Topotecan Hydrochloride (Page 6 of 6)

14.3 Cervical Cancer

The efficacy of topotecan hydrochloride for injection was evaluated in a multi-center, randomized (1:1), open-label study (Study GOG 0179) conducted in 147 patients with histologically confirmed Stage IV-B, recurrent, or persistent cervical cancer considered not amenable to curative treatment with surgery and/or radiation. Patients were randomized to topotecan hydrochloride for injection (0.75 mg/m² once daily intravenously for 3 consecutive days starting on Day 1 of a 21-day cycle) with cisplatin (50 mg/m² intravenously on Day 1) or cisplatin as a single agent. Fifty-six percent of patients treated with topotecan hydrochloride with cisplatin and 56% of patients treated with cisplatin had received prior cisplatin with or without other agents as first-line chemotherapy. The efficacy outcome measure was OS.

Median OS of eligible patients receiving topotecan hydrochloride with cisplatin was 9.4 months (95% CI: 7.9, 11.9) compared with 6.5 months (95% CI: 5.8, 8.8) among patients randomized to cisplatin alone with a log rank P — value of 0.033 (significance level was 0.044 after adjusting for the interim analysis). The unadjusted hazard ratio for OS was 0.76 (95% CI: 0.59, 0.98).

Figure 1. Kaplan-Meier Curves for Overall Survival in Cervical Cancer in Study GOG 0179

Figure 1. Overall Survival Curves Comparing Topotecan Hydrochloride plus Cisplatin versus Cisplatin Monotherapy in Cervical Cancer Patients

15 REFERENCES

1. ”OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html.

16 HOW SUPPLIED/STORAGE AND HANDLING

Topotecan Hydrochloride for Injection is supplied in 4-mg (free base) single-dose vials.

4 mg Single-Dose Vial — NDC 45963-615-56

Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.]

Protect from light in original carton.

Topotecan Hydrochloride for Injection is a cytotoxic drug. Follow applicable handling and disposal procedures.¹

Sterile, Nonpyrogenic, preservative-free.

The container closure is not made with natural rubber latex.

17 PATIENT COUNSELING INFORMATION

Myelosuppression

Inform patients that topotecan hydrochloride decreases blood cell counts such as white blood cells, platelets, and red blood cells. Advise patients to notify their healthcare provider promptly for fever, other signs of infection, or bleeding [see Warnings and Precautions (5.1)].

Interstitial Lung Disease (ILD)

Inform patients of the risks of severe ILD. Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms [see Warnings and Precautions (5.2)].

Embryo-Fetal Toxicity

Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus. Advise women to contact their healthcare provider if they become pregnant, or if pregnancy is suspected during treatment with topotecan hydrochloride for injection [see Warnings and Precautions (5.4), Use in Specific Populations (8.1, 8.3)].

Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of topotecan hydrochloride for injection [see Use in Specific Populations (8.1, 8.3)].

Advise males with a female partner of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of topotecan hydrochloride for injection [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].

Lactation

Advise women to discontinue breastfeeding during treatment and for 1 week after the last dose of topotecan hydrochloride for injection [see Use in Specific Populations (8.2)].

Infertility

Advise male and female patients of the potential risk for impaired fertility [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].

Asthenia and Fatigue

Advise patients that topotecan hydrochloride for injection may cause asthenia or fatigue. These symptoms may impair the ability to safely drive or operate machinery.

Manufactured In Romania By:
Sindan Pharma SRL
11 Ion Mihalache Blvd
Bucharest 1, Romania 011171

Manufactured For:
Teva Pharmaceuticals
Parsippany, NJ 07054

Rev. C 8/2022

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 45963-615-56

Topotecan
Hydrochloride
for Injection

4 mg*/ vial

MUST BE RECONSTITUTEDAND DILUTED

For Intravenous Use Only

CAUTION: Cytotoxic Agent

Rx only

1 Single-Dose Vial

TOPOTECAN HYDROCHLORIDE topotecan hydrochloride injection, powder, lyophilized, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:45963-615 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TOPOTECAN HYDROCHLORIDE (TOPOTECAN) TOPOTECAN 4 mg in 4 mL

Inactive Ingredients Ingredient Name Strength MANNITOL TARTARIC ACID HYDROCHLORIC ACID SODIUM HYDROXIDE

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:45963-615-56 1 VIAL in 1 CARTON contains a VIAL 1 4 mL in 1 VIAL This package is contained within the CARTON (45963-615-56)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090620 01/05/2015

Labeler — Actavis Pharma, Inc. (119723554)

Revised: 08/2022 Actavis Pharma, Inc.