nabumetone (Rx)

>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%)

Contraindications

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)

Cautions

Use caution in asthma (bronchial), bleeding disorders, cardiac disease, hepatic impairment, hypertension, renal impairment

May not be sufficiently activated in patients with hepatic dysfunction; use with caution

Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include elderly individuals, those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers

Risk of serious GI toxicity, including bleeding, ulcers, perforation

May cause drowsiness, dizziness, blured vision, and other neurologic effects

May decrease platelet adhesion and aggregation, prolonging bleeding time; monitor closely patients with history of coagulation disorders

May increase risk of hyperkalemia

May cause photosensitivity reactions

Severe skin reactions may occur; discontinue use at first sign of rash

Heart Failure(HF) risk

• NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
• NSAIDS should be avoided or withdrawn whenever possible
• AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134

Pregnancy category: C; D if used for prolonged periods or near term (premature closure of ductus arteriosus)

Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and approximately 2.6% of controls

Lactation: Unknown whether drug is excreted in breast milk; effect on infant unknown; do not give to nursing mothers

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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

Absorption

Onset: Several days

Peak serum time: 2-4 hr (PO)

Distribution

Protein bound: >99%

Vd: 29-82 L (6-methoxy-2-naphthylacetic acid [6-MNA] metabolite)

Metabolism

Metabolized in liver

Metabolites: 6-MNA (unchanged and conjugated), 4-(6-hydroxy-2-naphthyl)-butan-2-ol (conjugated), O-desmethyl-nabumetone (conjugated), unidentified minor metabolites

Enzymes inhibited: COX-1. COX-2

Elimination

Half-life: 24 hr (6-MNA)

Dialyzable: No

Excretion: Urine (80%), feces (9%)