Nabumetone (Relafen)

Nabumetone in Brief
  • Generic name : Nabumetone
  • Brand names: Relafen
  • Therapeutic class: Antiarthritic, Analgesic
  • Pharmacologic class: Non-Steroidal Anti-Inflammatory Drug (NSAID), 1-naphthaleneacetic acid derivative
  • FDA Approved: December 24, 1991
  • Pregnancy Category: C
  • Originally discovered: SmithKline Beecham, UK UK

Based on "Essential Pain Pharmacology"
written by Howard S. Smith, MD; Marco Pappagallo, MD

History

Nabumetone is unique among the NSAIDs in that it represents a new class of nonacidic Non-steroidal anti-inflammatory drugs (NSAIDs). It was developed by Beecham Pharmaceuticals 1.

The history of nabumetone is an interesting example of industrial competition. The patent status of this drug is one of the most complicated and controversial. Nabumetone was under patent up to the year 2002 in the USA.

One of the major side effects associated with NSAIDs is the significant ulceration of the gastric mucosa. To overcome this drawback, generally associated with the presence of a carboxylic function, SmithKline Beecham's researchers devoted their efforts to the discovery of a non-acidic NSAID.


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In 1973, Lake and Rose discovered nabumetone and filed the corresponding patent application in the UK1. The discovery claimed in the UK patent application was anticipated by an Indian research group with a publication in the Indian Journal of Chemistry. However, SmithKline Beecham's patents were granted worldwide because nabumetone was claimed to be a powder and the Indian publication described it as a pale yellow oil.

The original U.S. patent application was filed in 1973. In practical terms, the SmithKline Beecham patent office obtained an exclusivity of 28 years in the USA market.

FDA approved uses

  • Osteoarthritis (OA)
  • Rheumatoid arthritis (RA)

Off-label & Investigational uses

  • Mild-to-moderate pain, e.g. neck pain, muscle pain
  • Lower back pain 7, 8
  • Short-term treatment of soft-tissue injuries

Dosage

The recommended starting dosage is 1.000 mg as a single dose with or without food.

More symptomatic relief of severe or persistent symptoms can be obtained at doses of 1.500 or 2.000 mg per day.

Nabumetone Potency

Nabumetone is approximately 13 times more potent than aspirin, one-third as active as indomethacin, and half as active as diclofenac5. It is only half as active as aspirin as an analgesic. Nabumetone has greater mild analgesic activity than paracetamol4.


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Nabumetone "pros" and "cons"

Advantages:

  • Relatively low incidence of side effects2
  • Less damaging to the stomach than other traditional NSAIDs2
  • Little to no effect on renal function3
  • Well absorbed orally
  • Nabumetone is not associated with increased cardiovascular risk
  • Once daily dosing
  • Nabumetone is a safe alternative in NSAID-intolerant patients6.
  • Good anti-inflammatory properties
  • Could be useful in combo with other NSAIDs.

Disadvantages:

  • High doses are often needed
  • Very expensive
  • May cause pseudoporphyria (bullas on sun exposed skin) and photosensitivity
  • Active use of nabumetone may increase the risk of pancreatitis9

Mechanism of action

Nabumetone is a nonacidic, nonsteroidal anti-inflammatory drug that is rapidly metabolized after absorption to a major active metabolite, 6-methoxy-2-naphthylacetic acid. Nabumetone itself is non-acidic and exerts its pharmacological effects via the 6-methoxy-2-naphthylacetic acid (6-MNA). Unlike the parent compound (nabumetone is a poor inhibitor of prostaglandin synthesis) 6-MNA is a potent inhibitor of the cyclooxygenase enzyme and preferentially blocks 6-MNA activity. However, it is not purely selective.

6-MNA inhibits COX-2 more preferentially than COX-1, but can't be considered a selective COX-2 inhibitor.

Time to clear out of the system

Nabumetone has a long half-life about 20 to 24 hr. It takes about 5-6 days for nabumetone to clear out of the system.

The half-life of 6-methoxy-2-naphthylacetic acid does not change on repeated dosing, and no unexpected or irreversible accumulation occurs.

Further reading

References

  • 1. From Bench to Market: The Evolution of Chemical Synthesis. Walter Cabri , Romano Di Fabio, Oxford University Press, 2000, p.147-149
  • 2. Bannwarth B. Safety of the nonselective NSAID nabumetone: focus on gastrointestinal tolerability. Drug Saf. 2008;31(6):485-503. PubMed
  • 3. Giannessi D, Lazzerini G, Filipponi P, Mannarelli C, Vaiani G, Grossi E, De Caterina R. Effects of nabumetone, a new non-steroidal anti-inflammatory drug, on urinary prostaglandin excretion in man. Pharmacol Res. 1993 Oct-Nov;28(3):229-41.
  • 4. Boyle EA, Freeman PC, Mangan FR, Thomson MJ. Nabumetone (BRL 14777, 4-[6-methoxy-2-naphthyl]-butan-2-one): a new anti-inflammatory agent. J Pharm Pharmacol. 1982 Sep;34(9):562-9.
  • 5. Thomas L Lemke, David A Williams, Victoria F Roche. Foye's Principles of Medicinal Chemistry, 7th Edition; Lippincott Williams & Wilkins; 2012.
  • 6. Prieto A, De Barrio M, Martín E, et al. Tolerability to nabumetone in patients with nonsteroidal anti-inflammatory drug intolerance. J Allergy Clin Immunol. 2007 Apr;119(4):960-4. PubMed
  • 7. Reviews for Nabumetone to treat Back Pain on Drugs.com
  • 8. Riccieri V, Spadaro A, Iagnocco A. Treatment of acute rheumatic-articular diseases with nabumetone. Clin Ter. 1990 Aug 15-31;134(3-4):181-5.
  • 9. Hung SC, Liao KF, Hung HC, et al. Nabumetone use and risk of acute pancreatitis in a case-control study. Pancreatology. 2016 May-Jun;16(3):353-7. PubMed

Published: October 30, 2013
Last updated: January 28, 2017

Interesting facts
Nabumetone facts
  • Nabumetone is the only non-acid NSAID.
  • It is a ketone prodrug, converted to active acetic acid derivative, structurally similar to Naproxen.
  • Nabumetone is one of the least toxic NSAIDs.
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