Patient Group Direction (PGD) for the administration of melatonin for jet lag

1. Clinical condition or situation to which the direction applies

Indication

• Melatonin tablets are indicated for the short-term treatment and prevention of jet lag in

patients taking long-haul flights.

Objectives of care

• To reduce the symptoms associated with jet lag in patients taking long-haul flights.

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.

• Individuals from 18 years of age.

• Patients who have suffered from jet lag previously.

• Patients travelling on a long haul flight, especially when crossing several (5 or more) time zones.

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 the selected melatonin product. See section 2 and 6.1 of the relevant Summary of Product Characteristics (SPC).

• Individuals under 18 years of age.

• Known or suspected pregnancy.

• Breast-feeding individuals.

• Individuals with renal or hepatic impairment.

• Patients with a current seizure disorder or history of seizures. This includes patients with epilepsy or taking medicines for epileptic conditions.

• Patients with autoimmune diseases, e.g. type 1 diabetes, rheumatoid arthritis, psoriasis, inflammatory bowel disease, myasthenia gravis, etc.

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

Product Interactions).

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

Cautions

(including any relevant action to be taken)

Lactose

• Some products may contain lactose hence these should be avoided in patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose- galactose malabsorption.

  Undesirable effects

• Melatonin may cause drowsiness. Therefore, this product should be supplied with caution if the effects of drowsiness are likely to be associated with a risk to patient safety. Patients should exercise caution before driving or using machinery until they are reasonably certain that treatment does not adversely affect their performance (1) (2) (3). Alcohol and cigarette smoking

• Alcohol should be avoided during treatment, as it can reduce the effectiveness of melatonin on sleep. Furthermore, cigarette smoking should be avoided where possible, as it may decrease melatonin levels due to induction of CYP1A2 (1) (2) (3).

  Food

• Food can enhance the increase in plasma melatonin concentration. Intake of melatonin with carbohydrate-rich meals may impair blood glucose control for several hours. It is recommended that food is not consumed 2 h before and 2 h after intake of melatonin; ideally at least 3 hours after meal by persons with significantly impaired glucose tolerance or diabetes (1) (2) (3).

  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.

• Melatonin is metabolised mainly by the hepatic cytochrome P450 CYP1A enzymes, primarily CYP1A2. Therefore, interactions between melatonin and other active substances as a consequence of their effect on CYP1A enzymes are possible (1) (2) (3).

• Patients treated with fluvoxamine should avoid melatonin (1) (2) (3).

• Caution is indicated in patients taking 5- or 8-methoxypsoralen (5 or 8-MOP), since this agent increases melatonin levels by inhibiting its metabolism (1) (2) (3).

• Caution is indicated in patients taking cimetidine, since this agent increases plasma melatonin levels by inhibiting its metabolism by CYP2D (1) (2) (3).

• Caution should be exercised in patients receiving oestrogen therapy (e.g. in the form of contraceptives or hormone replacement therapy) (1) (2) (3).

• CYP1A2 inhibitors (such as quinolones) may increase systemic melatonin levels (1) (2) (3).

• CYP1A2 inducers (such as carbamazepine and rifampicin) may reduce plasma concentrations of melatonin (1) (2) (3).

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.

• Advise patients on the main symptoms of jet lag, and how steps can be taken to reduce symptoms without taking melatonin (4).

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.

• Advise patients on the main symptoms of jet lag, and how steps can be taken to reduce symptoms without taking melatonin (4).

2. Description of treatment

Name, strength & formulation of drug

Supplier

Name of

product

Composition

Pharmaceutical form

Excipients

Age indications

Pharma Nord UK

Melatonin

Melatonin 3mg

Film-coated tablet

• Magnesium stearate

• Colloid silica, anhydrous

• Maltodextrin

• Microcrystalline cellulose

• Croscarmellose sodium

  Film coating:

• Hypromellose

18 years and over

Pharma Nord UK

Syncrodin®

Melatonin 3mg

Film-coated tablet

• Magnesium stearate

• Colloid silica, anhydrous

• Maltodextrin

• Microcrystalline cellulose

• Croscarmellose sodium

  Film coating:

• Hypromellose

18 years and over

Colonis Pharma Ltd

Melatonin

Melatonin 3mg

Film-coated tablet

• Cellulose, Microcrystalline

• Maltodextrin

• Silica, Colloidal Anhydrous

• Magnesium Stearate

  Coating:

• Hypromellose

• Lactose monohydrate

• Titanium dioxide

• Macrogol 4000

18 years and over

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

2. Description of treatment – continued

Legal status

• POM – Prescription Only Medicine

Dose/dose range

• One 3 mg tablet (1) (2) (3).

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.

• Only products specified in this PGD are authorised for jet lag treatment, other

products (brands & generics) are not authorised.

Route/method of administration

• For oral administration.

• It is recommended that food is not consumed 2 h before and 2 h after intake of melatonin (1) (2) (3).

• Tablets should not be broken or crushed.

Frequency of administration

• One 3 mg tablet to be taken once daily (1) (2) (3).

• The patient should take the first dose 30 minutes before going to bed on the day they arrive at their destination (1) (2) (3).

• The patient should continue to take the tablets (30 minutes before going to bed) for a maximum of 5 days (1) (2) (3).

• The dose may be increased to 6 mg (2 tablets taken together) if the standard dose does not adequately alleviate symptoms. The dose that adequately alleviates symptoms should be taken for the shortest period (1) (2) (3).

• If required, the patient should start another treatment period on their return, taking their first dose 30 minutes before going to bed on the day they arrive back

from their destination, for a maximum of 5 days.

Follow up / minimum or maximum period

• Patients should be supplied a minimum of 10 tablets to cover a maximum of 5 days of treatment after arriving at the destination, and 5 days treatment following the return flight.

• A maximum of 20 tablets can be supplied under this PGD if the higher dose (6mg) is to be taken to cover a maximum of 5 days of treatment after arriving at the

destination, and 5 days treatment following the return flight.

3. Further aspects of treatment

Adverse reactions and their management

• Follow local SOP on adverse reactions and their management.

• Common side effects include (≥1/100 to <1/10): Headache and somnolence (1) (2) (3).

• Uncommon side effects include (≥1/1,000 to <1/100): Irritability; nervousness; restlessness; abnormal dreams; anxiety; dizziness; hypertension; abdominal pain; upper abdominal pain; dyspepsia; oral ulcers; dry mouth; nausea; pruritus; rash; dry skin; glycosuria; proteinuria; chest pain; malaise and weight increased (1) (2) (3).

• Rare side effects include (≥1/10,000 to <1/1,000): Leucopenia; thrombocytopenia; hypertriglyceridaemia; mood altered; aggressive behaviour; disorientation; libido increased; syncope; memory impairment; restless legs syndrome; paraesthesia; visual acuity reduced; vision blurred; lacrimation increased; palpitations; hot flushes; vomiting; flatulence; salivary hypersecretion; halitosis; gastritis; nail disorder; arthritis; muscle spasms; polyuria; haematuria; priapism; prostatitis; thirst and abnormal blood electrolytes (1) (2) (3).

• 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.

• Advise patients on the frequency of administration and how to take the tablets.

• Advise patients on how to store the tablets.

• 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.

  Management of jet lag

• Patients should be encouraged to have adequate sleep prior to travel to minimise jet lag after arrival to the destination (4).

• Advise patients that jet lag will likely be worse immediately after travel, and symptoms will improve gradually over 4 to 6 days (5).

• If appropriate, advise the traveller to consider adjusting their sleep schedule to match the destination time in the days prior to travel, and to adopt the destination time schedule from the time when they board the flight (6).

• Advise patients to eat light meals whilst flying and take every opportunity to sleep during the journey (4).

• Due to the potential for incorrectly timed intake of melatonin to have no effect, or to cause an adverse effect, on re-synchronisation following jet-lag, melatonin should not be taken before 20:00 hr or after 04:00 hr at destination (1).

• Measures should be taken to promote sleep after arrival, such as (6):

̵ Change sleep schedule to the new time zone as quickly as possible

̵ Go outside during the day

̵ Set an alarm to avoid oversleeping in the morning

3. Further aspects of treatment – 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 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.

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 melatonin, 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.

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; Melatonin Pharma Nord 3mg film-coated tablets. emc (Great Britain). [Online] 22 January 2020. [Cited: 17 March 2023.] https://www.medicines.org.uk/emc/product/11018/smpc.

2. Summary of Product Characteristics; Syncrodin 3 mg film-coated tablets. emc (Great Britain). [Online] 23 September 2020. [Cited: 17 March 2023.] https://www.medicines.org.uk/emc/product/11772.

3. Summary of Product Characteristics; Melatonin 3 mg film-coated tablets. emc (Great Britain). [Online] 05 October 2021. [Cited: 17 March 2023.] https://www.medicines.org.uk/emc/product/10405.

4. Sleep disorders - shift work and jet lag. Clinical Knowledge Summaries; The National Institute for Health and Care Excellence. [Online] November 2019. [Cited: 17 March 2023.] https://cks.nice.org.uk/topics/sleep-disorders-shift-work-jet-lag/.

5. Herxheimer, Andrew. Jet Lag. National Library of Medicine. [Online] 29 April 2014. [Cited: 17 March 2023.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006102/.

6. Jet lag. NHS. [Online] 03 August 2020. [Cited: 17 March 2023.] https://www.nhs.uk/conditions/jet-lag/.

Additional resources

1. Melatonin for the prevention and treatment of jet lag. National Library of Medicine. [Online] 2002. [Cited: May 05, 2022.] https://pubmed.ncbi.nlm.nih.gov/12076414/.

2. Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders. National Library of Medicine. [Online] November 01, 2007. [Cited: May 05, 2022.] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082098/.

3. BNF; The National Institute for Health and Care Excellence. Melatonin. [Online] [Cited: May 05, 2022.] https://bnf.nice.org.uk/drug/melatonin.html.

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.