Topotecan (oral)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
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Overview
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Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indication
HYCAMTIN capsules are indicated for the treatment 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.
Dosage
2.1 Recommended Dosing The recommended dose of HYCAMTIN capsules is 2.3 mg/m2/day orally once daily for 5 consecutive days repeated every 21 days. Round the dose to the nearest 0.25 mg, and prescribe the minimum number of 1-mg and 0.25-mg capsules. Prescribe the same number of capsules for each of the 5 dosing days.
Take HYCAMTIN capsules with or without food. Swallow capsules whole. Do not chew, crush, or divide the capsules. Do not prescribe a replacement dose for emesis.
Diarrhea:
Do not administer HYCAMTIN capsules to patients with Grade 3 or 4 diarrhea. After recovery to Grade 1 or less, reduce the dose of HYCAMTIN by 0.4 mg/m2/day for subsequent courses [see Warnings and Precautions (5.2)].
2.2 Dose Modification Guidelines Hematologic Toxicities:
Do not administer subsequent courses of HYCAMTIN capsules until neutrophils recover to greater than 1,000 cells/mm3, platelets recover to greater than 100,000 cells/mm3, hemoglobin levels recover to greater than or equal to 9.0 g/dL (with transfusion if necessary). Renal Impairment: The recommended starting doses of HYCAMTIN capsules in patients with moderate and severe renal impairment are as follows: Dose reduce HYCAMTIN capsules by 0.4 mg/m2/day for: neutrophil counts of less than 500 cells/mm3 associated with fever or infection or lasting for 7 days or more; neutrophil counts of 500 to 1,000 cells/mm3 lasting beyond day 21 of the treatment course; platelet counts less than 25,000 cells/mm3. Renal Impairment:
The recommended starting doses of HYCAMTIN capsules in patients with moderate and severe renal impairment are as follows:
Dosage Forms and Strengths
- HYCAMTIN capsules contain topotecan hydrochloride expressed as topotecan free base. The 0.25-mg capsules are opaque white to yellowish-white and imprinted with HYCAMTIN and 0.25 mg. The 1-mg capsules are opaque pink and imprinted with HYCAMTIN and 1 mg.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Topotecan (oral) in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Topotecan (oral) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Topotecan (oral) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Topotecan (oral) in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Topotecan (oral) in pediatric patients.
Contraindications
HYCAMTIN is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan.
Warnings
5.1 Bone Marrow Suppression Bone marrow suppression (primarily neutropenia) is a dose-limiting toxicity of HYCAMTIN. Neutropenia is not cumulative over time. The following data on myelosuppression are based on an integrated safety database from 4 thoracic malignancy trials (N = 682) using HYCAMTIN capsules at 2.3 mg/m2/day for 5 consecutive days. The median day for neutrophil and platelet nadirs occurred on Day 15.
Neutropenia:
Grade 4 neutropenia (<500 cells/mm3) occurred in 32% of patients with a median duration of 7 days and was most common during Course 1 of treatment (20% of patients). Clinical sequelae of neutropenia included infection (17%), febrile neutropenia (4%), sepsis (2%), and septic death (1%). Pancytopenia has been reported.
Topotecan can cause fatal typhlitis (neutropenic enterocolitis). Consider the possibility of typhlitis in patients presenting with fever, neutropenia, and abdominal pain [see Dosage and Administration (2.2)].
Thrombocytopenia:
Grade 4 thrombocytopenia (<10,000 cells/mm3) occurred in 6% of patients, with a median duration of 3 days.
Anemia:
Grade 3 or 4 anemia (<8 g/dL) occurred in 25% of patients.
Administer the first course of HYCAMTIN only to patients with a neutrophil count of ≥1,500 cells/mm3 and a platelet count ≥100,000 cells/mm3. Monitor peripheral blood cell counts frequently during treatment with HYCAMTIN. Refer to Section 2.2 for dose modification guidelines for hematological toxicities in subsequent courses.
5.2 Diarrhea Diarrhea, including severe and life-threatening diarrhea requiring hospitalization, can occur during treatment with HYCAMTIN capsules. Diarrhea caused by HYCAMTIN capsules can occur at the same time as drug-induced neutropenia and its sequelae. In the 682 patients who received HYCAMTIN capsules in the 4 lung cancer trials, the incidence of diarrhea caused by HYCAMTIN capsules was 22%, with 4% Grade 3 and 0.4% Grade 4.The incidence of Grade 3 or 4 diarrhea proximate (within 5 days) to Grade 3 or 4 neutropenia events in the group receiving HYCAMTIN capsules was 5%. The median time to onset of Grade 2 or worse diarrhea was 9 days in the group receiving HYCAMTIN capsules. Manage diarrhea caused by HYCAMTIN capsules aggressively. Do not administer HYCAMTIN capsules to patients with Grade 3 or 4 diarrhea. Reduce the dose of HYCAMTIN after recovery to Grade 1 or less [see Dosage and Administration (2.2)].
5.3 Interstitial Lung Disease Interstitial lung disease (ILD), including fatalities, has occurred with HYCAMTIN. Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic radiation, and use of pneumotoxic drugs and/or colony stimulating factors. Monitor patients for pulmonary symptoms indicative of interstitial lung disease (e.g., cough, fever, dyspnea, and/or hypoxia), and discontinue HYCAMTIN if a new diagnosis of ILD is confirmed.
5.4 Embryofetal Toxicity HYCAMTIN can cause fetal harm when administered to a pregnant woman. Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis. If this drug is used during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)].
Advise females of reproductive potential to use highly effective contraception during treatment and for at least 1 month after the last dose of HYCAMTIN. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking HYCAMTIN [see Use in Specific Populations (8.1, 8.7)].
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of HYCAMTIN capsules was evaluated in 682 patients with lung cancer (3 recurrent small cell lung cancer [SCLC] trials and 1 recurrent non-small cell lung cancer [NSCLC] trial) who received at least one dose of HYCAMTIN capsules. Patients in all four trials had advanced lung malignancies and received prior chemotherapy in the first-line setting. The dose regimen for HYCAMTIN capsules was 2.3 mg/m2/day for five consecutive days every 21 days. The median number of courses was 3 (range: 1 to 20) in these four trials. Table 2 describes the hematologic and non-hematologic adverse reactions in recurrent SCLC patients treated with HYCAMTIN capsules in the overall lung cancer patient population.
On-Study Death Due to Toxicity of HYCAMTIN: In the 682 patients who received HYCAMTIN capsules in the four lung cancer trials, 39 deaths (6%) occurred within 30 days after the last dose for a reason other than progressive disease: 13 due to hematologic toxicity, 5 due to non-hematologic toxicity (2 from diarrhea), and 21 due to other causes.
Postmarketing Experience
There is limited information regarding Topotecan (oral) Postmarketing Experience in the drug label.
Drug Interactions
Topotecan is a substrate for both P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Inhibitors of these transporters increase the systemic exposure to oral topotecan. Avoid concomitant use of P-gp inhibitors (e.g., amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir, ritonavir, quercetin, quinidine, ranolazine, ticagrelor, verapamil) and BCRP inhibitors (e.g., cyclosporine, eltrombopag) with HYCAMTIN capsules [see Clinical Pharmacology (12.3)].
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): D Risk Summary:
HYCAMTIN can cause fetal harm when administered to a pregnant woman. Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to a fetus.
Animal Data:
In rabbits, an IV dose of 0.10 mg/kg/day (about equal to the clinical IV dose on a mg/m2 basis) given on days 6 through 20 of gestation caused maternal toxicity, embryolethality, and reduced fetal body weight. In the rat, an IV dose of 0.23 mg/kg/day (about equal to the clinical IV dose on a mg/m2 basis) given for 14 days before mating through gestation day 6 caused fetal resorption, microphthalmia, pre-implant loss, and mild maternal toxicity. Administration of an IV dose of 0.10 mg/kg/day (about half the clinical IV dose on a mg/m2 basis) to rats on days 6 through 17 of gestation caused an increase in post-implantation mortality. This dose also caused an increase in total fetal malformations. The most frequent malformations were of the eye (microphthalmia, anophthalmia, rosette formation of the retina, coloboma of the retina, ectopic orbit), brain (dilated lateral and third ventricles), skull, and vertebrae.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Topotecan (oral) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Topotecan (oral) during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Topotecan (oral) in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Topotecan (oral) in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Topotecan (oral) in geriatric settings.
Gender
There is no FDA guidance on the use of Topotecan (oral) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Topotecan (oral) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Topotecan (oral) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Topotecan (oral) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Topotecan (oral) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Topotecan (oral) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Topotecan (oral) Administration in the drug label.
Monitoring
There is limited information regarding Topotecan (oral) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Topotecan (oral) and IV administrations.
Overdosage
There is limited information regarding Topotecan (oral) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Topotecan (oral) Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Topotecan (oral) Mechanism of Action in the drug label.
Structure
There is limited information regarding Topotecan (oral) Structure in the drug label.
Pharmacodynamics
There is limited information regarding Topotecan (oral) Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Topotecan (oral) Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Topotecan (oral) Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Topotecan (oral) Clinical Studies in the drug label.
How Supplied
There is limited information regarding Topotecan (oral) How Supplied in the drug label.
Storage
There is limited information regarding Topotecan (oral) Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Topotecan (oral) Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Topotecan (oral) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Topotecan (oral) Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Topotecan (oral) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.