RELAFEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RELAFEN (RELAFEN).
Nabumetone is a nonacidic nonsteroidal anti-inflammatory drug (NSAID) that is a prodrug, rapidly metabolized to the active metabolite 6-methoxy-2-naphthylacetic acid (6-MNA), which inhibits cyclooxygenase (COX) and thereby prostaglandin synthesis.
| Metabolism | Nabumetone is extensively metabolized in the liver to the active metabolite 6-MNA, primarily via CYP1A2 and to a lesser extent CYP2C9. 6-MNA is further metabolized and conjugated. |
| Excretion | Primarily renal (90% as metabolites, ~5% unchanged); biliary/fecal minor (<5%). |
| Half-life | Terminal elimination half-life approximately 24 hours (range 20-30 hours), allowing once-daily dosing. |
| Protein binding | >99% bound, primarily to albumin. |
| Volume of Distribution | 7-10 L (approximately 0.1-0.15 L/kg), indicating limited extravascular distribution. |
| Bioavailability | Oral: >80% (well absorbed); not administered parenterally. |
| Onset of Action | Oral: 1-2 hours for analgesic effect; 2 weeks for antiarthritic effect. |
| Duration of Action | Analgesic: 6-12 hours; anti-inflammatory: 12-24 hours with chronic dosing. |
| Molecular Weight | 228.29 |
1000 mg orally once daily, or 500 mg twice daily. Maximum dose 2000 mg/day.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-49 mL/min: reduce dose by 50%; CrCl <30 mL/min: not recommended. |
| Liver impairment | No specific recommendations; use caution in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for children <16 years; safety and efficacy not established. |
| Geriatric use | Reduce starting dose; maximum 1000 mg/day; monitor renal function. |
| 1st trimester | Avoid. NSAIDs may increase risk of miscarriage and congenital malformations. |
| 2nd trimester | Avoid unless absolutely necessary. May cause oligohydramnios and fetal renal impairment. |
| 3rd trimester | Contraindicated. Risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for RELAFEN (RELAFEN).
| Placental transfer | Nabumetone and its active metabolite cross the placenta. Fetal: maternal ratio for the active metabolite is approximately 0.5-1.0. |
| Breastfeeding | Nabumetone is excreted into breast milk in low concentrations. Due to potential adverse effects on the infant's renal function and platelet function, caution is advised. The American Academy of Pediatrics considers nabumetone compatible with breastfeeding, but alternative analgesics with a better safety profile are preferred. |
■ 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 risk factors may be at greater risk. RELAFEN is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
History of hypersensitivity to nabumetone or other NSAIDsActive peptic ulcer disease or GI bleedingSevere renal impairmentSevere hepatic impairmentThird trimester of pregnancy
| Precautions | Serious cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; hypertension; heart failure and edema; renal toxicity; anaphylactoid reactions; serious skin reactions (e.g., Stevens-Johnson syndrome); hematologic toxicity; hepatic effects; pre-existing asthma; masking of inflammation; and ophthalmic effects. |
| Food/Dietary | Avoid alcohol as it increases the risk of gastrointestinal bleeding. Taking with food or milk can reduce gastrointestinal irritation. Grapefruit juice has no significant interaction with nabumetone. |
Loading safety data…
| Lactation Rating | L3 - Limited Data |
| Teratogenic Risk | RELAFEN (nabumetone) is a nonsteroidal anti-inflammatory drug (NSAID). Avoid use during first and second trimesters unless benefit outweighs risk; may be associated with oligohydramnios and fetal renal impairment. Contraindicated in third trimester due to risk of premature closure of ductus arteriosus and fetal nephrotoxicity. |
| Fetal Monitoring | Monitor fetal ultrasound for oligohydramnios if used during pregnancy. In third trimester, monitor ductus arteriosus flow via fetal echocardiography if exposure occurs. Assess maternal renal function and bleeding time. |
| Fertility Effects | Nabumetone may impair female fertility via inhibition of prostaglandin synthesis, affecting ovulation. Reversible upon discontinuation. Not recommended in women attempting conception. |
| Clinical Pearls | RELAFEN (nabumetone) is a nonsteroidal anti-inflammatory drug (NSAID) with a non-acidic prodrug structure that requires hepatic conversion to its active metabolite. It has a relatively long half-life (approx. 22-30 hours) allowing once or twice daily dosing. Despite being a non-selective NSAID, it may have less gastrointestinal toxicity due to its non-acidic nature, but this is not definitively proven. Use with caution in elderly patients, renal impairment, and those with a history of GI bleeding. |
| Patient Advice | Take RELAFEN with food or milk to reduce stomach upset. · Do not take other NSAIDs (like ibuprofen or aspirin) while on this medication unless directed by your doctor. · Notify your doctor immediately if you experience signs of stomach bleeding (black/tarry stools, vomit that looks like coffee grounds) or cardiovascular events (chest pain, shortness of breath). · Avoid alcohol consumption as it increases the risk of gastrointestinal bleeding. · Report any new or worsening symptoms such as swelling, weight gain, or decreased urine output. · Do not double the dose if you miss one; take your next dose at the usual time. |