1. Clinical condition or situation to which the direction applies

Indication

• Active immunisation against disease caused by Vibrio cholerae serogroup O1.

Objectives of care

• To decrease morbidity and mortality from cholera in individuals who will be visiting

endemic/epidemic areas.

Inclusion criteria

• Valid consent has been obtained from the patient/carer who does not want to consult with their GP and would prefer to access vaccination from the PGD user.

• Patients from 2 years of age.

• Relief or disaster aid workers.

• Persons with itineraries in areas where cholera hotspots or epidemics are occurring.

• Travellers to potential cholera risk areas.

Exclusion criteria

(Refer to current and relevant SPC (Great Britain or Northern Ireland) and online Green Book guidance for additional details)

• Patients for whom no valid consent has been received.

• Hypersensitivity to the active substance(s), or to any of the excipients or trace residuals in Dukoral® vaccine or Vaxchora® vaccine. See section 2 and 6.1 of the relevant Summary of Product Characteristics (SPC).

• Hypersensitivity to formaldehyde (Dukoral® only).

• Had a confirmed anaphylactic reaction to a previous dose of oral cholera vaccine.

• Individuals under 2 years of age.

• Current acute febrile illness.

• Current acute gastrointestinal illness.

• Has an evolving neurological condition. (With an evolving neurological condition, immunisation should be deferred until the neurological condition has resolved or stabilised).

• Patients taking medications that would contraindicate the supply of Dukoral® vaccine or Vaxchora® vaccine (see Product interactions).

  Vaxchora® only

• Individuals with congenital immune deficiency or receiving immunosuppressive drugs or treatments.

• Patients with rare hereditary problems of galactose intolerance, congenital lactase deficiency, glucose-galactose malabsorption, fructose intolerance, or sucrose-isomaltase

insufficiency should not take Vaxchora®.

1. Clinical condition or situation to which the direction applies

Cautions

(including any relevant action to be taken)

Pregnancy and Breast-feeding

• Vaccines can be administered during pregnancy or breast-feeding where there is a high risk of infection, and the benefits of vaccination outweigh the risks. It is recommended that the appropriate healthcare professional (e.g. GP, midwife) is consulted prior to administration (1) (2).

  Protection against cholera

• Dukoral® and Vaxchora® only protects patients from cholerae serogroups included in the vaccine (to Vibrio cholerae serogroup O1) and will not protect patients against any other serogroups such as V. cholerae serogroup O139 or other species of Vibrio. Furthermore, not all recipients of Dukoral® and Vaxchora® will be fully protected against cholera (1) (2).

• There are only very limited data on protective efficacy of the Dukoral® and Vaxchora® in subjects aged 65 years and more (1) (2). If vaccinating elderly patients (over 65 years of age), the supplier should advise of the risk of reduced immunity.

  Immunosuppressed patients (Dukoral® only)

• Patients that are immunosuppressed due to disease or treatment, including asplenia or dysfunction of the spleen, or HIV infection (regardless of CD4 count), may not produce a sufficient protective antibody response following vaccination (3).

• Specialist advice may be required - see the Green Book chapters 6 & 7:

  • https://www.gov.uk/government/publications/contraindications-and-special- considerations-the-green-book-chapter-6

  • https://www.gov.uk/government/publications/immunisation-of-individuals- with-underlying-medical-conditions-the-green-book-chapter-7

    Sodium

• Dukoral® contains approximately 1.1 g sodium per dose, which should be taken into consideration by patients on a controlled sodium diet (2).

• Vaxchora® contains 863 mg of sodium per dose. This is equivalent to 43% of the recommended daily dietary intake of sodium for an adult. This should be taken into consideration by patients on a controlled sodium diet (1).

  Other considerations

• For patients with other health conditions, the risks and benefits of vaccination must be weighed on an individual basis. Refer to appropriate healthcare professional e.g. GP.

• Healthcare professionals must not delegate their responsibility and they have the right to refuse vaccination to eligible patients based on their own clinical judgement.

• Where there is doubt, vaccination should not be initiated until the patient has sought

advice from the appropriate healthcare professional.

1. Clinical condition or situation to which the direction applies – continued

Product interactions

• Prior to administration and where indicated, medication that the patient is using should be checked for product interactions using the British National Formulary (BNF) and SPC. This includes checking that the patient’s medication does not suggest conditions that are excluded from vaccination under this PGD.

• Cholera vaccine can be given at the same time as injected vaccines (3).

  Dukoral® (2)

• Dukoral® is acid labile. Food and/or drink will increase acid production in the stomach and the effect of the vaccine may be impaired. Important to ensure nil by mouth one hour before and one hour after administration.

  Vaxchora® (1)

• Eating and drinking should be avoided 60 minutes before and after oral ingestion of Vaxchora® (1).

• Concomitant administration of Vaxchora® with chloroquine should be avoided because protection against cholera may be diminished. Vaxchora® should be administered at least 10 days before beginning antimalarial prophylaxis with chloroquine.

• There should be an interval of 2 hours between the administration of Vaxchora® and of typhoid vaccine Ty21a (gastro-resistant capsules) as the buffer administered with Vaxchora® may affect the transit of the capsules through the gastrointestinal tract.

• Concomitant administration of Vaxchora® with systemic antibiotics active against V. cholerae should be avoided.

• Vaxchora® should not be administered to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.

• Oral or parenteral antibiotics should be avoided for 10 days following vaccination with

Vaxchora®.

Action if patient is excluded from the service

• The risk to the patient of not being vaccinated must be considered.

• If administration is postponed, arrange a future date for vaccination as appropriate.

• Discuss with patient and document the reasons for exclusion from vaccination under the PGD.

• If the patient has consented, refer them to their GP and/or inform their GP.

• Signpost to other services if appropriate.

• Give appropriate food, water and personal hygiene advice if travelling.

Action if patient declines the service

• Ensure patient/carer fully understands the risks of declining vaccination.

• Advise the patient/carer about the protective effects of the vaccine.

• Explain NHS eligibility for vaccination where appropriate.

• Reschedule vaccination if appropriate.

• Document the reasons for declining vaccination and any action taken, including advice given to the patient in their medication record.

• Refer patient to GP if appropriate.

• Give appropriate food, water and personal hygiene advice if travelling.

2. Description of vaccine

Name, strength & formulation of drug

Supplier

Name of

product

Composition

Pharmaceutical

form

Excipients

Age

indications

Valneva UK Limited

Dukoral®

Cholera vaccine (inactivated, oral)

Suspension and effervescent granules for oral suspension

One dose contains approximately 1.1 g sodium.

For a full list of excipients, see section 6.1 of the SPC

From 2 years

Emergent BioSolutions UK Ltd

Vaxchora®

Cholera vaccine (recombinant, live, oral)

Effervescent powder and powder for oral suspension

• Sucrose

• Hydrolysed casein

• Ascorbic acid

• Lactose

• Sodium bicarbonate

• Sodium carbonate

From 2 years

• For a full list of excipients, see section 2 and 6.1 of the relevant SPC.

Legal status

• POM – Prescription Only Medicine

Dose/dose range

Dukoral® (2)

• From 6 years: 2 doses containing 3 ml vaccine suspension.

• Between 2-5 years: 3 doses containing 3 ml vaccine suspension.

  Vaxchora® (1)

• Single oral dose.

Use of PGD outside terms of SPC

• This PGD covers vaccination in England, Scotland, Wales and Northern Ireland. Please note that Northern Ireland may have a separate SPC from Great Britain and guidance may differ. Please refer to the relevant SPC for more information.

• Although healthcare professionals have the right to refuse vaccination even where a

patient is eligible, they cannot override PGD exclusions.

2. Description of vaccine

Route/method of administration

Dukoral®

• All doses of Dukoral® are to be administered face to face with the healthcare professional (i.e. not for patient self-administration at home).

• The vaccine is intended for oral use (2).

• Before ingestion, the vaccine suspension should be mixed with a buffer (sodium hydrogen carbonate) solution. The sodium hydrogen carbonate is supplied as effervescent granules, which should be dissolved in 150 ml of cool water. Chlorinated water can be used (2).

• The vaccine vial should be gently shaken before adding vaccine suspension to the buffer solution and mixed well to obtain a colourless slightly opalescent solution (2).

• Once mixed, the solution should be drunk within 2 hours (2).

• Food and drink should be avoided 1 hour before and 1 hour after vaccination (2).

• Oral administration of other medicinal products should be avoided within 1 hour before and 1 hour after administration of Dukoral® (2).

• Children 2 to 5 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 (2). Vaxchora®

• Vaxchora® dose is to be administered face to face with the healthcare professional (i.e. not for patient self-administration at home).

• The vaccine is intended for oral use (1).

• Eating and drinking should be avoided 60 minutes before and after oral ingestion of Vaxchora® (1).

• To be mixed with bottled water and Vaxchora® active ingredient (1).

• The reconstituted vaccine forms a slightly cloudy suspension that may contain some white particulates (1).

• After reconstitution, the suspension should be drunk within 15 minutes (1).

• The patient should drink the full contents of the cup at once. Some residue may remain in the cup (1).

• Consumption of less than a half dose may result in decreased protection (1).

• If less than half the dose is consumed, consideration may be given to repeating a full dose of Vaxchora® within 72 hours (1).

• For instructions on reconstitution of Vaxchora® prior to administration, see section 6.6 of the product SPC.

• Children 2 to 5 years of age: ONLY, half (50 mL) of the buffer solution should be used

with the remaining discarded before proceeding to add the active component.

2. Description of vaccine – continued

Frequency of administration

Dukoral® (2)

• Individuals from 6 years of age: 2 doses separated by an interval of 1 – 6 weeks.

• Children between 2-5 years of age: 3 doses separated by an interval of 1 – 6 weeks.

• Note if more than 6 weeks have elapsed between doses, the primary course should be restarted.

• Immunisation should be completed at least 1 week prior to potential exposure to V. cholerae O1.

  Vaxchora® (1)

• A single oral dose should be administered at least 10 days prior to potential exposure to

V. cholerae O1.

Follow up / minimum or maximum period

Dukoral® (2)

• Individuals from 6 years of age: For continuous protection against cholera a single booster dose is recommended within 2 years.

• Children between 2-5 years of age: Single booster dose is recommended within 6 months.

  Vaxchora® (1)

• No data are available on revaccination interval.

• Follow available official recommendations regarding the need for boosters or further doses (See the Green Book Ch.14 and NaTHNaC).

• https://www.gov.uk/government/publications/cholera-the-green-book-chapter-14

• http://travelhealthpro.org.uk/factsheet/56/cholera

3. Further aspects of vaccination

Adverse reactions and their management

• Follow local SOP on adverse reactions and their management.

  Dukoral® (2)

• Uncommon side effects include (≥1/1,000 to <1/100): Headache, diarrhoea, abdominal cramps, abdominal pain, stomach/abdominal gurgling (gas) and abdominal discomfort.

• Rare side effects include (≥1/10,000 to <1/1,000): Loss of /or poor appetite, dizziness, respiratory symptoms (including rhinitis and cough), vomiting, nausea, fever and malaise.

• Very rare side effects include (<1/10,000): Dehydration, drowsiness, insomnia, fainting, reduced sense of taste, sore throat, dyspepsia, sweating, rash, joint pain, fatigue and shivers.

  Vaxchora® (1)

• Very common side effects include (≥1/10): Decreased appetite, headache, abdominal pain, nausea/vomiting and fatigue.

• Common side effects include (≥1/100 to <1/10): Diarrhoea.

• Uncommon side effects include (≥1/1,000 to <1/100): Dizziness, flatulence, constipation, abdominal distension, dyspepsia, abnormal faeces, dry mouth, eructation, rash, arthralgia and pyrexia.

• Rare side effects include (≥1/10,000 to <1/1,000): Chills.

• For a comprehensive list of all warnings, cautions and potential adverse reactions, refer

to the current BNF, current and relevant SPCs (Great Britain or Northern Ireland) and the Green Book - Immunisation against infectious disease.

Reporting procedure of adverse reactions

• Report to GP if appropriate & document in patient’s medication records.

• Follow local SOP for reporting of adverse events.

• Vaxchora® is a black triangle product and is subject to additional monitoring.

• All suspected adverse reactions must be reported via the Yellow Card scheme to the MHRA or on the website at https://yellowcard.mhra.gov.uk/

• An adverse reaction should be reported even if it is not certain that the medicine has caused it, if it is well recognised, or if other drugs were given at the same time.

• Further information is available online from https://yellowcard.mhra.gov.uk/

3. Further aspects of vaccination

Advice to patient / carer

Vaccine protection

• Explain protection level expected from vaccine. Advise patients that not all those who receive the vaccine will be fully protected, and the vaccine only protects against infections for which it has been developed (1) (2).

  Patient information

• Provide a patient information leaflet and discuss as required.

• Provide advice on and explain potential warnings.

• Advise on possible side effects and their management. If the symptoms do not resolve and/or the patient experiences other severe symptoms, they should be advised to contact their GP, NHS 111 or visit A&E

• Give appropriate food, water and personal hygiene advice if travelling. Patients should be aware that the vaccine does not protect them from all cholera, and not all recipients of the vaccine are fully protected. Therefore, it is still important to follow given advice to avoid diarrhoeal diseases.

• Advise that food, drink, and other oral medicines should be avoided for 1 hour before and after vaccination (1) (2).

• Patients who are on a controlled sodium diet need to be aware that the vaccines contain sodium and to make adjustments for that day (1) (2).

• Bacteria from Vaxchora® may be present in stools for at least 7 days after taking the vaccine (1). To prevent any contamination, hands should be washed thoroughly after visiting the toilet, changing nappies and before preparing food.

  Vaccine record

• Provide patient with a record of vaccination.

3. Further aspects of vaccination – continued

Records to be kept

• In all cases manual records including any risk assessment forms or computerised records should include:

  ̵ Patient’s name, address and date of birth;

  ̵ Name of immuniser;

  ̵ Dose, site and route of injection;

  ̵ Date of administration;

  ̵ Brand name, batch number & expiry date of vaccine;

  ̵ Confirmation that there are no contraindications; that side effects have been discussed; support literature given (if applicable) and any other advice given;

  ̵ That valid informed consent was given prior to administration;

  ̵ Details of any adverse reactions and actions taken;

  ̵ Signature and printed name and designation (in black ink) for paper records. For computer records, ensure data authentication of practitioner delivering care.

• GP may be notified, if the patient has consented for personalised information to be shared.

• Pharmacy/clinic records should be stored in line with relevant legislation and local policies. Generally, records should be kept for 8 years in adults and until 25 years of age

in children.

Additional facilities / requirements

• Policies and procedures must be in place for providing a private vaccination service including cold chain management, sharps disposal, needlestick injury, consent, record keeping and training requirements.

• Pharmaceutical refrigerator (or validated cool box for storing vaccines if running an

  “offsite” clinic).

• Resuscitation kit, including immediate access to 1:1000 epinephrine (adrenaline).

• Access to medical support (this may be via telephone).

• Disposal - equipment used for vaccination, including used vials or ampoules, should be disposed of at the end of a session by sealing in a proper, appropriately sized puncture-

resistant ‘sharps’ box (UN-approved, BS 320).

3. Further aspects of vaccination – continued

Additional facilities / requirements

PGD users must:

• Be familiar with and have online access to the latest edition of the Green Book, noting that clinical guidance may change and that the Green Book is frequently updated.

• Be aware of current clinical recommendations and be able to undertake administration (where applicable) and discuss any issues that may arise.

• Have been trained and assessed as being competent in the delivery of this medicine covered by this PGD.

• Maintain their skills, knowledge and professional level of competence in this area according to their individual code of professional conduct.

• Possess appropriate professional indemnity.

• Agree to work within the terms of the implementing PGD.

• Be aware of medicine handling, storage and administration guidelines.

• Regularly check BNF/BNFC / Green Book for contraindications, cautions and interactions. The superintendent/clinical lead of the implementing pharmacy/clinic will be responsible for:

• Providing adequate up-to-date clinical resources.

• Ensuring that staff using the PGD, have access to up-to-date resources.

• Ensuring that staff have received adequate training in all areas relevant to this PGD.

  Requirements for Continuing Professional Development (CPD)

• All staff involved in the implementation of this PGD should participate in adequate and appropriate Continual Professional Development to ensure procedures follow the most up to date clinical guidance.

  Facilities and supplies to be available

• Consultations carried out under the authorisation of this PGD should be completed in a private space, physically closed off from interruption such as a pharmacy consultation room, in order to ensure patient confidentiality.

• The following should be available:

  1. Safe storage areas for medicines and equipment

  2. Clean and tidy clinical rooms that allow confidentiality and patient privacy.

  3. Copies of the current PGD

  4. Access to a current BNF and Green Book

     Audit

• All health risk assessment, advice and medicine supply record forms should be stored in the pharmacy/clinic and will be audited by the implementing pharmacy/clinic in order to analyse service delivery. If the service is deemed insufficient, management staff, the superintendent/clinical lead and implementing healthcare professional will be informed

and an action plan drawn up to remedy the service.

3. Further aspects of vaccination – continued

Consent

• Prior to the administration and/or supply of a medicine, consent must be obtained, preferably written, from the patient, and documented either in the patient’s medical records/notes or on an administration form.

  The key points include:

• If a patient’s fitness and suitability cannot be established, supply should be deferred.

• There is no legal requirement for consent to be in writing but written consent serves to record the decision and the discussions that have taken place.

• Consent - either written or verbal - is required at the time of each supply.

• Consent remains valid unless the patient who gave it withdraws it. If there is new information between the time consent was given and when the supply is offered, including new evidence of risk, new medicines becoming available or where there is a significant change in the patient’s condition, it may be necessary for the patient to reconfirm their consent.

• Written and verbal information should be available in a form that can be easily understood by the person who will be giving the consent. Where English is not easily understood, translations and properly recognised interpreters should be used in order that they can make informed consent.

• The attendance of a patient for the supply/administration of treatment after an invitation to attend for this purpose may be viewed as acceptance that the patient may have the treatment/administration.

• Patients should also be informed about how data on the supply will be stored, who will be able to access that information and how that data may be used.

• Where consent is either refused or withdrawn, this decision must be documented.

• Consent obtained before the occasion upon which a patient attends for the

supply/administration is only an agreement for the patient to be included in this instance and does not mean that consent is in place for each future supply/administration.

4. References & Resources

For a comprehensive list of all warnings, cautions and potential adverse reactions, refer to the current BNF the current SPCs and the Green Book- Immunisation against infectious disease at: www.gov.uk/government/collections/immunisation-against-infectious-disease-the- green-book

References

1. Summary of Product Characteristics; Vaxchora effervescent powder and powder for oral suspension. European Medical Agency. [Online] https://www.ema.europa.eu/en/documents/product-information/vaxchora-epar-product-information_en.pdf.

2. Summary of Product Characteristics; Dukoral suspension and effervescent granules for oral suspension, Cholera vaccine (inactivated, oral). emc (Great Britain). [Online] May 10, 2021. [Cited: January 19, 2023.] https://www.medicines.org.uk/emc/product/5087.

3. Chapter 14; Cholera. The Green Book. [Online] December 2013. [Cited: January 19, 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/263838/Green-Book-Chapter- 14v2_0.pdf.

4. Chapter 8; Vaccine safety and the management of adverse events following immunisation. The Green Book. [Online] August 2012. [Cited: January 19, 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/147868/Green- Book-Chapter-8-v4_0.pdf.

5. Chapter 14a; COVID-19-SARS-CoV-2. The Green Book. [Online] September 04, 2022. [Cited: January 19, 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1057798/Greenbook-chapter-14a- 28Feb22.pdf.

Additional resources

1. Cholera. Travel Health Pro. [Online] October 3, 2019. [Cited: January 23, 2023.] https://travelhealthpro.org.uk/factsheet/56/cholera.

2. Patient Group Direction; Medicines practice guideline [MPG2]. National Institute for Health and Care Excellence. [Online] March 27, 2017. [Cited: January 23, 2023.] https://www.nice.org.uk/Guidance/MPG2.

3. Competency framework for health professionals using Patient Group Directions. National Institute for Health and Care Excellence.

[Online] January 4, 2018. [Cited: January 23, 2023.] https://www.nice.org.uk/guidance/mpg2/resources.