May 27, 2016
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Alimta

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Alimta




Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Premedication Regimen

Need For Folate And Vitamin B12 Supplementation

Patients treated with ALIMTA must be instructed to take folic acid and vitamin B12 as a prophylactic measure to reduce treatment-related hematologic and GI toxicity [see DOSAGE AND ADMINISTRATION]. In clinical studies, less overall toxicity and reductions in Grade 3/4 hematologic and nonhematologic toxicities such as neutropenia, febrile neutropenia, and infection with Grade 3/4 neutropenia were reported when pretreatment with folic acid and vitamin B12 was administered.

Corticosteroid Supplementation

Skin rash has been reported more frequently in patients not pretreated with a corticosteroid in clinical trials. Pretreatment with dexamethasone (or equivalent) reduces the incidence and severity of cutaneous reaction [see DOSAGE AND ADMINISTRATION].

Bone Marrow Suppression

ALIMTA can suppress bone marrow function, as manifested by neutropenia, thrombocytopenia, and anemia (or pancytopenia) [see ADVERSE REACTIONS]; myelosuppression is usually the dose-limiting toxicity. Dose reductions for subsequent cycles are based on nadir ANC, platelet count, and maximum nonhematologic toxicity seen in the previous cycle [see DOSAGE AND ADMINISTRATION].

Decreased Renal Function

ALIMTA is primarily eliminated unchanged by renal excretion. No dosage adjustment is needed in patients with creatinine clearance ≥ 45 mL/min. Insufficient numbers of patients have been studied with creatinine clearance < 45 mL/min to give a dose recommendation. Therefore, ALIMTA should not be administered to patients whose creatinine clearance is < 45 mL/min [see DOSAGE AND ADMINISTRATION].

One patient with severe renal impairment (creatinine clearance 19 mL/min) who did not receive folic acid and vitamin B12 died of drug-related toxicity following administration of ALIMTA alone.

Use With Non-Steroidal Anti-Inflammatory Drugs With Mild To Moderate Renal Insufficiency

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). Other NSAIDs should also be used with caution [see DRUG INTERACTIONS].

Required Laboratory Monitoring

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 [see DOSAGE AND ADMINISTRATION].

Pregnancy Category D

Based on its mechanism of action, ALIMTA can cause fetal harm when administered to a pregnant woman. Pemetrexed administered intraperitoneally to mice during organogenesis was embryotoxic, fetotoxic and teratogenic in mice at greater than 1/833rd the recommended human dose. If ALIMTA is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Women should be advised to use effective contraceptive measures to prevent pregnancy during treatment with ALIMTA [see Use in Specific Populations].

Third Space Fluid

The effect of third space fluid, such as pleural effusion and ascites, on ALIMTA is unknown. In patients with clinically significant third space fluid, consideration should be given to draining the effusion prior to ALIMTA administration.

Patient Counseling Information

See FDA-Approved Patient Labeling

Patients should be instructed to read the patient package insert carefully.

Need For Folic Acid And Vitamin B12

Patients treated with ALIMTA must be instructed to take folic acid and vitamin B i2 as a prophylactic measure to reduce treatment-related hematologic and gastrointestinal toxicity [see DOSAGE AND ADMINISTRATION].

Low Blood Cell Counts

Patients should be adequately informed of the risk of low blood cell counts and instructed to immediately contact their physician should any sign of infection develop including fever. Patients should also contact their physician if bleeding or symptoms of anemia occur.

Gastrointestinal Effects

Patients should be instructed to contact their physician if persistent vomiting, diarrhea, or signs of dehydration appear.

Concomitant Medications

Patients should be instructed to inform the physician if they are taking any concomitant prescription or over-the-counter medications including those for pain or inflammation such as non-steroidal anti-inflammatory drugs [see DRUG INTERACTIONS].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No carcinogenicity studies have been conducted with pemetrexed. Pemetrexed was clastogenic in the in vivo micronucleus assay in mouse bone marrow but was not mutagenic in multiple in vitro tests (Ames assay, CHO cell assay). Pemetrexed administered at i.v. doses of 0.1 mg/kg/day or greater to male mice (about 1/1666 the recommended human dose on a mg/m² basis) resulted in reduced fertility, hypospermia, and testicular atrophy.

Use In Specific Populations

Pregnancy

Teratogenic Effects

Pregnancy Category D [see WARNINGS AND PRECAUTIONS]

Based on its mechanism of action, ALIMTA can cause fetal harm when administered to a pregnant woman. There are no adequate and well controlled studies of ALIMTA in pregnant women. Pemetrexed was embryotoxic, fetotoxic, and teratogenic in mice. In mice, repeated intraperitoneal doses of pemetrexed when given during organogenesis caused fetal malformations (incomplete ossification of talus and skull bone; about 1/833rd the recommended intravenous human dose on a mg/m² basis), and cleft palate (1/33rd the recommended intravenous human dose on a mg/m² basis). Embryotoxicity was characterized by increased embryo-fetal deaths and reduced litter sizes. If ALIMTA is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to use effective contraceptive measures to prevent pregnancy during the treatment with ALIMTA.

Nursing Mothers

It is not known whether ALIMTA or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from ALIMTA, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug for the mother.

Pediatric Use

The safety and effectiveness of ALIMTA in pediatric patients have not been established.

Geriatric Use

ALIMTA is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Renal function monitoring is recommended with administration of ALIMTA. No dose reductions other than those recommended for all patients are necessary for patients 65 years of age or older [see DOSAGE AND ADMINISTRATION].

In the initial treatment non-small cell lung cancer clinical trial, 37.7% of patients treated with ALIMTA plus cisplatin were ≥ 65 years and Grade 3/4 neutropenia was greater as compared to patients < 65 years (19.9% versus 12.2%). For patients < 65 years, the HR for overall survival was 0.96 (95% CI: 0.83, 1.10) and for patients ≥ 65 years the HR was 0.88 (95% CI: 0.74, 1.06) in the intent to treat population.

In the maintenance non-small cell lung cancer trial 33.3% of patients treated with ALIMTA were ≥ 65 years and no differences were seen in Grade 3/4 adverse reactions as compared to patients < 65 years. For patients < 65 years, the HR for overall survival was 0.74 (95% CI: 0.58, 0.93) and for patients > 65 years the HR was 0.88 (95% CI: 0.65, 1.21) in the intent to treat population.

In the non-small cell lung cancer trial after prior chemotherapy, 29.7% patients treated with ALIMTA were ≥ 65 years and Grade 3/4 hypertension was greater as compared to patients < 65 years. For patients < 65 years, the HR for overall survival was 0.95 (95% CI: 0.76, 1.19), and for patients ≥ 65 years the HR was 1.15 (95% CI: 0.79, 1.68) in the intent to treat population.

The mesothelioma trial included 36.7% patients treated with ALIMTA plus cisplatin that were ≥ 65 years, and Grade ¾ fatigue, leukopenia, neutropenia, and thrombocytopenia were greater as compared to patients < 65 years. For patients < 65 years, the HR for overall survival was 0.71(95% CI: 0.53, 0.96) and for patients > 65 years, the HR was 0.85 (95% CI: 0.59, 1.22) in the intent to treat population.

Patients With Hepatic Impairment

There was no effect of elevated AST, ALT, or total bilirubin on the pharmacokinetics of pemetrexed [see CLINICAL PHARMACOLOGY].

Dose adjustments based on hepatic impairment experienced during treatment with ALIMTA are provided in Table 2 [see DOSAGE AND ADMINISTRATION].

Patients With Renal Impairment

ALIMTA is known to be primarily excreted by the kidneys. Decreased renal function will result in reduced clearance and greater exposure (AUC) to ALIMTA compared with patients with normal renal function [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]. Cisplatin coadministration with ALIMTA has not been studied in patients with moderate renal impairment.

Gender

In the initial treatment non-small cell lung cancer trial, 70% of patients were males and 30% females. For males the HR for overall survival was 0.97 (95% CI: 0.85, 1.10) and for females the HR was 0.86 (95% CI: 0.70, 1.06) in the intent to treat population.

In the maintenance non-small cell lung cancer trial, 73% of patients were males and 27% females. For males the HR for overall survival was 0.78 (95% CI: 0.63, 0.96) and for females the HR was 0.83 (95% CI: 0.56, 1.21) in the intent to treat population.

In the non-small cell lung cancer trial after prior chemotherapy, 72% of patients were males and 28% females. For males the HR for overall survival was 0.95 (95% CI: 0.76, 1.19) and for females the HR was 1.28 (95% CI: 0.86, 1.91) in the intent to treat population.

In the mesothelioma trial, 82% of patients were males and 18% females. For males the HR for overall survival was 0.85 (95% CI: 0.66, 1.09) and for females the HR was 0.48 (95% CI: 0.27, 0.85) in the intent to treat population.

Race

In the initial treatment non-small cell lung cancer trial, 78% of patients were Caucasians, 13% East/Southeast Asians, and 9% others. For Caucasians, the HR for overall survival was 0.92 (95% CI : 0.82, 1.04), for East/Southeast Asians the HR was 0.86 (95% CI: 0.61, 1.21), and for others the HR was 1.24 (95% CI: 0.84, 1.84) in the intent to treat population.

In the maintenance non-small cell lung cancer trial, 65% of patients were Caucasians, 23% East Asian, and 12% others. For Caucasians the HR for overall survival was 0.77 (95% CI: 0.62, 0.97), for East Asians was 1.05 (95% CI: 0.70, 1.59) and for others the HR was 0.46 (95% CI: 0.26, 0.79) in the intent to treat population.

In the non-small cell lung cancer trial after prior chemotherapy, 71% of patients were Caucasians and 29% others. For Caucasians the HR for overall survival was 0.91 (95% CI: 0.73, 1.15) and for others the HR was 1.27 (95% CI: 0.87, 1.87) in the intent to treat population.

In the mesothelioma trial, 92% of patients were Caucasians and 8% others. For Caucasians, the HR for overall survival was 0.77 (95% CI: 0.61, 0.97) and for others the HR was 0.86 (95% CI: 0.39, 1.90) in the intent to treat population.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 5/19/2016

Warnings
Precautions

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