Universal reference book for medicines
Product name: LONQUEX (LONQUEX)

Active substance: lipegfilgrastim

Type: Leukopoiesis stimulant

Manufacturer: Teva Pharmaceutical Industries (Israel) manufactured by IDT Biologika (Germany)
Composition, form of production and packaging

The solution for the sc administration is clear, colorless.

1 syringe

lipagfilgrastim 6 mg

Excipients: acetic acid ice - 0.36 mg, polysorbate 20 - 0.02 mg, sorbitol - 30 mg, sodium hydroxide 1M - to pH 5.0, water d / u - up to 0.6 ml.

0.6 ml - disposable syringes of colorless glass type I (1) - packings, cellular contour plastic (1) - packs cardboard.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2017.

PHARMACHOLOGIC EFFECT

Leukopoiesis stimulant.
Lipegfilgrastim is a covalent filgrastim conjugate bound to one molecule of methoxypolyethylene glycol through 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. Lipagfilgrastim is a prolonged form of filgrastim, due to reduced renal clearance. Lipagfilgrastim binds to the G-CSF receptor like filgrastim and pegfilgrastim.
Lipefilgrastim significantly increases the number of neutrophils in the peripheral blood in the first 24 hours after administration, causing a small increase in the number of monocytes and / or lymphocytes.
Due to the presence of a part of G-CSF in the lipepigligrastim molecule, this growth factor has the expected activity: it stimulates the proliferation of hematopoietic progenitor cells, their differentiation into mature cells and the release into the peripheral blood. G-CSF is a specific factor not only for neutrophils, it also has the effect on other progenitor cells that give from one to several differentiation lines, and to polypotent hematopoietic stem cells. In addition, G-CSF increases the phagocytic and antibacterial activity of neutrophils, enhancing the 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 in the treatment with lipegfylgrastim 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 lipegglilgrastim.
The effective dose is 6 mg lipagfilgrastima.
PHARMACOKINETICS

In healthy volunteers, after a single injection of lipagglilgrastim in different doses of C max in the blood plasma was achieved on average 10-30 hours, with the final T1/2 on the average being 32-49 hours.

In patients with breast cancer who received chemotherapy with a combination of doxorubicin and docetaxel, after a single injection of lipagglilgrastim at doses of 3, 4.5 or 6 mg, the first cycle of chemotherapy with C max lipgliglgrastim in the blood was achieved on average 47 hours, with the final T 1 / 2 on the average was 23-32 hours. After a single injection of lipagglilgrastim in doses of 3, 4.5 or 6 mg in the fourth cycle of chemotherapy C max in blood plasma was achieved on average 11 hours, while the final T 1/2 on average was 26-41 hours.

In patients with non-small cell lung cancer receiving chemotherapy with a combination of cisplatin and etoposide, the mean C max of lipagglilgrastima in the blood, equal to 317 ng / ml, was achieved on average 24 hours, and the mean final T 1/2 was approximately 28 hours after a single SC injections of lipagglilgrastim at a dose of 6 mg during the first cycle of chemotherapy.
After a single injection of lipagglilgrastim at a dose of 6 mg during the fourth cycle, the average C max in the blood was 149 ng / ml and was achieved on average 8 hours and the mean T 1/2 was approximately 34 hours.
The elimination of lipagglilgrastim decreases with an increase in its dose, which is probably associated with a decrease in the clearance of lipegfylgrastim mediated by neutrophils.
The clearance decreases with increasing dose of lipagfilgrastim. In accordance with the self-regulating mechanism of clearance, the concentration in the blood plasma of lipegilgrastim slowly decreases during the transient decrease in the number of neutrophils associated with chemotherapy and quickly - after the start of recovery of the number of neutrophils.
Pharmacokinetics in specific patient groups

Considering the effect of neutrophils on clearance, it is obvious that the pharmacokinetic indices of lipagfilgrastim do not change with renal or hepatic insufficiency.

Limited data suggest that the pharmacokinetics of lipagglilgrastim in elderly patients (65-74 years) is similar to that characteristic of young patients.
There is no pharmacokinetic data for lipagglilgrastim for patients over the age of 75 years.
The tendency to reduce the effects of lipagglilgrastim was observed in patients with an increase in body weight.
This can lead to a decrease in pharmacodynamic responses in patients with a large body weight (> 95 kg). Based on the available data, these patients can not be excluded from the subsequent reduction in efficacy.
INDICATIONS

- reduction in the duration of neutropenia and a decrease in the incidence of febrile neutropenia due to myelosuppressive cytotoxic chemotherapy for malignant diseases (with the exception of chronic myelogenous leukemia and myelodysplastic syndrome).

DOSING MODE

For adults, the drug is given as a single 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 the efficacy and safety of Lonquex in patients of different ages in clinical trials.
In this regard, there is no need for dose adjustment in elderly patients .
In patients with renal / hepatic insufficiency, dose adjustment is not required.

The safety and efficacy of Lonquex in children and adolescents under the age of 18 years have not been established (data not available).

Information on the technique of injection injections

Before the injection, special patient training is necessary.

1. You should get one blister from the refrigerator with a syringe and draw a syringe with the drug.

2. It is necessary to check the expiration date on the syringe label.
Do not use the drug if the last day of the month has expired.
3. It is necessary to check the appearance of the injection solution.
The solution should be clear, colorless and without visible solids. Do not use the drug if the solution is cloudy or contains visible particles.
4. You should hold the syringe at room temperature for 30 minutes or warm it in your hand for a few minutes.
Do not heat the drug in other ways (for example, in a microwave oven or in hot water).
5. Do not remove the protective cap from the needle until the preparation for the injection is complete.

6. Wash hands thoroughly.

7. You should choose a well-lit convenient place.
Arrange everything necessary for the injection (syringe with the drug, a napkin moistened with alcohol, a sterile gauze swab) in such a way that it is easy to take advantage of it.
8. Carefully, without rotating, pulling in a straight line, without touching the needle, remove the protective cap from the needle.

9. If there are small air bubbles in the syringe, gently tap the syringe with your finger, holding it with the needle up, so that the air bubbles gather at the top of the syringe, and slowly, with gentle pressure on the piston, remove all air from the syringe.
The syringe with the drug should not be shaken. Strong shaking can lead to the destruction of lipagfilgrastim and its inactivation.
10. The most optimal areas for injections are anterolateral hip surface and abdomen, except for the area around the navel.
If the injection is performed by another person, you can inject into the outer surface of the shoulder.
11. You should disinfect the skin at the injection site with an alcohol-soaked wipe, fold the skin into the fold with a thumb and index finger without pressure.

12. Fully insert the needle into the base of the skin fold at an angle of at least 45 degrees.

13. Gently pull the plunger of the syringe to make sure that there is no puncture of the vessel.
If blood appears in the syringe, it is necessary to remove the needle and insert it into another place.
14. After insertion of the needle, the solution should be administered under the skin, slowly and evenly pressing the syringe onto the plunger, while continuing to hold the skin in the fold.

15. Continue pressing on the syringe plunger until the entire solution is injected.
Stop pressing on the plunger of the syringe is possible only after the introduction of the entire dose of the drug. Immediately the needle safety device will work: the needle is removed from the injection site and, together with the syringe, automatically appears inside the protective device. If the syringe does not have a needle safety device, after injecting the entire dose of the drug, remove the needle from the injection site and put a protective cap on the needle.
16. Apply a sterile gauze pad to the injection site for a few seconds.

17. Each syringe should be used for only one injection.
Do not reinsert the solution remaining in the syringe.
Disposal of used syringes

The needle safety device prevents accidental needle pricks, so special precautions for disposal are not required.
Dispose of used syringes in accordance with the instructions of the medical institution or doctor. Syringes without safety device needles before disposal are placed in a container of durable material.
SIDE EFFECT

On the part of the hematopoiesis system: thrombocytopenia, leukocytosis, splenomegaly, symptoms of splenic rupture (pain in the upper left quadrant of the abdomen, pain in the upper part of the left shoulder), rupture of the spleen, in some cases with fatal outcome.

On the part of the immune system: hypersensitivity reactions, allergic skin reactions, urticaria, and Quincke's edema.

From the nervous system: headache, dizziness.

From the cardiovascular system: tachycardia.

On the part of the respiratory system: cough, shortness of breath, interstitial pneumonia, pulmonary edema, pulmonary infiltrates, pulmonary fibrosis, respiratory failure, adult respiratory distress syndrome (ARDS).

From the digestive system: nausea, pain in epigastrium.

From the skin and subcutaneous tissues: erythema, skin rash, itching, reaction at the injection site (pain, hyperemia, densification), alopecia, acute febrile neutrophilic dermatosis (Sweet syndrome), cutaneous vasculitis.

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

On the part of laboratory indicators: hypokalemia, hypophosphatemia, reversible increase in LDH activity, APF.

Other: fever, asthenia, fatigue, weight loss.

CONTRAINDICATIONS

- children and adolescence under 18;

- Hypersensitivity to lipagfilgrastimu (including colony stimulating factors: filgrastimu, pegfilgrastimu, Escherichia coli) or other components of the drug.

With caution should prescribe the drug for malignant and premalignant diseases of the myeloid nature (including acute myelogenous leukemia de novo and secondary);
sickle-cell anemia; application in combination with high-dosage chemotherapy; intolerance to fructose, insufficiency of sugarase / isomaltase, glucose-galactose malabsorption syndrome.
PREGNANCY AND LACTATION

The use of Lonquex during pregnancy is not recommended.
Pre-clinical studies have not revealed a toxic effect on reproductive function. Experience with pregnant women is limited.
It is not known whether lipagfilgrastim is excreted in breast milk, so it is not possible to exclude the possibility of side effects in children during breastfeeding.
The decision to stop breastfeeding or stop / stop treatment with Lonquex should be taken, given the expected benefit of breastfeeding for the baby and treatment with Lonquex for the mother.
APPLICATION FOR FUNCTIONS OF THE LIVER

Patients with renal insufficiency
correction of the dose is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Patients with hepatic insufficiency do not need a dose adjustment.

APPLICATION FOR CHILDREN

The drug is contraindicated for use in children and adolescents under 18 years of age: safety and efficacy have not been established (data not available).

APPLICATION IN ELDERLY PATIENTS

There were no significant differences in the efficacy and safety of Lonquex in patients of different ages in clinical trials.
In this regard, there is no need for dose adjustment in elderly patients.
SPECIAL INSTRUCTIONS

Treatment with Lonquex is done only under the supervision of a doctor who has experience with colony-stimulating factors, provided that the necessary diagnostic capabilities are available.

The safety and efficacy of Lonquex in patients receiving high-dose chemotherapy have not been studied.
Lonquex should not be used to increase the dose of cytotoxic chemotherapy above the dose set by the regimen.
Patients sensitive to G-CSF or its derivatives are also at a risk of developing hypersensitivity reactions to lipagglilgrastim in connection with possible cross-over-hypersensitivity.
These patients should not use lipegglilgrastim because of the risk of developing a cross-reaction.
Most drugs of biological origin can trigger a response in the form of the appearance of a certain level of anti-drug antibodies.
Such a humoral immune response may in some cases lead to the development of undesirable effects or loss of efficacy. If the patient does not respond to treatment, a further examination should be carried out.
With the development of a severe allergic reaction, appropriate therapy should be followed, followed by careful monitoring of the patient for several days.

Treatment with Lonquex does not prevent the development of thrombocytopenia and anemia caused by myelosuppressive chemotherapy.
The drug Lonquex can also cause thrombocytopenia, therefore it is recommended to regularly determine the number of platelets and the hematocrit. One-component or combined chemotherapeutic regimens known to be capable of causing severe thrombocytopenia should be used with caution.
Possible development of leukocytosis.
No adverse events directly related to leukocytosis have been reported. The increase in the number of leukocytes in the blood corresponds to the pharmacodynamic effects of lipagglilgrastim. Given the clinical effects of lipagglilgrastim and the possible risk of leukocytosis, lipagfilgrastim should be monitored regularly during the treatment with the number of leukocytes. If the number of white blood cells after the estimated minimum level exceeds 50 × 10 9 / L, treatment with lipagfilgrastim should be stopped immediately.
The increased hematopoietic activity of bone marrow in response to therapy with growth factors leads to transient positive changes in the visualization of bones, which should be taken into account when interpreting the results of radionuclide scintigraphy.

With myelodysplastic syndrome and chronic myelogenous leukemia, the efficacy and safety of Lonquex is not established.
Patients with the aforementioned diseases, as well as with premalignant lesions of the myeloid germ of hematopoiesis, use of Lonquex is not indicated. Particular attention should be paid to a differential diagnosis between the blast crisis of chronic myelogenous leukemia and acute myelogenous leukemia.
When G-CSF was used, cases of splenomegaly, which proceeded asymptomatically, and spleen rupture were recorded, incl.
with a lethal outcome. When applying the drug Lonquex should monitor the size of the spleen (clinical examination, ultrasound). Spleen rupture should be suspected when there is pain in the upper left quadrant of the abdomen and pain in the upper part of the left shoulder.
After applying the drug Lonquex, adverse effects from the lungs, in particular, on interstitial pneumonia, have been reported.
Patients with recent pulmonary infiltrates or pneumonia have a higher risk of developing such undesirable events. Symptoms of lung damage such as cough, fever and shortness of breath, combined with pulmonary infiltrates confirmed by radiographic examination, accompanied by impairment of lung function and an increase in the number of neutrophils, can serve as the first signs of ARDS. In this case, stop using Lonquex and carry out appropriate therapy.
The development of sickle cell crises was associated with the use of G-CSF or its derivatives in patients with sickle cell anemia.
Therefore, the drug Lonkveks need to be used with caution in patients with sickle cell disease, to carefully monitor appropriate clinical and laboratory parameters, taking into account the possible enlargement of the spleen and blood vessel development in the treatment of thrombosis drug Lonkveks.
In patients with an increased risk of hypokalemia due to concomitant disease or concurrent use of other drugs that cause hypokalemia, it is recommended to control the content of potassium in the blood plasma.
The sodium content of 0.6 ml of a solution Lonkveks drug (one syringe) is less than 1 mmol (23 mg) has no clinical significance.
Due to the fact that the drug enters Lonkveks sorbitol is not recommended to use this drug in patients with hereditary fructose intolerance, failure sucrase / isomaltase, malabsorption syndrome glucose-galactose.
Impact on the ability to drive vehicles and manage mechanisms

Lonkveks drug has no significant effect on the ability to drive vehicles and use machines. Patients should be warned of the possibility of dizziness. If dizziness should refrain from carrying out these activities.
OVERDOSE

Lonkveks overdoses of the drug were observed.
DRUG INTERACTION

Studies on the interaction Lonkveks preparation with other drugs have not been conducted.
Due to possible high sensitivity rapidly dividing myeloid cells to cytotoxic therapy Lonkveks drug should be administered within 24 hours after cytotoxic chemotherapy cycle.
Evaluation of the simultaneous application of the drug and Lonkveks any chemotherapeutic agent in patients has not been evaluated. In preclinical studies, it was shown that the simultaneous use of G-CSF and fluorouracil or other antimetabolite antineoplastic drugs group enhances myelosuppression.
Evaluation of safety and efficacy Lonkveks drug in patients receiving chemotherapeutic drugs whose use is accompanied by a delayed myelosuppression (e.g., nitrosoureas), was performed.
The possibility of interaction with lithium, which also increases the number of neutrophils in the peripheral blood is not specifically investigated. There is no evidence that this interaction may be dangerous.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

LQX-RU-00061
TERMS AND CONDITIONS OF STORAGE

The drug should be kept out of the reach of children, protected from light at a temperature of from 2 ° to 8 ° C.
Do not freeze. Shelf life - 2 years.
Alphabetical index of medicines:
A  B  V  G  D  E  J
Z  I  Y  K  L  M  N
O  P  R  S  T  U  F
H  C  CH  SH  E  U  Y
Privacy policy:
Copyright 2009 - 2017. Universal reference book of medicines. All rights reserved.
When using site materials, an active hyperlink is required!