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

Therapy may lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to increased incidence of CV events; patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs; use with caution in patients with hypertension; monitor blood pressure (BP) closely during initiation of treatment and throughout the course of therapy

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

Borderline elevations of 1 or more liver function tests may occur in up to15% of patients; laboratory abnormalities may progress, remain unchanged, or may be transient with continuing therapy; notable elevations of ALT or AST (approximately 3 or more times the upper limit of normal) reported in approximately 1% of patients in clinical trials with NSAIDs; If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue therapy

Severe and potentially fatal bronchospasm may occur in patients with aspirin-sensitive asthma; contraindicated; use caution in patients with other forms of asthma

Risk of serious GI toxicity, including bleeding, ulcers, perforation; to minimize potential risk for an adverse GI event in patients receiving therapy, use lowest effective dose for shortest possible duration; discontinue therapy if adverse GI effects occur; for high risk patients, consider alternate therapies that do not involve NSAIDs

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

Therapy inhibits platelet aggregation and have been shown to prolong bleeding time in some patients; unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible; patients receiving therapy who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored

May increase risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal; patients with known CV disease or risk factors for CV disease may be at greater risk; to minimize potential risk for an adverse CV event in patients treated with an NSAID, use lowest effective dose for shortest duration possible

May increase risk of hyperkalemia

Based on ultraviolet (U.V.) light photosensitivity testing, drug may be associated with more reactions to sun exposure than might be expected based on skin tanning types

Serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal may occur without warning; patients should be informed about signs and symptoms of serious skin manifestations and use of the drug should be discontinued at first appearance of skin rash or any other sign of hypersensitivity

Renal toxicity

• Long-term administration treatment may result in renal papillary necrosis and other renal injury; renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in these patients
• Administration of an NSAID results in a dose-dependent decrease in prostaglandin synthesis and, secondarily, in a reduction of renal blood flow, which may precipitate overt renal decompensation; recovery reported after discontinuation of therapy
• Ptients 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

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%)