Dosing and uses of Relafen (nabumetone)
Adult dosage forms and strengths
tablet
- 500mg
- 750mg
Osteoarthritis
1000 mg PO once daily initially; maintenance: 1000-2000 mg/day PO in single daily dose or divided q12hr; not to exceed 2000 mg/day
Rheumatoid Arthritis
1000 mg PO once daily initially; maintenance: 1000-2000 mg/day PO in single daily dose or divided q12hr; not to exceed 2000 mg/day
Dosing Modifications
Moderate renal impairment (CrCl: 30-49 mL/min): 750 mg/day initially; not to exceed 1500 mg/day
Severe renal impairment (CrCl: <30 mL/min): 500 mg/day initially; not to exceed 1000 mg/day
Pediatric dosage forms and strengths
Not recommended
Juvenile Rheumatoid Arthritis (Orphan)
Orphan indication sponsor
- Cook Pharma, 109 Graylyn Drive, Chapel Hill, NC 27516
Relafen (nabumetone) adverse (side) effects
>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%)
Warnings
Black box warnings
Cardiovascular risk
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
- Risk may increase with duration of use
- Patients with existing cardiovascular disease or risk factors for such disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in setting of coronary artery bypass graft (CABG) surgery
Gastrointestinal risk
- NSAIDs increase risk of serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation, which can be fatal
- GI adverse events may occur at any time during use and without warning symptoms
- Elderly patients are at greater risk for serious GI events
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 and lactation
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.
Pharmacology of Relafen (nabumetone)
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%)
