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Pemetrexed

January 01, 1970

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).[2].

Pemetrexed
Clinical data
Trade namesAlimta, Pemfexy, Ciambra, others
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: D
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityNA
Protein binding81%
MetabolismNegligible
Elimination half-life3.5 hours
ExcretionKidney
Identifiers
  • (2S)-2-{[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino}pentanedioic acid
CAS Number
  • 137281-23-3 N
PubChem CID
  • 135410875
DrugBank
  • DB00642 Y
ChemSpider
  • 393879 Y
UNII
  • 04Q9AIZ7NO
KEGG
  • D07472 Y
  • as salt: D06503 Y
ChEMBL
  • ChEMBL225072 Y
CompTox Dashboard (EPA)
  • DTXSID2048329
ECHA InfoCard100.205.735
Chemical and physical data
FormulaC20H21N5O6
Molar mass427.417 g·mol−1
3D model (JSmol)
  • Interactive image
  • Nc3nc2[nH]cc(CCc1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1)c2c(=O)[nH]3
  • InChI=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 Y
  • Key:WBXPDJSOTKVWSJ-ZDUSSCGKSA-N Y
 NY (what is this?)  (verify)

It is available as a generic medication.[6][7]

Medical use edit

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[8] for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery.[9] 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.[10][11][2]

Carboplatin edit

Pemetrexed is also recommended in combination with carboplatin and pembrolizumab for the first-line treatment of advanced non-small cell lung cancer.[12][13] 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.[14]

Supplementation edit

Patients are recommended to take folic acid and vitamin B12 supplement even if levels are normal when they are on pemetrexed therapy.[15][2] (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.[2]

Side effects edit

Pemetrexed, whether used alone or in combination with cisplatin, has these side effects:[2]

Mechanism of action edit

 
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[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 edit

Economics edit

In the United States, as of 2015, each vial of the medication costs between US$2,623 and US$3,100.[20]

Brand names edit

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

Research edit

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]

References edit

  1. ^ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  2. ^ a b c d e f "Alimta- pemetrexed disodium injection, powder, lyophilized, for solution". DailyMed. 25 March 2020. from the original on 20 October 2020. Retrieved 20 October 2020.
  3. ^ "Pemfexy- pemetrexed injection". DailyMed. 20 January 2022. from the original on 21 May 2022. Retrieved 20 May 2022.
  4. ^ "Alimta EPAR". European Medicines Agency. 17 September 2018. from the original on 18 January 2021. Retrieved 14 October 2022.
  5. ^ "Pemetrexed Baxter: Pending EC decision". European Medicines Agency. 14 October 2022. from the original on 14 October 2022. Retrieved 14 October 2022.
  6. ^ "2022 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. from the original on 30 June 2023. Retrieved 30 June 2023.
  7. ^ "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. from the original on 29 June 2023. Retrieved 29 June 2023.
  8. ^ Manegold C (August 2003). "Pemetrexed (Alimta, MTA, multitargeted antifolate, LY231514) for malignant pleural mesothelioma". Seminars in Oncology. 30 (4 Suppl 10): 32–36. doi:10.1016/S0093-7754(03)00283-5. PMID 12917819.
  9. ^ National Cancer Institute: FDA Approval for Pemetrexed Disodium 6 April 2015 at the Wayback Machine
  10. ^ Cohen MH, Justice R, Pazdur R (September 2009). "Approval summary: pemetrexed in the initial treatment of advanced/metastatic non-small cell lung cancer". The Oncologist. 14 (9): 930–935. doi:10.1634/theoncologist.2009-0092. PMID 19737998. S2CID 28209589.
  11. ^ Rossi A, Ricciardi S, Maione P, de Marinis F, Gridelli C (November 2009). "Pemetrexed in the treatment of advanced non-squamous lung cancer". Lung Cancer. 66 (2): 141–149. doi:10.1016/j.lungcan.2009.06.006. PMID 19577816.
  12. ^ Ettinger DS, et al. (PDF). NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network (NCCN). Archived from the original (PDF) on 23 March 2007.
  13. ^ Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. (KEYNOTE-189 Investigators) (May 2018). "Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer". The New England Journal of Medicine. 378 (22): 2078–2092. doi:10.1056/NEJMoa1801005. hdl:10138/298862. PMID 29658856.
  14. ^ Azzoli CG, Kris MG, Pfister DG (June 2007). "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. doi:10.1093/jnci/djk222. PMID 17551137.
  15. ^ Hazarika M, White RM, Johnson JR, Pazdur R (2004). "FDA drug approval summaries: pemetrexed (Alimta)". The Oncologist. 9 (5): 482–488. doi:10.1634/theoncologist.9-5-482. PMID 15477632. S2CID 11444611.
  16. ^ "Scientists Help Breast Cancer Survivor Lift the Fog of "Chemo Brain"" (PDF). Dialogue. James P Wilmot Cancer Center, University of Rochester Medical Center: 2–3. Fall 2007. Retrieved 1 December 2008.[permanent dead link]
  17. ^ "Oral Complications of Chemotherapy and Head/Neck Radiation". Cancer Topics – Coping with Cancer. National Cancer Institute. from the original on 6 December 2008. Retrieved 1 December 2008.
  18. ^ McLeod HL, Cassidy J, Powrie RH, Priest DG, Zorbas MA, Synold TW, et al. (July 2000). "Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034". Clinical Cancer Research. 6 (7): 2677–2684. PMID 10914709. from the original on 28 July 2009. Retrieved 2 December 2008.
  19. ^ Avendano C, Menendez JC (April 2008). Medicinal Chemistry of Anticancer Drugs. Amsterdam: Elsevier. p. 37. ISBN 978-0-444-52824-7.
  20. ^ Langreth R (29 June 2016). "Decoding Big Pharma's Secret Drug Pricing Practices". Bloomberg. from the original on 13 July 2016. Retrieved 15 July 2016.
  21. ^ "Pemfexy: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). from the original on 19 October 2020. Retrieved 13 February 2020.
  22. ^ Belani CP, Brodowicz T, Ciuleanu T, Kim JH, Krzakowski M, Laack E, et al. (June 2009). . Journal of Clinical Oncology. 27 (18 suppl). American Society of Clinical Oncology: CRA8000. doi:10.1200/jco.2009.27.18_suppl.cra8000. Archived from the original on 16 June 2009. Retrieved 22 July 2009.
  23. ^ Carteni G, Manegold C, Garcia GM, Siena S, Zielinski CC, Amadori D, et al. (May 2009). "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. doi:10.1016/j.lungcan.2008.08.013. PMID 19042053.

External links edit

  • "Pemetrexed disodium". NCI Drug Dictionary. National Cancer Institute.
  • "Pemetrexed disodium". National Cancer Institute. 5 October 2006.

January 01, 1970
pemetrexed, sold, under, brand, name, alimta, among, others, chemotherapy, medication, treatment, pleural, mesothelioma, small, cell, lung, cancer, nsclc, clinical, datatrade, namesalimta, pemfexy, ciambra, othersahfs, drugs, commonographlicense, dataus, daily. 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 2 PemetrexedClinical dataTrade namesAlimta Pemfexy Ciambra othersAHFS Drugs comMonographLicense dataUS DailyMed PemetrexedPregnancycategoryAU DRoutes ofadministrationIntravenousATC codeL01BA04 WHO Legal statusLegal statusAU S4 Prescription only 1 UK POM Prescription only US only 2 3 EU Rx only 4 5 Pharmacokinetic dataBioavailabilityNAProtein binding81 MetabolismNegligibleElimination half life3 5 hoursExcretionKidneyIdentifiersIUPAC name 2S 2 4 2 2 amino 4 oxo 1 7 dihydropyrrolo 2 3 d pyrimidin 5 yl ethyl benzoyl amino pentanedioic acidCAS Number137281 23 3 NPubChem CID135410875DrugBankDB00642 YChemSpider393879 YUNII04Q9AIZ7NOKEGGD07472 Yas salt D06503 YChEMBLChEMBL225072 YCompTox Dashboard EPA DTXSID2048329ECHA InfoCard100 205 735Chemical and physical dataFormulaC 20H 21N 5O 6Molar mass427 417 g mol 13D model JSmol Interactive imageSMILES Nc3nc2 nH cc CCc1ccc C O N C H CCC O O C O O cc1 c2c O nH 3InChI InChI 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 YKey WBXPDJSOTKVWSJ ZDUSSCGKSA N Y N Y what is this verify It is available as a generic medication 6 7 Contents 1 Medical use 1 1 Carboplatin 1 2 Supplementation 2 Side effects 3 Mechanism of action 4 Society and culture 4 1 Economics 4 2 Brand names 5 Research 6 References 7 External linksMedical use editIn 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 8 for patients whose disease is either unresectable or who are not otherwise candidates for curative surgery 9 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 10 11 2 Carboplatin edit Pemetrexed is also recommended in combination with carboplatin and pembrolizumab for the first line treatment of advanced non small cell lung cancer 12 13 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 14 Supplementation edit Patients are recommended to take folic acid and vitamin B12 supplement even if levels are normal when they are on pemetrexed therapy 15 2 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 2 Side effects editPemetrexed whether used alone or in combination with cisplatin has these side effects 2 Low blood cell counts as measured by a complete blood count This is a dose limiting toxicity Mental fatigue and sleepiness Fatigue can be reduced through an off label prescription of modafinil 16 Nausea and vomiting Pemetrexed s emetogenic effects are managed with prophylactic antiemetics Diarrhea Oral mucositis mouth throat or lip sores Oral ulcers can be mitigated by proper oral hygiene including rinsing of the mouth with salt water following consumption of food or drink 17 Loss of appetite Skin rash Physician prescribed glucocorticoids administered on the day prior day of and day after infusion typically avoid skin rashes ConstipationMechanism of action edit nbsp 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 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 editEconomics edit In the United States as of 2015 update each vial of the medication costs between US 2 623 and US 3 100 20 Brand names edit In February 2020 Pemfexy was approved for use in the United States 21 Research editA Phase III study showed benefits of maintenance use of pemetrexed for non squamous NSCLC 22 Activity has been shown in malignant peritoneal mesothelioma 23 References edit Prescription medicines registration of new generic medicines and biosimilar medicines 2017 Therapeutic Goods Administration TGA 21 June 2022 Retrieved 30 March 2024 a b c d e f Alimta pemetrexed disodium injection powder lyophilized for solution DailyMed 25 March 2020 Archived from the original on 20 October 2020 Retrieved 20 October 2020 Pemfexy pemetrexed injection DailyMed 20 January 2022 Archived from the original on 21 May 2022 Retrieved 20 May 2022 Alimta EPAR European Medicines Agency 17 September 2018 Archived from the original on 18 January 2021 Retrieved 14 October 2022 Pemetrexed Baxter Pending EC decision European Medicines Agency 14 October 2022 Archived from the original on 14 October 2022 Retrieved 14 October 2022 2022 First Generic Drug Approvals U S Food and Drug Administration FDA 3 March 2023 Archived from the original on 30 June 2023 Retrieved 30 June 2023 Competitive Generic Therapy Approvals U S Food and Drug Administration FDA 29 June 2023 Archived from the original on 29 June 2023 Retrieved 29 June 2023 Manegold C August 2003 Pemetrexed Alimta MTA multitargeted antifolate LY231514 for malignant pleural mesothelioma Seminars in Oncology 30 4 Suppl 10 32 36 doi 10 1016 S0093 7754 03 00283 5 PMID 12917819 National Cancer Institute FDA Approval for Pemetrexed Disodium Archived 6 April 2015 at the Wayback Machine Cohen MH Justice R Pazdur R September 2009 Approval summary pemetrexed in the initial treatment of advanced metastatic non small cell lung cancer The Oncologist 14 9 930 935 doi 10 1634 theoncologist 2009 0092 PMID 19737998 S2CID 28209589 Rossi A Ricciardi S Maione P de Marinis F Gridelli C November 2009 Pemetrexed in the treatment of advanced non squamous lung cancer Lung Cancer 66 2 141 149 doi 10 1016 j lungcan 2009 06 006 PMID 19577816 Ettinger DS et al Non small Cell Lung Cancer V 1 2007 PDF NCCN Clinical Practice Guidelines in Oncology National Comprehensive Cancer Network NCCN Archived from the original PDF on 23 March 2007 Gandhi L Rodriguez Abreu D Gadgeel S Esteban E Felip E De Angelis F et al KEYNOTE 189 Investigators May 2018 Pembrolizumab plus Chemotherapy in Metastatic Non Small Cell Lung Cancer The New England Journal of Medicine 378 22 2078 2092 doi 10 1056 NEJMoa1801005 hdl 10138 298862 PMID 29658856 Azzoli CG Kris MG Pfister DG June 2007 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 doi 10 1093 jnci djk222 PMID 17551137 Hazarika M White RM Johnson JR Pazdur R 2004 FDA drug approval summaries pemetrexed Alimta The Oncologist 9 5 482 488 doi 10 1634 theoncologist 9 5 482 PMID 15477632 S2CID 11444611 Scientists Help Breast Cancer Survivor Lift the Fog of Chemo Brain PDF Dialogue James P Wilmot Cancer Center University of Rochester Medical Center 2 3 Fall 2007 Retrieved 1 December 2008 permanent dead link Oral Complications of Chemotherapy and Head Neck Radiation Cancer Topics Coping with Cancer National Cancer Institute Archived from the original on 6 December 2008 Retrieved 1 December 2008 McLeod HL Cassidy J Powrie RH Priest DG Zorbas MA Synold TW et al July 2000 Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034 Clinical Cancer Research 6 7 2677 2684 PMID 10914709 Archived from the original on 28 July 2009 Retrieved 2 December 2008 Avendano C Menendez JC April 2008 Medicinal Chemistry of Anticancer Drugs Amsterdam Elsevier p 37 ISBN 978 0 444 52824 7 Langreth R 29 June 2016 Decoding Big Pharma s Secret Drug Pricing Practices Bloomberg Archived from the original on 13 July 2016 Retrieved 15 July 2016 Pemfexy FDA Approved Drugs U S Food and Drug Administration FDA Archived from the original on 19 October 2020 Retrieved 13 February 2020 Belani CP Brodowicz T Ciuleanu T Kim JH Krzakowski M Laack E et al June 2009 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 27 18 suppl American Society of Clinical Oncology CRA8000 doi 10 1200 jco 2009 27 18 suppl cra8000 Archived from the original on 16 June 2009 Retrieved 22 July 2009 Carteni G Manegold C Garcia GM Siena S Zielinski CC Amadori D et al May 2009 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 doi 10 1016 j lungcan 2008 08 013 PMID 19042053 External links edit Pemetrexed disodium NCI Drug Dictionary National Cancer Institute Pemetrexed disodium National Cancer Institute 5 October 2006 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Pemetrexed amp oldid 1216434034, wikipedia, wiki, book, books, library,

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