Topotecan 4mg/4ml Inj, 4ml
WARNING: Low blood cell counts may happen with this drug. Low blood cell counts may raise the chance of needing a blood transfusion or getting an infection or bleeding. If you have questions, talk with the doctor.Have your blood work and other lab tests checked as you have been told by your doctor. @ COMMON USES: It is used to treat cancer.
Drug Class
Antineoplastic agent
Pharmacologic Class
Topoisomerase I inhibitor
Pregnancy Category
Category D
FDA Approved
May 1996
DEA Schedule
Not Controlled
Overview
What is this medicine?
Topotecan is a chemotherapy drug used to treat certain types of cancer, including ovarian, small cell lung, and cervical cancer. It works by interfering with the growth of cancer cells, causing them to die. It is given as an injection into a vein.
How to Use This Medicine
Taking Your Medication Correctly
To ensure safe and effective use, take this medication exactly as directed by your doctor. Carefully read all the information provided to you and follow the instructions precisely. This medication is administered as an intravenous infusion, which means it is given slowly into a vein over a period of time.
Storing and Disposing of Your Medication
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.
What to Do If You Miss a Dose
If you miss a dose, contact your doctor immediately to receive guidance on the next steps to take.
To ensure safe and effective use, take this medication exactly as directed by your doctor. Carefully read all the information provided to you and follow the instructions precisely. This medication is administered as an intravenous infusion, which means it is given slowly into a vein over a period of time.
Storing and Disposing of Your Medication
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.
What to Do If You Miss a Dose
If you miss a dose, contact your doctor immediately to receive guidance on the next steps to take.
Lifestyle & Tips
- Avoid contact with people who are sick or have infections, as your immune system will be weakened.
- Report any signs of infection (fever, chills, sore throat) immediately.
- Avoid activities that could cause cuts, bruises, or injury due to increased risk of bleeding.
- Maintain good oral hygiene to prevent mouth sores.
- Stay well-hydrated and follow anti-nausea medication instructions.
- Discuss fertility preservation options before treatment, as it may affect fertility.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Ovarian Cancer (recurrent): 1.5 mg/m² IV infused over 30 minutes daily for 5 consecutive days, repeated every 21 days. Small Cell Lung Cancer (SCLC): 1.5 mg/m² IV infused over 30 minutes daily for 5 consecutive days, repeated every 21 days. Cervical Cancer (with cisplatin): 0.75 mg/m² IV infused over 30 minutes daily for 3 consecutive days, repeated every 21 days.
Dose Range:
0.75 - 1.5 mg
Condition-Specific Dosing:
Ovarian Cancer (recurrent):
1.5 mg/m² IV daily for 5 days, repeat every 21 days
Small Cell Lung Cancer (SCLC):
1.5 mg/m² IV daily for 5 days, repeat every 21 days
Cervical Cancer (with cisplatin):
0.75 mg/m² IV daily for 3 days, repeat every 21 days
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established (safety and efficacy not established in pediatric patients, though used off-label in some protocols)
Adolescent:
Not established (safety and efficacy not established in pediatric patients, though used off-label in some protocols)
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required for CrCl 40-60 mL/min.
Moderate:
For CrCl 20-39 mL/min: Reduce dose by 50% (e.g., 0.75 mg/m² for ovarian/SCLC, 0.375 mg/m² for cervical cancer).
Severe:
Not recommended for CrCl < 20 mL/min due to insufficient data and potential for increased toxicity.
Dialysis:
Not recommended for patients on dialysis due to insufficient data and potential for increased toxicity.
Hepatic Impairment:
Mild:
No dose adjustment required for bilirubin < 1.5 times ULN.
Moderate:
No dose adjustment required for bilirubin 1.5-3 times ULN.
Severe:
Not available (limited data, caution advised).
Pharmacology
Mechanism of Action
Topotecan is a topoisomerase I inhibitor. It binds to the topoisomerase I-DNA complex, preventing religation of the DNA strand after single-strand breaks. This leads to accumulation of DNA strand breaks, which are cytotoxic and ultimately lead to cell death, particularly in rapidly dividing cancer cells.
Pharmacokinetics
Absorption:
Bioavailability:
Not applicable (IV administration)
Tmax:
Not applicable (IV administration)
FoodEffect:
Not applicable (IV administration)
Distribution:
Vd:
Approximately 60 L/m²
ProteinBinding:
Approximately 35%
CnssPenetration:
Limited (low penetration into CSF)
Elimination:
HalfLife:
Approximately 2-3 hours (lactone form)
Clearance:
Approximately 67 L/h/m²
ExcretionRoute:
Renal (approximately 30-60% as unchanged drug and its carboxylate metabolite), fecal (approximately 20-30%)
Unchanged:
Approximately 30-50% (lactone form)
Pharmacodynamics
OnsetOfAction:
Rapid (due to IV administration)
PeakEffect:
Not applicable (continuous cytotoxic effect during and after infusion)
DurationOfAction:
Dependent on cell cycle effects and drug exposure, typically related to the 5-day dosing schedule and subsequent recovery period.
Safety & Warnings
BLACK BOX WARNING
Topotecan can cause severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Febrile neutropenia and neutropenic sepsis, sometimes fatal, have been reported. Monitor complete blood counts frequently. Do not administer Topotecan to patients with baseline neutrophil counts < 1,500 cells/mm³ or platelet counts < 100,000 cells/mm³.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Allergic Reaction: Rash, hives, itching, redness, swelling, blistering, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, abnormal vaginal bleeding, unexplained bruises, or uncontrollable bleeding.
Severe Diarrhea: Diarrhea accompanied by stomach cramps, nausea, vomiting, fever, or excessive fluid loss.
Lung Problems: Shortness of breath, difficulty breathing, new or worsening cough, or fever. These lung problems can be life-threatening and require immediate medical attention.
Bowel Problems: Severe stomach pain (with or without fever), tender stomach, or diarrhea. These bowel problems can be life-threatening and may occur as early as the first day of symptoms.
Tissue Damage: If the medication leaks from the vein, it can cause tissue damage. Notify your nurse immediately if you experience redness, burning, pain, swelling, blisters, skin sores, or fluid leakage at the injection site.
Other Possible Side Effects
Most medications can cause side effects, but many people experience none or only mild symptoms. If you're concerned about any of the following side effects or if they persist or worsen, contact your doctor:
Fatigue or weakness
Hair loss
Mouth irritation or sores
Constipation
Stomach pain
* Diarrhea, vomiting, nausea, upset stomach, or decreased appetite (common side effects that can be managed with your doctor's guidance)
If you experience any of these side effects or have concerns about other symptoms, don't hesitate to reach out to your doctor for advice. They can help you manage these side effects and provide guidance on what to do next.
Reporting Side Effects
If you have questions or concerns about side effects, you can contact your doctor or report them to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Allergic Reaction: Rash, hives, itching, redness, swelling, blistering, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, abnormal vaginal bleeding, unexplained bruises, or uncontrollable bleeding.
Severe Diarrhea: Diarrhea accompanied by stomach cramps, nausea, vomiting, fever, or excessive fluid loss.
Lung Problems: Shortness of breath, difficulty breathing, new or worsening cough, or fever. These lung problems can be life-threatening and require immediate medical attention.
Bowel Problems: Severe stomach pain (with or without fever), tender stomach, or diarrhea. These bowel problems can be life-threatening and may occur as early as the first day of symptoms.
Tissue Damage: If the medication leaks from the vein, it can cause tissue damage. Notify your nurse immediately if you experience redness, burning, pain, swelling, blisters, skin sores, or fluid leakage at the injection site.
Other Possible Side Effects
Most medications can cause side effects, but many people experience none or only mild symptoms. If you're concerned about any of the following side effects or if they persist or worsen, contact your doctor:
Fatigue or weakness
Hair loss
Mouth irritation or sores
Constipation
Stomach pain
* Diarrhea, vomiting, nausea, upset stomach, or decreased appetite (common side effects that can be managed with your doctor's guidance)
If you experience any of these side effects or have concerns about other symptoms, don't hesitate to reach out to your doctor for advice. They can help you manage these side effects and provide guidance on what to do next.
Reporting Side Effects
If you have questions or concerns about side effects, you can contact your doctor or report them to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever (especially 100.4°F or 38°C or higher)
- Chills
- Sore throat
- Unusual bleeding or bruising (e.g., nosebleeds, bleeding gums, petechiae)
- Extreme tiredness or weakness
- Shortness of breath
- Severe nausea or vomiting that doesn't improve with medication
- Severe diarrhea
- Severe mouth sores
- Signs of allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Low white blood cell count (leukopenia)
+ Low platelet count (thrombocytopenia)
+ Low red blood cell count (anemia)
* If you are breastfeeding, as you should not breastfeed while taking this medication and for 1 week after your last dose.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, including:
+ Low white blood cell count (leukopenia)
+ Low platelet count (thrombocytopenia)
+ Low red blood cell count (anemia)
* If you are breastfeeding, as you should not breastfeed while taking this medication and for 1 week after your last dose.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before operating a vehicle or engaging in any activity that requires your full attention, wait until you understand how this medication affects you.
You are at a higher risk of developing infections, some of which can be severe or life-threatening. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or the flu.
This medication may increase your likelihood of bleeding easily. To reduce the risk of injury, exercise caution in your daily activities. Additionally, use a soft-bristled toothbrush and an electric razor for shaving.
If you experience diarrhea, consult your doctor before attempting to treat it. Do not take any medication for diarrhea without first discussing it with your doctor.
Before receiving any vaccinations, consult your doctor. Certain vaccines may not be effective or may increase your risk of infection when taken with this medication.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
This medication may affect fertility, potentially making it difficult to conceive or father a child. If you plan to become pregnant or father a child, discuss this with your doctor before starting the medication.
This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you may become pregnant, use effective birth control while taking this medication and for 6 months after your last dose, unless otherwise instructed by your doctor. It is crucial to understand the duration for which you need to use birth control. If you become pregnant, notify your doctor immediately.
If your partner may become pregnant, you may need to use birth control while taking this medication and for a certain period after the last dose. Consult your doctor to discuss the necessary precautions.
Before operating a vehicle or engaging in any activity that requires your full attention, wait until you understand how this medication affects you.
You are at a higher risk of developing infections, some of which can be severe or life-threatening. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or the flu.
This medication may increase your likelihood of bleeding easily. To reduce the risk of injury, exercise caution in your daily activities. Additionally, use a soft-bristled toothbrush and an electric razor for shaving.
If you experience diarrhea, consult your doctor before attempting to treat it. Do not take any medication for diarrhea without first discussing it with your doctor.
Before receiving any vaccinations, consult your doctor. Certain vaccines may not be effective or may increase your risk of infection when taken with this medication.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
This medication may affect fertility, potentially making it difficult to conceive or father a child. If you plan to become pregnant or father a child, discuss this with your doctor before starting the medication.
This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you may become pregnant, use effective birth control while taking this medication and for 6 months after your last dose, unless otherwise instructed by your doctor. It is crucial to understand the duration for which you need to use birth control. If you become pregnant, notify your doctor immediately.
If your partner may become pregnant, you may need to use birth control while taking this medication and for a certain period after the last dose. Consult your doctor to discuss the necessary precautions.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (profound neutropenia, thrombocytopenia, anemia)
- Severe gastrointestinal toxicity (nausea, vomiting, diarrhea, mucositis)
What to Do:
There is no known antidote for topotecan overdose. Management is supportive, including transfusions (blood, platelets), antiemetics, antidiarrheals, and granulocyte colony-stimulating factors (G-CSFs) for neutropenia. Call 1-800-222-1222 (Poison Control) or seek immediate medical attention.
Drug Interactions
Major Interactions
- Live vaccines (increased risk of infection)
- Other myelosuppressive agents (additive myelosuppression)
- Cisplatin (used in combination for cervical cancer, but requires dose adjustment of topotecan due to increased myelosuppression)
Moderate Interactions
- Phenytoin (potential for decreased topotecan efficacy, though not well-established)
- Strong CYP2D6 inhibitors/inducers (minor interaction, unlikely to be clinically significant)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic parameters and assess for pre-existing myelosuppression, which is a major dose-limiting toxicity.
Timing: Prior to initiation of therapy
Renal function tests (Serum Creatinine, CrCl)
Rationale: Topotecan is primarily renally excreted; dose adjustments are required for renal impairment.
Timing: Prior to initiation of therapy
Hepatic function tests (Bilirubin, AST, ALT)
Rationale: To assess baseline liver function, though hepatic impairment generally does not require dose adjustment unless severe.
Timing: Prior to initiation of therapy
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: Weekly or prior to each cycle (Day 1 of each cycle and periodically during the cycle, e.g., Day 8 or 15)
Target: ANC ≥ 1,500 cells/mm³, Platelets ≥ 100,000 cells/mm³ for next cycle
Action Threshold: ANC < 1,500 cells/mm³ or Platelets < 100,000 cells/mm³ (delay treatment, reduce dose, or administer growth factors)
Renal function tests (Serum Creatinine)
Frequency: Prior to each cycle or as clinically indicated
Target: CrCl > 60 mL/min (for standard dose)
Action Threshold: CrCl 20-39 mL/min (reduce dose by 50%); CrCl < 20 mL/min (not recommended)
Clinical assessment for signs/symptoms of infection, bleeding, or anemia
Frequency: Daily during treatment days and periodically between cycles
Target: Absence of fever, chills, unusual bleeding, or excessive fatigue
Action Threshold: Fever (≥38°C), signs of infection, significant bleeding, or severe fatigue (investigate and manage promptly)
Symptom Monitoring
- Fever
- Chills
- Sore throat
- Unusual bleeding or bruising
- Fatigue
- Weakness
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Abdominal pain
- Hair loss (alopecia)
- Mouth sores (mucositis)
Special Patient Groups
Pregnancy
Topotecan can cause fetal harm when administered to a pregnant woman. It is classified as Pregnancy Category D. Women of childbearing potential should be advised to avoid becoming pregnant during therapy and use effective contraception.
Trimester-Specific Risks:
First Trimester:
High risk of major birth defects and embryo-fetal toxicity due to its mechanism of action (DNA synthesis inhibition).
Second Trimester:
Risk of fetal growth restriction, myelosuppression, and other adverse effects.
Third Trimester:
Risk of fetal myelosuppression and other adverse effects.
Lactation
It is not known whether topotecan is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated during topotecan therapy.
Infant Risk:
L5 (Contraindicated - high risk of significant adverse effects to the infant)
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. While used off-label in some pediatric oncology protocols, specific dosing and toxicity profiles may differ from adults. Close monitoring for myelosuppression and other adverse effects is crucial.
Geriatric Use
No overall differences in effectiveness were observed between older and younger patients. However, older patients may be more susceptible to myelosuppression and other toxicities, particularly if they have pre-existing renal impairment or other comorbidities. Dose selection for an elderly patient should be cautious, generally starting at the low end of the dosing range.
Clinical Information
Clinical Pearls
- Topotecan is a potent myelosuppressive agent; frequent CBC monitoring is critical, and dose adjustments or delays are common.
- Febrile neutropenia is a serious complication; educate patients on signs of infection and when to seek immediate medical attention.
- Administer antiemetics proactively to manage nausea and vomiting.
- Hydration is important to prevent dehydration, especially with gastrointestinal toxicities.
- The 5-day dosing schedule requires careful patient education and adherence.
- For cervical cancer, topotecan is used in combination with cisplatin, which can exacerbate myelosuppression and requires specific dose adjustments.
Alternative Therapies
- For Ovarian Cancer: Paclitaxel, Carboplatin, Doxorubicin (liposomal), Gemcitabine, Olaparib (PARP inhibitor), Niraparib, Rucaparib, Bevacizumab.
- For Small Cell Lung Cancer: Etoposide, Cisplatin, Carboplatin, Irinotecan, Lurbinectedin, Immunotherapy (e.g., atezolizumab, durvalumab).
- For Cervical Cancer: Cisplatin, Paclitaxel, Bevacizumab.
Cost & Coverage
Average Cost:
Varies widely, typically several hundred to over a thousand USD per vial depending on supplier and contract. per 4mg/4ml vial
Generic Available:
Yes
Insurance Coverage:
Specialty Tier / Tier 4 (requires prior authorization, often administered in a clinic/hospital setting)
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure safe use, never share your medication with others, and do not take medication prescribed to someone else. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion.
Proper disposal of unused or expired medications is crucial. Do not dispose of them by flushing down the toilet or pouring down the drain unless specifically instructed to do so. If you are unsure about the correct disposal method, consult your pharmacist for guidance. Many communities have drug take-back programs, which your pharmacist can help you locate.
Some medications may come with an additional patient information leaflet; check with your pharmacist to see if this applies to your prescription. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide detailed information about the overdose, including the name of the medication, the amount taken, and the time it occurred, to ensure prompt and effective treatment.
Proper disposal of unused or expired medications is crucial. Do not dispose of them by flushing down the toilet or pouring down the drain unless specifically instructed to do so. If you are unsure about the correct disposal method, consult your pharmacist for guidance. Many communities have drug take-back programs, which your pharmacist can help you locate.
Some medications may come with an additional patient information leaflet; check with your pharmacist to see if this applies to your prescription. If you have any questions or concerns about your medication, do not hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide detailed information about the overdose, including the name of the medication, the amount taken, and the time it occurred, to ensure prompt and effective treatment.