Version July 2025
Topotecan can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts of greater than or equal to 1,500/mm3 and platelet counts of greater than or equal to 100,000/mm3. Monitor blood cell counts.
Dosage guidance:
Safety: Baseline neutrophil count should be ≥1,500/mm3 and platelets should be ≥100,000/mm3 prior to treatment; for re-treatment, neutrophil count should be >1,000/mm3; platelets >100,000/mm3 and hemoglobin ≥9 g/dL (with transfusion as necessary).
Dosing: IV doses should generally not exceed 4 mg; verify dose prior to administration.
Clinical considerations: Refer to the protocol or institutional guidance for additional details of off-label dosing.
Cervical cancer, advanced, recurrent or persistent: IV: 0.75 mg/m2/day on days 1, 2, and 3 of a 21-day treatment cycle (in combination with cisplatin) for a maximum of 6 cycles (in nonresponders) or until disease progression or unacceptable toxicity (Ref) or 1.5 mg/m2 on days 1 to 5 (as a single agent; off label) of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Ewing sarcoma, relapsed or refractory (off-label use): IV: 0.75 mg/m2/day on days 1 to 5 of a 21-day treatment cycle (in combination with cyclophosphamide); continue until disease progression or unacceptable toxicity (Ref).
Ovarian cancer, metastatic: IV: 1.5 mg/m2/day on days 1 to 5 of a 21-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Off-label dosing/combinations:
Single agent therapy: IV: 1.25 mg/m2/day on days 1 to 5 of a 21-day treatment cycle or 4 mg/m2 on days 1, 8, and 15 every 28 days; continue until disease progression or unacceptable toxicity or a maximum of 12 months (Ref).
In combination with bevacizumab: IV: 1.25 mg/m2/day on days 1 to 5 of a 21-day treatment cycle (in combination with bevacizumab) or 4 mg/m2 on days 1, 8, and 15 of a 28-day treatment cycle (in combination with bevacizumab); continue until disease progression or unacceptable toxicity (Ref).
Primary CNS lymphoma, relapsed or refractory (off-label use): IV: 1.5 mg/m2 on days 1 to 5 of a 21-day treatment cycle for a maximum of 10 cycles or until disease progression or unacceptable toxicity (Ref) or 1.5 mg/m2 on days 1 to 5 of a 21-day treatment cycle for up to 6 cycles or until disease progression or unacceptable toxicity (Ref).
Rhabdomyosarcoma, metastatic (off-label use): Adults <21 years of age: IV: 0.75 mg/m2/day on days 1 to 5 of a 21-day treatment cycle for 2 cycles (window therapy; in combination with cyclophosphamide); if objective response occurred by week 6, follow with alternating cycles of vincristine, topotecan, and cyclophosphamide (VTC) with vincristine, dactinomycin, and cyclophosphamide (VAC) (Ref).
Small cell lung cancer, relapsed or progressive:
IV: 1.5 mg/m2/day on days 1 to 5 of a 21-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Oral: 2.3 mg/m2/day (round dose to the nearest 0.25 mg) on days 1 to 5 of a 21-day treatment cycle for at least 4 cycles (Ref).
Missed doses: Oral: If a dose if missed or patient vomits after a dose is administered, do not administer a replacement dose; administer the next dose at the scheduled time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: General recommendations are provided below. Also, refer to indication-specific institutional protocols, as numerous dosing schedules/adjustments exist depending on disease, response, and concomitant therapies.
Altered kidney function:
IV, Oral:
CrCl ≥60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 40 to 59 mL/minute: No dosage adjustment necessary. For IV topotecan, patients that have had extensive prior therapy (eg, platinum-containing chemotherapy, ≥2 chemotherapy regimens in the last 6 months, extensive radiation to bone marrow) are at increased risk of ≥ grade 3 adverse events (ie, thrombocytopenia, neutropenia). For these patients, as well as those with poor performance status or receiving concomitant nephrotoxic medications, consider administering 70% of the usual indication-specific dose (Ref).
CrCl 20 to 39 mL/minute: Administer 50% of the usual indication-specific dose (Ref).
CrCl <20 mL/minute: Avoid use if possible. If necessary, administer 25% of the usual indication-specific dose (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal SCr concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV, Oral: No data available, although theoretically renal clearance may be increased. No dosage adjustment recommended but monitor response closely (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (exact percentage unknown) (Ref):
IV, Oral: Avoid use if possible. If necessary, administer 25% of the usual indication-specific dose and monitor closely for myelosuppression. When scheduled dose falls on a dialysis day, administer after dialysis (Ref).
Peritoneal dialysis: IV, Oral: No data available. Avoid use if possible. If necessary, administer 25% of the usual indication-specific dose and monitor closely for myelosuppression (Ref).
CRRT: IV, Oral: No data available. Consider administering 50% of the usual indication-specific dose and monitor closely for myelosuppression (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV, Oral: No data available. Consider administering 25% of the usual indication-specific dose and monitor closely for myelosuppression. When scheduled dose falls on a PIRRT day, administer after PIRRT (Ref).
IV: There are no dosage adjustments provided in the manufacturer's labeling. A small phase I study in patients with hepatic impairment (total bilirubin >1.2 mg/dL), found no pharmacokinetic or pharmacodynamic alterations and suggests that dosage adjustment is not likely necessary (Ref).
Oral: There is no dosage adjustment provided in the manufacturer's labeling.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Withhold subsequent cycles until neutrophils recover to >1,000/mm3, platelets recover to >100,000/mm3, and hemoglobin recovers to ≥9 g/dL (with transfusion if necessary). Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
Combination therapy with cisplatin: IV:
Febrile neutropenia (neutrophils <1,000/mm3 with temperature of ≥38°C): Reduce topotecan to 0.6 mg/m2/day for subsequent cycles or administer granulocyte-colony stimulating factor (G-CSF) support beginning at least 24 hours after the last topotecan dose. If necessary, may further reduce dose to 0.45 mg/m2/day for subsequent cycles.
Platelets <25,000/mm3: Reduce topotecan to 0.6 mg/m2/day for subsequent cycles. If necessary, may further reduce dose to 0.45 mg/m2/day for subsequent cycles.
Single-agent therapy:
IV:
Neutrophils <500/mm3: Reduce dose to 1.25 mg/m2/day for subsequent cycles or administer G-CSF support beginning at least 24 hours after the last topotecan dose.
Platelets <25,000/mm3: Reduce dose to 1.25 mg/m2/day for subsequent cycles.
Oral:
Diarrhea (any grade): Treat with antidiarrheals at the first sign of diarrhea.
Diarrhea (grade 3 or 4): Withhold topotecan until recovery to ≤ grade 1, then reduce dose by 0.4 mg/m2/day for subsequent cycles.
Neutrophils <500/mm3 associated with fever or infection or lasting ≥7 days or neutrophils 500/mm3 to 1,000/mm3 lasting beyond day 21 of cycle: Reduce dose by 0.4 mg/m2/day for subsequent cycles.
Platelets <25,000/mm3: Reduce dose by 0.4 mg/m2/day for subsequent cycles.
Pulmonary toxicity: Interstitial lung disease (ILD): Permanently discontinue if ILD is confirmed.
Refer to adult dosing.
(For additional information see "Topotecan: Pediatric drug information")
Note: In adults, baseline neutrophil count should be ≥1,500/mm3 and platelets should be ≥100,000/mm3 prior to treatment; for retreatment, neutrophil count should be >1,000/mm3, platelets >100,000/mm3, and hemoglobin ≥9 g/dL; consult individual pediatric protocols for details regarding baseline neutrophil and platelet counts and hemoglobin. Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol. In pediatric patients, dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra precaution to verify dosing parameters during calculations. Oral topotecan is associated with a moderate emetic potential (depending on the dose) in pediatrics; antiemetics may be recommended to prevent nausea and vomiting (Ref).
Acute leukemias (acute lymphocytic leukemia or acute myeloid leukemia), relapsed or refractory: Limited data available: TVTC regimen:
Infants: IV: 0.03 mg/kg/day as a continuous infusion on days 0 to 4 (120 hours total) of a 14-day treatment protocol (in combination with thiotepa, clofarabine, vinorelbine, and intrathecal cytarabine). Patients without disease progression or significant toxicity may receive additional cycles upon hematologic recovery until hematopoietic stem cell transplant (HSCT) is available (Ref).
Children and Adolescents: IV: 1 mg/m2/day as a continuous infusion on days 0 to 4 (120 hours total) of a 14-day treatment protocol (in combination with thiotepa, clofarabine, vinorelbine, and intrathecal cytarabine). Patients without disease progression or significant toxicity may receive additional cycles upon hematologic recovery until HSCT is available (Ref).
Acute lymphoblastic leukemia, recurrent (first relapse): Limited data available: Children and Adolescents: Induction therapy: IV: 2.4 mg/m2/dose once daily for 7 to 9 days (Ref).
CNS malignancies, including gliomas: Limited data available:
Fixed dosing: Infants, Children, and Adolescents: Oral (using reconstituted lyophilized parenteral formulation): 0.8 mg/m2/dose once daily for 21 days of a 28-day cycle was used in 25 pediatric patients (median age: 9.2 years; range: 0.8 to 23 years) with recurrent brain tumors, including gliomas, medulloblastoma, and ependymoma; the reported median number of cycles: 1.9 [range: 0.5 to 15 cycles (months)] (Ref).
Dose escalation: Children ≥3 years and Adolescents: Oral (using reconstituted lyophilized parenteral formulation): Initial: 0.4 mg/m2/dose once daily was used in a trial of 32 pediatric patients (median age: 9.5 years; range: 3 to 18 years) with recurrent or progression of high-grade glioma; dosage was increased based upon patient tolerance and individual dose-limiting toxicity; doses were increased in 0.2 mg/m2 increments at weekly intervals for the first 2 weeks of therapy and then increased in 0.1 mg/m2 increments at weekly intervals up to the maximum dose of 2 mg/m2/day; once the patient's maximum tolerated dose was reached, the daily dose was decreased until toxicity became acceptable; reported final median maximum tolerated dose: 0.9 mg/m2/day (range: 0.6 to 2 mg/m2/day); median duration of therapy: 3 months (range: 21 days to 1 year) (Ref).
Hematopoietic stem cell transplant for neuroblastoma; autologous, conditioning regimen: Limited data available:
Children and Adolescents: IV: 2 mg/m2/dose on days −8 through −4 prior to stem cell transfusion (total dose: 10 mg/m2), in combination with carboplatin and thiotepa, was used in 21 patients (median age: 4.1 years; range: 1 to 29 years) with refractory solid tumors (neuroblastoma: n=11) (Ref). In a phase 1/2 trial of 51 patients (median age: 5.1 years; range: 1.5 to 21 years), an initial dose of: 3 mg/m2/dose on day −11 was used with subsequent doses (days −10 through −2; 10 days total of topotecan therapy) determined by pharmacokinetic analysis (target AUC: 100 ± 20 ng/mL/hour) and administered once daily (in combination with cyclophosphamide on days −6 through −2); the median reported topotecan dose was 3.1 mg/m2/day (range: 1.1 to 4.6 mg/m2/day) (Ref).
Neuroblastoma: Limited data available:
Induction: Infants, Children, and Adolescents:
Patient weight ≤12 kg: IV: Initial: 0.04 mg/kg/dose once daily for 5 days (in combination with cyclophosphamide); repeat cycle every 21 days for 2 cycles (Ref).
Patient weight >12 kg: IV: Initial: 1.2 mg/m2/dose once daily for 5 days (in combination with cyclophosphamide); repeat cycle every 21 days for 2 cycles (Ref).
Note: Pharmacokinetic analysis was used to guide topotecan therapy during the first 2 cycles using a target AUC: 50 to 70 ng/mL/hour; median dose for cycle 1 was 1.2 mg/m2/day (range: 0.75 to 2.1 mg/m2/day) and for cycle 2, the median dose was 1.3 mg/m2/day (range: 1.2 to 2.9 mg/m2/day) (Ref).
Untreated metastatic disease:
Monotherapy (window therapy): Children and Adolescents: IV: 2 mg/m2/dose once daily for 5 days; repeat cycle every 21 days for 2 cycles (Ref).
Topotecan and cyclophosphamide regimen (window therapy): Children and Adolescents: IV: 0.75 mg/m2/dose once daily for 5 days (in combination with cyclophosphamide); repeat cycle every 21 days for 2 cycles (Ref).
Recurrent or refractory:
IV:
Monotherapy: Children and Adolescents: IV: 2 mg/m2/dose once daily for 5 days (Ref).
Topotecan and cyclophosphamide regimen: Children and Adolescents:
Patient weight ≤12 kg: IV: 0.025 mg/kg/dose once daily for 5 days (in combination with cyclophosphamide); repeat cycle every 21 days (Ref).
Patient weight >12 kg: IV: 0.75 mg/m2/dose once daily for 5 days (in combination with cyclophosphamide); repeat cycle every 21 days (Ref).
Topotecan and etoposide regimen: Children and Adolescents: IV: 1 mg/m2/dose once daily on days 1 to 5 of a 28-day cycle (in combination with etoposide) or 1 mg/m2/day as a continuous infusion for days 1 to 7 (168 hour total infusion) of a 28-day cycle (in combination with etoposide) (Ref).
Topotecan/Vincristine/High-Dose Cyclophosphamide regimen (HD-CTV): Children and Adolescents: IV: 2 mg/m2/dose once daily on days 1 to 4 (total dose per cycle: 8 mg/m2) (in combination with cyclophosphamide and vincristine); in the trial, some patients received 2 courses (Ref).
Oral (using reconstituted lyophilized parenteral formulation): Children ≥2 years and Adolescents: 0.8 mg/m2/dose once daily for 14 days (in combination with oral cyclophosphamide); repeat cycle every 21 to 28 days (Ref). In a phase 1 dose escalation trial of 20 pediatric patients (median age: 10.6 years) with refractory solid tumors including neuroblastoma, patients received a daily dose of 1.8 mg/m2 once daily for 5 days, followed by 2 days of rest, then another 5 days of therapy (one cycle: 10 doses over 12 days); repeating this cycle every 28 days was shown to stabilize disease in some patients (Ref).
Pediatric solid tumors; recurrent or refractory or untreated metastatic including rhabdomyosarcoma and Ewing sarcoma: Limited data available:
IV:
Monotherapy: (window therapy): Children and Adolescents: IV: 2 to 2.4 mg/m2/dose once daily for 5 days every 21 days; dosing from an uncontrolled study in which patients (n=48) received topotecan as initial therapy, prior to other treatment (Ref).
Combination therapy: Children and Adolescents: IV: 0.75 mg/m2/dose once daily for 5 days every 21 days in combination with cyclophosphamide (Ref) or with cyclophosphamide and vincristine (VTC regimen) (Ref); this dosing has also been administered in combination with temozolomide in 28-day cycles (TOTEM regimen) (Ref).
Oral (using reconstituted lyophilized parenteral formulation or oral capsules [for patients able to swallow]): Note: When using oral capsules, doses were rounded to the nearest 0.25 mg:
Monotherapy: Children ≥3 years and Adolescents: Oral: 1.8 mg/m2 once daily for 5 days, followed by 2 days of rest, then another 5 days of therapy (10 doses over 12 days [days 1 to 5 and days 8 to 12]) of a 28-day cycle; repeat cycle every 28 days; dosing based on a phase 1 dose escalation trial of 20 pediatric patients (median age: 10.6 years) with refractory solid tumors (Ref).
Combination therapy: Children ≥3 years and Adolescents: Oral: 1.4 mg/m2 once daily for 5 days, followed by 2 days of rest, then another 5 days of therapy (10 doses over 12 days [days 1 to 5 and days 8 to 12]) of a 28-day cycle (in combination with sorafenib). Combination dosing based on a phase 1 dose escalation trial of 12 pediatric patients (median age: 13 years [range: 8 to 18 years]) with relapsed or refractory solid tumors; number of cycles received ranged from 1 to 8 (Ref).
Solid tumors with leptomeningeal metastases (including neuroblastoma, leukemia, CNS tumors), recurrent/refractory: Limited data available:
Intraventricular/Intra-Ommaya:
Blaney 2013: Children ≥3 years and Adolescents: 0.2 mg daily for 5 days (with dexamethasone); repeat every other week for 2 courses for induction, every 3 weeks for 2 courses for consolidation, then every 4 weeks for up to 11 courses for maintenance.
Groves 2008: Children ≥5 years and Adolescents: 0.4 mg twice weekly for 6 weeks (12 doses), then twice monthly for 4 months, then monthly thereafter until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management in pediatric patients if available.
Adults:
Withhold subsequent cycles until neutrophils recover to >1,000/mm3, platelets recover to >100,000/mm3, and hemoglobin recovers to ≥9 g/dL (with transfusion if necessary).
Combination therapy with cisplatin (cisplatin may also require dosage adjustment): IV:
Febrile neutropenia (neutrophils <1,000/mm3 with temperature of ≥38°C): Reduce topotecan to 0.6 mg/m2/day for subsequent cycles or administer granulocyte-colony stimulating factor (G-CSF) support beginning at least 24 hours after the last topotecan dose. If necessary, may further reduce dose to 0.45 mg/m2/day for subsequent cycles.
Platelets <25,000/mm3: Reduce topotecan to 0.6 mg/m2/day for subsequent cycles. If necessary, may further reduce dose to 0.45 mg/m2/day for subsequent cycles.
Single-agent therapy:
IV:
Neutrophils <500/mm3: Reduce dose to 1.25 mg/m2/day for subsequent cycles or administer G-CSF support beginning at least 24 hours after the last topotecan dose.
Platelets <25,000/mm3: Reduce dose to 1.25 mg/m2/day for subsequent cycles.
Oral:
Diarrhea (grade 3 or 4): Do not administer to patients with grade 3 or 4 diarrhea. Upon recovery to ≤ grade 1 toxicity, reduce dose by 0.4 mg/m2/day for subsequent cycles.
Neutrophils <500/mm3 associated with fever or infection or lasting ≥7 days or neutrophils 500/mm3 to 1,000/mm3 lasting beyond day 21: Reduce dose by 0.4 mg/m2/day for subsequent cycles.
Platelets <25,000/mm3: Reduce dose by 0.4 mg/m2/day for subsequent cycles.
Pulmonary toxicity: Interstitial lung disease (ILD): Permanently discontinue if ILD is confirmed.
Infants, Children, and Adolescents: Consult protocol for specific recommendations. Some centers have considered the following adjustments: IV:
Baseline: Initial dosing:
CrCl >40 mL/minute/1.73 m2: No adjustment necessary.
CrCl 20 to 40 mL/minute/1.73 m2: Administer 50% of dose.
CrCl <20 mL/minute/1.73 m2: Hold doses until renal function recovers (CrCl >20 mL/minute/1.73 m2).
During therapy:
CrCl >60 mL/minute/1.73 m2: No adjustment necessary.
CrCl 40 to 60 mL/minute/1.73 m2: Administer 50% of dose.
CrCl 20 to <40 mL/minute/1.73 m2: Administer 25% to 50% of dose.
CrCl <20 mL/minute/1.73 m2: Hold doses until renal function recovers (CrCl >20 mL/minute/1.73 m2).
Hemodialysis: Very limited data available; some data suggest that clearance of the lactone metabolite is similar to pediatric patients with normal renal function; a case report describes topotecan use in an anephric 6-year old diagnosed with Wilms tumor; the patient received 0.75 mg/m2/dose once daily for 5 days every 21 days with hemodialysis on day 2 and 4; on dialysis days, topotecan was administered ~2 hours before the start of the dialysis session; dosage reductions required for toxicity (myelosuppression) after cycle 4 (Ref).
Continuous renal replacement therapy (CRRT): Administer 50% of dose or reduce dose by 0.75 mg/m2/dose, if appropriate (Ref).
There are no pediatric specific recommendations; based on experience in adult patients, no adjustment may be necessary
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Fatigue (oral: 11% to 19%; intravenous: grades 3/4: 6% to 7%)
Dermatologic: Alopecia (oral: 10% to 20%)
Gastrointestinal: Nausea (oral: 27% to 33%; intravenous: grades 3/4: 8% to 10%), diarrhea (oral: 14% to 22%; intravenous: grades 3/4: 6%), vomiting (oral: 19% to 21%; intravenous: grades 3/4: 10%), anorexia (oral: 7% to 14%)
Hematologic & oncologic: Anemia (oral: 94% to 98%; grades 3/4: 25%; grade 3: 15% to 18%; grade 4: 7% to 10%; intravenous: grades 3/4: 37% to 42%), neutropenia (oral: 83% to 91%; grade 3: 24% to 28%; grade 4: 32% to 33%; intravenous: grade 4: 70% to 80%; nadir 12 to 15 days; duration: 7 days), thrombocytopenia (oral: 81%; grade 3: 29% to 30%; grade 4: 6% to 7%; intravenous: grade 4: 27% to 29%; nadir: 15 days; duration: 3 to 5 days), febrile neutropenia (intravenous: grade 3/4: 23% to 28%; grade 4: 5%; oral: grade 4: 4%), neutropenic infection (13% to 17%)
1% to 10%:
Central nervous system: Pain (intravenous: grades 3/4: 5%)
Gastrointestinal: Abdominal pain (intravenous: grades 3/4: 5% to 6%), constipation (intravenous: grades 3/4: 5%), intestinal obstruction (intravenous: grades 3/4: 5%)
Hepatic: Increased serum alanine aminotransferase (intravenous: grades 3/4: ≤4%). increased serum aspartate aminotransferase (intravenous: grades 3/4: ≤4%), increased serum bilirubin (intravenous: grades 3/4: <2%)
Neuromuscular & skeletal: Asthenia (intravenous: grades 3/4: 5% to 9%; oral: 3% to 7%)
Respiratory: Dyspnea (intravenous: grades 3/4: 6% to 9%), pneumonia (intravenous: grades 3/4: 8%)
Miscellaneous: Fever (oral: 5% to 7%), sepsis (2% to 4%)
Frequency not defined:
Hematologic & oncologic: Bone marrow depression
<1%, postmarketing, and/or case reports: Angioedema, arthralgia, chest pain, dermatitis (severe), gastrointestinal perforation, headache, hemorrhage (severe, associated with thrombocytopenia), hypersensitivity reaction, interstitial pulmonary disease, leukopenia, myalgia, neutropenic enterocolitis, nonimmune anaphylaxis, pancytopenia, pruritus (severe), stomatitis, typhlitis
Severe hypersensitivity to topotecan or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Severe renal impairment (CrCl <20 mL/minute); pregnancy; breastfeeding; preexisting severe bone marrow depression.
Concerns related to adverse effects:
• Bone marrow suppression: Topotecan may cause severe myelosuppression. Single-agent IV topotecan resulted in a median duration of grade 4 neutropenia of 7 days; neutropenia was most common during cycle 1. Grade 4 neutropenia associated with infection, as well as neutropenic fever, occurred; sepsis (sometimes fatal) has been reported. Grade 4 thrombocytopenia occurred with single-agent IV topotecan at a median duration of 5 days. Grade 4 neutropenia, grade 4 thrombocytopenia, and grades 3 and 4 anemia have occurred when IV topotecan was used in combination with cisplatin. For oral topotecan, the median day for neutrophil and platelet nadirs occurred on day 15; grade 4 neutropenia occurred with a median duration of 7 days and most commonly occurred during cycle 1. Clinical complications of neutropenia included infection, neutropenic fever, and sepsis (sometimes fatal). Grade 4 thrombocytopenia with oral topotecan occurred with a median duration of 3 days. Anemia (grades 3 or 4) has also been reported (with oral and IV single-agent topotecan). In a clinical study comparing IV to oral topotecan, granulocyte-colony stimulating factor support was administered in a higher percentage of patients receiving oral topotecan (Eckardt 2007).
• Extravasation: Topotecan IV is an irritant (Pérez Fidalgo 2012). Extravasation injuries (some severe) have been reported with IV topotecan; if extravasation occurs, discontinue infusion immediately and manage appropriately. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
• GI toxicity: Diarrhea may occur; diarrhea associated with oral topotecan may be severe and life-threatening (requiring hospitalization) and may occur at the same time as neutropenia. The median time to onset of grade 2 or worse diarrhea with oral topotecan was 9 days. The incidence of diarrhea due to oral topotecan may be higher in the elderly. GI perforation has been reported (postmarketing reports).
• Hypersensitivity: Hypersensitivity reactions, including allergic reaction, anaphylactoid reaction, and angioedema have been reported.
• Neutropenic enterocolitis: Topotecan-induced neutropenia may lead to fatal typhlitis (neutropenic enterocolitis); consider the possibility of typhlitis in patients presenting with neutropenia, fever, and abdominal pain.
• Pulmonary toxicity: Interstitial lung disease (ILD), including fatal ILD, has been reported. Risk factors for ILD include a history of ILD, pulmonary fibrosis, lung cancer, thoracic radiation, or the use of colony-stimulating factors or medications associated with pulmonary toxicity.
Other warnings/precautions:
• Medication safety: Topotecan overdoses have been reported; potential causes include omission of the leading zero and missing the decimal point when prescribing, preparing, and administering. Recommended intravenous doses should generally not exceed 4 mg in adults; verify dose prior to administration.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Hycamtin: 0.25 mg, 1 mg
Solution, Intravenous:
Generic: 4 mg/4 mL (4 mL)
Solution, Intravenous [preservative free]:
Generic: 4 mg/4 mL (4 mL)
Solution Reconstituted, Intravenous [preservative free]:
Hycamtin: 4 mg (1 ea)
Generic: 4 mg (1 ea)
May be product dependent
Capsules (Hycamtin Oral)
0.25 mg (per each): $145.65
1 mg (per each): $582.59
Solution (Topotecan HCl Intravenous)
4 mg/4 mL (per mL): $20.79 - $129.81
Solution (reconstituted) (Hycamtin Intravenous)
4 mg (per each): $1,526.51
Solution (reconstituted) (Topotecan HCl Intravenous)
4 mg (per each): $168.00 - $358.25
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 1 mg/mL (1 mL, 3 mL, 4 mL); 4 mg/4 mL (4 mL)
Solution Reconstituted, Intravenous:
Generic: 4 mg (1 ea)
IV: Administer as an IV infusion over 30 minutes. For combination chemotherapy with cisplatin, administer pretreatment hydration. IV topotecan is an irritant (Ref). Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. If extravasation occurs, discontinue infusion immediately and manage appropriately.
Oral: Administer with or without food. Swallow whole; do not open, crush, chew, or divide capsule. For patients unable to swallow capsules whole, reconstituted topotecan solution for injection (1 mg/mL concentration) may be mixed with up to 30 mL of acidic fruit juice (eg, apple, orange, grape) immediately prior to oral administration (Ref).
Oral topotecan is associated with a moderate emetic potential (depending on the dose) in pediatrics; antiemetics may be recommended to prevent nausea and vomiting (Ref).
Parenteral:
IV: Must be diluted prior to administration. Administer by intermittent IV infusion over 30 minutes or as a continuous infusion (over 1 or more days). Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. If extravasation occurs, discontinue infusion immediately and manage appropriately.
Intraventricular: Administer through an intraventricular or Ommaya reservoir at a rate of 2 mL/minute following removal of an isovolumetric amount of CSF; following administration, flush reservoir slowly with 2 mL of CSF or preservative-free NS (Ref).
Oral:
Capsules: May administer with or without food. Swallow capsule whole; do not crush, chew, or divide capsule.
Parenteral formulation; lyophilized powder for oral use. After reconstitution, mix dose in 30 mL of an acidic medium (eg, apple, grape, orange juice); Note: The reconstituted injectable solution is tasteless; the acidic medium serves as the vehicle only, not to mask the taste (Ref).
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Cervical cancer, advanced, recurrent or persistent: Injection: Treatment (in combination with cisplatin) of stage IVB, recurrent or persistent cervical cancer that is not amenable to curative treatment.
Ovarian cancer, metastatic: Injection: Treatment (as a single agent) of metastatic ovarian cancer after disease progression on or after initial or subsequent chemotherapy.
Small cell lung cancer, relapsed or progressive:
Injection: Treatment (as a single agent) of small cell lung cancer in patients with platinum-sensitive disease which has progressed at least 60 days after initiation of first-line chemotherapy.
Oral: Treatment (as a single agent) of relapsed small cell lung cancer in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy.
Ewing sarcoma, relapsed or refractory; Primary CNS lymphoma, relapsed or refractory; Rhabdomyosarcoma, metastatic
Hycamtin may be confused with Mycamine.
Topotecan may be confused with datopotamab deruxtecan, fam-trastuzumab deruxtecan, irinotecan (conventional), irinotecan (liposomal), sacituzumab govitecan.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Topotecan overdoses have been reported; potential causes include omission of the leading zero and missing the decimal point when prescribing, preparing, and administering. Recommended intravenous doses should generally not exceed 4 mg; verify dose prior to administration.
Substrate of BCRP, MATE1/2-K, P-glycoprotein (Major with inhibitors), P-glycoprotein (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Asciminib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Asciminib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
BCRP/ABCG2 Inhibitors: May increase serum concentration of Topotecan. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Elacestrant: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Erdafitinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider Therapy Modification
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fosphenytoin-Phenytoin: May decrease serum concentration of Topotecan. Management: Monitor topotecan response closely, and consider alternatives to phenytoin when possible. Systemic concentrations and effects of topotecan may be reduced. No specific guidelines for topotecan dose adjustment are available. Risk D: Consider Therapy Modification
Futibatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Futibatinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Gilteritinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Gilteritinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Granulocyte Colony-Stimulating Factors: May increase myelosuppressive effects of Topotecan. Granulocyte Colony-Stimulating Factors may increase adverse/toxic effects of Topotecan. Specifically, the risk for the development of interstitial lung disease may be increased. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of topotecan. Additionally, monitor patients closely for the development of interstitial lung disease with this combination. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Lasmiditan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Leniolisib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Levacetylleucine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lonafarnib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor
Lumacaftor and Ivacaftor: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Risk C: Monitor
Mitapivat: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Topotecan. Risk X: Avoid
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Platinum Derivatives: May increase adverse/toxic effects of Topotecan. Management: Consider administering platinum derivatives after topotecan when possible to minimize toxicity or using lower doses if administering platinum derivatives prior to topotecan. Monitor for hematologic toxicity (eg, neutropenia, thrombocytopenia). Risk D: Consider Therapy Modification
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Primaquine: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sparsentan: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Taurursodiol: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Taurursodiol: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Venetoclax: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Avoid concomitant use of venetoclax and oral p-glycoprotein (P-gp) substrates if possible. If combined use is unavoidable, administer the P-gp substrate at least 6 hours before venetoclax to minimize the potential for an interaction. Risk D: Consider Therapy Modification
Vimseltinib: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Management: Avoid concomitant use of vimseltinib and P-gp substrates when possible. If combined, administer vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy Modification
Voxilaprevir: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Xanomeline: May increase serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for at least 6 months after the last topotecan dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 3 months after the last topotecan dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to topotecan may cause fetal harm.
It is not known if topotecan is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week following the last topotecan dose.
CBC with differential (prior to treatment and frequently during treatment), kidney function tests, liver function tests (total bilirubin). Verify pregnancy status (prior to treatment initiation in patients who could become pregnant). Monitor for pulmonary signs/symptoms indicative of interstitial lung disease; monitor for diarrhea symptoms/hydration status. Monitor infusion site. Monitor adherence (for oral therapy).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Topotecan binds to topoisomerase I and stabilizes the cleavable complex so that religation of the cleaved DNA strand cannot occur. This results in the accumulation of cleavable complexes and single-strand DNA breaks. Topotecan acts in S phase of the cell cycle.
Note: Pharmacokinetic data in pediatric patients and young adults (0.4 to 22 years of age) demonstrated a high level of interpatient variability (43% to 57% dependent upon parameter evaluated) as well as intrapatient variability (20% to 22% dependent upon parameter evaluated) (Schaiquevich 2007).
Distribution: Vd:
Pediatric patients and young adults (0.4 to 22 years of age): Mean range: 32.2 to 32.7 L/m2 (Schaiquevich 2007).
Adults: 25 to 75 L/m2 (Hartmann 2006).
Protein binding: ~35%.
Metabolism: Undergoes a reversible, pH-dependent hydrolysis of the (active) lactone ring to yield a relatively inactive hydroxy acid in plasma (at pH of ≤4, the active ring is predominant; at physiologic pH, the ring-opened hydroxy acid form predominates); topotecan is metabolized in the liver to N-demethylated metabolite.
Bioavailability: Oral: Capsule: Adults: ~40%; data from pediatric patients (1 to 18 years of age) showed that, while highly variable, the reported median oral bioavailability with oral administration of the reconstituted parenteral solution is similar to adults (Daw 2004; Zamboni 1999).
Half-life elimination:
Pediatric patients (0 to 18 years of age): Lactone moiety: 2.58 hours ± 0.15 (range: 0.2 to 7.1 hours) (Santana 2005).
Adults: IV: 2 to 3 hours; Oral: 3 to 6 hours.
Time to peak, plasma:
Pediatric patients (1 to 18 years of age): Parenteral formulation (reconstituted lyophilized formulation): 0.75 to 2 hours (Zamboni 1999).
Adults: Oral: 1 to 2 hours; delayed with high-fat meal (3 to 4 hours).
Excretion:
IV: Urine (51%; ~3% as N-desmethyl topotecan); feces (18%; ~2% as N-desmethyl topotecan).
Oral: Urine (20%; 2% as N-desmethyl topotecan); feces (33%; <2% as N-desmethyl topotecan).
Clearance: Pediatric patients (0.4 to 18 years of age): GFR most significant determinant of clearance; a linear model with GFR has been observed; BSA is also a significant determinant of clearance and AUC more so than patient weight; infants <6 months have decreased clearance (Schaiquevich 2007). However, pharmacokinetic data from 6 pediatric patients with severe renal impairment (n=5: Unilateral nephrectomy; n=1: Anephric on hemodialysis) suggests that other mechanisms than GFR may assist with renal clearance; in these patients, overall systemic clearance was shown to be similar to matched controls (age, BSA, and Scr) despite decreased GFR (Iacono 2003; Iacono 2004).
Altered kidney function:
IV: The plasma clearance of topotecan lactone decreased by 33% in patients with CrCl 40 to 60 mL/minute and decreased 65% in patients with CrCl 20 to 39 mL/minute, compared to patients with CrCl >60 mL/minute.
Oral: The mean dose-normalized total topotecan and topotecan lactone AUC∞ increased in advanced cancer patients with kidney impairment compared to patients with CrCl >80 mL/minute. White patients with CrCl 50 to 79 mL/minute had a mean dose-normalized total topotecan and topotecan lactone AUC∞ of 70% and 34%, respectively; white patients with CrCl 30 to 49 mL/minute had a mean dose-normalized total topotecan and topotecan lactone AUC∞ of 108% and 80%, respectively; white patients with CrCl <30 mL/minute had a mean dose-normalized total topotecan and topotecan lactone AUC∞ of 227% and 114%, respectively, compared to patients with normal kidney function. Asian patients with CrCl 50 to 79 mL/minute had a mean dose-normalized total topotecan and topotecan lactone AUC∞ of 26% and 34%, respectively; Asian patients with CrCl 30 to 49 mL/minute had a mean dose-normalized total topotecan and topotecan lactone AUC∞ of 153% and 121%, respectively; Asian patients with CrCl <30 mL/minute had a mean dose-normalized total topotecan and topotecan lactone AUC∞ of 331% and 247%, respectively, compared to patients with normal kidney function.
Race/ethnicity: Following oral topotecan administration in patients with normal kidney function (CrCl >80 mL/minute), the AUC of topotecan lactone and total topotecan was 30% higher in Asian patients as compared to white patients.
