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. |
| Molecular Weight | 334.24 |
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 | Avoid unless benefit outweighs risk; associated with increased risk of spontaneous abortion and congenital malformations, particularly cardiac defects. |
| 2nd trimester | Use only if clearly needed; may cause oligohydramnios and premature ductus arteriosus constriction with prolonged use. |
| 3rd trimester | Contraindicated after 30 weeks gestation due to risk of premature closure of the ductus arteriosus and oligohydramnios. |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| FDA category | Positive |
| Placental transfer | Crosses placenta; fetal plasma levels approximately 50% of maternal levels. |
| Breastfeeding |
■ 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 |
History of hypersensitivity to diclofenac or other NSAIDsActive peptic ulcer disease or gastrointestinal bleedingSevere heart failure (NYHA Class IV)Coronary artery bypass graft (CABG) surgery perioperativelyThird trimester of pregnancy (after 30 weeks)
| 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). |
Loading safety data…
| Small amounts excreted in breast milk; minimal risk to infant at maternal doses up to 150 mg/day. Avoid in breastfeeding mothers with infants having bleeding disorders or thrombocytopenia. |
| Lactation Rating | L2 (Limited data - probably compatible) |
| 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. |
| 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. |
| Food/Dietary | Alcohol increases the risk of gastrointestinal bleeding. Avoid concurrent use. Taking with food may decrease GI irritation but does not eliminate bleeding risk. No significant food-drug interactions beyond alcohol. |
| Clinical Pearls | Diclofenac potassium has a faster onset of action than diclofenac sodium due to its higher aqueous solubility and rapid absorption. Use with caution in patients with cardiovascular disease, hypertension, or renal impairment. Avoid concurrent use with other NSAIDs, anticoagulants, or corticosteroids. Monitor renal function, hepatic enzymes, and blood pressure regularly. Discontinue if signs of gastrointestinal bleeding or hypersensitivity occur. Not recommended in patients with aspirin-sensitive asthma. |
| Patient Advice | Take with food or milk to reduce gastrointestinal upset. · Do not take with other NSAIDs (e.g., ibuprofen, naproxen) or aspirin unless directed by your doctor. · Avoid alcohol as it may increase the risk of stomach bleeding. · Report any signs of bleeding (e.g., black/tarry stools, vomit that looks like coffee grounds), chest pain, shortness of breath, or swelling immediately. · Do not use longer than recommended; long-term use increases risk of heart attack or stroke. · Store at room temperature away from moisture and heat. |