A 38 y/o male patient new to your clinic with hyperuricemia presents to your clinic. He has no other significant medical history and his labs (except uric acid ~ 11 mg/dL) are within normal limits. He's been treated with uricosuric agents to date but with only marginal results. Based on your assessment, he's an 'over-producer' of uric acid and you feel he'd be a good candidate for allopurinol. When you mention this to the patient, he states he had tried this drug in the past and had pruritic maculopapular rash, requiring discontinuing of the drug. He had no anaphylactic-type symptoms during this episode. He wasn't re-challenged.

Do you have any other therapy(ies) to offer him? If so, what and how?
 

 ** THANKS to Dr Jay Higgs for his help with this Pearl. **

Yes. Since he is only doing marginally better on a uricosuric agent, another uricosuric agent probably wouldn't cause significantly better results. Since he's an 'over-producer' of uric acid, allopurinol (a xanthine oxidase inhibitor) is probably the drug of choice. Even though this patient had a skin reaction to the agent in the past, he may be a candidate for a desensitization regimen.

** THIS IS NOT INDICATED for patients with SEVERE cutaneous/systemic reactions such as Steven Johnson syndrome, toxic epidermal necrolysis (TEN), erythema multiforme or exfoliative dermatitis with leukocytosis, acute hepatitis, and/or acute interstitial nephritis.

The patients most likely to experience this cutaneous reaction include elderly patients, patients with renal insufficiency [allopurinol needs dose adjustment in patients with decreased CrCl - starting with CrCls < 60 ml/min), co-administration of thiazide diuretics, abnormal T-lymphocyte-mediated immune responses, and/or genetic factors.

The article referenced below defines a 28-day desensitization protocol starting with extremely low doses (50 mcg) and a doubling the dose every 3 days until you reach a dose of 100mg. In the article listed below, 2 patients inadvertently stopped their desensitization regimen and were able to restart at half the previously tolerated dose they were on when they stopped. These 2 patients followed the gradual dose escalation from their new start point.

Oxypurinol (the active metabolite of allopurinol) is available and has been used in these patients but there's a 40% cross sensitivity reported in these patients.

The reference listed below suggests the following indications for desensitization in patients with allopurinol-induced maculopapular reactions:

1)    Patients with gout and renal insufficiency, and those requiring concomitant low-dose aspirin, which renders uricosurics ineffective

2)    Patients with gout, 'over-production' hyperuricemia, hyperuricosuria, and nephrolithiasis in whom uricosurics can increase the risk of stone formation, renal colic, and renal failure

3)    Patients with gout and 'underexcretion' hyperuricemia who are either allergic or intolerant to both probenecid and sulfinpyrazone (both uricosuric agents)

4)    Patients with malignancy-associated hyperuricemia due to cytolytic therapy for myeloproliferative or lymphoproliferative disorders; the resulting massive hyperuricemia precludes the use of a uricosuric agent.

REFERENCE:

-    Fam AG, Dunne SM, Iazzetta J, Paton TW. Efficacy and safety of desensitization to allopurinol following cutaneous reactions. Arthritis Rheum 2001;44:231-8.

This Pearl is meant for academic and educational purposes only. This Pearl is meant to raise important points regarding the safe and cost-effective pharmacotherapy of patients. It is not meant to be the definitive reference for the treatment or prophylaxis of various diseases. Although every effort is taken to ensure this Pearl is correct and factual, errors may occur. The Pharmacoeconomic Center assumes no liability for incorrect information or harm that may occur from the use of the information included in this Pearl.