Patient Group Direction (PGD) for the supply of acetazolamide 250mg tablets for altitude sickness

1. Clinical condition or situation to which the direction applies

Indication

• To prevent and reduce light to moderate symptoms of altitude sickness.

Objectives of care

• To prevent and reduce symptoms of altitude sickness in individuals travelling to high

altitudes.

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.

• 18 years of age and over.

• Individuals at risk of altitude sickness, including those travelling to altitudes more than 2500m (8202 feet) above sea level.

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 sulphonamides or other sulphonamide derivatives and to any active substance(s) or to any of the excipients or trace residuals in acetazolamide 250mg tablets. See section 2 and 6.1 of the relevant Summary of Product Characteristics (SPC).

• Patients under 18 years of age.

• Patients with renal or hepatic impairment.

• Patients with decreased sodium and/or potassium blood levels (suprarenal gland failure, hyperchloremic acidosis, hypokalaemia, hyponatremia, adrenocortical insufficiency, marked kidney and liver disease or dysfunction etc).

• Patients with severe depression, generalized anxiety disorder, psychosis, schizophrenia, suicide attempts, suicidal thoughts, self-endangering behaviour or any other psychiatric disorder.

• Known or suspected pregnancy.

• Breast-feeding individuals.

• Patients with conditions that are associated with, or predispose to, electrolyte and acid/base imbalances, such as patients with pulmonary obstruction, emphysema and patients with impaired alveolar ventilation.

• Patients with a past history of renal calculi (kidney stones), as they may be at increased risk of precipitating further calculi.

• Patients taking medications that would contraindicate the supply of acetazolamide 250mg tablets (see Product interactions).

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

Cautions

(including any relevant action to be taken)

Side effects

• Increased doses may increase the incidence of drowsiness and/or paraesthesia (1).

• Acetazolamide may cause electrolyte imbalances, including hyponatraemia and transient hypokalaemia, as well as metabolic acidosis (1).

• Acetazolamide may affect blood glucose levels, so particular caution should be taken in patients with impaired glucose tolerance (2).

• Metabolic acidosis has been reported in patients during treatment with acetazolamide (1).

• Patients should be advised on the symptoms of High altitude cerebral oedema (HACE) and High altitude pulmonary oedema (HAPE). Furthermore, patients should be made aware of the actions to take if either develops (3).

  Off-label use

• Acetazolamide is not licensed to prevent and treat altitude sickness, although it has long been used for this purpose. When supplying off-label, as part of the consent process, consider informing the patient/carer that the medication is being offered in accordance with national guidance but that this is outside the product licence.

• Acetazolamide is to be used as a prophylactic course to aid acclimatisation during ascension. Once acclimatised, acetazolamide is not necessary, unless early symptoms of altitude sickness appear.

  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.

  Aspirin

• Patients should be advised not to take aspirin, as concurrent administration with acetazolamide may result in severe acidosis and increase central nervous system toxicity (1). Amphetamine and Quinidine

• By increasing the pH of renal tubular urine, acetazolamide reduces the urinary excretion of amphetamine and quinidine and so may enhance the magnitude and the duration of effect of amphetamines and enhance the effect of quinidine (1).

  Ciclosporin

  Acetazolamide may elevate ciclosporin levels (1).

  Methenamine

• Acetazolamide may prevent the urinary antiseptic effect of methenamine (1).

  Lithium

• Acetazolamide increases lithium excretion and the blood lithium levels may be decreased (1).

  Sodium bicarbonate

• Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation (1).

  Folic acid antagonists

• Acetazolamide is a sulphonamide derivative. Sulphonamides may potentiate the effects of folic acid antagonists (1).

  Hypoglycaemics

• Possible potentiation of the effects of hypoglycaemics may occur (1).

  Oral anticoagulants

• Possible potentiation of the effects of oral anti-coagulant may occur (1).

  Cardiac glycosides or hypertensive agents

• Adjustment of dose may be required when acetazolamide tablets are given with cardiac glycosides or hypertensive agents (1).

  Anticonvulsants

• When given concomitantly, acetazolamide modifies the metabolism of phenytoin, leading to increased serum levels of phenytoin. Severe osteomalacia has been noted in a few patients taking acetazolamide in combination with other anticonvulsants. There have been isolated reports of reduced primidone and increased carbamazepine serum levels with concurrent administration of acetazolamide (1).

  Carbonic anhydrase inhibitors

• Because of possible additive effects, concomitant use with other carbonic anhydrase inhibitors is not advisable (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 or travel health clinic if appropriate.

• 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.

• The risk to the individual of not taking acetazolamide must be discussed with the traveller and considered.

• Advise about the risks of altitude sickness, and ways in which symptoms can be reduced.

Healthcare professionals should make patients aware of the life-threatening conditions (cerebral and pulmonary oedema) that can occur if altitude sickness is ignored.

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 and the risks of travelling to high altitudes without acetazolamide.

• 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.

• Healthcare professionals should make patients aware of the life-threatening conditions (cerebral and pulmonary oedema) that can occur if altitude sickness is ignored.

2. Description of treatment

Name, strength & formulation of drug

Supplier

Name of

product

Composition

Pharmaceutical form

Excipients

Age indications

*ADVANZ

Pharma

Acetazolamide

250mg acetazolamide

Tablets

• Dicalcium phosphate

• Corn starch

• Magnesium stearate

• Sodium starch glycolate

• Povidone

18 years and over

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

• *Any appropriate brand or generic can be supplied under this PGD (excipients may vary).

Legal status

• POM – Prescription Only Medicine

Dose/Dose range

• 125mg, twice daily (4).

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.

• Acetazolamide is not licensed to prevent and treat altitude sickness (see cautions).

• Please note that where medicine is supplied outside the terms of the marketing authorisation, this would constitute off-label use. Where a medicine is recommended off- label, as part of the consent process, consider informing the patient/carer that the medicine is being offered in accordance with national guidance but that this is outside the product licence.

• Although healthcare professionals have the right to refuse treatment even where a

patient is eligible, they cannot override PGD exclusions.

Route/Method of

administration

• Oral administration.

• Tablets should be halved for a 125mg dose.

Frequency of administration

• 125mg twice daily to be commenced 1 day prior to ascent and continued for 2 days once acclimatised to the high altitude or once descent has begun (4).

• Once acclimatised, treatment should be discontinued unless early symptoms of altitude sickness appear, and other treatment options have failed (4).

• If symptoms of altitude sickness appear after acclimatisation, patients should be advised to take antiemetics (e.g. promethazine) for nausea and paracetamol or ibuprofen for

headaches (3).

Quantity to supply

• 10 tablets.

Follow up / minimum or

maximum period

• A maximum of 10 tablets can be supplied using this PGD.

3. Further aspects of treatment

Adverse reactions and their management

• Follow local SOP on adverse reactions and their management.

• Ver common (≥1/10) or common side effects include (≥1/100 to <1/10):

  Haemorrhage; metabolic acidosis; nephrolithiasis; sensation abnormal (2).

• Uncommon side effects include (≥1/1,000 to <1/100): Bone marrow

  disorders; depression; dizziness; electrolyte imbalance; hearing impairment; hepatic disorders; leucopenia; nausea; renal colic; renal impairment; renal lesions; severe cutaneous adverse reactions (SCARs); skin reactions; thrombocytopenia; tinnitus; urinary tract discomfort; urine abnormalities; vomiting (2).

• Rare (≥1/10,000 to <1/1,000) or very rare (<1/10,000) side effects: Anaphylactic reaction; appetite

  disorder; confusion; diarrhoea; fatigue; fever; flushing; headache; irritability; libido decreased; paralysis; photosensitivity reaction; seizure (2).

• Frequency not known: Agranulocytosis; drowsiness; myopia; polyuria; suicidal behaviours; taste altered; thirst (2).

• For a comprehensive list of all warnings, cautions and potential adverse reactions, refer to the current BNF and SPC (Great Britain or Northern Ireland) and Travel Health Pro NaTHNaC

- Home (travelhealthpro.org.uk)

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.

• 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.

• Taking acetazolamide does not mean individuals can keep ascending if symptoms of altitude sickness appear. If symptoms appear, patients should stay at the same altitude until symptoms have completely disappeared.

• Advise patients that if they do not feel any better after 24 hours, to go down by at least 500m (about 1,600 feet) (3).

• Advise patients if using acetazolamide, they should still travel to high altitudes gradually and follow the general prevention advice (3).

• Advise patients to take 2-3 days to get used to high altitudes before going above 2,500m. Climbing more than 300-500m a day should also be avoided (3).

• Patients should be advised to take a rest day every 600-900m, or every 3-4 days (3).

• It is important that patients keep themselves hydrated during the entire trip and maintain an adequate energy intake (3).

3. Further aspects of treatment – continued

Advice to patient / carer

• Patients should avoid the following whilst travelling to high altitudes (3):

  ̵ Alcohol

  ̵ Smoking

  ̵ Strenuous exercise, especially in the first 24 hours

• Advise patients to use antipyretics if they get a headache during travel. Anti-sickness medication may also be advised for travel purposes (3).

• Patients should be advised not to take Aspirin.

• Advise patients of the common symptoms associated with altitude sickness (3):

  ̵ Headache

  ̵ Nausea

  ̵ Vomiting

  ̵ Poor appetite

  ̵ Dizziness

• Patients should be made aware of the risks if altitude sickness is ignored, including high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE).

• Symptoms of HACE can develop over a few hours, and include (3):

  ̵ Headache

  ̵ Weakness

  ̵ Nausea

  ̵ Vomiting

  ̵ Loss of co-ordination

  ̵ Confusion

  ̵ Hallucinations

• Symptoms of HAPE can develop over a few days, and include (3):

  ̵ Cyanosis

  ̵ Breathing difficulties (even whilst resting)

  ̵ Tightness in the chest

  ̵ Persistent cough

  ̵ Coughing of sputum

  ̵ Tiredness and weakness

• If patients experience any of these symptoms, they should descend immediately and seek immediate medical attention. Bottled oxygen should also be used, if possible (3).

• If HACE or HAPE are suspected, the individual should never carry any load.

• For further information, refer to the International Climbing and Mountaineering Federation (UIAA) recommendations.

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 acetazolamide 250mg tablets, 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.

  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; Acetazolamide 250mg Tablets. emc (Great Britain). [Online] 23 August 2019. [Cited: 28 April 2023.] https://www.medicines.org.uk/emc/product/2785.

2. Acetazolamide. BNF; The National Institute for Health and Care Excellence. [Online] [Cited: 28 April 2023.] https://bnf.nice.org.uk/drug/acetazolamide.html#sideEffects.

3. Altitude sickness. NHS. [Online] 13 March 2020. [Cited: 28 April 2023.] https://www.nhs.uk/conditions/altitude- sickness/.

4. Altitude Illness. Travel Health Pro. [Online] 09 February 2023. [Cited: 28 April 2023.] https://travelhealthpro.org.uk/factsheet/26/altitude-illness.

Additional resources

1. Patient Group Direction; Medicines practice guideline [MPG2]. National Institute for Health and Care Excellence.

   [Online] March 27, 2017. [Cited: April 29, 2023]. https://www.nice.org.uk/Guidance/MPG2.

2. Competency framework for health professionals using Patient Group Directions. National Institute for Health and Care Excellence. [Online] January 4, 2018. [Cited: April 29, 2023]. https://www.nice.org.uk/guidance/mpg2/resources.