Allopurinol

1. ALLOPURINOL
Most.SoniaKhatun
Roll:559
Department Of Pharmacy

2. Chemical Structure
eOxidase
Allopurinol isknownchemicallyas1,5 Dihydro-4H-
pyrazolo[3,4-d ]pyrimidin-4-one.
Category: Uricosuric agent(Antigout, Xanthin
Inhibitor)
History:
Allopurinol wasfirst synthesizedand reported in 1956 byRoland K.
Robins (1926-1992), in asearchfor antineoplasitic agents.
Allopurinol hasbeenmarketedin the United StatessinceAugust 19,
1966, whenit wasfirst approvedbyFDAunder the trade nameof
Zyloprim.Allopurinol wasmarketedat the time byBurroughs-
Wellcome.

3. Mechanism of Action
Allopurinol and its metabolite, oxypurinol (alloxanthine) decrease
the production of uric acid by inhibiting the action of xanthine
oxidase, the enzyme that converts hypoxanthine to xanthine and
xanthine to uric acid. Allopurinol also increases reutilization of
hypoxanthine and xanthine for nucleotide and nucleic acid
synthesis; the resultant increase in nucleotide concentration leads
to feedback inhibition of de novo purine synthesis. Allopurinol
thereby decreasesuric acid concentrations in both serumand urine
byinhibiting uricacid formation.

4. Indication
FDA-Labeled Indications
Calciumrenal calculus,recurrent
Cancer- Hyperuricemia
Gout
Hyperuricemia - Tumor lysis syndrome

5. Non-FDA Labeled Indications
Disorder of hematopoietic structure - Hyperuricemia
Hyperuricemia, thiazide-induced
Leishmaniasis
Malaria

6. Dosage & Route Of
Administration
Calcium renal calculus, recurrent: 200 to 300 mg Orally
asasingleor divided dose (2-3 times daily); maximum dose:
800 mg/day
Gout: (mild) 100-300 mg/day Orally as a single or divided
dose(2-3 times daily)
Adult dose

7. Gout: (moderate to severe) 400-600 mg/day Orally as a
single or divided dose (2-3 times daily); maximum dose 800
mg/day
Hyperuricemia - Tumor lysis syndrome: 600 to 800
mg/day Orally for 2 or 3 days; MAX daily dose, 800 mg , 12
hours to 3 daysprior to initiation of chemotherapy

8. Pediatric Dosing
Cancer - Hyperuricemia: (under 6 y) 150 mg PO daily,
evaluateresponseafter 48 hour and dose adjust accordingly
Cancer - Hyperuricemia: (6 to 10 y) 300 mg PO daily,
evaluateresponseafter 48 hour and doseadjust accordingly
Hyperuricemia - Tumor lysis syndrome: (under 6 years) 150
mgOrally oncedailyfor 2 to 3 days
Hyperuricemia - Tumor lysis syndrome: (6 to 10 years) 300
mgOrally oncedailyfor 2 to 3 days

9. Pharmacokinetics
• Rapidly absorbed in the upper
gastrointestinal tract
• It has plasma half-life of about 1 hour and
is rapidly into main metabolite,
oxipurinol.
• It is slowly excreted by the kidneys over
18-30hours
• Allupurinol excreted mainly via the
kidneys.

10. Contraindication & Precaution
Contraindications
Concomitant usewith didanosine
Hypersensitivityto allopurinol
Precautions
Allergicreaction mayoccur;discontinue at first sign
Liverdisease;monitoring recommended
Renal function, decreased; risk of worsening condition;
monitoring and dosageadjustment recommended

11. Pregnancy Category & Breast
Feeding
Pregnancy Category
Category -C
Breast Feeding
Compatible with breastfeeding

12. Adverse drug reactions
(ADRS)
Common
Dermatologic: Maculopapular eruption, Pruritus (less
than 1% )
Serious
Dermatologic: Rash (less than 1% ), Stevens-Johnson
syndrome (less than 1% ), Toxic epidermal necrolysis (less
than 1% )
Hematologic: Agranulocytosis, Aplastic anemia,
Eosinophilia, Myelosuppression,Thrombocytopenia
(0.6%)

13. 1% ),Hepatic: Granulomatous hepatitis (less than
Hepatic necrosis(lessthan 1% ), Hepatotoxicity
Immunologic: Immunehypersensitivityreaction
Renal: Renal failure (lessthan 1% )

14. Treatment In Allopurinol & Toxicity
Support:
Management Of Mild To Moderate Toxicity : Treatment is
symptomaticand supportive.
Management Of Severe Toxicity: Treatment is symptomatic
and supportive. In patients with acute allergic reaction, oxygen
therapy, bronchodilators, diphenhydramine, corticosteroids,
vasopressorsand epinephrinemaybe required.
Decontamination:
Airway management: Ensure adequate ventilation and
perform endotracheal intubation early in patients with severe
allergic reactions.
Antidote: None.

15. Hypersensitivity reaction:
Mild/Moderate: Antihistamines with or without
inhaled beta agonists, corticosteroids or epinephrine.
Severe: Oxygen,aggressiveairwaymanagement,
antihistamines, epinephrine (Adult: 0.3 to 0.5 mLof a1:1000
solutionsubcutaneously;
Child:0.01mL/kg, 0.5 mL max;may repeat in 20 to
30 min), corticosteroids, ECG monitoring, and IV fluids.

16. Monitoring of patient: Monitor renal function and liver enzymes in
symptomatic patients. Monitor CBC after significant overdose. Monitor
serumelectrolytesin patients with significantvomitingand/or diarrhea.
Enhanced elimination procedure: Allopurinol and oxypurinol are
removedduring hemodialysis.

17. This isnot an innocuous drug. it isnot recommended for
the treatment of asymptomatic hyperuricemia
Allopurinol should bediscontinued at the first appearanceof
skin rash or other signs of an allergic reaction
Allopurinol- Black box Warning

18. Patient Education
Warn patient to immediately report a skin rash or signs/symptoms of an allergic reaction
(painful urination, blood in the urine, irritation of the eyes, or swelling of the lips or
mouth) asdrug maycausesevere,sometimes fatal, hypersensitivityreactions.
Drug maycausediarrhea, nausea.
Instruct patient to report signs/symptoms of hepatotoxicity (anorexia, weight loss, or
pruritus).
Advisepatient that optimal benefitmaybedelayedfor 2 to 6 weeks.
Counselpatient to take drug after mealsto reducegastric irritation.
Encouragepatient to maintain adequatehydration duringtherapy to preventrenal stones
Take the missed dose as soon as you remember. If it is almost time for your next dose,
skip the missed dose and take the medicine at your next regularly scheduled time. Do not
take extramedicineto makeup the missed dose.