Alimta

Malignant Pleural Mesothelioma: ALIMTA in combination with cisplatin is indicated for the treatment of chemotherapy naive patients with unresectable malignant pleural mesothelioma.
Non-small cell lung cancer: ALIMTA 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.
ALIMTA 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. First line treatment should be a platinum based with other cytotoxics chemotherapy.
ALIMTA is indicated as a single-agent for the treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer after prior chemotherapy (as second line).
ALIMTA is not indicated for treatment of patients with squamous cell non-small cell lung cancer.

Posology: ALIMTA must only be administered under the supervision of a physician qualified in the use of anti-cancer chemotherapy.
ALIMTA in combination with cisplatin: The recommended dose of ALIMTA 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 (see also cisplatin Summary of Product Characteristics for specific dosing advice).
ALIMTA as single agent: In patients treated for non-small cell lung cancer after prior chemotherapy, the recommended dose of ALIMTA is 500 mg/m² BSA administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle.
Pre-medication 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.
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 ALIMTA used as a single agent or in combination with cisplatin.
Table 1 - Dose modification table for ALIMTA (as single agent or in combination) and cisplatin - Haemotologic toxicities
Nadir ANC <500/mm³ and nadir platelets ≥50,000/mm³
75% of previous dose (both ALIMTA and cisplatin)
Nadir platelets <50,000/mm³ regardless of nadir ANC
75% of previous dose (both ALIMTA and cisplatin)
Nadir platelets <50,000/mm³ with bleedinga, regardless of nadir ANC
50% of previous dose (both ALIMTA and cisplatin)
^a These criteria meet the National Cancer Institute Common Toxicity Criteria (CTC v2.0; NCI 1998) definition of ≥CTC Grade 2 bleeding.
If patients develop non-haematologic toxicities ≥Grade 3 (excluding neurotoxicity), ALIMTA should be withheld until resolution to less than or equal to the patient's pre-therapy value. Treatment should be resumed according to the guidelines in Table 2.
Table 2 - Dose modification table for ALIMTA (as single agent or in combination) and cisplatin - Non-haematologic toxicities ^a,b
Any Grade 3 or 4 toxicities except mucositis
Dose of ALIMTA (mg/m²): 75% of previous dose
Dose for cisplatin (mg/m²): 75% of previous dose
Any diarrhoea requiring hospitalisation (irrespective of grade) or grade 3 or 4 diarrhoea
Dose of ALIMTA (mg/m²): 75% of previous dose
Dose for cisplatin (mg/m²): 75% of previous dose
Any diarrhoea requiring hospitalisation (irrespective of grade) or grade 3 or 4 diarrhoea
Dose of ALIMTA (mg/m²): 50% of previous dose
Dose for cisplatin (mg/m²): 100% of previous dose
^a National Cancer Institute Common Toxicity Criteria (CTC v2.0; NCI 1998) b Excluding neurotoxicity
In the event of neurotoxicity, the recommended dose adjustment for ALIMTA and cisplatin is documented in Table 3. Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is observed.
Table 3 - Dose modification table for ALIMTA (as single agent or in combination) and cisplatin - Neurotoxicity
CTCa Grade: 0-1
Dose of ALIMTA (mg/m²): 100% of previous dose
Dose for cisplatin (mg/m²): 100% of previous dose
CTCa Grade: 2
Dose of ALIMTA (mg/m²): 100% of previous dose
Dose for cisplatin (mg/m²): 50% of previous dose
^a National Cancer Institute Common Toxicity Criteria (CTC v2.0; NCI 1998).
Treatment with ALIMTA should be discontinued if a patient experiences any haematologic or non haematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed.
Special populations: Elderly: In clinical studies, there has been no indication that patients 65 years of age or older are at increased risk of adverse reaction compared to patients younger than 65 years old. No dose reductions other than those recommended for all patients are necessary.
Paediatric population: ALIMTA is not recommended for use in children below 18 years of age due to insufficient data on safety and efficacy.
Patients with renal impairment (standard cockcroft and gault formula or glomerular filtration rate measured Tc99m-DPTA serum clearance method): 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.

Method of administration: ALIMTA is for intravenous use. ALIMTA should be administered as an intravenous infusion over 10 minutes on the first day of each 21-day cycle.

Hypersensitivity to the active substance or to any of the excipients.
Breast-feeding must be discontinued during pemetrexed therapy.
Concomitant yellow fever vaccine.

Cytotoxic Chemotherapy

L01BA04 - pemetrexed ; Belongs to the class of antimetabolites, folic acid analogues. Used in the treatment of cancer.

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