Topotecan Hydrochloride Prescribing Information
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). Grade 4 neutropenia associated with infection occurred in 13% and febrile neutropenia occurred in 5%. Sepsis occurred in 4% of patients and was fatal in 1%. Grade 4 thrombocytopenia occurred in 27%, with a median duration of 5 days. Grade 3 or 4 anemia occurred in 37% of patients.
Grade 4 neutropenia occurred in 48% and Grade 4 thrombocytopenia occurred in 7% of 147 patients. Grade 3 or 4 anemia occurred in 40% of patients.
Topotecan can cause fatal typhlitis (neutropenic enterocolitis). Consider the possibility of typhlitis in patients presenting with fever, neutropenia, and abdominal pain.
Administer the first cycle of topotecan hydrochloride for injection only to patients with a baseline neutrophil count of greater than or equal to 1,500/mm3and a platelet count greater than or equal to 100,000/mm3. Monitor blood counts frequently during treatment. Withhold and reduce dose of topotecan hydrochloride based on neutrophil counts, platelet counts and hemoglobin levels [see
| Boxed Warning | 05/2020 |
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 ] .History of severe hypersensitivity reactions to topotecan. | 05/2020 |
Warnings and Precautions (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). Grade 4 neutropenia associated with infection occurred in 13% and febrile neutropenia occurred in 5%. Sepsis occurred in 4% of patients and was fatal in 1%. Grade 4 thrombocytopenia occurred in 27%, with a median duration of 5 days. Grade 3 or 4 anemia occurred in 37% of patients. Combination with cisplatin Grade 4 neutropenia occurred in 48% and Grade 4 thrombocytopenia occurred in 7% of 147 patients. Grade 3 or 4 anemia occurred in 40% of patients. Topotecan can cause fatal typhlitis (neutropenic enterocolitis). Consider the possibility of typhlitis in patients presenting with fever, neutropenia, and abdominal pain. Administer the first cycle of topotecan hydrochloride for injection only to patients with a baseline neutrophil count of greater than or equal to 1,500/mm3and a platelet count greater than or equal to 100,000/mm3. Monitor blood counts frequently during treatment. Withhold and reduce dose of topotecan hydrochloride based on neutrophil counts, platelet counts and hemoglobin levels [see Dosage and Administration ].Interstitial lung disease (ILD), including fatalities, can occur with topotecan hydrochloride. Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic radiation, and use of pneumotoxic drugs or colony stimulating factors. Monitor for pulmonary symptoms indicative of ILD. Permanently discontinue topotecan hydrochloride for injection if ILD is confirmed. Extravasation, including severe cases, can occur with topotecan hydrochloride. If signs or symptoms of extravasation occur, immediately stop administration of topotecan hydrochloride and institute recommended management procedures [see Adverse Reactions ]. | 05/2020 |
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 Ovarian CancerTopotecan hydrochloride for injection, as a single agent, is indicated for the treatment of patients with metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy.
- 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 Small Cell Lung CancerTopotecan hydrochloride for injection, as a single agent, 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.
- Patients with Stage IV-B, recurrent, or persistent cervical cancer which is not amenable to curative treatment, in combination with cisplatin. ()
1.3 Cervical CancerTopotecan hydrochloride for injection in combination with cisplatin is indicated for the treatment of patients with Stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment.
- Ovarian cancer and small cell lung cancer: 1.5 mg/m2 by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day cycle. (,
2.2 Recommended Dosage for Ovarian CancerThe recommended dosage of topotecan hydrochloride is 1.5 mg/m2by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity.
)2.3 Recommended Dosage for Small Cell Lung Cancer (SCLC)The recommended dosage of topotecan hydrochloride is 1.5 mg/m2by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day cycle.
- Cervical cancer: 0.75 mg/m2 by intravenous infusion over 30 minutes on Days 1, 2, and 3 with cisplatin 50 mg/m2 on Day 1, of a 21-day cycle. ()
2.4 Recommended Dosage for Cervical CancerThe recommended dosage of topotecan hydrochloride is 0.75 mg/m2by intravenous infusion over 30 minutes daily on Days 1, 2, and 3 in combination with cisplatin 50 mg/m2on Day 1, of a 21-day cycle.
- Renal impairment: Reduce dose if creatinine clearance (CLcr) 20 to 39 mL/min. ()
2.6 Dosage Modification for Renal ImpairmentFor topotecan hydrochloride as a single agent, reduce the dose to 0.75 mg/m2/day for patients with creatinine clearance (CLcr) of 20 to 39 mL/min (calculated with the Cockcroft-Gault method using ideal body weight)
[see Clinical Pharmacology ].
For injection: 4 mg (topotecan free base) lyophilized powder in a single-dose vial for reconstitution; light yellow to greenish powder.
Lactation: Advise not to breastfeed. (
There are no data on the presence of topotecan or its metabolites in human milk or their effects on the breastfed infant or on milk production. Lactating rats excrete high concentrations of topotecan in milk
Following intravenous administration of topotecan to lactating rats at a dose of 4.72 mg/m2(about twice the 1.5 mg/m2clinical dose based on BSA), topotecan was excreted into milk at concentrations up to 48-fold higher than those in plasma.