DUKORAL Oral suspension / Granules Ref.[27525] Active ingredients: Cholera, inactivated, whole cell

No clinical data on protective efficacy of Dukoral against cholera after administration of booster doses are available.

Dukoral confers protection specific to Vibrio cholerae serogroup O1. Immunisation does not protect against V. cholerae serogroup O139 or other species of Vibrio.

In subjects infected with HIV, limited data are available on immunogenicity and safety of the vaccine. Vaccine protective efficacy has not been studied. Immunisation of HIV infected subjects could result in transient increases of viral load. Dukoral may not induce protective antibody levels in subjects with advanced HIV disease. However, an effectiveness study in a population with high HIV prevalence showed similar protection as in other populations.

Antibody response in vaccinees with endogenous or iatrogenic immunosuppression may be insufficient.

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.

Dukoral contains approximately 1.1 g sodium per dose, which should be taken into consideration by patients on a controlled sodium diet.

The vaccine does not provide complete protection and it is important to adhere additionally to standard protective measures to avoid cholera.

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

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

Preliminary results from a clinical study including a limited number of volunteers showed no interaction with the antibody response to Dukoral when a live oral vaccine (enterocapsules) against typhoid was given simultaneously with Dukoral. The immune response to live typhoid vaccine was not investigated in this study. Similarly, a yellow fever vaccine was given concomitantly with Dukoral, and there was no interaction observed with the immune response to the yellow fever vaccine. The immune responses to Dukoral were not studied. No other vaccines/medicinal products, including oral polio vaccine and antimalarials, have been given simultaneously with Dukoral in clinical studies.

No animal data on reproduction toxicity are available. Following careful benefit/risk assessment the vaccine may be administered during pregnancy and to breast-feeding women although no specific clinical studies have been performed to address this issue.

During a mass-vaccination campaign conducted in Zanzibar, 196 pregnant women had received at least one dose of Dukoral. There was no statistically significant evidence of a harmful effect of Dukoral exposure during pregnancy.

There is no evidence of an effect on the ability to drive and use machines.

The safety of Dukoral was assessed in clinical trials, including both adults and children from 2 years of age, conducted in endemic and non-endemic countries for cholera and enterotoxigenic Escherichia coli (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, such as gastrointestinal symptoms including abdominal pain, diarrhoea, loose stools, nausea and vomiting, occurred at similar frequencies in vaccine and placebo groups.

Frequency classification: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Metabolism and nutrition disorder

Rare: Loss of /or poor appetite

Very rare: Dehydration

Nervous system disorders

Uncommon: Headache

Rare: Dizziness

Very rare: Drowsiness, insomnia, fainting, reduced sense of taste

Respiratory, thoracic and mediastinal disorders

Rare: Respiratory symptoms (including rhinitis and cough)

Gastrointestinal disorders

Uncommon: Diarrhoea, abdominal cramps, abdominal pain, stomach/abdominal gurgling (gas), abdominal discomfort

Rare: Vomiting, nausea

Very rare: Sore throat, dyspepsia

Skin and subcutaneous tissue disorders

Very rare: Sweating, rash

Musculoskeletal and connective tissue disorders

Very rare: Joint pain

General disorders and administration site conditions

Rare: Fever, malaise

Very rare: Fatigue, shivers

Adverse reactions from post-marketing surveillance

Additional adverse reactions reported during post-marketing surveillance are listed below.

Infections and infestations: Gastroenteritis

Blood and lymphatic system disorders: Lymphadenitis

Nervous system disorders: Paraesthesia

Vascular disorders: Hypertension

Respiratory, thoracic and mediastinal disorders: Dyspnoea, increased sputum

Gastrointestinal disorders: Flatulence

Skin and subcutaneous tissue disorders: Urticaria, angioedema, pruritus

General disorders and administration site conditions: Pain, flu-like syndrome, asthenia, chills

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.