Miracon Science

antimetabolites

Active substances and pharmaceuticals concerned

Name of active substance Trade name Affected micronutrients
 Pemetrexed Alimta® Folic acid/ Vitamin B12
 5-Fluorouracil Fluorouracil“Accord“® Vitamin B1
(also benfotiamin)
Vitamin B6
Capecitabin Xeloda® Vitamin B6
Benfotiamin

Mechanism of interaction

Mechanism of interaction
Folic acid/
Vitamin B12		 Folic acid-dependent enzymes such as thymidylate synthase, dihydrofolate reductase and glycinamide-ribonucleotide formyl transferase are inhibited in pemetrexed therapy. This leads to a folic acid imbalance and subsequently to a vitamin B12 imbalance.
Vitamin B1 Therapy with 5-fluorouracil inhibits the coenzymatic activation of thiamine to active thiamine phosphate. The degradation of thiamine is also increased.
Vitamin B6 Therapy with capecitabine and 5-fluorouracil very often causes hand-foot syndrome as a side effect.  The 5-fluorouracil catabolites are likely responsible for this. In addition, the possibility of antipyridoxine activity of thethe amino group of these cytostatic drugs is currently discussed.

 

Consequences and possible symptoms of the interaction

Negative consequences of the interaction Possible symptoms
Folic acid Decrease in folic acid levels
  • Anorexia, pallor, depression, weakness, forgetfulness
  • Risk of neural tube defects during pregnancy
  • Impairment of erythropoiesis and development of pernicious anemia, thrombocytopenia, leukopenia and hyperhomocysteinemia 
  • Increased risk of stroke due to increased homocysteine levels
  • Increased risk of dementia and polyneuropathy
  • Glossitis, stomatitis, mucosal atrophy in the GIT and urogenital tract
Vitamin B1 Decrease in vitamin B1 levels
  • weight loss, loss of appetite, irritability, insomnia
  • Peripheral neuropathies, weakness, fatigue, foot burning
  • Anemia, thrombocytopenia
  • heart failure, tachycardia, edema (beriberi)
  • Polyneuropathies, Angiopathies
  • Wernicke encephalopathy (paresis of eye muscles, ataxia, psychoses, cerebellar atrophy), polyneuropathies
Positive consequences of the interaction Possible symptoms
Vitamin B6 Improvement of side effects
  • Delay in the development of the hand-foot syndrome.

 

Recommended Supplementation

Pharmaceutical substance Recommended supplementation Dosage
Pemetrexed Folic acid 0.4–1 mg/d p.o.
Vitamin B12 1 mg/every 2 months i.m.
5-Fluorouracil Vitamin B1 as benfotiamin 150–300 mg/d p.o.
Capecitabin und 5-Fluorouracil Vitamin B6 3 x 100 mg/d p.o.

 

Special instructions for use

Name of active substance Recommended supplementation
Antimetabolites Folic acid/
Vitamin B12		 WARNING: Use only under medical instruction and supervision.
Vitamin B1 Combined administration with vitamin B6 is advised.

 

References

References

Elasmar SA et al. Case report: hand-foot syndrome induced by the oral fluoropyrimidine S-1. Jpn J Clin Oncol. 2001 Apr;31(4):172-4.
Gröber U. Mikronährstoffe. Metabolic Tuning – Prävention – Therapie. 3. Auflage, 2011
Gröber U. Arzneimittel und Mikronährstoffe. Medikationsorientierte Supplementierung. 3. Akt. und erw. Auflage, 2014
Kwon KA et al. A case of 5-fluorouracil induced encephalopathy. Cancer Res Treat. 2010 Jun;42(2):118-20. doi: 10.4143/crt.2010.42.2.118. Epub 2010 Jun 30.
Niyikiza C et al. Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy. Mol Cancer Ther. 2002 May;1(7):545-52.
Ohe Y et al. Efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B12 in previously treated patients with non-small cell lung cancer. Clin Cancer Res. 2008 Jul 1;14(13):4206-12. doi: 10.1158/1078-0432.CCR-07-5143.
Stargrove Mitchell Bebel, Treasure Jonathan, McKee Dwight L.: Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies. 2008

 

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