Topotecan Hydrochloride

1 INDICATIONS AND USAGE Topotecan hydrochloride 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. ( 1.1 ) • 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. ( 1.2 ) • Patients with Stage IV-B, recurrent, or persistent cervical cancer which is not amenable to curative treatment, in combination with cisplatin.

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Myelosuppression [see Warnings and Precautions ( 5.1 )] • Interstitial Lung Disease (ILD) [see Warnings and Precautions ( 5.2 )] • Extravasation and Tissue Injury [see Warnings and Precautions ( 5.3 )] Ovarian cancer: • The most common Grade 3 or 4 hematologic adverse reactions (incidence > 5%) were: neutropenia, anemia, thrombocytopenia, and febrile neutropenia. ( 6.1 ) • The most common (incidence > 5%) non-hematologic adverse reactions (all Grades) were: nausea, vomiting, fatigue, diarrhea, and dyspnea. ( 6.1 ) SCLC: • The most common Grade 3 or 4 hematologic adverse reactions were (incidence > 5%): neutropenia, anemia, thrombocytopenia, and febrile neutropenia.

8.1 Pregnancy Risk Summary Based on animal data and its mechanism of action, topotecan hydrochloride can cause fetal harm when administered to a pregnant woman. There are no available clinical data on the use of topotecan hydrochloride in pregnancy. Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis at doses similar to the clinical dose (see Data ). Advise pregnant women of the potential risk to a fetus. In the U.S.

WARNING: MYELOSUPPRESSION Topotecan hydrochloride 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 [see Warnings and Precautions ( 5.1 )]. WARNING: MYELOSUPPRESSION See full prescribing information for complete boxed warning. Topotecan hydrochloride can cause severe myelosuppression. 5 WARNINGS AND PRECAUTIONS • Interstitial lung disease (ILD): Fatal cases have occurred. Permanently discontinue if ILD confirmed. ( 5.2 ) • Extravasation and tissue injury: Severe cases have occurred. If extravasation occurs, immediately stop administration and institute recommended management procedures. ( 5.3 ) • Embryo-Fetal toxicity: Can cause fetal harm. Advise patients of potential risk to the fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Myelosuppression Topotecan hydrochloride can cause severe myelosuppression. Single Agent Grade 4 neutropenia occurred in 78% of 879 patients, with a median duration of 7 days and was most common during Cycle 1 (58% of patients). 4 CONTRAINDICATIONS Topotecan hydrochloride is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan. Reactions have included anaphylactoid reactions [see Adverse Reactions ( 6.2 )] . History of severe hypersensitivity reactions to topotecan. ( 4 )