Topotecan Hydrochloride
FDA Drug Information • Also known as: Hycamtin, Topotecan Hydrochloride
- Brand Names
- Hycamtin, Topotecan Hydrochloride
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
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 [see Warnings and Precautions ( 5.1 )] . WARNING: MYELOSUPPRESSION See full prescribing information for complete boxed warning. HYCAMTIN can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts 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 ( 2.4 , 5.1 ).
Description
11 DESCRIPTION Topotecan is a topoisomerase inhibitor. The chemical name for topotecan hydrochloride is ( S )-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1 H -pyrano[3’,4’:6,7] indolizino [1,2- b ]quinoline-3,14-(4 H ,12 H )-dione monohydrochloride. The molecular formula is C 23 H 23 N 3 O 5
What Is Topotecan Hydrochloride Used For?
1 INDICATIONS AND USAGE 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 ( 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 ( 1.3 ) 1.1 Ovarian Cancer HYCAMTIN ® 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. 1.2 Small Cell Lung Cancer HYCAMTIN 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. 1.3 Cervical Cancer HYCAMTIN 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.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION 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 ( 2.2 , 2.3 ) 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 ( 2.4 ) Renal Impairment: Reduce dose if creatinine clearance (CLcr) 20 to 39 mL/min ( 2.6 ) 2.1 Important Safety Information Verify dosage using body surface area. Do not exceed a single dose of 4 mg intravenously. 2.2 Recommended Dosage for Ovarian Cancer The recommended dosage of HYCAMTIN for injection is 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 until disease progression or unacceptable toxicity. 2.3 Recommended Dosage for Small Cell Lung Cancer (SCLC) The recommended dosage of HYCAMTIN for injection is 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. 2.4 Recommended Dosage for Cervical Cancer The recommended dosage of HYCAMTIN for injection is 0.75 mg/m 2 by intravenous infusion over 30 minutes daily on Days 1, 2, and 3, in combination with cisplatin 50 mg/m 2 on Day 1, of a 21-day cycle. 2.5 Dosage Modifications for Adverse Reactions Hematologic Do not administer subsequent cycles of HYCAMTIN for injection until neutrophils recover to greater than 1,000/mm 3 , platelets recover to greater than 100,000/mm 3 , and hemoglobin levels recover to greater than or equal to 9 g/dL (with transfusion if necessary). For HYCAMTIN for injection as a single agent, reduce the dose to 1.25 mg/m 2 /day for: neutrophil counts of less than 500/mm 3 or administer granulocyte-colony stimulating factor (G-CSF) starting no sooner than 24 hours following the last dose platelet counts less than 25,000/mm 3 during previous cycle For HYCAMTIN for injection in combination with cisplatin, reduce the dose to 0.6 mg/m 2 /day (and further to 0.45 mg/m 2 if necessary) for: febrile neutropenia (defined as neutrophil counts less than 1,000/mm 3 with temperature of greater than or equal to 38.0°C (100.4°F) or administer G-CSF starting no sooner than 24 hours following the last dose platelet counts less than 25,000/mm 3 during previous cycle 2.6 Dosage Modification for Renal Impairment For HYCAMTIN for injection as a single agent, reduce the dose to 0.75 mg/m 2 /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 (12.3)] . 2.7 Preparation and Intravenous Administration Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit. Preparation Reconstitute each 4 mg vial of HYCAMTIN for injection with 4 mL Sterile Water for Injection, USP. Dilute the appropriate volume of the reconstituted solution in either 0.9% Sodium Chloride...
Side Effects (Adverse Reactions)
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. ( 6.1 ) The most common (incidence > 5%) non-hematologic adverse reactions (all Grades) were asthenia, dyspnea, nausea, pneumonia, abdominal pain, and fatigue. ( 6.1 ) Cervical Cancer The most common Grade 3 or 4 hematologic adverse reactions were (incidence > 5%) neutropenia, anemia, and thrombocytopenia. ( 6.1 ) The most common (incidence > 25% and ≥ 2% higher than cisplatin alone) non-hematologic adverse reactions were pain, vomiting, and infection/febrile neutropenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 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 HYCAMTIN for injection from eight trials in which 879 patients with ovarian cancer or small cell lung cancer (SCLC) received HYCAMTIN for injection 1.5 mg/m 2 by intravenous infusion daily for 5 consecutive days, starting on Day 1 of a 21 day cycle and from one trial (Study GOG 0179) in which 147 patients with cervical cancer received HYCAMTIN for injection 0.75 mg/m 2 by intravenous infusion daily on Days 1, 2, and 3, with cisplatin 50 mg/m 2 by intravenous infusion on Day 1, of a 21-day cycle. Ovarian Cancer The safety of HYCAMTIN for injection was evaluated in a randomized trial conducted in 226 patients with metastatic ovarian cancer (Study 039) [see Clinical Studies (14.1)] . Table 1 shows the incidence of Grade 3 and 4 hematologic and non-hematologic adverse reactions that occurred in patients receiving HYCAMTIN for injection. Table 1. Adverse Reactions Occurring in Greater than or Equal to 5% of Patients With Ovarian Cancer in Study 039 a Death related to sepsis occurred in 2% of patients receiving HYCAMTIN and 0% of patients receiving paclitaxel. b Pain includes body pain, skeletal pain, and back pain. Adverse Reactions HYCAMTIN for Injection (n = 112) Paclitaxel (n = 114) Grade 3-4 (%) Grade 3-4 (%) Hematologic Grade 4 neutropenia (< 500/mm 3 ) Grade 3 or 4 anemia (Hgb < 8 g/dL) Grade 4 thrombocytopenia (< 25,000/mm 3 ) Febrile neutropenia 80 41 27 23 21 6 3 4 Non-Hematologic Infections Sepsis a 5 2 Respiratory, thoracic, and mediastinal Dyspnea 6 5 Gastrointestinal Vomiting 10 3 Nausea 10 2 Diarrhea 6 1 Abdominal pain 5 4 Intestinal obstruction 5 4 Constipation 5 0 General and administrative site conditions Fatigue 7 6 Pain b 5 7 Asthenia 5 3 Small Cell Lung Cancer (SCLC) The safety of HYCAMTIN for injection was evaluated in randomized, comparative trial in patients with recurrent or progressive SCLC (Study 090) [see Clinical Studies (14.2)] . Table 2 shows the Grade 3 or 4 hematologic and non-hematologic adverse reactions in patients with SCLC. Table 2. Adverse Reactions Occurring in Greater than or Equal to 5% of Patients With Small Cell Lung Cancer in Study 090 a Death related to sepsis occurred in 3% of patients receiving HYCAMTIN and 1% of patients receiving CAV. b Pain includes body pain, skeletal...
Contraindications
4 CONTRAINDICATIONS HYCAMTIN 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 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on animal data and its mechanism of action, HYCAMTIN can cause fetal harm when administered to a pregnant woman. There are no available clinical data on the use of HYCAMTIN 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. general population, the background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data In rabbits, an intravenous dose of 0.10 mg/kg/day [about equal to the 1.5 mg/m 2 clinical dose based on body surface area (BSA)] given on Days 6 through 20 of gestation caused maternal toxicity, embryolethality and reduced fetal body weight. In the rat, an intravenous dose of 0.23 mg/kg/day (about equal to the 1.5 mg/m 2 clinical dose based on BSA) given for 14 days before mating through gestation Day 6 caused fetal resorption, microphthalmia, pre-implant loss, and mild maternal toxicity. Administration of an intravenous dose of 0.10 mg/kg/day (about half the 1.5 mg/m 2 clinical dose based on BSA) given to rats on Days 6 through 17 of gestation caused an increase in post-implantation mortality. This dose also caused an increase in total fetal malformations. The most frequent malformations were of the eye (microphthalmia, anophthalmia, rosette formation of the retina, coloboma of the retina, ectopic orbit), brain (dilated lateral and third ventricles), skull, and vertebrae.
Overdosage
10 OVERDOSAGE Overdoses (up to 10-fold of the recommended dose) have occurred in patients receiving intravenous topotecan. The primary complication of overdosage is myelosuppression. Elevated hepatic enzymes, mucositis, gastrointestinal toxicity, and skin toxicity have occurred with overdosages. If an overdose is suspected, monitor the patient closely for myelosuppression and institute supportive-care measures as appropriate.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING HYCAMTIN for injection is supplied as a sterile, lyophilized, buffered, light yellow to greenish powder for reconstitution in 4-mg (free base) single-dose vials. NDC 0078-0674-61 (package of 1) Store between 20°C and 25°C (68°F and 77°F) [see USP Controlled Room Temperature] in original carton. Protect from light. HYCAMTIN for injection is a cytotoxic drug. Follow applicable handling and disposal procedures. 1
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.