Module 3: Allopurinol Flashcards
What pharmacological category is allopurinol?
Xanthine Oxidase Inhibitor
What are common indications for allopurinol?
Used in the treatment of gout
Nephrolithiasis, prevention of recurrent calcium or uric acid stones
Tumor lysis syndrome, prevention of hyperuricemia associated with malignancy.
What is the MOA for allopurinol?
Inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase. Allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.
What are the pharmacokinetic considerations for allopurinol?
A: Oral - 90% from gI tract.
D: Vss: approx 0.8 +-0.13 L/kg
M: Rapidly oxidized via the liver to active metabolites, primarily oxypurinol.
E: Urine and feces
Onset: Gout - decreased serum and urine uric acid 2-3 days. Peak: 1 week or longer, normal serum urate levels achieved within 1-3 weeks.
Peak plasma: oral - 1.5 hours, oxypurinol - 23.5 +- 4.5 hours
Half-life elimination: Oral 1-2 hours. Oxypurinol approx 15 hours.
What are some special prescribing considerations for allopurinol (not related to pregnancy and breastfeeding)?
SCAR = severe cutaneous adverse reactions.
- test for HLA-B*5801 allele in patients = elevated risk
- Asian (Korean, Han Chinese, Thai) and African descent.
- avoid using long term when positive for allele
Allopurinol hypersensitivity syndrome (AHS)
- increased risk with renal impairment
- in absence of HLA-B*5801 or not high-risk, dose adjustment can be made
Liver impairment - do dosage adjustment needed unless allopurinol-induced liver injury is confirmed
What are pregnancy and lactation considerations for allopurinol?
Pregnancy = crosses placenta. Use during first trimester avoided. Close monitoring required.
Lactation = found in breastmilk. Not recommended until 1 week after last dose.
What are common side effects of allopurinol?
- increase in gout attack
- rash
- drowsiness
- abnormal liver function tests
- nausea, vomiting, diarrhea
- kidney problems
What are significant adverse effects of allopurinol?
Acute gout attack
Hypersensitivity reactions (allopurinol hypersensitivity syndrome = AHS)
- maculopapular rash to SCAR
- drug reaction with eosinophilia and systemic symptoms (DRESS)
- hepatotoxicity usually assoc with AHS and DRESS
NOTE: DRESS = rare, potentially life-threatening reaction to certain medications that can affect the skin, blood and internal organs.
What are significant drug interactions with allopurinol?
- Azathioprine and 6-mercaptopurine increases bone marrow depressant properties - doses of these drugs should be decreased
- Use with ampicillin or amoxicillin increases risk of rash
- Use with oral hypoglycemic agents and warfarin increase effects of these drugs
- Use with thiazide diuretics or ACE inhibitors increase risk of hypersensitivity reactions
- Large doses of allopurinol may increase risk of theophylline toxicity
- May increase cyclosporine levels
What are contraindications/ cautions for use of allopurinol?
Hypersensitivity
+HLA-B*5801 allele (increased risk for SCAR)
Dose reduction with renal impairment
