Topotecan

HYCAMTIN for injection is a topoisomerase inhibitor indicated for treatment of: Patients with metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy, as a single agent. Patients with small cell lung cancer (SCLC) platinum-sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy, as a single agent. Patients with Stage IV-B, recurrent, or persistent cervical cancer which is not amenable to curative treatment, in combination with cisplatin

Topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks. Topotecan binds to the topoisomerase I‑DNA complex and prevents re-ligation of these single-strand breaks. The cytotoxicity of topotecan is thought to be due to double-strand DNA damage produced during DNA synthesis, when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I, and DNA. Mammalian cells cannot efficiently repair these double-strand breaks.

Ovarian Cancer and Small Cell Lung Cancer: 1.5 mg/m 2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day cycle. Cervical Cancer: 0.75 mg/m 2 by intravenous infusion over 30 minutes on Days 1, 2, and 3, with cisplatin 50 mg/m 2 on Day 1, of a 21-day cycle. Renal Impairment: Reduce dose if creatinine clearance (CLcr) 20 to 39 mL/min

HYCAMTIN is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan. Reactions have included anaphylactoid reactions. History of severe hypersensitivity reactions to topotecan

Boxed warning (myelosuppression hycamtin): can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts of greater than or equal to 1,500/mm 3 and platelet counts greater than or equal to 100,000/mm 3. Monitor blood cell counts. WARNING: MYELOSUPPRESSION HYCAMTIN can cause severe myelosuppression. Interstitial Lung Disease (ILD): Fatal cases have occurred. Permanently discontinue if ILD confirmed. Extravasation and Tissue Injury: Severe cases have occurred. If extravasation occurs, immediately stop administration and institute recommended management procedures. Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential risk to the fetus and to use effectives contraception.

The following serious adverse reactions are described elsewhere in the labeling: Myelosuppression Interstitial Lung Disease (ILD) Extravasation and Tissue Injury Ovarian Cancer The most common Grade 3 or 4 hematologic adverse reactions (incidence > 5%) were neutropenia, anemia, thrombocytopenia, and febrile neutropenia. The most common (incidence > 5%) non-hematologic adverse reactions (all Grades) were nausea, vomiting, fatigue, diarrhea, and dyspnea. SCLC The most common Grade 3 or 4 hematologic adverse reactions were (incidence > 5%) neutropenia, anemia, thrombocytopenia, and febrile neutropenia. The most common (incidence > 5%) non-hematologic adverse reactions (all Grades) were asthenia, dyspnea, nausea, pneumonia, abdominal pain, and fatigue. Cervical Cancer The most common Grade 3 or 4 hematologic adverse reactions were (incidence > 5%) neutropenia, anemia, and thrombocytopenia.

Store between 20°C and 25°C (68°F and 77°F) in original carton. Protect from light.