      Document 0245
 DOCN  DRG0245
 UNIQUE IDENTIFIER        DRG-0002
 NAME OF SUBSTANCE        Leucovorin calcium [USAN 1995]
 REGISTRY NUMBER          1492-18-8
 RELATED REGISTRY NUMBER  6035-45-6 (pentahydrate)
 RELATED REGISTRY NUMBER  58-05-9 (leucovorin)
 STANDARD CHEMICAL NAME   N-(4-(((2-Amino-5-formyl-1,4,5,6,7,8-hexahydr-
                          o-4-oxo-6-
                          pteridinyl)methyl)amino)benzoyl)-L-glutamic
                          acid, calcium salt pentahydrate [USAN 1995]
 SYNONYMS                 Calcium folinate [USAN 1995]
 SYNONYMS                 Wellcovorin [USAN 1995]
 SYNONYMS                 Citrovorum factor [Merck Index 1989]
 SYNONYMS                 Folinic acid-SF [Merck Index 1989]
 SYNONYMS                 Calcium salt of the following:
 SYNONYMS                 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic
                          acid [Merck Index 1989]
 SYNONYMS                 N-(p-(((2-Amino-5-formyl-5,6,7,8-tetrahydro-4-
                          -hydroxy-6-pteridinyl)methyl)amino)benzoyl)gl-
                          utamic acid [Merck Index 1989]
 SYNONYMS                 5-Formyl-5,6,7,8-tetrahydrofolic acid [Merck
                          Index 1989]
 SYNONYMS                 CF [Merck Index 1989]
 SYNONYMS                 Leuconostoc citrovorum 8081 growth factor
                          [Merck Index 1989]
 SYNONYMS                 Leucosar [USAN 1993]
 SYNONYMS                 Rescufolin [Merck Index 1989]
 SYNONYMS                 Rescuvolin [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 008
 PROTOCOL ID NUMBERS      NIAID ACTG 009
 PROTOCOL ID NUMBERS      NIAID ACTG 018
 PROTOCOL ID NUMBERS      NIAID ACTG 029
 PROTOCOL ID NUMBERS      NIAID ACTG 030
 PROTOCOL ID NUMBERS      NIAID ACTG 031
 PROTOCOL ID NUMBERS      NIAID ACTG 039
 PROTOCOL ID NUMBERS      NIAID ACTG 074
 PROTOCOL ID NUMBERS      NIAID ACTG 077 Pilot
 PROTOCOL ID NUMBERS      NIAID ACTG 102
 PROTOCOL ID NUMBERS      NIAID ACTG 142
 PROTOCOL ID NUMBERS      NIAID ACTG 154
 PROTOCOL ID NUMBERS      NIAID ACTG 156
 PROTOCOL ID NUMBERS      NIAID ACTG 237
 PROTOCOL ID NUMBERS      NIAID NS 401
 PROTOCOL ID NUMBERS      NIAID TX 301
 PROTOCOL ID NUMBERS      NIAID 88 CC-85
 PROTOCOL ID NUMBERS      NIAID 89 CC-02
 PROTOCOL ID NUMBERS      NIAID 89 CC-59
 PROTOCOL ID NUMBERS      NCI 90 C-34
 PROTOCOL ID NUMBERS      FDA 056A
 PROTOCOL ID NUMBERS      FDA 224A
 PROTOCOL ID NUMBERS      FDA 132A
 PROTOCOL ID NUMBERS      FDA 132B
 PROTOCOL ID NUMBERS      FDA 132C
 PROTOCOL ID NUMBERS      FDA 132D
 SECONDARY SOURCE ID      NSC-3590 (calcium salt) [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Leucovorin itself is an
                          intermediate product of the metabolism of
                          folic acid; the active form into which folic
                          acid is converted in vivo, ascorbic acid
                          being a necessary factor in the conversion
                          process. Leucovorin rapidly enters the
                          general body pool of reduced folates
                          following parenteral administration.  Oral
                          and intramuscular dosing of 15 mg produced a
                          peak serum folate level of about 1 micromolar
                          in about 1.7 and 0.7 hours, respectively,
                          with a serum folate half-life of about 4-6
                          hours. Since it is a reduced folic acid,
                          leucovorin is not affected by folic acid
                          antagonists that block dihydrofolate
                          reductase. [PDR 1989] [USP DI 1989] [Merck
                          Index 1989]
 DISEASES STUDIED/TREATED Prevention of mucositis and bone marrow
                          toxicity associated with trimetrexate when
                          the latter is used for treatment of
                          Pneumocystis carinii pneumonia (PCP) in AIDS
                          patients [NIAID ACTG 039]
 CLASSIFICATION CODE      Antianemic [PDR 1995]
 CLASSIFICATION CODE      Antidote for folic acid antagonists [PDR
                          1995]
 OTHER MAJOR USES         Treatment of toxicity and adverse effects of
                          inadvertently administered overdoses of folic
                          acid antagonists; treatment of megaloblastic
                          anemias due to sprue, nutritional deficiency,
                          pregnancy, and infancy; treatment of advanced
                          colorectal cancer [PDR 1995]
 SUBSTANCE INTERACTIONS   Leucovorin may interact with barbiturate or
                          hydantoin anticonvulsants, primidone, and
                          central nervous system depressants.
                          Leucovorin is a specific antiodote for the
                          hematopoietic toxicity of methotrexate and
                          other strong inhibitors of dihydrofolate
                          reductase. May enhance the toxicity  of
                          fluorouracil. [USP DI 1995] [PDR 1993]
 ADVERSE EFFECTS          May cause allergic reactions. [PDR 1995]
 CONTRAINDICATIONS        Should not be used for treating pernicious
                          anemia and other megaloblastic anemias
                          secondary to the lack of vitamin B12; a
                          hematologic remission may occur while
                          neurologic manifestations remain progressive.
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DESCRIPTION: Reduced form of folic acid [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C20H21CaN7O7 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 511.51 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water; insoluble in
                          alcohol [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Off-white to light
                          beige amorphous odorless powder [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Vials reconstituted with
                          Bacteriostatic Water for Injection are stable
                          for 7 days.
 CHEMICAL/PHYSICAL DATA   STABILITY: Vials reconstituted with Water for
                          Injection should be used immediately.
 CHEMICAL/PHYSICAL DATA   STABILITY: Vials added to parenteral
                          admixture solutions  retain at least 90% of
                          their labeled potency for 24 hours. [USP DI
                          1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: pKa 3.1, 4.8 and 10.4 [USP
                          DI 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Parenteral 50, 100, 350mg vials
                          for reconstitution; tablets (5, 10, 15, 25mg)
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous infusion;
                          intramuscular; oral. [USP DI 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store parenteral vials prior to
                          recostitution below 40C, preferably between
                          15 and 30C, unless other wise specified by
                          the manufacturer; protect from light. [USP DI
                          1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store tablets below 40C, preferably
                          between 15 and 30C, in a well closed
                          container, unless otherwise specified by the
                          manufacturer; protect from light. [USP DI
                          1995]
 MANUFACTURERS            Glaxo Wellcome
 REFERENCES               Bozzette SA, Forthal D, Sattler FR, Kemper C,
                          Richman DD, Tilles JG, Leedom J, McCutchan
                          JA. The tolerance for zidovudine plus thrice
                          weekly or daily trimethoprim-sulfamethoxazole
                          with and without leucovorin for primary
                          prophylaxis in advanced HIV disease.
                          California Collaborative Treatment Group. Am
                          J Med; VOL 98,ISS 2,1995,P177-82.
 REFERENCES               Safrin S, Lee BL, Sande MA. Adjunctive
                          folinic acid with
                          trimethoprim-sulfamethoxazole for
                          Pneumocystis carinii pneumonia in AIDS
                          patients is associated with an increased risk
                          of therapeutic failure and death. J Infect
                          Dis 1994 Oct;170(4):912-7.
 REFERENCES               Sattler FR, Frame P, Davis R, Nichols L,
                          Shelton B, Akil B, Baughman R, Hughlett C,
                          Weiss W, Boylen CT, et al. Trimetrexate with
                          leucovorin versus
                          trimethoprim-sulfamethoxazole for moderate to
                          severe episodes of Pneumocystis carinii
                          pneumonia in patients with AIDS: a
                          prospective, controlled multicenter
                          investigation of the AIDS Clinical Trials
                          Group Protocol 029/031. J Infect Dis 1994
                          Jul;170(1):165-72.
 REFERENCES               Safrin S, Lee BL, Sande MA. Adjunctive
                          folinic acid with
                          trimethoprim-sulfamethoxazole for
                          Pneumocystis carinii pneumonia in AIDS
                          patients is associated with an increased risk
                          of therapeutic failure and death. J Infect
                          Dis;VOL 170, ISS 4, 1994, P912-7.
 REFERENCES               Crine L, Corfmat Y, Julien C, Echard M, et
                          al. Plasma levels of leucovorin (LV)
                          stereoisomers in Pneumocystis carinii
                          pneumonia (PCP) of AIDS patients treated with
                          trimethoprimsulfamethoxazole (TMP-SMX). Int
                          Conf AIDS. 1993 Jun 6-11;9(1):502(abstract
                          no. PO-B30-2204).
 REFERENCES               Masur H, Polis MA, Tuazon CU, Ogata-Arakaki
                          D, et al. Salvage trial of
                          Trimetrexate-leucovorin for the treatment of
                          cerebral toxoplasmosis in patients with AIDS.
                          J Infect Dis 1993 Jun;167(6):1422-6.
 REFERENCES               Taillan B, Pesce A, Garnier G,Vinti H,
                          Fuzibet JG, Cassuto JP, Dujardin P. AIDS
                          related malignant lymphoma: results of MACOP
                          B chemotherapy. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B108 (abstract no. PoB 3127).
 REFERENCES               Falloon J, Kovacs J, Allegra C, O'Neill D,
                          Tuazon C, Frame P, Dohn M, Joseph P,
                          Feuerstein I, LaFon S, et al. A pilot study
                          of piritrexim (PTX) with leucovorin (LCV) for
                          the treatment of pneumocystis pneumonia. Int
                          Conf AIDS 1990 Jun 20-23;6(1)221 (abstract
                          no. Th.B.399).
 REFERENCES               Schneider AM, Straus DJ, Schluger AE,
                          Lowenthal DA, Koziner B, Lee BJ, Wong G,
                          Clarkson BD. Treatment results with an
                          aggressive chemotherapeutic regimen (MACOP-B)
                          for intermediate- and some high-grade
                          non-Hodgkin's lymphomas. J Clin Oncol. 1990
                          Jan;8(1):94-102.
 REFERENCES               Sattler FR, Allegra CJ, Verdegem TD, Akil B,
                          Tuazon CU, Hughlett C, Ogata-Arakaki D,
                          Feinberg J, Shelhamer J, Lane HC, et al.
                          Trimetrexate-leucovorin dosage evaluation
                          study for treatment of Pneumocystis carinii
                          pneumonia. J Infect Dis 1990 Jan;
                          161(1):91-6.
 ENTRY MONTH              8906
 LAST REVISION DATE       960612
 

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