Originally published online: https://bit.ly/3N9DSzF
Daniel Grace. Primary care attitudes towards the prescription of acetazolamide for altitude illness. Authorea. June 01, 2022.
Acute mountain sickness (AMS) is characterized by symptoms of headache, light-headedness, fatigue, nausea, and insomnia, at altitudes above 2,500m in those poorly acclimatized to such conditions. The risk of AMS increases with altitude, and, if left untreated, can progress to high altitude cerebral oedema and death. In non-indigenous populations, the incidence of AMS ranges from between 14% and 53% in the Himalayas and 47% and 75% on Mount Kilimanjaro. This latter figure is likely a result of the speed at which trekking companies elect to climb Kilimanjaro, with many ascending over 4 or 5 days, and only 17% of companies adhering to the WMS guidelines for safe ascent5.
Figure 1: The risk factors for developing Acute Mountain Sickness according to the Wilderness Medical Society guidelines7
Multiple trials have established a role for acetazolamide (trade name Diamox®) in the prevention of AMS. The recommended adult dose for prophylaxis is 125 mg twice daily7. This has been shown to be non-inferior to higher doses with a much better side-effect profile, which in turn increases compliance. Acetazolamide can also be used to treat AMS, with a 250mg dose twice daily. It can also be considered as an adjunct in the treatment of high altitude cerebral oedema (HACE)7, however ensuring appropriate descent is by far the most important strategy when managing both of these conditions.
It is estimated that over 100 million people travel to altitude every year, yet many expedition companies do not carry the necessary medications to treat or prevent altitude illness. Indeed, a recent study by Pattenden et al found that up to 48% of commercial operators going to destinations such as Kilimanjaro, Aconcagua and Everest Base Camp, do not keep acetazolamide, dexamethasone or nifedipine in their medical field kits.
Various explanations were given to the authors of that paper regarding why these medications were not stocked, and these predominantly focused upon the legal issues surrounding the administration, supply, and carriage of these medications10. One verbatim quote received from one expedition company in Pattenden’s study stated, “we would expect customers to approach their GP (general practitioner) for guidance in this field and gain their own medication if required10.”
In the UK, 69% of trekkers seek pre-travel advice from their family doctor, however the prescribing of acetazolamide for travel is a private service which does not form part of the General Medical Services (GMS) contract. Furthermore, the majority of general practitioners do not have formal travel medicine or altitude medicine training and GMC guidance states that “as outlined in ‘Good medical practice’, you must recognise and work within the limits of your competence and you must keep your knowledge and skills up to date.”
It is also important to appreciate that according to the British National Formulary (BNF), acetazolamide is only licenced for the management of glaucoma. The summary of product characteristics (SmPC) document for acetazolamide expands on this, stating that it can also be used as a diuretic and as an adjunct in the management of epilepsy, however there is no mention of its use in altitude illness.
Whilst Williamson et al, have provided a useful “10-minute consultation” guideline9, which was published in the BMJ in 2018, for readers who may consult with a traveller going to altitude, the author of this study wanted to investigate how acetazolamide prescribing was perceived in primary care, given some of the aforementioned points.
A questionnaire was designed to obtain quantitative and qualitative data on the topic of Acetazolamide prescribing in primary care. The questions were phrased to encompass the generic name and the trade name of Diamox®. The questionnaire was constructed using Google Forms and posted in two well-known Facebook groups, made up of primary care staff.
The survey was live for a two-week period, during which 221 responses were recorded. Of these, 220 were from primary care staff and one was from secondary care, which was therefore discounted.
Table 1: Cohort Survey Responses
The study sample breakdown consisted predominantly of doctors, with 101 GP partners (45.9%), 79 salaried GPs (35.9%), 30 locum GPs (13.6%), 3 GP trainees (1.4%), 2 military GPs (0.9%) and 1 private GP (0.5%). In addition, there were 3 advanced nurse practitioners (1.4%) and 1 clinical pharmacist (0.5%) within the sample population.
Out of the 220 clinicians surveyed, 25 (11.4%) had received additional specialist training in travel or expedition medicine whilst 195 (88.6%) had not.
In terms of clinicians who had previously prescribed acetazolamide for patients going to altitude, 53 (24.1%) had done this, whereas 167 (75.9%) had not. Future prescribing attitudes were similar, with 40 clinicians (18.2%) happy to prescribe acetazolamide for those going to altitude and 180 (81.7%) not feeling comfortable doing this.
The principal reasons underpinning this reluctance to prescribe were “a lack of knowledge or training” (146 responses; 66.4%), “it does not form part of the GP GMS contract” (138 responses; 62.7%) and “I do not have appropriate indemnity cover for this work” (125 responses; 56.8%).
In addition, “time constraints” were mentioned by 33 (15%) of answers whilst “other’ was chosen by 25 (11.4%). The qualitative findings from the survey support these quantitative results and also provide some interesting ethical and medicolegal insights.
Figure 2: Sample Demographics
Figure 3: Clinician attitudes to prescribing acetazolamide
Figure 4: Reasons behind clinician reluctance to prescribe acetazolamide
Figure 5: Reasons why clinicians would prescribe acetazolamide
Figure 6: Reasons why clinicians would not want to prescribe Acetazolamide
The majority of clinicians surveyed had little or no additional expedition or travel medicine training, and this was a key factor behind their reluctance to prescribe acetazolamide to patients going to altitude. Conversely, those who had gained further qualifications were often happier to prescribe. A small number of clinicians, who had either personal experience of taking acetazolamide, or had researched the available evidence-base, were also more likely to prescribe it, as they felt able to give appropriate safety netting advice to patients and advise them accordingly.
Some clinicians were understandably worried about acetazolamide providing trekkers with “false reassurance,” citing that this might encourage riskier ascent profiles, or that unwell patients might not descend when required, resulting in adverse patient outcomes and possible litigation.
A lack of appropriate medical indemnity was a significant reason as to why clinicians would not prescribe acetazolamide. Indeed, GMC guidance states that clinicians should “prescribe medicine or treatment, including repeat prescriptions, only [if they] have adequate knowledge of the patient’s health, and are satisfied that the medicine or treatment serves the patient’s needs12.”
As discussed previously, acetazolamide can be used for both the prophylaxis and treatment of AMS. If a patient is participating in a high-altitude trek overseas, can the original prescribing clinician be confident that the prescription they have issued is serving the patient’s best needs if they are unable to assess the patient, and can they therefore justify writing the prescription in the first place?
The Medical Protection Society (MPS) cautions against the prescription of “just in case” medications for use abroad, a view that is shared by The Medical and Dental Defence Union of Scotland (MDDUS), who advise against “agreeing to issue prescriptions to patients who are overseas without proper assessment,” stating that “members would not be represented if action was taken against them in another country where harm had arisen as a result of their provision of medical advice16.”
Another significant argument against prescribing, was the belief that travel medicine prescriptions, such as this, are a private non-NHS service. There were several common sub-themes, with many suggesting that individuals with enough financial reserves to go on such a trip should also be able to see a private clinician for their travel needs. Others felt that medication requests such as this would further stretch general practice at a time when there is unprecedented demand for appointments, which has been worsened by the COVID-19 pandemic.
Whilst it is important to acknowledge that the new GP contract, which runs to 2024, states that “all practices will be expected to offer […] NHS travel vaccinations to their registered eligible population,” it is equally important to appreciate that this is vastly different to providing a comprehensive travel clinic service that offers specialist advice regarding travel to altitude. As discussed above, such a service would require additional indemnity and training in order to optimise patient safety.
There were some limitations to this study, in that the sample size of 201 clinicians is perhaps not fully representative of all primary care prescribers. Additionally, the posting of the survey on social media platforms to obtain this sample may have created an additional source of bias, however, overall, the findings of this study highlight that the prescription of acetazolamide for altitude illnesses in primary care should be avoided. Expedition and travel companies should take heed and should stop signposting potential participants to their GP for this and should instead encourage them to consult with a travel health professional or a doctor with specialist experience in expedition or altitude medicine.
 Ritchie ND, Baggott AV, Todd A, T W. Acetazolamide for the Prevention of Acute Mountain Sickness—A Systematic Review and Meta‐analysis. J Travel Med. 2012 Sep 1;19(5):298–307.  Shah NM, Windsor JS, Meijer H, Hillebrandt D. Are UK Commercial Expeditions Complying with Wilderness Medical Society Guidelines on Ascent Rates to Altitude? J Travel Med. 2011 May 1;18(3):214–6.  Davies AJ, Kalson NS, Stokes S, Earl MD, Whitehead AG, Frost H, et al. Determinants of Summiting Success and Acute Mountain Sickness on Mt Kilimanjaro (5895m). Wilderness & Environmental Medicine. 2009 Dec 1;20(4):311–7.  Luks AM, McIntosh SE, Grissom CK, Auerbach PS, Rodway GW, Schoene RB, et al. Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2014 Update. Wilderness & Environmental Medicine. 2014 Dec 1;25(4):S4–14.  Basnyat B, Gertsch JH, Holck PS, Johnson EW, Luks AM, Donham BP, et al. Acetazolamide 125 mg BD is not significantly different from 375 mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial. High Alt Med Biol. 2006;7(1):17–27.  Williamson J, Oakeshott P, Dallimore J. Altitude sickness and acetazolamide. BMJ. 2018 May 31;361:k2153.  Pattenden HA, Shah NM, Hillebrandt D, Rodger M, Windsor JS. Do British commercial mountaineering expeditions carry drugs to treat high altitude illnesses? J Travel Med. 2012 Jul;19(4):250–2.  Croughs M, Van Gompel A, Van den Ende J. Acute Mountain Sickness in Travelers Who Consulted a Pre‐Travel Clinic. J Travel Med. 2011 Sep 1;18(5):337–43.  Good practice in prescribing and managing medicines and devices [Internet]. [cited 2022 Feb 14]. Available from: https://www.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/good-practice-in-prescribing-and-managing-medicines-and-devices  Excellence N-TNI for H and C. BNF: British National Formulary - NICE [Internet]. NICE; [cited 2022 Feb 14]. Available from: https://bnf.nice.org.uk/drug/acetazolamide.html  Acetazolamide 250mg Tablets - Summary of Product Characteristics (SmPC) - (emc) [Internet]. [cited 2022 Feb 14]. Available from: https://www.medicines.org.uk/emc/product/2785/smpc  Holiday prescribing [Internet]. Articles. [cited 2022 Apr 30]. Available from: https://www.medicalprotection.org/uk/articles  Prescribing for patients overseas [Internet]. MDDUS. [cited 2022 Apr 30]. Available from: https://www.mddus.com/advice-and-support/advice-library/prescribing-for-patients-overseas  British Medical Association. Update to the GP Contract Agreement 2020/21- 2023/24 [Internet]. [cited 2022 Apr 30]. Available from: https://www.bma.org.uk/media/2024/gp-contract-agreement-feb-2020.pdf