Allopurinol

Aka: Allopurinol, Zyloprim, Xanthine Oxidase Inhibitor

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II. Indications: Uric Acid Lowering Therapy In Gout

  1. Gout Prophylaxis (first-line agent)
    1. Uric Acid over-producers (Uric Acid > 750 mg/24h)
    2. Used in Uric Acid under-excreters as well
  2. Criteria
    1. Recurrent episode of gout (>=2 attacks per year, and consider for 1 gout flare/year)
    2. Tophaceous gout
    3. Radiographic damage attributable to gout
    4. Nephrolithiasis

III. Indications: Other

  1. Tumor Lysis Syndrome Prevention
  2. Calcium oxylate stone Prevention (in Calcium Nephrolithiasis)

IV. Precautions

  1. Avoid use with Azathioprine (causes toxic levels)
  2. Avoid in Renal Failure (or use low dose)
  3. Do not use for asymptomatic Hyperuricemia
  4. Genetic Testing (HLA B5801)
    1. Obtain prior to use if risk of severe Hypersensitivity skin reaction
    2. Risks include southeast asian (esp. Hans Chinese, Thai, Korean) and African American
  5. Avoid in acute gout attack (wait at least 4-6 weeks after acute attack)
    1. However, more recent data suggests safety in starting during acute attack (per email, Dr. John Rasor)
      1. Eminaga (2016) Rheumatol Int 36(12):1747-52 +PMID:27761603 [PubMed]
      2. Hill (2015) J Clin Rheumatol 21(3):120-5 +PMID:25807090 [PubMed]
      3. Taylor (2012) Am J Med 125(11):1126-1134 +PMID:23098865 [PubMed]

V. Mechanism

  1. Xanthine oxidase
    1. Enzyme that converts oxypurines (including Nucleic Acids) to Uric Acid
  2. Xanthine Oxidase Inhibitor
    1. Allopurinol is an isomer of hypoxanthine and is metabolized to the active oxypurinol
    2. Oxypurinol inhibits xanthine oxidase Enzyme Activity, thereby inhibiting Uric Acid formation
    3. Oxypurinol is renally excreted
    4. Allopurinol increases renal xanthine excretion (since it is not converted to Uric Acid)
      1. Renal xanthines may crystallize in the renal tubules resulting in obstructive uropathy

VI. Medications

  1. Allopurinol Tablets: 100 mg, 300 mg

VII. Dosing: Gouty Arthritis

  1. See Gouty Arthritis
  2. Use concurrent antiinflammatory agent when starting to prevent triggering attack
    1. Wait to start Allopurinol until at least 6-8 weeks symptom-free from last attack
      1. However, see precautions above for recent data suggesting safety in starting with acute attack
    2. Antiinflammatory agent options to start concurrently with Allopurinol (continue for first 3-6 months)
      1. NSAIDS (avoid in Chronic Kidney Disease, heart disease or liver disease)
        1. Aleve 220 mg (OTC) orally twice daily or
        2. Naprosyn 250 mg orally twice daily or
        3. Indomethacin 25 mg orally twice daily
      2. Prednisone (if NSAIDs contraindicated)
        1. Maintenance: 10 mg orally daily, then 5 mg orally daily for 3-6 months
        2. Acute Exacerbation (start at first symptoms of gout recurrence): 40 mg orally for 1-3 days
          1. Have available as emergency prescription
      3. Colchicine
        1. Colchicine was a first line agent for Allopurinol initiation (but now too expensive)
          1. Generic preparations were removed from market
        2. Colchicine 0.6 mg PO daily to twice daily
  3. Allopurinol 100-300 mg/day
    1. Use lowest dose to keep Uric Acid <6 mg/dl (<5 mg/dl if symptomatic)
      1. Probenacid may be used with Allopurinol if GFR>50 ml/min and normal Urine Uric Acid normal
      2. Duzallo (Allopurinol with Lesinurad) is an expensive alternative to Probenacid and Allopurinol
    2. Initiating dose
      1. Start: 100 mg daily for 2 weeks
      2. Next: 200 mg daily for 2 weeks
      3. Next: 300 mg daily (most effective dose for most patients)
      4. Some patients require higher doses
        1. Moderate to high dosing is 400 to 600 mg/day
        2. High doses may be needed up to 600 to 800 mg/day) to maintain Uric Acid <6 mg/dl
    3. Adjust starting dose for Renal Function
      1. GFR >90 ml/min: 300 mg daily
      2. GFR 60-89 ml/min: 200 mg daily
      3. GFR 30-59 ml/min: 100 mg daily
      4. GFR 10-29 ml/min (or Cr >1.5): 50 mg daily (maximum dose 300 mg/day)
      5. GFR <10 ml/minute: Avoid or use with caution

VIII. Dosing: Tumor Lysis Syndrome Prevention

  1. Start 24 to 48 hours before Chemotherapy
  2. Adult
    1. IV: 200 to 400 mg/m2/day (max 600 mg/day) IV in one infusion or divided every 6 to 12 hours
    2. Oral: 600 mg orally daily (or in divided doses)
  3. Child
    1. IV: 200 mg/m2/day (max 600 mg/day) IV in one infusion or divided every 6 to 12 hours
    2. Oral: 10 mg/kg/day (max: 800 mg/day) orally divided every 8 hours
      1. Age <6 years: 150 mg orally daily or divided every 8 hours
      2. Age 6 to 10 years: 300 orally daily or divided every 8 hoiurs

IX. Dosing: Miscellaneous

  1. Calcium Oxalate Stone prevention
    1. Indicated in Calcium Oxalate Stones regardless of Uric Acid level
    2. Start Allopurinol 100 mg orally daily
    3. Advance to 2 to 3 times daily

X. Adverse Effects (more common with renal dysfunction)

  1. May precipitate acute gout attack (never start during active gout attack)
    1. See Dosing above for protocol using NSAIDs or Colchicine concurrently
  2. Severe Hypersensitivity Syndrome (presents as dermatitis, Pruritus)
    1. Varies from mild rash to Stevens Johnson Syndrome
    2. Genetic Testing (HLA B5801) prior to use if Hans Chinese, Thai or if CKD 3, Korean
    3. Stop Allopurinol if this occurs
    4. Increased risk when concurrent use of Bendamustine, Thiazide Diuretics, Ampicillin or Amoxicillin
  3. Toxic Hepatitis
  4. Gastrointestinal (Nausea, Diarrhea)
  5. Myelosuppression (Cytopenias)
  6. Nephrotoxicity
    1. Maximize hydration before dosing (esp. IV dosing)

XI. Safety

  1. Unknown safety in pregnancy
  2. Considered safe in Lactation
  3. Monitoring: Obtain 6 weeks after starting Allopurinol
    1. Complete Blood Count (CBC)
    2. Alanine Aminotransferase (ALT)
    3. Serum Creatinine
    4. Serum Uric Acid

XII. Drug Interactions

  1. Mercaptopurine
    1. Reduce Mercaptopurine dose by 75% (Increased toxicity risk)
  2. Azathioprine
    1. Reduce Azathioprine dose by 75% (Increased toxicity risk)
  3. Warfarin
    1. Allopurinal increases INR
  4. Capecitabine
    1. Do not use with Allopurinol
  5. Pegloticase
    1. Do not use with Allopurinol

XIII. Resources

  1. Allopurinol (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fbac3b4f-dc23-4359-ac3f-2b3fdde41af2

XIV. References

  1. (2018) Presc Lett 25(9):50-1
  2. Eggebeen (2007) Am Fam Physician 76:801-12 [PubMed]
  3. Hainer (2014) Am Fam Physician 90(12): 831-6 [PubMed]

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Cost: Medications

allopurinol (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ALLOPURINOL 100 MG TABLET Generic $0.05 each
ALLOPURINOL 300 MG TABLET Generic $0.07 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

Ontology: Allopurinol (C0002144)

Definition (CHV) a kind of gout treatment drug
Definition (NCI) A structural isomer of hypoxanthine. Allopurinol inhibits xanthine oxidase, an enzyme that converts oxypurines to uric acid. By blocking the production of uric acid, this agent decreases serum and urine concentrations of uric acid, thereby providing protection against uric acid-mediated end organ damage in conditions associated with excessive production of uric acid, i.e. the massive cell lysis associated with the treatment of some malignancies. (NCI04)
Definition (NCI_NCI-GLOSS) A drug that lowers high levels of uric acid (a byproduct of metabolism) in the blood caused by some cancer treatments.
Definition (MSH) A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.
Definition (CSP) drug used to treat gout and other conditions in which there is an excessive buildup of uric acid.
Definition (PDQ) A structural isomer of hypoxanthine. Allopurinol inhibits xanthine oxidase, an enzyme that converts oxypurines to uric acid. By blocking the production of uric acid, this agent decreases serum and urine concentrations of uric acid, thereby providing protection against uric acid-mediated end organ damage in conditions associated with excessive production of uric acid, i.e. the massive cell lysis associated with the treatment of some malignancies. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38452&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38452&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C224" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D000493
SnomedCT 391735003, 387135004, 25246002
LNC LP17988-4, MTHU024809
English Allopurinol, 4H-Pyrazolo(3,4-d)pyrimidin-4-one, 1,5-dihydro-, 1H-Pyrazolo[3,4-d]pyrimidin-4-ol, 4-Hydroxypyrazolo[3,4-d]pyrimidine, 1,5-Dihydro-4H-pyrazolo[3,4-d]pryimidin-4-one, allopurinol, 4'-HPP, allopurinol (medication), ALLOPURINOL, Allopurinol [Chemical/Ingredient], allopurinol sodium (as allopurinol), Allopurinol - chemical (substance), Allopurinol - chemical, 1,5-Dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one, Allopurinol (product), Allopurinol (substance), ALLO
Swedish Allopurinol
Czech alopurinol
Finnish Allopurinoli
Russian ALLOPURINOL, АЛЛОПУРИНОЛ
Japanese アロプリノール
Croatian ALOPURINOL
Polish Allopurinol, Zyloprin
Spanish alopurinol - sustancia química (sustancia), alopurinol - sustancia química, alopurinol (producto), alopurinol (sustancia), alopurinol, Alopurinol
French Allopurinol
German Allopurinol
Italian Allopurinolo
Portuguese Alopurinol
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Zyloprim (C0701096)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D000493
English zyloric, zyloprim, Zyloric, Glaxo Wellcome Brand of Allopurinol, Wellcome Brand of Allopurinol, Allopurinol Wellcome Brand, Zyloprim
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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