DICLOFENAC POTASSIUM
Clinical safety rating: avoid
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
Nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis, which mediates pain, inflammation, and fever.
| Metabolism | Primarily hepatic via CYP2C9; minor pathways include glucuronidation and sulfation. |
| Excretion | Approximately 50% of a dose is eliminated via first-pass hepatic metabolism; renal excretion accounts for ~65% of the administered dose as metabolites (<1% unchanged drug); fecal excretion <20%. |
| Half-life | Terminal elimination half-life is ~1.1 hours (range 0.9–1.6 h). Short half-life supports frequent dosing (e.g., every 6–8 hours) for sustained analgesia. |
| Protein binding | 99.5% bound primarily to serum albumin. |
| Volume of Distribution | 0.17–0.19 L/kg; low Vd indicates limited tissue distribution, primarily in plasma and extracellular fluid. |
| Bioavailability | Oral immediate-release: ~50% (significant first-pass metabolism). Rectal: ~80% (less first-pass). Topical ophthalmic: systemic bioavailability low (<1%). Topical gel: ~6–10%. |
| Onset of Action | Oral immediate-release: 20–30 min (peak plasma 30–60 min); topical: onset varies (24–48 h for chronic pain); ophthalmic: 30 min; rectal: ~30–60 min. |
| Duration of Action | Oral immediate-release: 4–6 hours; topical: sustained with regular use; ophthalmic: up to 4–6 hours after single dose. |
50 mg orally twice daily or 75 mg orally once daily; maximum 150 mg/day. Alternatively, 75 mg intramuscularly once daily (short-term).
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-60 mL/min: no adjustment; monitor renal function. GFR <30 mL/min: contraindicated or use with extreme caution; avoid if possible. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%; maximum 100 mg/day. Child-Pugh C: contraindicated. |
| Pediatric use | ≥1 year: 0.5-2 mg/kg/day orally divided 2-3 times; maximum 150 mg/day. Not recommended for <1 year. |
| Geriatric use | Use lowest effective dose; may increase risk of GI bleeding and renal impairment. Consider starting at 25 mg twice daily; maximum 100 mg/day. |
| 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.
| FDA category | Positive |
| Breastfeeding | Excreted in small amounts (M/P ratio 0.1-0.2). Considered compatible with breastfeeding; use lowest effective dose and shortest duration due to theoretical risk of infant gastrointestinal or renal effects. |
| Teratogenic Risk | First trimester: Risk of spontaneous abortion and cardiac defects (adjusted OR ~1.3). Second and third trimesters: Premature closure of ductus arteriosus, oligohydramnios, necrotizing enterocolitis, intracranial hemorrhage. Avoid after 30 weeks gestation. |
■ FDA Black Box Warning
Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Risk increases with duration of use and in patients with cardiovascular risk factors. Also, increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal.
| Common Effects | inflammation |
| Serious Effects |
Hypersensitivity to diclofenac or any NSAID; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; coronary artery bypass graft (CABG) surgery; active gastrointestinal bleeding or perforation; advanced renal disease; severe heart failure (NYHA Class IV); pregnancy (third trimester, may cause premature closure of ductus arteriosus); history of gastrointestinal ulcer/bleeding (relative).
| Precautions | Cardiovascular risk (including serious thrombotic events), gastrointestinal risk (bleeding, ulceration, perforation), hypertension, fluid retention, renal toxicity (especially in elderly, preexisting renal disease, or concurrent use of ACE inhibitors/ARBs/diuretics), hepatic effects (elevated liver enzymes, rare severe hepatotoxicity), anaphylactoid reactions, asthma exacerbation in aspirin-sensitive patients, hematologic effects (anemia, bleeding), withdrawal symptoms (if used chronically). |
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| Fetal Monitoring | Monitor amniotic fluid volume via ultrasound, fetal echocardiography for ductus arteriosus patency, and maternal renal function. Assess for premature labor signs. |
| Fertility Effects | Reversible inhibition of ovulation and implantation via prostaglandin synthesis inhibition (NSAID class effect). Indicated as an effect that may impair female fertility; discontinuation typically reverses effect. |