Pemetrexed

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Chemical compound

title: "Pemetrexed" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["mammalian-dihydrofolate-reductase-inhibitors", "drugs-developed-by-eli-lilly-and-company", "pyrrolopyrimidines", "benzamides", "antifolates", "thymidylate-synthase-inhibitors", "purines"] description: "Chemical compound" topic_path: "general/mammalian-dihydrofolate-reductase-inhibitors" source: "https://en.wikipedia.org/wiki/Pemetrexed" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

::data[format=table title="Infobox drug"]

FieldValue
Verifiedfieldschanged
verifiedrevid464197624
imagePemetrexed.svg
image_classskin-invert-image
image2Pemetrexed ball-and-stick.png
image_class2bg-transparent
tradenameAlimta, Pemfexy, Ciambra, others
Drugs.com
DailyMedIDPemetrexed
pregnancy_AUD
routes_of_administrationIntravenous
ATC_prefixL01
ATC_suffixBA04
legal_AUS4
legal_AU_comment
legal_UKPOM
legal_USRx-only
legal_US_comment
legal_EURx-only
legal_EU_comment
bioavailabilityNA
protein_bound81%
metabolismNegligible
elimination_half-life3.5 hours
excretionKidney
index2_labelas salt
CAS_number_Ref
CAS_number137281-23-3
PubChem135410875
DrugBank_Ref
DrugBankDB00642
ChemSpiderID_Ref
ChemSpiderID393879
UNII_Ref
UNII04Q9AIZ7NO
KEGG_Ref
KEGGD07472
KEGG2_Ref
KEGG2D06503
ChEMBL_Ref
ChEMBL225072
IUPAC_name(2S)-2-{[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino}pentanedioic acid
C20
smilesNc3nc2[nH]cc(CCc1ccc(C(=O)NC@@HC(=O)O)cc1)c2c(=O)[nH]3
StdInChI_Ref
StdInChI1S/C20H21N5O6/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29)/t13-/m0/s1
StdInChIKey_Ref
StdInChIKeyWBXPDJSOTKVWSJ-ZDUSSCGKSA-N
::

| Verifiedfields = changed | verifiedrevid = 464197624 | image = Pemetrexed.svg | image_class = skin-invert-image | image2 = Pemetrexed ball-and-stick.png | image_class2 = bg-transparent

| tradename = Alimta, Pemfexy, Ciambra, others | Drugs.com = | DailyMedID = Pemetrexed | pregnancy_AU = D | routes_of_administration = Intravenous | ATC_prefix = L01 | ATC_suffix = BA04 | ATC_supplemental =

| legal_AU = S4 | legal_AU_comment = | legal_UK = POM | legal_US = Rx-only | legal_US_comment = | legal_EU = Rx-only | legal_EU_comment =

| bioavailability = NA | protein_bound = 81% | metabolism = Negligible | elimination_half-life = 3.5 hours | excretion = Kidney

| index2_label = as salt | CAS_number_Ref = | CAS_number = 137281-23-3 | PubChem = 135410875 | DrugBank_Ref = | DrugBank = DB00642 | ChemSpiderID_Ref = | ChemSpiderID = 393879 | UNII_Ref = | UNII = 04Q9AIZ7NO | KEGG_Ref = | KEGG = D07472 | KEGG2_Ref = | KEGG2 = D06503 | ChEMBL_Ref = | ChEMBL = 225072

| IUPAC_name = (2S)-2-{[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino}pentanedioic acid | C=20 | H=21 | N=5 | O=6 | smiles = Nc3nc2[nH]cc(CCc1ccc(C(=O)NC@@HC(=O)O)cc1)c2c(=O)[nH]3 | StdInChI_Ref = | StdInChI = 1S/C20H21N5O6/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29)/t13-/m0/s1 | StdInChIKey_Ref = | StdInChIKey = WBXPDJSOTKVWSJ-ZDUSSCGKSA-N

Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC).

It is available as a generic medication.

Medical use

In February 2004, the U.S. Food and Drug Administration (FDA) approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of the mesothelium, the thin layer of tissue that covers many of the internal organs, in combination with cisplatin for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery. In September 2008, the FDA granted approval as a first-line treatment, in combination with cisplatin, against locally advanced and metastatic non-small cell lung cancer (NSCLC) in patients with non-squamous histology.

Carboplatin

Pemetrexed is also recommended in combination with carboplatin and pembrolizumab for the first-line treatment of advanced non-small cell lung cancer. However, the relative efficacy or toxicity of pemetrexed-cisplatin versus pemetrexed-carboplatin has not been established beyond what is generally thought about cisplatin or carboplatin doublet drug therapy.

Supplementation

Patients are recommended to take folic acid and vitamin B12 supplement even if levels are normal when they are on pemetrexed therapy. (In clinical trials for mesothelioma, folic acid and B12 supplementation reduced the frequency of adverse events.) It is also recommended for patients to be on a glucocorticoid (e.g. dexamethasone) on the day prior, day of, and day after pemetrexed infusion to avoid skin rashes.

Drug interaction

The administration of cisplatin and vitamin B12 concomitantly does not modify the pharmacokinetics of the pemetrexed. It was recently shown that pemetrexed may play a role in cisplatin resistance in lung cancer by increasing the expression of Orai3 calcium channels as well as the expression of certain ABC transporters like MDR1 and MRP-5 responsible for cisplatin efflux and therefore a reduction of the effect of cisplatin As current therapies are based on the co-administration of pemetrexed and cisplatin, there may be interactions between pemetrexed and cisplatin, including a reduction in the therapeutic effects of cisplatin caused by pemetrexed.

Mechanism of action

::figure[src="https://upload.wikimedia.org/wikipedia/commons/8/89/Pathway_of_tetrahydrofolate_and_antimetabolites.pdf" caption="Pathway of tetrahydrofolate and antimetabolites"] ::

Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis—thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.

Society and culture

Economics

In the United States, , each vial of the medication costs between and .

Brand names

In February 2020, Pemfexy was approved for use in the United States.

Research

A Phase III study showed benefits of maintenance use of pemetrexed for non-squamous NSCLC.{{cite journal | vauthors = Belani CP, Brodowicz T, Ciuleanu T, Kim JH, Krzakowski M, Laack E, Wu YL, Peterson P, Krejcy K, Zielinski C | display-authors = 6 | title = Maintenance pemetrexed (Pem) plus best supportive care (BSC) versus placebo (Plac) plus BSC: A randomized phase III study in advanced non-small cell lung cancer (NSCLC). | journal = Journal of Clinical Oncology | date = June 2009 | volume = 27 | issue = 18 suppl | article-number = CRA8000 | publisher = American Society of Clinical Oncology | doi = 10.1200/jco.2009.27.18_suppl.cra8000 | url = http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33019 | access-date = 22 July 2009 | archive-date = 16 June 2009 | archive-url = https://web.archive.org/web/20090616132533/http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33019 | url-access = subscription }} Activity has been shown in malignant peritoneal mesothelioma.

References

References

  1. (21 June 2022). "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017".
  2. (20 January 2022). "Pemfexy- pemetrexed injection".
  3. (17 September 2018). "Alimta EPAR".
  4. (14 October 2022). "Pemetrexed Baxter: Pending EC decision".
  5. (3 March 2023). "2022 First Generic Drug Approvals".
  6. (29 June 2023). "Competitive Generic Therapy Approvals".
  7. (August 2003). "Pemetrexed (Alimta, MTA, multitargeted antifolate, LY231514) for malignant pleural mesothelioma". Seminars in Oncology.
  8. National Cancer Institute: [http://www.cancer.gov/cancertopics/druginfo/fda-pemetrexed-disodium#malignant_pleural FDA Approval for Pemetrexed Disodium] {{Webarchive. link. (6 April 2015)
  9. (September 2009). "Approval summary: pemetrexed in the initial treatment of advanced/metastatic non-small cell lung cancer". The Oncologist.
  10. (November 2009). "Pemetrexed in the treatment of advanced non-squamous lung cancer". Lung Cancer.
  11. "Non-small Cell Lung Cancer V.1.2007". National Comprehensive Cancer Network (NCCN).
  12. (May 2018). "Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer". The New England Journal of Medicine.
  13. (June 2007). "Cisplatin versus carboplatin for patients with metastatic non-small-cell lung cancer--an old rivalry renewed". Journal of the National Cancer Institute.
  14. (2004). "FDA drug approval summaries: pemetrexed (Alimta)". The Oncologist.
  15. (25 March 2020). "Alimta- pemetrexed disodium injection, powder, lyophilized, for solution".
  16. (26 September 2024). "Characterization and implication of the Orai3 channel and ABC type transporters in the phenomenon of chemoresistance to cisplatin and pemetrexed in lung cancer.".
  17. (July 2000). "Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034". Clinical Cancer Research.
  18. (April 2008). "Medicinal Chemistry of Anticancer Drugs". [[Elsevier]].
  19. (29 June 2016). "Decoding Big Pharma's Secret Drug Pricing Practices". Bloomberg.
  20. "Pemfexy: FDA-Approved Drugs".
  21. (May 2009). "Malignant peritoneal mesothelioma-Results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent". Lung Cancer.

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::

mammalian-dihydrofolate-reductase-inhibitorsdrugs-developed-by-eli-lilly-and-companypyrrolopyrimidinesbenzamidesantifolatesthymidylate-synthase-inhibitorspurines