Alimta ® (pemetrexed for injection)

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Alimta® (pemetrexed): Vitamin Supplementation

Prior to pemetrexed treatment, initiate vitamin supplementation consisting of oral folic acid and IM vitamin B12 to reduce severity of pemetrexed toxicity.


Detailed Information

Folic acid

To reduce toxicity, patients treated with pemetrexed must be instructed to take a folic acid preparation or a multivitamin with folic acid

  • as a daily oral low-dose
  • initiated during the 7-day period preceding the first dose of pemetrexed, and for at least 5 doses, and
  • during the full course of therapy and for 21 days after the last dose of pemetrexed.1

In clinical trials, the dose of folic acid studied ranged from 350 to 1000 μg. The most commonly used dose of oral folic acid in clinical trials was 400 μg.2

Vitamin B12

Patients must also receive vitamin B12

  • as an IM injection
  • initiated the week preceding the first dose of pemetrexed, and
  • every 3 cycles thereafter.1

Subsequent vitamin B12 injections may be given the same day as pemetrexed.1 In clinical trials, the dose of vitamin B12 received was 1000 μg.2

Effects of Vitamin Supplementation on Toxicity

In the phase 3 malignant pleural mesothelioma (MPM) registration trial, pretreatment with folic acid and vitamin B12 led to overall less toxicity and reduction in grade 3/4 hematologic and nonhematologic toxicities such as

  • neutropenia
  • febrile neutropenia, and
  • infection with grade 3/4 neutropenia.2,3

Therefore, patients treated with pemetrexed must be instructed to take folic acid and vitamin B12 as a prophylactic measure to reduce treatment-related toxicity.2

Effects of Vitamin Supplementation on Pharmacokinetics

The pharmacokinetics (PK) of pemetrexed is not influenced by oral folic acid and IM vitamin B12 supplementation.2


1Alimta [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands

2Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636-2644.

Date of Last Review: 27 May 2021

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