ALIMTA PACKAGE INSERT PDF

Download a comprehensive resource that helps support your needs in the following areas: dosing and administration, billing and coding, product distribution and specifications, and Lilly PatientOne Co-pay Program information for ALIMTA. Patients with autoimmune disease that required systemic therapy within 2 years of treatment, a medical condition that required immunosuppression, or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks were ineligible. ALIMTA is indicated as a single agent for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Continuation maintenance therapy is ongoing or continued use of one or more first-line medications after first-line treatment completion in patients with stable disease or better. Assess creatinine clearance prior to each cycle. Aspirin, administered in low to moderate doses mg every 6 hours , does not affect the pharmacokinetics of pemetrexed.

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If you are a consumer or patient please visit this version. History of severe hypersensitivity reaction to pemetrexed. ALIMTA is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery.

Obtain complete blood count on Days 1, 8, and 15 of each cycle. Assess creatinine clearance prior to each cycle. For dosing modifications for cisplatin, carboplatin, or pembrolizumab, refer to their prescribing information. ALIMTA can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection.

The risk of myelosuppression is increased in patients who do not receive vitamin supplementation. Obtain a complete blood count at the beginning of each cycle. Withhold ALIMTA for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation.

Monitor patients for inflammation or blistering in areas of previous radiation treatment. If concomitant ibuprofen use cannot be avoided, monitor patients more frequently for ALIMTA adverse reactions, including myelosuppression, renal, and gastrointestinal toxicity [see Dosage and Administration 2. Based on findings from animal studies and its mechanism of action, ALIMTA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus.

Advise females of reproductive potential to use effective contraception during treatment with ALIMTA and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALIMTA and for 3 months after the final dose [see Use in Specific Populations 8. The following adverse reactions are discussed in greater detail in other sections of the labeling:. Because clinical trials are conducted under widely varying conditions, adverse reactions rates cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.

Seventy-two percent of patients received carboplatin. All patients were fully supplemented with folic acid and vitamin B Patients unable to stop using aspirin or other non-steroidal anti-inflammatory drugs or unable to take folic acid, vitamin B 12 or corticosteroids were also excluded from the study. Study JMDB was not designed to demonstrate a statistically significant reduction in adverse reaction rates for ALIMTA, as compared to the control arm, for any specified adverse reaction listed in Table 4.

Patients in both study arms were fully supplemented with folic acid and vitamin B The requirement for transfusions 9. Patients in both study arms received folic acid and vitamin B 12 supplementation. Dose reductions for adverse reactions occurred in 3. Patients unable to discontinue aspirin or other non-steroidal anti-inflammatory drugs or unable to take folic acid, vitamin B 12 or corticosteroids were also excluded from the study.

Study JMEI is not designed to demonstrate a statistically significant reduction in adverse reaction rates for ALIMTA, as compared to the control arm, for any specified adverse reaction listed in the Table 7 below.

Patients unable to stop using aspirin or other non-steroidal anti-inflammatory drugs were also excluded from the study. The most common adverse reaction resulting in dose delay was neutropenia. Study JMCH was not designed to demonstrate a statistically significant reduction in adverse reaction rates for ALIMTA, as compared to the control arm, for any specified adverse reaction listed in the table below.

Table 8 provides the ADRs for subgroup of patients treated with ALIMTA in combination with cisplatin patients or cisplatin alone patients who received full supplementation with folic acid and vitamin B 12 during study therapy. Exploratory Subgroup Analyses based on Vitamin Supplementation. Table 9 provides the results of exploratory analyses of the frequency and severity of NCI CTCAE Grade 3 or 4 adverse reactions reported in more ALIMTA-treated patients who did not receive vitamin supplementation never supplemented as compared with those who received vitamin supplementation with daily folic acid and vitamin B 12 from the time of enrollment in Study JMCH fully-supplemented.

The following adverse reactions occurred more frequently in patients who were fully vitamin supplemented than in patients who were never supplemented:. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Based on findings from animal studies and its mechanism of action, ALIMTA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology Advise pregnant women of the potential risk to a fetus [see Use in Special Populations 8.

In the U. Pemetrexed was teratogenic in mice. Daily dosing of pemetrexed by intravenous injection to pregnant mice during the period of organogenesis increased the incidence of fetal malformations cleft palate; protruding tongue; enlarged or misshaped kidney; and fused lumbar vertebra at doses based on BSA 0.

At doses, based on BSA, greater than or equal to 0. There is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production.

Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with ALIMTA and for 3 months after the final dose [see Nonclinical Toxicology It is not known whether these effects on fertility are reversible [see Nonclinical Toxicology The safety and pharmacokinetics of ALIMTA were evaluated in two clinical studies conducted in pediatric patients with recurrent solid tumors.

Patients in both studies received concomitant vitamin B 12 and folic acid supplementation and dexamethasone. No tumor responses were observed.

Adverse reactions observed in pediatric patients were similar to those observed in adults. Pemetrexed exposure AUC and C max appeared to increase proportionally with dose. Average clearance 2. No overall differences in effectiveness were observed between these patients and younger patients.

The incidences of Grade anemia, fatigue, thrombocytopenia, hypertension, and neutropenia were higher in patients 65 years of age and older as compared to younger patients: in at least one of five randomized clinical trials. It is not known whether pemetrexed is dialyzable. The structural formula is as follows:. ALIMTA is a sterile white-to-light yellow or green-yellow lyophilized powder in single-dose vials to be reconstituted for intravenous infusion.

ALIMTA is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase.

Based on population pharmacodynamic analyses, the depth of the absolute neutrophil counts ANC nadir correlates with the systemic exposure to pemetrexed and supplementation with folic acid and vitamin B There is no cumulative effect of pemetrexed exposure on ANC nadir over multiple treatment cycles.

Pemetrexed total systemic exposure AUC and maximum plasma concentration C max increased proportionally with increase of dose. The pharmacokinetics of pemetrexed did not change over multiple treatment cycles. Pemetrexed has a steady-state volume of distribution of The total systemic clearance of pemetrexed is As renal function decreases, the clearance of pemetrexed decreases and exposure AUC of pemetrexed increases. In vitro studies indicated that pemetrexed is a substrate of OAT3 organic anion transporter 3 , a transporter that is involved in the active secretion of pemetrexed.

Age 26 to 80 years and sex had no clinically meaningful effect on the systemic exposure of pemetrexed based on population pharmacokinetic analyses. The pharmacokinetics of pemetrexed were similar in Whites and Blacks or African Americans. Insufficient data are available for other ethnic groups. Pemetrexed has not been formally studied in patients with hepatic impairment.

Pharmacokinetic analyses of pemetrexed included patients with impaired renal function. Plasma clearance of pemetrexed decreases as renal function decreases, with a resultant increase in systemic exposure. The pemetrexed plasma concentrations in patients with various solid tumors with stable, mild to moderate third-space fluid were comparable to those observed in patients without third space fluid collections.

The effect of severe third space fluid on pharmacokinetics is not known. Pemetrexed is a substrate for OAT3. In vitro data predict that at clinically relevant concentrations, other NSAIDs naproxen, diclofenac, celecoxib would not inhibit the uptake of pemetrexed by OAT3 and would not increase the AUC of pemetrexed to a clinically significant extent.

Pemetrexed is a substrate for OAT4. Cisplatin does not affect the pharmacokinetics of pemetrexed and the pharmacokinetics of total platinum are unaltered by pemetrexed. Neither folic acid nor vitamin B 12 affect the pharmacokinetics of pemetrexed. No carcinogenicity studies have been conducted with pemetrexed. Pemetrexed was clastogenic in an in vivo micronucleus assay in mouse bone marrow but was not mutagenic in multiple in vitro tests Ames assay, Chinese Hamster Ovary cell assay.

Initial Treatment in Combination with Pembrolizumab and Platinum. Patients were randomized to one of the following treatment arms:. Patients randomized to placebo, ALIMTA, and platinum chemotherapy were offered pembrolizumab as a single agent at the time of disease progression. The primary efficacy outcome measure was overall survival. In pre-specified analyses assessing the impact of NSCLC histology on overall survival, clinically relevant differences in survival according to histology were observed.

These subgroup analyses are shown in Table 12 and Figures 3 and 4. Patients in both study arms received folic acid, vitamin B 12 , and dexamethasone [see Dosage and Administration 2. Randomization was carried out using a minimization approach [Pocock and Simon ] using the following factors: gender, ECOG PS 0 versus 1 , response to prior chemotherapy complete or partial response versus stable disease , history of brain metastases yes versus no , non-platinum component of induction therapy docetaxel versus gemcitabine versus paclitaxel , and disease stage IIIb versus IV.

The major efficacy outcome measures were progression-free survival based on assessment by independent review and overall survival; both were measured from the date of randomization in Study JMEN. Median time from initiation of platinum-based chemotherapy to randomization was 3. Patients in both arms received folic acid, vitamin B 12 , and dexamethasone.

The main efficacy outcome measure was investigator-assessed progression-free survival PFS and an additional efficacy outcome measure was overall survival OS ; PFS and OS were measured from the time of randomization. The study was designed to show that overall survival with ALIMTA was non-inferior to docetaxel, as the major efficacy outcome measure, and that overall survival was superior for patients randomized to ALIMTA compared to docetaxel, as a secondary outcome measure.

A total of patients were enrolled with patients randomized to ALIMTA and patients randomized to docetaxel. The efficacy results in the overall population and in subgroup analyses based on histologic subtype are provided in Tables 16 and 17 , respectively.

Study JMEI did not show an improvement in overall survival in the intent-to-treat population. Randomization was stratified by multiple baseline variables including KPS, histologic subtype epithelial, mixed, sarcomatoid, other , and gender.

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Pemetrexed (Alimta)

If you are a consumer or patient please visit this version. History of severe hypersensitivity reaction to pemetrexed. ALIMTA is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. Obtain complete blood count on Days 1, 8, and 15 of each cycle.

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Pemetrexed inhibits the activity of several folate-dependent enzymes involved in the synthesis of thymidine and purine nucleotides, such as thymidylate synthase TS , dihydrofolate reductase DHFR , and glycinamide ribonucleotide formyltransferase GARFT. Supportive care examples: [1]. For conciseness and simplicity, HemOnc. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex , Lexicomp , UpToDate courtesy of Lexicomp , or the prescribing information. From HemOnc. Jump to: navigation , search.

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Like cisplatin, carboplatin contains platinum. Cisplatin contains platinum. PD-L1 is a checkpoint protein found on cancer cells. T-cells develop from stem cells in the bone marrow and help protect the body from infection.

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