ETODOLAC
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis, which mediates inflammation, pain, and fever.
| Metabolism | Primarily hepatic via CYP2C9 and CYP2C19; undergoes glucuronidation. Metabolites are inactive. |
| Excretion | Renal excretion (72% as metabolites, including glucuronides and hydroxylated derivatives, less than 1% unchanged); fecal excretion (16%, primarily as metabolites); biliary excretion contributes to enterohepatic recirculation. |
| Half-life | Terminal elimination half-life is approximately 6.5-7.5 hours (range 5-8 hours). With multiple dosing, the half-life remains unchanged, indicating linear kinetics. No accumulation in normal renal function. |
| Protein binding | 99% bound to plasma albumin, primarily at binding site 1 (warfarin site). Binding is saturable at supratherapeutic concentrations. |
| Volume of Distribution | Volume of distribution is approximately 0.4 L/kg (range 0.3-0.5 L/kg). This represents distribution into total body water and is consistent with extensive protein binding. Lower Vd in elderly due to changes in body composition. |
| Bioavailability | Oral bioavailability is 80-100% (immediate-release); the drug is completely absorbed. Extended-release formulations have slightly lower bioavailability (approximately 80%) due to retention in formulation. Food does not affect extent of absorption. |
| Onset of Action | Oral: Onset of analgesia occurs within 30 minutes (peak effect 1.5-2 hours). Extended-release formulations show later onset (1-2 hours). Topical: Not available. Intravenous: Not applicable. |
| Duration of Action | Duration of analgesia is 4-6 hours for immediate-release formulations. Extended-release provides up to 24-hour pain relief with once-daily dosing. Clinical duration correlates with plasma levels above the minimum effective concentration. |
200-400 mg orally every 6-8 hours as needed; maximum 1200 mg/day. Extended-release: 400-1000 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl 15-50 mL/min: reduce dose by 50%. CrCl <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: contraindicated. |
| Pediatric use | Not recommended for children <18 years. For juvenile idiopathic arthritis (off-label): 20-30 kg: 200 mg/day; 30-45 kg: 300 mg/day; >45 kg: 400 mg/day, divided into 2-3 doses. |
| Geriatric use | Initiate at lowest effective dose (200 mg twice daily). Maximum 400 mg/day. Monitor renal function and GI bleeding 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 | Etodolac is excreted into breast milk in low concentrations. The milk-to-plasma ratio is approximately 0.4. Due to limited data, caution is advised. Use is not recommended in breastfeeding women, particularly with prolonged use or high doses. |
| Teratogenic Risk | Etodolac is a nonsteroidal anti-inflammatory drug (NSAID). Use during the first and second trimesters is associated with a small increased risk of miscarriage and cardiac defects. Use during the third trimester is contraindicated due to risk of premature closure of the ductus arteriosus, oligohydramnios, and neonatal renal impairment. |
■ FDA Black Box Warning
Nonsteroidal 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 for cardiovascular disease may be at greater risk. ETODOLAC is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | pain |
| Serious Effects |
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in CABG surgery; advanced renal disease; known hypersensitivity to etodolac or any component.
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; renal toxicity; elevation of liver enzymes; anaphylactoid reactions; hypertension; congestive heart failure; serious skin reactions (e.g., Stevens-Johnson syndrome); hematologic toxicity; use in late pregnancy (risk of premature closure of ductus arteriosus). |
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| Fetal Monitoring | Monitor maternal renal function, blood pressure, and signs of gastrointestinal bleeding. Perform fetal ultrasound to assess amniotic fluid volume and ductus arteriosus patency if used in the third trimester. Monitor neonatal renal function and cardiovascular status if exposure occurs near term. |
| Fertility Effects | Etodolac may impair female fertility by inhibiting prostaglandin synthesis, potentially affecting ovulation. This effect is reversible upon discontinuation. No specific data on male fertility. |