Neostim

General characteristics. Structure:

Active agent – molgramosty 150 mkg.

Excipients: Mannitolum, albumine human serumal, sodium phosphate disubstituted, sodium hydrophosphate, sodium phosphate monosubstituted.

Pharmacological properties:

Pharmacodynamics. Neostim – a recombinant human granulotsitarnomakrofagalny colony stimulating factor, represents water-soluble neglikozilirovanny protein. Consists of 127 amino acids, has molecular weight 14447 дальтон. It is formed by Escherichia coli strain bearing the plasmid received by means of genetic engineering containing a gene of a granulotsitarnomakrofagalny colony stimulating factor of the person. Natural human GM-KSF is the major regulatory factor providing growth, maturing and functional activity of many blood cells. GM-KSF possesses polyvalent action on various sprouts of the hemopoietic progenitors of the hemopoietic system that leads to formation of granulocytes, monocytes/macrophages and T lymphocytes. Drug considerably increases the maintenance of leukocytes in blood, mainly, of neutrophils, and, to a lesser extent, oyat growth of tumor cells. After single parenteral administration effect of drug is shown in 1-4 hours and reaches peak in 6-18 hours.

Pharmacokinetics. At hypodermic administration of drug in doses from 5 to 20 mkg/kg and at intravenous administration of drug in doses from 5 to 25 mkg/kg of value of the area under a curve "concentration time" directly depend on dose size. After hypodermic introduction the maximum concentration of a molgramostim in serum were reached in 3-4 hours. The elimination half-life of a molgramostim after intravenous administration made 1-2 hours and after hypodermic introduction – 2-3 hours.

Indications to use:

- patients, to whom myelosuppressive therapy (antineoplastic therapy), for the purpose of reduction of expressiveness of a neutropenia is carried out that reduces risk of development of infections and allows to observe the chemotherapy mode fully

- patients with the insufficiency of a marrowy hemopoiesis caused by other reasons for the purpose of decrease in risk of development of the infections arising owing to a leukopenia

- the patients who are exposed to autologous or singenny transplantation of marrow for the purpose of acceleration of recovery of myeloid blood formation

- patients with a Cytomegaloviral retinitis at HIV infection, in addition to therapy gantsikloviry, for the purpose of decrease in expressiveness of the neutropenia caused gantsikloviry and full observance of the recommended mode of dosing of a gantsiklovir.

Route of administration and doses:

Subcutaneous injections or intravenous infusions. The mode of dosing is set taking into account indications. Neostim's dose is usually established in micrograms, but in certain cases use the International Units (1 mkg is equal to 0,0111 million ME).

At myelosuppressive therapy: Neostim appoint in a daily dose 5-10 mkg/kg subcutaneously. Treatment is begun in 24 hours after the end of cytotoxic therapy and continued within 7-10 days.

At miyelodisplastichesky syndromes and aplastic anemia: on 3 mkg/kg of 1 times a day subcutaneously. Usually manifestation of medical effect of drug (increase in quantity of leukocytes in blood) requires from 2 to 4 days. In the subsequent the daily dose is selected so that the maintenance of leukocytes in blood was supported at the done level.

At transplantation of marrow: Neostim enter intravenously kapelno (within 4-6 hours) in a daily dose of 10 mkg/kg. Administration of drug is begun next day after performing transplantation of marrow. Therapy is carried out to achievement of absolute maintenance of neutrophils ≥ 1000/mkl. The maximum duration of treatment makes 30 days.

At the leukopenias caused by infections (including HIV infection) drug appoint in a dose 1-5 mkg/kg of 1 times a day subcutaneously. At patients with HIV infection which carries out treatment by a zidovudine or a combination of a zidovudine and alpha interferon Neostim appoint in a dose 1-3 mkg/kg subcutaneously. Increase in number of leukocytes is noted in 2-4 days of treatment. Further, for maintenance of desirable level of leukocytes (usually less 1000/mkl) the daily dose of Neostim is korrigirut by each 3-5 days.

As addition to treatment gantsikloviry a Cytomegaloviral retinitis at HIV infection: Neostim appoint in a dose 5 mkg/kg of 1 times a day subcutaneously. After introduction of the fifth dose of drug its dose is korrigirut for maintenance of number of neutrophils and leukocytes in blood at the sufficient level (usually ≥1000 мкл or ‹20000 мкл, respectively).

Features of use:

Neostim has to be applied under control of the doctor having experience of treatment of oncological and hematologic diseases or infectious diseases. The first dose of Neostim should be entered having provided careful medical observation of the patient. At emergence of allergic reactions Neostim it is necessary to cancel immediately and in the subsequent not to apply. At development of pleurisy and/or a pericardis Neostim it is necessary to cancel.

Neostim patients should appoint with care with a neutropenia, receiving chemotherapy concerning myeloid malignant diseases. At such patients the advantage of reduction of the period of a neutropenia should be correlated to theoretical risk of strengthening of the tumoral growth connected with stimulation by cytokine. Neostim the patients having after the termination of chemotherapy more than 5% of myeloblasts in marrow and/or in peripheral blood should not appoint.

At the patients having diseases of lungs at treatment molgramostimy the tendency to depression of function of external respiration and development of an asthma is noted, such patients demand attentive observation.

It must be kept in mind that use of chemotherapeutic antineoplastic drugs in high doses (along with molgramostimy) can increase risk of development of thrombocytopenia and anemia.

Side effects:

At transfer of side effects the following characteristics of frequency of occurrence of the undesirable phenomena are used: very much part of ≥10%; often ≥1% ‹10%; infrequently ≥0,1% ‹1%; seldom ≥0,01% ‹0,1%; very seldom ‹0,01%.

From the alimentary system: often – nausea, vomiting, anorexia, diarrhea; infrequently – stomatitis, abdominal pains.

From a nervous system: often – feeling of fatigue, an adynamy; infrequently – a headache, dizziness, paresthesias, confusion of consciousness; seldom – spasms, increase in intracranial pressure, faints, disturbances of cerebral circulation.

From a respiratory organs: often – an asthma; infrequently – a bronchospasm, a fluid lungs, pleurisy; seldom – emergence of pulmonary infiltrates.

From cardiovascular system: infrequently – arterial hypotonia, disturbances of a heart rhythm, heart failure, a pericardis; seldom – the increased capillary permeability, trombotichesky disturbances.

From integuments and skin appendages: often – rash; infrequently – an itch, the increased sweating.

From laboratory indicators: decrease in a chasla of thrombocytes, hemoglobin and level of albumine of blood serum is most often noted. Also increase in absolute and relative maintenance of eosinophils in blood is observed.

Allergic reactions: infrequently – a bronchospasm, a Quincke's disease, an acute anaphylaxis.

Local reactions: morbidity in the place of hypodermic administration of drug.

Others: often – a mialgiya, fever, a fever; infrequently – nonspecific thorax pains; seldom – an aggravation or development of autoimmune diseases.

Interaction with other medicines:

Because use of a molgramostim is connected with decrease in concentration of albumine in blood serum, change of doses of those medicines which are characterized by high extent of linkng with blood plasma albumine can be required.

Contraindications:

- hypersensitivity to a molgramostim or any other component of drug

- simultaneous use of extensive radiation therapy (because of the increased risk of development of heavy complications from lungs)

- drug is not used for the purpose of increase in intensity of cytotoxic chemotherapy above the doses established in the corresponding modes

- a Werlhof's disease of autoimmune genesis in the anamnesis

- myeloleukemia

- pregnancy and period of feeding by a breast.

Overdose:

Symptoms: tachycardia, lowering of arterial pressure, диспноэ and grippopodobny phenomena.

Treatment: symptomatic under control of the vital functions.

Storage conditions:

At a temperature from 2 ºС to 8 ºС in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for intravenous and hypodermic administration on 150 mkg in the bottles from borosilicate glass corked by traffic jams and rolled by a cap aluminum or combined. On 1 bottle in the blister from a PVC film. On 1 blister with the application instruction in a cardboard pack.