ophthalmic formulations)","Not for use during labor and delivery (may inhibit uterine contractions and affect fetal circulation)"] |