NABUMETONE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Nonsteroidal anti-inflammatory drug (NSAID) that acts as a non-selective inhibitor of cyclooxygenase (COX-1 and COX-2), reducing prostaglandin synthesis. Its active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA), is responsible for its therapeutic effects.
| Metabolism | Prodrug metabolized extensively in the liver to the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) via first-pass metabolism; primarily metabolized by CYP1A2 and CYP2C9. |
| Excretion | Approximately 80% of a dose is excreted in urine as metabolites (primarily 6-methoxy-2-naphthylacetic acid and its glucuronide conjugates), with about 10% excreted in feces. Biliary excretion is minimal. |
| Half-life | Terminal elimination half-life is approximately 22-30 hours in healthy adults, allowing once-daily dosing. Steady state is achieved after 3-5 days. |
| Protein binding | Greater than 99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.6-0.7 L/kg, indicating distribution into total body water and tissues. |
| Bioavailability | Oral bioavailability is absolute, as nabumetone is a prodrug completely converted to active metabolite 6-methoxy-2-naphthylacetic acid after first-pass metabolism. |
| Onset of Action | Oral: Onset of analgesic effect occurs within 1-2 hours after administration. |
| Duration of Action | Duration of analgesic and anti-inflammatory effect is approximately 24 hours with once-daily dosing, consistent with its long half-life. |
| Molecular Weight | 228.29 |
1000 mg orally once daily with food; may increase to 1500-2000 mg/day in divided doses if needed.
| Dosage form | TABLET |
| Renal impairment | GFR 30-49 mL/min: reduce dose to 50% of normal; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: contraindicated. |
| Pediatric use | Not recommended for pediatric patients as safety and efficacy have not been established. |
| Geriatric use | Use lowest effective dose, not to exceed 1000 mg/day; monitor renal function closely. |
| 1st trimester | Avoid: NSAIDs in first trimester associated with increased risk of miscarriage and congenital anomalies; use only if clearly needed. |
| 2nd trimester | Caution: Use lowest effective dose for shortest duration; avoid during oligohydramnios or premature labor. |
| 3rd trimester | Contraindicated: Risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment; avoid after 30 weeks. |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| Placental transfer | Crosses placenta; peak fetal concentrations approximately 10% of maternal plasma levels. |
| Breastfeeding | Very low levels in breast milk; considered compatible with breastfeeding. However, due to risk of neonatal adverse effects, use lowest effective dose for shortest duration. |
■ FDA Black Box Warning
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. Nabumetone is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | rheumatoid arthritis |
| Serious Effects |
Hypersensitivity to nabumetone or any NSAIDHistory of asthma, urticaria, or allergic-type reactions after aspirin or NSAIDsActive peptic ulcer or gastrointestinal bleedingSevere heart failure (NYHA class III-IV)Severe hepatic impairmentSevere renal impairment (CrCl <30 mL/min)Perioperative pain in coronary artery bypass graft (CABG) surgeryThird trimester of pregnancy
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; renal toxicity; hepatic effects; hypertension; exacerbation of asthma; anemia; fluid retention and edema; serious skin reactions such as Stevens-Johnson syndrome; use in late pregnancy should be avoided. |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | NSAIDs including nabumetone are generally avoided in pregnancy, especially during the first and third trimesters. First trimester: possible increased risk of miscarriage and congenital malformations (e.g., cardiac defects) based on epidemiological data. Second trimester: considered relatively safer but should be used with caution. Third trimester (after 30 weeks): associated with premature closure of the ductus arteriosus, oligohydramnios, and fetal renal impairment; risk of neonatal complications including pulmonary hypertension and persistent pulmonary hypertension of the newborn (PPHN). |
| Fetal Monitoring | Monitor fetal growth, amniotic fluid volume, and ductus arteriosus patency via ultrasound, especially if used in the third trimester. Monitor maternal renal function, blood pressure, and signs of gastrointestinal bleeding. In neonates exposed in utero, observe for signs of respiratory distress, persistent pulmonary hypertension, and renal dysfunction. |
| Fertility Effects | Nabumetone, like other NSAIDs, may impair female fertility by inhibiting prostaglandin synthesis, leading to delayed or disrupted ovulation. This effect is reversible upon discontinuation. Limited data on male fertility; no significant adverse effects reported. |
| Food/Dietary | Take with food or milk to minimize gastrointestinal irritation. Avoid alcohol due to additive risk of gastric bleeding. |
| Clinical Pearls | Prodrug that is hepatically converted to active metabolite; lower GI toxicity than other NSAIDs; can be used in patients with sulfonamide allergy; dose adjustment needed in renal impairment (CrCl <30 mL/min); avoid in severe hepatic impairment; monitor renal function, liver enzymes, and CBC in long-term use. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Do not take with aspirin, other NSAIDs, or blood thinners without consulting doctor. · Report signs of bleeding (black/bloody stools, vomiting blood), persistent stomach pain, or skin rash. · May cause dizziness or drowsiness; avoid driving if affected. · Avoid alcohol while taking this medication to reduce stomach bleeding risk. |