Pneumosil/pneumosil vaccine for prevention of pneumococcal infection, polysaccharide, conjugated (10-valent, adsorbed)

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT PNEUMOSIL PNEUMOSIL Vaccine for prevention of pneumococcal infection, polysaccharide, conjugate (10-valent, adsorbed)

Composition:

Active substances: Purified pneumococcal polysaccharide antigens, conjugated;

1 dose (0.5 mL) contains:

serotype polysaccharides 1*, 5*, 6A*, 7F*, 9V*, 14*, 19A*, 19F*, 23F* – 2 mcg each;

serotype 6B* polysaccharide – 4 mcg;

*conjugated to carrier protein CRM197 19–48 mcg;

Excipients: aluminium (as aluminium phosphate), L-histidine, succinic acid, sodium chloride, polysorbate-20, water for injections.

Pharmaceutical form. Injection suspension.

Main physicochemical properties: white suspension, which may form a sediment upon storage and does not contain foreign particles/flocs.

Pharmacotherapeutic group. Antiinfectives for systemic use. Bacterial vaccines. Pneumococcal purified polysaccharide conjugated antigen. ATC code J07A L02.

Immunological and biological properties.

Pharmacodynamics.

PNEUMOSIL vaccine contains capsular polysaccharide antigens of Streptococcus pneumoniae serotypes 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F and 23F, individually conjugated to the non-toxic diphtheria toxin protein CRM197. The polysaccharides are chemically activated and then covalently linked to the carrier protein CRM197 to form glycoconjugates.

To produce PNEUMOSIL vaccine, individual conjugates are mixed, followed by addition of polysorbate-20 and aluminium phosphate. The vaccine efficacy is determined by the quantity of polysaccharide antigens and the ratio of polysaccharides to protein in individual glycoconjugates. PNEUMOSIL vaccine meets the requirements of the World Health Organization (WHO), Indian Pharmacopoeia (IP) and British Pharmacopoeia (BP) based on tests conducted according to methods described in WHO TRS 977, IP and BP.

Pharmacokinetics.

Assessment of pharmacokinetic properties is not required for vaccines.

Clinical characteristics.

Indications.

For active immunization of infants and children aged 6 weeks to 2 years to prevent invasive diseases, pneumonia, and acute otitis media caused by Streptococcus pneumoniae serotypes 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, and 23F.

The use of PNEUMOSIL vaccine should be based on official recommendations, taking into account the risk of disease in different age groups as well as epidemiological data in various geographical regions.

For vaccination in Ukraine, vaccination schedules, contraindications, and interactions with other medicinal products should be in accordance with current regulatory documents issued by the Ministry of Health of Ukraine.

Contraindications.

Hypersensitivity to the active substances, excipients, or any component of the vaccine, including diphtheria toxoid.

As with other vaccines, administration of PNEUMOSIL vaccine should be postponed in individuals with acute febrile illnesses. However, the presence of mild minor infections, such as a common cold, is not a reason to delay vaccination.

Interaction with other medicinal products and other forms of interaction.

PNEUMOSIL vaccine can be administered simultaneously with other vaccines, both monovalent and combination vaccines containing antigens against diphtheria, tetanus, pertussis (whole-cell component), Haemophilus influenzae type b (Hib), poliomyelitis (IPV or OPV), rotavirus, yellow fever, hepatitis B, measles, and rubella. Clinical studies have shown that immune responses to the administered vaccines and their safety profiles were not altered when given concomitantly. Studies with other pneumococcal conjugate vaccines administered simultaneously with mumps, varicella, meningococcal infection (serogroups A, C, W, and Y), and rotavirus vaccines have demonstrated that immune responses to pneumococcal conjugate vaccines and co-administered vaccines were not affected. In clinical trials of other pneumococcal conjugate vaccines administered simultaneously with rotavirus vaccine or hepatitis A vaccine, but injected at different body sites or by different routes, no changes in safety profile for infants were observed.

Different vaccines should always be administered at different injection sites.

Clinical studies with PNEUMOSIL vaccine were conducted in India and The Gambia involving infants and young children. In a phase 1/2 clinical study conducted in The Gambia, no impact of PNEUMOSIL vaccine on immune response to any component of pentavalent vaccine was observed when administered simultaneously.

In a phase 3 clinical study in The Gambia, when PNEUMOSIL vaccine was administered concomitantly with EPI vaccines during the 3-dose primary vaccination schedule (at ages 6, 10, and 14 weeks), namely pentavalent vaccine (with whole-cell pertussis component) (DTwP-HepB-Hib), poliomyelitis vaccine (OPV, IPV), and oral rotavirus vaccine, non-inferior immune responses to all EPI vaccines were demonstrated.

The booster dose of PNEUMOSIL vaccine was administered concomitantly with standard EPI vaccines in The Gambia (measles-rubella vaccine and yellow fever virus vaccine). Administration of the booster dose did not affect the immune responses to the co-administered EPI vaccines. A high serological response rate to yellow fever virus vaccine in the PNEUMOSIL-vaccinated group indicates that PNEUMOSIL vaccine does not interfere with the immune response to yellow fever virus vaccine. There are no known published data on simultaneous administration of another pneumococcal conjugate vaccine with yellow fever virus vaccine.

Special precautions for use.

It is recommended to collect a history of any symptoms and adverse reactions following previous vaccinations prior to vaccination.

PNEUMOSIL vaccine must not be administered intravascularly and must not be injected into the gluteal area.

PNEUMOSIL vaccine must not be administered intravenously, subcutaneously, or intradermally, as the safety and immunogenicity of these routes of administration have not been evaluated.

As with all injectable vaccines, appropriate medical treatment and supervision must always be readily available in case of rare anaphylactic reactions following vaccine administration. Therefore, patients should be kept under medical observation for at least 30 minutes after vaccination.

As with the use of all injectable vaccines, appropriate medical treatment and patient monitoring must always be available in the event of a rare anaphylactic reaction following vaccine administration.

IMMEDIATE ADMINISTRATION OF EPINEPHRINE (1:1000) IN CASE OF ACUTE ANAPHYLACTIC REACTION TO ANY VACCINE COMPONENT. In severe anaphylaxis, the initial dose of epinephrine should be administered intramuscularly or subcutaneously at a dose of 0.1–0.5 mg (0.1–0.5 mL of 1:1000 injection). The single dose should not exceed 1 mg (1 mL). For children, including infants, the recommended dose of epinephrine is 0.01 mg/kg (0.01 mL/kg of 1:1000 injection). The single dose for children should not exceed 0.5 mg (0.5 mL). The cornerstone of treatment for severe anaphylaxis is the immediate administration of epinephrine, which can be life-saving. Epinephrine should be administered at the first sign or suspicion of anaphylaxis.

As with other vaccines, administration of PNEUMOSIL should be postponed in individuals with acute febrile illnesses. However, the presence of mild, minor infections, such as a common cold, is not a reason to delay vaccination.

As with intramuscular administration of other injectable vaccines, PNEUMOSIL should be administered with caution to individuals with thrombocytopenia or coagulation disorders, as well as to those receiving anticoagulant therapy.

PNEUMOSIL is not indicated for the treatment of active infection.

As with any other vaccine, protective immune response may not be achieved in vaccinated individuals.

Syncope (fainting) may occur during or shortly after any injectable vaccination as a psychogenic response to needle injection. Vaccination should be performed only while the recipient is in a sitting or lying position, and the individual should remain in that position (sitting or lying) for 15 minutes after vaccination to prevent the risk of injury.

When administering primary immunization to very preterm infants (≤28 weeks of gestation), the potential risk of apnea and the need for respiratory monitoring for 48–72 hours after vaccination should be considered, especially if the infant has a history of respiratory immaturity. Since the benefit of vaccination in this group of infants is high, vaccination should not be refused or delayed.

Safety and immunogenicity data for PNEUMOSIL vaccine in children at high risk of invasive pneumococcal disease (e.g., children with congenital or acquired asplenia, HIV infection, malignancies, nephrotic syndrome) are not available. In such children, immune response to active immunization may be reduced due to impaired immune reactivity. Limited data have shown that other pneumococcal conjugate vaccines elicit immune responses in children with HIV, sickle cell anemia, and preterm infants, with a safety profile similar to that in low-risk groups. The use of PNEUMOSIL vaccine in high-risk patients should be considered on an individual basis.

Use during pregnancy or breastfeeding.

There are no data on the use of PNEUMOSIL vaccine during pregnancy or breastfeeding.

Ability to influence the speed of reactions while driving or operating machinery.

Not applicable to this group.

Administration and Dosage

The vaccine should be administered intramuscularly.

The preferred site of injection is the anterolateral aspect of the thigh for infants or the deltoid muscle of the upper arm for older children.

One dose of the vaccine is 0.5 mL.

Before administration, PNEUMOSIL vaccine should be:

• visually inspected for any foreign particles and/or changes in physical appearance. If any foreign particulate matter or alteration in appearance is observed, the vial should be discarded;
• shaken to homogenize the suspension (to obtain a uniform white, cloudy suspension), as a white sediment with a clear supernatant liquid may form during storage.

If the vaccine has been frozen, it must be discarded.

VIAL VACCINE MONITORING (VVM)

Vial Vaccine Monitors (VVMs) are located on the caps of PNEUMOSIL vaccine vials manufactured by Serum Institute of India Pvt. Ltd., India. This temperature-sensitive time indicator shows the cumulative heat exposure the vaccine vial has experienced. The VVM alerts the end-user to potential degradation of vaccine quality due to heat exposure.

Interpretation of the VVM is simple: the key factor is the color of the inner square, which changes over time. If the color of the square is lighter than the surrounding circle, the vaccine may be used. If the color of the square is the same as or darker than the outer circle, the vaccine must not be used and should be discarded.

Immunization Schedule

The immunization schedule with PNEUMOSIL should follow official recommendations.

Primary vaccination schedule for infants consists of 3 doses administered at the ages of 6, 10, and 14 weeks, or at 2, 3, and 4 months, or at 2, 4, and 6 months, followed by a booster dose at 9–10 months or 12–15 months, or without a booster dose, depending on the recommended schedule.

The minimum interval between doses is 4 weeks. The booster dose should be administered at least 6 months after the last dose of the primary vaccination series.

Table 1

Vaccination schedule for infants and children aged 6 weeks to 6 months of age

a Dose 1 can be administered at the age of 6 weeks or at the age of 2 months.

b The recommended interval between doses is 4–8 weeks.

c The booster (fourth) dose is recommended at least 6 months after the last dose of the primary vaccination series and can be administered from the age of 9 months onwards (preferably at 12–15 months of age).

Vaccination schedule for children aged 7 months to 2 years who have not previously been vaccinated with PNEUMOSIL.

Table 2

Vaccination schedule for unvaccinated children aged 7 months to 2 years

Children.

PNEUMOSIL is indicated for use in children from 6 weeks of age up to 2 years of age (see sections "Indications", "Dosage and Administration"). Safety and efficacy in children under 6 weeks of age have not been established.

Overdose.

No cases of overdose have been reported.

Side effects

The safety of PNEUMOSIL vaccine was based on clinical studies involving 1,828 healthy children who received 5,416 doses for primary vaccination. In addition, 428 children received a booster dose of PNEUMOSIL vaccine after completing the primary vaccination series. In all studies, PNEUMOSIL vaccine was administered when necessary simultaneously with other vaccines recommended for children.

Safety was also evaluated in 57 children of the second year of life who had not been previously vaccinated; all children received two doses of the vaccine.

PNEUMOSIL vaccine was also used for booster vaccination in 56 children who had received another pneumococcal conjugate vaccine during primary vaccination.

The majority of observed reactions following vaccination were of mild or moderate severity and transient in nature.

In most studies, the most commonly reported adverse reactions in infants after primary vaccination were injection site pain, fever, and irritability, reported in approximately 49%, 52%, and 32% of vaccinated infants, respectively. No increase in frequency or severity was observed after administration of subsequent doses of the primary series. After administration of the booster dose, injection site pain was the most commonly reported adverse reaction, occurring in approximately 8% of vaccinated individuals.

In a Phase 3 clinical study conducted in India, injection site pain, fever, and irritability were similarly observed in infants as the most common adverse reactions during primary vaccination, with no change in frequency or severity after subsequent doses of the primary series. Most observed adverse reactions were mild to moderate in intensity and resolved completely.

Reactions at the injection site and systemic reactions after toddler vaccination or booster vaccination in the second year of life were similar to those observed after primary vaccination.

In comparative studies, the frequency and severity of local and general adverse reactions reported within 7 days after vaccination were similar to those observed after vaccination with other pneumococcal conjugate vaccines.

Adverse reactions (i.e., events considered related to vaccination) were classified by frequency across all age groups. Frequency is defined according to the following categories:

Very common: ≥ 1/10
Common: ≥ 1/100 and < 1/10
Uncommon: ≥ 1/1,000 and < 1/100
Rare: ≥ 1/10,000 and < 1/1,000
Very rare: < 1/10,000
Not known: cannot be estimated from available data.

The list of adverse reactions is presented in Table 3.

Table 3

Shelf life.

36 months.

Storage conditions.

Store at a temperature of 2 to 8 °C.

DO NOT FREEZE.

Keep out of reach of children.

Incompatibility.

PNEUMOSIL vaccine must not be mixed with other vaccines/medicinal products in the same syringe.

Packaging.

1 dose (0.5 mL) of injection suspension in a vial (2 mL capacity); 50 vials per cardboard box.

1 dose (0.5 mL) of injection suspension in a vial (4 mL capacity); 50 vials per cardboard box.

Prescription status. Prescription only.

Manufacturer. Serum Institute of India Pvt. Ltd., India

Serum Institute of India Pvt. Ltd., India

Manufacturer's address and site of operations.

212/2, Hadapsar, Pune – 411028, India

212/2, Hadapsar, Pune – 411028, India

Marketing Authorization Holder: LLC "Pharma Life", Ukraine.

Address of the Marketing Authorization Holder.

2 D. Apostola Street, Lviv, Ukraine, 79040; tel. (032) 297-16-88.