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ALIMTA (pemetrexed for injection), for Intravenous
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ALIMTA safely and effectively. See full prescribing information for ALIMTA.
ALIMTA (pemetrexed for injection), for Intravenous Use
Initial U.S. Approval: 2004
RECENT MAJOR CHANGES
Dosage and Administration, Premedication Regimen and Concurrent Medications (2.3) 10/2012
Warnings and Precautions, Requirement for Premedication and Concomitant Medication to Reduce Toxicity (5.1) 10/2012
Warnings and Precautions, Required Laboratory Monitoring (5.5) 10/2012
INDICATIONS AND USAGE
ALIMTA® is a folate analog metabolic inhibitor indicated for:
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Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer:
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Initial treatment in combination with cisplatin. (1.1)
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Maintenance treatment of patients whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. (1.2)
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After prior chemotherapy as a single-agent. (1.3)
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Mesothelioma: in combination with cisplatin. (1.4)
Limitations of Use:
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ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer. (1.5)
DOSAGE AND ADMINISTRATION
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Combination use in Non-Small Cell Lung Cancer and Mesothelioma: Recommended dose of ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with cisplatin 75 mg/m2 i.v. beginning 30 minutes after ALIMTA administration. (2.1)
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Single-Agent use in Non-Small Cell Lung Cancer: Recommended dose of ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle. (2.2)
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Prior to initiating ALIMTA, initiate supplementation with oral folic acid and intramuscular vitamin B12. Continue folic acid and vitamin B12 supplementation throughout treatment. Administer corticosteroids the day before, the day of, and the day after ALIMTA administration. (2.3)
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Dose Reductions: Dose reductions or discontinuation may be needed based on toxicities from the preceding cycle of therapy. (2.4)
DOSAGE FORMS AND STRENGTHS
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100 mg vial for injection (3)
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500 mg vial for injection (3)
CONTRAINDICATIONS
History of severe hypersensitivity reaction to pemetrexed. (4)
WARNINGS AND PRECAUTIONS
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Premedication regimen: Prior to treatment with ALIMTA, initiate supplementation with oral folic acid and intramuscular vitamin B12 to reduce the severity of hematologic and gastrointestinal toxicity of ALIMTA. (5.1)
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Bone marrow suppression: Reduce doses for subsequent cycles based on hematologic and nonhematologic toxicities. (5.2)
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Renal function: Do not administer when CrCl <45 mL/min. (2.4, 5.3)
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NSAIDs with renal insufficiency: Use caution in patients with mild to moderate renal insufficiency (CrCl 45-79 mL/min). (5.4)
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Lab monitoring: Do not initiate a cycle unless ANC ≥1500 cells/mm3, platelets ≥100,000 cells/mm3, and CrCl ≥45 mL/min. (5.5)
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Pregnancy: Fetal harm can occur when administered to a pregnant woman. Women should be advised to use effective contraception measures to prevent pregnancy during treatment with ALIMTA. (5.6)
The most common adverse reactions (incidence ≥20%) with single-agent use are fatigue, nausea, and anorexia. Additional common adverse reactions when used in combination with cisplatin include vomiting, neutropenia, leukopenia, anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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NSAIDs: Use caution with NSAIDs. (7.1)
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Nephrotoxic drugs: Concomitant use of these drugs and/or substances which are tubularly secreted may result in delayed clearance. (7.2)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 2/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Nonsquamous Non-Small Cell Lung Cancer – Combination with Cisplatin
ALIMTA® is indicated in combination with cisplatin therapy for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer.
1.2 Nonsquamous Non-Small Cell Lung Cancer – Maintenance
ALIMTA is indicated for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
1.3 Nonsquamous Non-Small Cell Lung Cancer – After Prior 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.
1.4 Mesothelioma
ALIMTA 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 curative surgery.
1.5 Limitations of Use
ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer. [see Clinical Studies (14.1, 14.2, 14.3)]
2 DOSAGE AND ADMINISTRATION
2.1 Combination Use with Cisplatin for Nonsquamous Non-Small Cell Lung Cancer or Malignant Pleural Mesothelioma
The recommended dose of ALIMTA is 500 mg/m2 administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle. The recommended dose of cisplatin is 75 mg/m2 infused over 2 hours beginning approximately 30 minutes after the end of ALIMTA administration. See cisplatin package insert for more information.
2.2 Single-Agent Use as Maintenance Following First-Line Therapy, or as a Second-Line Therapy
The recommended dose of ALIMTA is 500 mg/m2 administered as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle.
2.3 Premedication Regimen and Concurrent Medications
Vitamin Supplementation
Instruct patients to initiate folic acid 400 mcg to 1000 mcg orally once daily beginning 7 days before the first dose of ALIMTA. Continue folic acid during the full course of therapy and for 21 days after the last dose of ALIMTA [see Warnings and Precautions (5.1)].
Administer vitamin B12 1 mg intramuscularly 1 week prior to the first dose of ALIMTA and every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as treatment with ALIMTA [see Warnings and Precautions (5.1)].
Corticosteroids
Administer dexamethasone 4 mg by mouth twice daily the day before, the day of, and the day after ALIMTA administration [see Warnings and Precautions (5.1)].
2.4 Laboratory Monitoring and Dose Reduction/Discontinuation Recommendations
Monitoring
Complete blood cell counts, including platelet counts, should be performed on all patients receiving ALIMTA. Patients should be monitored for nadir and recovery, which were tested in the clinical study before each dose and on days 8 and 15 of each cycle. Patients should not begin a new cycle of treatment unless the ANC is ≥1500 cells/mm3, the platelet count is ≥100,000 cells/mm3, and creatinine clearance is ≥45 mL/min. Periodic chemistry tests should be performed to eva luate renal and hepatic function [see Warnings and Precautions (5.5)].
Dose Reduction Recommendations
Dose adjustments at the start of a subsequent cycle should be based on nadir hematologic counts or maximum nonhematologic 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 in Tables 1-3, which are suitable for using ALIMTA as a single-agent or in combination with cisplatin.
If patients develop nonhematologic toxicities (excluding neurotoxicity) ≥Grade 3, treatment should be withheld until resolution to less than or equal to the patient's pre-therapy value. Treatment should be resumed according to guidelines in Table 2.
In the event of neurotoxicity, the recommended dose adjustments for ALIMTA and cisplatin are described in Table 3. Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is experienced.
Discontinuation Recommendation
ALIMTA therapy should be discontinued if a patient experiences any hematologic or nonhematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed.
Renally Impaired Patients
In clinical studies, patients with creatinine clearance ≥45 mL/min required no dose adjustments other than those recommended for all patients. Insufficient numbers of patients with creatinine clearance below 45 mL/min have been treated to make dosage recommendations for this group of patients [see Clinical Pharmacology (12.3)]. Therefore, ALIMTA should not be administered to patients whose creatinine clearance is <45 mL/min using the standard Cockcroft and Gault formula (below) or GFR measured by Tc99m-DTPA serum clearance method:
Caution should be exercised when administering ALIMTA concurrently with NSAIDs to patients whose creatinine clearance is <80 mL/min [see Drug Interactions (7.1)].
2.5 Preparation and Administration Precautions
As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of infusion solutions of ALIMTA. The use of gloves is recommended. If a solution of ALIMTA contacts the skin, wash the skin immediately and thoroughly with soap and water. If ALIMTA contacts the mucous membranes, flush thoroughly with water. Several published guidelines for handling and disposal of anticancer agents are available [see References (15)].
ALIMTA is not a vesicant. There is no specific antidote for extravasation of ALIMTA. To date, there have been few reported cases of ALIMTA extravasation, which were not assessed as serious by the investigator. ALIMTA extravasation should be managed with local standard practice for extravasation as with other non-vesicants.
2.6 Preparation for Intravenous Infusion Administration
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Use aseptic technique during the reconstitution and further dilution of ALIMTA for intravenous infusion administration.
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Calculate the dose of ALIMTA and determine the number of vials needed. Vials contain either 100 mg or 500 mg of ALIMTA. The vials contain an excess of ALIMTA to facilitate delivery of label amount.
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Reconstitute each 100-mg vial with 4.2 ml of 0.9% Sodium Chloride Injection (preservative free). Reconstitute each 500-mg vial with 20 mL of 0.9% Sodium Chloride Injection (preservative free). Reconstitution of either size vial gives a solution containing 25 mg/mL ALIMTA. Gently swirl each vial until the powder is completely dissolved. The resulting solution is clear and ranges in color from colorless to yellow or green-yellow without adversely affecting product quality. The pH of the reconstituted ALIMTA solution is between 6.6 and 7.8. FURTHER DILUTION IS REQUIRED.
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Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter is observed, do not administer.
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An appropriate quantity of the reconstituted ALIMTA solution must be further diluted into a solution of 0.9% Sodium Chloride Injection (preservative free), so that the total volume of solution is 100 ml. ALIMTA is administered as an intravenous infusion over 10 minutes.
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Chemical and physical stability of reconstituted and infusion solutions of ALIMTA were demonstrated for up to 24 hours following initial reconstitution, when stored refrigerated. When prepared as directed, reconstitution and infusion solutions of ALIMTA contain no antimicrobial preservatives. Discard any unused portion.
Reconstitution and further dilution prior to intravenous infusion is only recommended with 0.9% Sodium Chloride Injection (preservative free). ALIMTA is physically incompatible with diluents containing calcium, including Lactated Ringer's Injection, USP and Ringer's Injection, USP and therefore these should not be used. Coadministration of ALIMTA with other drugs and diluents has not been studied, and therefore is not recommended. ALIMTA is compatible with standard polyvinyl chloride (PVC) administration sets and intravenous solution bags.
3 DOSAGE FORMS AND STRENGTHS
ALIMTA, pemetrexed for injection, is a white to either light-yellow o |
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