Pemetrexed (Alimta)

General information

Class/mechanism: Folate analog, antimetabolite. Pemetrexed inhibits the activity of several folate-dependent enzymes involved in the synthesis of thymidine and purine nucleotides, such as thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT).
Route: IV
Extravasation: neutral

Supportive care examples:

• Patients should take daily folic acid (example dose: 1mg PO daily) while on therapy and at least 5 doses in the 7 days before starting Pemetrexed (Alimta) therapy.
• Vitamin B12 1000mcg should be given during the week before the first dose of Pemetrexed (Alimta) and then every 3 cycles thereafter.
• Dexamethasone 4mg PO twice per day the day before, the day of, and day after Pemetrexed (Alimta) helps to reduce the incidence and severity of cutaneous reactions.

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established (work in progress)

• Malignant pleural mesothelioma
• Non-small cell lung cancer, nonsquamous

Diseases for which it is used

• Breast cancer
• Cervical cancer
• Non-small cell lung cancer
• Ovarian cancer
• Urothelial carcinoma

Diseases for which it is contraindicated

• Non-small cell lung cancer, squamous

Patient drug information

• Brief patient counseling information can be found in the Pemetrexed (Alimta) package insert
• Pemetrexed (Alimta) patient drug information (Chemocare)
• Pemetrexed (Alimta) patient drug information (UpToDate)

History of changes in FDA indication

Malignant pleural mesothelioma

• 2004-02-04: Initial approval in combination with cisplatin is indicated for the treatment of patients with malignant pleural mesothelioma whose disease is either unresectable or who are otherwise not candidates for curative surgery. (Based on EMPHACIS)
• 2008-09-26: Indication revised for mesothelioma in combination with cisplatin. (Based on EMPHACIS)

Non-small cell lung cancer

• 2004-08-19: Accelerated approval as a single-agent for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after prior chemotherapy. (New disease entity; based on JMEI)

Non-small cell lung cancer, nonsquamous

• 2008-09-26: Accelerated approval for nonsquamous non-small cell lung cancer initial treatment in combination with cisplatin. (Based on JMDB)
• 2008-09-26: Accelerated approval for nonsquamous non-small cell lung cancer as a single-agent after prior chemotherapy. (Based on JMEI)
• 2009-07-02: Converted to regular approval and additional indication for nonsquamous non-small cell lung cancer: Maintenance treatment of patients whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. (Based on JMEN & PARAMOUNT)
  • Limitation: "not indicated for the treatment of patients with squamous cell non-small cell lung cancer."
• 2018-06-04: Accelerated approval in combination with pembrolizumab and carboplatin for first-line treatment of metastatic non-squamous NSCLC. (Based on KEYNOTE-189)
  • 2019-01-30: Converted to regular approval

History of changes in EMA indication

• 2004-09-20: Initial marketing authorization as Alimta.

History of changes in Health Canada indication

• 2004-05-21: Initial notice of compliance (details unavailable)
• 2007-01-11: New indication as monotherapy for patients with locally advanced or metastatic non-small cell lung cancer after prior chemotherapy.
• 2008-09-02: New indication in combination with cisplatin therapy for the initial treatment of good performance status patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.
• 2010-05-11: New indication as mintenance treatment of locally advanced or metastatic nonsquamous non-small cell lung cancer, in a good performance status patients without disease progression immediately following four cycles of first-line platinum doublet chemotherapy, excluding pemetrexed.
• 2013-05-09: Revised monotherapy indication to permit continuous Alimta maintenance treatment in patients with advanced nonsquamous NSCLC, immediately following Alimta-containing first-line platinum doublet chemotherapy.

History of changes in PMDA indication

• 2007-01-04: Initial approval for use to treat malignant pleural mesothelioma in combination with cisplatin.
• 2009-05-20: New additional indication for the treatment of unresectable advanced or recurrent non-small cell lung cancer.

Also known as

• Generic name: pemetrexed disodium
• Brand names: Alimta, Antifol, Armisarte, Ciambra, Kabipem, Pemcure, Pemetero, Pemetra, Pemetrex, Pemex, Pemfexy, Pemgem, Pemibenz, Pemnat, Pemrydi, Pexotra