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  • Alimta
    / Eli Lilly


    Active Ingredient
    Pemetrexed 500 mg, 100 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    1 x 100 mg

    partial basket chart 80343 9610

    Vial

    1 x 500 mg

    partial basket chart 11485 1928

    Dosage

    ALIMTA in combination with cisplatin: The recommended dose of this drug is 500 mg/m2 of body surface area (BSA) administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle. The recommended dose of cisplatin is 75 mg/m2 BSA infused over two hours approximately 30 minutes after completion of the pemetrexed infusion on the first day of each 21-day cycle. Patients must receive adequate anti-emetic treatment and appropriate hydration prior to and/or after receiving cisplatin.
    ALIMTA as single agent: In patients treated for non-small cell lung cancer after prior chemotherapy, the recommended dose of this drug is 500 mg/m2 BSA administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle.
    Premedication regimen: To reduce the incidence and severity of skin reactions, a corticosteroid should be given the day prior to, on the day of, and the day after pemetrexed administration. The corticosteroid should be equivalent to 4 mg of dexamethasone administered orally twice a day.
    To reduce toxicity, patients treated with pemetrexed must also receive vitamin supplementation . Patients must take oral folic acid or a multivitamin containing folic acid (350 to 1000 micrograms) on a daily basis. At least five doses of folic acid must be taken during the seven days preceding the first dose of pemetrexed, and dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed. Patients must also receive an intramuscular injection of vitamin B12 (1000 micrograms) in the week preceding the first dose of pemetrexed and once every three cycles thereafter. Subsequent vitamin B12 injections may be given on the same day as pemetrexed.
    Monitoring: Patients receiving pemetrexed should be monitored before each dose with a complete blood count, including a differential white cell count (WCC) and platelet count. Prior to each chemotherapy administration blood chemistry tests should be collected to evaluate renal and hepatic function. Before the start of any cycle of chemotherapy, patients are required to have the following: absolute neutrophil count (ANC) should be ≥ 1500 cells/mm3 and platelets should be ≥100,000 cells/mm3.
    Creatinine clearance should be ≥45 ml/min. The total bilirubin should be≤ 1.5 times upper limit of normal. Alkaline phosphatase (AP), aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) should be ≤ 3 times upper limit of normal. Alkaline phosphatase, AST and ALT≤ 5 times upper limit of normal is acceptable if liver has tumour involvement.
    Elderly:  No dose reductions other than those recommended for all patients are necessary.
    Paediatric population: There is no relevant use in the paediatric population in malignant pleural mesothelioma and non-small cell lung cancer.
    Patients with renal impairment: Pemetrexed is primarily eliminated unchanged by renal excretion. In clinical studies, patients with creatinine clearance of  ≥ 45 ml/min required no dose adjustments other than those recommended for all patients. There are insufficient data on the use of pemetrexed in patients with creatinine clearance below 45 ml/min; therefore the use of pemetrexed is not recommended.
    Patients with hepatic impairment: No relationships between AST (SGOT), ALT (SGPT), or total bilirubin and pemetrexed pharmacokinetics were identified. However, patients with hepatic impairment such as bilirubin > 1.5 times the upper limit of normal and/or aminotransferase > 3.0 times the upper limit of normal (hepatic metastases absent) or > 5.0 times the upper limit of normal (hepatic metastases present) have not been specifically studied.
    Dose adjustments: Dose adjustments at the start of a subsequent cycle should be based on nadir haematologic counts or maximum non-haematologic toxicity from the preceding cycle of therapy. Treatment may be delayed to allow sufficient time for recovery. Upon recovery patients should be retreated using the guidelines which are applicable for this drug used as a single agent or in combination with cisplatin. See prescribing information for full details.
    It should be administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle.
    For full details see prescribing information.


    Indications

    Malignant pleural mesothelioma: 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 curatible surgery.
    Non-small cell lung cancer: In combination with cisplatin is indicated for the first line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. It is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy. The drug is indicated as monotherapy for the second line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.


    Contra-Indications

    There are no data from the use of pemetrexed in pregnant women but pemetrexed, like other anti-metabolites, is suspected to cause serious birth defects when administered during pregnancy.
    Breast-feeding must be discontinued during pemetrexed therapy.
    There is no relevant use in the paediatric population.


    Special Precautions

    Pemetrexed can suppress bone marrow function as manifested by neutropenia, thrombocytopenia and anaemia (or pancytopenia). Myelosuppression is usually the dose-limiting toxicity. Patients should be monitored for myelosuppression during therapy and pemetrexed should not be given to patients until absolute neutrophil count (ANC) returns to ≥ 1500 cells/mm3 and platelet count returns to ≥ 100,000 cells/mm3. Dose reductions for subsequent cycles are based on nadir ANC, platelet count and maximum non-haematologic toxicity seen from the previous cycle. Less toxicity and reduction in Grade 3/4 haematologic and non-haematologic toxicities such as neutropenia, febrile neutropenia and infection with Grade 3/4 neutropenia were reported when pre-treatment with folic acid and vitamin B12 was administered. Therefore, all patients treated with pemetrexed must be instructed to take folic acid and vitamin B12 as a prophylactic measure to reduce treatment-related toxicity. Skin reactions have been reported in patients not pre-treated with a corticosteroid. Pre-treatment with dexamethasone (or equivalent) can reduce the incidence and severity of skin reactions. An insufficient number of patients have been studied with creatinine clearance of below 45 ml/min. Therefore, the use of pemetrexed in patients with creatinine clearance of < 45 ml/min is not recommended. Patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 ml/min) should avoid taking non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin (> 1.3 g daily) for 2 days before, on the day of, and 2 days following pemetrexed administration. In patients with mild to moderate renal insufficiency eligible for pemetrexed therapy NSAIDs with long elimination half-lives should be interrupted for at least 5 days prior to, on the day of, and at least 2 days following pemetrexed administration. Serious renal events, including acute renal failure, have been reported with pemetrexed alone or in association with other chemotherapeutic agents. Many of the patients in whom these occurred had underlying risk factors for the development of renal events including dehydration or pre-existing hypertension or diabetes. The effect of third space fluid, such as pleural effusion or ascites, on pemetrexed is not fully defined. A phase 2 study of pemetrexed in 31 solid tumour patients with stable third space fluid demonstrated no difference in pemetrexed dose normalized plasma concentrations or clearance compared to patients without third space fluid collections. Thus, drainage of third space fluid collection prior to pemetrexed treatment should be considered, but may not be necessary. Due to the gastrointestinal toxicity of pemetrexed given in combination with cisplatin, severe dehydration has been observed. Therefore, patients should receive adequate antiemetic treatment and appropriate hydration prior to and/or after receiving treatment. Serious cardiovascular events, including myocardial infarction and cerebrovascular events have been uncommonly reported during clinical studies with pemetrexed, usually when given in combination with another cytotoxic agent. Most of the patients in whom these events have been observed had pre-existing cardiovascular risk factors. Immunodepressed status is common in cancer patients. As a result, concomitant use of live attenuated vaccines is not recommended. Pemetrexed can have genetically damaging effects. Sexually mature males are advised not to father a child during the treatment and up to 6 months thereafter. Contraceptive measures or abstinence are recommended. Owing to the possibility of pemetrexed treatment causing irreversible infertility, men are advised to seek counselling on sperm storage before starting treatment. Women of childbearing potential must use effective contraception during treatment with pemetrexed. Cases of radiation pneumonitis have been reported in patients treated with radiation either prior, during or subsequent to their pemetrexed therapy. Particular attention should be paid to these patients and caution exercised with use of other radiosensitising agents. Cases of radiation recall have been reported in patients who received radiotherapy weeks or years previously.
    For full details see prescribing information.


    Side Effects

    Bone marrow suppression manifested as anaemia, neutropenia, leukopenia, thrombocytopenia and gastrointestinal toxicities, manifested as anorexia, nausea, vomiting, diarrhoea, constipation, pharyngitis, mucositis, and stomatitis.


    Drug interactions

    Concomitant administration of nephrotoxic drugs (e.g. aminoglycoside, loop diuretics, platinum compounds, cyclosporin) and substances that are also tubularly secreted (e.g. probenecid, penicillin), could result in delayed clearance of Alimta. This combination should be used with caution. If necessary, creatinine clearance should be closely monitored. Caution should be made when administering higher doses of NSAIDs or aspirin, concurrently with pemetrexed to patients with normal function (creatinine clearance > 80 ml/min). In patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 ml/min), the concomitant administration of pemetrexed with NSAIDs (e.g. ibuprofen) or aspirin at a higher dose should be avoided for 2 days before, on the day of, and 2 days following pemetrexed administration. In the absence of data regarding potential interaction with NSAIDs having longer half-lives such as piroxicam or rofecoxib, the concomitant administration with pemetrexed in patients with mild to moderate renal insufficiency should be interrupted for at least 5 days prior to, on the day of, and at least 2 days following pemetrexed administration. If concomitant administration of NSAIDs is necessary, patients should be monitored closely for toxicity, especially myelosuppression and gastrointestinal toxicity. The high intra-individual variability of the coagulation status during diseases and the possibility of interaction between oral anticoagulants and anticancer chemotherapy require increased frequency of INR (International Normalised Ratio) monitoring, if it is decided to treat the patient with oral anticoagulants. Concomitant use contraindicated: Yellow fever vaccine: risk of fatal generalised vaccinale disease. Concomitant use not recommended: Live attenuated vaccines risk of systemic, possibly fatal, disease. The risk is increased in subjects who are already immunosuppressed by their underlying disease. Use an inactivated vaccine where it exists (poliomyelitis).
    For full details see prescribing information.


    Pregnancy and Lactation

    Contraception in males and females: Women of childbearing potential must use effective contraception during treatment with pemetrexed. Pemetrexed can have genetically damaging effects. Sexually mature males are advised not to father a child during the treatment and up to 6 months thereafter. Contraceptive measures or abstinence are recommended.
    Pregnancy: There are no data from the use of pemetrexed in pregnant women but pemetrexed, like other anti-metabolites, is suspected to cause serious birth defects when administered during pregnancy. Animal studies have shown reproductive toxicity. Pemetrexed should not be used during pregnancy unless clearly necessary, after a careful consideration of the needs of the mother and the risk for the foetus.
    Breastfeeding: It is not known whether pemetrexed is excreted in human milk and adverse reactions on the suckling child cannot be excluded. Breast-feeding must be discontinued during pemetrexed therapy.
    Fertility: Owing to the possibility of pemetrexed treatment causing irreversible infertility, men are advised to seek counselling on sperm storage before starting treatment.


    Overdose

    Reported symptoms of overdose include neutropenia, anaemia, thrombocytopenia, mucositis, sensory polyneuropathy and rash. Anticipated complications of overdose include bone marrow suppression as manifested by neutropenia, thrombocytopenia and anaemia. In addition, infection with or without fever, diarrhoea, and/or mucositis may be seen. In the event of suspected overdose, patients should be monitored with blood counts and should receive supportive therapy as necessary. The use of calcium folinate / folinic acid in the management of pemetrexed overdose should be considered.


    Manufacturer
    Lilly France S.A.S.
    Licence holder
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