Brands, Medical Use, Clinical Data
Drug Category
- Antineoplastic Agents
- Antimetabolites
- Enzyme Inhibitors
- Folic Acid Antagonists
Dosage Forms
- Powder for solution
- Intravenous infusion
Brands / Synonyms
Alimta; Pemetrexed Disodium
Indications
For the treatment of malignant pleural mesothelioma and locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy
Pharmacology
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.
Mechanism of Action
Pemetrexed 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. Pemetrexed 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.
Absorption
Not Available
Toxicity
Not Available
Biotrnasformation / Drug Metabolism
Metabolized by Cytochrome P450 Enzymes
Contraindications
ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed or to
any other ingredient used in the formulation.
Drug Interactions
ALIMTA is primarily eliminated unchanged renally as a result of glomerular filtration and tubular secretion.
Concomitant administration of nephrotoxic drugs could result in delayed clearance of ALIMTA. Concomitant
administration of substances that are also tubularly secreted (e.g., probenecid) could potentially result in delayed
clearance of ALIMTA.
Although ibuprofen (400 mg qid) can be administered with ALIMTA in patients with normal renal function (creatinine
clearance ³80 mL/min), caution should be used when administering ibuprofen
concurrently with ALIMTA to patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79
mL/min). Patients with mild to moderate renal insufficiency should avoid taking NSAIDs with short elimination
half-lives for a period of 2 days before, the day of, and 2 days following administration of ALIMTA.
In the absence of data regarding potential interaction between ALIMTA and NSAIDs with longer half-lives, all
patients taking these NSAIDs should interrupt dosing for at least 5 days before, the day of, and 2 days following
ALIMTA administration. If concomitant administration of an NSAID is necessary, patients should be monitored closely
for toxicity, especially myelosuppression, renal, and gastrointestinal toxicity.
Drug/Laboratory Test Interactions
None known.
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