CONTENTS

Inactivated rabies vaccine prepared on Vero cells.

PRESENTATION

Vial 1 dose + syringe (diluent) 0.5 mL x 1's, 5's.

DESCRIPTION

Each 0.5 mL-dose contains rabies virus*, Wistar Rabies PM/WI38 1503-3M strain (inactivated) ³2.5 iu**.

*Produced on VERO cells.

**Quantity measured according to the international standard and the NIH test.

It also contains the following ingredients: Powder: Maltose and human albumin. Solvent: Sodium chloride and water for injections.

ACTIONS: Pharmacology: Inactivated vaccine used for the prevention of rabies in individuals at a risk of infection and for treatment after confirmed or possible infection with rabies virus.

A serum antibody titre ³0.5 iu/mL, considered by WHO to confer protection, is reached after the injection of 3 doses on D0, D7 and D28 (or D21). This immunity must be maintained with an initial booster injection 1 year later, followed by booster injections every 5 years.

INDICATIONS

Pre-exposure Prevention of Rabies (Pre-exposure Vaccination): Pre-exposure vaccination should be offered to subjects at high risk of contamination by the rabies virus. All persons at a permanent risk eg, diagnostic, research or production laboratory staff working with rabies virus, should be vaccinated. A serological test is recommended every 6 months.

Pre-exposure vaccination should also be considered for subjects at frequent risk of exposure to the rabies virus eg, veterinarians and their assistants, animal handlers; those who are in contact with species likely to have rabies (dogs, cats, skunks, raccoons, bats) eg, gamekeepers, hunters, forestry workers, speleologists and taxidermists.

Individuals living or travelling in enzootic areas.

In areas where the enzootic level of rabies is low, veterinarians and assistants (including students), animal handlers and wildlife officers (gamekeepers) are considered to be at occasional risk of exposure and should receive a primary vaccination against rabies.

Serological tests for rabies antibodies should be performed at regular intervals in accordance with the subject's risk exposure. Systematic booster injections should be administered in accordance with the subject's risk exposure.

Post-Exposure Prevention of Rabies (Post-Exposure Vaccination): At the slightest risk of contamination, post-exposure vaccination should be performed as soon as possible.

In some countries, vaccination must be performed in a specialized rabies treatment centre.

Post-exposure treatment includes local, nonspecific treatment of the injury, passive immunization with rabies immunoglobulins (RIGs) and vaccination, depending on the type injury and the status of the animal (see Tables 1 and 2).

DOSAGE & ADMINISTRATION

The vaccination schedule should be adapted in accordance with the circumstances of the vaccination and the patient's rabies immune status.

Pre-exposure Vaccination: Three doses of Verorab (0.5 mL) should be administered on D0, D7 and D28 or D21.

Booster Injection After Pre-exposure Vaccination: A booster injection of Verorab (0.5 mL) will be administered 1 year after primary vaccination, followed by a booster injection every 5 years. See Table 3.

Verorab can be administered as a booster injection after primary vaccination with a rabies vaccine prepared on diploid or Vero cells.

Post-Exposure Vaccination: First-Aid: Local Treatment of the Wound: All bites and scratches should be immediately flushed out and washed with soap or detergent. Doing so can enable efficient elimination of the rabies virus at the infection site.

A 70% alcohol solution, a tincture (or solution) of iodine or a 0.1% quaternary ammonium solution can then be applied (provided that there are no remaining traces of soap, because these products neutralize each other).

Depending on the severity of the injuries, rabies immunoglobulins (RIGs) may need to be administered in association with the vaccine. In this case, refer to the Instructions for Use in the RIG package leaflet.

If necessary, treatment can be supplemented by the administration of a tetanus prophylactic and/or course of antibiotics.

Fully Immunized Subjects: Two booster doses of Verorab (0.5 mL) should be administered on D0 and D3.

Administration of rabies immunoglobulins (RIGs) is not necessary and should not be done in this case, since booster injection is always followed by an anamnestic response.

Previously immunized subjects should be able to document the following: Full pre- or post-exposure rabies vaccination, by a cell culture vaccine; a documented rabies antibody titre 0.5 iu/mL.

In case of doubt, if the booster injection was administered >5 years ago or in the case of incomplete vaccination, the patient should not be considered to be completely immunized and complete post-exposure treatment should be initiated. See Table 4.

Non-Immunized Subjects: Five doses of Verorab (0.5 mL) should be administered on D0, D3, D7, D14 and D28. Rabies immunoglobulins (RIGs) should be administered at the same time as the 1st injection in the case of a severe injury (category III according to the WHO rabies risk classification). Equine and human immunoglobulins can be used with Verorab.

Internationally recognized RIG dosage is as follows: Human rabies immunoglobulins: 20 iu/kg body weight; equine rabies immunoglobulins: 40 iu/kg body weight.

Because RIGs may partially inhibit active antibody production, no more than the recommended dose should be administered.

The vaccine should be injected contralaterally to the RIG administration sites.

In enzootic rabies areas, the administration of 2 injections on D0 may be justified eg, in the case of lesions that are extremely severe or located near the nervous system or when the subject is immunodeficient or did not come in for a medical consultation immediately after exposure.

Vaccination Via Intradermal Route: Pre-exposure Vaccination: Primary Vaccination: As according to WHO, Verorab may be given intradermally (0.1 mL dose on D0, D7 and D28 or D21).

However, IM injections are preferable if antimalarial chemoprophylaxis (eg, chloroquine) is being used concurrently or there is a possibility of an immunocompromised state (antibody response may be impaired if the intradermal method is used).

Booster Injections: A booster injection of Verorab (0.5 mL) will be administered 1 year after primary vaccination, followed by a booster injection every 5 years.

Post-Exposure Vaccination: Intradermal Schedule: Verorab is of sufficient potency to allow its safe use in the WHO recommended intradermal post-exposure regimen in countries where relevant national authorities have approved the intradermal route for rabies post-exposure treatment.

If Verorab is administered by the intradermal route, the following instructions and warnings must be strictly adhered to.

Dosage: One intradermal dose comprises 0.1 mL of reconstituted vaccine ie, 1/5 of the IM dose. For Verorab, the administration schedule recommended by WHO is:

Non-Immunized Individuals: The 2-site intradermal regimen "2-2-2-0-1-1" includes: 2 injections of 0.1 mL at 2 sites on days D0, D3, D7; 1 injection of 0.1 mL at 1 site on days D28 (or D30) and D90.

The 2-site intradermal regimen "2-2-2-0-2" (known as updated Thai Red Cross regimen, also recommended by WHO) prescribes 2 injection of 0.1 mL at 2 sites on days D0, D3, D7 and D28 can be applied too.

Fully Immunized Individuals: 2 injections of 0.1 mL on D0, D3. This schedule should not apply to immunocompromised patients.

Administration: Verorab is administered by the IM route, into the deltoid area in adults or the anterolateral area of the thigh in infants and toddlers. Do not inject in the gluteal area. The intradermal (ID) injection may be used as an alternative, on upper or forearm.

Do not inject by the intravascular route. Ensure that the needle does not penetrate a blood vessel before vaccine injection. Do not administer by the SC route.

CONTRAINDICATIONS

Pre-Exposure: Vaccination should be postponed in case of fever or acute illness.

Hypersensitivity to any of the components Verorab, polymyxin B, streptomycin or neomycin.

Post-Exposure: Because rabies is always fatal, there is no contraindication to post-exposure vaccination.

Intradermal Route: The intradermal route must not be used in individuals receiving long-term corticosteroid or other immunosuppressive therapy or chloroquine; immunocompromised individuals; with severe wounds, especially to the head and neck or presenting late for consultation particularly children.

PRECAUTIONS

As is the case with all injectable vaccines, it is recommended to have appropriate medical treatment readily available in case of anaphylactic reaction immediately after vaccination, particularly a post-exposure vaccination in subjects with a known hypersensitivity to polymyxin B, streptomycin or neomycin.

Do not inject the vaccine into the gluteal area, because weaker levels of neutralising antibodies have been observed when this area is used.

Regular serological tests are necessary. These serological tests are performed by verifying the complete neutralisation of a reference virus, by the Rapid Fluorescent Focus Inhibition Test (RFFIT) method. This test should be done every 6 months in people at permanent risk of exposure and every 2-3 years after each booster dose injection in subjects at discontinuous risk of exposure. If the antibody level is under that considered to be protective ie, 0.5 iu/mL (RFFIT), a booster injection should be administered.

When the vaccine is administered to subjects with a known immunodeficiency due to an immunosuppressive illness or a concomitant immunosuppressive treatment (eg, corticosteroids), a serological test of their antibody level should be done 2-4 weeks after vaccination. If the antibody level is lower than that considered to be protective ie, 0.5 iu/mL (RFFIT), an additional injection should be administered.

Effects on the Ability to Drive or Operate Machinery: Post-vaccination dizziness has been frequently reported. This can temporarily affect ability to drive and use machines.

Use in pregnancy & lactation: Because of the severity of the disease, the vaccination schedule must not be modified as a result of pregnancy. Consult the physician immediately if pregnancy is discovered during a vaccination series.

Verorab may be used during lactation.

ADVERSE REACTIONS

Minor Local Reactions: Pain, erythema, edema, pruritus and induration at the injection site.

General Reactions: Moderate fever, shivering, malaise, asthenia, headaches, dizziness, arthralgia, myalgia, GI disorders (nausea, abdominal pain).

Exceptional cases of anaphylactoid reactions, urticaria, rash.

INTERACTIONS

Corticosteroids and other immunosuppressive treatments may interfere with antibody production and cause the failure of the vaccination.

Immunoglobulins must be administered at a different site from that of the vaccine (the contralateral side).

CAUTIONS FOR USAGE

Instructions for Use/Handling and Disposal: Reconstitution: Take the cap off the vaccine vial.

Inject the solvent from the ampoule into the vial of powder.

Shake gently to obtain a homogenous suspension of the vaccine. The reconstituted vaccine appears as a limpid liquid.

Immediately withdraw 0.5 mL of suspension for IM administration.

The vaccine may be used up to 8 hrs after reconstitution, provided it is maintained at 2-8°C. Unused vaccine must be discarded after 8 hrs.

Any unused product or waste should be disposed of in accordance with the regulations in effect.

Special Precautions for the Intradermal Route: It is essential that intradermal administration of Verorab be carried out only by medical staff trained in this technique in order to ensure that the vaccine is delivered intradermally and not SC.

For the intradermal route, a sterile syringe with fixed needle (insulin type) is preferred. Correct intradermal injection should result in a raised papule with an "orange peel" appearance. If the vaccine is injected too deeply into the skin and a papule is not seen, the needle should be withdrawn and reinserted nearby. If there is a complete failure to inject intradermally at more than half of the multiple injection sites, an extra intradermal dose should be given in the opposite site.

Special Storage Conditions for Intradermal Route: Verorab does not contain a preservative; therefore, great care must be taken to avoid contamination of reconstituted vaccine.

The vaccine may be used up to 8 hrs after reconstitution provided it is maintained at 2-8°C. Unused vaccine must be discarded after 8 hrs. Using aseptic technique, a dose of vaccine may be withdrawn from a vial and the remainder used for another patient provided that the vial is stored in a refrigerator between 2-8°C. A new sterile needle and syringe must be used to withdraw and administer each dose of vaccine for each patient to avoid cross infection.

STORAGE

Store in the refrigerator (2-8°C). Do not freeze.

The reconstituted vaccine should be administered immediately.

Shelf-Life: 36 months.

CONTENTS

Inactivated influenza vaccine (split virion).

PRESENTATION

Prefilled syringe 0.25 mL x 1's. 0.5 mL x 1's.

DESCRIPTION

Each 0.25- and 0.5-mL dose contains split influenza virus*, inactivated containing antigens equivalent to the following strains: A/Brisbane/59/2007 (H1N1)-like strain (A/Brisbane/59/2007 (IVR-148)), A/Brisbane/10/2007 (H3N2)-like strain (A/Uruguay/716/2007 (NYMC X-175C)) and B/Brisbane/60/2008-like strain (B/Brisbane/60/2008) 7.5 and 15 mcg HA**, respectively.

*Propagated in fertilised hen's eggs from healthy chicken flocks.

**Haemagglutinin.

Vaxigrip also contains the following excipients: Buffer solution containing sodium chloride, disodium phosphate dihydrate, potassium dihydrogen phosphate, potassium chloride and water for injection.

The vaccine complies with the WHO recommendations (Northern hemisphere) and EU decision for the 2009/2010 season.

INDICATIONS

Prevention of influenza, particularly in subjects with high-risk associated complications.

DOSAGE & ADMINISTRATION

Adults and Children ³36 months: One 0.5-mL dose.

Children 6-35 months: One 0.25-mL dose.

If the child has not been previously vaccinated, a 2nd dose should be given after at least 4 weeks.

Administration: Administer by IM or deep SC route. The vaccine should be brought to room temperature before use. Shake before use.

For children, when 1 dose of 0.25 mL is indicated, push the plunger stopper exactly to the edge of the mark of the syringe to eliminate half of the volume. The remaining volume should be injected.

CONTRAINDICATIONS

Hypersensitivity to influenza vaccine, to any of the excipients of Vaxigrip, to eggs, chicken proteins, neomycin, formaldehyde or octoxinol-9.

In case of illness with a high temperature or acute infection, the vaccination should be postponed until after the patient has recovered.

PRECAUTIONS

As with all injectable vaccines, appropriate medical treatment and supervision should be readily available in case of an anaphylactic reaction following the administration of the vaccine.

Poor immune response (immunodeficiency or taking medicines affecting the immune system), the doctor will decide if the patient should receive the vaccine.

Blood test within the days following the flu vaccination; false-positive blood test results have been observed in a few patients who had recently been vaccinated.

As with all vaccines, Vaxigrip may not fully protect all persons who are vaccinated.

Effects on the Ability to Drive or Operate Machinery: Vaxigrip is unlikely to affect the ability to drive vehicles or use machines.

Use in pregnancy & lactation: Limited data about flu vaccination in pregnant women do not indicate that the vaccine would have harmful effects on the pregnancy or the baby. The use of this vaccine may be considered from the 2nd trimester of pregnancy. For pregnant women with a risk of complications from influenza, administration of the vaccine is recommended, irrespective of the stage of pregnancy.

Vaxigrip may be used during lactation.

SIDE EFFECTS

During clinical trials, the following side effects have been observed. Their frequencies have been estimated as Common (affects 1-10 users in 100): Headache, sweating, muscular pain (myalgia), joint pain (arthralgia); fever, generally feeling unwell (malaise), shivering, fatigue; local reactions: Redness, swelling, pain, bruising (ecchymosis), hardness (induration) around the area where the vaccine is injected. These reactions usually disappear within 1-2 days without treatment.

In addition to the common side effects listed previously, the following side effects occurred during post-marketing experience: In rare cases, allergic reactions leading to medical emergency with a failure of the circulatory system to maintain adequate blood flow to the different organs (shock).

In very rare cases, swelling most apparent in the head and neck, including the face, lips, tongue, throat or any other part of the body (angioedema).

Skin reactions that may spread throughout the body including itchiness of the skin (pruritus, urticaria), rash.

Blood vessel inflammation which may result in skin rashes (vasculitis) and in very rare cases, temporary kidney problems.

Pain situated on the nerve route (neuralgia), anomalies in the perception of touch, pain, heat and cold (paraesthesia), fits (convulsions) associated with fever, neurological disorders that may result in stiff neck, confusion, numbness, pain and weakness of the limbs, loss of balance, loss of reflexes, paralysis of part or all the body (encephalomyelitis, neuritis, Guillain-Barre syndrome).

Temporary reduction in the number of certain types of particles in the blood called platelets; a low number of these can result in excessive bruising or bleeding (transient thrombocytopenia), temporary swelling of the glands in the neck, armpit or groin (transient lymphadenopathy).

INTERACTIONS

Vaxigrip can be given at the same time as other vaccines by using separate limbs. In this case, the side effects may be intensified.

The immunological response may decrease in case of immunosuppressant treatment eg, corticosteroids, cytotoxic drugs or radiotherapy.

STORAGE

Store in a refrigerator(2-8°C). Do not freeze. Keep the syringe in the outer carton in order to protect from light.

Shelf-Life: 1 year.

CONTENTS

Polysaccharide of Salmonella typhi.

PRESENTATION

Prefilled syringe 25 mcg/0.5 mL x 1's.

DESCRIPTION

Each 0.5-mL dose contains polysaccharide of Salmonella typhi Ty2 strain 25 mcg.

It also contains the following ingredients: Phenol and a buffer solution containing sodium chloride, disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate and water for injection.

INDICATIONS

Prevention of typhoid fever in adults and children >2 years.

Typhim Vi is especially indicated for travellers to endemic areas, migrants, healthcare professionals and military personnel.

DOSAGE & ADMINISTRATION

A single injection ensures protection. Revaccination should be performed every 3 years if the risk of exposure continues.

The vaccination schedule is the same for children and adults.

Typhim Vi should be administered by IM or SC routes.

CONTRAINDICATIONS

Hypersensitivity to any of the components of Typhim Vi.

Do not inject by IM route to patients with bleeding disorders eg, hemophilia or thrombocytopenia.

Use in children: Typhim Vi is not indicated in children <2 years because efficacy is not adequate in this age group.

PRECAUTIONS

Fever, acute disease, progressive chronic disease (vaccination should be postponed).

Typhim Vi must not be injected by the intravascular route, make sure the needle does not penetrate a blood vessel.

Typhim Vi protects against typhoid fever bacterium (Salmonella typhi), but not against related bacteria (Salmonella paratyphi A or B).

For any vaccine, adverse events following immunization should be monitored. Although anaphylactic reaction is rare, medications for anaphylaxis treatment should always be available at the time of vaccination.

Use in pregnancy & lactation: Because of the seriousness of the disease and in case of high risk of exposure to typhoid fever, pregnancy is not a reason not to administer the vaccine.

Typhim Vi should be used during pregnancy only when advised by the physician.

Typhim Vi may be used during lactation.

SIDE EFFECTS

The effects reported after vaccination are usually moderate and of short duration.

Local Injection Site Reactions: Pain, swelling, redness.

Rare General Reactions: Fever, tiredness, headache, malaise, joint and muscle pain, nausea, abdominal pain.

Very Rare Allergic Reactions: Itching, skin rash, urticaria.

Isolated cases of serum sickness and serious allergic reactions (anaphylactic reactions) have been reported.

INTERACTIONS

Typhim Vi may be given together with other vaccines (hepatitis A, yellow fever, diphtheria, tetanus, poliomyelitis, rabies, meningitis A + C and hepatitis B) during the same vaccination session.

STORAGE

Store in a refrigerator (2-8°C). Do not freeze.

Shelf-Life: 36 months.

CONTENTS

Live attenuated measles, mumps and rubella virus.

PRESENTATION

Vial (freeze-dried powd for susp for inj) 1 dose + syringe 0.5 mL (diluent).

DESCRIPTION

Each dose of vaccine contains measles virus (Schwarz strain) cultivated on primary culture of chicken embryo cells at least 1000 CCID50, mumps virus (Urabe AM-9 strain) cultivated in embryonated hen eggs at least 5000 CCID50, rubella virus (Wistar RA 27/3M strain) activated on human diploid cells at least 1000 CCID50. It also contains human albumin for lyophilization and water for injections 0.5 mL as diluent.

*CCID50=TCID50=cell culture infectious dose 50%.

Trimovax is generally a homogenous pellet varying from yellow to pinkish beige.

After reconstitiution with the provided diluent, Trimovax is a clear solution varying from yellow to pinkish yellow.

INDICATIONS

Combined prevention of measles, mumps and rubella, from 12 months of age in children of both sexes.

DOSAGE & ADMINISTRATION

The 1st injection is administered from 12 months of age. A 2nd injection is recommended between 3 and 6 years.

Trimovax should be administered by SC or IM route.

Any reconstituted vaccine should be used immediately.

CONTRAINDICATIONS

History of severe hypersensitivity to any component of Trimovax or following a previous administration of Trimovax or a vaccine containing the same components or constituents (see Warnings).

Intramuscular route should not be administered for individuals with bleeding disorders eg, hemophilia or thrombocytopenia or malignant diseases.

Trimovax should not be administered to anyone with congenital or acquired immune deficiency impairing cellular immunity, including immunosuppressive therapies eg, chemotherapy, high doses of systemic corticosteroids given generally for ³14 days.

Use in pregnancy: As with all live attenuated vaccines, pregnancy constitutes a contraindication.

Immunization of women of childbearing age may only be carried out after checking that the woman is not pregnant. Pregnancy should be avoided 2 months following administration of the vaccine.

WARNINGS

In the case of individuals receiving immunosuppressive treatment, a 3-month delay after the end of the treatment should be observed before vaccine administration.

The immunization of women in childbearing age may be carried out only after checking that the woman is not pregnant (see Use in pregnancy under Contraindications).

Neomycin is used in the manufacturing process of Trimovax. As each dose may contain residual amounts of neomycin (<25 mcg/dose), caution must be exercised when Trimovax is administered to subjects with hypersensitivity to this antibiotic (and other antibiotic of the same class).

As each dose may contain residual amounts of ovalbumine (<1 mcg/dose), caution must be exercised when the vaccine is administered to subjects with true egg allergy.

Generally, vaccination must be postponed in cases of moderate or severe febrile and/or acute disease or severe infections.

Caution must be exercised when the vaccine is administered to subjects with convulsion history.

Recent injection of immunoglobulins (see Interactions).

PRECAUTIONS

Do not inject via the intravascular route.

Avoid contact between the vaccine and disinfectant products used for cleaning the injection site since they may inactivate the vaccine viruses.

As with all injectable vaccines, supervision and adrenaline used for the control of immediate allergic reactions must be available in case of an anaphylactic event following administration of the vaccine.

Use in lactation: Trimovax is not contraindicated in lactation.

ADVERSE REACTIONS

Based on data gathered from Trimovax post-marketing surveillance, the reported reactions are as follows: The adverse events are ranked under headings of frequency, using the following convention: Rare: 0.01% and 0.1%; very rare: 0.01%, including isolated reports.

General Disorder and Administration Site Conditions: Rare: Pain, induration, nodule, local urticaria, febrile reaction (pyrexia).

Skin and Subcutaneous Tissue Disorders: Rare: Lymphadenopathy. Very Rare: Erythematous or maculopapular rash.

Blood and Lymphatic System Disorders: Very Rare: Thrombocytopenic purpura, thrombocytopenia with a risk of haemorrhage in severe cases (1/100,000 doses).

Immune System Disorders: Very Rare: Allergic reaction including urticaria and face oedema.

Respiratory, Thoracic and Mediastinal Disorders: Very Rare: Rhinopharyngeal and cough.

Nervous System Disorders: Very Rare: Meningitis, meningoencephalitis, febrile convulsion.

Infections and Infestations: Very Rare: Orchitis.

Musculoskeletal and Connective Tissue Disorders: Very Rare: Arthralgia.

INTERACTIONS

In order to avoid neutralization of the attenuated viruses contained in the vaccine, vaccination must generally not be performed within 3 months of injection of human immunoglobulins or blood products containing immunoglobulins eg, blood or plasma.

For the same reason, immunoglobulins should not be administered for 2 weeks following immunization. To prevent the potential risk of interference, a 4-week delay should be observed before and after injection of any live attenuated vaccine.

Tuberculin tests may transiently show false negative results subsequent to vaccination.

STORAGE

Store between 2°C and 8°C. Protect from light.

Shelf-Life: 24 months.