1 INDICATIONS AND USAGE Topotecan Injection is indicated for the treatment of patients with small cell lung cancer (SCLC) with platinum-sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy.

Topotecan Injection is a topoisomerase inhibitor indicated for treatment of small cell lung cancer (SCLC) platinum-sensitive disease in patients who progressed at least 60 days after initiation of first-line chemotherapy.

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6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] Interstitial Lung Disease [see Warnings and Precautions (5.2) ] Extravasation and Tissue Injury [see Warnings and Precautions (5.3) ] The most common Grade 3 or 4 hematologic adverse reactions (incidence >5%) were: neutropenia , anemia , thrombocytopenia, and febrile neutropenia.

( 6.1 ) The most common non-hematologic adverse reactions (incidence >5%) (all grades) were asthenia, dyspnea, nausea, pneumonia, abdominal pain, and fatigue.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc.

at 1-800-441-4100 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 data in Warnings and Precautions reflect exposure to topotecan from 8 trials in which 879 patients with small cell lung cancer (SCLC) and other solid tumors received topotecan 1.5 mg/m 2 by intravenous infusion daily for 5 consecutive days, starting on Day 1 of a 21-day cycle.

Small Cell Lung Cancer (SCLC) The safety of topotecan was evaluated in randomized, comparative trial in patients with recurrent or progressive SCLC (Study 090) [see Clinical Studies (14.1) ].

Table 1 shows the Grade 3 or 4 hematologic and non-hematologic adverse reactions in patients with SCLC.

Table 1.

Adverse Reactions Occurring in ≥5% of Patients with Small Cell Lung Cancer in Study 090 Adverse Reactions Topotecan (n = 107) CAV CAV = cyclophosphamide, doxorubicin and vincristine.

(n = 104) Grade 3–4 (%) Grade 3–4 (%) Hematologic Grade 4 neutropenia (< 500/mm 3 ) 70 72 Grade 3 or 4 anemia (Hgb < 8 g/dL) 42 20 Grade 4 thrombocytopenia (< 25,000/mm 3 ) 29 5 Febrile neutropenia 28 26 Non-Hematologic Respiratory, thoracic, and mediastinal Dyspnea 9 14 Pneumonia 8 6 General and administrative site conditions Asthenia 9 7 Fatigue 6 10 Pain Pain includes body pain, skeletal pain, and back pain.

5 7 Gastrointestinal Nausea 8 6 Abdominal pain 6 4 Infections Sepsis Death related to sepsis occurred in 3% of patients receiving topotecan and 1% of patients receiving CAV.

5 5 Hepatobiliary Disorders Based on 879 patients with small cell lung cancer or another solid tumor who were treated with topotecan, Grade 3 or 4 elevated aspartate (AST) or alanine transaminase (ALT) occurred in 4% and Grade 3 or 4 elevated bilirubin occurred in less than 2% of patients.

6.2 Postmarketing Experience The following reactions have been identified during postapproval use of topotecan.

Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Severe bleeding (in association with thrombocytopenia) Hypersensitivity Allergic manifestations, anaphylactoid reactions, angioedema Gastrointestinal Abdominal pain potentially associated with neutropenic enterocolitis, gastrointestinal perforation Pulmonary Interstitial lung disease Skin and Subcutaneous Tissue Severe dermatitis, severe pruritus General and Administration Site Conditions Extravasation, mucosal inflammation