Allopurinol

Class: Xanthine Oxidase Inhibitor; Antigout
Dosage Forms.Tablet: 100 mg, 200 mg, 300 mg

MOA. Allopurinol decreases the production of uric acid by inhibiting the action of xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid.

• Gout, mild: 100-300 mg po daily max dose 800 mg/d
• Gout, moderate to severe: 400-600 mg po daily in 2-3 divided doses, max dose 800 mg/d
• Hyperuricemia, tumor lysis syndrome: Children <6 y, 50 mg po tid or 150 mg po daily for 2-3 d; Children 6-10 y, 100 mg po tid or 300 mg po daily for 2-3 d; Adults, 600-800 mg/d po daily in 2-3 divided doses for 2-3 d; starting 12 h-3 d prior to chemotherapy
• Nephrolithiasis prophylaxis due to calcium stones: 300 mg/d divided in 1-3 doses
• Off-Label Uses:
• Nephrolithiasis prophylaxis due to uric acid stones: 300 mg/d divided in 1-3 doses

Dose Adjustment Hepatic	Not required	Absorption	F = 80-90%, no effect of food on absorption
Dose Adjustment Renal	CrCl >30-60 mL/min: 50 mg po daily initially; CrCl >15-30 mL/min: 50 mg po every other day initially; CrCl 5-10 mL/min: 50 mg po twice weekly initially; CrCl <5 mL/min: 50 mg po once weekly initially	Distribution	Vd = 1.6-2.43 L/kg; <1% protein bound
Dialyzable	Yes, 100 mg po 3 times weekly administered post-dialysis	Metabolism	Hepatic (78%) and red blood cells
Box Warnings	None	Elimination	Renal 80% with a half-life of 2 h (parent compound), 15-25 h (active metabolite, oxypurinol)
Contraindications	Hypersensitivity to allopurinol, concurrent use of didanosine	Pharmacogenetics	None known
Briggs Pregnancy Recommendation		Limited human data—no relevant animal data
Briggs Breastfeeding Recommendation		Limited human data—potential toxicity

• Use with mercaptopurine and azathioprine ↑ bone marrow depressant properties–doses of these drugs should be ↓.
• Use with ampicillin or amoxicillin ↑ risk of rash.
• Use with oral hypoglycemic agents and warfarin ↑ effects of these drugs.
• Use with thiazide diuretics or ACE inhibitors ↑ risk of hypersensitivity reactions.
• Large doses of allopurinol may ↑ risk of theophylline toxicity.
• May ↑ cyclosporine levels.

• CV: Bradycardia, flushing, heart failure (reported with IV administration), hypertension, hypotension
• Derm: Rash (discontinue drug at first sign of rash), DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria 
• GI: Diarrhea, hepatitis, nausea, vomiting
• GU: Hematuria, renal failure
• Hemat: Bone marrow depression
• Neuro: Drowsiness 
• Misc: HYPERSENSITIVITY REACTIONS

*CAPITALS indicate life-threatening. Underline indicate most frequent.

• Efficacy Monitoring Parameters: Resolution of clinical signs of gout (pain, stiffness), serum uric acid concentrations measured after 48 h of therapy.
• Toxicity Monitoring Parameters: LFTs, renal function, CBC.
• Key Patient Counseling Points: Take after meals to lessen gastric irritation. Maintain adequate hydration during therapy to prevent kidney stones. Patient should avoid alcohol and caffeine while taking allopurinol. Seek medical attention if signs and symptoms of myelosuppression, agranulocytosis (severe neutropenia), or Stevens-Johnson syndrome (flulike symptoms, spreading red rash, or skin/mucous membrane blistering) occur.
• Clinical Pearls: Allopurinol for injection is also available and has been designated an orphan product for use in the treatment of elevated serum or urinary uric acid levels secondary to lymphomas, leukemias, or solid tumors in patients intolerant of oral therapy. Since not for acute treatment, patient adherence is critical to treatment success. Full effect of allopurinol in chronic gout may take 2-6 wk, slow-dose titration is recommended.