THERAPEUTICS

Brands

• Cataflam, Cambia, Dyloject, Pennsaid, Solaraze, Voltaren, Zipsor, Zorvolex

Generic?

• Yes

Class

• Non-steroidal anti-inflammatory drug (NSAID)

Commonly Prescribed for

(FDA approved in bold)

• Acute migraine attacks in adults (Cambia only)

• For relief of mild to moderate acute pain of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, trauma, fractures, renal colic, surgery

• Primary dysmenorrhea

How the Drug Works

• Like other NSAIDs, it binds competitively to cyclo-oxygenase (predominantly COX-1) thus inhibiting synthesis of proinflammatory thromboxane (TXA2) and prostaglandins (PGE2). The inhibition is serum concentration dependent

• Emerging evidence suggests it inhibits leukotriene synthesis, stimulates nitric oxide-cGMP antinociceptive pathway, increases plasma β-endorphin levels, and inhibits NMDA pathway. It may inhibit substrate P, NMDA receptor hyperalgesia, peroxisome proliferator activated receptor gamma (PPARgamma); block acid-sensing ion channels; and lower substance P and interleukin-6 production

How Long Until It Works

• Acute migraine: less than 2 hours

• Pain: within 30 minutes

If It Works

• Continue to use

If It Doesn't Work

• Migraine: add triptan, dihydroergotamine, antiemetic, or another NSAID Best Augmenting Combos for Partial Response or Treatment-Resistance

• Migraine: combine with triptan or antiemetic

Tests

• Monitor blood pressure

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• COX-1 is required for maintaining production of prostanoids, including prostacyclin (PGI2) for GI mucosal protection and platelet aggregation inhibition

Notable AEs

• Dyspepsia, dizziness, nausea, diarrhea most common

• Inhibition of platelet aggregation is usually mild

• Elevation in hepatic transaminases (usually borderline)

Life-Threatening or Dangerous AEs

• Fatal cardiovascular thrombotic events (myocardial infarction, stroke)

• GI ulceration, perforation, and bleeding

• New-onset or worsening of hypertension

• Renal papillary necrosis or other renal injury

• Anaphylactoid reactions in patients with the aspirin triad (nasal polyps, asthma, aspirin intolerance)

• Stevens-Johnson syndrome, toxic epidermal necrolysis

Weight Gain

• Unusual

Sedation

• Not unusual