Synagis - Instructions, Application For Premature Babies, Price, Reviews

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Synagis

Synagis: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Use in childhood
10. 10. Drug interactions
11. 11. Analogs
12. 12. Terms and conditions of storage
13. 13. Terms of dispensing from pharmacies
14. 14. Reviews
15. 15. Price in pharmacies

Latin name: Synagis

ATX code: J06BB16

Active ingredient: palivizumab (Palivizumab)

Manufacturer: Boehringer Ingelheim Pharma, GmbH und Co. KG (Boehringer Ingelheim Pharma, GmbH & Co. KG) (Germany); Pharmstandard-UfaVITA OJSC (Russia)

Description and photo update: 2019-25-12

Sinagis is a drug used to prevent infections of the lower respiratory tract caused by respiratory syncytial virus (RSV) in young children at high risk of developing RSV disease.

Release form and composition

Synagis is produced in the following dosage forms:

• lyophilisate for the preparation of a solution for intramuscular (i / m) administration: homogeneous, white or almost white (50 or 100 mg in a vial with a capacity of 4 or 10 ml, respectively, sealed with a cork, rolled in a cap with an aluminum lid; in a plastic container, 1 bottle, in a cardboard box 1 plastic container);
• solution for intramuscular injection: colorless or slightly yellowish, transparent or slightly opalescent liquid, with the possible presence of small translucent particles [0.5 or 1 ml each (nominal volume) in a 2R bottle made of colorless transparent glass, with an annular ledge / annular groove on the inner surface of the neck, sealed with a stopper and crimped with an aluminum cap with a polypropylene cap; 1 bottle in a plastic container, 1 plastic container in a cardboard box].

Each pack also contains instructions for using Synagis.

1 bottle with lyophilisate contains:

• active substance: palivizumab - 50 or 100 mg *;
• additional components: histidine, glycine, mannitol.

1 ml of solution contains:

• active substance: palivizumab - 100 mg **;
• additional components: histidine, glycine, water for injection.

Notes

* The vial contains an excess of palivizumab (73 and 122 mg for 50 and 100 mg, respectively) to ensure that the full dose of active ingredient is extracted.

** the bottle contains an excess of the agent for a guaranteed set in the syringe of the appropriate dose of 50 or 100 mg; the volume of the solution is 0.7 ± 0.1 ml (volume 0.5 ml) or 1.2 ml ± 0.1 ml (volume 1 ml).

Pharmacological properties

Pharmacodynamics

Palivizumab is a humanized monoclonal antibody (MCA) of the IgG _1K class that interacts with epitope A (part of the macromolecule) of the fusion protein antigen (protein F) of RSV. The palivizumab molecule consists of 95% human and 5% murine amino acid sequences. Palivizumab has a pronounced neutralizing and inhibitory effect on fusion proteins of RSV subtype A and RSV subtype B.

With a plasma content of palivizumab of about 30 μg / ml in the blood of cotton rats, it showed a decrease in the intensity of RSV replication by about 99%.

Resistance

The active substance interacts with the highly conserved part of the extracellular domain of the mature RSV F protein (antigenic region A or antigenic region II), covering amino acids 262 to 275. A distinctive feature of all RSV mutations that cause resistance to palivizumab was the replacement of amino acids in this region of protein F. No resistance of RSV to drug binding was recorded in the case of non-polymorphic or polymorphic amino acid substitutions in protein F, with the exception of antigenic region A. Of 126 RSV isolates selected from patients who did not respond to drug prophylaxis, at least one of the amino acid was found in 8 substitutions associated with palivizumab resistance (K272E / Q, S275F / L, or N262D), the total frequency of these mutations was 6.3%.

Based on the analysis of clinical data, it was not possible to reveal the relationship between amino acid substitutions in site A and the severity of RSV infection in children who received palivizumab for prophylaxis and who developed RSV infection of the lower respiratory tract. Two cases of mutations associated with drug resistance were identified in an analysis of 254 clinical isolates of RSV in individuals who had not previously received palivizumab. Thus, the frequency of mutations caused by resistance to the active substance was 0.79%.

Immunogenicity

In the course of clinical trials, it was determined that during the initial course of treatment with the drug in 1% of cases, antibodies specific to palivizumab, characterized by a low titer, were formed. During the repeated course of therapy, 55 of 56 children did not detect antibodies, including two cases of their detection during the initial course. The antigenic activity of the drug in children with congenital heart disease has not been studied.

In an additional four studies involving 4337 patients [including children born at 35 weeks gestation and earlier, aged 6 months and under or under 2 years of age with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital heart defects (CHD)], the occurrence of antibodies to palivizumab at different points of observation were recorded in 0-1.5% of children. The relationship between the presence of antibodies to palivizumab and the development of side effects has not been identified.

It can be considered proven that the formation of antibodies to the drug is temporary and has no clinical significance.

Pharmacokinetics

According to the research results, in adult volunteers, the pharmacokinetic profile of palivizumab was similar to the profile of human IgG ₁ antibodies, taking into account the ratio of the volume of distribution (Vd) with an average value of 57 ml / kg, and the half-life (T _1/2) with an average value of 18 days. In studies in children, after one intramuscular injection of the agent at a dose of 15 mg / kg, the average T _1/2 was 20 days.

30 days after the 1st injection, the minimum concentration (C _min) of the active substance in the blood serum was 40 μg / ml, after the 2nd injection - 60 μg / ml, after the 3rd and 4th - 70 μg / ml. The drug was administered intramuscularly once a month.

The safety and pharmacokinetics of Sinagis in the form of a solution and in the form of a lyophilisate when administered intramuscularly at a dose of 15 mg / kg was evaluated in a crossover study in 153 preterm infants under 6 months of age. According to the results of this study, the serum C _{min of} palivizumab in the blood when using both dosage forms of the drug was the same.

Indications for use

Synagis is recommended for the prophylaxis of severe RSV-induced lower respiratory tract infection in children with a high risk of RSV lesions, which include:

• Children under 6 months of age, born at 35 weeks gestation or earlier;
• Children under 2 years of age who have required treatment for BPD in the past 6 months
• children under 2 years of age with hemodynamically significant CHD.

Contraindications

A contraindication to the use of Sinagis is the presence of hypersensitivity to any of the constituents of the drug or to other human MCA.

Sinagis, instructions for use: method and dosage

A solution (including prepared from a lyophilisate) Sinagis is administered i / m.

Injections are made mainly in the outer lateral region of the thigh, since frequent injection into the gluteus muscle exacerbates the risk of damage to the sciatic nerve. It is necessary to inject under standard aseptic conditions, with a dose volume exceeding 1 ml, the solution should be injected into several places.

A single dose of Sinagis is 15 mg / kg. The drug use regimen consists of 5 injections carried out with an interval of 1 month during the seasonal increase in the incidence caused by RSV. The first injection is preferably done before the onset of the RSV season. An increase in the effect and other benefits with longer use of the agent has not been established.

The monthly dose of Sinagis (ml) is calculated by the formula: body weight (kg) × 15 mg / kg ÷ 100 mg / ml.

The effectiveness of the drug when used in doses less than 15 mg / kg or when administered less frequently than once a month during the period of RSV infection has not been determined.

Children who have undergone heart bypass surgery are advised to administer Sinagis at a dose of 15 mg / kg immediately after reaching a stable state to ensure the required level of palivizumab in serum.

In order to reduce the risk of reinfection for children infected with RSV while using Sinagis, it is recommended to continue its monthly administration throughout the RSV incidence season.

When diluting Sinagis in the form of a lyophilisate, only sterile water for injection is required to prepare a solution for intramuscular administration. Do not mix the drug with other drugs or solvents. Since an excess of palivizumab is placed in the lyophilisate vials, this allows you to extract its dose in full (50 or 100 mg).

The procedure for diluting Sinagis lyophilisate:

1. Remove the plastic cap from the bottle, wipe the rubber stopper with a cloth moistened with alcohol.
2. Pierce the bottle cap and slowly inject water for injection along its side wall at a dose of 0.6 ml (for 50 mg) or 1 ml (for 100 mg), avoid the formation of foam.
3. After completing the addition of water, tilt the bottle slightly and gently rotate it for 30 seconds.
4. Do not shake the bottle.
5. Leave the drug at room temperature for at least 20 minutes. The resulting solution should be transparent or slightly opalescent, colorless or pale yellow, with the possible presence of transparent small particles of a protein nature (after preparation according to the above method, the concentration of the solution is 100 mg / ml).
6. Use the drug within 3 hours after preparation, since it does not contain preservatives.
7. Dispose of the solution remaining in the vial.

Synagis in the form of a solution for intramuscular administration does not require dilution. It is forbidden to mix it with the drug in the form of a lyophilisate. Do not shake the bottle and stir the drug in it strongly. Before use, it is necessary to make a visual assessment of the solution, if there are visible particles in it or in case of a color change, Synagis cannot be used.

The rules for the introduction of Sinagis solution:

1. Put a sterile needle on a sterile syringe, observing the rules of asepsis.
2. Remove the plastic cap from the bottle, treat the rubber stopper with a disinfectant.
3. Puncture the stopper, insert the needle into the vial and draw the prescribed volume of solution into the syringe.
4. Inject.
5. Dispose of unused solution.

The solution for i / m administration is produced in vials that contain only 1 dose, the solution does not contain preservatives. After the solution is drawn into the syringe, it is impossible to inject it back into the vial. The contents of one bottle are for single administration only.

Do not reuse needles and syringes to avoid the transmission of any infectious agents.

Side effects

When using Sinagis, the most severe side effects included anaphylaxis and other immediate hypersensitivity reactions; the most common adverse events are rash, injection site reactions and fever. In the course of studies on the use of the drug in children in the control group and in the group using the drug, the side effects were similar. These disorders were transient, and their severity was mild or moderate.

No clinically significant differences were found in relation to adverse events when conducting studies on the prevention of RSV by Synagis in premature infants and infants with BPD, as well as in subgroups of infants, divided by clinical category, age, sex, intrauterine growth, race / ethnicity, country of residence or by the serum level of palivizumab in the blood. There were no differences in the safety profile between children without an acute form of RSV infection and children hospitalized with this diagnosis.

The cancellation of Synagis due to the occurrence of undesirable reactions was extremely rare and amounted to about 0.2%. The number of deaths was approximately equal in the palivizumab and placebo groups, and no association was found with the drug.

Violations noted in clinical studies and in the process of post-registration use of Synagis:

• immune system: with an unknown frequency - anaphylaxis, anaphylactic shock (including fatal cases) *;
• blood and lymphatic system: infrequently - thrombocytopenia *;
• nervous system: infrequently - convulsions *;
• skin and subcutaneous tissue: very often - rash; infrequently - urticaria *;
• respiratory system, chest and mediastinal organs: often - apnea *;
• general disorders and disorders at the place of i / m injection: very often - an increase in body temperature; often - reactions at the injection site.

Note

* adverse reactions recorded during post-registration use (it was not always possible to reliably assess the frequency of development of these effects or to determine the relationship with the effect of palivizumab).

In the process of post-registration studies of Sinagis in premature infants, there was a slight increase in the incidence of asthma, but a causal relationship with therapy was not identified.

Overdose

In three identified cases of Sinagis overdose, when used in doses of 20.25; 21.1 and 22.27 mg / kg, no adverse events were observed. In the course of post-marketing studies, there have been reports of an overdose of palivizumab at a dose of up to 85 mg / kg. The undesirable reactions developing in some cases did not differ from those with the use of the drug at a dose of 15 mg / kg.

If an overdose is suspected, the patient's condition should be monitored for the timely detection of the development of side effects and the immediate implementation of appropriate symptomatic therapy.

special instructions

The introduction of Synagis may be accompanied by the development of immediate allergic reactions, including anaphylactic (cases of anaphylactic shock and anaphylaxis, sometimes fatal) are extremely rare. Therefore, after injection, patients should be under medical supervision for at least 30 minutes, and the room in which the procedure is carried out should be provided with drugs for anti-shock therapy.

Acute, moderate / severe infectious disease or febrile condition may require a delay in the use of Sinagis, unless the physician believes that refusing to administer it poses a greater risk. A mild upper respiratory tract infection or other mild febrile condition cannot be a reason for delaying drug administration.

In the presence of thrombocytopenia or any disorders of the blood coagulation system, Sinagis should be used with caution.

Official studies to study the effectiveness of Sinagis when it was prescribed for the 2nd course of treatment during the next seasonal rise in the incidence of RSV were not carried out. After patients received prophylaxis with the drug in the previous season of RSV, the likelihood of the risk of increased infection in the subsequent season was not completely excluded in the course of relevant studies.

Pediatric use

Synagis is used in pediatrics according to indications, according to the prescribed dosage regimen.

Drug interactions

Studies on the interaction of palivizumab with other drugs / drugs have not yet been conducted, as a result of which there is no data on such an interaction.

In a phase III clinical study, premature infants and infants with BPD were administered palivizumab simultaneously with influenza vaccine, vaccines for the prevention of infectious diseases, glucocorticosteroids (GCS), and bronchodilators. There was no increase in the incidence of adverse events among patients receiving these drugs. Since MCA are specific only for RSV, Synagis is not expected to interfere with the development of immunity during vaccination.

Palivizumab is able to influence the results of immunochemical diagnostic tests for RSV, including some tests based on the detection of antibodies. In addition, the active ingredient inhibits the replication of viruses in cell culture and can change the results of analyzes based on the growth of these infectious agents in cell culture. This interaction can lead to false negative results of diagnostic tests for RSV. Against the background of drug treatment, in order to reliably establish a diagnosis, the results of such tests should be considered taking into account clinical data.

The use of palivizumab does not affect the results of polymerase chain reaction (PCR) tests using reverse transcriptase.

Analogs

There is no information about the analogues of Synagis.

Terms and conditions of storage

Store out of the reach of children at 2–8 ° C, without freezing.

Shelf life: for solution - 3 years, for lyophilisate - 4 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Synagis

The few reviews about Synagis are rather ambiguous. Many parents of premature babies under 6 months of age, children under 2 years of age with BPD and hemodynamically significant CHD, note the positive experience of using the drug for the immunization of RSV infection. Since this disease is extremely dangerous for weakened infants in the first year of life, passive immunoprophylaxis of RSV with the help of Synagis, in their opinion, is vital for young children at high risk.

However, in some cases, parents are unhappy with the fact that Synagis is only valid for 1 month, and when using coursework during the RSV rise season, 5 injections are required at a frequency of 1 time per month. Occasionally, reviews express doubts about the advisability of using the drug, since it has not yet been sufficiently studied and can negatively affect innate immunity. At the same time, there is no certainty that the child will not fall ill with RSV infection in the epidemic season following the treatment. Discontent is also expressed due to the appointment of a mandatory 2nd course of prevention, for which the drug is paid, in contrast to the 1st. Considering the high cost of Synagis, and the fact that the course includes 5 injections, such immunization of a child is too expensive for many.

The price of Synagis in pharmacies

The price of Synagis in the form of a lyophilisate for the preparation of a solution for intramuscular administration can be for 1 bottle: a dose of 50 mg - 50-60 thousand rubles, a dose of 100 mg - 91-100 thousand rubles.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!