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Clinician’s Corner: Gout Prevention

Ground Rules for GOUT PREVENTION:

  • Patients after an acute gouty arthritis attack are candidates for long term prevention aimed at reducing the serum uric acid levels. Don’t start prevention therapy while having gout attack
  • Goal of chronic therapy is to decrease future attacks, and reduce body stores of urate, and reversing the effects of urate deposits.
  • The most widely recommended goal range of urate-lowering therapy the magic number for serum urate is less than 6 mg/dL. Urate levels over 11mg/dl is a significant risk for kidney stones.

XANTHINE OXIDASE INHIBITORS:

ALLOPURINOL (Zyloprim®) is available in tablets of 100mg & 300mg strengths.  This drug was first approved 1966. Blocks the formation of uric acid in the body.

INDICATIONS FOR USE: Control of gout and hyperuricemia.  Management of patients with primary and secondary sign/symptoms of gout (frequent gout attacks, tophi, joint destruction, uric acid lithiasis & nephropathy).  Allopurinol is not an innocuous drug and should not be taken “as needed.”

RECOMMENDED DOSE: start low to prevent acute gouty flare-ups.

Start patients with good kidney function with 100mg daily.  Increase by 100mg each week until uric acid level is 6mg/dl or less.   Average dose is 200-300mg for mild gout.  For patients with severe tophaceous gout may need 400-600mg/day.

May be dosed once daily, however if over 300mg/day is required, divided doses. Maximum=800mg/day to get uric acid level under 6mg/dL.  Take with food or mild to minimize GI upset.  Must have good kidney function for this dose of 800mg.

Patients need to take NSAID (Motrin or Aleve)  or colchicine when starting to prevent acute flare.

WARNINGS/PRECAUTIONS/ADVERSE EFFECTS

  • A rash might occur during therapy, which should be reported to practitioner at once. This rash may be simple rash or serious Stevens-Johnson syndrome (which is exfoliative and erythematous). Asian patients should be tested to see if they are at risk.

DRUG INTERACTIONS:

Increase in skin rash with Amoxicillin and Ampicillin.

Have your Thompson Pharmacist check for 6-mercaptopurine (Purinethol) and azathioprine (Imuran) on your pharmacy profile. These are serious drug interactions.

PATIENT EDUCATION—allopurinol

  • Report sign of rash, painful urination, blood in urine immediately to practitioner
  • Continue acute therapy. Optimal allopurinol may take 2-6 weeks.
  • Increase fluid intake to decrease renal stones
  • Take with food to minimize stomach upset.

Febuxostat (Uloric)  40mg and 80 mg  (approved 2009)       cost: over $380/month
Mechanism:  xanthine oxidase inhibitor.

Will lower uric acid more effectively, than allopurinol, but does NOT prevent gout flares any more effectively then allopurinol.

BLACK BOX WARNING: Febuxostat has a higher risk of death than allopurinol

For both xanthine oxidase inhibitors: Azathioprine (Imuran) & 6-mercaptopurine (Purinethol)  both are chemo drugs & immunosuppressants are metabolized by xanthine oxidase pathway.  Allopurinol & febuxostat will increase the levels of these drugs to dangerous levels

URICOSURIC:

PROBENECID  (Benemid®)  (ColBenemid®  has colchicine added) 500mg tablets

MECHANISM OF ACTION: uricosuric: promotes excretion of uric acid in the kidney.

Do NOT start until acute attack has subsided.   Take with food.

WARNINGS/PRECAUTIONS/ADVERSE EFFECTS

  • 10% patients may develop uric acid stones. Advise drinking 2 liters of water per day
  • Pregnancy Category: B
  • Avoid with kidney stones or reduced kidney function.

PATIENT EDUCATION

  • Drink at least 2 liters of water per day to decrease uric acid stone formation.
  • Take with food if GI upset occurs.
  • Avoid Aspirin may antagonize uricosuric effect

LOSARTAN (Cozaar®)

Losartan has a mild effect on kidneys to increase uric acid excretion, that maxes out at 50mg dose. Other ARBs like irbesartan do NOT have a similar uricosuric effect.  Good drug to consider for hypertensive patients with hyperuricemia. Lots of our Thompson Pharmacy patients take this drug for blood pressure.

VITAMIN–C (ascorbic Acid)
Might help increase renal excretion of uric acid and reduce gout flares.

Suggested dose 500 to 1000 mg/day from food or supplements. Expect a maximum of 0.5mg/dl lowering