indication

For acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.

pharmacology

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.

mechanism of action

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.

toxicity

The one overdose occurred in a 17-year-old female patient who had a history of abdominal pain and was hospitalized for increased abdominal pain following ingestion of 30 nabumetone tablets (15 grams total). Stools were negative for occult blood and there was no fall in serum hemoglobin concentration. The patient had no other symptoms.

biotransformation

Undergoes rapid biotransformation to the principal active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). Approximately 35% of a 1000 mg oral dose of nabumetone is converted to 6MNA and 50% is converted into unidentified metabolites which are subsequently excreted in the urine.

absorption

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.

half life

Approximately 23 hours for the active metabolite, 6MNA. Increased in patients with renal insufficiency.

route of elimination

Approximately 35% of a 1000 mg oral dose of nabumetone is converted to 6MNA and 50% is converted into unidentified metabolites which are subsequently excreted in the urine.

drug interactions

Acenocoumarol: The NSAID, nabumetone, may increase the anticoagulant effect of acenocoumarol.

Alendronate: Increased risk of gastric toxicity

Anisindione: The NSAID, nabumetone, may increase the anticoagulant effect anisindione.

Colesevelam: Bile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.

Cyclosporine: Monitor for nephrotoxicity

Dicumarol: The NSAID, nabumetone, may increase the anticoagulant effect of dicumarol.

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Methotrexate: The NSAID, nabumetone, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.

Telmisartan: Concomitant use of Telmisartan and Nabumetone may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.

Timolol: The NSAID, Nabumetone, may antagonize the antihypertensive effect of Timolol.

Trandolapril: The NSAID, Nabumetone, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Nabumetone is initiated, discontinued or dose changed.

Treprostinil: The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Nabumetone. Monitor for increased bleeding during concomitant thearpy.

Warfarin: The antiplatelet effects of nabumetone may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.