Vivotif^®

The composition in terms of active ingredients is as follows:

- Salmonella enterica serovar Typhi (abbr. S. typhi) Ty21a not less than 2 x 10⁹ viable cells

Quantities expressed per capsule

Enteric-coated capsule, for oral administration to humans.

For active oral immunisation against typhoid fever in children aged 6 years and over, adults and elderly.

Posology

Children aged 6 years and above, adults and elderly: One capsule is to be taken on day 1. The second capsule should be taken on day 3 and the third capsule on day 5.

Unless the immunisation schedule of 3 vaccine capsules is completed, an optimal immune response may not be achieved.

Even after three doses, not all recipients of Vivotif will be fully protected against typhoid fever. Therefore, travellers should take all necessary precautions to avoid contact with or ingestion of potentially contaminated food or water.

Protection against typhoid fever commences approximately 7-10 days after ingesting the third dose of vaccine.

Under conditions of repeated or continuous exposure to S. typhi protection persists for at least 3 years.

In the case of travel from a non-endemic area to an area where typhoid fever is endemic, an annual booster consisting of three doses is recommended.

Children under 6 years: Safety and efficacy have not been established in children under 6 years of age.

Method of administration

The blister containing the vaccine capsules should be inspected to ensure that the foil seal and capsules are intact.

The capsule should be taken approximately one hour before a meal with a cold or lukewarm (temperature not to exceed body temperature, e.g. 37°C [98.6°F]) drink on alternate days, e.g. days 1, 3 and 5. The vaccine capsule should not be chewed and should be swallowed as soon as possible after placing in the mouth.

Vivotif must not be administered:

- To persons known to be hypersensitive to any component of the vaccine or the enteric-coated capsule (see section 6.1).

- To persons with congenital or acquired immune deficiency (including patients receiving immunosuppressive or antimitotic drugs).

- During an acute febrile illness or during an acute gastrointestinal illness. Vaccination should be postponed until after recovery.

None known.

As the growth of vaccine organisms may be inhibited by sulphonamides or antibiotics, vaccination should not commence within 3 days after completing treatment with any antibacterial agents. Also, it is preferable that antibacterial therapy should not commence within 3 days after the last dose of Vivotif.

If malaria prophylaxis is also required, the fixed combination of atovaquone and proguanil can be given concomitantly with Vivotif. Doses of mefloquine and Vivotif should be separated by at least 12 hours. For other antimalarials, there should be an interval of at least 3 days between the last dose of Vivotif and the first dose of malaria prophylaxis.

Vivotif may be administered concomitantly with the live attenuated vaccines yellow fever vaccine and oral polio vaccine.

Animal reproduction studies have not been conducted with Vivotif. It is not known whether Vivotif can cause foetal harm when administered to pregnant women or can affect reproduction capacity. Vivotif should be given to a pregnant woman only if clearly needed.

There are no data regarding administration of Vivotif to nursing mothers. It is not known if Vivotif is excreted in human milk.

None known.

The following adverse reactions were reported commonly (<1/10 but >1/100) in clinical studies:

Gastrointestinal disorders

Abdominal pain, nausea, diarrhoea, vomiting

General disorders and administration site conditions

Fever, influenza-like illness

Nervous system disorders

Headache

Skin and subcutaneous tissue disorders

Rash

The following additional adverse reactions have been reported very rarely (approximately <1/10,000) during post-marketing surveillance:

Skin reactions such as dermatitis, exanthema, pruritus, urticaria.

Anaphylaxis.

Asthenia, malaise, tiredness, shivering.

Paraesthesiae, dizziness.

Arthralgia, myalgia.

Doses five-fold higher than the recommended dose do not produce vomiting, abdominal distress or fever. However overdosing can increase the possibility of shedding the S. typhi Ty21a organisms in the faeces.

As a result of irreversible changes in cell wall biosynthesis, the Ty21a strain is devoid of pathogenicity but is able to elicit an immune response against S. typhi.

Excretion of the vaccine strain after administering doses approximately 50 times greater than those in the present vaccine was assessed by taking stool or rectal swabs daily for 7 days following the last dose of vaccine. The rate of excretion of the vaccine strain in the stools was low, and the vaccine strain could not be recovered from small bowel aspirates one or more days after vaccination. Sera for determination of antibodies to O, H and Vi antigens were obtained prior to vaccination and biweekly for 8 weeks. Fourfold or greater responses in titre of O antibody only were observed. There was no correlation between faecal excretion of the strain Ty21a organisms and seroconversion with respect to titre of any of the antibodies tested.

Not applicable.

There is no other relevant information other than presented in the sections above.

The excipients contained in the preparation are as follows:

Sucrose (Saccharose) Ph. Eur

Ascorbic acid (E300) Ph. Eur

Casein hydrolysate HSE

(Hy-Case SF Sheffield)

Lactose - anhydrous NF/USP, Ph.Eur

Magnesium stearate (E470) Ph. Eur.

Inactivated S. typhi Ty21a bacteria HSE

Capsule:

Gelatin

Titanium dioxide (white) (E171)

Titanium dioxide (red) (E171)

Erythrosine red No.3 (E127)

Ferric oxide (yellow) (E172)

Ferric oxide (red) (E172)

Capsule coating:

HydroxypropyImethyl-cellulose- phthalate

(HP-MCP) - 50

Ethylene glycol

Dibutyl phthalate

Diethyl phthalate

None known.

In blister packs: 18 months from date of packing, unopened, at 2-8°C.

After opening blister: not applicable.

Store at 2-8°C. Protect from light.

Blister packs (PVC/PE/PVDC 250/30/90). Each blister pack contains 3 capsules.

No special instructions.

Crucell Italy S.r.l

Via Zambeletti 25

I – 20021 Baranzate (MI)

Ltaly

PL 15747/0001

23 June 2009

08 June 2010

POM