Lonquex - instructions for use, dose, side effects, contraindications

Active substanceLipagfilgrastimLipagfilgrastim

Similar drugsTo uncover

solution PC

Teva Pharmaceutical Enterprises Co., Ltd. Israel

Dosage form: & nbsphypodermic solution

Composition:1 syringe contains active substance lipagfilgrastim (in terms of protein) 6.0 mg;

Excipients: acetic acid ice 0.36 mg, polysorbate-20 0.02 mg, sorbitol 30.0 mg, sodium hydroxide (1 M) to pH 5.0, water for injection up to 0.6 ml.

Description:Transparent colorless liquid.

Pharmacotherapeutic group:Leukopoiesis stimulant

ATX: & nbsp

L.03.A.A Colony-stimulating factors

L.03.A.A.14 Lipagfilgrastim

Pharmacodynamics:

Lipagfilgrastim 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 - 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 lipegfilgrastimom and pegfilgrastimom in general is similar,the incidence of febrile neutropenia was significantly higher in the placebo group compared to the group of patients treated with lipegglilgrastim, the effective dose was 6 mg lipagglilgrastim.

Pharmacokinetics:

In healthy volunteers, after a single subcutaneous (sc) injection of different doses, the maximum concentration (Cmah) lipagfilgrastima in blood plasma was achieved on the average after 10-30 hours, with the final half-life (T1 / 2) on the average being 32-49 hours.

Special patient groups

In patients with breast cancer who received chemotherapy with a combination of doxorubicin and docetaxel, after a single injection of 3, 4, 5 or 6 mg of lipagglilgrastim in the first cycle of chemotherapy Cmlipagfilgrastima in the blood was achieved on average 47 hours, with the final T1 / 2 averaged 23-32 hours. After a single injection of 3, 4.5 or 6 mg lipagfilgrastima in the fourth cycle of chemotherapy Cmlipagfilgrastima in blood plasma was achieved on average 11 hours, while the final T1 / 2 averaged 26-41 hours.

In patients with non-small cell lung cancer receiving chemotherapy with a combination of cisplatin and etoposide, the mean Cmlipigfilgrastima in blood, equal to 317 ng / ml, was achieved on average after 24 hours, and the mean final T1 / 2 was approximately 28 hours after a single injection of 6 mg lipagglilgrastim during the first cycle of chemotherapy. After a single injection of 6 mg lipagfilgrastima during the fourth cycle, the average Cmlipagglilgrastima in blood 149 ng / ml was achieved on average 8 hours, and the average T1 / 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.

Patients with renal or hepatic insufficiency

Given the effect of neutrophils on clearance, it is clear that the pharmacokinetic indices of lipagglilgrastim do not change with renal or hepatic insufficiency.

Elderly patients

Limited data suggest that the pharmacokinetics of lipagglilgrastim in elderly patients (65-74 g) is similar to that characteristic of young patients. There is no pharmacokinetic data for lipagglilgrastim for patients over the age of 75 years.

Patients with excessive body weight

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 of 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).

Contraindications:

Hypersensitivity to lipegfilgrastimu (including colony-stimulating factors: filgrastimu, pegfilgrastimu; Escherichia coli) or other components of the drug; children's age till 18 years.

Carefully:

Malignant and premalignant diseases of myeloid nature (including acute myelogenous leukemia de novo and secondary); sickle-cell anemia; use 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 with breast milk. Therefore, it is impossible 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.

Data on the effect of Lonquex on fertility are not available.

Dosing and Administration:

Adults - in the form of a single sc injection in a dose of 6 mg (one syringe) 24 hours after the end of each cycle of cytotoxic chemotherapy.

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.

Patients with renal / hepatic insufficiency

Correction of the dose is not required.

Childhood

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

Information for the patient on the technique of injection of injections

Before the injection, it is necessary to undergo special training from the attending physician or nurse. If you are not sure that you can inject yourself, or if you have questions, ask your doctor or nurse for help.

Self-administration of the drug

1. Remove from the refrigerator one blister with a syringe and remove the syringe from the drug.

2. Be sure to check the expiry date on the syringe label. Do not use if the last day of the specified month has expired.

3. 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. To feel more comfortable during the injection, 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 your hands thoroughly.

7. Choose a well-lit place, convenient for you. Arrange everything necessary for injection (a syringe with a 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, as shown in Figures 1 and 2.

9. If you have 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. Now you can use a syringe for injecting.

11. The most optimal areas for injections are the anterolateral hip surface and abdomen, except for the area around the navel (see Figure 3). If the injection is performed by another person, you can inject into the outer surface of the shoulder (see Figure 4).

12. Disinfect the skin at the injection site with an alcohol-moistened napkin, collect the skin into the fold with a thumb and index finger without pressure (see Figure 5).

13. Fully insert the needle into the base of the skin fold at an angle of at least 45 degrees (see Figure 6).

14. Gently pull the plunger of the syringe to make sure that there is no puncture of the vessel. If blood appears in the syringe, remove the needle and enter it into another place.

15. After insertion of the needle, start injecting the solution under the skin, slowly and evenly pressing the syringe onto the piston, while continuing to hold the skin in the fold (see Figure 7).

16. Continue pressing the plunger of the syringe until all of the solution has been 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 is triggered: the needle is removed from the injection site and together with a syringe is automatically inside the protective device (see Figure 8..). If the syringe has a needle safety device after administration of the entire dose withdraw the needle from the injection site and attach to the needle protective cap.

17. For a few seconds, attach a sterile gauze swab to the injection site.

18. Use each syringe for only one injection. Do not reinsert the solution remaining in the syringe.

If you encounter any problems, please contact us for help or advice from a doctor or nurse.

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 effects:

On the part of the blood and lymphatic system: thrombocytopenia, leukocytosis, splenomegaly, symptoms of rupture of the spleen - 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.

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

From the nervous system: headache, dizziness.

Co cardiovascular system: tachycardia.

From the respiratory system, chest and mediastinum: 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, denseness), alopecia, acute febrile neutrophilic dermatosis (Sweet syndrome), cutaneous vasculitis.

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

From the laboratory indicators: hypokalemia, hypophosphatemia, reversible increase in lactate dehydrogenase activity, alkaline phosphatase.

Other: fever, asthenia, fatigue, weight loss.

Overdose:

There were no cases of drug overdose Lonquex.

Interaction:

Studies on the interaction of Lonquex with other drugs have not been conducted.

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

Evaluation of simultaneous application of Lonquex and some chemotherapy in patients was not performed. In preclinical studies, it was shown that the simultaneous use of G-CSF and fluorouracil or other antitumor drugs of the antimetabolite group enhances myelosuppression.

An evaluation of the safety and efficacy of Lonquex in patients receiving chemotherapeutic drugs whose use is associated with delayed myelosuppression (for example, nitrosourea derivatives) has not been evaluated.The possibility of interaction with lithium, which also contributes to an increase in the number of neutrophils in peripheral blood, has not been specifically investigated. There is no evidence that this interaction can be dangerous.

Special instructions:

Treatment with Lonquex should be 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 lipagfilgrastim in connection with 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, he should undergo further examination.

With the development of a severe allergic reaction, appropriate therapy should be conducted 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 x 109 / L, treatment with lipagfilgrastim should be immediately stopped.

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, asymptomatic, and splitting of the spleen, including those with a fatal outcome, were reported. 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 may have a higher risk of developing such adverse 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 the sickle-cell crisis was associated with the use of G-CSF or its derivatives in patients with sickle-cell anemia. Therefore, the Lonquex drug should be used with caution in patients with sickle cell disease, carefully monitor the relevant clinical and laboratory indicators, taking into account the possible increase in the spleen and the development of blood vessel thrombosis during therapy with Lonquex.

In patients with an increased risk of hypokalemia due to concomitant disease or simultaneous use of other drugs that cause hypokalemia, it is recommended to monitor the potassium content in the blood plasma.

The sodium content of 0.6 ml of the Lonquex solution (one syringe) of less than 1 mmol (23 mg) is not clinically relevant.

Due to the fact that the composition of the drug Lonquex included sorbitol, this drug is not recommended in patients with hereditary fructose intolerance, sugarase / isomaltase insufficiency, glucose-galactose malabsorption syndrome. The drug Lonquex can be stored at a temperature of 15-25 ° C not more than 72 hours. Do not use the drug stored at a temperature of 15-25 ° C for more than 72 hours.

Effect on the ability to drive transp. cf. and fur:The drug Lonquex does not have a significant effect on the ability to drive vehicles and work with mechanisms. Patients should be warned about the possibility of developing dizziness. When dizziness occurs, you should refrain from performing these activities.

Form release / dosage:

A solution for subcutaneous administration of 6 mg / 0.6 ml.

Packaging:

For 0.6 ml of the drug in a disposable syringe made of colorless glass type I (Hebrew Pharm.) With a plastic piston and a rubber piston seal, with a fixed needle protected by a double cap consisting of an internal elastomeric and an outer hard plastic part. The syringe can additionally be provided with a needle safety device. 1 syringe in plastic contour pack; 1 contour pack together with instructions for use in a cardboard pack equipped with a first-opening control system (a transparent film sticker is provided on each of the valves).

Storage conditions:

Store at a temperature of 2 to 8 ° C in a dark place. Do not freeze. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002515

Date of registration:26.06.2014 / 11.11.2016

Expiration Date:26.06.2019

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

IDT BIOLOGIKA, GmbH Germany

Representation: & nbspTeva Teva Israel