ALLOPURINOL
Y09PHD0103
V/VI Pharm.D
Dept. Of Pharmacy Practice
Run By: Chalapathi Institute Of Pharmaceutical Sciences
GGH...
Chemical Structure
Allopurinol is known chemically as 1,5 Dihydro-4Hpyrazolo[3,4-d ]pyrimidin-4-one.
Category: Uricosuric ...
Brands & Prices In India
Trade Name &Mnfu.
Company Name

Dosage Form &
strength

PRICE (Rps)

ALLGORIC TAB
KAMRON LAB

100...
Mechanism Of
Action
Allopurinol and its metabolite, oxypurinol (alloxanthine),
decrease the production of uric acid by inh...
Allopurinol thereby decreases uric acid concentrations
in both serum and urine by inhibiting uric acid
formation.
Schematic diagram of the purine
degradation pathway
oxypurinol
allopurinol
inhibits xanthine
oxidase
uric acid
Indications
FDA-Labeled Indications
Calcium renal calculus, recurrent
Cancer - Hyperuricemia
Gout
Hyperuricemia - Tumor ly...
Non-FDA Labeled Indications
Disorder of hematopoietic structure - Hyperuricemia
Hyperuricemia, thiazide-induced
Leishmania...
Dosage &Route Of
Administration

ADULT DOSING

Calcium renal calculus, recurrent: 200 to 300 mg Orally

as a single or div...
Gout: (moderate to severe) 400-600 mg/day Orally as a

single or divided dose (2-3 times daily); maximum dose 800
mg/day

...
Pediatric Dosing
Cancer - Hyperuricemia: (under 6 y) 150 mg PO daily,

evaluate response after 48 hour and dose adjust acc...
Dose Adjustments
Maintenance dose should be based on serum uric acid
determinations performed 48 hours after initial dose
...
Pharmacokinetics
Absorption
Tmax, Oral: 1.5 hours (allopurinol), 4.5 hours
(oxipurinol) 
Bioavailability, Oral: 80% to 90%...
Excretion
Renal clearance: approx GFR (allopurinol) ; 16.5
mL/minute (oxipurinol) 
Renal: approximately 80%, Feces: 20% 
T...
Contraindications &
Precautions
Contraindications
Concomitant use with didanosine 
Hypersensitivity to allopurinol 

Preca...
Pregnancy Category & Breast
Feeding
Pregnancy Category
Category -C

Breast Feeding
Compatible with breastfeeding
Adverse drug reactions
(ADRS)

Common
Dermatologic: Maculopapular eruption, Pruritus (less
than 1% )
Serious
Dermatologic:...
Hepatic: Granulomatous hepatitis (less than 1% ),
Hepatic necrosis (less than 1% ), Hepatotoxicity
Immunologic: Immune hyp...
Drug-Drug  Interactions  
DRUGS

SEVERIT
Y

SUMMARY

ALLOPURINOL -DIDANOSINE

 Contraindicated

result in increased serum ...
ALUMINUM
HYDROXIDE -ALLOPURINOL

Moderate

may result in decreased
allopurinol
effectiveness(Separate by 2
hours) decre A
...
Monitoring
Serum uric acid levels; goal of serum uric acid level in adults
is 6 mg/dL or less 
Hyperuricosuria: 24-hour ur...
Treatment In Allopurinol
Toxicity

Support:
Management Of Mild To Moderate Toxicity : Treatment
is symptomatic and support...
Myelosuppression:
(leukocytosis,
leukopenia,
eosinophilia,
thrombocytopenia, granulocytopenia, and fatal bone marrow
suppr...
Monitoring of patient: Monitor renal function and liver enzymes in
symptomatic patients. Monitor CBC after significant ove...
Allopurinol – black box warning
THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT
RECOMMENDED FOR THE TREATMENT OF
ASYMPTOMATIC HYP...
Patient Education
Warn patient to immediately report a skin rash or signs/symptoms of an allergic
reaction (painful urinat...
REFFERENCES
http://reference.medscape.com/drug/zyloprim-aloprim-allopurinol342811#91
http://www.micromedexsolutions.com
ht...
Allopurinol drug information
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Allopurinol drug information

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Allopurinol drug information

  1. 1. ALLOPURINOL Y09PHD0103 V/VI Pharm.D Dept. Of Pharmacy Practice Run By: Chalapathi Institute Of Pharmaceutical Sciences GGH, Guntur
  2. 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. 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. 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. 5. Allopurinol thereby decreases uric acid concentrations in both serum and urine by inhibiting uric acid formation.
  6. 6. Schematic diagram of the purine degradation pathway
  7. 7. oxypurinol allopurinol inhibits xanthine oxidase uric acid
  8. 8. Indications FDA-Labeled Indications Calcium renal calculus, recurrent Cancer - Hyperuricemia Gout Hyperuricemia - Tumor lysis syndrome
  9. 9. Non-FDA Labeled Indications Disorder of hematopoietic structure - Hyperuricemia Hyperuricemia, thiazide-induced Leishmaniasis Malaria
  10. 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. 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. 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. 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. 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. 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. 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. 17. Pregnancy Category & Breast Feeding Pregnancy Category Category -C Breast Feeding Compatible with breastfeeding
  18. 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. 19. Hepatic: Granulomatous hepatitis (less than 1% ), Hepatic necrosis (less than 1% ), Hepatotoxicity Immunologic: Immune hypersensitivity reaction Renal: Renal failure (less than 1% )
  20. 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. 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. 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. 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. 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. 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. 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. 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. 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
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