Pemetrexed Folic acid

Pemetrexed Pemetrexed 500 mg/m2 (day 1), vitamin B12 1 mg IM 1-2 weeks before treatment initiation and every 9 weeks thereafter, folic acid 1 mg daily beginning 3 weeks before treatment initiation 21 days 5-6%... 

Uses w/ cisplatin in nonresectable mesothelioma NSCLC Action Antifolate antineoplastic Dose 500 mg/m IV over 10 min q3wk hold if CrCl <45 mLAnin give w/ vit Bi2 (1000 meg IM q9wk) folic acid (350-1000 meg PO daily) start 1 wk before dexamethasone 4 mg PO bid x 3 start 1 d before each Rx Caution [D, -] w/ renal/hepatic/ BM impair Contra Component sensitivity Disp IV SE Neutropenia, thrombocytopenia, N/V/D, anorexia, stomatitis, renal failure, neuropathy, fevCT, fatigue, mood changes, dyspnea, anaphylactic Rxns Interactions t Effects W/ NSAIDs, probenecid d/t decreased pemetrexed EMS Monitor for S/Sxs of Infxn OD May cause profound BM suppression, mucous membrane irritation, D, and rash symptomatic and supportive... 

Pemetrexed is chemically similar to folic acid. It inhibits three enzymes used in purine and pyrimidine synthesis - thymidylate synthetase, dihydrofolate reductase, and glycinamide ribonucleotide formyl transferase. By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA. In 2004 it was approved for treatment of malignant pleural mesothelioma and as a second-line agent for the treatment of non-small cell lung cancer. Adverse effects include gastrointestinal complaints, bone marrow suppression, alopecia, allergic and neurotoxic reactions. 

Pemetrexed is a multitargeted antifolate that inhibits at least three biosynthetic pathways in thymidine and purine synthesis (see Table 124—11). In addition to inhibition of DHFR, it also inhibits thymidine synthase and glycinamide ribonucleotide formyltransferase, decreasing the risk of development of drug resistance. Supplementation of folic acid and vitamin B12 is required to decrease myelosuppression... 

Pemetrexed is a folic-acid antagonist that disrupts folate-dependent metabolic processes essential for cell replication. It is indicated in combination with cisplatin for the treatment of malignant pleural mesothelioma in patients whose disease is unresectable or who are otherwise not candidates for curative surgery and as a single agent for the treatment of locally advanced or metastatic non-small-cell lung cancer after prior chemotherapy. 

Because folic acid and many of its analogs are hydrophilic, they cross the blood—brain barrier poorly and require specific transport mechanisms to enter mammalian cells. Three inward folate transport systems are found on mammalian cells (I) a folate receptor, which has high (fffin-ity for folic acid but much reduced ability to transport methotrexate and other analogs (2) the reduced folate transporter, the majortransitproteinfor methotrexate, raltitrexed, pemetrexed, and most... 

Pemetrexed toxicity mirrors that of methotrexate, with the additional feature of a prominent erythematous and pruritic rash in 40% of patients. Dexamethasone, 4 mg twice-daily on days —1, 0, and +1, markedly diminishes this toxicity. Unpredictably severe myelosuppression with pemetrexed, seen especially in patients with preexisting homocystinemia and possibly reflecting folate deficiency, is largely eliminated by concurrent administration of low doses o/folic acid, 0.35—1 mg/day beginning 1—2 weeks prior to pemetrexed and continuing while the drug is administered. Intramuscular vitamin Bj2(I mg) is given with the first dose of pemetrexed to correct possible Bj2 deficiency. There is no evidence that these small doses of folate and Bj compromise the therapeutic effect. 

Oral folic acid and intramuscular vitamin B12 has been reported to not alter the pharmacokinetics of pemetrexed and because these vitamins were found to decrease pemetrexed toxicity, it is recommended that all patients receiving pemetrexed should receive folic acid and Bj2 supplements. - ... 

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