Patient Group Direction (PGD) for the administration of Rifaximin 200mg tablets (Xifaxanta®) for Travellers’ Diarrhoea

1. Clinical condition or situation to which the direction applies

Indication

• Treatment of travellers’ diarrhoea.

Objectives of care

• To treat and reduce the symptoms of the gastro-intestinal tract infections that lead to

traveller’s diarrhoea in patients.

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 treatment from the PGD user.

• Patients with travellers' diarrhoea that is not associated with any of the following:

  • Fever

  • Bloody diarrhoea

  • Eight or more unformed stools in the previous 24 h

  • Occult blood or leucocytes in the stool

• Patients from 18 years of age.

Exclusion criteria

(Refer to current and relevant SPC (Great Britain or Northern Ireland) and online British National Formulary (BNF) 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 Xifaxanta®. See section 2 and 6.1 of the relevant SPC.

• Known history of rifamycin hypersensitivity.

• Patients under 18 years of age.

• Known or suspected pregnancy.

• Breast feeding individuals.

• Cases of intestinal obstruction.

• Patients with travellers' diarrhoea caused by invasive enteric pathogens such as Campylobacter jejuni, Salmonella spp. and Shighella, which typically produce dysentery- like diarrhoea characterised by fever, blood in the stool and high stool frequency.

• Patients taking:

  ̵ Warfarin

  ̵ Another rifamycin antibacterial agent

  ̵ P-glycoprotein inhibitors (e.g. ciclosporin)

• Patients with renal impairment.

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

Cautions

(including any relevant action to be taken)

Antibiotic-associated colitis

• Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including rifaximin. The potential association of rifaximin treatment with CDAD and pseudomembranous colitis (PMC) cannot be ruled out. In such cases, rifaximin should be immediately discontinued, and the patient referred for the appropriate treatment (1).

  Treatment

• Although there is evidence that rifaximin is effective for treating travellers' diarrhoea, it is not effective for treating diarrhoea caused by invasive enteric pathogens such as Salmonella, Shigella, Campylobacter. Since it is difficult for travellers to distinguish between invasive and non-invasive diarrhoea, the use of rifaximin as ‘stand by’ treatment is not recommended (1).

• If symptoms worsen treatment with rifaximin should be interrupted (1).

• If symptoms have not resolved after 3 days of treatment, or recur shortly afterwards, a second course of rifaximin should not be administered (1).

  Other considerations

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

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

advice from the appropriate healthcare professional.

Product interactions

• Prior to supply 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 treatment under this PGD.

  Ciclosporin

• Ciclosporin very markedly increases the exposure to rifaximin (2).

  Warfarin

• Both decreases and increases in international normalized ratio have been reported in patients maintained on warfarin and prescribed rifaximin. If co-administration is necessary, the international normalized ratio should be carefully monitored with the addition or withdrawal of rifaximin. Adjustments in the dose of oral anticoagulants may be necessary (1) (2).

  Charcoal

• In case of administration of charcoal, rifaximin should be taken at least 2 hours after that administration (1).

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

Action if patient is excluded from the service

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

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

• Signpost to other services if appropriate.

• Document the reasons for exclusion and any action taken, in the patient’s medication

  record.

• When treatment is postponed reschedule as appropriate.

Action if patient declines the service

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

• Advise the patient/carer about the benefits of the service.

• Refer patient to GP if appropriate.

• Document the reasons for declining the service and any action taken, including advice given to the patient.

• Reschedule treatment if appropriate.

• Explain NHS eligibility for this service where appropriate.

• Advise about protective effects of the rifaximin and the risks of infection and disease complications.

• offer appropriate travel hygiene advice.

2. Description of treatment

Name, strength & formulation of drug

Supplier

Name of product

Composition

Pharmaceutical form

Excipients

Age indications

Tablet core:

Sodium starch glycolate type A

glycerol distearate

colloidal anhydrous silica

Norgine Ltd

Xifaxanta®200mg film coated tablets

Rifaximin 200 mg.

Pink, circular biconvex film-coated tablets, with “AW” embossed

on one side.

talc

microcrystalline cellulose

Tablet coat hypromellose

18 years and over

titanium dioxide (E171)

disodium edetate

propylene glycol

red iron oxide (E172)

• 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

• 200 mg

Use of PGD outside terms of SPC

• This PGD covers treatment 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 treatment even where a

patient is eligible, they cannot override PGD exclusions.

Route/method of

administration

• Tablets are to be taken orally with a glass of water (1).

• Tablets should not be crushed or chewed (3).

Frequency of

administration

• 200 mg every 8 hours for three days (1) (3).

Quantity to supply

• Total 9 doses; 9 x 200mg tablets (1)

Follow up / minimum or

maximum period

• Rifaximin must not be used for more than 3 days, even if symptoms continue a second

course of treatment must not be taken (1) (3).

3. Further aspects of treatment

Adverse reactions

• Follow local SOP on adverse reactions and their management.

• Very common side effects include (≥1/10): headache, nausea, vomiting, diarrhoea, constipation (1).

• Common side effects include (≥1/100 to <1/10): dry mouth, dyspepsia, gastritis, gastro- oesophageal reflux disease, abdominal pain upper, flatulence, eructation, abdominal distension, dizziness, dysgeusia (1).

• Uncommon side effects include (≥1/1,000 to <1/100): dehydration, tachycardia, urticaria (1).

• Rare side effects include (≥1/10,000 to <1/1,000): anaphylactic reaction, acute renal failure, renal impairment (1).

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

to the current BNF and SPC (Great Britain or Northern Ireland).

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 treatment – continued

Advice to patient/carer

Patient information

• Provide a patient information leaflet and discuss as required.

• Provide advice on & explain potential warnings & side effects and request to report them if they occur.

• Advise on possible side effects and their management. If the symptoms persist, or the patient experiences other severe symptoms then they should be advised to contact their GP, call NHS 111 or visit A&E.

• Patients should be informed that despite the negligible absorption of the drug (less than 1%), like all rifamycin derivatives, rifaximin may cause a reddish discolouration of the urine (1).

• Patients should be advised on the self-management of travellers’ diarrhoea and when

  medical advice should be sought e.g:

  • Blood stained stools;

  • Fever;

  • Dehydration;

  • Frequent, watery stools;

  • Repeated vomiting;

  • Diarrhoea persists for more than 3 or 4 days;

• Warn about the risk of waterborne infection and avoidance of contaminated recreational water.

• Travellers should be advised about appropriate vaccination against other intestinal

infections such as cholera, hepatitis A, and typhoid.

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 supplier;

  ̵ Dose, site and route of administration;

  ̵ Date of administration/supply;

  ̵ Brand name, batch number & expiry date of product;

  ̵ 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/supply;

  ̵ 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, so long as 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.

3. Further aspects of treatment – continued

Additional facilities / requirements

• Medication supplied using this PGD must be labelled with the same labelling requirements which patients would otherwise have received if the medicine had been supplied against a prescription and indicate in the patient’s medication record that the medicine was supplied via a PGD.

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

  PGD user must:

• Be familiar with and have online access to the most recent information regarding Xifaxanta® such as information from the relevant SPC and the BNF.

• Be able to assess the patient’s capacity to understand the nature and purpose of the

  supply in order for the patient to give or refuse consent.

• Be aware of current clinical recommendations and be able to undertake supply and discuss any issues that may arise.

• Have been trained in the delivery of this medicine covered by this PGD.

• Maintain their skills, knowledge and their own 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 supply guidelines.

• Have an SOP for providing a private PGD service at the pharmacy/clinic, with the appropriate procedures and policies in place, including consent, record keeping, competency and training requirements.

  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 CPD 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 relevant SPC.

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 treatment – 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 SPCs.

References

1. Summary of Product Characteristics; XIFAXANTA 200 mg Film-coated Tablets. emc (Great Britain). [Online] 30 October 2020. [Cited: 29 April 2022.] https://www.medicines.org.uk/emc/product/4752/smpc.

2. Rifaximin. BNF; The National Institute for Health and Care Excellence. [Online] [Cited: 29 April 2022.] https://bnf.nice.org.uk/drug/rifaximin..

3. Patient Information Leaflet; Xifaxanta. emc(Great Britain). [Online] October 2020. [Cited: 29 April 2022.] https://www.medicines.org.uk/emc/files/pil.4752.pdf.

Additional resources

1. diarrhoea-prevention and advice for travellers. Clinical Knowledge Summaries; The National Institute for Health and Care Excellence. [Online] February 2019. [Cited: April 29, 2022.] https://cks.nice.org.uk/topics/diarrhoea-prevention- advice-for-travellers/.

2. Diarrhoea and Vomiting. NHS. [Online] December 07, 2020. [Cited: April 29, 2022.] https://www.nhs.uk/conditions/diarrhoea-and-vomiting/.

3. Traveller's Diarrhoea. NaTHNaC; TravelHealthPro. [Online] August 23, 2019. [Cited: April 29, 2022.]

https://travelhealthpro.org.uk/factsheet/53/travellers-diarrhoea.