Pemetrexed Explained

Verifiedfields:changed
Verifiedrevid:464197624
Tradename:Alimta, Pemfexy, Ciambra, others
Dailymedid:Pemetrexed
Pregnancy Au:D
Routes Of Administration:Intravenous
Atc Prefix:L01
Atc Suffix:BA04
Legal Au:S4
Legal Au Comment:[1]
Legal Uk:POM
Legal Us:Rx-only
Legal Us Comment:[2]
Legal Eu:Rx-only
Legal Eu Comment:[3] [4]
Bioavailability:NA
Protein Bound:81%
Metabolism:Negligible
Elimination Half-Life:3.5 hours
Excretion:Kidney
Index2 Label:as salt
Cas Number:137281-23-3
Pubchem:135410875
Drugbank:DB00642
Chemspiderid:393879
Unii:04Q9AIZ7NO
Kegg:D07472
Kegg2:D06503
Chembl:225072
Iupac Name:(2S)-2-pentanedioic acid
C:20
H:21
N:5
O:6
Smiles:Nc3nc2[nH]cc(CCc1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1)c2c(=O)[nH]3
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: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.[5] [6]

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[7] for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery.[8] 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.[9] [10]

Carboplatin

Pemetrexed is also recommended in combination with carboplatin and pembrolizumab for the first-line treatment of advanced non-small cell lung cancer.[11] [12] 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.[13]

Supplementation

Patients are recommended to take folic acid and vitamin B12 supplement even if levels are normal when they are on pemetrexed therapy.[14] [15] (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.

Side effects

Pemetrexed, whether used alone or in combination with cisplatin, has these side effects:

Mechanism of action

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[18] [19] (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 .[20]

Brand names

In February 2020, Pemfexy was approved for use in the United States.[21]

Research

A Phase III study showed benefits of maintenance use of pemetrexed for non-squamous NSCLC.[22] Activity has been shown in malignant peritoneal mesothelioma.[23]

External links

Notes and References

  1. Web site: Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 . Therapeutic Goods Administration (TGA) . 21 June 2022 . 30 March 2024.
  2. Web site: Pemfexy- pemetrexed injection . DailyMed . 20 January 2022 . 20 May 2022 . 21 May 2022 . https://web.archive.org/web/20220521021818/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2308f4e8-21c8-49c1-a5b8-deb8610bac6a . live .
  3. Web site: Alimta EPAR . European Medicines Agency . 17 September 2018 . 14 October 2022 . 18 January 2021 . https://web.archive.org/web/20210118214202/https://www.ema.europa.eu/en/medicines/human/EPAR/alimta . live .
  4. Web site: Pemetrexed Baxter: Pending EC decision . European Medicines Agency . 14 October 2022 . 14 October 2022 . 14 October 2022 . https://web.archive.org/web/20221014175806/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/pemetrexed-baxter . live .
  5. Web site: 2022 First Generic Drug Approvals . U.S. Food and Drug Administration (FDA) . 3 March 2023 . https://web.archive.org/web/20230630003602/https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/2022-first-generic-drug-approvals . 30 June 2023 . live . 30 June 2023.
  6. Web site: Competitive Generic Therapy Approvals . U.S. Food and Drug Administration (FDA) . 29 June 2023 . 29 June 2023 . 29 June 2023 . https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals . live .
  7. Manegold C . Pemetrexed (Alimta, MTA, multitargeted antifolate, LY231514) for malignant pleural mesothelioma . Seminars in Oncology . 30 . 4 Suppl 10 . 32–36 . August 2003 . 12917819 . 10.1016/S0093-7754(03)00283-5 .
  8. National Cancer Institute: FDA Approval for Pemetrexed Disodium
  9. Cohen MH, Justice R, Pazdur R . Approval summary: pemetrexed in the initial treatment of advanced/metastatic non-small cell lung cancer . The Oncologist . 14 . 9 . 930–935 . September 2009 . 19737998 . 10.1634/theoncologist.2009-0092 . 28209589 . free .
  10. Rossi A, Ricciardi S, Maione P, de Marinis F, Gridelli C . Pemetrexed in the treatment of advanced non-squamous lung cancer . Lung Cancer . 66 . 2 . 141–149 . November 2009 . 19577816 . 10.1016/j.lungcan.2009.06.006 .
  11. Web site: Ettinger DS, etal . NCCN Clinical Practice Guidelines in Oncology . Non-small Cell Lung Cancer V.1.2007 . National Comprehensive Cancer Network (NCCN) . https://web.archive.org/web/20070323012050/https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf . 23 March 2007 .
  12. Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC . 6 . Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer . The New England Journal of Medicine . 378 . 22 . 2078–2092 . May 2018 . 29658856 . 10.1056/NEJMoa1801005 . KEYNOTE-189 Investigators . free . 10138/298862 . free .
  13. Azzoli CG, Kris MG, Pfister DG . Cisplatin versus carboplatin for patients with metastatic non-small-cell lung cancer--an old rivalry renewed . Journal of the National Cancer Institute . 99 . 11 . 828–829 . June 2007 . 17551137 . 10.1093/jnci/djk222 . free .
  14. Hazarika M, White RM, Johnson JR, Pazdur R . FDA drug approval summaries: pemetrexed (Alimta) . The Oncologist . 9 . 5 . 482–488 . 2004 . 15477632 . 10.1634/theoncologist.9-5-482 . 11444611 .
  15. Web site: Alimta- pemetrexed disodium injection, powder, lyophilized, for solution . DailyMed . 25 March 2020 . 20 October 2020 . 20 October 2020 . https://web.archive.org/web/20201020074626/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f5a860f3-37ec-429c-ae04-9c88d7c55c08 . live .
  16. Scientists Help Breast Cancer Survivor Lift the Fog of "Chemo Brain" . Dialogue . Fall 2007 . 2–3 . James P Wilmot Cancer Center, University of Rochester Medical Center . 1 December 2008 .
  17. Web site: Oral Complications of Chemotherapy and Head/Neck Radiation . Cancer Topics – Coping with Cancer . . 1 December 2008. 6 December 2008. https://web.archive.org/web/20081206081959/http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/Patient/page5 . live .
  18. McLeod HL, Cassidy J, Powrie RH, Priest DG, Zorbas MA, Synold TW, Shibata S, Spicer D, Bissett D, Pithavala YK, Collier MA, Paradiso LJ, Roberts JD . 6 . Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034 . Clinical Cancer Research . 6 . 7 . 2677–2684 . July 2000 . 10914709 . 2 December 2008 . live . https://web.archive.org/web/20090728001330/http://clincancerres.aacrjournals.org/cgi/content/abstract/6/7/2677 . 28 July 2009 .
  19. Book: Avendano C, Menendez JC . Medicinal Chemistry of Anticancer Drugs . . April 2008 . Amsterdam . 37 . 978-0-444-52824-7 .
  20. News: Langreth R . Decoding Big Pharma's Secret Drug Pricing Practices. 15 July 2016. Bloomberg. 29 June 2016. 13 July 2016. https://web.archive.org/web/20160713133019/http://www.bloomberg.com/graphics/2016-drug-prices/. live.
  21. Web site: Pemfexy: FDA-Approved Drugs . U.S. Food and Drug Administration (FDA) . 13 February 2020 . 19 October 2020 . https://web.archive.org/web/20201019041806/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209472 . live .
  22. Belani CP, Brodowicz T, Ciuleanu T, Kim JH, Krzakowski M, Laack E, Wu YL, Peterson P, Krejcy K, Zielinski C . 6 . 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 of Clinical Oncology . June 2009 . 27 . 18 suppl . CRA8000 . . 10.1200/jco.2009.27.18_suppl.cra8000 . 22 July 2009 . 16 June 2009. https://web.archive.org/web/20090616132533/http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33019 . dead .
  23. Carteni G, Manegold C, Garcia GM, Siena S, Zielinski CC, Amadori D, Liu Y, Blatter J, Visseren-Grul C, Stahel R . 6 . Malignant peritoneal mesothelioma-Results from the International Expanded Access Program using pemetrexed alone or in combination with a platinum agent . Lung Cancer . 64 . 2 . 211–218 . May 2009 . 19042053 . 10.1016/j.lungcan.2008.08.013 .

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