Pemetrexed

What it is and how it works

Mechanism of Action Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. In vitro studies show that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase.

Indications

Pemetrexed for injection is a folate analog metabolic inhibitor indicated: in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC. as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy. Limitations of Use: Pemetrexed for injection is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer. initial treatment, in combination with cisplatin, of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.

Dosage and administration (summary)

The recommended dose of pemetrexed for injection administered with pembrolizumab and platinum chemotherapy in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m 2 as an intravenous infusion over 10 minutes, administered after pembrolizumab and prior to platinum chemotherapy, on Day 1 of each 21-day cycle. The recommended dose of pemetrexed for injection, administered as a single agent or with cisplatin, in patients with creatinine clearance of 45 mL/minute or greater is 500 mg/m² as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle.

Contraindications

Pemetrexed for Injection is contraindicated in patients with a history of severe hypersensitivity reaction to pemetrexed . History of severe hypersensitivity reaction to pemetrexed.

Warnings and precautions

Myelosuppression: Can cause severe bone marrow suppression resulting in cytopenia and an increased risk of infection. Do not administer pemetrexed when the absolute neutrophil count is less than 1500 cells/mm 3 and platelets are less than 100,000 cells/mm 3 . Initiate supplementation with oral folic acid and intramuscular vitamin B 12 to reduce the severity of hematologic and gastrointestinal toxicity of pemetrexed. ( 2.4 , 5.1 ) Renal Failure: Can cause severe, and sometimes fatal, renal failure. Do not administer when creatinine clearance is less than 45 mL/min.

Pregnancy

Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, pemetrexed can cause fetal harm when administered to a pregnant woman . There are no available data on pemetrexed use in pregnant women.

Storage and supply

How Supplied Pemetrexed for Injection, USP is a white to either light-yellow or green-yellow lyophilized cake or powder available in sterile single-dose vials for reconstitution for intravenous infusion.

Source: Pemetrexed Disodium (Pemetrexed) — US FDA prescribing information, 2023-04-26, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.