Lonvex 6 mg/0.6 ml, 0.6 ml syringe

Leukopoiesis stimulator. Lipagfilgrastim is a covalent conjugate of filgrastim bound to one molecule of methoxypolyethylene glycol via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine.

Human granulocyte colony stimulating factor (G-CSF) is a glycoprotein that regulates the formation of functionally active neutrophils and their release into the peripheral blood from the bone marrow. Filgrastim is a non-glycosylated recombinant human G-CSF with an additional methionine residue. Lipegfilgrastim is a prolonged form of filgrastim due to reduced renal clearance. Lipegfilgrastim binds to the G-CSF receptor similarly to filgrastim and pegfilgrastim.

Lipegfilgrastim significantly increases the number of neutrophils in peripheral blood in the first 24 hours after administration, causing a slight increase in the number of monocytes and/or lymphocytes.

Due to the presence of a part of G-CSF in the molecule of lipaegfilgrastim this growth factor has the expected activity: it stimulates the proliferation of hematopoietic progenitor cells, their differentiation into mature cells and release into the peripheral blood. G-CSF is a specific factor not only for neutrophils, it also has an effect on other progenitor cells, which give one to several differentiation lines, and on polypotent hematopoietic stem cells. In addition, G-CSF increases the phagocytic and antibacterial activity of neutrophils, enhancing cellular mechanisms of anti-infective immunity by priming neutrophils.

According to clinical studies it was found that the duration of severe neutropenia in the first cycle of chemotherapy when treated with lipegfilgrastim and pegfilgrastim is generally similar, the incidence of febrile neutropenia is significantly higher in the placebo group compared to the group of patients treated with lipegfilgrastim. The effective dose is 6 mg of lipegfilgrastim.

Indications

Active ingredient

Composition

1 syringe lipegfilgrastim 6 mg

Excipients:

glacial acetic acid – 0.36 mg,

Polysorbate 20 – 0.02 mg,

sorbitol – 30 mg,

sodium hydroxide 1M – to pH 5.0,

water d/i – to 0.6 ml.

Interaction

There have been no studies on the study of interaction of the drug Loncvex with other medicinal products.

Because of the possible high sensitivity of rapidly dividing myeloid cells to cytotoxic therapy, the drug Lonnex should be administered 24 hours after the end of the cycle of cytotoxic chemotherapy.

The concomitant use of Lonnex and any chemotherapeutic drug has not been evaluated in patients. In preclinical studies, concomitant use of G-CSF and fluorouracil or other anticancer drugs of the antimetabolite group has been shown to increase myelosuppression.

The safety and efficacy of Lonnex have not been evaluated in patients who received chemotherapeutic agents with delayed myelosuppression (e.g., nitrosourea derivatives).

The possibility of interaction with lithium, which also contributes to increased neutrophil counts in peripheral blood, has not been specifically investigated. There is no evidence that this interaction could be harmful.

Directions for use

In adults, the drug is administered as a single oral injection at a dose of 6 mg (1 syringe) 24 hours after the end of each cycle of cytotoxic chemotherapy.

There were no significant differences in efficacy and safety of Longvex in patients of different ages in clinical trials. Therefore, there is no need for dose adjustment in elderly patients.

Dose adjustment is not required in patients with renal/hepatic impairment.

The safety and effectiveness of Longvex in children and adolescents under 18 years of age has not been established (no data available).

Information on the technique of performing p/k injections

Special training of the patient is required before the injection.

1. One blister of the syringe should be removed from the refrigerator and the syringe with the medication should be removed.

2. Check the expiration date on the label of the syringe. Do not use the product if the last day of that month has expired.

3. The appearance of the injection solution should be checked. The solution should be clear, colorless and without visible solid particles. The drug should not be used if the solution is cloudy or contains visible particles.

4. The syringe should be kept at room temperature for 30 minutes or warmed in the hand for several minutes. The product should not be heated by other means (e.g. microwave or hot water).

5. Do not remove the protective cap from the needle until the preparation for the injection is complete.

6. Your hands should be washed thoroughly.

7. Choose a well-lit, comfortable area. Place everything necessary for the injection (syringe containing the medication, alcohol-soaked napkin, sterile gauze swab) in a place where it can be easily used.

8. Carefully, without turning, pulling in a straight line without touching the needle, remove the protective cap from the needle.

Special Instructions

The treatment with Lonnex is performed only under the supervision of a physician experienced in the use of colony-stimulating factors with the necessary diagnostic capabilities.

The safety and efficacy of Lonnex have not been studied in patients who received high-dose chemotherapy. Loncvex should not be used to increase the dose of cytotoxic chemotherapy above the established dosing regimen.

Patients who are sensitive to G-CSF or its derivatives are also at risk of hypersensitivity reactions to lipegafilgrastim due to possible cross-sensitivity. Lipegfilgrastim should not be used in these patients due to the risk of cross-reaction.

Most drugs of biological origin can elicit a response in the form of some level of anti-drug antibodies. This humoral immune response may in some cases lead to the development of adverse effects or loss of efficacy. If the patient does not respond to treatment, further evaluation should be done.

If a severe allergic reaction develops, appropriate therapy should be given, followed by close monitoring of the patient for several days.

The treatment with Longvex does not prevent the development of thrombocytopenia and anemia due to myelosuppressive chemotherapy. Longvex may also cause thrombocytopenia, therefore it is recommended to determine the platelet count and hematocrit index regularly. Caution should be exercised when using single-component or combination chemotherapy regimens known to cause severe thrombocytopenia.

The development of leukocytosis is possible. No adverse events directly related to leukocytosis have been reported. The increase in the number of leukocytes in the blood is consistent with the pharmacodynamic effects of lipegfilgrastim. Given the clinical effects of lipegfilgrastim and the possible risk of leukocytosis, leukocyte counts should be monitored regularly during treatment with lipegfilgrastim. If the leukocyte count exceeds 50×109/l after the expected minimum level, treatment with lipegfilgrastim should be discontinued immediately.

The increased hematopoietic activity of the bone marrow in response to growth factor therapy leads to transient positive changes in bone imaging, which should be taken into account when interpreting radionuclide scintigraphy results.

In myelodysplastic syndrome and chronic myeloleukemia, the efficacy and safety of Longvex have not been established. In patients with the above mentioned diseases as well as with pre-tumorous lesions of myeloid hematopoiesis the use of Longvex is not indicated. Particular attention should be paid to the differential diagnosis between blastic crisis of chronic myeloleukemia and acute myeloleukemia.

Contraindications

– children and adolescents under 18 years of age;

– hypersensitivity to lipegfilgrastim (including colony stimulating factors: filgrastim, pegfilgrastim; Escherichia coli) or other components of the drug.

The drug should be used with caution in malignant and pre-tumor diseases of myeloid nature (including acute myeloleukemia de novo and secondary); sickle cell anemia; usage in combination with high-dose chemotherapy; fructose intolerance, insufficiency of sugar/isomaltase, glucose-galactose malabsorption syndrome.

Side effects

Blood system disorders: thrombocytopenia, leukocytosis, splenomegaly, spleen rupture symptoms (pain in the upper left quadrant of the abdomen, pain in the upper left shoulder), spleen rupture, in some cases with lethal outcome.

Immune system disorders: hypersensitivity reactions, allergic skin reactions, urticaria, Quincke’s edema.

Nervous system disorders: headache, dizziness.

Cardiovascular system disorders: tachycardia.

Respiratory system disorders: cough, dyspnea, interstitial pneumonia, pulmonary edema, pulmonary infiltrates, pulmonary fibrosis, respiratory failure, adult respiratory distress syndrome (ARDS).

Digestive system disorders: nausea, epigastric pain.

Skin and subcutaneous tissue disorders: erythema, skin rash, itching, reaction at the injection site (pain, hyperemia, thickening), alopecia, acute febrile neutrophilic dermatosis (Sweet’s syndrome), cutaneous vasculitis.

Muscular system disorders: mild to moderate bone and muscle pain, which is usually transient, joint pain, pain in the neck and chest.

Laboratory findings: hypokalemia, hypophosphatemia, reversible increase in LDH and alkaline phosphatase activity.

Others: fever, asthenia, fatigue, weight loss.

Overdose