Overview
11. DESCRIPTION Pemetrexed is a folate analog metabolic inhibitor. The drug substance, Pemetrexed Disodium Hemipentahydrate, has the chemical name disodium N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl] benzoyl]-L-glutamic acid hemipentahydrate, with a molecular formula of C 20 H 19 N 5 Na 2 O 6 •2.5 H 2 O and a molecular weight of 516.41.
Mechanism of Action
12. CLINICAL PHARMACOLOGY 12.1 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. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. 12.
Indications
- 1. INDICATIONS AND USAGE PEMRYDI RTU ® 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. ( 1.1 ) in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC. ( 1.
Common Doses
- 45 mL
- 500 mg
- 400 mcg
- 000 mcg
Dosage
2. DOSAGE AND ADMINISTRATION The recommended dose of PEMRYDI RTU 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. ( 2.1 ) The recommended dose of PEMRYDI RTU, administered as a single agent or with cisplatin, in patients with creatinine clearance of 45 mL/minute or greater is 500 mg/m 2 as an intravenous infusion over 10...
Contraindications
- 4. CONTRAINDICATIONS PEMRYDI RTU is contraindicated in patients with a history of severe hypersensitivity reaction to pemetrexed [see Adverse Reactions (6.1) ]. History of severe hypersensitivity reaction to pemetrexed. ( 4 )
Side Effects
- 6. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] Renal failure [see Warnings and Precautions (5.2) ] Bullous and exfoliative skin toxicity [see Warning and Precautions (5.3) ] Interstitial pneumonitis [see Warnings and Precautions (5.4) ] Radiation recall [see Warnings and Precautions (5.5) ] The most common adverse reactions (incidence ≥ 20%) of pemetrexed, when administered as a single agent are fatigue, nausea, and anorexia. ( 6.
Interactions
- 7. DRUG INTERACTIONS Effects of Ibuprofen on Pemetrexed Ibuprofen increases exposure (AUC) of pemetrexed [see Clinical Pharmacology ( 12.3 ) ] . In patients with creatinine clearance between 45 mL/min and 79 mL/min: Avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of PEMRYDI RTU [see Dosage and Administration ( 2.5 ) ] . Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided.