Patient Group Direction (PGD) for the supply of doxycycline for the prophylaxis of malaria

1. Clinical condition or situation to which the direction applies

Indication

• Chemoprophylaxis of plasmodium falciparum malaria where there is doxycycline

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.

• Adults and children from 12 years of age: after risk assessment, and evaluation of travel plans, doxycycline 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 doxycycline 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.

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

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

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

̵ http://www.travax.nhs.uk/

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), any of the tetracyclines or to any of the excipients or trace residuals in selected doxycycline product. See section 2 and 6.1 of the relevant Summary of Product Characteristics (SPC).

• Individuals under 12 years of age.

• Known or suspected pregnancy.

• Breastfeeding patients.

• Patients with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrose-isomaltase insufficiency should not take doxycycline.

• Patients taking medications that would contraindicate the supply of doxycycline (see

  Product Interactions).

• Known to have a bleeding disorder or those taking medication to prevent their blood clotting.

• Systemic lupus erythematosus.

• Patients with Myasthenia Gravis.

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

Cautions

(including any relevant action to be taken)

Patients with hepatic impairment

• Doxycycline should be administered with caution to patients with hepatic impairment or those receiving potentially hepatotoxic drugs (1).

  Serious skin reactions

• Serious skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens- Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline. If serious skin reactions occur, doxycycline should be discontinued immediately (1).

  Oesophagitis

• Instances of oesophagitis and oesophageal ulcerations have been reported in patients receiving capsule and tablet forms of drugs in the tetracycline class, including doxycycline. Most of these patients took medications immediately before going to bed or with inadequate amounts of fluid (1).

  Missed doses

• A missed dose of doxycycline should be taken as soon as possible. If it is almost time for the next dose, the missed dose should be skipped and go back to the regular dosing schedule. Do not take 2 doses at once.

  Antacids

• The absorption of doxycycline may be impaired by concurrently administered antacids containing aluminium, calcium, magnesium, or bismuth-containing products, iron, multivitamins with minerals or iron, urinary alkalinizers (e.g., sodium

bicarbonate). Dosages should be separated by the maximum possible interval (1).

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

Cautions

(including any relevant action to be taken)

Photosensitivity

• Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including doxycycline. Patients likely to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs and treatment should be discontinued at the first evidence of skin erythema. Photoonycholysis has also been reported in patients receiving doxycycline (1).

  Oral live typhoid vaccines

• Should preferably not be started within 3 days after the last dose of oral typhoid vaccine as doxycycline possibly reduces the efficacy of oral typhoid vaccine if given simultaneously (2).

  Effects on ability to drive and use machines

• Visual disturbances such as blurring of vision may occur during treatment with doxycycline and in such cases; patients must refrain from driving or operating machinery (1).

  Planning a pregnancy

• Women of childbearing potential travelling to malarious areas in which multiple resistant P. falciparum is found and who are receiving doxycycline for the treatment and prophylaxis of malaria should take reliable contraceptive precautions for the entire duration of therapy and for one week after the last dose of doxycycline. Benign intracranial hypertension

• Benign intracranial hypertension (pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline. Benign intracranial hypertension (pseudotumor cerebri) is usually transient, however cases of permanent visual loss secondary to benign intracranial hypertension (pseudotumor cerebri) have been reported with tetracyclines including doxycycline. If visual disturbances occur during

treatment, refer patient to GP or A&E for ophthalmologic evaluation (1).

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

Cautions

(including any relevant action to be taken)

Microbial overgrowth (1)

• The use of antibiotics may occasionally result in over-growth of non-susceptible organisms including Candida.

• If a resistant organism appears, the antibiotic should be discontinued and the patient referred appropriately.

• Pseudomembranous colitis has been reported with nearly all antibacterial agents, including doxycycline, and has ranged in severity from mild to life-threatening. Patients with severe diarrhoea after taking doxycycline should be advised to seek medical attention.

  Clostridium difficile (1)

• Clostridium difficile Associated diarrhoea (CDAD) has been reported with use of doxycycline and can range in severity from mild diarrhoea to fatal colitis.

• CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

  Alcohol

• Alcohol may decrease the half-life of doxycycline. Patients should be advised to reduce alcohol intake during treatment (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.

• Medications that would contraindicate the supply of doxycycline include, but not limited to, are warfarin, tretinoin, isotretinoin, alitretinoin, acitretin, acenocoumarol, phenindione, lithium, ciclosporin, carbamazepine, phenytoin, etc (3).

• Caution is advised in administering tetracyclines with methoxyflurane (1).

• It is advisable to avoid giving doxycycline in conjunction with penicillin (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.

• 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.

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

  record.

• When treatment is postponed reschedule as appropriate.

  Pregnancy (2)

• Pregnant women should be advised to avoid travel to malaria 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. The risks and benefits of

antimalarial chemoprophylaxis needs to be discussed.

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(s)

Excipients

Age indications

*Varied

Doxycycline

**100mg doxycycline

1. Capsules

2. Dispersible tablets

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

12 years and over

• *Any equivalent brand or generic may be supplied.

• **50mg capsules may be supplied if required.

• 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 or 48 hours prior to entering a malaria-endemic area, continued during the period of exposure and for 28 days after leaving the area (1).

• One 100mg doxycycline capsules/tablets or two 50mg doxycycline capsules daily, orally in

adults and children over the age of 12 years (1).

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

Capsules

• The capsules can be taken with food and must be swallowed whole with a full glass of water (8 oz/240 mL) to help reduce the risk of throat or oesophagus irritation (1).

• Do not break, crush, or chew doxycycline capsules before swallowing.

• Do not lie down for 60 minutes after taking doxycycline capsules (2).

  Dispersible Tablets (4)

• The tablets are administered by drinking a suspension of the tablets in a small amount of water.

• This should be done in the sitting or standing position and well before retiring at night to reduce the risk of oesophageal irritation and ulceration.

• If gastric irritation occurs, it is recommended that they can be given with food or milk.

Frequency of

administration

• The stated oral dose is to be taken at the same time each day.

Quantity to supply

• Sufficient supply to provide prophylaxis for the duration of travel, beginning 1-2 days before travel to malarial areas and for 4 weeks after traveller leaves malarial areas (1).

Follow up / minimum or maximum period

• Dependent on time spent in malaria-endemic area.

• Refer to ACMP current guidelines for further information on long term use.

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

3. Further aspects of treatment

Adverse Reactions

• Follow local SOP on adverse reactions and their management.

• Common side effects include (≥1/100 to <1/10): Hypersensitivity (including anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, exacerbation of systemic lupus erythematosus, serum sickness), headache, hypotension, nausea, vomiting, photosensitivity reaction, rash including maculopapular and erythematous rashes, Henoch- Schonlein purpura, urticaria, pericarditis, tachycardia, dyspnoea and peripheral oedema (1).

• Uncommon side effects include (≥1/1,000 to <1/100): Vaginal infection and dyspepsia

  (1).

• Rare side effects include (≥1/10,000 to <1/1,000): Candida Infection, pseudomembranous colitis, clostridium difficile colitis, haemolytic anaemia, neutropenia, thrombocytopenia, eosinophilia, Jarisch- Herxheimer reaction, porphyria, brown-black microscopic discolouration of thyroid glands, decreased appetite, benign intracranial hypertension, anxiety, tinnitus, flushing, pancreatitis, oesophageal ulcer, oesophagitis, enterocolitis, inflammatory lesions (with monilial overgrowth) in the anogenital region, dysphagia, abdominal pain, diarrhoea, glossitis, stomatitis, hepatic failure, hepatitis, hepatotoxicity, jaundice, hepatic function abnormal, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), angioedema, toxic epidermal necrolysis, Stevens- Johnson syndrome, erythema multiforme, dermatitis exfoliative, photoonycholysis, skin hyperpigmentation, arthralgia and myalgia (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.

3. Further aspects of treatment – continued

Advice to patient / carer

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 (2):

  ̵ Awareness of risk

  ̵ Bite prevention

  ̵ Chemoprophylaxis

  ̵ Diagnose malaria promptly and treat without delay

• The Advisory Committee on Malaria Prevention (ACMP) recommends the following repellents (2):

  ̵ 50% DEET based insect repellent as first choice

  ̵ 20% Picaridin based insect repellent

  ̵ Eucalyptus citriodora oil

  ̵ 3-ethylaminoproprionate containing repellent

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

• 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. Cough and diarrhoea may also occur (5).

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 doxycycline such as information from the product 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.

• All PGD users must be familiar with and have online access to the latest edition of the Guidelines for malaria prevention in travellers from the UK, noting that clinical guidance may change and that these guidelines are regularly updated.

• Have online access during a consultation for malaria chemoprophylaxis with ACMP guidelines, travelhealthpro.org.uk, fitfortravel.nhs.uk, or travax.nhs.uk (professional

subscription).

3. Further Aspects of Treatment – continued

Additional facilities / 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; Doxycycline 100mg Capsules. emc (Great Britain). [Online] 2022, 05 February. [Cited: 22 April 2022.] https://www.medicines.org.uk/emc/product/4063/smpc.

2. Guidelines for malaria prevention in travellers from the UK 2021. Public Health England. [Online] [Cited: 22 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.

3. Doxycycline. BNF; The National Institute for Health and Care Excellence. [Online] [Cited: 22 April 2022.] https://bnf.nice.org.uk/interaction/doxycycline-2.html.

4. Summary of Product Characteristics; Vibramycin-D Dispersible Tablets 100mg. emc (Great Britain). [Online] 29 July 2021. [Cited: 22 April 2022.] https://www.medicines.org.uk/emc/product/6262/smpc.

5. Malaria, prophylaxis. BNF; The National Institute for Health and Care Excellence. [Online] [Cited: 22 April 2022.] https://bnf.nice.org.uk/treatment-summary/malaria-prophylaxis.html?msclkid=f6d5f3f1c25211eca5b249fcbf14d8ed.

Additional resources

1. Malaria . Travel Health Pro. [Online] June 02, 2021. [Cited: April 22, 2022.] https://travelhealthpro.org.uk/factsheet/52/malaria.

2. Medicines: packaging, labelling and patient information leaflets. GOV.UK. [Online] December 31, 2020. [Cited: April 22, 2022.] https://www.gov.uk/guidance/medicines-packaging-labelling-and-patient-information-leaflets.

3. Faculty of Sexual & Reproductive Healthcare Clinical Guidance. Faculty of Sexual Health and Reproductive Healthcare. [Online] January 2011. [Cited: April 22, 2022.] https://www.travax.nhs.uk/media/14546/guidance_on_antibiotics_and_chc_feb_2011.pdf.

4. 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.

5. 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.