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warnings and cautions
5 WARNINGS AND PRECAUTIONS • Myelosuppression: Can cause severe bone marrow suppression resulting in cytopenia and an increased risk of infection. Do not administer pemetrexed for injection when the absolute neutrophil count is less than 1500 cells/mm 3 and platelets are less than 100,000 cells/mm 3 .Initiate supplementation with oral folic acid and intramuscular vitamin B 12 to reduce the severity of hematologic and gastrointestinal toxicity of pemetrexed for injection ( 2.4 , 5.1 ) • Renal Failure:Can cause severe, and sometimes fatal, renal failure. Do not administer when creatinine clearance is less than 45 mL/min. ( 2.3 , 5.2 ) • Bullous and Exfoliative Skin Toxicity: Permanently discontinue for severe and life-threatening bullous, blistering or exfoliating skin toxicity. ( 5.3 ) • Interstitial Pneumonitis: Withhold for acute onset of new or progressive unexplained pulmonary symptoms. Permanently discontinue if pneumonitis is confirmed. ( 5.4 ) • Radiation Recall: Can occur in patients who received radiation weeks to years previously; permanently discontinue for signs of radiation recall. ( 5.5 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 Myelosuppression and Increased Risk of Myelosuppression without Vitamin Supplementation Pemetrexed forinjection 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. In Study JMCH, incidences of Grade 3 to 4 neutropenia (38% versus 23%), thrombocytopenia (9% versus 5%), febrile neutropenia (9% versus 0.6%), and neutropenic infection (6% versus 0) were higher in patients who received pemetrexed plus cisplatin without vitamin supplementation as compared to patients who were fully supplemented with folic acid and vitamin B 12 prior to and throughout pemetrexed plus cisplatin treatment. Initiate supplementation with oral folic acid and intramuscular vitamin B 12 prior to the first dose of pemetrexed; continue vitamin supplementation during treatment and for 21 days after the last dose of pemetrexed to reduce the severity of hematologic and gastrointestinal toxicity of pemetrexed for injection [see Dosage and Administration ( 2.4 ) ]. Obtain a co...
warnings and cautions
5.7 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, pemetrexed can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and increased malformations at doses lower than the recommended human dose of 500 mg/m 2 . Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with pemetrexed and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with pemetrexed and for 3 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.1 ) ].
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adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Myelosuppression [see Warnings and Precautions ( 5.1 ) ] • Renal failure [see Warnings and Precautions ( 5.2 ) ] • Bullous and exfoliative skin toxicity [see Warning and Precautions ( 5.3 )] • Interstitial pneumonitis [see Warnings and Precautions ( 5.4 ) ] • Radiation recall [see Warnings and Precautions ( 5.5 ) ] • The most common adverse reactions (incidence ≥20%) of pemetrexed for injection, when administered as a single agent are fatigue, nausea, and anorexia. (6.1) • The most common adverse reactions (incidence ≥20%) of pemetrexed for injection when administered with cisplatin are vomiting, neutropenia, anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation. ( 6.1 ) • The most common adverse reactions (incidence ≥20%) of pemetrexed for injection when administered in combination with pembrolizumab and platinum chemotherapy are fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. REDDY’S LABORATORIES Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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. In clinical trials, the most common adverse reactions (incidence ≥20%) of pemetrexed for injection, when administered as a single agent, are fatigue, nausea, and anorexia. The most common adverse reactions (incidence ≥20%) of pemetrexed for injection, when administered in combination with cisplatin are vomiting, neutropenia, anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation. The most common adverse reactions (incidence ≥20%) of pemetrexed for injection, when administered in combination with pembrolizumab and platinum chemotherapy, are fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia. Non-Squamous NSCLC First-line Treatment of Metastatic Non-squamous NSCLC with Pembrolizumab and Platinum Chemotherapy The safety of pemetrexed for injection, in combination with pembrolizumab and investigator’s choice of platinu...
adverse reactions table
• The most common adverse reactions (incidence ≥20%) of pemetrexed for injection when administered in combination with pembrolizumab and platinum chemotherapy are fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia. (6.1)