PEMETREXED- pemetrexed disodium injection, powder, lyophilized, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

Pemetrexed Disodium Hemipentahydrate (UNII: F4GSH45R4C) (Pemetrexed - UNII:04Q9AIZ7NO)

Available from:

Biocon Pharma Inc

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Pemetrexed for injection is 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 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. 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 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. 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 [see Clinical Studies (14.1)] . Pemetrexed for injection is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. Pemetrexed for injection is contraindicated in patients with a history of severe hypersensitivity reaction to pemetrexed [see Adverse Reactions (6.1)] . Risk Summary Based on findings from animal studies and its mechanism of action, pemetrexed can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ]. There are no available data on pemetrexed use in pregnant women. In animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and malformations at doses lower than the recommended human dose of 500 mg/m2  [see Data ]. Advise pregnant women of the potential risk to a fetus [see Use in Special Populations (8.3) ].  In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.  Data Animal Data Pemetrexed was teratogenic in mice. Daily dosing of pemetrexed by intravenous injection to pregnant mice during the period of organogenesis increased the incidence of fetal malformations (cleft palate; protruding tongue; enlarged or misshaped kidney; and fused lumbar vertebra) at doses (based on BSA) 0.03 times the human dose of 500 mg/m2 . At doses, based on BSA, greater than or equal to 0.0012 times the 500 mg/m2 human dose, pemetrexed administration resulted in dose-dependent increases in developmental delays (incomplete ossification of talus and skull bone; and decreased fetal weight). Risk Summary  There is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from pemetrexed, advise women not to breastfeed during treatment with pemetrexed and for one week after the last dose. Based on animal data pemetrexed can cause malformations and developmental delays when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating Pemetrexed Injection [see Use in Specific Populations (8.1)]. Contraception Females Because of the potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment with pemetrexed and for 6 months after the last dose. Males Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with pemetrexed and for 3 months after the last dose [see Nonclinical Toxicology (13.1)] . Infertility Males Pemetrexed may impair fertility in males of reproductive potential. It is not known whether these effects on fertility are reversible [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of pemetrexed in pediatric patients have not been established. The safety and pharmacokinetics of pemetrexed were evaluated in two clinical studies conducted in pediatric patients with recurrent solid tumors. (NCT00070473 N=32 and NCT00520936 N=72). Patients in both studies received concomitant vitamin B12 and folic acid supplementation and dexamethasone. No tumor responses were observed. Adverse reactions observed in pediatric patients were similar to those observed in adults. Single-dose pharmacokinetics of pemetrexed were evaluated in 22 patients age 4 to 18 years enrolled in NCT00070473 were within range of values in adults. Of the 3,946 patients enrolled in clinical studies of pemetrexed, 34% were 65 and over and 4%  were 75 and over. No overall differences in effectiveness were observed between these patients and younger patients. The incidences of Grade 3-4 anemia, fatigue, thrombocytopenia, hypertension, and neutropenia were higher in patients 65 years of age and older as compared to younger patients: in at least one of five randomized clinical trials. [see Adverse Reactions (6.1) and Clinical Studies ( 14.1 , 14.2)]. Pemetrexed is primarily excreted by the kidneys. Decreased renal function results in reduced clearance and greater exposure (AUC) to pemetrexed compared with patients with normal renal function [Warnings and Precautions ( 5.2 , 5.6 ) and Clinical Pharmacology ( 12.3 ) ]. No dose is recommended for patients with creatinine clearance less than 45 mL/min [see Dosage and Administration (2.3)] .

Product summary:

How Supplied   Pemetrexed for injection, USP is a white to either light yellow or green-yellow lyophilized powder or cake supplied in single-dose vials for reconstitution for intravenous infusion.   NDC 70377-022-11: Carton containing one (1) single-dose vial of 1000 mg pemetrexed.   Storage and Handling   Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Pemetrexed for injection, USP is a hazardous drug. Follow applicable special handling and disposal procedures.1

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

PEMETREXED- PEMETREXED DISODIUM INJECTION, POWDER, LYOPHILIZED, FOR
SOLUTION
BIOCON PHARMA INC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PEMETREXED FOR
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
PEMETREXED FOR
INJECTION.
PEMETREXED FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2004
INDICATIONS AND USAGE
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. (_1.1_)
• in combination with cisplatin for the initial treatment of
patients with locally advanced or metastatic, non-
squamous NSCLC. _(1.1)_
• 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. _(1.1)_
• as a single agent for the treatment of patients with recurrent,
metastatic non-squamous, NSCLC after
prior chemotherapy. _(1.1)_
Limitations of Use: Pemetrexed for injection is not indicated for the
treatment of patients with squamous
cell, non-small cell lung cancer. _(1.1)_
• 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. _(1.2)_
DOSAGE AND ADMINISTRATION
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 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 pemetrexed for injection, administered as a
single agent or with cis