TY  - CHAP
M1  - Book, Section
TI  - LEUCOVORIN CALCIUM
A1  - Birnbaum, Kathy
A2  - Olson, Kent R.
A2  - Anderson, Ilene B.
A2  - Benowitz, Neal L.
A2  - Blanc, Paul D.
A2  - Clark, Richard F.
A2  - Kearney, Thomas E.
A2  - Kim-Katz, Susan Y.
A2  - Wu, Alan H. B.
PY  - 2018
T2  - Poisoning & Drug Overdose, 7e
AB  - Pharmacology.  Leucovorin  (folinic  acid  or  citrovorum  factor)  is  a  metabolically  functional  form  of  folic  acid.  Unlike  folic  acid,  leucovorin  does  not  require  reduction  by  dihydrofolate  reductase,  and,  therefore,  it  can  participate  directly  in  the  one-carbon  transfer  reactions  necessary  for  purine  biosynthesis  and  cellular  DNA  and  RNA  production.  In  animal  models  of  methanol  intoxication,  replacement  of  a  deficiency  of  leucovorin  and  folic  acid  can  reduce  morbidity  and  mortality  because  these  agents  catalyze  the  oxidation  of  the  highly  toxic  metabolite  formic  acid  to  nontoxic  products.  However,  there  is  no  evidence  that  their  administration  in  the  absence  of  a  deficiency  is  effective.IndicationsFolic  acid  antagonists  (eg,  methotrexate,  trimethoprim,  and  pyrimethamine).  Note:  Leucovorin  treatment  is  essential  because  cells  are  incapable  of  using  folic  acid  owing  to  inhibition  of  dihydrofolate  reductase.Methanol  poisoning.  Leucovorin  is  the  preferred  form  of  folic  acid  to  enhance  the  breakdown  of  formic  acid;  if  leucovorin  is  not  available,  then  use  folic  acid.Contraindications.  No  known  contraindications.Adverse  effectsAllergic  reactions  as  a  result  of  prior  sensitization  have  been  reported.Hypercalcemia  from  the  calcium  salt  may  occur  (limit  infusion  rate  to  160  mg/min  in  adults).Use  in  pregnancy.  FDA  Category  C  (indeterminate).  This  does  not  preclude  its  acute,  short-term  use  in  a  seriously  symptomatic  patient  (Introduction).Drug  or  laboratory  interactions.  Leucovorin  bypasses  the  antifolate  effect  of  methotrexate.Dosage  and  method  of  administrationMethotrexate  poisoning.  Note:  Efficacy  depends  on  early  administration.  Leucovorin  should  be  given  within  1  hour  of  poisoning,  if  possible;  do  not  wait  for  methotrexate  levels  to  initiate  therapy.  The  drug  should  be  given  intravenously.  The  most  effective  dose  and  duration  of  treatment  are  uncertain.Methotrexate  level  unknown.  Administer  intravenously  a  dose  equal  to  or  greater  than  the  dose  of  methotrexate.  Leucovorin  doses  typically  range  from  10  to  25  mg/m2  every  6  hours,  but  doses  of  up  to  1,000  mg/m2  have  been  used.  Most  serious  cases  are  treated  with  100  mg/m2  (or  about  150  mg  in  an  average-size  adult)  IV  over  15–30  minutes,  followed  by  10  mg/m2  (or  ~15  mg)  IV  every  6  hours  for  at  least  3  days,  or  until  the  serum  methotrexate  level  falls  below  0.01  mcmol/L  or  is  undetectable.Elevated  methotrexate  level  or  elevated  serum  creatinineIf  the  24-hour  serum  creatinine  increases  50%  in  the  first  24  hours  after  methotrexate  or  if  the  24-hour  methotrexate  level  exceeds  5  mcmol/L  or  if  the  48-hour  methotrexate  level  exceeds  0.9  mcmol/L,  increase  the  leucovorin  dose  to  100  mg/m2  intravenously  every  3  hours  until  the  methotrexate  level  is  less  than  0.01  mcmol/L  or  is  undetectable.If  the  24-hour  serum  creatinine  increases  100%  in  the  first  24  hours  after  methotrexate  or  if  the  24-hour  methotrexate  level  reaches  or  exceeds  50  mcmol/L  or  if  the  48-hour  methotrexate  level  reaches  or  exceeds  5  mcmol/L,  increase  the  leucovorin  dose  to  150  mg  intravenously  every  3  hours  until  the  methotrexate  level  is  less  than  1  mcmol/L.  Then  give  a  dose  of  15  mg  intravenously  every  3  hours  until  the  methotrexate  level  is  less  than  0.01  mcmol/L  or  is  undetectable.Other  folic  acid  antagonists.  Administer  5–15  mg/d  IM,  IV,  or  PO  for  5–7  days.Methanol  poisoning.  For  adults  and  children,  give  1  mg/kg  (up  to  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1174607473
ER  -