Patient Group Direction (PGD) for the administration of Japanese encephalitis vaccine

1. Clinical condition or situation to which the direction applies

Indication

• For active immunisation against Japanese encephalitis for individuals at high risk of

exposure.

Objectives of care

• To reduce morbidity and mortality from Japanese encephalitis.

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 6 months of age.

• Travellers intending to travel to countries where Japanese encephalitis is a risk as per the risk assessment that takes into consideration their itinerary, season of travel, duration of stay and planned activities.

• Patients at risk of exposure in the course of their occupation, e.g. research laboratory

staff.

Exclusion criteria (Refer to current and relevant SmPC (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 IXIARO® vaccine. See section 2 and 6.1 of the relevant Summary of Product Characteristics (SmPC).

• Hypersensitivity to the residues protamine sulphate, formaldehyde, bovine serum albumin, host cell DNA, sodium metabisulphite and host cell protein.

• Individuals who show hypersensitivity reactions after receiving the first dose of the vaccine should not be given the second dose.

• Individuals under 6 months of age.

• Known or suspected pregnancy.

• Breast-feeding individuals.

• Acute febrile illness/conditions – postpone administration until completely recovered.

• Has an evolving neurological condition. (With an evolving neurological condition,

immunisation should be deferred until the neurological condition has resolved or stabilised).

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

Cautions

(including any relevant action to be taken)

Bleeding disorders

• IXIARO® should be given with caution to patients with thrombocytopenia or any coagulation disorder (including those taking anticoagulants) since bleeding may occur following intramuscular administration to these patients (1). It is recommended that the appropriate healthcare professional (e.g. GP) is consulted prior to injection, to determine if intramuscular injection is suitable and if vaccination should be scheduled shortly after the patient receives their medication/treatment to reduce bleeding. If the vaccine is offered, the patient/carer should be informed about the risk of bleeding from the injection.

• Patients on stable anticoagulation therapy, including patients on warfarin who are up- to-date with their scheduled International Normalised Ratio (INR) testing and whose latest INR was below the upper threshold of their therapeutic range, can receive intramuscular vaccination. If in any doubt, the clinician responsible for prescribing or

  monitoring the patient’s anticoagulant therapy should be consulted prior to injection (2).

• The vaccine may alternatively be administered by the subcutaneous route to individuals with bleeding disorders (1) (N.B. There is a lack of evidence that subcutaneous injection is any safer than intramuscular injection in individuals taking anticoagulants, and injection by this route is more likely to cause local reactions) (3). Healthcare professionals who are not professionally competent to perform SC injections should refer the individual(s) to a suitable alternative provider.

  Syncope

• Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that procedures are in place to avoid injury from faints

  (4).

  Immunosuppressed patients

• 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 (5).

• 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

  Protection against encephalitis

• Protection against Japanese encephalitis is not ensured until the second dose has been received (1).

• IXIARO® will not protect against encephalitis caused by other micro-organisms, such as tick-borne encephalitis. Furthermore, vaccination may not result in protection in all cases (1).

  Other considerations

• 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 SmPC. This includes checking that the patient’s medication does not suggest conditions that are excluded from vaccination under this PGD.

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.

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.

2. Description of vaccine

Name, strength & formulation of drug

Supplier

Name of

product

Composition

Pharmaceutical form

Excipients

Age

indications

Valneva UK Limited

IXIARO®

Japanese encephalitis virus strain SA14-14-2 (inactivated)

Suspension for injection

Phosphate buffered saline consisting of:

• Sodium chloride

• Potassium dihydrogen phosphate

• Disodium hydrogen phosphate

• Water for injections

6 months and over

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

Legal status

• POM – Prescription Only Medicine (1)

Dose/dose range

• Children from 6 months to < 3 years of age: 0.25 ml (1)

• From 3 years of age: 0.5 ml (1)

Use of PGD outside terms of SmPC

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

• Although healthcare professionals have the right to refuse vaccination even where a patient is eligible, they cannot override PGD exclusions.

• For children (from 6 months of age) and adults 65 years of age and older, although not licensed for these age groups due to lack of data, the rapid schedule can be used in circumstances where there is genuinely insufficient time to complete the standard schedule prior to travel. There are no data to suggest that the rapid schedule would be harmful for these travellers (6). Refer to Frequency of administration. Where a vaccine is recommended off-label, as part of the consent process, inform the individual/carer that the vaccine is being offered in accordance with national guidance but that this is outside

the product licence.

Route/method of administration

• The vaccine should be inspected for any foreign particulate matter and /or for any variation of physical aspect prior to administration. If either is observed the vaccine should not be administered.

• For intramuscular injection. The vaccine must not be injected intravascularly and must not be mixed with other vaccines in the same syringe (1).

• For patients with bleeding disorders, a fine needle (equal to 23 gauge or finer calibre) should be used for the vaccination, followed by firm pressure applied to the site (without rubbing) for at least 2 minutes (2). Alternatively, vaccination can be given by subcutaneous injection to reduce risk of bleeding (see cautions) (1).

• The preferred site of injection is the deltoid muscle of the upper arm (1).

• In children 6 months through to 35 months, the preferred sites for intramuscular injection are the anterolateral aspect of the thigh (if suitably trained), or the deltoid muscle if muscle mass is adequate (7).

• Where two or more injections need to be administered at the same time, they should be given at separate sites, preferably in different limbs. If more than one injection is to be

given in the same limb, they should be administered at least 2.5cm apart (7).

2. Description of vaccine – continued

Frequency of administration

• It is recommended that patients who received the first dose of IXIARO® complete the primary 2-dose vaccination course with IXIARO® (1).

• The primary immunisation should be completed at least one week prior to potential exposure to Japanese encephalitis virus (JEV) (1).

• If the primary immunisation of two injections is not completed, full protection against the disease might not be achieved. There is data that a second injection given up to 11 months after the first dose results in high seroconversion rates (1).

• In situations where the primary course plus initial booster has been interrupted, the schedule should be resumed, and not restarted (6).

  Children from 6 months to < 3 years of age

• The primary vaccination series consists of two separate doses of 0.25 ml.

• Conventional schedule (1):

  ̵ First dose at day 0.

  ̵ Second dose: 28 days after first dose.

• *Rapid schedule (6):

  ̵ First dose at day 0.

  ̵ Second dose: 7 days after first dose.

• See section 6.6 of the SmPC for instructions on preparing a 0.25 ml dose for children aged 6 months to < 3 years.

  Children and Adults (3 years and over)

• Conventional schedule (1):

  ̵ First dose at day 0.

  ̵ Second dose: 28 days after first dose.

• *Rapid schedule (6):

  ̵ First dose at day 0.

  ̵ Second dose: 7 days after first dose.

• * For children (from 6 months of age) and adults 65 years of age and older, although not licensed for these age groups due to lack of data, the rapid schedule can be used in circumstances where there is genuinely insufficient time to complete the standard schedule prior to travel. There are no data to suggest that the rapid schedule would be

harmful for these travellers (6).

2. Description of vaccine – continued

Follow up / minimum or maximum period

Children and adolescents (1)

• Children from 6 months to < 3 years of age should receive a single 0.25 ml booster dose. Children and adolescents from 3 years to < 18 years of age should receive a single 0.5 ml booster dose.

• A booster dose (third dose) should be given within the second year (i.e. 12 - 24 months) after primary immunisation, prior to potential re-exposure to JEV.

• Children and adolescents at continuous risk for acquiring Japanese encephalitis (residing in endemic areas) should receive a booster dose at month 12 after primary immunisation. There is no long-term seroprotection data beyond two years after the first booster immunisation has been generated.

  Adults (1)

• A booster dose (third dose) should be given within the second year (i.e. 12 - 24 months) after primary immunisation, prior to potential re-exposure to JEV.

• Persons at continuous risk for acquiring Japanese encephalitis (adults 65 years and over, laboratory staff and persons residing in endemic areas) should receive a booster dose (third dose) at month 12 after primary immunisation.

• For adults aged 18–64, long-term seroprotection data following a first booster dose administered 12 - 24 months after primary immunisation suggest that a second booster (fourth dose) should be given 10 years after the first booster dose, prior to potential exposure to JEV.

• The length of protection following a booster dose (3rd dose) for adults 65 years and over is

not known.

3. Further aspects of vaccination

Adverse reactions and their management

• Follow local SOP on adverse reactions and their management.

• Very common side effects include (≥1/10): Headache; myalgia; injection site pain; injection site tenderness and fatigue (1).

• Common side effects include (≥1/100 to <1/10): Nausea; influenza like illness; pyrexia; and other injection site reactions e.g. redness, hardening, swelling, itching (1).

• Uncommon side effects include (≥1/1,000 to <1/100): Lymphadenopathy; migraine; dizziness; vertigo; vomiting; diarrhoea; abdominal pain; rash; pruritus; hyperhidrosis; chills; malaise and asthenia (1).

• Rare side effects include (≥1/10,000 to <1/1,000): Thrombocytopenia; paraesthesia; neuritis; dysgeusia; syncope; eyelid oedema; palpitations; tachycardia; dyspnoea; urticaria; erythema; pain in extremity and oedema peripheral (1).

• Emergency equipment must be available including immediate access to epinephrine (adrenaline) 1:1000 for intramuscular (IM) injection. Please refer to resuscitation council guidelines.

• Healthcare professionals should confirm with patients that they are fit to leave the premises after a period of observation. Patients should not leave if they are feeling at all unwell without speaking to the healthcare professional.

• The onset of anaphylaxis is rapid, typically within minutes, and its clinical course is unpredictable with variable severity and clinical features. Due to the unpredictable nature of anaphylactic reactions, it is not possible to define a particular time period over which all patients should be observed following immunisation to ensure they do not develop anaphylaxis.

• In the event that the patient exhibits signs of anaphylaxis after injection, healthcare professionals must seek urgent medical attention.

• Advise the patient to consult their GP if there is a severe local reaction at the injection site, if they have a fever or if any other serious symptoms develop.

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

to the current BNF, current and relevant SmPCs (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.

• 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 – continued

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).

  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.

• Advise patients on mosquito bite avoidance, refer to Scenario: Management in primary care | Management | Insect bites and stings | CKS | NICE.

  Vaccine record

• Provide patient with a record of vaccination.

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.

3. Further aspects of vaccination – continued

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).

  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 and SmPCs.

References

1. Summary of Product Characteristics; IXIARO suspension for injection - Japanese encephalitis vaccine (inactivated, adsorbed). emc (Great Britain). [Online] 29 March 2023. [Cited: 07 July 2023.] https://www.medicines.org.uk/emc/product/6534.

2. Chapter 14a; COVID-19-SARS-CoV-2. The Green Book. [Online] 26 April 2023. [Cited: 07 July 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1057798/Greenbook-chapter-14a- 28Feb22.pdf.

3. Chapter 19; Influenza. The Green Book. [Online] 16 September 2022. [Cited: 07 July 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/931139/Green_book_chapter_19_ influenza_V7_OCT_2020.pdf.

4. Chapter 8: Vaccine safety and the management of adverse events following immunisation. The Green Book. [Online] August 2012. [Cited: 07 July 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/147868/Green-Book-Chapter-8- v4_0.pdf.

5. Chapter 7; Immunisation of individuals with underlying medical conditions. The Green Book. [Online] January 2020. [Cited: 07 July 2023.]

   https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/857279/Greenbook_chapter_7_I mmunsing_immunosupressed.pdf.

6. Chapter 20; Japanese encephalitis. The Green Book. [Online] June 2018. [Cited: 07 July 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/715006/Greenbook_chapter_20 Japanese_encephalitis_v3.pdf.

7. Chapter 4; Immunisation procedures. The Green Book. [Online] 20 March 2013. [Cited: 07 July 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/147915/Green-Book-Chapter- 4.pdf.

Additional resources

1. Chapter 6; Contraindications and special considerations. The Green Book. [Online] August 2017. [Cited: July 07, 2023.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/655225/Greenbook_chapter_6.pd f.

2. Patient Group Direction; Medicines practice guideline [MPG2]. National Institute for Health and Care Excellence. [Online] March 27, 2017. [Cited: July 07, 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: July 07, 2023.] https://www.nice.org.uk/guidance/mpg2/resources.