[vc_row][vc_column][vc_tta_tour color=”peacoc” active_section=”1″][vc_tta_section title=”Description” tab_id=”1587814602310-455b0101-930d”][vc_column_text]Pemetrexed disodium heptahydrate has the chemical name L-Glutamine acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-,disodium salt, heptahydrate. It is a white to almost-white solid with a molecular formula of C20H19N5Na2O67H2O \u00a0and a molecular weight of 597.49. The Structural formula is as follows:<\/p>\n
![\"Antifol\"](\"https:\/\/i0.wp.com\/www.zuviuslifesciences.in\/media\/23325\/antifol.jpg?ssl=1\")
[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Composition” tab_id=”1593250992409-617e0c2e-8c3a”][vc_column_text]Each 100 mg vial contains:
\nPemetrexed Disodium IP Equivalent to
\nPemetrexed\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026.100 mg
\nMannitol \u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026106 mg<\/p>\n
Each 500 mg vial contains:
\nPemetrexed Disodium IP Equivalent to
\nPemetrexed\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026.500 mg
\nMannitol \u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026\u2026500 mg[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Mechanism of Action” tab_id=”1584624217032-a15849ed-97bb”][vc_column_text]<\/p>\n
[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Pharmacokinetics” tab_id=”1584624217050-ebb8ae5e-43a6″][vc_column_text]<\/p>\n
The pharmacokinetics of Pemetrexed administered as a single-agent in doses ranging from 0.2 to 838 mg\/m2 infused over a 10-minute period have been evaluated in \u00a0426 cancer patients with a variety of solids tumors. Pemetrexed total systemic exposure (AUC) and maximum plasma concentration (Cmax) increases proportionally with dose. The pharmacokinetics of Pemetrexed do not change over multiple treatment cycles.<\/p>\n
Pemetrexed has a \u00a0steady-state volume of distribution of 16.1 liters. Pemetrexed is approximately \u00a081% bound to plasma proteins. Binding is not affected by the degree of renal impairment.<\/p>\n
[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Indications” tab_id=”1584624459062-96fb7e5b-0e23″][vc_column_text]A. Nonsquamous Non-Small Cell \u00a0Lung Cancer-Combination with Cisplatin<\/strong><\/p>\n Pemetrexed is indicated in combination with cisplatin therapy for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer.<\/p>\n B. Nonsquamous Non-Small Cell \u00a0Lung Cancer-Maintenance<\/strong><\/p>\n Pemetrexed is indicated for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.<\/p>\n C. Nonsquamous Non-Small Cell \u00a0Lung Cancer \u2013 After Prior Chemotherapy<\/strong><\/p>\n Pemetrexed is indicated as a single-agent for the treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer after prior chemotherapy.<\/p>\n D. Mesothelioma<\/strong><\/p>\n Pemetrexed in combination with cisplatin is indicated for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.<\/p>\n Limitations of Use<\/strong> Pemetrexate is not indicated for the treatment of patients with squamous cell non-small cell lung cancer.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Dosage & Administration” tab_id=”1584624839401-59481bbb-bdc7″][vc_column_text]<\/p>\n The recommended dose of Pemetrexed is 500 mg\/m2infused over 2 hours beginning approximately 30 minutes after the end of the cycle. The recommended dose of cisplatin is 75 mg\/m2infused over 2 hours beginning approximately 30 minutes after the end of Pemetrexed administration.<\/p>\n Single-Agent Use as Maintenance Following First-Line Therapy, or as a Second-Line Therapy\u00a0The recommended dose of Pemetrexed is 500 mg\/m2 administered as an intravenous infusion over 10minutes on Day 1 of each 21-day cycle.<\/p>\n Folic acid 400 mcg to 1000 mcg orally to be initiated once daily, beginning 7 days before the first<\/p>\n The dose of Pemetrexed. Continue folic acid during the full course of therapy and for 21 days the last dose of Pemetrexed.<\/p>\n Vitamin B12 1mg intramuscularly 1 week prior to the first dose of Pemetrexed and every 3 cycles thereafter to be administered. Subsequent vitamin B12 injections may be given the same day as treatment with Pemetrexed.<\/p>\n Administer dexamethasone 4mg by mouth twice daily the day before, the day of, and the day after Pemetrexed administration.<\/p>\n Table 1: Dose Reduction for Pemetrexed (single-agent or in combination) and Cisplatin- Hematologic Toxicities<\/strong><\/p>\n If patients develop nonhematologic toxicities (excluding neurotoxicity)=Grade 3, treatment should be withheld until resolution to less than or equal to the patient\u2019s pre-therapy value. Treatment should be resumed according to guidelines in Table 2.<\/p>\n Table 2: Dose Reduction for Pemetrexed (single-agent or in combination) and Cisplatin-Nonhematologic Toxicities<\/strong><\/p>\n in the event of neurotoxicity, the recommended dose adjustments for Pemetrexed and cisplatin are described in Table 3. Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is experienced.<\/p>\n Table 3: Dose Reduction for Pemetrexed (single-agent or in combination) and Cisplatin – Neurotoxicity<\/strong><\/p>\n Discontinuation Recommendation:<\/strong><\/p>\n Pemetrexed therapy should be discontinued if a patient experiences any hematologic or nonhematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if grade 3 or 4 neurotoxicity is observed.<\/p>\n Renal Impaired Patients:<\/strong><\/p>\n In clinical studies, patients with creatinine clearance = 45 ml\/min required no dose adjustments other than those recommended for all patients. Insufficient numbers of patients with creatinine clearance below 45 ml\/min have been treated to make dosage recommendations for this group of patients. Therefore, Pemetrexed should not be administered to patients whose creatinine clearance is < 45ml\/min using the standard Cockcroft and Gault formula (below) or GFR measured by Tc99m-DTPA serum clearance method:<\/p>\n Caution should be exercised when administering Pemetrexed concurrently with NSAIDs to patients whose creatinine clearance is <80 ml\/min<\/p>\n USE IN SPECIFIC POPULATIONS<\/strong><\/p>\n i. Pregnancy-Teratogenic Effects-Pregnancy Category D<\/strong><\/p>\n Embryotoxicity was characterized by increased embryo-fetal deaths and reduced litter size. If Pemetrexed is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.<\/p>\n ii. Nursing Mothers<\/strong><\/p>\n it is not known whether Pemetrexed or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Pemetrexed, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug for the mother.<\/p>\n iii. Pediatric Use<\/strong><\/p>\n The efficacy of Pemetrexed in pediatric patients has not been demonstrated. The most common toxicities reported were hematological (Leukopenia, Neutropenia \/ Granulocytopenia, Anemia, thrombocytopenia, and Lymphopenia), liver function abnormalities (increased ALT\/AST), fatigue, and nausea.<\/p>\n iv. Geriatric Use<\/strong><\/p>\n Pemetrexed is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Renal fusion monitoring is recommended with the administration of Pemetrexed. No dose reductions other than those recommended for all patients are necessary for patients 65 years of age or older.<\/p>\n v. Patients with Hepatic Impairment<\/strong><\/p>\n There was no effect of elevated AST, ALT, or total bilirubin on the pharmacokinetics of Pemetrexed.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Warnings” tab_id=”1584625017135-3ffdd9c5-1bd6″][vc_column_text]i. Bone \u00a0Marrow Suppression<\/strong><\/p>\n Pemetrexed \u00a0can suppress bone marrow function, as manifested by Neutropenia. \u00a0Thrombocytopenia, and Anemia (or pancytopenia): myelosuppression is usually the \u00a0dose-limiting toxicity. Dose reductions for subsequent cycles are based on \u00a0nadir ANC, platelet count, and maximum non hematologic toxicity seen in the \u00a0previous cycle.<\/p>\n ii. \u00a0Decreased Renal Function<\/strong><\/p>\n Pemetrexed \u00a0is primarily eliminated unchanged by renal excretion. No dosage adjustment is \u00a0needed in patients with creatinine = 45ml\/min. Use with Non-Steroidal \u00a0Anti-Inflammatory Drugs (NSAIDs) with Mild to Moderate Renal Insufficiency \u00a0caution should be used when administering NSAIDs concurrently with Pemetrexed to \u00a0patients with mild to moderate renal insufficiency caution should be used when \u00a0administering NSAIDs concurrently with Pemetrexed to patients with mild to \u00a0moderate renal insufficiency (creatinine clearance from 45 to 79ml\/min.<\/p>\n iii. \u00a0Required Laboratory Monitoring<\/strong><\/p>\n Obtain a \u00a0complete blood count and renal function tests at the beginning of each cycle \u00a0and as needed. Do not initiate a cycle of treatment unless the ANC is = 1500 \u00a0cells\/mm3, and creatinine clearance is = 45 ml\/min.<\/p>\n iv. \u00a0Nonclinical Toxicology<\/strong><\/p>\n Carcinogenesis, Mutagenesis, Impairment of Fertility[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Precautions” tab_id=”1587808637782-6ed24bad-7751″][vc_column_text]Each \u00a0100mg vial to be reconstituted with 4.22 ml of 0.9% (w\/v) Sodium Chloride \u00a0Injection IP and gently mixed so that the powder is completely dissolved.<\/p>\n Each 500mg vial to be reconstituted with 20ml of \u00a00.9% (w\/v) Sodium Chloride IP and gently mixed so that the powder is complety \u00a0dissolved. The resulting solution is clear and ranges in color from colorless \u00a0to yellow or green-yellow chemical and physical stability of reconstituted and \u00a0infusion solutions of Pemetrexed were demonstrated for up to 24 hours following \u00a0initial reconstitution, when stored refrigerated, 2-8\u00b0C (36-46\u00b0F). When \u00a0prepared as directed, reconstituted and infusion solutions of Pemetrexed \u00a0contain no antimicrobial preservatives. Unused portion is discarded. Pemetrexed \u00a0is not light sensitive.<\/p>\n Each \u00a0100mg vial to be reconstituted with 4.22 ml of 0.9% (w\/v) Sodium Chloride \u00a0Injection IP and gently mixed so that the powder is completely dissolved.<\/p>\n Each 500mg vial to be reconstituted with 20ml of \u00a00.9% (w\/v) Sodium Chloride IP and gently mixed so that the powder is complety \u00a0dissolved. The resulting solution is clear and ranges in color from colorless \u00a0to yellow or green-yellow chemical and physical stability of reconstituted and \u00a0infusion solutions of Pemetrexed were demonstrated for up to 24 hours following \u00a0initial reconstitution, when stored refrigerated, 2-8\u00b0C (36-46\u00b0F). When \u00a0prepared as directed, reconstituted and infusion solutions of Pemetrexed \u00a0contain no antimicrobial preservatives. Unused portion is discarded. Pemetrexed \u00a0is not light sensitive.<\/p>\n Each \u00a0100mg vial to be reconstituted with 4.22 ml of 0.9% (w\/v) Sodium Chloride \u00a0Injection IP and gently mixed so that the powder is completely dissolved.<\/p>\n Each 500mg vial to be reconstituted with 20ml of \u00a00.9% (w\/v) Sodium Chloride IP and gently mixed so that the powder is completely dissolved. The resulting solution is clear and ranges in color from colorless to yellow or green-yellow chemical and physical stability of reconstituted and infusion solutions of Pemetrexed were demonstrated for up to 24 hours following initial reconstitution, when stored refrigerated, 2-8\u00b0C (36-46\u00b0F). When prepared as directed, reconstituted and infusion solutions of Pemetrexed contain no antimicrobial preservatives. The unused portion is discarded. Pemetrexed is not light sensitive.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Adverse Reactions (Side Effects)” tab_id=”1587812330006-86cccd10-63d1″][vc_column_text]The most \u00a0common adverse reaction (incidence=20%) during therapy with Pemetrexed as a \u00a0single-agent were fatigue, nausea, and anorexia. Additional common adverse \u00a0reactions (incidence=20%) during therapy with Pemetrexed when used in \u00a0combination with cisplatin included vomiting, neutropenia, leukopenia, anemia, \u00a0stomatitis\/pharyngitis, thrombocytopenia, and constipation.<\/p>\n Clinically \u00a0relevant adverse reactions occurring in < 5% of patients that received \u00a0Pemetrexed Treatment but >5% of patients that received Docetaxel include CTC \u00a0Grade \u00be febrile neutropenia (1.9% Pemetrexed, 12.7% Docetaxel).[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Drug Interactions” tab_id=”1587812369059-f5b91b55-8fed”][vc_column_text]Non-Steroidal Anti-Inflammatory \u00a0Drugs (NSAIDs)<\/p>\n No dose adjustment of Pemetrexed \u00a0is needed with concomitant NSAIDs in patients with normal renal function. \u00a0Caution should be used when administering NSAIDs concurrently with Pemetrexed \u00a0to patients with mild to moderate renal insufficiency (creatinine clearance \u00a0form 45 to 79 ml\/min).<\/p>\n <\/p>\n NSAIDs with short elimination \u00a0half-lives (e.g. diclofenac, indomethacin) should be avoided for a period of 2 \u00a0days before, the day of, and 2 days following administration of Pemetrexed. \u00a0Nephrotoxic Drugs.<\/p>\n Pemetrexed is primarily eliminated \u00a0unchanged renally as a result of glomerular filtration and tubular secretion. \u00a0Concomitant administration of nephrotoxic drugs could result in delayed \u00a0clearance of Pemetrexed. Concomitant administration of substances that are also \u00a0tubularly secreted (e.g. probenecid) could potentially result in delayed \u00a0clearance of Pemetrexed.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Overdose & Contradiction” tab_id=”1587812398768-c6cb414e-2e90″][vc_column_text]OVERDOSE<\/strong><\/p>\n There have been few cases of Pemetrexed overdose. Reported toxicities included neutropenia, anemia, thrompocytopenia, mucositis, and rash. Anticipated complications of overdose include bone marrow suppression as manifested by neutropenia, thrombocytopenia, and anemia. In addition, infection with or without fever, diarrhea, and mucositis may be seen. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating physician.<\/p>\n CONTRAINDICATION<\/strong><\/p>\n Pemetrexed is contraindicated in patients who have a history of severe hypersensitivity reactions to Pemetrexed.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Storage” tab_id=”1587813927799-585d2f81-fcdb”][vc_column_text]Pemetrexed \u00a0injection, should be stored at 25\u00b0C (77\u00b0F); excursions permitted to 15-30\u00b0C \u00a0(59-86\u00b0F).<\/p>\n The use \u00a0of gloves is recommended. If a solution of Pemetrexed contacts the skin, wash \u00a0the skin immediately and thoroughly with soap and water. If Pemetrexed contacts \u00a0the mucous membranes, flush thoroughly with water. Pemetrexed is not a \u00a0vesicant. There is no specific antidote for extravasation of Pemetrexed. \u00a0Pemetrexed extravasation should be managed with local standard practice for \u00a0extravasation as with other non-vesicants.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Presentation” tab_id=”1587814105044-095e8d3d-15ec”][vc_column_text]Antifol\u00a0TM<\/sup>:<\/strong>\u00a0Single vial of Pemetrexed injection 100mg and 500mg[\/vc_column_text][\/vc_tta_section][\/vc_tta_tour][\/vc_column][\/vc_row]<\/p>\n","protected":false},"excerpt":{"rendered":"\n\n
\n
\n
\n
\n\n
\n Nadir ANC < 500\/mm3 and nadir platelets 50,000\/ mm3<\/td>\n 75% of previous dose (Pemetrexed and cisplatin).<\/td>\n<\/tr>\n \n Nadir platelets < 50,000\/ mm3without bleeding regardless of nadir ANC.<\/td>\n 75% of previous dose (Pemetrexed and cisplatin).<\/td>\n<\/tr>\n \n Nadir platelets < 50,000\/ mm3without bleeding regardless of nadir ANC.<\/td>\n 50% of previous dose (Pemetrexed and cisplatin).<\/td>\n<\/tr>\n \n *These criteria meet the CTC version 2.0 (NCI 1998) definition of = CTC Grade 2 bleeding.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n \n\n
\n <\/td>\n DOSE OF Pemetrexed (MG\/M2<\/sup>)<\/strong><\/td>\n DOSE OF CISPLATIN (MG\/M2<\/sup>)<\/strong><\/td>\n<\/tr>\n \n Any Grade 3 or 4 toxicities except mucositis<\/td>\n 75% of previous dose<\/td>\n 75% of previous dose<\/td>\n<\/tr>\n \n Any diarrhea requiring hospitalization (irrespective of Grade) or Grade 3 or 4 diarrhea<\/td>\n 75% of previous dose<\/td>\n 75% of previous dose<\/td>\n<\/tr>\n \n Grade 3 or 4 mucositis<\/td>\n 50% of previous dose<\/td>\n 100% of previous dose<\/td>\n<\/tr>\n \n a NCI Common Toxicity Criteria (CTC)<\/td>\n <\/td>\n <\/td>\n<\/tr>\n \n b Excluding neurotoxicity (see Table 3).<\/td>\n <\/td>\n <\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n \n\n
\n CTCGRADE<\/strong><\/td>\n DOSE OF Pemetrexed (MG\/M2<\/sup>)<\/strong><\/td>\n DOSE OF CISPLATIN (MG\/M2<\/sup>)<\/strong><\/td>\n<\/tr>\n \n 0-1<\/td>\n 100% of previous dose<\/td>\n 100% of previous dose<\/td>\n<\/tr>\n \n 2<\/td>\n 100% of previous dose<\/td>\n 50% of previous dose<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n \n\n
\n <\/td>\n (weight in kg) x (140-age)<\/td>\n<\/tr>\n \n Males :<\/strong><\/td>\n (72) x serum creatinine (mg\/100ml.)<\/td>\n<\/tr>\n \n Females :<\/strong><\/td>\n estimated creatinine clearance for males x 0.85<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Pemetrexed Inj – 100MG , 500MG<\/h3>\n