Dukoral

Food and drink should be avoided 1 hour before and 1 hour after vaccination as the vaccine is acid labile. Food and/or drink may increase acid production in the stomach and the effect of the vaccine may be impaired.

DUKORAL should only be mixed with the supplied effervescent granules dissolved in water.

The administration of an encapsulated oral typhoid vaccine and DUKORAL [Oral, Inactivated Travellers’ Diarrhea and Cholera Vaccine] should be separated by at least 8 hours.

Oral administration of other vaccines and medicinal products should be avoided 1 hour before and 1 hour after vaccination.

DUKORAL has been administered concomitantly with yellow fever vaccine to 55 subjects. The yellow fever antibody response was similar to that seen in the 58 subjects who received the yellow fever vaccine alone. However, no results are available to evaluate the safety of concomitant administration of the two vaccines or to evaluate the immune response to DUKORAL when administered with yellow fever vaccine.

There are obvious practical advantages to giving more than one vaccine at the same time, especially in preparation for foreign travel or when there is doubt that the patient will return for further doses of vaccine. Most of the commonly used antigens can safely be given simultaneously. No increase in the frequency or severity of clinically significant side effects has been observed. The immune response to each antigen is generally adequate and comparable to that found in patients receiving these vaccines at separate times.

Mix the vaccine according to the directions below:

Step 1: Dissolve the powder from the sachet in 5 oz. (150 mL) of cool water.

For adults and children 6 years and older—proceed to Step 2.

For children 2 to 6 years—discard half the mixture and proceed to Step 2.

Step 2: Shake the small glass vial that contains the vaccine to mix it well.

Step 3: Open the vial and add the vaccine to the liquid in the glass. Stir well and drink immediately.

If the mixture is not drunk immediately, it should be consumed within 2 hours of mixing. Keep it at room temperature.

Do not eat or drink for 1 hour before and 1 hour after taking the vaccine.

Do not take any other medicine for 1 hour before and 1 hour after taking the vaccine.

Use only cool water to mix the vaccine. (See How to Prepare DUKORAL.) Do not use any other liquid.

3 doses orally at least 1 week apart and finishing at least 1 week before departure.

• 1^st dose at least 3 weeks before departure; 2^nd dose 1 week later; 3^rd dose 1 week later and at least one week before departure.

  
  

• Protection against cholera starts after 1 week and will last for 6 months for children 2 to 6 years.

  
  

• If more than 6 weeks elapse between the 1^st and 2^nd dose, the primary immunization should be re-started.

2 doses orally at least 1 week apart.

If the second dose is missed, it can be taken at any time within six weeks. Food and drink are to be avoided for 1 hour before and 1 hour after.

2 doses orally at least 1 week apart.

If the patient received the last dose between 6 months and 5 years before, one booster dose will renew the protection.

If the patient received the last dose between 3 months and 5 years before, one booster dose will renew the protection.

If the patient received the last dose between 2 and 5 years before, one booster dose will renew the protection.

Additional adverse reactions reported (very rare <1/10 000) during post-marketing surveillance, following distribution of approximately 7 000 000 vaccine doses, are listed below:

Rare: loss of or poor appetite. Very rare: dehydration.

The safety of DUKORAL [Oral, Inactivated Travellers’ Diarrhea and Cholera Vaccine] was assessed in clinical trials, including both adults and children, conducted in endemic and non-endemic countries for cholera and ETEC producing heat-labile enterotoxin (LT). Over 94 000 doses of DUKORAL were administered during the clinical trials. Evaluation of safety varied between trials with respect to mode of surveillance, definition of symptoms and time of follow-up. In the majority of studies adverse events were assessed by passive surveillance. The most frequently reported adverse reactions occurred at similar frequencies in vaccine and placebo groups. These included gastrointestinal symptoms including abdominal pain, diarrhea, loose stools, nausea and vomiting.

hypertension.

Physicians, nurses and pharmacists should report any adverse occurrences temporally related to the administration of the product in accordance with local requirements and to the Global Pharmacovigilance Department, Sanofi Pasteur Limited, 1755 Steeles Avenue West, Toronto, ON, M2R 3T4, Canada. 1-888-621-1146 (phone) or 416-667-2435 (fax).

pain, flu-syndrome, asthenia, chills.

In clinical trials conducted in Bangladesh, Peru and Sweden, gastrointestinal symptoms were reported with similar frequency in vaccine and placebo groups. No serious adverse reactions were reported.

paraesthesia.

Rare: respiratory symptoms (including rhinitis and cough).

dyspnoea, increased sputum.

lymphadenitis.

Very common: ≥1/10 (≥10%). Common (frequent): ≥1/100 and <1/10 (≥1% and <10%). Uncommon (infrequent): ≥1/1000 and <1/100 (≥0.1% and <1%). Rare: ≥1/10 000 and <1/1000 (≥0.01% and <0.1%). Very rare: <1/10 000 (<0.01%), including isolated reports.

urticaria, angioedema, pruritus.

flatulence.

gastroenteritis.

Very rare: joint pain.

DUKORAL has been given to persons over the age of 65 in clinical trials, but there are only very limited data on protective efficacy of the vaccine in this age group. However, this group can be expected to be at risk of more severe complications of disease if infected by ETEC or cholera and therefore may obtain greater benefit from vaccination.

As with any vaccine, immunization with DUKORAL [Oral, Inactivated Travellers’ Diarrhea and Cholera Vaccine] may not protect 100% of susceptible persons.

Travellers should use care in the choice of food and water supply and use good hygienic measures.

Immunocompromised persons (whether from disease or treatment) may not obtain the expected immune response. If possible, consideration should be given to delaying vaccination until after the completion of any immunosuppressive treatment.

DUKORAL can be given to HIV-infected persons. Clinical trials have shown no vaccine-associated adverse events and no change in disease clinical progression. Limited data are available on immunogenicity and safety of the vaccine. Vaccine protective efficacy has not been studied among HIV-infected persons. However, in a field study in Mozambique the protective efficacy was 84% in a population with approximately 25% HIV prevalence.

Formaldehyde is used during the manufacturing process and trace amounts may be present in the final product. Caution should be taken in subjects with known hypersensitivity to formaldehyde.

As with all products, the possibility of allergic reactions in persons sensitive to components of the vaccine should be evaluated.

DUKORAL confers protection specific to V. cholerae serogroup O1. DUKORAL has not been demonstrated to protect against cholera caused by V. cholerae serogroup O139 or other species of Vibrio.

Do not administer this vaccine parenterally. This vaccine must be taken orally (by mouth).

Before administration, take all appropriate precautions to prevent adverse reactions. This includes a review of the patient’s history concerning possible hypersensitivity to the vaccine or similar vaccine, previous immunization history, the presence of any contraindications to immunization and current health status.

Before administration of any vaccine, health-care providers should inform the patient, parent or guardian of the benefits and risks of immunization, inquire about the recent health status of the patient and comply with any local requirements regarding information to be provided to the patient before immunization and the importance of completing the immunization series.

DUKORAL has been given to children between 1 and 2 years of age in safety and immunogenicity studies, but the protective efficacy has not been studied in this age group. Therefore, DUKORAL is not recommended for children less than 2 years of age.

The effect of DUKORAL [Oral, Inactivated Travellers’ Diarrhea and Cholera Vaccine] on embryo-fetal development has not been assessed and animal studies on reproductive toxicity have not been conducted. No specific clinical studies have been performed to address this issue. The vaccine is therefore not recommended for use in pregnancy. However, DUKORAL is an inactivated vaccine that does not replicate. DUKORAL is also given orally and acts locally in the intestine. Therefore, in theory, DUKORAL should not pose any risk to the human fetus. Administration of DUKORAL to pregnant women may be considered after careful evaluation of the benefits and risks.

DUKORAL may be given to lactating women.

DUKORAL [Oral, Inactivated Travellers’ Diarrhea and Cholera Vaccine] consists of killed V. cholerae and the non-toxic recombinant cholera toxin B subunit. The vaccine acts locally in the gastrointestinal tract to induce an IgA antitoxic and antibacterial response (including memory) comparable to that induced by cholera disease itself. The protection against cholera is specific for both biotype and serotype. O-antigens as well as toxin B subunit will induce immunity. Most ETEC strains produce an enterotoxin which is structurally, pathophysiologically and immunologically similar to cholera toxin. This enterotoxin is neutralized by antibodies against cholera toxin B subunit. Hence, the vaccine confers protection against ETEC, as well as cholera.

In clinical trials DUKORAL has been shown to prevent TD caused by enterotoxigenic E. coli and cholera caused by V. cholerae O1 (classical and El Tor biotypes). Protection against ETEC diarrhea and cholera can be expected about one week after the primary immunization series is completed.

Clinical results have revealed a protective efficacy against cholera of 80-85% for the first six months in all age categories. In adults and children over the age of 6, protective efficacy over a 3-year follow-up period averaged about 63% (without a booster dose). Children under the age of 2 were not examined, but protective efficacy in the 2-6 year age range was satisfactory for the first six months.

Protective efficacy with reference to all TD will vary depending on the prevalence of ETEC. There are considerable variations between different seasons and geographic areas. Protective efficacy against ETEC lasts about 3 months.