Nabumetone

Indications

Nabumetone is used for: Pain and inflammation associated with musculoskeletal and joint disorders, Osteoarthritis, Rheumatoid Arthritis

Adult Dose

Oral Adult Osteoarthritis 1g PO once daily initially; maintenance: 1-2 g/day PO in single daily dose or divided q12hr; not to exceed 2 g/day Rheumatoid Arthritis 1 g PO once daily initially; maintenance: 1-2 g/day PO in single daily dose or divided q12hr; not to exceed 2 g/day Elderly: 500 mg daily may be adequate in certain patients. Max: 1 g daily.

Child Dose

Not recommended

Renal Dose

Renal impairment: CrCl (ml/min) Dosage Recommendation 30-49 Max initial dose: 750 mg once daily. Increase if needed to a max dose of 1.5 g daily. <30 Max initial dose: 500 mg once daily. Increase if needed to a max dose of 1 g daily.

Administration

Should taken with food.

Contra Indications

Absolute: Aspirin allergy, severe renal impairment; perioperative pain in setting of coronary artery bypass graft (CABG) surgery Relative: Duodenal/gastric/peptic ulcer, stomatitis, systemic lupus erythematosus, ulcerative colitis, late pregnancy (may cause premature closure of ductus arteriosus)

Precautions

Pre-existing CV risk factors or disease; fluid retention, CHF, hypertension. History of GI disease (bleeding or ulcers). Elderly or debilitated patients. Other forms of asthma. Hepatic impairment; closely monitor patients with any abnormal LFT. Renal impairment; rehydrate patient prior to therapy and closely monitor renal function. Withhold for at least 4-6 half-lives prior to surgical or dental procedures.

Pregnancy-Lactation

Pregnancy category: C; D if used for prolonged periods or near term (premature closure of ductus arteriosus) Lactation: Unknown whether drug is excreted in breast milk; effect on infant unknown; do not give to nursing mothers

Interactions

Antihypertensive effects of hypotensive agents may be reduced. May increase ciclosporin levels. Increased risk of seizures with fluoroquinolones. May reduce efficacy of diuretics. May diminish the cardioprotective effect of acetylated salicylates. Alcohol may enhance gastric mucosal irritation. Potentially Fatal: Increased risk of bleeding with anticoagulants (e.g. warfarin, heparin, LMWHs) and antiplatelet agents (e.g. ticlopidine, clopidogrel, aspirin, abciximab, dipyridamole, eptifibatide, tirofiban). Increased risk of GI ulceration with corticosteroids. Severe bone marrow suppression, aplastic anaemia and GI toxicity may occur with methotrexate.

Adverse Effects

Side effects of Nabumetone : >10% Diarrhea (14%), Dyspepsia (13%), Abdominal pain (12%) 1-10% Constipation (3-9%), Dizziness (3-9%), Edema (3-9%), Flatulence (3-9%), Headache (3-9%), Nausea (3-9%), Positive stool guaiac (3-9%), Pruritus (3-9%), Rash (3-9%), Tinnitus (3-9%), Dry mouth (1-3%), Fatigue (1-3%), Gastritis (1-3%), Increased sweating (1-3%), Insomnia (1-3%), Nervousness (1-3%), Somnolence (1-3%), Stomatitis (1-3%), Vomiting (1-3%)

Mechanism of Action

Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2 May inhibit chemotaxis, alter lymphocyte activity, decrease proinflammatory cytokine activity, and inhibit neutrophil aggregation; these effects may contribute to anti-inflammatory activity