Nabumetone dosing

NABUMETONE Recommended starting dose is 1,000 mg as a single dose with or without food. Some patients may obtain more symptomatic relief from 1,500 to 2,000 mg/day. Nabumetone can be given either once or twice/day. Dosages greater than 2,000 mg/day have not been studied. 

Nabumetone selectively inhibits COX-2. It is metabolised into 6-methoxy-2-naphthylacetic acid (MNA), that is a potent inhibitor of COX-2. It has no inhibitory effect on COX-1 which is responsible for prostaglandin synthesis in gastric mucosa, thereby minimising the risk of problems like ulcers and hypertension. After oral administration 80% of dose is excreted in the urine. Peak plasma concentration is reached after 2.5 to 4 hours. 

Nabumetone is the only nonacid NSAID in current use it is converted to the active acetic acid derivative in the body. It is given as a ketone prodrug that resembles naproxen in structure (Figure 36-1). Its half-life of more than 24 hours (Table 36-1) permits once-daily dosing, and the drug does not appear to undergo enterohepatic circulation. Renal impairment results in a doubling of its half-life and a 30% increase in the area under the curve. 

Nabumetone [Relafen] Initially 1000 mg/d in a single dose or 2 divided doses. Can be increased to 1500-2000 mg/d in 2 divided doses if needed... 

After repeated once-daily doses, nabumetone accumulates in elderly patients but not in others it is therefore wise to reduce the dose in elderly patients. 

Nabumetone. Nabumetone. 4-(6-mcthoxy-2-naphthyl)-2-butanone (Relafen), serves os a pmdnig to its aetive metabolite. 6-methoxy-2-naphthylacetic acid. Like the other aryla-cetic acid drugs, it is used in short- ur long-term management of RA and OA. It is available as tablets (500 and 750 mg), with a recommended. single daily dose of 1.000 mg. 

Clinical trials with nabumetone (Relafen) have indicated substantial efficacy in the treatment of rheumatoid arthritis and osteoarthritis, with a relatively low incidence of side effects. The dose typically is 1000 mg given once daily. The drug also has off-label use in the short-term treatment of soft-tissue injuries. 

In the carrageenan-induced rat paw assay, nabumetone is approximately 13 times more potent than aspirin, one-third as active as indomethacin, and half as active as diclofenac. It is only half as active as aspirin as an analgetic, as measured by the phenylquinone-induced writhing assay in mice. Despite its lower potency, the advantages of nabumetone may reside in its favorable gastric irritancy profile. The ratio of gastric irritancy dose in rats to anti-inflammatory activity in rats (ED50) for nabumetone is 21.25, whereas this ratio is 0.41 for aspirin, 0.55 for indomethacin, 0.72 for diclofenac, 3.00 for tolmetin, and 7.85 for zomepirac. 

Nabumetone is indicated for the acute and chronic treatment of the signs and symptoms of osteoarthritis and rheumatoid arthritis. The recommended starting dosage is 1,000 mg as a singie dose with or without food. More symptomatic reiief of severe or persistent symp-toms may be obtained at doses of 1,500 or 2,000 mg/day. 

The absorption of a single 1-g dose of nabumetone (as assessed by AUC and maximum plasma level) was not significantly altered by 160 mL of aluminium hydroxide suspension (Aludrox) in 15 healthy fasted subjects. ... 

Aspirin 600 mg four times daily caused a 15% reduction in the plasma levels of diflunisal 250 mg twice daily for 3 days. Single-dose studies have shown that the absorption of nabumetone 1 g is not significantly altered by aspirin 1.5 g. The plasma levels of tolmetin 1.2 g daily were slightly reduced by aspirin 3.9 g daily. ... 

The absorption of a single 1-g dose of nabumetone was increased by food and milk, as shown by an increase of about 50% in the maximum levels and a 40% increase in the AUC, 24- However, the AUC0.72 was not significantly increased. " ... 

Nabumetone. In a single-dose study, the absorption of nabumetone 1 g was not significantly altered by paracetamol 1.5 g. ... 

On the basis of the above studies, no coumarin dose adjustment would be expected to be needed with nabumetone. However, care is still needed with every NSAID , (p.427), because, to a greater or lesser extent, they irritate the stomach lining, which can result in gastrointestinal bleeding, which will be more severe in anticoagulated patients. 

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