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. |
| Molecular Weight | 376.4 |
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 | Avoid due to risk of spontaneous abortion and potential for teratogenicity; NSAIDs are generally not recommended in first trimester. |
| 2nd trimester | Use only if clearly needed; monitor for oligohydramnios and fetal ductus arteriosus constriction. |
| 3rd trimester | Contraindicated due to risk of premature ductus arteriosus closure, oligohydramnios, and fetal renal impairment. |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious bleeding and renal impairment.
| Placental transfer | Crosses placenta; fetal serum concentrations are approximately 10% of maternal levels. |
| Breastfeeding | Excreted in breast milk in low amounts; due to risk of kernicterus in neonates with hemolytic disease, avoid if breastfeeding a jaundiced or preterm infant. Generally considered compatible if used short-term. |
■ 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 |
Active peptic ulcer diseaseHistory of gastrointestinal bleeding or perforationSevere renal impairment (CrCl <30 mL/min)Hypersensitivity to ketorolac or other NSAIDsPatients at risk for bleeding (e.g., hemorrhagic diathesis, incomplete hemostasis)Concurrent aspirin or other NSAIDsAdvanced renal diseaseDuring labor and delivery (due to increased risk of maternal and fetal bleeding)All trimesters of pregnancy (especially third) as per some guidelines; third trimester is absolute
Loading safety data…
| Lactation Rating | L2 (Probably Compatible) – John's Hopkins rating; or 'Safe' per some sources. |
| 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. |
| 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) |
| Food/Dietary | Take with food or milk to minimize gastrointestinal irritation. Avoid concomitant use of alcohol as it increases risk of GI bleeding. No specific food interactions; however, high-fat meals may delay absorption but not affect overall efficacy. |
| Clinical Pearls | Ketorolac is a potent NSAID for short-term management of moderate to severe acute pain, not to exceed 5 days due to increased risk of GI bleeding, renal impairment, and cardiovascular events. Contraindicated in patients with active peptic ulcer disease, recent GI bleeding, advanced renal impairment, or at risk for bleeding (e.g., concurrent anticoagulants). Administer with food to reduce GI irritation; avoid use in patients with aspirin-sensitive asthma. Monitor renal function, liver enzymes, and signs of bleeding. Intramuscular injection should be given deeply and slowly; IV bolus over at least 15 seconds. Use lowest effective dose for shortest duration; not for minor or chronic pain. Not recommended for pediatric patients or during labor/delivery. |
| Patient Advice | Take this medication exactly as prescribed, usually every 6 to 8 hours, for the shortest time needed (no more than 5 days). · Take with food or a full glass of milk to reduce stomach upset. · Avoid alcohol, aspirin, or other NSAIDs (like ibuprofen, naproxen) while taking this drug. · Stop taking and contact your doctor immediately if you experience signs of bleeding (black tarry stools, vomit that looks like coffee grounds, unusual bruising), chest pain, shortness of breath, weakness on one side of the body, or slurred speech. · Do not use this medicine if you have a history of stomach ulcers, bleeding problems, severe kidney disease, or if you are breastfeeding or in late pregnancy. · Tell your doctor about all medications you take, including blood thinners, steroids, diuretics, and lithium. |