Dukoral

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



2 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Dukoral suspension and effervescent granules for oral suspension 
Cholera vaccine (inactivated, oral) 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each dose of vaccine suspension (3 ml) contains: 
 

− A total of 1.25x1011 bacteria of the following strains: 
Vibrio cholerae O1 Inaba, classical biotype (heat inactivated) 31.25x109 bacteria* 
Vibrio cholerae O1 Inaba, El Tor biotype (formalin inactivated) 31.25x109 bacteria* 
Vibrio cholerae O1 Ogawa, classical biotype (heat inactivated) 31.25x109 bacteria* 
Vibrio cholerae O1 Ogawa, classical biotype (formalin inactivated) 31.25x109 bacteria* 

− Recombinant cholera toxin B subunit (rCTB) 1 mg 
(produced in V. cholerae O1 Inaba, classical biotype strain 213.) 

 
* Bacterial count before inactivation. 
 
Excipients: 
Sodium dihydrogen phosphate dihydrate 2.0 mg, disodium hydrogen phosphate dihydrate 9.4 mg, 
sodium chloride 26 mg, sodium hydrogen carbonate 3600 mg, sodium carbonate anhydrous 400 mg, 
saccharin sodium 30 mg, sodium citrate 6 mg. 
 
One dose contains approximately 1.1 g sodium. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension and effervescent granules for oral suspension: 
– Suspension for oral suspension  

- Granules for oral suspension in a sachet.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Dukoral is indicated for active immunisation against disease caused by Vibrio cholerae serogroup O1 
in adults and children from 2 years of age who will be visiting endemic/epidemic areas. 
 
The use of Dukoral should be determined on the basis of official recommendations taking into 
consideration the variability of epidemiology and the risk of contracting disease in different 
geographical areas and travelling conditions. 
 
Dukoral should not replace standard protective measures. In the event of diarrhoea measures of 
rehydration should be instituted. 
 
4.2 Posology and method of administration 
 
Posology 



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Primary vaccination schedule 
The standard primary course of vaccination with Dukoral against cholera consists of 2 doses for 
adults and children from 6 years of age. Children 2 to below 6 years of age should receive 3 doses. 
Doses are to be administered at intervals of at least one week. If more than 6 weeks have elapsed 
between doses, the primary immunisation course should be re-started. 
 
Immunisation should be completed at least 1 week prior to potential exposure to V. cholerae O1. 
 
Booster dose 
For continuous protection against cholera a single booster dose is recommended within 2 years for 
adults and children from 6 years of age, and within 6 months for children aged 2 to below 6 years. No 
clinical efficacy data has been generated on repeat booster dosing. However, immunological and 
duration of protection data suggest that if up to 2 years have elapsed since the last vaccination for 
adults and up to 6 months for children aged 2 to below 6 years a single booster dose should be given. 
If more than 2 years have elapsed since the last vaccination (more than 6 months for children aged 2 
to below 6 years) the primary course should be repeated. 
 
Children less than 2 years 
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 to be used in children less than 2 years of age.  
 
Elderly 
There are only very limited data on protective efficacy of the vaccine in subjects aged 65 years and 
more. 
 
Method of administration 
The vaccine is intended for oral use. Before ingestion, the suspension should be mixed with the buffer 
(sodium hydrogen carbonate) solution. The sodium hydrogen carbonate is supplied as effervescent 
granules, which should be dissolved in a glass of cool water (approx. 150 ml). Chlorinated water can 
be used. The suspension should then be mixed with the buffer solution and drunk within 2 hours. 
Food and drink should be avoided 1 hour before and 1 hour after vaccination. Oral administration of 
other medicinal products should be avoided within 1 hour before and 1 hour after administration of 
Dukoral. 
 
Children 2 to below 6 years of age: half of the buffer solution is poured away and the remaining part 
(approx. 75 ml) is mixed with the entire contents of the  vial. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or to 
formaldehyde. 
 
Administration of Dukoral should be postponed for subjects suffering from acute gastrointestinal 
illness or acute febrile illness.  
 
4.4 Special warnings and precautions for use 
 
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 



4 
 

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.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
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.  
 
4.6 Fertility, pregnancy and lactation 
 
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. 
 
4.7 Effects on ability to drive and use machines 
 
There is no evidence of an effect on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
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 



5 
 

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. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


6 
 

4.9 Overdose 
 
Data on overdose are limited. Adverse reactions reported are consistent with those seen after the 
recommended dosing. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Bacterial vaccines, ATC-code: J07AE01 
 
Mechanism of action 

The vaccine contains killed whole V. cholerae O1 bacteria and the recombinant non-toxic B-subunit 
of the cholera toxin (CTB). Bacterial strains of both Inaba and Ogawa serotypes and of El Tor and 
Classical biotypes are included in the vaccine. Dukoral is taken orally with bicarbonate buffer, which 
protects the antigens from the gastric acid. The vaccine acts by inducing antibodies against both the 
bacterial components and CTB. The antibacterial intestinal antibodies prevent the bacteria from 
attaching to the intestinal wall thereby impeding colonisation of V. cholerae O1. The anti-toxin 
intestinal antibodies prevent the cholera toxin from binding to the intestinal mucosal surface thereby 
preventing the toxin-mediated diarrhoeal symptoms.  
 
The heat-labile toxin (LT) of enterotoxigenic E. coli (ETEC ) is structurally, functionally and 
immunologically similar to CTB. The two toxins cross-react immunologically.  
 
Efficacy against cholera  

Efficacy against cholera was assessed in three randomised double-blind placebo-controlled clinical 
trials conducted in Bangladesh (endemic region) and in Peru (non-endemic region). The number of 
patients enrolled, dosage regimens and follow-up periods are shown in the following table. 
 

Study 
location 

Year Dosage regimen  Number 
(Age groups) 

Follow up 

Cholera  

Bangladesh  1985-88 3 doses at 6 week intervals 89,152 
(2-65 years) 

6 months-5 years 

Peru, 
military 

 

1994 2 doses 7-11 days apart 1,563 
(18-65 years) 

5 months 

Peru, 
Pampas  

1993-95 2 doses 2 weeks apart with a booster 
dose 1 year later 

21,924 
(2-65 years) 

2 years 

 
In the Bangladesh field trial, protective efficacy of Dukoral in the overall population was 85% 
(95%CI: 56, 95, per-protocol analysis) for the initial 6 months of follow-up. Duration of vaccine 
protection differed by age, lasting for 6 months in children and for 2 years in adults (see table below). 
An exploratory analysis suggested that 2 vaccine doses seemed as effective as 3 doses in adults.   
 
Table: Protective efficacy against cholera in the Bangladesh study (per-protocol analysis)  
 Protective efficacy, % (95% CI) 
 Adults and children >6 

year 
Children 2-6 

years 
6 months 76 (30, 92) 100 
1st year 76 (60, 85) 44 (10, 65) 
2nd year 60 (36, 76) 33 (-23, 64) 

 



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In the second trial, conducted in Peru and enrolling military recruits, the short-term protective efficacy 
against cholera after 2 vaccine doses was 85% (95%CI: 36, 97, per-protocol analysis). The third 
study, a field trial conducted in Peru, failed to show any protective efficacy against cholera during the 
first year. Following a booster dose 10-12 months after primary immunisation, the protective efficacy 
during the second year was 60.5% (95%CI: 28,79).  
 
Protective effectiveness against cholera was evaluated during two mass-vaccination campaigns 
conducted in Mozambique (December 2003 – January 2004) and Zanzibar (February 2009 – May 
2010).  
 
In the case-control study conducted during the mass vaccination campaign in Mozambique, protective 
effectiveness of 2 doses of Dukoral was 84% (95% CI: 43, 95, per-protocol analysis; p=0.005) for the 
initial 5 months of follow-up.  
 
In the longitudinal cohort-analysis conducted during the mass-vaccination campaign in Zanzibar, 
protective effectiveness after 2 doses of Dukoral was 79% (95% CI, 47, 92) for a follow-up period of 
15 months. In addition to the direct protection, it was shown that Dukoral provides significant indirect 
(herd) protection in the studied setting. 
 
Protective efficacy of Dukoral against cholera has not been studied following repeated booster 
vaccination. 
 
Immunogenicity 

No established immunological correlates of protection against cholera after oral vaccination have 
been identified. There is a poor correlation between serum antibody responses, including vibriocidal 
antibody response, and protection. Locally produced secretory IgA antibodies in the intestine 
probably mediate protective immunity. 

The vaccine induced intestinal antitoxin IgA responses in 70-100% of vaccinated subjects. Serum 
vibriocidal antibodies against the bacterial components were seen in 35-55% of vaccinated subjects 
and antitoxic antibodies in 78-87% of vaccinated subjects. A booster dose elicited an anamnestic 
response indicative of an immune memory. The duration of the immunological memory was estimated 
to last for at least 2 years in adults.  
 
5.2 Pharmacokinetic properties 
 
Not applicable. 
 
5.3 Preclinical safety data 
 
No preclinical safety testing with the vaccine has been conducted. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 

- suspension for oral suspension: 
 

Sodium dihydrogen phosphate dihydrate 
Disodium hydrogen phosphate dihydrate 
Sodium chloride 
Water for injections 
 
- granules for oral suspension in a sachet :: 
 

Sodium hydrogen carbonate 



8 
 

Citric acid 
Sodium carbonate, anhydrous 
Saccharin sodium  
Sodium citrate 
Raspberry flavour 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other 
medicinal products. 
 
6.3 Shelf life 
 
3 years. 
 
After the effervescent granules have been dissolved in water and the vaccine suspension has been 
added, the mixture should be drunk within 2 hours. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
 
Product in the unopened vial and sachet, stored in the outer carton, is stable at temperatures up to 
25oC for a period of 14 days. At the end of this period the product should be used or discarded. 
 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
The vaccine suspension is filled in a volume of 3 ml in vials (type I glass) with a rubber stopper 
(bromobutyl rubber) and a screw cap. 
The effervescent granules are filled in an amount of 5.6 g in sachets with an inner layer of 
polyester/LD-polyethylene and an outer layer of aluminium/LD-polyethylene. 
 
Each dose of vaccine is supplied as one vial of suspension together with one sachet of effervescent 
granules. 
 
Pack sizes: 1x1 dose, 2x1 dose, 20x1 dose 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
The effervescent granules should be dissolved in approximately 150 ml of cool water to get the buffer 
solution. The vaccine vial should be shaken gently and the vaccine suspension should then be added 
to the buffer solution and mixed well to get the colourless slightly opalescent oral suspension. 
Children 2 to below 6 years of age: half of the buffer solution is poured away and the remaining part 
(approx. 75 ml) is mixed with the entire contents of the vaccine vial. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 



9 
 

7. MARKETING AUTHORISATION HOLDER 
 
Valneva Sweden AB 
S-105 21 Stockholm 
Sweden 
+46 (0)8 735 1000 
infodukoral@valneva.com 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/03/263/001-003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 April 2004 
Date of latest renewal: 25 March 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
MM/YYYY 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMA) http://www.ema.europa.eu/. 
 

mailto:infodukoral@valneva.com
http://www.emea.europa.eu/


10 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

 
 
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE 

SUBSTANCES AND MANUFACTURER RESPONSIBLE 
FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



11 
 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturers of the biological active substances 
 
Valneva Sweden AB 
SE-105 21 Stockholm 
Sweden 
 
Name and address of the manufacturer responsible for batch release 
 
Valneva Sweden AB 
SE-105 21 Stockholm 
Sweden 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
 
Medicinal product subject to medical prescription. 
 
• Official batch release  
 
In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken 
by a state laboratory or a laboratory designated for that purpose 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
The holder of this marketing authorisation must inform the European Commission about the 
marketing plans for the medicinal product authorised by this decision. 
 

 
• Periodic Safety Update Reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk Management Plan (RMP) 
 
Not applicable. 
 



12 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



13 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



14 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
DUKORAL – 1 dose package, 2x1 dose package, 20x1 dose package (outer sleeve)  
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
DUKORAL suspension and effervescent granules for oral suspension 
Cholera vaccine (inactivated, oral) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCES 
 
Active substances: 1 dose contains  
− 31.25x109 bacteria* of each of the following V. cholerae O1 strains: Inaba classical biotype (heat 

inactivated), Inaba El Tor biotype (formalin inactivated), Ogawa classical biotype (heat 
inactivated), Ogawa classical biotype (formalin inactivated).  

− Recombinant cholera toxin B subunit (rCTB) 1 mg. 
 
*bacterial content prior to inactivation 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
3 ml of suspension in a vial and 5.6 g of effervescent granules in a sachet. 
1 dose 
2x1 dose 
20x1 dose 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For oral use. 
Mix suspension with buffer solution before drinking. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 



15 
 

 
EXP MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Valneva Sweden AB 
105 21 Stockholm, Sweden 
 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/263/001 1 dose 
EU/1/03/263/002 2x1 dose 
EU/1/03/263/003 20x1 dose 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
 
16. INFORMATION IN BRAILLE 
 
DUKORAL 
 
 
17. UNIQUE IDENTIFIER 
 
2D barcode carrying the unique identifier included.  
 
 



16 
 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN: 
NN: 



17 
 

 
 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
DUKORAL – 20x1 dose package (inner carton for 20 vaccine vials) 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
DUKORAL suspension 
Cholera vaccine (inactivated, oral) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCES 
 
Active substances: 1 dose contains  
− 31.25x109 bacteria* of each of the following V. cholerae O1 strains: Inaba classical biotype (heat 

inactivated), Inaba El Tor biotype (formalin inactivated), Ogawa classical biotype (heat 
inactivated), Ogawa classical biotype (formalin inactivated).  

− Recombinant cholera toxin B subunit (rCTB) 1 mg. 
 
*bacterial content prior to inactivation 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
3 ml of suspension in a vial. 
20x1 dose. 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For oral use. 
Mix suspension with buffer solution before drinking. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
 
 
8. EXPIRY DATE 



18 
 

 
EXP MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Valneva Sweden AB 
105 21 Stockholm, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/263/003 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 



19 
 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
DUKORAL – 20x1 dose package (inner carton for 20 sodium hydrogen carbonate sachets) 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Sodium hydrogen carbonate 
Effervescent granules 
 
 
2. STATEMENT OF ACTIVE SUBSTANCES 
 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sodium. See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
20 x 5.6 g  
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be used with DUKORAL. 
For oral use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 



20 
 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Valneva Sweden AB 
105 21 Stockholm, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/03/263/003 
 
 
13. BATCH NUMBER 
 
Lot  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
 



21 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
DUKORAL, vial label 1 dose 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
DUKORAL suspension  
Oral use. 
 
 
2. METHOD OF ADMINISTRATION 
 
Read the package leaflet before use.  
 
 
3. EXPIRY DATE 
 
EXP MM/YYYY 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 dose (3 ml) 
 
 
6. OTHER 
 
 
 
 
 



22 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Sodium hydrogen carbonate 5.6 g, sachet 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Sodium hydrogen carbonate effervescent granules 
Oral use. 
 
2. METHOD OF ADMINISTRATION 
 
To be used with DUKORAL. 
Read the package leaflet before use. 
 
 
3. EXPIRY DATE 
 
EXP MM/YYYY 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5.6 g 
 
6. OTHER 
 
Valneva Sweden AB, Sweden 



23 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



24 
 

PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

DUKORAL suspension and effervescent granules for oral suspension 
Cholera vaccine (inactivated, oral) 

 
Read all of this leaflet carefully before you start using this vaccine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, nurse or pharmacist. 
- This vaccine has been prescribed for you only. Do not pass it on to others. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See Section 4. 
- Make sure to mix the vaccine with buffer solution as described in this leaflet. See Section 3. 
 
What is in this leaflet:  
1. What Dukoral is and what it is used for 
2. What you need to know before you use Dukoral 
3. How to use Dukoral 
4. Possible side effects 
5 How to store Dukoral 
6. Contents of the pack and other information 
 
 
1. What Dukoral is and what it is used for 
 
Dukoral is an oral vaccine against cholera that stimulates the immunological defence in the gut. The 
vaccine protects adults and children from 2 years of age against cholera.  
 
Dukoral causes your body to produce its own protection against cholera. After getting the vaccine, 
your body will make substances called antibodies, which fight the cholera bacteria and toxin that 
cause diarrhoea.  
 
2. What you need to know before you use Dukoral 
 
Do not use Dukoral 

• if you are allergic to any ingredient of the vaccine or to formaldehyde. 
• if you have an acute stomach disorder or infection with fever (vaccination should be delayed). 

 
 
Warnings and precautions 
Talk to your doctor before taking Dukoral 

• if you take a medical treatment that affects the immune system   
• if you have a disease of the immune system (including HIV infection).  

The vaccine may provide you with a lower level of protection than it does for people with healthy 
immune systems. 
 
The vaccine does not provide complete protection and it is important to adhere to dietary and hygiene 
advice to avoid diarrhoeal diseases. 
 
Children 
Do not give this vaccine to children younger than 2 years since the protection has not been studied in 
this group. 
 
Other medicines and Dukoral 
Please tell your doctor if you are taking or have recently taken any other medicines. 
Do not take other medicine starting 1 hour before until 1 hour after taking the vaccine.  



25 
 

 
Using Dukoral with food and drink 
Avoid food and drink starting 1 hour before until 1 hour after the vaccination. 
 
Pregnancy and breast-feeding 
If you are pregnant, think you may be pregnant or are planning to have a baby or are breast-feeding, 
ask your doctor before taking the vaccine.  
 
Driving and using machines 
 There are no reasons to suspect that Dukoral will affect your ability to drive or handle machines 
 
Dukoral contains sodium 
Dukoral contains approximately 1.1 g sodium per dose. Please take this into consideration if you are 
on a controlled sodium diet. 
 
 
3. How to use Dukoral 
Always use this medicine exactly as described in this leaflet or as your doctor has told you. Check 
with your doctor if you are not sure. 
Adults and children from 6 years of age: The primary vaccination is 2 doses taken orally (by mouth) 
at least 1 week (up to 6 weeks) apart.  

• Take the 1st dose no later than 2 weeks before you leave for your trip. 
• Take the 2nd dose at least 1 week after the 1st dose and at least 1 week before your trip.  

It takes about 1 week after the last dose for protection to begin. 
For continuous protection, re-vaccination is recommended within 2 years. If you had your last dose of 
vaccine less than 2 years ago a single dose will renew your protection. If more than 2 years have 
passed since you had the last vaccine dose, the primary vaccination (2 doses) should be repeated. 
 
Children of 2 to below 6 years of age: The primary vaccination is 3 doses taken orally (by mouth) at 
least 1 week (up to 6 weeks) apart. Only half of the amount of the buffer solution should be mixed 
with the vaccine.  

• Give the 1st dose to the child no later than 3 weeks before you leave for your trip.  
• Give the 2nd dose to the child at least 1 week after the 1st dose.  
• Give the 3rd dose at least one week after the 2nd dose and at least one week before your trip. 

 
It takes about 1 week after the last dose for protection to begin. 
For continuous protection, re-vaccination is recommended within 6 months. If less than 6 months 
have passed since the last vaccination a single dose will renew the protection. If more than 6 months 
have passed since the last vaccination, the primary vaccination (3 doses) should be repeated. 
 
The suspensionsupplied in a single-dose glass vial is a whitish suspension.. Each vial comes with one 
sachet package that contains white effervescent granules of sodium hydrogen carbonate.  The 
effervescent granules should be dissolved in a glass of cool water, and the resulting buffer solution 
should be mixed with the suspension. It is important to use the buffer solution, as it protects the 
vaccine from the gastric acid. 
 
Drink the entire mixture within 2 hours after mixing with the buffer solution. 



26 
 

 
Instructions for use: 
 
 

 
 

 
 
If you take more Dukoral than you should 
If you take the doses less than one week apart, contact your doctor, pharmacist or nurse. 
Because each vial of Dukoral contains only one dose, overdosage is unlikely.  
If you have taken more than one dose at one time, please contact your doctor, pharmacist or nurse. 
 
If you forget to take Dukoral. 
You can take the 2nd dose of Dukoral up to 6 weeks after the 1st dose (children of 2 to below 6 years 
have to take 3 doses). If more than 6 weeks have passed, contact your doctor, pharmacist or nurse. 
 
If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse. 
 
4. Possible side effects 
 
Like all medicines, Dukoral can cause side effects, although not everybody gets them. 
Contact a doctor immediately if you experience the following serious side effects: 

• severe diarrhoea with loss of water from the body  
• serious allergic reactions causing swelling of the face or throat and breathlessness  

 
Other side effects: 
Uncommon side effects (may affect up to 1 in a 100 people)  

• Diarrhoea, stomach pain, stomach cramps, gurgling stomach, bloated stomach, stomach gas and 
general stomach discomfort  

• Headache 
 

1. To prepare the buffer solution,dissolve the effervescent granules in a glass of cool water 
(approx. 150 ml) by gently stirring.  
Do not use any other liquid. 
For children of 2 to below6 years: pour away half of the buffer solution.  
 

2. Shake the Dukoral® suspension vial (1 vial = 1 dose). 
 
3. Pour the content of the Dukoral® suspension vial into the glass of buffer solution (see 1).  

Mix by gently stirring. 
 
 
4. Drink the entire mixture within 2 hours. Avoid food and drink starting 1 hour before 

 until 1 hour after drinking the mixture.  
 



27 
 

Rare side effects (may affect up to 1 in a 1,000 people) 
• Fever 
• Generally feeling unwell, feeling dizzy  
• Nausea (feeling sick), vomiting, loss of /or poor appetite 
•  Swelling irritation inside the nose, and cough. 

 
Very rare side effects (may affect up to 1 in a 10,000 people)  

• Rash  
• Sore throat, reduced sense of taste 
• Fatigue/feeling tired  
• Sweating, shivering 
• Joint pain 
• Difficulty in sleeping 

 
Other side effects (frequency cannot be estimated from the available data) 

• Flu -like symptoms, chestiness, chills, general pain, weakness 
• Hives, itching 
• Swelling of the lymph glands 
• Numbness or pins and needles 
• High blood pressure 

 
Reporting of side effects 
If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via 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. How to store Dukoral 
 
Keep this medicine out of the sight and reach of children. 
Do not use Dukoral after the expiry date which is stated on the carton after EXP. The expiry date 
refers to the last day of that month. 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
 
Product in the unopened vial and sachet, stored in the outer carton, is stable at temperatures up to 
25oC for a period of 14 days. At the end of this period the product should be used or discarded. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Dukoral contains 
• The active substances are: 

31.25x109 bacteria* of each of the following V. cholerae O1 strains: Inaba classical biotype 
(heat inactivated), Inaba El Tor biotype (formalin inactivated), Ogawa classical biotype (heat 
inactivated), Ogawa classical biotype (formalin inactivated).  
Recombinant cholera toxin B subunit (rCTB) 1 mg. 
*bacterial content prior to inactivation 

 
• The other ingredients in the vaccine suspension are sodium dihydrogen phosphate, disodium 

hydrogen phosphate, sodium chloride and water for injections. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


28 
 

• The effervescent granules contain sodium hydrogen carbonate, citric acid, sodium carbonate, 
saccharin sodium, sodium citrate and raspberry flavour. 

 
What Dukoral looks like and contents of the pack 
Dukoral is presented as a suspension and effervescent granules for oral suspension. The suspension is 
a whitish suspension supplied in a vial. The effervescent granules are white with a raspberry flavour 
and are supplied in a sachet. 
 
Dukoral is available in packs of 1, 2 and 20 doses. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer  
Valneva Sweden AB, 105 21 Stockholm, Sweden.  
infodukoral@valneva.com 
 
This leaflet was last revised in MM/YYYY 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 
This leaflet is available in all EU/EEA languages on the European Medicines Agency website. 
 
 

mailto:infodukoral@valneva.com
http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT  
	A. LABELLING
	B. PACKAGE LEAFLET