KETOPROFEN
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, reducing prostaglandin synthesis; also inhibits leukotriene synthesis and has direct membrane-stabilizing effects.
| Metabolism | Hepatic metabolism via cytochrome P450 (CYP) enzymes, primarily CYP3A4 and CYP2C9; conjugation with glucuronic acid; minor hydrolysis to metabolites. |
| Excretion | Renal: ~80% (60% as glucuronide conjugates, 20% as unchanged drug); Biliary/Fecal: ~20% via bile. |
| Half-life | Terminal elimination half-life: 2-4 hours; clinical context: short half-life allows for quick drug clearance but requires frequent dosing; may be prolonged in elderly or renal impairment. |
| Protein binding | 99% bound, primarily to albumin; free fraction increases in hypoalbuminemia. |
| Volume of Distribution | 0.1-0.2 L/kg; clinical meaning: low Vd indicates limited tissue distribution, primarily confined to plasma and extracellular fluid; higher in elderly due to increased body fat. |
| Bioavailability | Oral: ~90% (capsules); Topical: 5-10% (systemic absorption); Rectal: ~80%; Intramuscular: ~100%. |
| Onset of Action | Oral: 30-60 minutes; Topical: 2-4 hours (local effect); Rectal: 30-60 minutes; Intramuscular: 20-30 minutes. |
| Duration of Action | Oral: 4-6 hours; Topical: 6-8 hours; Rectal: 4-6 hours; Intramuscular: 4-6 hours; clinical note: analgesic effect may outlast plasma levels due to synovial fluid accumulation. |
Oral: 75 mg three times daily or 50 mg four times daily; maximum 300 mg/day. Intravenous: 100 mg every 12-24 hours, infused over 15-30 minutes.
| Dosage form | CAPSULE |
| Renal impairment | CrCl >50 mL/min: no adjustment. CrCl 25-50 mL/min: reduce dose to 50% of normal. CrCl <25 mL/min: avoid use or maximum 50 mg twice daily. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use. |
| Pediatric use | Children ≥6 months: oral 1-2 mg/kg/day divided every 6-8 hours; maximum 4 mg/kg/day. Not to exceed adult maximum. |
| Geriatric use | Initiate at lowest effective dose (e.g., 50 mg twice daily); use short duration; monitor renal function, GI bleeding, and cardiovascular risk. |
| 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 cardiovascular thrombotic events and GI bleeding.
| Breastfeeding | Compatible with caution. Small amounts excreted in breast milk (M/P ratio ~0.01-0.1). Due to risk of infant toxicity (e.g., gastrointestinal effects, renal impairment), consider alternative analgesics. Monitor infant for drowsiness, poor feeding, or rash. |
| Teratogenic Risk | First trimester: Avoid due to risk of spontaneous abortion and major congenital malformations (cardiac, gastroschisis). Second trimester: Avoid if possible; associated with oligohydramnios, constriction of ductus arteriosus. Third trimester: Contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, fetal nephrotoxicity, and periventricular hemorrhage. |
■ FDA Black Box Warning
Non-steroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors may be at greater risk. NSAIDs are contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | inflammation |
| Serious Effects |
History of hypersensitivity to ketoprofen, aspirin, or other NSAIDs; active peptic ulcer disease; history of gastrointestinal bleeding or perforation; severe renal impairment; severe hepatic impairment; during perioperative pain in CABG surgery.
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; hypertension; congestive heart failure; renal toxicity; anaphylactoid reactions; serious skin reactions; hematologic toxicity; hepatic toxicity; use with caution in patients with asthma or history of GI bleeding. |
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| Fetal Monitoring | Monitor maternal renal function, blood pressure, and amniotic fluid volume (ultrasound). Fetal echocardiography for ductus arteriosus patency if used in second trimester. Assess fetal growth and development. In third trimester, avoid use; if exposure occurs, monitor for oligohydramnios and neonatal complications. |
| Fertility Effects | Reversible inhibition of ovulation through prostaglandin synthesis inhibition. Use may delay conception; discontinue if pregnancy desired. Men: May impair spermatozoa motility and viability. |