WARNING: BONE MARROW SUPPRESSION HYCAMTIN ® can cause severe myelosuppression. Administer only to patients with neutrophil counts of ≥1,500 cells/mm 3 and platelet counts ≥100,000 cells/mm 3 . Monitor blood cell counts. WARNING: BONE MARROW SUPPRESSION See full prescribing information for complete boxed warning HYCAMTIN can cause severe myelosuppression. Administer only to patients with baseline neutrophil counts of ≥1,500 cells/mm 3 and a platelet count ≥100,000 cells/mm 3 . Monitor blood cell counts (5.1).
openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS • Bone marrow suppression: Administer HYCAMTIN only to patients with adequate bone marrow reserves. Monitor peripheral blood counts. ( 5.1 ) Adjust dose as needed. ( 2.2 ) • Diarrhea: Severe diarrhea can occur and may require hospitalization. ( 5.2 ) Withhold for severe diarrhea. Reduce dose upon recovery. ( 2.2 ) • Interstitial lung disease (ILD): Fatal cases have occurred. Permanently discontinue for confirmed ILD. ( 5.3 ) • Embryofetal toxicity: Can cause fetal harm. Advise women of potential risk to the fetus. ( 5.4 , 8.1 ) 5.1 Bone Marrow Suppression Bone marrow suppression (primarily neutropenia) is a dose-limiting toxicity of HYCAMTIN. Neutropenia is not cumulative over time. The following data on myelosuppression are based on an integrated safety database from 4 thoracic malignancy trials (N = 682) using HYCAMTIN capsules at 2.3 mg/m 2 /day for 5 consecutive days. The median day for neutrophil and platelet nadirs occurred on Day 15. Neutropenia: Grade 4 neutropenia (<500 cells/mm 3 ) occurred in 32% of patients with a median duration of 7 days and was most common during Course 1 of treatment (20% of patients). Clinical sequelae of neutropenia included infection (17%), febrile neutropenia (4%), sepsis (2%), and septic death (1%). Pancytopenia has been reported. Topotecan can cause fatal typhlitis (neutropenic enterocolitis). Consider the possibility of typhlitis in patients presenting with fever, neutropenia, and abdominal pain [see Dosage and Administration (2.2)]. Thrombocytopenia: Grade 4 thrombocytopenia (<10,000 cells/mm 3 ) occurred in 6% of patients, with a median duration of 3 days. Anemia: Grade 3 or 4 anemia (<8 g/dL) occurred in 25% of patients. Administer the first course of HYCAMTIN only to patients with a neutrophil count of ≥1,500 cells/mm 3 and a platelet count ≥100,000 cells/mm 3 . Monitor peripheral blood cell counts frequently during treatment with HYCAMTIN. Refer to Section 2.2 for dose modification guidelines for hematological toxicities in subsequent courses. 5.2 Diarrhea Diarrhea, including severe and life-threatening diarrhea requiring hospitalization, can occur during treatment with HYCAMTIN capsules. Diarrhea caused by HYCAMTIN capsules can occur at the same time as drug-induced neutropenia and its sequelae. In the 682 patients who received HYCAMTIN capsules in the 4 lung cancer trials, the incidence of diarrhea caused by HYCAMTIN capsules was 22%, with 4% Grade 3 and 0.4% Grade 4.The incidence of Grade 3 or 4 diarrhea proximate (within 5 days) to Grade 3 or 4 neutropenia events in the group receiving HYCAMTIN capsules was 5%. The median time to onset of Grade 2 or worse diarrhea was 9 days in the group receiving HYCAMTIN capsules. Manage diarrhea caused by HYCAMTIN capsules aggressively. Do not administer HYCAMTIN capsules to patients with Grade 3 or 4 diarrhea. Reduce the dose of HYCAMTIN after recovery to Grade 1 or less [see Dosage and Administration (2.2)]. 5.3 Interstitial Lung Disease Interstitial lung disease (ILD), including fatalities, has occurred with HYCAMTIN. Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic radiation, and use of pneumotoxic drugs and/or colony stimulating factors. Monitor patients for pulmonary symptoms indicative of interstitial lung disease (e.g., cough, fever, dyspnea, and/or hypoxia), and discontinue HYCAMTIN if a new diagnosis of ILD is confirmed. 5.4 Embryofetal Toxicity HYCAMTIN can cause fetal harm when administered to a pregnant woman. Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis. If this drug is used during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use highly effective contraception during treatment and for at least 1 month after the last dose of HYCAMTIN. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking HYCAMTIN [see Use in Specific Populations (8.1, 8.7)] .
6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: • Bone Marrow Suppression [see Warnings and Precautions (5.1)] • Diarrhea [see Warnings and Precautions (5.2)] • Interstitial Lung Disease [see Warnings and Precautions (5.3)] The most common Grade 3 or 4 hematologic adverse reactions with HYCAMTIN capsules were neutropenia (56%), anemia (25%), and thrombocytopenia (35%). The most common (≥10%) non-hematologic adverse reactions (all grades) were nausea (33%), diarrhea (22%), vomiting (21%), alopecia (20%), and fatigue (19%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 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 reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of HYCAMTIN capsules was evaluated in 682 patients with lung cancer (3 recurrent small cell lung cancer [SCLC] trials and 1 recurrent non-small cell lung cancer [NSCLC] trial) who received at least one dose of HYCAMTIN capsules. Patients in all four trials had advanced lung malignancies and received prior chemotherapy in the first-line setting. The dose regimen for HYCAMTIN capsules was 2.3 mg/m 2 /day for five consecutive days every 21 days. The median number of courses was 3 (range: 1 to 20) in these four trials. Table 2 describes the hematologic and non-hematologic adverse reactions in recurrent SCLC patients treated with HYCAMTIN capsules in the overall lung cancer patient population. Table 2. Incidence (≥5%) of Adverse Reactions in Small Cell Lung Cancer Patients Treated With HYCAMTIN Capsules Plus BSC and in Four Lung Cancer Trials Adverse Reaction HYCAMTIN Capsules + BSC HYCAMTIN Capsules Lung Cancer Population (N = 70) (N = 682) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) Hematologic Anemia 94 15 10 98 18 7 Neutropenia 91 28 33 83 24 32 Thrombocytopenia 81 30 7 81 29 6 Non-hematologic Nausea 27 1 0 33 3 0 Diarrhea 14 4 1 22 4 0.4 Vomiting 19 1 0 21 3 0.4 Alopecia 10 0 0 20 0.1 0 Fatigue 11 0 0 19 4 0.1 Anorexia 7 0 0 14 2 0 Asthenia 3 0 0 7 2 0 Pyrexia 7 1 0 5 1 1 BSC = Best Supportive Care. N = Total number of patients treated. Adverse reactions were graded using NCI Common Toxicity Criteria Version 2.0. On-Study Death Due to Toxicity of HYCAMTIN: In the 682 patients who received HYCAMTIN capsules in the four lung cancer trials, 39 deaths (6%) occurred within 30 days after the last dose for a reason other than progressive disease: 13 due to hematologic toxicity, 5 due to non-hematologic toxicity (2 from diarrhea), and 21 due to other causes.