Pemetrexed inhibits thymidylate transferase. Pemetrexed is administered as a solution via injection into a vein and is usually given once every 21 days.
Antimetabolites, the class of chemotherapeutic drugs Pemetrexed belongs to, are quite similar to normal substances that exist within a human cell. When these substances are incorporated into the cellular metabolism, the cells are unable to divide. Antimetabolites target cells at specific cell phases and are classified according to the substances they interfere with.
Pemetrexed, which is an antifolate,
interferes with cell metabolic processes that are dependent on
folate and are required for cell replication. Premetrexed inhibits
three enzymes that are required for purine and pyrimidine synthesis.
These three enzymes are thymidylate synthase (TS), dihydrofolate
reductase (DHFR), and glycinamide ribonucleotide formyl transferase
(GARFT). When Premetrexed inhibits the formation of precursor
purine and pyrimidine nucleotides, it prevents the formation of
DNA and RNA required for growth and survival of both cancer and
normal cells.
Dosage and Administration: Pemetrexed and Non-Small Cell Lung Cancer
Pemetrexed has a 10-minute outpatient infusion.
Dosing and method of administration for pemetrexed
pemetrexed (single agent) dosing and scheduling—21 day cycle
Folic Acid
Daily low-dose 350µg to 1000µg by mouth (the most commonly used
dose of oral folic acid in clinical trials was 400µg). At least
5 daily doses must be taken during this 7-day period preceding
the first dose of pemetrexed and continuing throughout treatment
and for 21 days after the last dose of pemetrexed.
Vitamin B12 - every 3 cycles
IM injection of 1000µg. Patients must receive one IM injection
during the week preceding the first dose of pemetrexed and every
3 cycles thereafter.
Dexamethasone
4 mg by mouth twice daily on the day before, day of, and the day
after treatment to help prevent skin rash.
pemetrexed
Day 1
500 mg/m2 infused over 10 minutes every 21 days.
Supplementation with vitamin B12 and folic acid helps control
the hematologic and GI toxicities of pemetrexed.
- In clinical studies, less overall toxicity and reductions in grades 3/4 hematologic and nonhematologic toxicities, such as neutropenia, febrile neutropenia, and infection with grades 3/4 neutropenia, were reported when pretreatment with folic acid and vitamin B12 was administered.
- Supplementation is an essential part of pemetrexed treatment.
- Vitamin supplementation should begin one week prior to the start of therapy with pemetrexed.
Dosing Modifications for NSCLC
Hematological Toxicities Dose of pemetrexed (mg/m2)
Nadir ANC <500/mm3 and nadir platelets =50,000/mm3 75% of previous
dose
Nadir platelets <50,000/mm3 regardless of nadir ANC 50% of
previous dose
Nonhematological Toxicities*,†
Any grade 3‡ or 4 toxicities except mucositis 75% of previous
dose
Any diarrhea requiring hospitalization (irrespective of grade)
or grade 3 or 4 diarrhea. 75% of previous dose
Grade 3/4 mucositis 50% of previous dose
Neurotoxicity
CTC grade
0–1 100% of previous dose
2 100% of previous dose
- pemetrexed therapy should be discontinued if a patient experiences any hematologic or nonhematologic grades 3/4 toxicity after 2 dose reductions (except grade 3 transaminase elevations), or immediately if grades 3 or 4 neurotoxicity is observed.
- Patients receiving pemetrexed therapy should be monitored for nadir and recovery before each dose and on days 8 and 15 after pemetrexed adminsitration with a complete blood count, including a differential and platelet count. Periodic blood counts and chemistry tests should be collected to evaluate hematologic, renal, and hepatic function.
- Refer to NCI CTC (version 2.0)
† Excluding neurotoxicity
‡ Except grade 3 transaminase elevation
See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information for safety and dosing guidelines.
In February 2004 United States Food and Drug Administration (FDA) approved Pemetrexed for treating Malignant Pleural Mesothelioma (MPM) in combination with cisplatin, which is a chemotherapeutic drug that contains platinum. Combination of Pemetrexed with cisplatin is the first and only drug that FDA has approved for MPM treatment when it is not possible to perform surgery.
FDA approved the drug in July 2004 to be used as a second line agent for treating metastatic or advanced Non-Small Cell Lung Cancer (NSCLC).
The drug is also used as a single agent or in combination with other chemotherapy drugs to treat different types of cancers, including bladder cancer, colorectal carcinoma, breast cancer, and cervical cancer.
Pemetrexed is developed and marketed the Indianapolis-based company, Eli Lilly and Company.
Pemetrexed Availability
Alimta, the name of the drug with which Pemetrexed is marketed, is supplied in the form of a sterile lyophilized powder that is meant for intravenous infusion. Color of Almita is white to either light yellow or green-yellow lyophilized solid. The drug is available in single-dose 100 mg or 500 mg vials.
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