Topotecan (HCl)

Topotecan (HCl) is intravenous antineoplastic (anticancer) agent. Topotecan, similar to irinotecan, is a derivative of Camptothecin (CPT), a cytotoxic plant alkaloid isolated from the Chinese tree Camptotheca acuminata. It, along with Irinotecan, is the first of a new class of antineoplastic, the topoisomerase-I inhibitors. Topotecan is a second-line treatment for ovarian carcinoma. It has also been investigated for treatment of non-small-cell lung carcinoma, and for chronic myelomonocytic leukemia (CMML). As a single agent, topotecan offers equal response rates to other antineoplastic for lung or ovarian carcinomas. Its role in combination therapy has not yet been well defined. Topotecan was FDA approved May 29, 1996 for the treatment of metastatic ovarian carcinoma.

Topotecan (HCl) is primarily indicated in conditions like Ovarian cancer, Cervical cancer, Small cell lung cancer, and can also be given in adjunctive therapy as an alternative drug of choice in Metastatic ovarian cancer.

Topotecan (HCl) is contraindicated in conditions like Bone marrow depression.

The severe or irreversible adverse effects of Topotecan (HCl), which give rise to further complications include Thrombocytopenia, Hyperbilirubinemia, Neutropenia, Anemia. The symptomatic adverse reactions produced by Topotecan (HCl) are more or less tolerable and if they become severe, they can be treated symptomatically, these include Sepsis, Nausea, Vomiting, Fatigue, Alopecia, Malaise, GI disturbance, Asthenia, Intestinal obstruction, Pyrexia, Asthenia.

Risk of dose-limiting and potentially fatal myelosuppression, manifested commonly as neutropenia, thrombocytopenia, and anemia. Pancytopenia reported. Myelosuppression occurs frequently, may be severe, and may require transfusions. Neutrophil nadirs usually occur at day 12 and 15 with IV and oral administration, respectively. Platelet nadirs usually occur at day 15 with IV and oral administration. Median duration of neutropenia is 7 days with IV and oral administration and median duration of thrombocytopenia is 5 and 3 days with IV and oral administration, respectively. Median nadir for anemia occurs at day 15. Careful hematologic monitoring required; perform peripheral blood cell counts prior to and at frequent intervals during therapy. Withhold subsequent courses of therapy until neutrophil count is >1000/mm 3 , platelet count is >100,000/mm 3 , and hemoglobin is ≥9 g/dL (with transfusion if necessary). Neutropenic colitis, a sequela of drug-induced neutropenia, has been reported and can be fatal. Consider possibility of neutropenic colitis if patients present with fever, neutropenia, and abdominal pain. Diarrhea occurs commonly in patients receiving topotecan capsules; may be severe, life-threatening, and require hospitalization.. Diarrhea may occur at the same time as neutropenia and its sequelae. (See Neutropenic Colitis under Cautions.) If diarrhea occurs, manage aggressively (e.g., antidiarrheal and anti-infective therapy, changes in fluid and diet requirements, hospitalization). Nausea, vomiting, abdominal pain, constipation, intestinal obstruction, and stomatitis reported. May cause fetal harm; teratogenicity and embryolethality demonstrated in animals. Avoid pregnancy during therapy. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard. Extravasation may result in mild local effects (e.g., erythema, bruising). Possible asthenia or fatigue. Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Distributed in high concentrations into milk in rats; not known whether topotecan is distributed into human milk. Discontinue nursing because of potential risk to nursing infants. (See Contraindications under Cautions.) Safety and efficacy not established. Oral administration: increased risk of diarrhea relative to younger patients. IV administration: No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out. Substantially eliminated by kidneys; assess renal function periodically and select dosage with caution since geriatric patients more likely to have decreased renal function. Pharmacokinetics not substantially altered in patients with impaired hepatic function (i.e., plasma bilirubin >1.5 to <10 mg/dL). Decreased clearance; increased risk of toxicity in patients with renal impairment. Dosage adjustments recommended depending on degree of renal impairment. (See Renal Impairment under Dosage and Administration.)

Risk of dose-limiting and potentially fatal myelosuppression, manifested commonly as neutropenia, thrombocytopenia, and anemia. Pancytopenia reported. Myelosuppression occurs frequently, may be severe, and may require transfusions. Neutrophil nadirs usually occur at day 12 and 15 with IV and oral administration, respectively. Platelet nadirs usually occur at day 15 with IV and oral administration. Median duration of neutropenia is 7 days with IV and oral administration and median duration of thrombocytopenia is 5 and 3 days with IV and oral administration, respectively. Median nadir for anemia occurs at day 15. Careful hematologic monitoring required; perform peripheral blood cell counts prior to and at frequent intervals during therapy. Withhold subsequent courses of therapy until neutrophil count is >1000/mm 3 , platelet count is >100,000/mm 3 , and hemoglobin is ≥9 g/dL (with transfusion if necessary). Neutropenic colitis, a sequela of drug-induced neutropenia, has been reported and can be fatal. Consider possibility of neutropenic colitis if patients present with fever, neutropenia, and abdominal pain. Diarrhea occurs commonly in patients receiving topotecan capsules; may be severe, life-threatening, and require hospitalization.. Diarrhea may occur at the same time as neutropenia and its sequelae. (See Neutropenic Colitis under Cautions.) If diarrhea occurs, manage aggressively (e.g., antidiarrheal and anti-infective therapy, changes in fluid and diet requirements, hospitalization). Nausea, vomiting, abdominal pain, constipation, intestinal obstruction, and stomatitis reported. May cause fetal harm; teratogenicity and embryolethality demonstrated in animals. Avoid pregnancy during therapy. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard. Extravasation may result in mild local effects (e.g., erythema, bruising). Possible asthenia or fatigue. Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Distributed in high concentrations into milk in rats; not known whether topotecan is distributed into human milk. Discontinue nursing because of potential risk to nursing infants. (See Contraindications under Cautions.) Safety and efficacy not established. Oral administration: increased risk of diarrhea relative to younger patients. IV administration: No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out. Substantially eliminated by kidneys; assess renal function periodically and select dosage with caution since geriatric patients more likely to have decreased renal function. Pharmacokinetics not substantially altered in patients with impaired hepatic function (i.e., plasma bilirubin >1.5 to <10 mg/dL). Decreased clearance; increased risk of toxicity in patients with renal impairment. Dosage adjustments recommended depending on degree of renal impairment. (See Renal Impairment under Dosage and Administration.)

1.5 mg/sq.meter (3 (3)) 24 hourly IV Inf — Initially for 5 Days

( ) — Not recommended in this age group

( ) — Not recommended in this age group

Does not inhibit CYP isoenzymes 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E, 3A, or 4A or dihydropyrimidine dehydrogenase in vitro.

Inj Store at room temperature, Between 20°C-25°C. Protect from Sunlight.