Instructions Pentaxim powder vial suspension for injection syringe 0.5ml No. 1
Composition
active ingredients:
Diphtheria, tetanus, pertussis (acellular, component), poliomyelitis (inactivated) vaccine (adsorbed) and Haemophilus influenzae type b conjugate vaccine
1 immunizing dose of vaccine (0.5 ml) after dilution contains:
Active ingredients:
diphtheria toxoid(1) ≥ 30 IU(2) (3)
tetanus toxoid(1) ≥ 40 IU(3) (4)
Bordetella pertussis antigens:
pertussis toxoid(1) 25 mcg
filamentous hemagglutinin(1) 25 mcg
inactivated poliovirus(5):
type 1 (Mahoney strain) 40 D-units(6) (7)
type 2 (strain MEF-1) 8 D-units(6) (7)
type 3 (Saukett strain) 32 D-units(6) (7)
Haemophilus influenzae type b polysaccharide 10 mcg
conjugated with tetanus protein 18–30 mcg
(1) adsorbed on hydrated aluminum hydroxide (corresponding to 0.3 mg Al3+)
(2) as the average value
(3) or equivalent activity determined by immunogenicity assessment
(4) as the lower limit of the confidence interval (p=0.95)
(5) obtained on Vero cells
(6) D – antigenic units
(7) or an equivalent amount of antigen determined by an appropriate immunochemical method
excipients: sucrose, trometamol, concentrated hydrochloric acid to adjust pH, medium 199 with Hanks' salts without phenol red (a mixture of amino acids including phenylalanine (12.5 μg), mineral salts, vitamins and other components including glucose diluted in water for injection), glacial acetic acid and/or sodium hydroxide to adjust pH, formaldehyde, phenoxyethanol, anhydrous ethanol, water for injection.
Pentaxim® may contain trace amounts of glutaraldehyde, neomycin, streptomycin and polymyxin B (see section "Contraindications").
Dosage form
Suspension for injection and powder.
Main physicochemical properties: white powder of Haemophilus influenzae type b polysaccharide and sterile, cloudy, whitish suspension of diphtheria and tetanus toxoids, acellular component of pertussis (adsorbed on hydrated aluminum hydroxide), inactivated poliomyelitis virus.
Pharmacotherapeutic group
Combined antibacterial and antiviral vaccines.
ATX code J07C A06.
Pharmacological properties
Immunological and biological properties.
Pharmacodynamics.
Diphtheria and tetanus toxins are detoxified using formaldehyde, then purified.
The polio vaccine is produced from cultured polio viruses types 1, 2, and 3 on the Vero cell line, purified, and then inactivated with formaldehyde.
The acellular components of pertussis (pertussis toxin [PT] and filamentous hemagglutinin [FHA]) are extracted from Bordetella pertussis cultures and then purified. Pertussis toxin, detoxified using glutaraldehyde, corresponds to pertussis toxoid (PTxd). FHA is native. Pertussis toxoid and FHA have been identified as the two components that are most important in protecting the body against pertussis.
The capsular polysaccharide PRP (polyribosyl-ribitol-phosphate (PRP)) is extracted from a culture of Haemophilus influenzae type b and combined by conjugation with tetanus protein (T) to produce a PRP-T conjugate vaccine.
The capsular polysaccharide PRP induces an anti-PRP serological response in humans. However, as with all polysaccharide antigens, the immune response is not thymus-dependent and is characterized by low immunogenicity in infants and the absence of a booster effect before the patient reaches 15 months of age. The covalent bond between the capsular polysaccharide of Haemophilus influenzae type b and the carrier protein, tetanus protein, allows the conjugate vaccine to act as a thymus-dependent antigen that induces a specific anti-PRP serological response in infants and to obtain a booster effect.
Immune response after primary vaccination
Immunogenicity studies in infants showed that one month after the third dose of primary vaccination, all (100%) children achieved seroprotective antibody levels (> 0.01 IU/ml) to both diphtheria and tetanus antigens.
Regarding pertussis, in more than 88% of young children, one month after completing the primary immunization course, the titers of antibodies to pertussis toxoid or PHA increased 4-fold.
At least 99% of children after immunization had seroprotective antibody titers against poliovirus types 1, 2, and 3 (level ≥ 5 inversely proportional to the dilution in the seroneutralization reaction).
At least 97.2% of infants achieved PRP antibody titers above 0.15 μg/ml one month after the third dose of the primary vaccination course.
Immune response after booster vaccination
After the first booster dose (patients' age: 16–18 months), all children developed protective antibodies to diphtheria toxins (> 0.1 IU/ml), tetanus (> 0.1 IU/ml), and polioviruses (level ≥ 5 in the reciprocal of the dilution in the seroneutralization reaction).
A further study of the immunogenicity of the pertussis component in children aged 5–6 years showed that antibody titers to PT and FHA in children who received primary and booster vaccination with acellular combination vaccines were at least equivalent to the titers observed in children of the same age vaccinated with whole-cell combination pertussis vaccines.
Pharmacokinetics.
Not applicable.
Indication
Pentaxim® vaccine is indicated for the combined prevention of diphtheria, tetanus, pertussis, poliomyelitis and invasive infections caused by Haemophilus influenzae type b (such as meningitis, septicemia, cellulitis, arthritis, epiglottitis, etc.):
for the primary immunization course of infants aged 2 months and older;
for booster vaccination one year after the primary vaccination course during the second year of life.
Pentaxim® vaccine does not provide protection against infections caused by other types of Haemophilus influenzae, as well as against meningitis caused by other microorganisms.
Contraindication
Hypersensitivity:
to any of the active ingredients of Pentaxim®;
to any of the excipients;
to glutaraldehyde, neomycin, streptomycin or polymyxin B (which are used in the manufacturing process and may be present in trace amounts) (see the "Composition" section);
to the pertussis vaccine (acellular or whole-cell component).
The occurrence of a life-threatening reaction after a previous administration of this vaccine or a vaccine containing the same substances.
Vaccination should be postponed in case of fever or acute illness.
Progressive encephalopathy.
Encephalopathy occurring within 7 days of a previous dose of any vaccine containing pertussis antigens (whole-cell or acellular pertussis vaccines).
Special safety precautions
After use, all vaccine residues, syringes and vials must be destroyed in a safe manner in accordance with current requirements for the disposal of biological waste in accordance with current regulatory enactments of Ukraine.
Interaction with other medicinal products and other types of interactions
Pentaxim® vaccine can be administered simultaneously with the vaccine for the prevention of measles, mumps and rubella or with the vaccine for the prevention of hepatitis B, but provided that it is administered into two separate areas of the body.
Impact on laboratory test results
Because the Haemophilus influenzae type b (Hib) antigen, which is a capsular polysaccharide, is excreted in the urine, a positive urine test for this pathogen may occur for 1–2 weeks after vaccination. Other tests should be performed to confirm Hib infection during this period.
As with other vaccines, an adequate immunological response may not be obtained in immunocompromised patients or those treated with immunosuppressive drugs.
Before vaccination, you must inform your doctor about taking any medications or vaccines.
Application features
The immunogenicity of Pentaxim® vaccine may be reduced by immunosuppressive treatment or immunodeficiency. Therefore, it is recommended to wait until the treatment or illness is over before vaccination. However, vaccination of individuals with chronic immunodeficiency, such as HIV infection, is recommended, even though the immune response may be limited.
If Guillain-Barré syndrome or brachial neuritis has developed after a previous administration of a tetanus toxoid-containing vaccine, the decision to continue using any tetanus toxoid-containing vaccine should be based on careful consideration of the potential benefits and possible risks of continued vaccination. Vaccination is usually justified for infants with an incomplete primary immunization schedule (e.g., if they have received fewer than three doses).
Do not administer the vaccine intravascularly: make sure that the needle does not enter a blood vessel.
Do not administer the vaccine intradermally.
Vaccination should be preceded by a medical history (particularly for previous vaccinations and adverse events that may have occurred) and a clinical examination. Like all injectable vaccines, Pentaxim® should be administered with caution to individuals with thrombocytopenia or blood clotting disorders, as bleeding may occur after intramuscular administration in these individuals.
Before vaccination, a complete medical history should be taken (especially regarding vaccination history and any adverse reactions) and a clinical examination should be performed.
Syncope (fainting), as a psychogenic reaction to a needle stick, can occur after or even before any vaccination. Appropriate procedures should be followed to prevent injury from fainting and to manage syncopal reactions.
If any of the following symptoms are known to have been associated in time with the receipt of a vaccine containing a pertussis component, further use of that vaccine should be reconsidered:
temperature ≥ 40 °C for 48 hours, not associated with any other identified cause;
collapse or shock-like state (hypotonic-hyporesponsive syndrome) within 48 hours after vaccination;
prolonged, inconsolable crying lasting ≥ 3 hours, occurring within 48 hours after vaccination;
A history of febrile seizures unrelated to previous vaccine administration is not a contraindication to vaccination. In this case, it is very important to measure body temperature within 48 hours after vaccination and regularly use antipyretics as prescribed by a doctor for 48 hours.
A history of afebrile seizures unrelated to previous vaccine administration should be evaluated by a specialist before deciding to vaccinate.
In case of lower limb edema after vaccination with a vaccine containing Haemophilus influenzae type b, both vaccines – the vaccine for the prevention of diphtheria, tetanus, pertussis, poliomyelitis and the vaccine for the prevention of infections caused by Haemophilus influenzae type b – should be administered in different areas of the body and on different days.
As with all injectable vaccines, adequate emergency medical treatment should be readily available in the unlikely event of an anaphylactic reaction and close supervision should be provided.
Patients should be under medical supervision for 30 minutes after vaccine administration.
Pentaxim® vaccine does not provide protection against infections caused by Haemophilus influenzae serotypes other than Haemophilus influenzae type b, as well as against meningitis caused by other microorganisms.
The potential risk of apnoea and the need for monitoring respiratory function for 48–72 hours should be considered when administering primary immunisation to very premature infants (born ≤ 28 weeks of gestation) and especially to infants with a history of respiratory immaturity. Since the benefit of vaccination is high in this group of infants, vaccination should not be withheld or postponed.
For effects on laboratory test results, see section "Interaction with other medicinal products and other types of interactions".
This medicine contains phenylalanine, ethanol and sodium
12.5 mcg of phenylalanine in each 0.5 ml dose. Phenylalanine may be harmful to people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body is unable to excrete it properly;
2 mg of alcohol (ethanol) in each 0.5 ml dose. The small amount of alcohol in this medicine will not have any noticeable effect;
less than 1 mmol (23 mg) sodium/dose, i.e. essentially sodium-free.
Traceability
In order to improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product should be clearly recorded.
Like any injectable vaccine, PENTAXIM should be administered with caution in cases of thrombocytopenia or coagulation disorders because intramuscular injection can cause bleeding in these patients. Vaccination must be preceded by a medical history (particularly for previous vaccinations and adverse events that may have occurred) and a clinical examination. Use during pregnancy or breastfeeding. Not applicable. The Pentaxim® vaccine is intended for use in pediatrics only.
Ability to influence reaction speed when driving vehicles or other mechanisms
Not applicable. Pentaxim® vaccine is intended for pediatric use only.
Method of administration and doses
When carrying out immunization in Ukraine, one should be guided by the current orders of the Ministry of Health of Ukraine regarding immunization regimens, contraindications, and interactions with other medical immunobiological drugs.
Vaccination is carried out by medical personnel in preventive vaccination rooms of medical and preventive institutions.
Method of application
The vaccine is administered intramuscularly. The recommended vaccination site for infants is the anterolateral surface of the thigh (middle third), for older children - the deltoid muscle.
Dosage
The primary vaccination course consists of three doses of 0.5 ml vaccine administered 1–2 months apart. A booster dose is administered in the 2nd year of life.
In all cases of violation of the vaccination schedule, the doctor must be guided by the current Orders of the Ministry of Health of Ukraine on preventive vaccinations and instructions for the use of vaccines.
Instructions for use of the vaccine
For syringes without an attached needle, the replacement needle must be firmly attached by rotating it a quarter turn relative to the syringe.
Reconstitute the solution by adding the suspension (combined vaccine for the prevention of diphtheria, tetanus, pertussis (acellular component) and poliomyelitis adsorbed) to the vial with the powder (vaccine for the prevention of infections caused by Haemophilus influenzae type b, conjugated). Shake until the powder is completely dissolved. After reconstitution, the vaccine has the appearance of a cloudy whitish suspension, which is completely normal.
The vaccine is used immediately after recovery.
Do not use the vaccine if there is discoloration or foreign matter.
Any unused product or waste material should be disposed of in accordance with local requirements.
Children
The Pentaxim® vaccine is used in children from 2 months of age (see sections “Indications”, “Method of administration and dosage”).
Overdose
Information is missing.
Side effects
Adverse reactions are classified depending on the frequency of their occurrence:
very common: ≥ 10%
common: ≥ 1% and < 10%
uncommon: ≥ 0.1% and < 1%
rare: ≥ 0.01% and < 0.1%
very rare: < 0.01%
Based on spontaneous reports, some adverse reactions have been identified that have been observed very rarely after the administration of Pentaxim® vaccine. Because the reporting was spontaneous and the population size is unknown, it is not always possible to accurately estimate the incidence rate or establish a cause-and-effect relationship between the use of the vaccine and these reactions. Therefore, these adverse reactions have a frequency of occurrence of "not known".
During clinical trials among children receiving Pentaxim® as a primary vaccination, the most commonly reported reactions were injection site reactions, abnormal crying, irritability, and fever.
These symptoms usually appear within 48 hours after vaccination and may last for 48–72 hours. They resolve spontaneously without the need for specific treatment.
The incidence of injection site reactions tends to increase with booster vaccination compared to primary immunization.
Immune system disorders
Not known: immediate-type hypersensitivity reactions such as facial oedema, angioedema, angioedema, anaphylactic reactions and anaphylactic shock.
Metabolism and eating disorders
Very common: loss of appetite.
Mental disorders
Very common: nervousness, irritability, abnormal crying.
Common: insomnia, sleep disorders.
Uncommon: prolonged inconsolable crying.
Nervous system disorders
Very common: drowsiness.
Not known: febrile or afebrile convulsions, hypotonic-hyporesponsive syndrome.
Gastrointestinal disorders
Very common: vomiting.
Common: diarrhea.
Skin and subcutaneous tissue disorders
Not known: rash, erythema, urticaria.
General disorders and administration site conditions
Very common: injection site erythema, fever ≥ 38°C, injection site swelling, injection site pain.
Common: injection site induration.
Uncommon: fever ≥ 39°C, injection site redness and swelling ≥ 5 cm.
Rare: fever >40°C.
Swelling of one or both lower extremities following administration of a vaccine containing Haemophilus influenzae type b. These reactions usually appear a few hours after the primary immunization course and resolve spontaneously without sequelae within 24 hours. These reactions may be accompanied by cyanosis, erythema, transient purpura, and excessive crying.
Not known: severe injection site reaction (> 50 mm), including extensive swelling of the limb, which may extend from the injection site to one or both adjacent joints. These reactions occur within 24-72 hours after vaccination and may be accompanied by symptoms such as erythema, local fever, tenderness or pain at the injection site. The symptoms resolve spontaneously within 3-5 days. The likelihood of developing such reactions depends on the number of previous doses of acellular pertussis-containing vaccines, with the risk increasing after the 4th and 5th doses.
Potential adverse reactions (i.e. adverse events that have been reported with other vaccines containing one or more antigenic components similar to Pentaxim®).
Cases of brachial neuritis and Guillain-Barré syndrome have been reported following administration of a vaccine containing tetanus toxoid.
Additional information regarding individual populations
Apnea in very premature infants (born ≤ 28 weeks of gestation) (see section "Special warnings and precautions for use").
Reporting of adverse reactions.
Reporting adverse reactions during the post-marketing period is an important measure. This allows for continuous monitoring of the benefit/risk balance of this medicine. If you experience any adverse reactions, please inform your doctor.
Healthcare professionals should report any adverse reactions using the adverse reaction reporting system in Ukraine.
Expiration date
3 years.
The vaccine is used immediately after recovery.
Storage conditions
The vaccine should be stored at 2 to 8°C (in a refrigerator). Do not freeze.
Protect from light. Keep out of the reach of children.
Do not use the drug after the expiration date indicated on the package.
For storage conditions of the reconstituted vaccine, see the section “Expiration date”.
Incompatibility
In the absence of compatibility studies, this vaccine should not be mixed with other medicinal products.
Packaging
1 vial of powder and 1 pre-filled syringe (0.5 ml) with attached needle (or 2 separate needles) containing suspension for injection, in a cardboard box.
1 vial of powder and 1 pre-filled syringe (0.5 ml) with attached needle (or 2 separate needles) containing suspension for injection in a standard export packaging, which is contained in a cardboard box, with instructions for medical use.
Vacation category
According to the recipe.
Producer
Sanofi Pasteur, France.
Sanofi-Aventis Zrt., Hungary / Sanofi-Aventis Zrt., Hungary.
Location of manufacturers and their business addresses.
1541 Avenue Marcel Mérieux, 69280 Marcy l'Étoile, France.
1541 avenue Marcel Merieux, 69280 Marcy l'Etoile, France.
Parc Industriel d'Incarville, 27100 Val-de-Roi, France.
Building 5, Kampona Utca 1, Budapest XXII, 1225, Hungary.
Building Dc5, Campona Utca 1, Budapest XXII, 1225, Hungary.
Applicant
Sanofi Pasteur
Location of the applicant.
14 Espace Henry Vallée 69007 Lyon, France / 14 Espace Henry Vallée 69007 Lyon, France
