Pronounced antitumor fotemustine activity was confirmed experimentally.
The composition fotemustine molecule includes bioisostere alanine (amino-1-ethylphosphonic acid) which facilitates the penetration of the drug into cells and passing the blood-brain barrier.
Following intravenous infusion, the plasma kinetics of elimination of the drug is mono- or biexponential character with a short half-life.
The drug is almost completely metabolized. Plasma protein binding is low (25-30%). Fotemustine penetrates the blood-brain barrier.
• Hypersensitivity testosterone enanthate injection to fotemustine or drugs group of nitrosoureas, or to any of the excipients.
• Women with childbearing potential who do not keep reliable contraceptive measures.
• Pregnancy and lactation.
• Combined use with yellow fever vaccine (see. Section “interaction with other medicinal products and other forms of interaction”). use in children and adolescents is not recommended to use the drug in children and adolescents under 18 years since efficacy and safety have not been established for this age group.
Application of pregnancy and during breastfeeding
Data on the use of the drug in pregnant women is limited. Data from animal studies are insufficient to assess reproductive toxicity. Breastfeeding period is not known whether the output fotemustine or its metabolites in breast milk in humans. In this connection, we can not exclude the risk of unwanted exposure to newborns / infants.
The drug should be used with caution in patients with alcoholism, in patients with liver disease or epilepsy.
Dosing and Administration
• To avoid extravasation, before the introduction of fotemustine make sure that the needle for intravenous administration is correctly inserted into a vein. In the event of extravasation, stop the infusion, remove the contents extravasates as much as possible and fix the limb in a good condition.
• When monotherapy used as induction therapy at a dose of 100 mg / m² in 1, 8 and 15 days. Similar courses are repeated with an interval of 4-5 weeks.
• as maintenance therapy is administered at the same dose one time every 3 weeks.
• In the combined chemotherapy drug is administered at a dose of 100 mg / m² days 1 and 8.
Patients receiving, before each dose necessary to control the number of platelets, leukocytes and granulocytes in the blood. In the case of hematological toxicity of the drug dose Myustoforan® can be reduced or administration of the drug should be postponed in accordance.
The most commonly observed in clinical studies, side effects from the hematopoietic system. These toxic effects were delayed fotemustine, manifested anemia (14%), thrombocytopenia (40.3%) and leukopenia (46.3%) and reached maximum severity at 4-5 and 5-6 weeks after the start of induction therapy. It is also possible the development of pancytopenia.
Hematological toxicity in patients receiving fotemustine may be exacerbated in the case of prior chemotherapy, and / or combination therapy with other drugs that have toxic effects on the blood system.
Elderly patients may experience more pronounced toxic effects on the hematopoietic system and gastrointestinal . intestinal tract
The incidence of adverse reactions that have been observed on the background of fotemustine therapy is given in the following grading: very common (> 1/10); common (> 1/100, <1/10); uncommon (> 1/1000, <1/100); rare (> 1/10000, <1/1000); very rare (<1/10000), unspecified frequency (frequency can not be calculated from the available data). From the side of hematopoiesis Very common:thrombocytopenia, leukopenia (grade 3-4), anemia (grade 3-4). From the digestive system often: nausea, vomiting, growing for 2 hours after the start of injection; transient moderate reversible increase in the activity of “liver” transaminases, alkaline phosphatase and serum concentrations of bilirubin. Often: diarrhea, abdominal pain. unspecified frequency: hepatitis. Nervous system Uncommon: transient neurological symptoms (disturbance of consciousness, paresthesia, testosterone enanthate injection taste sensitivity loss ). From the urinary system Uncommon: transient increase in urea concentration in the blood serum. skin and subcutaneous tissue disorders Uncommon: pruritus. General disorders and at the injection site Common: fever, phlebitis (swelling, pain, redness over the affected vein) in injection site in the event of extravasation (see. sections “Special instructions” and “dosage and administration”). The respiratory system simultaneous administration with dacarbazine were marked by rare cases of toxicity to the respiratory system (adult respiratory distress syndrome) (see . See “interaction with other medicinal products and other forms of interaction”). in applying fotemustine, also described toxicity to the respiratory system (interstitial pneumopathy). Neoplasms benign, malignant and unspecified (including cysts and polyps) The use of anticancer drugs, and particularly – alkylating compounds associated with risk of myelodysplastic syndrome and acute myeloid leukemia. Rare cases of complications have been described in the application fotemustine high cumulative doses of monotherapy and in combination with other chemotherapeutic drugs, in combination with radiotherapy and without it.
Specific antidotes Myustoforana an overdose are not known. Treatment consists in stopping the administration and conduct of maintenance therapy with enhanced monitoring of hematological parameters.
The interaction characteristic of cytotoxic drugs
in patients with cancer are at increased risk of thrombosis, so they are often prescribed anticoagulants. In patients receiving anticoagulants should be more frequently monitor the “rate of the international normalized ratio (MHO), since these patients have a variability of blood clotting, which is complicated by the risk of interaction anticoagulants for oral and antitumor agents. Combinations of drugs whose use is contraindicated • The vaccine against yellow fever The risk of fatal systemic complications of post-vaccination (see section “Contraindications” section.). Adverse drug combinations • Phenytoin (and, presumably, fosphenytoin): risk of seizures because, while the application, due to lower absorption at the level of the digestive . tract, serum concentration of phenytoin / fosphenytoin may decreaseThere is a risk of increasing toxicity or reduce the effectiveness of fotemustine, due to increasing the activity of its metabolism in the liver, caused by phenytoin / phosphenes ton. • Live and attenuated vaccines (except yellow fever vaccine): risk of systemic diseases induced by vaccines, which can be fatal. The risk is higher in patients with immunosuppressive conditions due to existing medical conditions. For these patients, vaccination should be used inactivated vaccines, if any, (eg, polio vaccine). Combinations of drugs whose use requires caution Immunosuppressant-pronounced suppression of the immune system and the risk of lymphoproliferation.
Interaction specific to fotemustine
combination of drugs, the use of which requires caution
When administered fotemustine and dacarbazine in high doses during one day cases of toxicity to the respiratory system (adult respiratory distress syndrome). It was marked
Avoid the simultaneous use of dacarbazine and fotemustine Recommended the interval between administration of the last dose fotemustine and the first dose of dacarbazine is 1 week (see. “dosage and administration” section).
• Treatment with Myustoforan ® should only be undertaken under the supervision of a physician who is experienced in the use of antineoplastic therapy.
• If, after previous treatment with cytotoxic agents was less than 4 weeks (and in the case of treatment with nitrosourea – 6 weeks)., Not recommended medication
• prescribe medication Myustoforan ® is possible only when the number of platelets in the peripheral blood of at least 100,000 / microliter and granulocytes -. not less than 2,000 cells / mm
• blood tests should be performed prior to each ordinary administration of the drug with an appropriate dose adjustment depending on hematological parameters (see “method section. . dosage and administration »)
• between the start of induction therapy and maintenance therapy is recommended the start of the interval – 8 weeks. Between the two cycles of maintenance treatment recommended interval -. 3 weeks
• Purpose maintenance therapy is possible, if the number of platelets in peripheral blood of at least 100,000 / ul and granulocytes -. No less than 2000 / l
• Recommended regularly assess liver function during and after induction chemotherapy.
• Testosterone enanthate injection is contraindicated during pregnancy, as well as women with childbearing potential, do not comply with reliable contraceptive measures (see section “Contraindications»).
• Men and women with childbearing potential during and for at least 6 months after treatment fotemustine should use reliable contraceptive measures
• When working with the preparation Myustoforan ® should observe the necessary rules for the use and disposal of cytotoxic drugs. Pregnant women working with drug Myustoforan ® prohibited. When working with the drug recommended by the use of latex gloves and masks. In case of contact with skin or mucous membranes, these areas should be thoroughly washed with soap and water. In case of contact with the drug in the eye should be rinsed with plenty of water. Avoid inhalation of the drug.
• The product contains 80% ethanol solution, ie, 1.3 g of ethanol per 100 mg fotemustine, equivalent to 32 ml of beer, wine 13.3 ml. Such an amount of ethanol can be dangerous to patients suffering from alcoholism. In appointing the drug to patients at risk (eg, liver disease or epilepsy), also keep in mind that it contains ethanol.
• Elderly patients: fotemustine toxicity was compared in patients aged 60 years and older. Thrombocytopenia (grade 3), leukopenia (grade 3) and toxic effects on the gastrointestinal tract (grade 3) were significantly more common in patients over the age of 60 years.
• To avoid extravasation, before the introduction of fotemustine make the needle for intravenous administration is correctly inserted into a vein. In the event of extravasation, stop the infusion, remove the contents extravasates as much as possible and fix the limb in a good condition.
Effects on ability to drive vehicles, machinery
Research was conducted to assess the effect on the ability to drive vehicles. However, it is not recommended to drive vehicles and doing other potentially hazardous activities that require high concentration and psychomotor speed reactions, immediately after the fotemustine.
Powder for solution for infusion together with the solvent, 208 mg.
208 mg powder vial of brown glass. Capped vial and elastomeric stopper run-aluminum cap.
In 4 ml vial colorless glass coated with a white ring fracture. The vial and ampoule are placed in blisters, plastic, white with colorless plastic cover, and together with the instructions for medical use are put in cardboard box.