PROQUAD powder and solvent for injectable suspension in pre-filled syringe

2. What you need to know before you receive ProQuad

Do not use ProQuad

• If the person to be vaccinated is allergic to any vaccine against varicella or measles, mumps, or rubella, or to any of the other components of this vaccine (listed in section 6) including neomycin.
• If the person to be vaccinated has bleeding disorders or any type of cancer that affects the immune system.
• If the person to be vaccinated is receiving treatment or taking medication that may weaken the immune system (except for low-dose corticosteroid therapy for asthma or replacement therapy).
• If the person to be vaccinated has a weakened immune system due to a disease (including AIDS).
• If the person to be vaccinated has a family history of congenital or hereditary immunodeficiency, unless the person's immune competence has been demonstrated.
• If the person to be vaccinated has active untreated tuberculosis.
• If the person to be vaccinated has any disease with a fever over 38.5°C; however, a lower fever is not in itself a reason to delay vaccination.
• If the person to be vaccinated is pregnant (also, pregnancy should be avoided for 1 month after vaccination, see Pregnancy and lactation).

Warnings and precautions

If the person to be vaccinated experiences any of the following problems, consult their doctor or pharmacist before being vaccinated with ProQuad:

• An allergic reaction to egg or any product containing egg.
• Personal or family history of allergies or seizures (attacks).
• An adverse effect after vaccination with measles, mumps, and/or rubella vaccines that involves bruising or bleeding for longer than usual.
• HIV infection without symptoms of HIV disease. However, vaccination may be less effective than for uninfected individuals (see Do not use ProQuad).

If you have a coagulation disorder or low platelet count, the injection will be given under the skin.

In rare circumstances, it is possible to contract varicella, including severe varicella, from a person who has been vaccinated with ProQuad. This can occur in people who have not been previously vaccinated against varicella or who have not had varicella, as well as in people who are in one of the following categories:

• Individuals with low resistance to diseases.
• Pregnant women who have never had varicella or have not been vaccinated against varicella.
• Newborns whose mothers have never had varicella or have not been vaccinated against varicella.

Whenever possible, people who have been vaccinated with ProQuad should try to avoid close contact, until 6 weeks after vaccination, with anyone who is in one of the above categories. Inform your doctor if someone is in one of the above categories and is expected to be in close contact with the person being vaccinated.

As with other vaccines, ProQuad may not completely protect all vaccinated individuals. Additionally, if the person to be vaccinated has already been exposed to measles, mumps, rubella, or varicella viruses but has not yet developed the disease, ProQuad may not be able to prevent the onset of the disease.

Other medicines and ProQuad

Tell your doctor or pharmacist if the vaccinated person is using or has recently used other medicines (or other vaccines).

ProQuad can be given at the same time as other pediatric vaccines such as Prevenar and/or hepatitis A vaccine, or with vaccines that contain diphtheria, tetanus, acellular pertussis, Haemophilus influenzaetype b, inactivated poliomyelitis, or hepatitis B. A different injection site will be used for each vaccine.

The doctor may delay vaccination for at least 3 months after a blood or plasma transfusion or after the administration of immunoglobulin (Ig) or varicella-zoster immunoglobulin (IgVZ). After vaccination with ProQuad, Ig or IgVZ should not be given for 1 month, unless your doctor tells you otherwise.

If a tuberculin test is to be performed, it should be done before, at any time, simultaneously with, or 4 to 6 weeks after vaccination with ProQuad.

Tell your doctor if the vaccinated person has recently received a vaccine or is scheduled to receive one in the near future. Your doctor will determine when to administer ProQuad.

The use of salicylates (e.g., acetylsalicylic acid, a substance found in many medicines used to relieve pain and reduce fever) should be avoided during the 6 weeks following vaccination with ProQuad.

Pregnancy and lactation

ProQuad should not be given to pregnant women. Women of childbearing age should take precautions to avoid pregnancy for 1 month after vaccination.

Tell your doctor if you are breast-feeding or plan to breast-feed. Your doctor will decide whether you should receive ProQuad.

If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this vaccine.

ProQuad contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; i.e., it is essentially "sodium-free".

ProQuad contains potassium

This medicine contains potassium, less than 1 mmol (39 mg) per dose; i.e., it is essentially "potassium-free".

ProQuad contains sorbitol

This medicine contains 16 mg of sorbitol per dose. The additive effect of medicines containing sorbitol (or fructose) administered concomitantly and the intake of sorbitol (or fructose) in the diet should be taken into account.

3. How to use ProQuad

ProQuad should be injected into the muscle or under the skin, either in the outer aspect of the thigh or in the upper arm.

The recommended injection sites for intramuscular injections are the thigh area in young children, while for other ages, the upper arm is preferred.

If the person to be vaccinated has a coagulation disorder or low platelet count, the vaccine should be given under the skin because bleeding may occur after intramuscular administration.

ProQuad should not be injected directly into any blood vessel.

ProQuad is administered by injection as follows:

• Children between 9 and 12 months of age:

ProQuad can be given from 9 months of age. To ensure optimal protection against varicella and measles, two doses of ProQuad should be given with an interval of at least 3 months.

• Individuals 12 months of age and older:

To ensure optimal protection against varicella, two doses of ProQuad should be given with an interval of at least 1 month.

The appropriate time and number of injections will be determined by your doctor according to official recommendations.

Instructions for reconstitution intended for medical or healthcare professionals are included at the end of the leaflet.

If you miss a dose of ProQuad

Your doctor will decide when to give you the missed dose.

4. Possible side effects

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

Allergic reactions (hives) can occur. Some of these reactions can be serious and can include difficulty breathing or swallowing. If the vaccinated person experiences an allergic reaction, call their doctor immediately.

Other side effects have been reported after the administration of ProQuad, and some of them were serious. These included:

• Uncommon (may affect up to 1 in 100 people): febrile seizures.
• Rare (may affect up to 1 in 1,000 people): unsteadiness while walking.

The following side effects were most frequently reported with the use of ProQuad:

• Very common (may affect more than 1 in 10 people): injection site reactions including pain/tenderness/redness, fever (38.9°C or higher);
• Common (may affect up to 1 in 10 people): injection site reactions including swelling or painful lump; irritability; rash (including measles-like rash, varicella-like rash, and injection site rash); upper respiratory tract infection; vomiting and diarrhea.

Other side effects have been reported with the administration of at least one of the following vaccines: ProQuad, previous formulations of monovalent and combination vaccines against measles, mumps, and rubella manufactured by Merck Sharp & Dohme LLC, Rahway, NJ 07065, USA (hereinafter MSD), or Varicella Virus Vaccine Live (Oka/Merck). These adverse events included:

• Uncommon (may affect up to 1 in 100 people): cough
• Rare (may affect up to 1 in 1,000 people): skin infection; varicella.
• Unknown (cannot be estimated from the available data): unusual bleeding or painful bruising under the skin; testicular inflammation; tingling of the skin, herpes zoster (shingles); brain inflammation (encephalitis); inflammation of the membranes covering the brain and spinal cord not caused by a bacterial infection (aseptic meningitis), severe skin reactions; stroke; febrile seizures; joint pain and/or swelling (which may be transient or chronic); lung inflammation (pneumonia/pneumonitis).

Your doctor has a more comprehensive list of side effects for ProQuad and for the components of ProQuad (vaccines against measles, mumps, and rubella manufactured by MSD and Varicella Virus Vaccine Live (Oka/Merck)).

Reporting of side effects

If you experience any side effects, talk to 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 ProQuad

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

Do not use this vaccine after the expiry date stated on the outer packaging after EXP. The expiry date is the last day of the month stated.

Store and transport refrigerated (between 2°C and 8°C).

Do not freeze.

Keep the vial in the outer packaging 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

ProQuad composition

After reconstitution, one dose (approximately 0.5 ml) contains:

The active ingredients are:

Mumps virus1 Enders’ Edmonston strain (live, attenuated) not less than 3.00 log10 TCID50*

Mumps virus1 Jeryl Lynn strain (Level B) (live, attenuated) not less than 4.30 log10 TCID50*

Rubella virus2 Wistar RA 27/3 strain (live, attenuated) not less than 3.00 log10 TCID50*

Varicella virus3 Oka/Merck strain (live, attenuated) not less than 3.99 log10 PFU**

• Dose that infects 50% of tissue cultures

** Plaque-forming units

(1) Produced in chicken embryo cells.

(2) Produced in human diploid lung fibroblasts (WI-38).

(3) Produced in human diploid cells (MRC-5).

The other components are:

Powder

Sucrose, hydrolyzed gelatin, urea, sodium chloride, sorbitol (E-420), monosodium glutamate, sodium phosphate, sodium bicarbonate, potassium phosphate, potassium chloride, 199 medium with Hanks' salts, MEM, neomycin, phenol red, hydrochloric acid (HCl), and sodium hydroxide (NaOH).

Solvent

Water for injectable preparations.

Product appearance and container contents

The vaccine is a powder for injectable suspension contained in a single-dose vial, which must be mixed with the supplied solvent.

The powder is a compact crystalline mass of white to pale yellow color, and the solvent is a clear colorless liquid.

ProQuad is available in packs of 1, 10, and 20. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, Netherlands

For more information about 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: https://www.ema.europa.eu.

This information is intended for healthcare professionals only:

Before mixing with the solvent, the vaccine powder is a compact crystalline mass of white to pale yellow color. The solvent is a clear colorless liquid. When fully reconstituted, the vaccine is a pale yellow to light pink liquid.

For reconstitution of the vaccine, use only the supplied solvent, as it does not contain preservatives or other antiviral substances that could inactivate the vaccine.

It is essential to use a new sterile syringe and needle for each individual to prevent the transmission of infectious agents from one person to another.

A separate needle should be used for reconstitution and another needle for injection.

ProQuad should not be mixed in the same syringe with other vaccines.

Reconstitution instructions

To attach the needle, place it firmly on the syringe and secure it with a twist.

Inject the entire contents of the solvent syringe into the vial containing the powder. Gently swirl to mix completely.

The reconstituted vaccine should be inspected visually for any foreign particles and/or changes in physical appearance before administration. If any of the above are observed, discard the vaccine.

It is recommended that the vaccine be administered immediately after reconstitution to minimize loss of potency. Discard the reconstituted vaccine if not used within 30 minutes.

Do not freeze the reconstituted vaccine.

Withdraw the entire contents of the reconstituted vaccine from the vial into a syringe, change the needle, and inject the entire contents subcutaneously or intramuscularly.

Unused products or waste materials should be disposed of in accordance with local requirements.

See also Section 3 How to use ProQuad