Recommended Topic Related To:

Hycamtin Capsules

"The U.S. Food and Drug Administration today approved Gilotrif (afatinib) for patients with late stage (metastatic) non-small cell lung cancer (NSCLC) whose tumors express specific types of epidermal growth factor receptor (EGFR) gene mutations, a"...

Hycamtin Capsules

Hycamtin Capsules

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

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 studies (N = 682) using HYCAMTIN capsules (topotecan capsules) at 2.3 mg/m²/day for 5 consecutive days. The median day for neutrophil, red blood cell, 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). Infection, sepsis, and febrile neutropenia occurred in 17%, 2%, and 4% of patients, respectively. Death due to sepsis occurred in 1% of patients. Pancytopenia has been reported.

Topotecan-induced neutropenia can lead to neutropenic colitis. Fatalities due to neutropenic colitis have been reported. In patients presenting with fever, neutropenia, and a compatible pattern of abdominal pain, the possibility of neutropenic colitis should be considered. [See DOSAGE AND ADMINISTRATION.]

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.

Monitoring of Bone Marrow Function

HYCAMTIN should be administered only in patients with adequate bone marrow reserves, including a baseline neutrophil count of ≥ 1,500 cells/mm³ and a platelet count ≥ 100,000 cells/mm³. Frequent monitoring of peripheral blood cell counts should be instituted during treatment with HYCAMTIN.

Diarrhea

Diarrhea, including severe diarrhea requiring hospitalization, has been reported during treatment with HYCAMTIN capsules (topotecan capsules) . Diarrhea related to HYCAMTIN capsules (topotecan capsules) can occur at the same time as drug-related neutropenia and its sequelae. Communication with patients prior to drug administration regarding these side effects and proactive management of early and all signs and symptoms of diarrhea is important. Treatment-related diarrhea is associated with significant morbidity and may be life-threatening. Should diarrhea occur during treatment with HYCAMTIN capsules (topotecan capsules) , physicians are advised to aggressively manage diarrhea. Clinical guidelines describing the aggressive management of diarrhea include specific recommendations on patient communication and awareness, recognition of early warning signs, use of anti­diarrheals and antibiotics, changes in fluid intake and diet, and need for hospitalization.

Of the 682 patients who received HYCAMTIN capsules (topotecan capsules) in the 4 thoracic cancer studies, the overall incidence of drug-related diarrhea was 22%, including 4% with Grade 3 and 0.4% with Grade 4. Drug-related diarrhea was more frequent in patients ≥ 65 years of age (28%) compared to those < 65 years of age (19%). [See ADVERSE REACTIONS and Use in Specific Populations.]

Interstitial Lung Disease

HYCAMTIN has been associated with reports of interstitial lung disease (ILD), some of which have been fatal [see ADVERSE REACTIONS]. Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, and use of pneumotoxic drugs and/or colony stimulating factors. Patients should be monitored for pulmonary symptoms indicative of interstitial lung disease (e.g., cough, fever, dyspnea, and/or hypoxia), and HYCAMTIN should be discontinued if a new diagnosis of ILD is confirmed.

Pregnancy

Pregnancy Category D

HYCAMTIN may cause fetal harm when administered to a pregnant woman. The effects of topotecan on pregnant women have not been studied. Women should be warned to avoid becoming pregnant. [See CONTRAINDICATIONS .] 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. An IV dose of 0.10 mg/kg/day (about half the clinical IV dose on a mg/m² basis) given to rats on days 6 through 17 of gestation caused an increase in post-implantation mortality. This dose also caused an increase in total fetal malformations. The most frequent malformations were of the eye (microphthalmia, anophthalmia, rosette formation of the retina, coloboma of the retina, ectopic orbit), brain (dilated lateral and third ventricles), skull, and vertebrae. 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 the fetus.

Drug Interactions

P-glycoprotein inhibitors (e.g., cyclosporine A, elacridar, ketoconazole, ritonavir, and saquinavir) can cause significant increases in topotecan exposure. The concomitant use of P-glycoprotein inhibitors with HYCAMTIN capsules should be avoided. [See DRUG INTERACTIONS.]

Patient Counseling Information

See FDA-approved patient labeling.

Bone Marrow Suppression

Patients should be informed that HYCAMTIN decreases blood cell counts such as white blood cells, platelets, and red blood cells. Patients who develop fever or other signs of infection such as chills, cough, or burning pain on urination while on therapy should notify their physician promptly. Patients should be told that frequent blood tests will be performed while taking HYCAMTIN to monitor for the occurrence of bone marrow suppression.

Pregnancy

Patients should be advised to use effective contraceptive measures to prevent pregnancy and to avoid breastfeeding during treatment with HYCAMTIN.

Diarrhea

Patients should be informed that HYCAMTIN capsules (topotecan capsules) cause diarrhea which may be severe in some cases. Patients should be told how to manage and/or prevent diarrhea and to inform their physician if severe diarrhea occurs during treatment with HYCAMTIN capsules (topotecan capsules) .

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity testing of topotecan has not been done. Nevertheless, topotecan is known to be genotoxic to mammalian cells and is a probable carcinogen. Topotecan was mutagenic to L5178Y mouse lymphoma cells and clastogenic to cultured human lymphocytes with and without metabolic activation. It was also clastogenic to mouse bone marrow. Topotecan did not cause mutations in bacterial cells.

Topotecan given to female rats prior to mating at a dose of 1.4 mg/m² IV (about 3/5th of the oral clinical dose on a mg/m² basis) caused superovulation possibly related to inhibition of follicular atresia. This dose given to pregnant female rats also caused increased pre-implantation loss. Studies in dogs given 0.4 mg/m² IV (about 1/6th the oral clinical dose on a mg/m² basis) of topotecan daily for a month suggest that treatment may cause an increase in the incidence of multinucleated spermatogonial giant cells in the testes. Topotecan may impair fertility in women and men.

Use In Specific Populations

Pregnancy

Pregnancy Category D. [See CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS.]

Nursing Mothers

HYCAMTIN is contraindicated during breastfeeding [see CONTRAINDICATIONS].

Rats excrete high concentrations of topotecan into milk. Lactating female rats given 4.72 mg/m² IV (about twice the clinical dose on a mg/m² basis) excreted topotecan into milk at concentrations up to 48-fold higher than those in plasma. It is not known whether the drug is excreted in human milk. Breastfeeding should be discontinued when women are receiving HYCAMTIN.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the 682 patients with thoracic cancer in 4 clinical studies who received HYCAMTIN capsules (topotecan capsules) , 33% (n = 225) were 65 years of age and older, while 4.8% (n = 33) were 75 years of age and older. Treatment-related diarrhea was more frequent in patients ≥ 65 years of age (28%) compared to those < 65 years of age (19%). [See WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS.] Among patients ≥ 65 years of age, those receiving HYCAMTIN capsules plus BSC showed a survival benefit compared to those receiving BSC alone.

There were no apparent differences in the pharmacokinetics of topotecan in elderly patients with creatinine clearance of ≥ 60 mL/minute [see CLINICAL PHARMACOLOGY].

This drug is known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function [see DOSAGE AND ADMINISTRATION].

Renal Impairment

A cross-study analysis of data collected from 217 patients with advanced solid tumors indicated that exposure (AUC0 -∞ ) to topotecan lactone, the pharmacologically active moiety, was 10% and 20% higher in patients with mild renal (CLcr = 50-80 mL/min) and moderate renal (CLcr = 30-49 mL/min) impairment, respectively, than in patients with normal renal function (CLcr > 80 mL/min) [see DOSAGE AND ADMINISTRATION].

Hepatic Impairment

In a population pharmacokinetic analysis involving oral topotecan administered at doses of 0.15-2.7 mg/m²/day to 118 cancer patients, the pharmacokinetics of total topotecan did not differ significantly based on patient serum bilirubin, ALT, or AST. No dosage adjustment appeared to be required for patients with impaired hepatic function (serum bilirubin of > 1.5 mg/dL).

Last reviewed on RxList: 7/26/2010
This monograph has been modified to include the generic and brand name in many instances.

A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Cancer

Get the latest treatment options.

Related Drugs
Health Resources
advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations