Index of drugs

The monotherapy drug is indicated for the treatment of patients with ovarian cancer with metastases for whom first- or next-stage chemotherapy has been ineffective, and in patients with recurrent small cell lung cancer, in whom re-treatment with first-line chemotherapy was considered inappropriate. Topotecan in combination with Cisplatin is indicated for the treatment of patients with cervical cancer recurrent after radiotherapy and for patients with stage IVB disease stage. In patients who have previously received Cisplatin, the use of combination therapy is warranted in the case of a long period without treatment.

1 vial contains 4 mg of topotecan in the form of hydrochloride.

An anti-cancer drug that works by suppressing topoisomerase-I (an enzyme involved in DNA replication by reducing torsional tension against moving replication forks). Topotecan inhibits the effect of topoisomerase-I by stabilizing the covalent enzyme complex and the separated DNA strands, which is an intermediate step in the catalytic process. The consequence of topotecan inhibition of topoisomerase-I is the induction of single-stranded DNA strands associated with the protein in the cell. After intravenous administration of topotecan at doses of 0.5-1.5 mg / m² pc. in a 30-minute infusion, every day for 5 days, topotecan showed a relatively short half-life (2-3 h). Topotecan binds approximately 35% of plasma proteins. The main mechanism of elimination of the drug is the hydrolysis of the lactone ring to an open-ring carboxylic derivative. In a small part it is metabolized to the N-demethyl derivative. Metabolism accounts for less than 10% of drug elimination. Approximately 51% of the dose is excreted in the urine as total topotecan and 3% as the N-demethyl derivative. The excretion of total topotecan in the faeces is 18%, while 1.7% is the N-demethyl derivative of topotecan.

Severe hypersensitivity to topotecan or to any of the excipients. Breastfeeding period. Severe bone marrow suppression prior to the first cycle, confirmed by an initial neutrophil count <1.5 x 10⁹/ l and / or the platelet count <100 x 10⁹/ L.

The complete blood count including the platelet count should be monitored regularly. Topotecan may cause severe myelosuppression (reports of myelosuppression leading to sepsis and cases of death from sepsis), neutropenia, which may lead to colitis (deaths due to neutropenic colitis have been reported, patients with fever, neutropenia and abdominal pain should take into account the possibility of neutropenic colitis), interstitial lung disease (sometimes fatal, risk factors are: a history of interstitial lung disease, pulmonary fibrosis, lung cancer, exposure of the chest organs to ionizing radiation, use of pneumotoxic drugs and / or colony growth factors - patients should be observed for signs of respiratory disease indicative of the development of interstitial lung disease: cough, fever, dus nosocephaly and / or hypoxia, and if the diagnosis of interstitial lung disease is confirmed, topotecan should be discontinued). Treatment with topotecan monotherapy or topotecan with cisplatin is often associated with the occurrence of clinically significant thrombocytopenia; this should be borne in mind when prescribing topotecan, eg in patients with an increased risk of bleeding associated with the presence of a tumor. As predicted, patients in poor general condition (PS> 1) are less responsive to treatment and the incidence of complications such as fever, infection and sepsis increases. During the treatment, a systematic assessment of the patient's general condition is very important to assess whether he has deteriorated to PS = 3.Topotecan is not recommended in patients with severe renal impairment (creatinine clearance <20 ml / min) or severe hepatic impairment due to cirrhosis (serum bilirubin ≥ 10 mg / dl) (no data). In a small group of patients with impaired liver function (serum bilirubin in the range of 1.5-10 mg / dl), a topical dose of 1.5 mg / m was used intravenously² pc, administered for 5 days, every 3 weeks. Reductions in topotecan clearance were observed; however, there is insufficient data to determine dose recommendations for this group of patients. There is limited experience in pediatric use, therefore it is not possible to prescribe the use of topotecan in children and adolescents.

In non-clinical studies, topotecan showed lethal effects on the embryo and fetus and caused fetal malformations. Like other cytotoxic preparations, topotecan may cause fetal damage and therefore women of childbearing potential should be advised to avoid becoming pregnant during treatment with topotecan. If topotecan is used during pregnancy, or if you become pregnant during treatment with topotecan, you must be informed of the potential risk to your fetus. As with any chemotherapy with cytotoxic drugs, effective contraception is recommended if either partner is treated with topotecan. The use of topotecan is contraindicated during breast-feeding. It is not known if topotecan is excreted in breast milk. When starting treatment with topotecan, breast-feeding should be discontinued. Like other cytotoxic preparations, topotecan is genotoxic and its effect on fertility can not be ruled out, including in men.

Very common: infection; neutropenic fever, neutropenia, thrombocytopenia, anemia, leukopenia; anorexia (which can be severe); nausea, vomiting and diarrhea (all of which may be severe), constipation, abdominal pain and mucositis; alopecia; fever, weakness, fatigue. Common: sepsis (deaths due to sepsis have been reported); hypersensitivity reactions, including rash; hyperbilirubinemia; itching; bad mood. Rare: anaphylactic reaction, angioneurotic edema, urticaria; interstitial lung disease (some cases fatal). Very rare: extravasation (mild). Neutropenia-mediated colitis, including fatal cases, has been reported as a complication of topotecan-induced neutropenia.

Topotecan should only be used in specialized centers that conduct cytotoxic chemotherapy and should be administered only under the supervision of a physician experienced in conducting chemotherapy. When using a combination therapy with cisplatin, it is necessary to read the full information about cisplatin. Before starting the first course of treatment with topotecan, the neutrophil count must be ≥ 1.5 x 10⁹/ l, the platelet count must be ≥100 x 10⁹/ l and hemoglobin must be ≥9 g / dl (after blood transfusion if necessary).
Ovarian cancer and small cell lung cancer. The recommended starting dose of topotecan is 1.5 mg / m² pc / day, given in a 30-minute intravenous infusion, every day, for 5 consecutive days, every 3 weeks counting from the first day of the course. If the treatment is well tolerated, it can be continued until the disease progresses. Subsequent doses should not be re-administered until the number of granulocytes reaches ≥1 x 10⁹/ l, number of plates ≥100 x 10⁹/ l, and hemoglobin ≥9 g / dl (after blood transfusion, if necessary). The standard oncology practice for dealing with neutropenia includes either the additional administration of other drugs (e.g., G-CSF) or the reduction of the dose of topotecan to maintain an adequate number of neutrophils. If a dose reduction has been selected in patients with severe neutropenia (neutrophil count <0.5 x 10⁹/ l), lasting 7 days or longer, or severe neutropenia accompanied by fever or infection, or in patients who have been delayed due to neutropenia, the dose should be reduced by 0.25 mg / m² pc / dose up to 1.25 mg / m² pc / day (or if necessary, reduce the Next dose to 1.0 mg / m² pc./dobę). Similarly, reduce doses if the platelet count falls below 25 x 10⁹/ L.In clinical trials, topotecan was discontinued when the dose was reduced to 1.0 mg / m² pc. and it was necessary to reduce the dose further due to side effects.Cervical cancer. The recommended starting dose of topotecan is 0.75 mg / m² pc / day, given as a 30-minute intravenous infusion, every day on days 1, 2 and 3. Cisplatin is administered as an intravenous infusion on day 1 at a dose of 50 mg / m² pc / day after administration of topotecan. The above treatment regimen is repeated every 21 days for 6 cycles or until disease progression. Subsequent doses should not be re-administered until the neutrophil count reaches ≥1,5x10⁹/ l, number of plates ≥100x10⁹/ l, and hemoglobin ≥9 g / dl (after blood transfusion, if necessary). The standard oncology practice for dealing with neutropenia includes either the additional administration of other drugs (e.g., G-CSF) or the reduction of the dose of topotecan to maintain an adequate number of neutrophils. If a dose reduction has been selected in patients with severe neutropenia (neutrophil count less than 0.5 x 10⁹/ l), lasting 7 days or longer, or severe neutropenia accompanied by fever or infection, or in patients who have been delayed due to neutropenia, the dose should be reduced by 20% to 0.60 mg / m² pc / day during subsequent courses of therapy (or, if necessary, reduce the next dose to 0.45 mg / m² pc./dobę). Similarly, the dose should be reduced if the platelet count falls below 25x10⁹/ L.Patients with impaired renal function. In patients with moderate renal impairment, the dose of topotecan should be reduced - the recommended dose in patients with monotherapy of ovarian cancer or small cell lung cancer with a creatinine clearance of 20-39 ml / min is 0.75 mg / m² pc / day for 5 consecutive days; lack of sufficient data to determine the principles of selecting the dose of topotecan in patients with a creatinine clearance <20 ml / min. In patients with cervical cancer treated in clinical trials with topotecan / cisplatin, treatment was initiated only if serum creatinine was ≤1.5 mg / dl. If the creatinine concentration exceeds 1.5 mg / dL during topotecan and cisplatin therapy, it is recommended to check the full information on cisplatin with regard to dose reduction or continuation of therapy. After cisplatin has been discontinued, it should be noted that there is insufficient data on the continuation of topotecan monotherapy in patients with cervical cancer.
Before administration, the preparation should be reconstituted in 4 ml of water and then diluted with 9 mg / ml (0.9%) sodium chloride intravenous infusion or 50 mg / ml (5%) solution of Glucose for intravenous infusion to obtain the final concentration of topotecan between 0.01 and 0.5 mg / ml solution for injection.