Moustoforan® (Mustophoran®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceFotemustineFotemustine
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  • Moustoforan®
    powder d / infusion 
    Servier Laboratories     France
    • Dosage form: & nbspPowder for solution for infusion
    Composition:

    1 bottle of powder contains: active substance: fotemustine 208 mg

    Excipients: no

    1 ampoule with a solvent contains: Ethanol 96% - 3.35 ml, water for injection - a sufficient amount up to a volume of 4 ml.

    Description:

    Powder of light yellow color. Solvent: a clear, colorless solution with a characteristic ethanol smell.

    Pharmacotherapeutic group:antitumor agent-alkylating compound
    ATX: & nbsp

    L.01.A.D.05   Fotemustine

    Pharmacodynamics:

    Fotemustine is a cytostatic antimitotic drug from the group of nitrosourea, which has an alkylating and carbamylating action. The pronounced antitumor activity of fotemustine was confirmed experimentally.

    The composition of the molecule fotemustina includes bioisostere alanine (amino-1-ethylphosphonic acid), which facilitates the penetration of the drug into cells and passage through the blood-brain barrier.

    Pharmacokinetics:

    After intravenous infusion, the kinetics of elimination of the drug from plasma is mono- or bi-exponential with a short half-life.

    The drug is almost completely metabolized. Binding to plasma proteins is low (25-30%). Fotemustine penetrates the blood-brain barrier.

    Indications:

    • Disseminated malignant melanoma, including metastases in the brain.

    • Malignant brain tumors.

    Contraindications:

    • Hypersensitivity to fotemustine, or preparations of the group of derivatives of nitrosourea, or to any of the excipients.
    • Pregnancy and the period of feeding the chest.
    • Combined use with vaccine yellow fever (see section "Interaction with other medicines and other forms of interaction ").

    Application in children and adolescents

    It is not recommended to use the drug in children and adolescents under 18 because effectiveness and safety for this no age group.


    Carefully:The drug should be used with caution in patients with alcoholism, patients with liver disease and epilepsy.
    Pregnancy and lactation:
    Pregnancy
    Data on the use of the drug Moustoforan® by pregnant women are limited.Animal studies are not sufficient to assess reproductive toxicity.
    Lactation
    It is not known whether fotemustine or its metabolites with breast milk. Therefore, the risk of unwanted exposure to newborns / infants can not be ruled out. Fertility
    Animal toxicity studies have identified the effects of fotemustine on the fertility of males.

    Dosing and Administration:

    - In monotherapy, the drug is used as induction therapy at a dose of 100 mg / m2 at 1, 8 and .15 days. Similar courses are repeated at intervals of 4-5 weeks.

    -As maintenance therapy, Moustoforan is administered at the same dose every 3 weeks.

    -In combination chemotherapy, the drug is administered at a dose of 100 mg / m2 on days 1 and 8.

    In patients receiving Mystophoran, before every injection is necessary control the number of platelets, leukocytes and granulocytes in the blood. In the case of development of hematological toxicity, the dose of the drug Mystophoran may be reduced, or the administration of the drug should be postponed in accordance with the following scheme:

    Absolute

    quantity

    neutrophils

    (in 1 μl)

    amount

    platelets

    (in 1 μl)

    % of

    previous

    th dose

    > 2000 and

    > 100 000

    100 %

    2000 > N

    >1500

    100 000> N

    >80000

    75%

    1500 > N

    >1000


    50%

    < 1000

    N < 80 000

    Postpone

    introduction

    - Use in combination with dacarbazine

    When fotemustine and dacarbazine were administered at high doses for one day, cases of pulmonary toxicity (respiratory distress syndrome adults).

    The simultaneous use of dacarbazine and fotemustine should be avoided (see section "Interaction with other drugs and other forms of interaction ").

    If the combined use of these drugs is necessary, the following treatment regimen is recommended:

    Induction therapy:

    - fotemustine in a dose of 100 mg / m2 on days 1 and 8,

    - dacarbazine in a dose of 250 mg / m2 at 15, 16, 17 and 18 days.

    Then you should 'do a 5-week break in treatment.

    Supportive therapy: every 3 weeks

    - fotemustine in a dose of 100 mg / m2 per day,

    - dacarbazine in a dose of 250 mg / m2 at 2,3,4 and 5 days.



    Side effects:
    Most often in clinical trials there were side effects from the hematopoiesis system. These toxic effects of fotemustine were delayed and manifested anemia (14 %),
    thrombocytopenia (40.3%) and leukopenia (46.3%) and reaches a maximum severity at 4-5 and 5-6 weeks after initiation of induction therapy. It is also possible to develop pancytopenia.Hematologic toxicity with fotemustine may worsen in the case of previous chemotherapy and / or combination therapy with other drugs that have a toxic effect on the hematopoiesis system.
    Older patients may have more severe toxic effects on the hematopoietic system and the gastrointestinal tract.
    The incidence of adverse reactions that have been observed with fotemustine therapy is shown in the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), unspecified frequency (frequency can not be calculated from available data).
    On the part of the hematopoiesis system
    Very often: thrombocytopenia, leukopenia (3-4 degrees), anemia (3-4 degrees).
    From the digestive system
    Often: nausea and vomiting, developing within 2 hours after
    the beginning of the drug administration; moderate reversible increase
    activity "hepatic" transaminases, alkaline phosphatase and serum bilirubin concentrations.
    Often: diarrhea, abdominal pain.
    Unspecified frequency: hepatitis.
    From the nervous system
    Infrequently: transient neurological symptoms (impaired consciousness, paresthesia, loss of taste sensitivity).
    From the urinary system
    Infrequently: transient increase in urea concentration in blood serum.
    From the skin and subcutaneous tissues
    Infrequently: itching.

    Other

    Often: fever, phlebitis at the site of administration preparation.

    From the respiratory system

    With simultaneous administration with dacarbazine cases of toxicity in respiratory (respiratory distress syndrome) (see section "Interaction with other medicinal means and other forms interaction ").

    Neoplasms are benign, malignant and unspecified (including cysts and polyps)

    The use of antitumor drugs, and especially - alkylating compounds, is associated with a risk of myelodysplastic syndrome and acute myelogenous leukemia. Rare cases of such complications have been described using fotemustine in high cumulative doses in monotherapy and in combination with other chemotherapeutic drugs, in combination with radiation therapy and without it.

    Overdose:

    Specific antidotes for overdose of Mystoforan are not known. Treatment consists in stopping the administration of the drug and performing maintenance therapy with increased monitoring of hematological parameters

    Interaction:

    Interaction, characteristic for cytotoxic drugs Patients with. malignant neoplasms increased the risk of thrombosis, so they are often prescribed anticoagulants. Against the background of taking anticoagulants, the indicator of the International Normalized Ratio (MNO) should be more often monitored, since in such patients there is a variability in the coagulation capacity of the blood, which is complicated by the risk of interaction of anticoagulants for ingestion and antitumor agents.

    Combinations of drugs, application which is contraindicated

    Yellow fever vaccine The risk of developing fatal systemic post-vaccination complications (see the section "Contraindications").

    Unwanted combinations of drugs

    - With the simultaneous administration of phenytoin, due to decreased absorption at the level of the digestive tract, the concentration of phenytoin in the blood serum can be reduced.

    - During and after treatment (at least in for 3 months) vaccination should be avoided "alive" and "weakened" vaccines.

    To vaccinate such patients, inactivated vaccines should be used (eg, polio vaccine). Combinations of drugs, the use of which requires caution Immunosuppressants-marked inhibition of the immune system and the risk of lymphoproliferation.

    Interaction specific for fotemustina Combinations of drugs, the use of which requires caution.

    - Dacarbazine

    With the administration of fotemustine and dacarbazine in high doses, cases of pulmonary toxicity (adult respiratory distress syndrome) were observed for one day. Do not use fotemustine and dacarbazine Simultaneously. The recommended interval between the administration of the last dose of fotemustine and the first dose of dacarbazine is 1 week (see section "Method of administration and dose").


    Special instructions:

    • Treatment with Moustoforan® should be conducted only under the control of a doctor with experience antitumor therapy.
    • If after previous treatment cytostatic agents have passed less than 4 weeks (and in case of treatment preparations of nitrosourea-6 weeks), the drug should not be prescribed recommended.
    • Treatment with Moustoforan® can be carried out only with a platelet count in the peripheral blood of at least 100,000 / μL and granulocytes - at least 2000 / μL.
    • The blood test should be performed before each next injection of the drug with appropriate dose adjustment, depending on the hematological parameters.
    • Between the onset of induction therapy and the beginning of maintenance therapy is recommended interval - 8 weeks.
    • Between the two cycles of maintenance therapy, the recommended interval is 3 weeks.
    • The purpose of maintenance therapy is possible if the number of platelets in the peripheral blood is not less than 100,000 / μl and granulocytes - not less than 2000 / μl.
    • It is recommended that the liver function indicators be evaluated regularly during and after induction chemotherapy.
    • Men and women during and for at least 6 months after graduation should use reliable contraceptive measures
    • When working with the drug Moustoforan®, the necessary rules for the use and destruction of cytotoxic drugs should be observed. Pregnant women work with the drug Mystophoran is prohibited. When working with the drug recommended the use of latex gloves and masks.In case of contact with the skin or mucous membranes, these areas should be thoroughly rinsed with soap and water. If the product gets into the eyes, they should be rinsed with plenty of water. Avoid inhalation of the drug.
    • The preparation contains 80% ethanol solution, i.e. 1.3 g of ethanol per 100 mg of fotemustine, equivalent to 32 ml of beer, 13.3 ml of wine. This amount of ethanol can be dangerous for patients suffering from alcoholism. When prescribing a drug for patients with liver disease and epilepsy, it should also be remembered that it includes ethanol.
    • Older patients: toxicity fotemustine was compared in patients under 60 years of age. Thrombocytopenia (grade 3), leukopenia (grade 3), and toxic effects on the gastrointestinal tract (grade 3) much more often occurred in patients over the age of 60 years.
    • To avoid a hemorrhage before introduction of fotemustine make sure that the needle for intravenous administration is correctly inserted into the vein. When hemorrhage stop the infusion, inject intravenously a 5% dextrose solution (4 ml / min), fix the limb and apply the ice pack to the injection site to avoid diffusion of the infusion solution.


    Effect on the ability to drive transp. cf. and fur:
    Studies to assess the impact on the ability to drive vehicles was not conducted. Nevertheless, it is not recommended to drive vehicles and engage in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions, immediately after taking fotemustine.

    Form release / dosage:
    Powder for the preparation of a solution for infusions complete with a solvent, 208 mg.

    Packaging:
    Powder
    For 208 mg of powder in a bottle of brown glass. The bottle is sealed with an elastomer stopper and covered with an aluminum cap.
    Solvent
    For 4 ml in a vial of colorless glass with a white collar ring applied. The vial and ampoule are placed in a white plastic contour acrylic package with a colorless plastic lid and, together with instructions for medical use, are embedded in a cardboard box.
    Storage conditions:
    At a temperature of 2 to 8 ° C in a place protected from light and inaccessible to children.

    Shelf life:
    Powder for solution for infusion: 2 years
    Solvent: 3 years
    Do not use after the expiration date stated on the package.
    The finished solution should be used immediately after preparation.

    Terms of leave from pharmacies:On prescription
    Registration number:П N014231 / 01
    Date of registration:31.05.2007
    The owner of the registration certificate:Servier LaboratoriesServier Laboratories France
    Manufacturer: & nbsp
    Representation: & nbspServier Laboratories Servier Laboratories France
    Information update date: & nbsp29.10.2015
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