Hycamtin (topotecan HCl)

Dosage of oral and IV topotecan hydrochloride is expressed in terms of topotecan. Dosage of the drug must be individualized based on body surface area and patient tolerance.

In patients with impaired renal function receiving oral or IV topotecan monotherapy, the dosage of topotecan must be modified in response to the degree of renal impairment.

For patients receiving oral topotecan for treatment of small cell lung cancer, dosage adjustment is notrecommended for patients with creatinine clearance of 50-80 mL/minute; however, for patients with creatinine clearance of 30-49 mL/minute, the dosage of oral topotecan should be reduced to 1.8 mg/m2 daily (rounded to the nearest 0.25 mg). The manufacturer states that insufficient data are available to provide a dosage recommendation for oral topotecan in patients with creatinine clearance less than 30 mL/minute.

For patients receiving IV topotecan, no dosage adjustment is recommended for patients with creatinine clearance of 40-60 mL/minute; however the dosage of IV topotecan should be reduced to 0.75 mg/m2 in patients with creatinine clearance of 20-39 mL/minute. The manufacturer states that insufficient data are available to provide a dosage recommendation for IV topotecan in patients with creatinine clearance less than 19 mL/minute.

In patients with cervical cancer, therapy with IV topotecan and cisplatin should be initiated only in those with serum creatinine concentrations of 1.5 mg/dL or less. In the clinical trial, cisplatin therapy was discontinued in patients with a serum creatinine concentration exceeding 1.5 mg/dL. No data are available regarding the safety or efficacy of continued therapy with topotecan following discontinuance of cisplatin therapy in patients with cervical cancer.

In geriatric patients, no adjustments in either oral or IV topotecan dosage appear to be required other than those related to decreases in renal function with age. Because geriatric patients are more likely to have decreased renal function and because patients with renal impairment may be at increased risk of topotecan-induced toxicity, care should be taken in dosage selection for patients in this age group and renal function should be monitored.

Clinically important alterations in the pharmacokinetics of oral or IV topotecan in patients with impaired hepatic function (i.e., plasma bilirubin greater than 1.5 to less than 15 mg/dL) have not been observed to date, and the manufacturer makes no specific recommendations for dosage modification in such patients.

The dose-limiting toxicity of topotecan therapy is myelosuppression. Because neutropenia occurs frequently during topotecan therapy and may be severe and potentially fatal, it is essential that bone marrow function be monitored through evaluation of peripheral blood cell counts before and during topotecan therapy.

Before the initial course of therapy with either oral or IV topotecan, patients must have a baseline neutrophil count of at least 1500/mm3 and a platelet count of at least 100,000/mm3. Bone marrow reserves should be evaluated frequently during topotecan therapy using peripheral blood cell counts, and subsequent courses of therapy should be withheld until the neutrophil count exceeds 1000/mm3, platelet count exceeds 100,000/mm3, and hemoglobin concentration is at least 9 g/dL (with transfusion if necessary).

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There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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Topotecan can cause fetal toxicity when administered to pregnant women. The manufacturer states that use of oral topotecan is contraindicated in pregnant women.

Reproduction studies in rabbits receiving an IV topotecan dosage of 0.1 mg/kg daily (approximately equivalent to the IV clinical dose in humans on a mg/m2 basis) on gestation days 6-20 revealed evidence of maternal toxicity, embryolethality, and reduced fetal body weight. Reproduction studies in rats receiving an IV topotecan dosage of 0.23 mg/kg daily (approximately equivalent to the IV clinical dose in humans on a mg/m2 basis) for 14 days before mating through gestation day 6 showed fetal resorption, microphthalmia, preimplant loss, and mild maternal toxicity. The offspring of rats receiving an IV topotecan dosage of 0.1 mg/kg daily (approximately equivalent to half the IV clinical dose in humans on a mg/m2 basis) on gestation days 6-17 experienced an increase in postimplantation mortality and total fetal malformations. The most frequent malformations affected the eye (microphthalmia, anophthalmia, rosette formation of the retina, coloboma of the retina, ectopic orbit), brain (dilated lateral and third ventricles), skull, and vertebrae.

There are no adequate and well-controlled studies to date using topotecan in pregnant women. If topotecan is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus. Women of childbearing potential should be advised to use effective contraceptive measures to avoid becoming pregnant during therapy with topotecan.

In lactating rats receiving IV topotecan at a dosage of 4.72 mg/m2, high concentrations of the drug (i.e., up to 48 times higher than plasma concentrations) were distributed into milk. It is not known whether topotecan is distributed into human milk. The manufacturer states that use of oral topotecan is contraindicated in nursing women. Because of the potential for serious adverse reactions to topotecan in nursing infants, nursing should be discontinued during therapy.

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