Пеметрекседа динатрия гептагидрат
Пеметрекседа динатрия гептагидрат Uses, Dosage, Side Effects, Food Interaction and all others data.
Пеметрекседа динатрия гептагидрат is a thymidylate synthase inhibitor. It works by inhibiting thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase and aminoimidazole carboxamide ribonucleotide formyltransferase, the enzymes involved in folate metabolism and DNA synthesis, thus inhibiting purine and thymidine nucleotide and protein synthesis.
Preclinical studies have shown that pemetrexed inhibits the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052). Studies with the MSTO-211H mesothelioma cell line showed synergistic effects when pemetrexed was combined concurrently with cisplatin.
Trade Name | Пеметрекседа динатрия гептагидрат |
Availability | Prescription only |
Generic | Pemetrexed |
Pemetrexed Other Names | Pemetrexed |
Related Drugs | Opdivo, methotrexate, Keytruda, pembrolizumab, cisplatin, Tagrisso, Avastin, nivolumab, ipilimumab, Alimta |
Type | |
Formula | C20H21N5O6 |
Weight | Average: 427.4106 Monoisotopic: 427.149183429 |
Protein binding | 81% |
Groups | Approved, Investigational |
Therapeutic Class | Cytotoxic Chemotherapy |
Manufacturer | |
Available Country | Russia |
Last Updated: | September 19, 2023 at 7:00 am |
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Uses
Пеметрекседа динатрия гептагидрат is used for:
- Initial treatment of patients with locally advanced or metastatic, non-squamous, non-small cell lung cancer (NSCLC) in combination with cisplatin.
- 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.
- Treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy, as a single agent.
Пеметрекседа динатрия гептагидрат is also used to associated treatment for these conditions: Mesothelioma, Ovarian Cancer, Pleural Mesotheliomas, Urothelial carcinoma ureter metastatic, Locally advanced nonsquamous non-small cell lung cancer, Metastatic nonsquamous non-small cell lung cancer, Recurrent, IV-B Cervical cancer, Unresectable Thymoma
How Пеметрекседа динатрия гептагидрат works
Пеметрекседа динатрия гептагидрат is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Пеметрекседа динатрия гептагидрат is transported into cells by both 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. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Dosage
Пеметрекседа динатрия гептагидрат dosage
Recommended Dosage And Schedule For Non-Squamous NSCLC:
- The recommended dose of Пеметрекседа динатрия гептагидрат in combination with cisplatin for initial treatment of NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m² as an intravenous infusion over 10 minutes administered prior to cisplatin on Day 1 of each 21-day cycle for up to six cycles in the absence of disease progression or unacceptable toxicity.
- The recommended dose of Пеметрекседа динатрия гептагидрат for maintenance treatment of NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m² as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity after four cycles of platinum-based first-line chemotherapy.
- The recommended dose of Пеметрекседа динатрия гептагидрат for treatment of recurrent NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m² as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
Recommended Dosage And Schedule For Mesothelioma: The recommended dose of Пеметрекседа динатрия гептагидрат, administered in combination with cisplatin, in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m² as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
Side Effects
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Myelosuppression
- Renal failure
- Bullous and exfoliative skin toxicity
- Interstitial pneumonitis
- Radiation recall
Precaution
Monitor CBC. Premedication with folate and vitamin B12 are recommended as prophylaxis against haematological and GI toxicity during treatment. Pre-treatment with a corticosteroid also reduces the incidence and severity of skin reactions. Caution when used in renal or hepatic impairment. Not recommended for use in pregnancy and lactation.
Interaction
High doses of NSAIDs and aspirin may reduce the elimination of pemetrexed; avoid usage 2 days (5 days for longer-acting NSAIDs) before, during and 2 days after treatment with pemetrexed in patients with impaired renal function. Additive GI side effects when used with SSRIs, acetylcholinesterase inhibitors, aripiprazole or ziprasidone. Additive sedation when used with psychotropics. Concurrent use with nephrotoxic drugs (e.g. aminoglycosides, loop diuretics, platinum compounds and ciclosporin) may decrease pemetrexed clearance, thus increasing the risk of toxicity. Clearance may be reduced when used with drugs that are cleared by tubular secretion e.g. probenecid and penicillin.
Food Interaction
- Administer folic acid supplement. Folic acid supplement of 400 to 1000 mcg daily should be given 7 days before treatment with pemetrexed and continued until 21 days after discontinuation of pemetrexed to reduce the risk of hematologic and gastrointestinal toxicities.
- Administer vitamin supplements. Administration of vitamin B12 intramuscular supplement one week before treatment with pemetrexed and every three cycles will reduce the risk of hematological and gastrointestinal toxicities.
Пеметрекседа динатрия гептагидрат Drug Interaction
Moderate: aspirin, aspirin, carboplatinUnknown: paclitaxel protein-bound, fluticasone / salmeterol, lorazepam, bevacizumab, apixaban, pembrolizumab, guaifenesin, acetaminophen / hydrocodone, acetaminophen, bismuth subsalicylate, tiotropium, acetaminophen / diphenhydramine, albuterol, cyanocobalamin, cholecalciferol, ezetimibe, ondansetron
Пеметрекседа динатрия гептагидрат Disease Interaction
Major: myelosuppressionModerate: liver dysfunction, renal dysfunction
Volume of Distribution
- 16.1 L
Half Life
3.5 hours
Clearance
- 91.8 mL/min [Cancer patients with normal renal function receiving 0.2 to 838 mg/m2 infusion over a 10-minute period]
Elimination Route
Пеметрекседа динатрия гептагидрат is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration.
Pregnancy & Breastfeeding use
Pregnancy Category D. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Lactation: Advise women not to breastfeed during treatment with Пеметрекседа динатрия гептагидрат and for 1 week after the final dose
Contraindication
Пеметрекседа динатрия гептагидрат is contraindicated in patients with a history of severe hypersensitivity reaction to pemetrexed
Special Warning
Renal Impairment: Пеметрекседа динатрия гептагидрат dosing recommendations are provided for patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater. There is no recommended dose for patients whose creatinine clearance is less than 45 mL/min
Pediatric Use: The safety and effectiveness of Пеметрекседа динатрия гептагидрат in pediatric patients have not been established.
Geriatric Use: Of the 3,946 patients enrolled in clinical studies of Пеметрекседа динатрия гептагидрат, 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.
Acute Overdose
No drugs are approved for the treatment of Пеметрекседа динатрия гептагидрат overdose. Based on animal studies, administration of leucovorin may mitigate the toxicities of Пеметрекседа динатрия гептагидрат overdosage. It is not known whether pemetrexed is dialyzable.
Storage Condition
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Innovators Monograph
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Пеметрекседа динатрия гептагидрат contains Pemetrexed see full prescribing information from innovator Пеметрекседа динатрия гептагидрат Monograph, Пеметрекседа динатрия гептагидрат MSDS, Пеметрекседа динатрия гептагидрат FDA label