DICLOFENAC
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Diclofenac inhibits cyclooxygenase (COX) enzymes, primarily COX-2, reducing prostaglandin synthesis, thereby exerting analgesic, anti-inflammatory, and antipyretic effects.
| Metabolism | Primarily hepatic via CYP2C9 (major) and CYP3A4 (minor); undergoes glucuronidation. Metabolites include 4'-hydroxydiclofenac, 5-hydroxydiclofenac, and 3'-hydroxydiclofenac. |
| Excretion | Renal (65% as metabolites, <1% unchanged); biliary/fecal (35% as metabolites). |
| Half-life | Terminal elimination half-life ~2 h (diclofenac immediate-release); enterohepatic recirculation may produce secondary peaks. Clinical context: Short half-life requires multiple daily dosing for sustained effect. |
| Protein binding | >99% bound primarily to serum albumin. |
| Volume of Distribution | 0.1-0.2 L/kg (low distribution, reflects high protein binding). Clinical meaning: Limited extravascular distribution; primarily remains in vascular space. |
| Bioavailability | Oral immediate-release: ~50% due to extensive first-pass metabolism; Topical: <10% systemic; Ophthalmic: minimal; IV: 100%. |
| Onset of Action | Oral immediate-release: ~30 min; Oral enteric-coated: delayed up to 1-2 h; Topical: 2-4 h; IV: within minutes; Ophthalmic: 30 min for ocular inflammation. |
| Duration of Action | Oral immediate-release: 4-8 h; Oral extended-release: 12-24 h; Topical: 4-6 h; IV: 6-8 h. Clinical notes: Analgesic duration shorter than anti-inflammatory effect; enterohepatic circulation may prolong terminal phase. |
Oral: 50 mg twice daily or 75 mg twice daily; maximum 150 mg/day. Topical: apply 4 times daily. IM: 75 mg once daily.
| Dosage form | CAPSULE |
| Renal impairment | GFR >30 mL/min: no adjustment. GFR 15-30 mL/min: use with caution, reduce dose, avoid if possible. GFR <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | Children ≥1 year: oral 0.5-1 mg/kg/dose twice daily; maximum 3 mg/kg/day or 150 mg/day. Children ≥14 years: same as adult. |
| Geriatric use | Start at lowest effective dose, e.g., 25-50 mg/day oral; increase cautiously. Avoid NSAIDs in advanced age due to GI and renal risks. |
| 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 | Excreted in breast milk in low amounts; M/P ratio not reported. Use with caution; avoid in breastfeeding mothers with infants with thrombocytopenia or platelet dysfunction. Consider risk of infant renal impairment. |
| Teratogenic Risk | First trimester: Increased risk of spontaneous abortion and congenital malformations (cardiac defects, gastroschisis) due to prostaglandin synthesis inhibition. Second trimester: Risk of oligohydramnios and fetal renal impairment with prolonged use. Third trimester: Avoid after 30 weeks gestation; risk of premature closure of ductus arteriosus, persistent pulmonary hypertension of the newborn, and oligohydramnios. |
■ 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. Diclofenac is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | inflammation |
| Serious Effects |
["Known hypersensitivity to diclofenac or any component of the formulation","History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs","Perioperative pain in the setting of CABG surgery","Active GI bleeding","Severe uncontrolled heart failure","Advanced renal disease (unless dialysis is ongoing)","Third trimester of pregnancy"]
| Precautions | ["Cardiovascular risk: increased risk of thrombotic events, hypertension, and heart failure.","Gastrointestinal risk: increased risk of serious GI adverse events including bleeding, ulceration, and perforation.","Renal toxicity: monitor renal function in patients with preexisting renal disease, dehydration, or concomitant nephrotoxic agents.","Hepatic toxicity: elevated liver enzymes; rare cases of severe hepatic reactions.","Anaphylactoid reactions: can occur in patients with or without known NSAID hypersensitivity.","Fluid retention and edema: use with caution in patients with hypertension or heart failure.","Skin reactions: serious cutaneous adverse reactions such as Stevens-Johnson syndrome and DRESS.","Hematologic: prolonged bleeding time; use with caution in patients with coagulation disorders."] |
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| Fetal Monitoring | Monitor fetal ultrasound for oligohydramnios and ductus arteriosus patency after 30 weeks gestation. Assess maternal renal function and blood pressure regularly. Monitor for signs of premature labor or maternal gastrointestinal bleeding. |
| Fertility Effects | Reversible inhibition of ovulation in women due to prostaglandin-mediated follicular rupture. May delay conception. Long-term use may impair endometrial receptivity. No significant effect on male fertility. |