Topotecan

When ATH:
L01XX17

Characteristic.

Semisynthetic analogue of camptothecin (alkaloid, isolated from the stems of bushes Campotheca acuminata). Topotecan hydrochloride - crystalline powder, Insoluble in water.

Pharmacological action.
Antitumor, citocidnoe, immunosuppressive.

Application.

Ovarian cancer (metastatic form of a failed application therapy first line or subsequent therapy), small cell and non-small cell lung cancer, myelodysplastic syndrome, myelomonotsytarnыy chronic leukemia.

Contraindications.

Hypersensitivity, mielodeprescia (число нейтрофилов — менее 1,5·10⁹/л и тромбоцитов не более 100·10⁹/l), anemia (hemoglobin level is less 90 g / l), severe renal dysfunction (Cl creatinine less than 20 ml / min), pregnancy, lactation.

Restrictions apply.

Infection (incl. enable vetryanaya, herpes zoster), inhibition of renal function (Cl creatinine 20-39 ml / min), prior cytotoxic or radiation therapy, childhood (safety and effectiveness in children have not identified).

Pregnancy and breast-feeding.

Contraindicated in pregnancy.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

At the time of treatment should stop breastfeeding.

Side effects.

Cardio-vascular system and blood (hematopoiesis, hemostasis): dose-dependent hematotoxicity - anemia (hemoglobin level no more 100 g / l - 95%, to 80 g / l - 40%), neutropenia (less than 1.5 10⁹/- 98%, до 0,5·10⁹/- 81%), leukopenia (до 3,0·10⁹/- 98%, менее 1,0·10⁹/- 32%), thrombocytopenia (менее 75·10⁹/- 63%, до 25·10⁹/- 26%), angiostaxis, bleeding, incl. hidden.

From the digestive tract: nausea (79%), vomiting (58%), diarrhea (42%), constipation (39%), abdominal pain (33%), stomatitis (24%), anorexia, ileus.

From the nervous system and sensory organs: headache (21%), paresthesia (9%), fatiguability, asthenia.

Allergic reactions: anaphylactoid reactions (discoloration of skin, rash, urticaria and other.), respiratory failure, angioedema, dermatitis.

Other: totalynaya alopecia (42%), dyspnoea (20%), sepsis (0,7% - lethal), fever, the development of infections, arthralgia, bruising and redness at the injection site (in case extravasation).

Cooperation.

Other myelotoxicity drugs, Radiation therapy may potentiate the neutropenia. Immunosuppressive (azathioprine, khlorambutsil, glucocorticoids, cyclophosphamide, mercaptopurine et al.) increases the risk of infections. Weakens the effectiveness of immunization inactivated vaccines; using vaccines, containing live viruses, enhances viral replication and side effects of vaccination. Against the background of NSAIDs increases the risk of bleeding.

Overdose.

Symptoms: severe bone marrow depression, fever, bleeding.

Treatment: hospitalization, monitoring vital functions; simptomaticheskaya therapy; if necessary - transfusion of blood components, the appointment of broad-spectrum antibiotics. Spetsificheskiy antidote unknown.

Dosing and Administration.

Ovarian Cancer, non-small cell lung cancer - / In infusion for 30 min dose 1,5 mg / m² per day 5 days in a row; again with a break in 21 day. Cell Lung Cancer - 1.5–2 mg / m² day / in infusion for 30 m 5 days in a row; repeatedly with an interval of 21 day. The duration of therapy for at least 4 rates. Myelodysplastic syndrome, myelomonotsytarnыy chronic leukemia - 2 mg / m²/day in a 24-hour infusion 5 consecutive days every 3-4 weeks to achieve remission, then 1 once a month. Against the background of impaired renal function (Cl creatinine 20-39 ml / min) the recommended dose 0,75 mg / m². In severe neutropenia (менее 0,5·10⁹/l, continuing more 7 days, the dose for the subsequent course is reduced to 0,25 mg / m² assigned or colony stimulating factor (filgrastim) through 24 hours after the last dose.

Precautions.

Use only under medical supervision, with experience of chemotherapy. There must be adequate measures and tools for the diagnosis and treatment of possible complications. Before and during treatment is necessary to determine hemoglobin or hematocrit, the number of leukocytes and platelets. The development of neutropenia necessitates careful observation with a view to timely diagnosis of the symptoms of infection. In the event of thrombocytopenia advised extreme caution when performing invasive procedures, Regular inspection of places on / in the, skin and mucous membranes (for signs of bleeding), control of blood in the urine, vomit, Kale. The patients must be carefully shave, manicure, brush your teeth, dentists use threads and toothpicks; avoid falls and other injuries, as well as the intake of alcohol and acetylsalicylic acid, increase the risk of gastrointestinal bleeding. In the case of expression gematotoksichnosti subsequent treatment possible, if the hemoglobin level has reached 90 g / l, число нейтрофилов не менее 1,0·10⁹л/ и тромбоцитов более 100·10⁹/l. During treatment should use appropriate contraceptive measures. In case of contact with skin or mucous membranes must be thoroughly rinsed with water mucosal, and skin - with soap and water. Dissolution, dilution and administration of the preparation is carried out by trained medical staff with the protection (gloves, mask, clothing and other.).

Cautions.

Preparation of the solution: 4 mg of the drug is dissolved when added to the vial 4 ml of sterile water for injection. Concentration of the resulting solution, having a yellow or yellow-green color, is 1 mg / ml. By subsequent dilution 5% or dextrose 0,9% sodium chloride solution for injection, a solution with a concentration of 25-50 μg / ml is obtained.

Cooperation