Patient Group Direction (PGD) for the supply of atovaquone/proguanil for the prophylaxis of malaria

1. Clinical condition or situation to which the direction applies

Indication

• Chemoprophylaxis of Plasmodium falciparum malaria where there is

atovaquone/proguanil sensitivity.

Objectives of care

• Malaria prevention in travellers to endemic areas thereby reducing morbidity.

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.

• After risk assessment and evaluation of travel plans, atovaquone/proguanil is deemed to be the most appropriate chemoprophylactic agent when at moderate to high risk of exposure going to malaria endemic areas of the world where there is atovaquone/proguanil sensitive P. falciparum malaria.

• The need for chemoprophylactic agents in patients travelling to low risk areas should be considered if patients are unsure about their itinerary or are at risk of malaria complications.

• Patients from 12 months of age.

• Risk must be identified with reference to current recognised sources such as:

  • http://travelhealthpro.org.uk/country-information/

  • http://www.fitfortravel.nhs.uk/home.aspx

  • http://www.travax.nhs.uk/

  • https://www.gov.uk/government/publications/malaria-prevention- guidelines-for-travellers-from-the-uk

• Additional tablets can be supplied if the patient has misplaced tablets or extended

their stay.

Exclusion criteria

(Refer to current and relevant SPC (Great Britain or Northern Ireland), British National Formulary (BNF) and PHE Advisory Committee on Malaria Prevention (ACMP) 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 atovaquone/proguanil tablets. See section 2 and 6.1 of the relevant Summary of Product Characteristics (SPC).

• Individuals under 12 months of age.

• Patients under 11kg in bodyweight.

• Known or suspected pregnancy.

• Breast-feeding individuals.

• Patients with severe hepatic impairment.

• Patients with severe renal impairment (creatinine clearance < 30mL/minute).

• Patients receiving renal dialysis.

• Patients taking medications that would contraindicate the supply of atovaquone/proguanil (see Product Interactions).

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

Cautions

(including any relevant action to be taken)

Repeat dosing (1) (2)

• A repeat dose of atovaquone/proguanil should be taken if vomiting occurs within 1 hour of dosing.

• In the event of diarrhoea, normal dosing should be continued.

  Lactose

• Some atovaquone/proguanil medicinal products contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine (3). Planning a Pregnancy

• Women of childbearing potential travelling to malarious areas in which multiple resistant P. falciparum is found and who are receiving atovaquone/proguanil for the treatment and prophylaxis of malaria should take reliable contraceptive precautions for the entire duration of therapy and for two weeks after the last dose of atovaquone/proguanil.

  Children (4)

• Children are at particular risk of severe and fatal malaria; therefore, parents should be advised against taking infants and young children to malarious areas without adequate precautions.

• If travel is unavoidable, infants and children should be well protected against mosquito bites and receive appropriate malaria chemoprophylaxis.

• It is important that the child’s carers understand the importance of trying to ensure

  that the child properly completes the full course of prophylactic medication.

• Parents should supervise children’s chemoprophylaxis, as some regimens can be difficult whilst being cautious not to exceed maximum recommended doses, since antimalarials can be particularly toxic to children.

  Allergic reactions

• Occasionally, severe allergic reactions (including anaphylaxis) have been reported in patients taking atovaquone/proguanil tablets. If patients experience an allergic reaction to atovaquone/proguanil, treatment should be discontinued promptly, and medical advice should be sought immediately (1) (2).

  Oral anticoagulants

• Caution is advised when initiating or withdrawing malaria prophylaxis or treatment with atovaquone/proguanil in patients on continuous treatment with oral anticoagulants. The dose of the oral anticoagulant may need to be adjusted during treatment or after its withdrawal, based on INR results (1) (2).

  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.

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

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.

• Concomitant administration of rifampicin, rifabutin, metoclopramide, efavirenz or boosted protease-inhibitors and tetracycline is not recommended (1) (2).

• Proguanil may potentiate the effect of warfarin and other coumarin based anticoagulants which may lead to an increase in the risk of haemorrhage (1) (2).

• Proguanil is predicted to increase the risk of adverse effects when given with

pyrimethamine (5).

Action if patient is excluded from the service

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

• The risk to the individual of not taking chemoprophylaxis must be considered and discussed with the traveller. Document advice given.

• Offer the patient written information on how to avoid mosquito bites and how to recognise the symptoms of malaria infection, based on current guidelines together with general travel health advice.

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

• Signpost to other services if appropriate.

• When treatment is postponed reschedule as appropriate.

  Pregnancy (4)

• Pregnant women should be advised not to travel to malarious areas.

• In the event that travel is unavoidable, the pregnant traveller must be informed of the risks which malaria presents, including an increased risk of developing severe malaria and a higher risk of fatality compared to non-pregnant women. Diagnosis of

falciparum malaria in pregnancy can be particularly difficult.

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.

• Offer the patient written information on how to avoid mosquito bites and how to recognise the symptoms of malaria infection, based on current guidelines together with general travel health advice.

2. Description of treatment

Name, strength & formulation of drug

Supplier

Name of

product

Composition

Pharmaceutical

form

Excipients

Weight indications

GlaxoSmithKline

*Malarone®

250 mg atovaquone

and 100 mg proguanil hydrochloride

Film-coated tablet

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

Over 40 kg

*Malarone® paediatric

62.5 mg atovaquone and 25 mg proguanil

hydrochloride

Film-coated tablet

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

11-40 kg

• *Any suitable generic equivalent may be dispensed, please refer to individual product SPC for contraindications and interactions.

• 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

• Prophylaxis for both adults and children should be initiated 24-48 hrs prior to entering a malaria-endemic area, continued during the period of exposure and for 7 days after leaving the area (1) (2).

  Adults:

• Adult and children weighing over 40 kg: One atovaquone/proguanil 250/100mg tablet daily (1).

• Adult tablets are not recommended for malaria prophylaxis in persons 40kg or under. In adults weighing 40 kg or under, paediatric doses may be offered as per paediatric guidelines (1).

  Children:

• Weight should be used for the purpose of children’s dosage calculation including

children who are over or under-weight.

Table of atovaquone/proguanil dose for 62.5/25mg (paediatric) and 250/100mg (Adult) tablets: (2)

Weight

Number of tablets

11-20 kg

1 paediatric tablet

21-30 kg

2 paediatric tablets

31-40 kg

3 paediatric tablets

Over 40 kg

1 adult tablet

2. Description of treatment – continued

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

• The tablets should be taken with food or a milky drink (to ensure maximum absorption) at the same time each day (1) (2).

• If necessary, the tablets can be crushed and mixed with jam (or similar) before

administration (4).

Frequency of administration

Daily prophylaxis should: (1) (2)

• Commence 24-48 hours prior to entering a malaria-endemic area;

• Continue during the period of the stay;

• Continue for 7 days after leaving the area;

Quantity to supply

• Sufficient supply to provide prophylaxis for the duration of travel, beginning 1-2 days before travel to malarial areas and for 7 days after traveller leaves malarial areas (1)

(2).

Follow up / minimum or maximum period

• Dependent on time spent in malaria-endemic area.

• Can be used confidently for travel up to 1 year. Longer term use possible if justified by the risk of exposure to malaria (4).

• For further information on long term use, refer to ACMP guidelines. https://www.gov.uk/government/publications/malaria-prevention-guidelines-for-

travellers-from-the-uk

3. Further aspects of treatment

Adverse reactions and their management

• Follow local SOP on adverse reactions and their management.

• Very common side effects include (≥1/10): Headache, nausea, vomiting, diarrhoea and abdominal pain (1) (2).

• Common side effects include (≥1/100 to <1/10): Anaemia, neutropenia, allergic reactions, hyponatraemia, anorexia, abnormal dreams, depression, insomnia, dizziness, elevated liver enzymes, pruritus, rash, fever and cough (1) (2).

• Uncommon side effects include (≥1/1,000 to <1/100): Elevated amylase levels, anxiety, palpitations, stomatitis, hair loss and urticaria (1) (2).

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

Advice to patient / carer

Patient information

• Provide a patient information leaflet and discuss as required.

• Ensure that the patient understands the dosing schedule and emphasize the importance of adhering to the schedule to achieve effective chemoprophylaxis.

• 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.

  Malaria prevention

• Discuss and explain current guidelines on malaria prevention and how to recognise signs and symptoms of malaria infection. A useful tool is the widely recognised ABCD approach to malaria prophylaxis (4):

  • Awareness of risk

  • Bite prevention

  • Chemoprophylaxis

  • Diagnose malaria promptly and treat without delay

• The Advisory Committee on Malaria Prevention (ACMP) recommends the following repellents (4):

  • 50% DEET based insect repellent as first choice

  • 20% Picaridin based insect repellent

  • Eucalyptus citriodora oil

  • 3-ethylaminoproprionate

• Explain to the patient that whilst no regime can provide total protection from becoming infected, taking sensible precautions will reduce risks.

• DEET and Picaridin (20%) is recommended for pregnant women as there is evidence

that it has no adverse effects on mother or unborn child (4).

3. Further aspects of treatment – continued

Advice to patient / carer

• Travellers should be warned if any illness occurs within 1 year and especially within 3 months of return that it might be malaria even if all recommended precautions against malaria were taken. They should go immediately to a doctor and specifically mention their exposure to malaria. Symptoms of malaria vary but typically include: fever, headache, fatigue, and muscle aches. Coughing and diarrhoea may also occur (6).

• Patients with a condition that can suppress their immune system or take medications that

can suppress their immune system or do not have a spleen (or a functioning spleen) have a higher risk of developing severe malaria (4).

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 and until 25 years of age in

children.

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 [insert medicine], 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; Malarone 250 mg/100 mg film-coated tablets. emc (Great Britain). [Online] 06 January 2021. [Cited: 25 April 2022.] https://www.medicines.org.uk/emc/product/947/smpc#PREGNANCY.

2. Summary of Product Characteristics; Malarone paediatric 62.5 mg/25 mg film-coated tablets. emc (Great Britain). [Online] 06 January 2021. [Cited: 25 April 2022.] https://www.medicines.org.uk/emc/product/1662#CLINICAL_PRECAUTIONS.

3. Summary of Product Characteristics; Atovaquone/Proguanil Hydrochloride 250 mg/100 mg Film-coated tablets. emc (Great Britain).

   [Online] 2017, 05 July . [Cited: 25 April 2022.] https://www.medicines.org.uk/emc/product/638/smpc#CLINICAL_PRECAUTIONS.

4. Guidelines for malaria prevention in travellers from the UK. Public Health England. [Online] 2021. [Cited: 25 April 2022.] https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1002275/Guidelines_for_malaria_pre vention_in_travellers_from_the_UK_2021-1.pdf.

5. Proguanil. BNF; The National Institute for Health and Care Excellence. [Online] [Cited: 25 April 2022.] https://bnfc.nice.org.uk/interaction/proguanil.html.

6. Malaria, prophylaxis. BNF; The National Institute for Health and Care Excellence. [Online] [Cited: 25 April 2022.] https://bnf.nice.org.uk/treatment-summary/malaria-prophylaxis.html?msclkid=f6d5f3f1c25211eca5b249fcbf14d8ed.

Additional resources

1. Malaria. NHS. [Online] February 18, 2022. [Cited: April 25, 2022.] https://www.nhs.uk/conditions/malaria/?msclkid=f6de5e7cc47f11eca7a696e70e74c2bd.

2. Patient Group Direction; Medicines practice guideline [MPG2]. National Institute for Health and Care Excellence. [Online] March 27, 2017. [Cited: February 11, 2022.] 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: February 11, 2022.] https://www.nice.org.uk/guidance/mpg2/resources.