1. ALLOPURINOL
Y09PHD0103
V/VI Pharm.D
Dept. Of Pharmacy Practice
Run By: Chalapathi Institute Of Pharmaceutical Sciences
GGH, Guntur

2. Chemical Structure
Allopurinol is known chemically as 1,5 Dihydro-4Hpyrazolo[3,4-d ]pyrimidin-4-one.
Category: Uricosuric agent(Antigout, Xanthine Oxidase
Inhibitor)
History:
Allopurinol was first synthesized and reported in 1956 by Roland K.
Robins (1926-1992), in a search for antineoplasitic agents.
Allopurinol has been marketed in the United States since August 19,
1966, when it was first approved by FDA under the trade name of
Zyloprim. Allopurinol was marketed at the time by BurroughsWellcome.

3. Brands & Prices In India
Trade Name &Mnfu.
Company Name
Dosage Form &
strength
PRICE (Rps)
ALLGORIC TAB
KAMRON LAB
100mg
300 mg
10 - 19.70
10- 40.00
APLLINOL TAB
SYNTONIC LIFE SCIENCES
100 mg
300mg
10
- 27.30
10 - 49.00
CIPLORIC, TAB
CIPLA
100 mg
300mg
10- 25.85
10- 49.80
LODIRIC TAB , CAP-SR
NOVARTIS
100mg
250mg
10- 20.00
10- 65.00
UREKA TAB
CHEMO BIOLOGICAL
100mg
300mg
10-18.50
10-48.00
ZYLORIC TAB
GLAXO SMITHKLINE
100mg
300mg
10-34.25
10-81.75

4. 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.

5. Allopurinol thereby decreases uric acid concentrations
in both serum and urine by inhibiting uric acid
formation.

6. Schematic diagram of the purine
degradation pathway

7. oxypurinol
allopurinol
inhibits xanthine
oxidase
uric acid

8. Indications
FDA-Labeled Indications
Calcium renal calculus, recurrent
Cancer - Hyperuricemia
Gout
Hyperuricemia - Tumor lysis syndrome

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

10. Dosage &Route Of
Administration
ADULT DOSING
Calcium renal calculus, recurrent: 200 to 300 mg Orally
as a single or 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)

11. 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 days prior to initiation of chemotherapy

12. Pediatric Dosing
Cancer - Hyperuricemia: (under 6 y) 150 mg PO daily,
evaluate response after 48 hour and dose adjust accordingly
Cancer - Hyperuricemia: (6 to 10 y) 300 mg PO daily,
evaluate response after 48 hour and dose adjust
accordingly
Hyperuricemia - Tumor lysis syndrome: (under 6 years) 150
mg Orally once daily for 2 to 3 days
Hyperuricemia - Tumor lysis syndrome: (6 to 10 years) 300
mg Orally once daily for 2 to 3 days

13. Dose Adjustments
Maintenance dose should be based on serum uric acid
determinations performed 48 hours after initial dose
Renal impairment: CrCL 10 to 20 mL/min, 200 mg daily
Renal impairment: CrCL 3 to 10 mL/min, 100 mg daily
Renal impairment: CrCL less than 3 mL/min, 100 mg at
extended intervals greater than every 24 hours

14. Pharmacokinetics
Absorption
Tmax, Oral: 1.5 hours (allopurinol), 4.5 hours
(oxipurinol)
Bioavailability, Oral: 80% to 90%
Onset: Initial effect: 2-3 d, peak effect: 7-14 days
Distribution
Vd: 1.6 L/kg (allopurinol)
Protein Bound: <1%
Metabolism
Liver: 70%
Oxypurinol: active

15. Excretion
Renal clearance: approx GFR (allopurinol) ; 16.5
mL/minute (oxipurinol)
Renal: approximately 80%, Feces: 20%
Total body clearance: 15.7 mL/min/kg .
Elimination Half Life
Allopurinol: 1 to 2 hours ; Oxipurinol: 15 h (range 12
to 30 h)
Administration
Oral - better tolerated if administered following meals

16. Contraindications &
Precautions
Contraindications
Concomitant use with didanosine
Hypersensitivity to allopurinol
Precautions
Allergic reaction may occur; discontinue at first sign
Liver disease; monitoring recommended
Renal function, decreased; risk of worsening condition;
monitoring and dosage adjustment recommended

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

18. 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%
)

19. Hepatic: Granulomatous hepatitis (less than 1% ),
Hepatic necrosis (less than 1% ), Hepatotoxicity
Immunologic: Immune hypersensitivity reaction
Renal: Renal failure (less than 1% )

20. Drug-Drug Interactions
DRUGS
SEVERIT
Y
SUMMARY
ALLOPURINOL -DIDANOSINE
Contraindicated
result in increased serum concentrations
of didanosine. (Decre M)
AZATHIOPRINE -ALLOPURINOL
Major
result in azathioprine toxicity by decre M
(nausea, vomiting, leukopenia, anemia).
MERCAPTOPURINE -ALLOPURINOL
Major
result in mercaptopurine toxicity by decre
M (bone marrow suppression, nausea,
vomiting). Management: reduce dose to
25-35% during concurrent admin.

21. ALUMINUM
HYDROXIDE -ALLOPURINOL
Moderate
may result in decreased
allopurinol
effectiveness(Separate by 2
hours) decre A
CYCLOSPORINE -ALLOPURINOL
Moderate
result in an increased risk of
cyclosporine toxicity (renal
dysfunction, cholestasis,
paresthesias). unknown mechanism
WARFARIN
POTASSIUM -ALLOPURINOL
Moderate
result in an increased risk of
bleeding. (Decre M)
Management: consider monitoring
CT, aPTT, INR and administer vitk accordingly

22. Monitoring
Serum uric acid levels; goal of serum uric acid level in adults
is 6 mg/dL or less
Hyperuricosuria: 24-hour urinary urate excretion to
determine best dose and frequency for efficacy
Pain relief is indicative of efficacy
Liver function tests; periodically with preexisting liver disease,
or if anorexia, weight loss, or pruritus develop in any patient
renal function tests; periodically if renal impairment is present
or if concomitant conditions affecting renal function (eg,
hypertension, diabetes mellitus) are present

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

24. Myelosuppression:
(leukocytosis,
leukopenia,
eosinophilia,
thrombocytopenia, granulocytopenia, and fatal bone marrow
suppression); these effects may be the result of concomitant use of other
myelosuppressive drugs.
Treat severe neutropenia with filgrastim 5 mcg/kg/day IV infused over 4
hours. Monitor serial CBC with differential.
Hypersensitivity reaction:
Mild/Moderate: Antihistamines with or without inhaled beta agonists,
corticosteroids or epinephrine.
Severe: Oxygen, aggressive airway management, antihistamines, epinephrine
(Adult: 0.3 to 0.5 mL of a 1:1000 solution subcutaneously;
Child: 0.01 mL/kg, 0.5 mL max; may repeat in 20 to 30 min),
corticosteroids, ECG monitoring, and IV fluids.

25. Monitoring of patient: Monitor renal function and liver enzymes in
symptomatic patients. Monitor CBC after significant overdose. Monitor
serum electrolytes in patients with significant vomiting and/or diarrhea.
Enhanced elimination procedure: Allopurinol and oxypurinol are
removed during hemodialysis.

26. Allopurinol – black box warning
THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT
RECOMMENDED FOR THE TREATMENT OF
ASYMPTOMATIC HYPERURICEMIA
ALLOPURINOL SHOULD BE DISCONTINUED AT
THE FIRST APPEARANCE OF SKIN RASH OR
OTHER SIGNS OF AN ALLERGIC REACTION

27. 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) as drug may cause severe, sometimes fatal, hypersensitivity reactions.
Drug may cause diarrhea, nausea.
Instruct patient to report signs/symptoms of hepatotoxicity (anorexia, weight loss, or
pruritus).
Advise patient that optimal benefit may be delayed for 2 to 6 weeks.
Counsel patient to take drug after meals to reduce gastric irritation.
Encourage patient to maintain adequate hydration during therapy to prevent renal
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 extra medicine to make up the missed dose.

28. REFFERENCES
http://reference.medscape.com/drug/zyloprim-aloprim-allopurinol342811#91
http://www.micromedexsolutions.com
http://www.drugsupdate.com/generic/view/115
http://www.drugs.com/allopurinol.html
http://www.medlineindia.com/metabolism/allopurinol.htm
http://www.drugsupdate.com/brand/showavailablebrands/115/2