      Document 0191
 DOCN  DRG0191
 UNIQUE IDENTIFIER        DRG-0056
 NAME OF SUBSTANCE        Allopurinol [USAN 1996]
 REGISTRY NUMBER          315-30-0
 STANDARD CHEMICAL NAME   4H-Pyrazolo(3,4-d)pyrimidin-4-one,
                          1,5-dihydro- [USAN 1996]
 SYNONYMS                 1H-Pyrazolo(3,4-d)pyrimidin-4-ol [Merck Index
                          1989]
 SYNONYMS                 4-Hydroxypyrazolo(3,4-d)pyrimidine [Merck
                          Index 1989]
 SYNONYMS                 HHP [Merck Index 1989]
 SYNONYMS                 BW 56158 [Merck Index 1989]
 SYNONYMS                 Al-100 [Merck Index 1989]
 SYNONYMS                 Adenock [Merck Index 1989]
 SYNONYMS                 Alositol [Merck Index 1989]
 SYNONYMS                 Allozym [Merck Index 1989]
 SYNONYMS                 Allural [Merck Index 1989]
 SYNONYMS                 Aluline [Merck Index 1989]
 SYNONYMS                 Anoprolin [Merck Index 1989]
 SYNONYMS                 Anzief [Merck Index 1989]
 SYNONYMS                 Apurol [Merck Index 1989]
 SYNONYMS                 Apurin [Merck Index 1989]
 SYNONYMS                 Bleminol [Merck Index 1989]
 SYNONYMS                 Bloxanth [Merck Index 1989]
 SYNONYMS                 Caplenal [Merck Index 1989]
 SYNONYMS                 Cellidrin [Merck Index 1989]
 SYNONYMS                 Dabroson [Merck Index 1989]
 SYNONYMS                 Embarin [Merck Index 1989]
 SYNONYMS                 Epidropal [Merck Index 1989]
 SYNONYMS                 Foligan [Merck Index 1989]
 SYNONYMS                 Gichtex [Merck Index 1989]
 SYNONYMS                 Ketanrift [Merck Index 1989]
 SYNONYMS                 Ketobun-A [Merck Index 1989]
 SYNONYMS                 Lysuron [Merck Index 1989]
 SYNONYMS                 Miniplanor [Merck Index 1989]
 SYNONYMS                 Monarch [Merck Index 1989]
 SYNONYMS                 Nektrohan [Merck Index 1989]
 SYNONYMS                 Remid [Merck Index 1989]
 SYNONYMS                 Riball [Merck Index 1989]
 SYNONYMS                 Suspendol [Merck Index 1989]
 SYNONYMS                 Takanarumin [Merck Index 1989]
 SYNONYMS                 Urbol [Merck Index 1989]
 SYNONYMS                 Uricemil [Merck Index 1989]
 SYNONYMS                 Urobenyl [Merck Index 1989]
 SYNONYMS                 Urosin [Merck Index 1989]
 SYNONYMS                 Urtias 100 [Merck Index 1989]
 SYNONYMS                 Xanturat [Merck Index 1989]
 SYNONYMS                 Zyloric [Merck Index 1989]
 SYNONYMS                 1,5-Dihydro-4H-pyrazolo(3,4-d)pyrimidin-4-one
                          [PDR 1995]
 SYNONYMS                 Lopurin [AHFS Drug Information 1995]
 SYNONYMS                 Zyloprim [PDR 1995]
 SYNONYMS                 Allo-puren [Merck Index 1989]
 SYNONYMS                 Apulonga [Merck Index 1989]
 SYNONYMS                 Cosuric [Merck Index 1989]
 SYNONYMS                 dura AL [Merck Index 1989]
 SYNONYMS                 Geapur [Merck Index 1989]
 SYNONYMS                 Hamarin [Merck Index 1989]
 SYNONYMS                 Hexanurat [Merck Index 1989]
 SYNONYMS                 Ledopur [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 008
 PROTOCOL ID NUMBERS      NIAID ACTG 142
 IND NUMBER               BB 30026
 SECONDARY SOURCE ID      NSC-1390 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Acts on purine catabolism,
                          without disrupting the biosynthesis of
                          purines.  It reduces the production of uric
                          acid by inhibiting the biochemical reactions
                          immediately preceding its formation.
                          Inhibits xanthine oxidase, the enzyme
                          responsible for the conversion of
                          hypoxanthine to xanthine and of xanthine to
                          uric acid, the end product of purine
                          metabolism in man.  Allopurinol is
                          metabolized to the corresponding xanthine
                          analog oxipurinol (alloxanthine), which also
                          is an inhibitor of xanthine oxidase.
                          Reutilization of both hypoxanthine and
                          xanthine for nucleotide and nucleic acid
                          synthesis is enhanced when their oxidations
                          are inhibited by allopurinol and oxipurinal.
                          This reutilization does not disrupt normal
                          nucleic anabolism.  Allopurinol is
                          approximately 90 percent absorbed from the
                          gastrointestinal tract.  Peak plasma levels
                          generally occur at 1.5 hours and after a
                          single oral dose of 300 mg, maximum plasma
                          levels of about 3 ug/ml of allopurinol and
                          6.5 ug/ml of oxipurinol are produced.
                          Approximately 20 percent of ingested drug is
                          excreted in the feces.  Plasma half-life is
                          about 1-2 hours.  Oxypurinol, however, has a
                          plasma half-life of about 15.0 hours.
                          Allopurinol is cleared essentially by
                          glomerular filtration, but oxipurinol is
                          reabsorbed in the kidney tubules in a manner
                          similar to the reabsorption of uric acid.
                          [PDR 1995]
 DISEASES STUDIED/TREATED Especially useful in preventing hyperuricemia
                          and uric acid nephropathy resulting from
                          tissue breakdown after cancer chemotherapy or
                          radiation therapy [AHFS Drug Information
                          1995]
 CLASSIFICATION CODE      Xanthine oxidase inhibitor [AHFS Drug
                          Information 1995]
 OTHER MAJOR USES         Treatment of primary or secondary gout [PDR
                          1990] Management of elevated uric acid levels
                          in cancer chemotherapy. Management of
                          patients with recurrent calcium oxalate
                          calculi [PDR 1995]
 SUBSTANCE INTERACTIONS   In patients receiving mercaptopurine or
                          azathioprine, the concomitant administration
                          of 300-600 mg allopurinol per day requires a
                          reduction in dose to approximately one-third
                          to one-fourth of the usual dose of
                          mercaptopurine or azathioprine.  Subsequent
                          adjustment of doses of these two drugs should
                          be made on the basis of therapeutic response
                          and the appearance of toxic effects.
                          Occurrence of hypersensitivity reactions to
                          allopurinol may be increased in patients with
                          decreased renal function receiving thiazides
                          and allopurinol concurrently. The half-life
                          of the anticoagulant dicumarol has been
                          reported to be prolonged by allopurinol.  An
                          increase in the frequency of skin rash has
                          been reported among patients receiving
                          ampicillin or amoxicillin concurrently with
                          allopurinol compared to patients who are not
                          receiving both drugs.  Enhanced bone marrow
                          suppression by cyclophosphamide and other
                          cytotoxic agents has been reported among
                          patients with neoplastic disease, except
                          leukemia, in the presence of allopurinol.
                          However, in a well-controlled study of
                          patients with lymphoma on combination
                          therapy, allopurinol did not increase the
                          marrow toxicity of patients treated with
                          cyclophosphamide, doxorubicin, bleomycin,
                          procarbazine, and/or mechlorethamine.
                          Chlorpropamide's plasma half-life may be
                          prolonged by allopurinol, since allopurinol
                          and chlorpropamide may compete for excretion
                          in the renal tubule.  The risk of
                          hypoglycemia secondary to this mechanism may
                          be increased if these two drugs are given
                          concomitantly in the presence of renal
                          insufficiency. [PDR 1995]
 ADVERSE EFFECTS          The most frequent event following initiation
                          of allopurinol treatment was an increase in
                          acute attacks of gout, originally 6 percent,
                          now , 1 percent.  The most frequent adverse
                          reaction to allopurinol is skin rash, which
                          can be severe and sometimes fatal.  Some
                          patients with the most severe reaction also
                          had fever, chills, arthralgias, cholestatic
                          jaundice, eosinophilia, and mild leukocytosis
                          or leukopenia.  The most common reactions,
                          probably causally related are diarrhea,
                          nausea, alkaline phosphatase increase,
                          SGOT/SGPT increase, acute attacks of gout,
                          rash, maculopapular rash. Other reactions,
                          with an incidence < 1 percent, probably
                          causally related are: ecchymosis, fever,
                          headache, necrotizing angitis, vasculitis,
                          hepatic necrosis, granulomatous hepatitis,
                          hepatomegaly hyperbilirubinemia, cholestatic
                          jaundice, vomiting, intermittant abdominal
                          pain, gastritis, dyspepsia, thrombocytopenia,
                          eosinophilia, leukocytosis leukopenia,
                          myopathy, arthalgias, peripheral neuropathy,
                          neuritis, paresthesia, somnolence, epistaxis,
                          erythema multiform exudativum
                          (Stevens-Johnson syndrome), toxic epidermal
                          necrolysis (Lyell's syndrome),
                          hypersensitivity vasculitis, purpura,
                          vescular bullous dermatitis, exfoliative
                          dermatitis, eczematoid dermatitis, pruritis,
                          urticaria, alopecia, onycholysis, lichen
                          planus, taste loss/perversion, renal failure,
                          uremia.  Reactions with an incidence of, 1
                          percent, causal relationship unknown,
                          include: malaise, pericarditis, peripheral
                          vascular disease, thrombophlebitis,
                          bradycardia, vasodilation, infertility
                          (male), hypercalcemia, gynecomastia (male),
                          hemorrhagic pancreatitis, gastrointestinal
                          bleeding stomatitis, salivary gland swelling,
                          hyperlipidemia, tongue edema, anorexia,
                          aplastic anemia, agranulocytosis eosinophilic
                          fibrohistiocytic lesion of the bone marrow,
                          pancytopenia, prothrombin decrease, anemia,
                          hemolytic anemia, reticulocytosis,
                          lymphadenopathy, lymphocytosis, myalgia,
                          optic neuritis, confusion, dizziness,
                          vertigo, foot drop, decreases in libido,
                          depression, amnesia, pharyngitis, rhinitis,
                          furunculosis, facial edema, sweating, skin
                          edema, cataracts, macular retinitis, iritis,
                          conjunctivitis, amblyopia, nephritis,
                          impotence, primary hematuria, albuminuria.
                          [PDR 1995]
 CONTRAINDICATIONS        Patients who have developed a severe reaction
                          to allopurinol should not be restarted on the
                          drug. Treatment should be discontinued at the
                          first sign of a skin rash. In patients with
                          pre-existing liver disease, periodic liver
                          function tests are recommended during early
                          stages of treatment. Hypersensitivity
                          reactions to allopurinol may be increased in
                          patients with decreased renal functions
                          Experience with the drug during human
                          pregnancy is limited, but because of adverse
                          effects in some animal studies, allopurinol
                          should be used during pregnancy only if
                          clearly needed. Since the effects of
                          allopurinol on the nursing infant are
                          unknown, caution should be used when the drug
                          is administered to nursing women. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Structural analogue of
                          hypoxanthine [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C5H4N4O [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 136.11 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: > 350 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C44.13%,
                          H2.96%, N41.17%, O11.76% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: 0.48 mg/ml in water; 0.3 mg/ml in
                          ethanol; 4.6 mg/ml in DMSO [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM:  Tablets (100 and 300 mg). [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY:  Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE:  Store at 15-25 C in a dry place.
                          [PDR 1995]
 MANUFACTURERS            Barr Laboratories Incorporated
 MANUFACTURERS            Geneva Generics Incorporated
 MANUFACTURERS            Par Pharmaceuticals Incorporated
 MANUFACTURERS            Boots Pharmaceuticals Incorporated
 MANUFACTURERS            Glaxo Wellcome
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                          leukemia. Acta Haematol. 1994;91(4):171-4.
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 ENTRY MONTH              8909
 LAST REVISION DATE       960612
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
