testosterone cypionate injection

Treatment with testosterone cypionate injection significantly reduces the duration of febrile neutropenia, the need for antibiotic treatment and hospitalization after induction chemotherapy for acute myeloid leukemia, without affecting the frequency of fever and infection.

The use , both independently and after chemotherapy, mobilizes hematopoietic stem cell yield in peripheral blood flow. Transplantation of autologous peripheral blood stem cells (PBSC) is carried out after the treatment with high doses of cytotoxic drugs or bone marrow transplantation, instead of, or in addition thereto. PBSC transplantation can also be administered after (high) myelosuppressive cytotoxic therapy. The use of PBSC mobilized using , accelerates restoration of hematopoiesis, reduces the risk of haemorrhagic complications and the need for platelet transfusions. In children and adults with TXH (severe congenital, periodic, idiopathic neutropenia)  consistently increases the number of neutrophils in the peripheral blood, reduces the incidence of infectious complications.

Appointment of the drug in patients with HIV infection allows to maintain a normal neutrophil count and follow the recommended doses of antiviral and / or other myelosuppressive therapy. Signs of increased HIV replication when using the drug  has been noted.

As with other hematopoietic growth factors G-CSF stimulated human endothelial cells in vitro.

Preclinical safety data

The carcinogenic properties of filgrastim have not been studied. Filgrastim did not induce mutations in the genomes of bacteria, regardless of whether the enzyme system necessary for the metabolism of the drug.

It has been found that certain malignant cells have receptors on their surfaces to G-CSF. The probability that filgrastim may be a growth factor for any type of tumor can not be excluded.

In studies in rats of both sexes were not observed any influence on the course of pregnancy and fertility when used filgrastim at doses up to 500 mg / kg.

In studies on rats and rabbits filgrastim did not have a teratogenic effect. In rabbits, there was an increased incidence of miscarriage, but fetal abnormalities were noted.

Pharmacokinetics

Suction

After subcutaneous (s / c) introduction of filgrastim is rapidly absorbed, and in 2-8 hours, reaches its maximum serum concentration. The half-life after intravenous (i / v), or s / c administration is typically from 2 to 4 hours. The clearance and half-life are dependent on the dose and the number of neutrophils. Given the dependence of the clearance of the number of neutrophils, its saturation with increasing concentration of filgrastim and reducing neutropenia, can talk about the predominance of the linear nature of the clearance and the linear nature of pharmacokinetics. The absolute bioavailability after s / to the introduction of 62% at a dose of 375 mg and 72% at a dose of 750 micrograms. Filgrastim after cessation of the concentration decreases to values endogenous values within 24 hours.

In healthy volunteers and patients with cancer before chemotherapy has been shown to decrease the plasma concentrations of filgrastim in its repeated administration. The increase in clearance of filgrastim in this case is dose-dependent, and the extent of this increase may depend on the degree of neutrophilia in the recipients, which is consistent with an increase in neytrofilzavisimogo clearance with an increase in neutrophil pool. Patients receiving filgrastim after chemotherapy, the concentration of drug in plasma remained at the same level until the beginning of the recovery of hematopoiesis.

Distribution
The on / and s / c administration of filgrastim observed a positive linear relationship between the administered dose and the serum concentration. After p / administration of therapeutic doses of its concentration above 10 ng / ml for 8-16 hours. The volume of distribution is 150 ml / kg.

Withdrawal
Long-term appointment of filgrastim (up to 28 days) after autologous bone marrow transplantation does not lead to accumulation and the change in half-life.
Regardless of the route of administration, the elimination of filgrastim takes place according to the rules of the kinetics of the 1st order. The half – 3.5 hours, a clearance is 0.6 ml / min / kg.

Pharmacokinetics in special patient groups
have children after chemotherapy pharmacokinetics of filgrastim is similar to that in adult patients receiving a given weight the same dose that leads to the conclusion independence pharmacokinetics of filgrastim on age.
Pharmacokinetic data from over 65 years are no patients.

The instructions for use filgrastim studies have shown that the pharmacokinetics and pharmacodynamics in patients with severe renal or hepatic functions similar to those in healthy subjects. Therefore, in these cases, the need for dose adjustment is absent.

In patients with end-stage renal failure showed a trend toward an increase in systemic exposure of filgrastim in comparison with healthy volunteers and patients with creatinine clearance 30-60 ml / min.

testimony

Adults and children

Neutropenia, febrile neutropenia in patients receiving intensive myelosuppressive cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndrome), as well as neutropenia and its clinical consequences in patients receiving myeloablative therapy followed by allogeneic or autologous bone marrow transplantation, with an increased the risk of a prolonged and severe neutropenia.

Mobilization of autologous peripheral blood stem cells (autologous PBSC), including after myelosuppressive therapy, as well as the mobilization of peripheral blood stem cells from a healthy donor (allogeneic PBSC).

Severe congenital, intermittent or idiopathic neutropenia (absolute neutrophil count (ANC) less than or equal to 0.5 x 10 9 / l) in children and adults with severe or recurrent infections in history to increase the number of neutrophils, as well as to reduce the frequency and duration of the infection.

Persistent neutropenia (ANC less than or equal to 1.0 x 10 9 / l) in patients with advanced HIV infection to reduce the risk of bacterial infections when it is impossible to use other methods of treatment.

Neutropenia in patients with acute myeloid leukemia receiving induction chemotherapy or consolidating, to reduce its duration and clinical consequences.

Contraindications:
Hypersensitivity to the drug or its components in history.
Severe congenital neutropenia (Kostmann’s syndrome) with cytogenetic disorders (see. “Safety Precautions” section).
Neupogen ® should not be used to increase the dose of cytotoxic chemotherapy drugs above recommended.
Co-administration of cytotoxic chemotherapy and radiation therapy.

Dosing and Administration

Adults and children

Daily n / a or a short in / infusion (30 minute) 5% glucose solution (see. Subsection “Notes on breeding” under “DOSAGE AND ADMINISTRATION”) as long as the number of neutrophils can not pass the expected minimum (nadir) and returns to the normal range. Preferred n / a route of administration.

Standard regimens of cytotoxic chemotherapy

At 0.5 million units (5 micrograms) / kg 1 time a day every day n / a or a short in / infusion (30 minute) 5% glucose solution. In most cases, the preferred n / a route of administration. There is evidence that at / in the introduction of the drug occurs shortening of the duration of the effect. However, it remains unclear clinical significance of these data. Choosing the route of administration should depend on the individual characteristics of the patient and the clinical picture of the disease. The first dose of the drug Neupogen ® is administered no earlier than 24 hours after completion of cytotoxic chemotherapy. Daily administration Neupogen ® should continue as long as the number of neutrophils exceeds the expected minimum, and will not reach normal values. After the course of chemotherapy (standard circuit) for the treatment of solid tumors, lymphomas and lymphoid leukemia therapy duration to achieve the desired effect, generally up to 14 days. Following induction and consolidation therapy of acute myeloid leukemia the duration of the use of testosterone cypionate injection can be increased to 38 days, depending on the type, dose and use the scheme of cytotoxic chemotherapy.

A transient increase in neutrophil count is usually observed after 1-2 days after the start of treatment with . To achieve a stable therapeutic effect should continue therapy with  as long as the number of neutrophils exceeds the expected minimum, and will not reach normal values. Do not cancel  prematurely, before the transfer of the number of neutrophils through the expected minimum.

Use in children – see “Features of the application of the drug in pregnant women, women during the period of breastfeeding, children and adults with chronic diseases.”.

Following myeloablative therapy with bone marrow transplantation

Daily n / a or / in in the form of infusion in 20 ml of 5% glucose solution (see. Subsection “Notes on breeding” under “DOSAGE AND ADMINISTRATION”). Initial dose -. 1.0 million units (10 micrograms) / kg per day / drip for 30 minutes or 24 hours, or by continuous p / infusion within 24 h first dose of  it should be administered no earlier than 24 hours after cytotoxic chemotherapy and in bone marrow transplantation – not later than 24 hours after bone marrow infusion. The duration of therapy less than 28 days (the effectiveness and safety of treatment lasting longer than 28 days have not been established).

Mobilization of peripheral blood stem cells (PBSC) in patients receiving myelosuppressive and myeloablative therapy with autologous PBSC transfusion with (or without) a bone marrow transplant

To mobilize PBSC – by 1.0 million units (10 micrograms) / kg per day by s / c injection of 1 times a day, or a continuous 24-hour p / infusion (20 ml of 5% glucose solution (see section “Notes on breeding. “section” dosage and administration “)) for 5-7 days in a row, at the same time is usually enough for one or two leukapheresis procedure in a row on the 5th, 6th days. In some cases, the possibility of further leukapheresis. Appointment of the drug  should continue until the last leukapheresis.

To mobilize PBSC – by 1.0 million units (10 micrograms) / kg per day by s / c injection of 1 times a day, or a continuous 24-hour p / infusion (20 ml of 5% glucose solution (see section “Notes on breeding. “section” dosage and administration “)) for 5-7 days in a row, at the same time is usually enough for one or two leukapheresis procedure in a row on the 5th, 6th days. In some cases, the possibility of further leukapheresis. Appointment of the drug testosterone cypionate injection should continue until the last leukapheresis.

To mobilize PBSC after myelosuppressive chemotherapy – 0.5 million units (5 micrograms) / kg per day by daily s / c injection, starting on the first day after completion of chemotherapy and as long as the number of neutrophils can not pass through the expected minimum and reaches normal values. Leukapheresis be carried out during the period when the ANC rises from less than 0.5 x 10 9 / L to more than 5.0 x 10 9 / L. Patients not receiving intensive chemotherapy, one leukapheresis is enough. In some cases, it is recommended to conduct additional leukapheresis.

 

Severe chronic neutropenia (TXH)

Daily, n / a, once or divided into multiple administrations. In congenital neutropenia: the initial dose – 1.2 million units (12 micrograms) / kg per day; idiopathic neutropenia or intermittent: 0.5 million units (5 micrograms) / kg per day to a stable excess neutrophil 1.5 x 10 9 / L. After achieving a therapeutic effect should be to determine the minimum effective dose to maintain this level. To maintain the desired number of neutrophils requires prolonged daily administration. After 1-2 weeks of treatment, depending on the patient response to therapy, the starting dose can be doubled or halved. Subsequently, every 1-2 weeks can produce individual dose adjustment to maintain the number of neutrophils in the range of 1.5-10 × 10 9 / L. Patients with severe infections scheme can be applied with more rapid increase in dose.In 97% of patients responded positively to treatment, the full therapeutic effect is observed at doses up to 24 mg / kg per day. Safety prolonged administration Neupogen ® at doses greater than 24 mg / kg per day in patients with TXH not installed.

Use in children – see “Features of the application of the drug in pregnant women, women during the period of breastfeeding, children and adults with chronic diseases.”.

Neutropenia in HIV infection

The initial dose of 0.1-0.4 million IU (4.1 mg) / kg once a day n / k to achieve and to maintain a normal neutrophil count (more than 2.0 x 10 9 / L). In more than 90% of patients responded positively to treatment, the normalization of the number of neutrophils usually occurs within 2 days. A small number of patients (10% less) to achieve the required normal number of neutrophils administering doses to 1.0 million IU (10 micrograms) / kg per day testosterone cypionate injection (maximum daily dose of less than 10 mg / kg). After achieving a therapeutic effect requires the introduction of the minimum effective dose to maintain a normal number of neutrophils. The recommended maintenance dose is 300 micrograms a day n / k on average 3 times a week, alternating pattern (every other day). Subsequently, the individual may require dose adjustment and long-term use of the drug to maintain the average neutrophil count> 2.0 x 10 9 / L.

Specific guidance on dosing

Recommendations for dosing in special patient groups refer to “Features of the application of the drug in pregnant women, women during the period of breastfeeding, children and adults with chronic diseases.”

Instructions for dilution

Neupogen ® diluted only 5% glucose solution. When this is not permitted dilution of 0.9% sodium chloride solution. It introduced the drug to a final concentration of less than 1 5 micrograms per ml.

If Neupogen ® diluted to a concentration of at least 1.5 MU (15 ug) in 1 ml, the solution should be added to human serum albumin in an amount that the final concentration of albumin was 2 mg / ml. For example, in a final volume of 20 ml, the total dose filgrastim less than 30 million units (300 micrograms) to be administered with the addition of 0.2 ml of 20% albumin solution.

Divorced  can adsorb to glass and plastics. However, at a dilution of 5% glucose solution is compatible with glass and some plastics, including polyvinyl chloride, polyolefin (a copolymer of polypropylene and polyethylene) and polypropylene.

Ready solution  is stored at a temperature between 2 and 8 ° C for up to a day.

Precautionary measures

Treatment with  should only be done under the supervision of an oncologist or hematologist with experience in the use of G-CSF, with the necessary diagnostic capabilities. Mobilization and apheresis procedures should be performed in cell oncology or hematology center with experience in this field and the possibility of adequate monitoring of hematopoietic progenitor cells.

a) The growth of malignant cells

The safety and efficacy of in patients with myelodysplastic syndrome or chronic myelogenous leukemia have not been established, so it is not shown in these diseases. Pa parbol