Allopurinol

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Dosage 4 Dosage-adjustment-in-renal-failure 5 Pharmacokinetics 6 Monitor 7 Adverse-effects 8 Drug-interactions 9 Mechanism-of-action 10 More General Terms 11 Internet Database 12 References

Introduction

• Tradenames: Zyloprim, Lopurin, Zurinol.

Indications

• gout maintenance therapy:

• do not use as lone therapy during an acute attack of gout
• allopurinol may precipitate an attack of gout
• drug of choice if patient has history of renal stones or renal insufficiency
• 200-300 mg PO QD/ BID* [1,2]

• prevention of chemotherapy-induced acute tumor lysis syndrome
• improves exercise tolerance in patients with chronic stable angina pectoris [8]
• may improve outcomes in patients with heart failure & gout [9]

Dosage

• gout:

• start 100 mg PO QD
• do not initiate during acute exacerbation of gout

• tumor lysis syndrome

• 600-800 mg QD with maintainance of high fluid intake

• chronic stable angina pectoris

• 600 mg PO QD [8]

• * use in combination with colchicine 0.6 mg QD# during 1st 3-6 months of therapy # dose reduction with renal failuure [6]
• Tabs: 100 & 300 mg.
• Injection:

Dosage-adjustment-in-renal-failure

*  creatinine clearance        dosage 
*     60 mL/min               200 mg QD  
*     40 mL/min               150 mg QD 
*     20 mL/min               100 mg QD 
*     10 mL/min               100 mg QOD 
*   < 10 mL/min               100 mg 3 x/week

Pharmacokinetics

• bioavailability following oral administration is 80-90%
• peak plasma levels occur 2-6 hours after oral administration
• peak plasma leves 30 minutes after IV administration
• serum urate levels

• generally decrease within 24-48 hours

• delay may occur due to dissolution of urate crystals

• normal serum urate levels generally within 1-3 weeks

• widely distributed to body tissues, including breast milk)
• metabolized in liver to active metabolite oxypurinol
• 1/2life of allopurinol is 1-3 hours
• 1/2life of oxypurinol is 18-30 hours
• allopurinol (12%) & oxypurinol excreted in the urine
  

• elimination via kidney

Monitor

• serum creatinine every 6 months [7]

Adverse-effects

• common (> 10%)

• rash*, generally maculopapular
• exfoliative, urticarial or purpuric lesions

• less common (1-10%)#

• drowsiness, fever/ chills, nausea/vomiting, diarrhea, abdominal pain, gastritis, dyspepsia, alopecia, increased LFTs ( ALP, AST, ALT, bilirubin), jaundice, hepatomegaly

• uncommon (< 1%)

• hepatic necrosis, vasculitis, headache, somnolence, toxic epidermal necrolysis, Stevens-Johnson syndrome, bone marrow suppression, idiosyncratic reaction (fever/ chills, nausea/vomiting, eosinophilia, arthralgias), thrombophlebitis, peripheral neuropathy, paresthesias, neuritis, cataracts, renal impairment, epistaxis

• can worsen acute attack of gout with initiation of therapy
• * increased incidence of cutaneous & generalized hypersensitivity reactions in the elderly [5]
• # risk of adverse effects is greater with renal failure

Drug-interactions

• ampicillin & amoxicillin: increase in incidence of rash
• cyclophosphamide: increase in myelosuppression
• avoid use in combination with theophylline, mercaptopurine, or azathioprine; these drugs are metabolized by xanthine oxidase, thus may accumulate to toxic levels
• thiazide diuretics: increase in incidence of skin reactions

Mechanism-of-action

• structural analog of hypoxanthine
• reversibly inhibits xanthine dehydrogenase & xanthine oxidase
• diminishes formation of uric acid*
• diminished renal tubular resorption of uric acid

• increased renal tubular resorption of Ca+2
• reduced hypercalciuria
• attenuation of hypocalcemia

• xanthine oxidase inhibitors can reduce myocardial oxygen consumption for a particular stroke volume [8]

• * clearance of hypoxanthine & xanthine at least 10 times that of uric acid

More General Terms

• enzyme inhibitor
• anti-inflammatory agent
• metabolic agent (metabolic modifier)
• hypouricemic agent

Internet Database

PubChem: 2094
PubChem: 5281000
PubChem: 5270529

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
5. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
6. Journal Watch 25(3):24, 2005 Borstad GC, Bryant LR, Abel MP, Scroggie DA, Harris MD, Alloway JA. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol. 2004 Dec;31(12):2429-32. PMID: [1]
7. Anvita Health guideline :id 1637
   - Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: [2] (subscription needed) [3]
8. Noman A et al Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial Lancet 8 June 2010 PMID: [4] doi:10.1016/S0140-6736(10)60391-1 [5]
9. Thanassoulis G et al. Gout, allopurinol use, and heart failure outcomes. Arch Intern Med 2010 Aug 9; 170:1358. PMID: [6]

allopurinol (Zyloprim, Lopurin, Zurinol)