Topotecan: manufacturer, instruction manual, price, reviews, analogs

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Topotecan refers to antitumor agents of plant origin and has a Latin name - Topotecanum, belonging to the genus Topotecani.

The drug is used in the treatment of malignant neoplasms of the broncho-pulmonary system and ovaries. Topotecan is prescribed for myeloid leukemia, with unspecified and myelodysplastic syndromes. The drug has antitumor, immunosuppressive and cytocidal effects.

Composition, form and packaging

Topotecan is a lyophilizate used for the preparation of infusions.

The substance is a porous mass with a yellow tinge. Produced in vials of 4 mg of pure substance. Topotecan hydrochloride in the vial contains 4.35 mg.

Excipients are:

• mannitol 48 mg;
• tartaric acid 20 mg;
• Na hydroxide to pH 2.8-3.2.

The bottles are made of glass, transparent in color, volume 8 ml, packed in cardboard packs.

There is a powder of 2.5 mg in vials. Topotecan-Aktavis is available in 5 ml vials with 1 mg substance in cardboard packs.

Manufacturer

Holds a license for the production of Topotekan Aktavis Group from Iceland, and produces the drug in Romania, the company Sindan-Pharma.

Indications for use

Topotecan is indicated for lung cancer in small cell and non-small cell form, ovarian cancer. It is indicated in the metastatic form of ovarian cancer, if the first-line therapy did not bring the expected results.

Refer to topotecan for diagnosis: myelodysplastic syndrome or chronic myelomonocytic leukemia.

Contraindications

Among the contraindications to the appointment of Topotecan, it should be noted:

• hypersensitivity to the drug;
• period of bearing of the child and lactation;
• impaired renal function in severe form( Cl creatinine less than 20 mL / min);
• anemia( hemoglobin level less than 90 g / l);
• expressed myelosuppression, before the start of the first course of treatment, when the baseline level of neutrophilic granulocytes was <1.5 • 109 / L and / or platelet count ≤ 100 • 109 / L.

There are some limitations to the use of Topotecan:

• chicken pox and other infections;
• radiation or cytotoxic therapy before administration;
• children, because the effect of the drug on the children's body is not fully understood.

If a woman is pregnant, then the drug is not prescribed( it affects the fetus), and when breastfeeding, stop breastfeeding. When taking the drug, couples of childbearing age are recommended to use reliable means of protection from unwanted pregnancy. Topotecan belongs to antineoplastic agents.

At the heart of the antitumor activity of topotecan is the inhibition of the enzyme, which takes a direct part in the replication of DNA.

Topotecan inhibits topoisomerase-I and results in the induction of protein-associated single DNA strand breaks.

With iv injection of topotecan in a 30-minute intravenous infusion at a dose of 0.5-1.5 mg / m2 for 5 days, the drug has a high clearance( 64 l / h), which is about 2/3 of the hepatic blood flow.

Complete cleansing from concomitant substances after 5 days of IV topotecan administration is 71-76% of the applied dose. About 51% of the drug is excreted in the urine. Elimination with feces of total topotecan is 18%.

With the introduction of the drug for 5 days, no changes in pharmacokinetic parameters were noted. The binding of topotecan to plasma proteins is low( 35%), and the distribution between blood cells and plasma is uniform. Less than 10% of topotecan is metabolized.

In patients with hepatic insufficiency, the plasma clearance of the drug decreases by approximately 67% compared with that in the control group.

In the population study, there is no significant dependence of topotecan clearance on age, body weight, and ascites.

The pharmacokinetics of topotecan have been studied in children receiving a 24-hour continuous topotecan infusion at a dose of 2-7.5 mg / m2 body surface area or a 72-hour continuous infusion at a dose of 0.75-1.95 mg / m2 / day. In both cases, the clearance was similar to that in adults with the same dosing regimens.

Plasma clearance and volume of distribution is slightly higher in men than in women, but these differences are mainly due to the surface area of ​​the body.

The simultaneous administration of topotecan with granisetron, ondansetron, morphine or GCS did not have a significant effect on the pharmacokinetics of topotecan.

Instruction for use Topotecan: dosage

The amount of the drug and its dose directly depends on the disease.

• For ovarian cancer, non-small cell lung cancer - IV infusion for 30 minutes at a dose of 1.5 mg / m2 per day for 5 consecutive days. Repeat the procedure after 21 days to achieve the desired parameters.
• Small cell lung cancer is calculated to be 1.5-2 mg / m2 per day IV infusion over 30 min for 5 consecutive days;repeatedly with the same interval. The duration of therapy involves at least 4 courses.
• Myelodysplastic syndrome and chronic myelomonocytic leukemia are treated with another technique. Calculation of 2 mg / m2 / day as a 24-hour infusion for 5 consecutive days every 3-4 weeks until remission is achieved. Then repeat once a month.
• In the case of impaired renal function ( Cl creatinine 20-39 ml / min), the recommended dose is 0.75 mg / m2.
• With cervical cancer, begins with - 0.75 mg / m2 daily 30-minute IV infusion once a day at 1;2 and 3-rd day. The courses are repeated after 3 weeks while saving the parameters, and the number of repetitions can reach 6 if progress is maintained.

The preparation is dissolved and diluted immediately before use. To dissolve 4 mg of topotecan into the vial, add 4 ml of sterile water for injection. Such a solution will contain topotecan in a concentration of 1 mg / ml.

Further dilution of this solution is carried out by appropriate volumes or 0.9% of the sodium chloride solution for intravenous infusions, or 5% by the dextrose solution for intravenous infusions in order to obtain p-ra with the required concentration of topotecan 25-50mcg / ml.

Side effects of

1. Cardiovascular system and blood:
   • severe and moderate anemia( hemoglobin level is not more than 100 g / l - 95%, up to 80 g / l - 40%);
   • febrile neutropenia( less than 1.5 · 109 / L - 98%, up to 0.5 · 109 / L - 81%);
   • leukopenia( up to 3.0 · 109 / L - 98%, less than 1.0 · 109 / L - 32%);
   • thrombocytopenia( less than 75 · 109 / L - 63%, up to 25 · 109 / L - 26%);
   • hemorrhage, bleeding, incl.hidden.
2. On the part of the digestive system: nausea, vomiting, diarrhea, constipation, abdominal pain, stomatitis, anorexia, intestinal obstruction.
3. From the nervous system and sensory organs: headache( 21%), paresthesia( 9%), fatigue, asthenia.
4. Allergic reactions: anaphylactoid reactions( skin discoloration, rash, hives, etc.), breathing disorder, angioedema, dermatitis.

There are also possible manifestations:

• total alopecia( 42%);
• dyspnea( 20%);
• sepsis( 0.7% - lethal);
• fever;
• swelling;
• development of infections;
• hyperbilirubinemia;
• arthralgia;
• bruising and redness at the injection site.

Overdose

When the dose is exceeded, there may be severe bone marrow depression, stomatitis, fever, myelosuppression, bleeding.

For removal from this condition, hospitalization, monitoring of vital functions, symptomatic therapy is necessary.

If necessary - transfusion of blood components, the appointment of antibiotics of a wide spectrum of action. The specific antidote is unknown.

Special instructions

Use of the drug is recommended under the supervision of a physician with experience in chemotherapy. Medical personnel should provide adequate measures and facilities for diagnosis and treatment of possible complications.

Before and during treatment, it is necessary to determine hemoglobin or hematocrit, the number of leukocytes and platelets.

The development of neutropenia causes the need for careful monitoring in order to timely diagnose the symptoms of infection. When thrombocytopenia occurs, extreme caution is recommended when performing invasive procedures, regular examination of iv / injection sites, skin and mucous membranes( to detect signs of bleeding), control of blood in urine, vomit, feces.

For such patients, there is a risk of injury during shaving, manicure, dental cleaning. With a low content of platelets in the blood should use dental floss and toothpicks with caution;avoid falls and other injuries, as well as taking alcohol and acetylsalicylic acid, increasing the risk of gastrointestinal bleeding.

In the case of manifestation of hematotoxicity, a subsequent course of treatment is possible if the hemoglobin level has reached 90 g / L, the number of neutrophils is not less than 1.0 · 109 L / and the platelet count is more than 100 · 109 / L.

Adequate contraceptive measures should be used during treatment. In case of contact with the skin or mucous membranes, the mucous membranes should be thoroughly washed with water and the skin with water and soap. Dissolution, dilution and administration of the drug are carried out by trained medical personnel with observance of protective measures( gloves, mask, clothing, etc.).

Drug Interaction

When taking cytotoxic drugs in combination or additionally, the myelosuppressive effect may be enhanced. In such cases, you can not do without reducing the dose of the drug. Other myelotoxic drugs, radiation therapy can potentiate neutropenia.

Immunosuppressants increase the likelihood of infection. Weaken the effectiveness of immunization with inactivated vaccines;when using vaccines containing live viruses, enhances the replication of the virus and the side effects of vaccination.

Topotecan prices in Moscow

Topotecan can be purchased in Moscow for rubles or euros, depending on where to order the drug.

Analogues of the preparation

The main active substance of Topotecan corresponds to Gikamtin. Other analogues are: Verotecan, Topotokan-Aktavis, Vistopoktek.

Synonyms for medicines

Synonyms for topotecan are Hycamtin, Potactasol.

Reviews

Emma:

Treatment with topotecan proved to be difficult. My hemoglobin greatly decreased and I had borderline anemia. A whole month was a break in taking the drug. My doctor said that the treatment of Topotekan was cruel and he did not really help me. My tumors grew a little and the doctor changed the drug to another. I was glad, because Topotecan exhausted me very much, I always felt tired. Although the doctor explained my fatigue with anemia. I do not know if this is a side effect of the drug, just rest, as much as possible while taking it and watch for nosebleeds.

Sheila:

My doctor said that you can adapt to Topotecan, because its effect is very good. I had the first infusion yesterday and until now I have not felt any negative reactions. I know that this can happen in a few days. My blood tests were relatively normal and I was a little tired the next day. I have not lost my hair and they continue to grow. In some other patients, I have seen severe abdominal pain and diarrhea.

Conditions for dispensing from pharmacies

The drug is dispensed from pharmacies by prescription.

Storage conditions and expiration date

Store Topotecan in a dark place at a temperature of no higher than 25 ° C.Children should not have access to the drug! Shelf life - 36 months.