NABUMETONE (NON OPIOID ANALGESIC)

Introduction
Non-opioid analgesic, NSAID, preferential COX-2 inhibitor

Pharmacodynamic
Nabumetone is a naphthylalkanone. Is is a non-selective prostaglandin G/H synthase (a.k.a.
cyclooxygenase or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2
(COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to
prostaglandin G2 and prostaglandin G2 to prostaglandin H2. Prostaglandin H2 is the
precursor to a number of prostaglandins involved in fever, pain, swelling, inflammation, and
platelet aggregation. The parent compound is a prodrug that undergoes hepatic
biotransformation to the active compound, 6-methoxy-2-naphthylacetic acid (6MNA). The
analgesic, antipyretic and anti-inflammatory effects of NSAIDs occur as a result of decreased
prostaglandin synthesis.
The parent compound is a prodrug, which undergoes hepatic biotransformation to the active
component, 6-methoxy-2-naphthylacetic acid (6MNA), that is a potent inhibitor of
prostaglandin synthesis, most likely through binding to the COX-2 and COX-1 receptors.
Well absorbed from the gastrointestinal tract. Coadministration of food increases the rate of
absorption and subsequent appearance of 6MNA (the active metabolite) in the plasma but
does not affect the extent of conversion of nabumetone into 6MNA.

Indication
Nabumetone are indicated for relief of signs and symptoms of osteoarthritis, rheumatoid
arthritis and cancer pain.

Contraindication
Nabumetone are contraindicated in patients with known hypersensitivity to nabumetone or its
excipients.

Nabumetone should not be given to patients who have experienced asthma, urticaria, or
allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal,
anaphylactic-like reactions to NSAIDs have been reported in such patients.

Dosage
Dose reduction is not necessary in patients with mildmoderate renal impairment, but is
advisable in severe renal impairment (creatinine clearance <30ml/min).
Typically:
start with 1g o.d. (each evening)
if necessary, increase to 500mg o.m. and 1g each e
vening
if necessary, increase further to 1g b.d.
in very elderly (80+ years) frail patients, start
with 500mg, and limit to 1g daily.
Supply
Nabumetone (non-proprietary)
Tablets 500mg, 28 days @ 1g o.d.
Relifex(Meda)
Tablets 500mg, 28 days @ 1g o.d.
Oral suspension(sugar-free) 500mg/5ml, vanilla with buttermint flavour, 28 days @ 1g o.d.

Side effect
Nabumetone may cause some unwanted effects. Although not all of these side effects may
occur, if they do occur they may need medical attention.
More common
Headache, itching skin, nausea, rash, stomach pain, swelling
Less common
Burning feeling in chest or stomach, indigestion, stomach upset, swelling or inflammation of
the mouth, tenderness in stomach area, vomiting
Rare
Bleeding gums, blistering, peeling, loosening of skin, bloody or black, tarry stools, bloody or
cloudy urine, burning upper abdominal pain, changes in vision, chest pain, chills, claycolored stools, constipation, cough, dark-colored urine, diarrhea, difficult or labored
breathing, difficulty swallowing, dizziness, dry cough, dry mouth, fast heartbeat, fever, fluidfilled skin blisters, general feeling of tiredness or weakness, greatly decreased frequency of

urination or amount of urine, high blood pressure, hives or welts, increased sensitivity of skin
to sunlight, increased thirst, joint pain, stiffness, or swelling, large, hive-like swelling on face,
eyelids, lips, tongue, throat, hands, legs, feet, sex organs, light-colored stools, loss of appetite,
muscle pain, pain in lower back or side, pinpoint red spots on skin, puffiness or swelling of
the eyelids or around the eyes, face, lips or tongue, rapid breathing, red irritated eyes, red skin
lesions, often with a purple center, redness or other discoloration of skin, severe or continuing
stomach pain, severe sunburn, shortness of breath, skin thinness, sore throat, sores, ulcers, or
white spots in mouth or on lips, stomach bloating, burning, or cramping swelling of face,
fingers, feet or lower legs, tightness in chest, unpleasant breath odor, unusual bleeding or
bruising, unusual tiredness or weakness, vaginal bleeding, vomiting of blood or material that
looks like coffee grounds, weight gain or loss, wheezing, yellow eyes or skin

Special precaution
Severe renal impairment (creatinine clearance <30ml/min), active or previous peptic
ulceration (see p.000), history of dyspepsia, irritable bowel syndrome, fluid retention, CHF.
6-MNA is highly protein-bound and may displace other highly bound drugs from plasma
proteins, e.g. phenytoin, sulphonylureas. Although nabumetone does not normally alter
platelet aggregation or affect the INR in anticoagulated patients, there is an isolated report of
haemarthrosis and raised INR in a patient taking warfarin. Thus, if nabumetone is prescribed
to a patient already taking warfarin, monitor the INR weekly for 34 weeks and adjust the
dose of warfarin if necessary