openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Adverse reactions sections page 1 of 2 · 6 matching rows.
adverse reactions
6 ADVERSE REACTIONS Small cell lung cancer: • The most common hematologic adverse reactions were: neutropenia (97%), leukopenia (97%), anemia (89%), and thrombocytopenia (69%). (6.1) • The most common (>25%) non-hematologic adverse reactions (all grades) were: nausea, alopecia, vomiting, sepsis or pyrexia/infection with neutropenia, diarrhea, constipation, fatigue, and pyrexia. (6.1) Cervical cancer (Topotecan Injection plus cisplatin): • The most common hematologic adverse reactions (all grades) were: anemia (94%), leukopenia (91%), neutropenia (89%), and thrombocytopenia (74%). (6.1) • The most common (>25%) non-hematologic adverse reactions (all grades) were: pain, nausea, vomiting, and infection/febrile neutropenia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Small Cell Lung Cancer Data in the following section are based on the combined experiences of the 879 patients studied, including 426 patients with small cell lung cancer treated with topotecan. Table 1 lists the principle hematologic adverse reactions and Table 2 lists non-hematologic adverse reactions occurring in at least 15% of patients. Table 1. Hematologic Adverse Reactions Experienced in ≥15% of Patients, Including 426 Patients With Small Cell Lung Cancer, Receiving Topotecan Hematologic Adverse Reaction Patients (n=879) % Incidence Neutropenia <1,500 cells/mm 3 <500 cells/mm 3 97 78 Leukopenia <3,000 cells/mm 3 <1,000 cells/mm 3 97 32 Thrombocytopenia <75,000/mm 3 <25,000/mm 3 69 27 Anemia <10 g/dL <8 g/dL 89 37 Table 2. Non-hematologic Adverse Reactions Experienced by ≥15% of 879 Patients, Including 426 Patients With Small Cell Lung Cancer, Receiving Topotecan Non-hematologic Adverse Reaction Percentage of Patients with Adverse Reaction (879 Patients) All Grades Grade 3 Grade 4 Infections and infestations Sepsis or pyrexia/infection with neutropenia a 43 NR 23 Metabolism and nutrition disorders Anorexia 19 2 <1 Nervous system disorders Headache 18 1 <1 Respiratory, thoracic, and mediastinal disorders Dyspnea 22 5 3 Coughing 15 1 0 Gastrointestinal disorders Nausea 64 7 1 Vomiting 45 4 1 Diarrhea 32 3 1 Constipation 29 2 1 Abdominal pain 22 2 2 Stomatitis 18 1 <1 Skin and subcutaneous tissue disorders Alopecia 49 NA NA Rash b 16 1 0 General disorders and administrative site conditions Fatigue 29 5 0 Pyrexia 28 1 <1 Pain c 23 2 1 Asthenia 25 4 2 NA = Not applicable NR = Not reported separately a Does not include Grade 1 sepsis or pyrexia b Rash also includes pruritus, rash erythematous, urticaria, dermatitis, bullous eruption, and maculopapular rash. c Pain includes body pain, back pain, and skeletal pain. Nervous System Disorders Paresthesia occurred in 7% of patients but was generally grade 1. Hepatobiliary Disorders Grade 1 transient elevations in hepatic enzymes occurred in 8% of patients. Greater elevations, grade 3/4, occurred in 4%. Grade 3/4 elevated bilirubin occurred in <2% of patients. Table 3 shows the grade 3/4 hematologic and major non-hematologic adverse reactions in the topotecan/CAV comparator trial in small cell lung cancer. Table 3. Adverse Reactions Experienced by ≥5% of Small Cell Lung Cancer Patients Randomized to Receive Topotecan or CAV Adverse Reaction Topotecan (n=107) CAV (n=104) Hematologic Grade 3/4 % % Grade 4 neutropenia (<500 cells/mm 3 ) 70 72 Grade 3/4 anemia (Hgb <8 g dL) 42 20 Grade 4 thrombocytopenia (<25,000 plts/mm 3 ) 29 5 Pyrexia/Grade 4 neutropenia 28 26 Non-hematologic Grade 3/4 % % Infections and infestations Documented sepsis a 5 5 Respiratory, thoracic, and mediastinal disorders Dyspnea 9 14 Pneumonia 8 6 Gastrointestinal disorders Abdominal pain 6 4 Nausea 8 6 General disorders and administrative site conditions Fatigue 6 10 Asthenia 9 7 Pain b 5 7 a Death related to sepsis occurred in 3% of patients receiving topotecan, and 1% of patients receiving CAV b Pain includes body pain, skeletal pain, and back pain. Cervical Cancer In the comparative trial with Topotecan Injection plus cisplatin versus cisplatin in patients with cervical cancer, the most common dose-limiting adverse reaction was myelosuppression. Table 4 shows the hematologic adverse reactions and Table 5 shows the non-hematologic adverse reactions in patients with cervical cancer. Table 4. Hematologic Adverse Reactions in Patients with Cervical Cancer Treated with Topotecan Injection Plus Cisplatin or Cisplatin Monotherapy a Hematologic Adverse Reaction Topotecan Injection Plus Cisplatin (n = 140) Cisplatin (n = 144) Anemia All grades (Hgb <12 g/dL) 131 (94%) 130 (90%) Grade 3 (Hgb <8 to 6.5 g/dL) 47 (34%) 28 (19%) Grade 4 (Hgb <6.5 g/dL) 9 (6%) 5 (3%) Leukopenia All grades (<3,800 cells/mm 3 ) 128 (91%) 43 (30%) Grade 3 (<2,000 to 1,000 cells/mm 3 ) 58 (41%) 1 (1%) Grade 4 (<1,000 cells/mm 3 ) 35 (25%) 0 (0%) Neutropenia All grades (<2,000 cells/mm 3 ) 125 (89%) 28 (19%) Grade 3 (<1,000 to 500 cells/mm 3 ) 36 (26%) 1 (1%) Grade 4 (<500 cells/mm 3 ) 67 (48%) 1 (1%) Thrombocytopenia All grades (<130,000 cells/mm 3 ) 104 (74%) 21 (15%) Grade 3 (<50,000 to 10,000 cells/mm 3 ) 36 (26%) 5 (3%) Grade 4 (<10,000 cells/mm 3 ) 10 (7%) 0 (0%) a Includes patients who were eligible and treated. Table 5. Non-hematologic Adverse Reactions Experienced by ≥ 5% of Patients with Cervical Cancer Treated with Topotecan Injection Plus Cisplatin or Cisplatin Monotherapy a Topotecan Injection Plus Cisplatin Cisplatin (n = 140) (n = 144) Adverse Reaction All Grades b Grade 3 Grade 4 All Grades b Grade 3 Grade 4 General disorders and administrative site conditions Constitutional c 96 (69%) 11 (8%) 0 89 (62%) 17 (12%) 0 Pain d 82 (59%) 28 (20%) 3 (2%) 72 (50%) 18 (13%) 5 (3%) Gastrointestinal disorders Vomiting 56 (40%) 20 (14%) 2 (1%) 53 (37%) 13 (9%) 0 Nausea 77 (55%) 18 (13%) 2 (1%) 79 (55%) 13 (9%) 0 Stomatitis-pharyngitis 8 (6%) 1 (<1%) 0 0 0 0 Other 88 (63%) 16 (11%) 4 (3%) 80 (56%) 12 (8%) 3 (2%) Dermatology 67 (48%) 1 (<1%) 0 29 (20%) 0 0 Metabolic-Laboratory 55 (39%) 13 (9%) 7 (5%) 44 (31%) 14 (10%) 1 (<1%) Genitourinary 51 (36%) 9 (6%) 9 (6%) 49 (34%) 7 (5%) 7 (5%) Nervous system disorders Neuropathy 4 (3%) 1 (<1%) 0 3 (2%) 1 (<1%) 0 Other 49 (35%) 3 (2%) 1 (<1%) 43 (30%) 7 (5%) 2 (1%) Infection-febrile neutropenia 39 (28%) 21 (15%) 5 (4%) 26 (18%) 11 (8%) 0 Cardiovascular 35 (25%) 7 (5%) 6 (4%) 22 (15%) 8 (6%) 3 (2%) Hepatic 34 (24%) 5 (4%) 2 (1%) 23 (16%) 2 (1%) 0 Pulmonary 24 (17%) 4 (3%) 0 23 (16%) 5 (3%) 3 (2%) Vascular disorders Hemorrhage 21 (15%) 8 (6%) 1 (<1%) 20 (14%) 3 (2%) 1 (<1%) Coagulation 8 (6%) 4 (3%) 3 (2%) 10 (7%) 7 (5%) 0 Musculoskeletal 19 (14%) 3 (2%) 0 7 (5%) 1 (<1%) 1 (<1%) Allergy-Immunology 8 (6%) 2 (1%) 1 (<1%) 4 (3%) 0 1 (<1%) Endocrine 8 (6%) 0 0 4 (3%) 2 (1%) 0 Sexual reproduction function 7 (5%) 0 0 10 (7%) 1 (<1%) 0 Ocular-visual 7 (5%) 0 0 7 (5%) 1 (<1%) 0 Data were collected using NCI Common Toxicity Criteria, v. 2. a Includes patients who were eligible and treated. b Grades 1 through 4 only. There were 3 patients who experienced grade 5 deaths with investigator-designated attribution. One was a grade 5 hemorrhage in which the drug-related thrombocytopenia aggravated the event. A second patient experienced bowel obstruction, cardiac arrest, pleural effusion and respiratory failure which were not treatment related but probably aggravated by treatment. A third patient experienced a pulmonary embolism and adult respiratory distress syndrome, the latter was indirectly treatment-related. c Constitutional includes fatigue (lethargy, malaise, asthenia), fever (in the absence of neutropenia), rigors, chills, sweating, and weight gain or loss. d Pain includes abdominal pain or cramping, arthralgia, bone pain, chest pain (non-cardiac and non-pleuritic), dysmenorrhea, dyspareunia, earache, headache, hepatic pain, myalgia, neuropathic pain, pain due to radiation, pelvic pain, pleuritic pain, rectal or perirectal pain, and tumor pain. 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials or listed in other sections of the prescribing information, the following reactions have been identified during post-marketing use of Topotecan Injection. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Topotecan Injection. Blood and Lymphatic System Disorders: Severe bleeding (in association with thrombocytopenia). [see Warnings and Precautions ( 5.1 ) ] Immune System Disorders: Allergic manifestations; Anaphylactoid reactions. Gastrointestinal Disorders: Abdominal pain potentially associated with neutropenic colitis. [see Warnings and Precautions ( 5.2 ) ] Pulmonary Disorders: Interstitial lung disease [see Warnings and Precautions ( 5.3 ) ] Skin and Subcutaneous Tissue Disorders: Angioedema, severe dermatitis, severe pruritus General Disorders and Administration Site Conditions: Inadvertent extravasation [see Warnings and Precautions ( 5.5 ) ]