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.
Reduced duration of neutropenia and reduced incidence of febrile neutropenia due to myelosuppressive cytotoxic chemotherapy for malignant diseases (except for chronic myeloleukosis and myelodysplastic syndrome).
1 syringe lipegfilgrastim 6 mg
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.
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.
10. The most optimal areas for injection are the anterolateral surface of the thighs and the abdomen, except for the area around the navel. If another person is administering the injection, it is possible to inject into the outer surface of the upper arm.
11. the skin at the injection site should be disinfected with an alcohol-moistened wipe, gather the skin in a fold with your thumb and forefinger without pressure.
12. Insert the needle fully into the base of the skin fold at an angle of at least 45 degrees.
13. Carefully pull on the syringe plunger to make sure that the vessel has not been punctured. If there is blood in the syringe, you must remove the needle and insert it elsewhere.
14. Once the needle is inserted, the solution should be injected under the skin, pressing slowly and evenly on the syringe plunger while continuing to hold the skin in the fold.
15. Continue to apply pressure to the syringe plunger until all of the solution has been injected. Stop squeezing the syringe only after the entire dose of solution has been injected. The needle safety device will activate immediately: the needle is withdrawn from the injection site and is automatically inside the safety device with the syringe. If the syringe does not have a needle safety device, after the entire dose is delivered, the needle must be removed from the injection site and the needle safety cap put on the needle.
16. Place a sterile gauze swab over the injection site for a few seconds.
17. Each syringe should only be used for one injection. The remaining solution in the syringe should not be re-injected.
The disposal of used syringes
The needle safety device prevents accidental needle pricks, so no special disposal precautions are required. Dispose of used syringes according to the instructions of the healthcare provider or physician. Syringes without a needle safety device are placed in a durable container before disposal.
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.
Lung adverse events, particularly interstitial pneumonia, have been reported after use of Loncvex. Patients with a recent history of lung infiltrates or pneumonia have a higher risk of developing these adverse events. Symptoms of lung involvement, such as cough, fever, and dyspnea combined with lung infiltrates confirmed by X-ray examination, accompanied by worsening of lung function and increased neutrophil count may be the first signs of RDSV. In this case, the use of Longvex should be discontinued and appropriate therapy should be carried out.
The development of sickle cell crisis has been associated with the use of G-CSF or its derivatives in patients with sickle cell anemia. Therefore, Longvex should be used with caution in patients with sickle cell anemia, carefully monitoring the relevant clinical and laboratory parameters, taking into account possible spleen enlargement and development of blood vessel thrombosis during therapy with Longvex.
In patients with an increased risk of hypokalemia due to concomitant disease or concomitant use of other drugs that cause hypokalemia, it is recommended to monitor plasma potassium.
The sodium content of 0.6 mL of Longvex solution (one syringe) less than 1 mmol (23 mg) is not clinically relevant.
Because Longvex contains sorbitol, it is not recommended for use in patients with hereditary fructose intolerance, insufficiency of sucrose/isomaltase, and glucose-galactose malabsorption syndrome.
Influence on driving and operating machinery
Loncvex has no significant effect on the ability to drive vehicles and operate machinery. Patients should be warned about the possibility of dizziness. In case of dizziness, patients should refrain from performing the specified activities.
– 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.
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.
No cases of overdose of the drug Lonkveks were noted.
|Conditions of storage|
The drug should be kept out of reach of children, protected from light at 2° to 8°C.
solution for injection
Buy Lonvex 6 mg/0.6 ml, 0.6 ml syringe with delivery to USA, UK, Europe and over 120 other countries.