HEXYON Injectable Suspension in Pre-filled Syringe

2. What you need to know before your child is given Hexyon

In order to ensure that Hexyon is suitable for your child, it is important that you inform your doctor or nurse if your child has any of the following characteristics. If there is anything you do not understand, ask your doctor, pharmacist, or nurse.

Do not use Hexyon if your child:

• has had a respiratory disorder or swelling of the face (anaphylactic reaction) after administration of Hexyon.
• has had an allergic reaction

• to the active substances,
• to any of the other components listed in section 6,
• to glutaraldehyde, formaldehyde, neomycin, streptomycin, and polymyxin B, as these substances are used during the manufacturing process,
• after previous administration of Hexyon or any other vaccine that contains diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Hib.

• has had a severe reaction that affects the brain (encephalopathy) within 7 days of administration of a previous dose of a pertussis vaccine (acellular or whole cell).
• has an uncontrolled or severe disease that affects the brain and nervous system (uncontrolled neurological disorder) or uncontrolled epilepsy.

Warnings and precautions

Before vaccination, consult your doctor, pharmacist, or nurse if your child:

• has a moderate or high temperature or an acute illness (fever, sore throat, cough, cold, or flu). It may be necessary to delay vaccination with Hexyon until your child feels better.
• has experienced any of the following adverse events after receiving a pertussis vaccine, the decision to administer further doses of vaccine containing the pertussis component should be carefully evaluated:

• fever of 40°C or higher within 48 hours of vaccination that was not due to any other identifiable cause.
• collapse or shock-like state with hypotonic-hyporesponsive episode (weakness) within 48 hours of vaccination.
• prolonged crying, lasting 3 hours or more, within 48 hours of vaccination.
• seizures (convulsions) with or without fever, within 3 days of vaccination.

• has previously had Guillain-Barré syndrome (temporary inflammation of the nerves that causes pain, paralysis, and sensitivity disorders) or brachial neuritis (severe pain and reduced mobility in the arm and shoulder) after administration of a vaccine that contains tetanus toxoid (an inactivated form of tetanus toxoid). In this case, your doctor will evaluate the decision to administer any vaccine that contains tetanus toxoid.
• is receiving treatment that suppresses their immune system (the body's natural defenses) or has any disease that causes immunodeficiency. In these cases, the immune response to the vaccine may be reduced. Therefore, it is recommended to delay vaccination until the end of treatment or disease. However, children with long-term problems with their immune system, such as HIV infection (AIDS), may be given Hexyon, but protection may not be as good as in children with a healthy immune system.
• has a chronic or acute illness, including chronic kidney failure or kidney failure.
• has any undiagnosed or uncontrolled brain disease or uncontrolled epilepsy. Your doctor will evaluate the potential benefits of vaccination.
• has any blood disorder that causes easy bruising or prolonged bleeding after minor cuts. Your doctor will advise on the convenience or not of administering Hexyon to your child.

Use of Hexyon with other vaccines or medicines

Tell your doctor or nurse if your child is using, has recently used, or might use any other medicine or vaccine.

Hexyon can be administered at the same time as other vaccines, such as pneumococcal vaccines, measles-mumps-rubella vaccines, varicella vaccines, rotavirus vaccines, or meningococcal vaccines.

When administered at the same time as other vaccines, Hexyon will be administered in different injection sites.

Fainting can occur after, or even before, any injection with a needle. Therefore, inform your doctor or nurse if your child has fainted with a previous injection.

Hexyon contains phenylalanine, potassium, and sodium

Hexyon contains 85 micrograms of phenylalanine per 0.5 ml dose. Phenylalanine may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

Hexyon contains less than 1 mmol of potassium (39 mg) and less than 1 mmol of sodium (23 mg) per dose, i.e., it is essentially "potassium-free" and "sodium-free".

3. How to use Hexyon

Hexyon will be administered to your child by a doctor or nurse who is properly trained in the use of vaccines and equipped to respond to any rare, severe allergic reaction that may occur after injection (see section 4 "Possible side effects").

Hexyon is administered by injection into a muscle (intramuscularly, IM) in the upper leg or arm of your child. The vaccine should never be administered into a blood vessel or under or into the skin.

The recommended dose is as follows:

Primary vaccination cycle (primary vaccination)

Your child will receive two injections administered at an interval of two months or three injections administered at an interval of one to two months (at least four weeks apart). This vaccine should be used according to the local vaccination schedule.

Additional injections (booster vaccination)

After the primary vaccination cycle, your child will receive a booster dose, according to local recommendations, at least 6 months after the last dose of the primary vaccination cycle. Your doctor will advise on when this dose should be administered.

If your child misses a dose of Hexyon

If your child misses a scheduled injection, it is important that you inform your doctor or nurse, they will decide when to administer the missed dose.

It is important to follow the doctor's or nurse's instructions to ensure your child completes the vaccination cycle. Otherwise, your child may not be fully protected against the diseases.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this vaccine can cause side effects, although not everybody gets them.

Severe allergic reactions (anaphylactic reaction)

If any of the following symptoms occur after leaving the place where your child received the injection, you should consult a doctor IMMEDIATELY:

• difficulty breathing
• bluish discoloration of the tongue or lips
• rash
• swelling of the face or throat
• sudden and severe discomfort with a drop in blood pressure that causes dizziness and loss of consciousness, rapid heart rate associated with respiratory disorders

When these signs and symptoms (signs or symptoms of an anaphylactic reaction) occur, they usually develop rapidly after injection and while the child is still in the clinic or doctor's office.

The possibility of severe allergic reactions occurring after receiving this vaccine is rare (may affect up to 1 in 1,000 people).

Other side effects

If your child experiences any of the following side effects, consult your doctor, nurse, or pharmacist.

• Very common side effects (may affect more than 1 in 10 people) are:

• loss of appetite (anorexia)
• crying
• sleepiness (somnolence)
• vomiting
• fever (temperature of 38°C or higher)
• irritability
• pain, redness, or swelling at the injection site

• Common side effects (may affect up to 1 in 10 people) are:

• abnormal crying (prolonged crying)
• diarrhea
• hardening at the injection site (induration)

• Uncommon side effects (may affect up to 1 in 100 people) are:

• allergic reaction
• high fever (temperature of 39.6°C or higher)
• lump (nodule) at the injection site

• Rare side effects (may affect up to 1 in 1,000 people) are:

• rash
• extensive reactions at the injection site (larger than 5 cm), including extensive swelling of a limb that extends from the injection site beyond one or both joints. These reactions start within 24-72 hours after vaccination, may be associated with redness, heat, pain, or swelling at the injection site, and resolve within 3-5 days without treatment.
• seizures (convulsions) with or without fever.

• Very rare side effects (may affect up to 1 in 10,000 people) are:

• episodes in which your child enters a shock-like state or becomes pale, weak, and unresponsive for a period (hypotonic-hyporesponsive episodes, HHE).

Possible side effects

Other side effects have been reported occasionally with other vaccines that contain diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, or Hib, and not directly with Hexyon:

• Guillain-Barré syndrome (temporary inflammation of the nerves that causes pain, paralysis, and sensitivity disorders), severe pain, and reduced mobility in the arm and shoulder (brachial neuritis) have been reported after administration of a vaccine that contains tetanus toxoid.
• Polyradiculoneuritis (inflammation of the nerves that causes sensory disorders or weakness in the arms and/or legs), facial paralysis, visual disorders, blindness, or sudden loss of vision (optic neuritis), inflammatory disease of the brain and spinal cord (demyelination of the central nervous system, multiple sclerosis) have been reported after administration of vaccines that contain the hepatitis B antigen.
• Brain inflammation or infection (encephalopathy/encephalitis).
• In children born very prematurely (at 28 weeks of gestation or earlier), longer intervals between breaths than normal may occur for 2-3 days after vaccination.
• Swelling or inflammation of the brain. This can cause a range of symptoms, including headache, confusion, and seizures.
• Swelling of one or both feet and lower limbs. This may occur with a bluish discoloration of the skin (cyanosis), redness, small areas of bleeding under the skin (transient purpura), and severe crying, after administration of vaccines that contain Haemophilus influenzaetype b. If this reaction occurs, it will mainly happen after the first injections and will be seen in the first hours after vaccination. All symptoms will resolve completely within 24 hours without treatment.

Reporting of side effects

If your child experiences any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Hexyon

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and label after EXP. The expiry date is the last day of the month shown.

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Keep the container in the outer carton to protect it from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Hexyon

The active principles per dose (0.5 ml)1 are:

1 Adsorbed on hydrated aluminum hydroxide (0.6 mg Al3+)

2 As lower confidence limit (p=0.95) and not less than 30 UI as mean value

3 As lower confidence limit (p=0.95)

4 Or equivalent activity determined by immunogenicity evaluation

5 Grown on Vero cells

6 These antigen quantities are strictly the same as those previously expressed as 40-8-32 units of antigen D, for virus types 1, 2, and 3 respectively, when measured by another suitable immunochemical method.

7 Produced in Hansenula polymorpha yeast cells using recombinant DNA technology

The other components are:

Disodium hydrogen phosphate, potassium dihydrogen phosphate, trometamol, sucrose, essential amino acids including L-phenylalanine, sodium hydroxide and/or acetic acid and/or hydrochloric acid (for pH adjustment) and water for injectable preparations.

The vaccine may contain traces of glutaraldehyde, formaldehyde, neomycin, streptomycin, and polymyxin B.

Appearance of the Product and Container Contents

Hexyon is supplied as an injectable suspension in a pre-filled syringe (0.5 ml).

Hexyon is available in packs of 1, 10, or 50 pre-filled syringes without a fixed needle.

Hexyon is available in packs of 1 or 10 pre-filled syringes with 1 separate needle.

Hexyon is available in packs of 1 or 10 pre-filled syringes with 2 separate needles.

Hexyon is available in a multipack of 5 packs, each containing 10 pre-filled syringes without a fixed needle.

Hexyon is available in packs of 1 or 10 pre-filled syringes with 1 or 10 separate safety needles.

Only some pack sizes may be marketed.

After shaking, the normal appearance of the vaccine is a turbid white suspension.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sanofi Winthrop Industrie, 82 Avenue Raspail, 94250 Gentilly, France

Manufacturer

Sanofi Winthrop Industrie, 1541 avenue Marcel Mérieux, 69280 Marcy l'Etoile, France

Sanofi Winthrop Industrie, Voie de L’Institut - Parc Industriel d'Incarville, BP 101, 27100 Val de Reuil, France

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

The most recent approved information on this vaccine is available at the following URL: https://hexyon.info.sanofi or by scanning the QR code with your mobile phone (smartphone):

[QR code to be included]

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This information is intended solely for healthcare professionals:

• Shake the pre-filled syringe to make the contents homogeneous.
• Hexyon must not be mixed with other medicinal products.
• Hexyon should be administered by the intramuscular route. The recommended injection sites are the anterolateral upper thigh (preferred site) or the deltoid muscle in older children (possibly from 15 months of age).

Must not be administered by the intradermal or intravenous route. Do not administer by intravascular injection: ensure that the needle has not penetrated a blood vessel.

• Do not use the pre-filled syringes if the carton is damaged.

Preparation for Administration

The syringe with the suspension for injection should be inspected visually before administration. In the event of foreign particles, leaks, premature plunger activation, or defective tip sealing, discard the pre-filled syringe.

The syringe is designed for single use and must not be reused.

Instructions for Use of the Luer Lock Pre-filled Syringe

Image A: Luer Lock Syringe with Cap on the Rigid End

Instructions for Use of the Safety Needle with the Luer Lock Syringe

Follow steps 1 and 2 described above to prepare the Luer Lock syringe and attach the needle.

Disposal of unused medicinal products and all materials that have come into contact with them should be done in accordance with local regulations.