Dosing & Uses
Dosage Forms & Strengths
powder for injection
- 4mg/vial
capsule
- 0.25mg
- 1mg
Small Cell Lung Cancer
Indicated for SCLC sensitive disease after failure of first-line chemotherapy
Cervical Cancer
Indicated for combination therapy with cisplatin for stage IV-B, recurrent or persistent cervical carcinoma which cannot be treated with surgery and/or radiation therapy
0.75 mg/m² IV infused over 30 min on Days 1,2, & 3 (with cisplatin 50 mg/m² on Day 1); repeat at 21-day cycles
Ovarian Cancer
Indicated for metastatic ovarian cancer after failure of initial or subsequent chemotherapy
Dosage Modifications
Renal impairment
- IV infusion (monotherapy)
- Mild (CrCl 40-60 mL/min): No dosage adjustment necessary
- Moderate (CrCl 20-39 mL/min): Decrease dose to 0.75 mg/m² PO qDay
- Severe (CrCl <20 mL/min): Safety and efficacy has not been established
- Capsules
- CrCl 30-49 mL/min: Decrease dose to 1.5 mg/m² PO day
- CrCl <30 mL/min: 0.6 mg/m² PO Day
- Dose may be increased after first course by 0.4 mg/m²/day if no severe hematologic or gastrointestinal toxicities occur
Hematologic toxicities
- Do not administer subsequent courses of until neutrophils recover to >1,000 cells/mm³, platelets recover to >100,000 cells/mm³, hemoglobin levels recover to ≥9.0 g/dL (with transfusion if necessary)
- IV infusion (monotherapy)
- Neutrophil count <500 cells/mm³: Reduce dose to 1.25 mg/m² alternatively, granulocyte-colony stimulating factor (G-CSF) starting no sooner than 24 hours after topotecan administration has been completed
- Platelet count < 25.000 cells/mm³ during previous cycle: Reduce dose to 1.25 mg/m²
- Combination therapy with cisplatin
- Severe neutropenia (neutrophil counts <1,000 cells/mm³ with temperature of ≥38.0°C (100.4°F)): Reduce dose to 0.60 mg/m² (and further to 0.45 mg/m² if necessary); alternatively, G-CSF starting no sooner than 24 hours after topotecan administration has been completed
- Platelet count <25.000 cells/mm³: Reduce dose to 0.60 mg/m² (and further to 0.45 mg/m² if necessary)
Diarrhea (capsules only)
- Do not administer to patients with Grade 3 or 4 diarrhea
- After recovery to ≤Grade 1, reduce the dose by 0.4 mg/m²/day PO for subsequent courses
Dosing Considerations
Verify dose using body surface area prior to dispensing
Recommended dosage should generally not exceed 4 mg IV
Prior to administration of the first treatment course, baseline counts for neutrophils should be >1,500/mm³ and platelets >100,000/mm³
Monitor: CBC
Safety and effectiveness not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
IV infusion
- Ovarian cancer
- Neutropenia, grade 4 (80%)
- Anemia, grade 3 or 4 (41%)
- Thrombocytopenia, grade 4 (27%)
- Febrile neutropenia (23%)
- Small cell lung cancer
- Neutropenia, grade 4 (70%)
- Anemia, grade 3 or 4 (42%)
- Thrombocytopenia. grade 4 (29%)
- Cervical cancer (Combination therapy with cisplatin)
- Constitutional, grade 3 or 4 (69%)
- Pain, grade 3 or 4 (59%)
- Neutropenia, grade 4 (48%)
- Vomiting, grade 3 or 4 (40%)
- Anemia, grade 3 (34%)
- Thrombocytopenia, grade 3 (26%)
- Neutropenia, grade 3 (26%)
Capsule
- All grades
- Anemia (98%)
- Sepsis (43%)
- Nausea (33%)
- Thrombocytopenia (29%)
- Neutropenia (24%)
- Grade 3 or 4
- Neutropenia (24-32%)
- Thrombocytopenia (6-29%)
- Anemia (7-18%)
1-10%
IV infusion
- Ovarian cancer
- Nausea, grade 3 or 4 (10%)
- Vomiting, grade 3 or 4 (10%)
- Fatigue, grade 3 or 4 (7%)
- Dyspnea, grade 3 or 4 (6%)
- Diarrhea, grade 3 or 4 (6%)
- Sepsis, grade 3 or 4 (5%)
- Abdominal pain, grade 3 or 4 (5%)
- Constipation, grade 3 or 4 (5%)
- Intestinal obstruction, grade 3 or 4 (5%)
- Asthenia, grade 3 or 4 (5%)
- Pain, grade 3 or 4 (5%)
- Small cell lung cancer
- Neutropenia, grade 4 (9%)
- Asthenia, grade 3 or 4 (9%)
- Pneumonia, grade 3 or 4 (8%)
- Nausea, grade 3 or 4 (8%)
- Abdominal pain, grade 3 or 4 (6%)
- Fatigue, grade 3 or 4 (6%)
- Sepsis, grade 3 or 4 (5%)
- Cervical cancer (Combination therapy with cisplatin)
- Thrombocytopenia, grade 4 (7%)
- Stomatitis-pharyngitis, grade 3 or 4 (6%)
Capsule
- All grades
- Pyrexia (5%)
- Asthenia (7%)
- Grade 3 or 4
- Diarrhea (4%)
- Fatigue (4%)
- Nausea (3%)
- Vomiting (3%)
- Anorexia (2%)
- Asthenia (2%)
- Pyrexia (1%)
<1%
Oral
- Diarrhea, grade 4 (0.4%)
- Vomiting, grade 4 (0.4%)
- Fatigue, grade 4 (0.1%)
- Alopecia, grade 3 (0.1%)
Postmarketing Reports
Blood and lymphatic system disorders: Myelosuppression, severe bleeding (in association with thrombocytopenia
Immune system disorders: Allergic manifestations, anaphylactoid reactions
Gastrointestinal Disorders: Gastrointestinal perforation; mucosal inflammation, abdominal pain potentially associated with neutropenic enterocolitis
Pulmonary disorders: Interstitial lung disease
Skin and subcutaneous tissue disorders: Angioedema, severe dermatitis, severe pruritus
General disorders and administration site conditions: Extravasation
Hepatobiliary disorders: Grade 1 transient elevations in hepatic enzymes (8%); Grade 3/4 (4%); Grade 3/4 elevated bilirubin (<2%)
Warnings
Black Box Warnings
Administer only to patients with baseline neutrophil counts of 1500 cells/mm³or higher and a platelet count of 100,000 cells/mm³ or higher; monitor blood cell counts
To assess the occurrence of bone marrow suppression, blood cell counts should be monitored
Contraindications
Hypersensitivity reactions to drug or any components
Cautions
Administer to patients with bone marrow suppression only if patient has adequate bone marrow reserves; monitor peripheral blood counts and adjust dose as needed
PO: Do NOT redose if ANC <1500/mm³; Plt 100,000 <mm³; Hgb <9 g/dL
Avoid use in pregnancy; can cause fetal harm; advise women of potential risk to fetus
Neutropenia: pancytopenia has been reported
Grade 4 thrombocytopenia and grade 3-4 anemia reported; withhold and reduce dose based on neutrophil counts, platelet counts and hemoglobin levels
Fatal cases of interstitial lung disease have occurred; permanently discontinue for confirmed ILD
If extravasation occurs, immediately stop administration and institute recommended management procedures; severe cases reported
PO: If patient vomits after taking capsule, do NOT repeat dose
PO: If diarrhea occurs, treat aggressively, potentially life-threatening
Monitor patients presenting with neutropenia, fever and abdominal pain; fatal typhlitis reported in patients with neutropenic enterocolitisas
Monitor patients presenting with cough, fever, dyspnea and/or hypoxia and a histroy of lung disease as fatalities due to interstitial lung disease have been reported
Combination with cisplatin
- Administer first cycle of topotecan for injection only to patients with a baseline neutrophil count ≥1,500/mm³ and a platelet count ≥100,000/mm³; monitor blood counts frequently during treatment; withhold and reduce dose based on neutrophil counts, platelet counts and hemoglobin levels
Pregnancy & Lactation
Pregnancy
Based on animal data and its mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; there are no available clinical data on use of therapy in pregnancy; drug caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis at doses similar to the clinical dose.); advise pregnant women of potential risk to fetus
Verify pregnancy status of females of reproductive potential prior to initiating therapy
Contraception
- Advise females of reproductive potential to use effective contraception during treatment and for 6 months after last dose
Infertility
- Females: Therapy can have both acute and long-term effects on fertility
- Males: Effects on spermatogenesis occurred in animals administered topotecan; therapy may damage spermatozoa, resulting in possible genetic and fetal abnormalities; advise males with a female partner of reproductive potential to use effective contraception during treatment and for 3 months after the last dose
Lactation
There are no data on presence of drug or its metabolites in human milk or their effects on breastfed infant or on milk production; lactating rats excrete high concentrations of drug in milk
Because of potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 1 week after last dose
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Binds to topoisomerase I to produce double-strand breaks in DNA
Absorption
Bioavailability: 40% (PO)
Peak plasma time: 1-2 hr (PO)
Distribution
Protein Bound: 35%
Metabolism
Hepatic
Excretion
Half-life, terminal: 2-3 hr (IV); 3-6 hr (PO)
Excretion, PO: 35% feces; 22% urine
Excretion, IV: 20% feces; 54% urine
Administration
IV Incompatibilities
Y-site: dexamethasone sodium phosphate, fluorouracil, mitomycin, ticarcillin-clavulanate(?)
IV Compatibilities
Solution: D5W, NS
Y-site: carbopolatin, cisplatin, cimetidine, cyclophosphamide, doxorubicin, etoposide, gemcitabine, granisetron, ifosfamide, methylprednisolone Na-succinate, metoclopramide, ondansetro, paclitaxel, prochlorperazine, vincristine
IV Preparation
No preservatives-reconstitute immediately prior to use
Reconstitute in 4 mL SWI to obtain a 1 mg/mL solution
No preservatives-use immediately
Dilute in 50-250 mL NS or D5W; stability is pH dependent although topotecan may be further diluted in NS
IV Administration
Infuse over 30 min
Storage
Injection
- Unopened vials: Store at 20-25°C (68-77°F); protect from light in original carton; vials contain no preservative, contents should be used immediately after reconstitution
- Reconstituted vials: Store at 20-25°C (68-77°F) and ambient lighting conditions for 24 hr
- Diluted solutions: Store at 20-25°C (68-77°F) for ≤4 hr or under refrigerated at 2-8°C (36-46°F) for ≤12 hr
Capsule
- Store refrigerated 2-8ºC (36-46ºF); store bottles protected from light in original outer cartons
Images
Patient Handout
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
