Diuretics: reducing harm

Diuretics are a valuable class of medicines commonly used in the treatment of hypertension and heart failure.¹ However, they are often overused.²

Older people are particularly vulnerable to their adverse effects, which commonly include fluid and electrolyte disturbances, renal impairment and metabolic abnormalities including hyperglycaemia and hyperlipidaemia.^1, 3-7 Diuretics can also cause dermatitis³, urinary urgency² and secondary gout in older people.⁷

Most diuretic-related adverse effects can be avoided or minimised with appropriate use, by closely monitoring patients and by adjusting the dose of the diuretic as needed.⁸

Monitor fluid status, electrolytes and renal function

Most diuretic-induced adverse effects are dose-related and can be minimised or avoided by selecting the lowest dose necessary for effective blood pressure or volume control, close monitoring (see Table 1) and adjusting the dose of the diuretic as needed.^{3, 8, 10, 11} As a general guide, once the patient and treatment is stable, check fluid status, electrolytes and renal function at each re-prescription, or once every three to six months. Monitor more frequently if your patient becomes acutely unwell or treatments change.¹²

A medicines review can be particularly beneficial

Older patients taking a diuretic who are frail or cognitively impaired, or have renal impairment, comorbid complexity or polypharmacy, are more likely to experience adverse effects.^{4, 8, 11, 12, 14} In this population, diuretic-induced adverse effects can contribute to dehydration, falls and fractures, declining attention and cognitive function, worsening renal impairment, reduced quality of life, and institutionalisation.^{2, 5, 10, 14-16}

A collaborative medicines review can be particularly beneficial in detecting, preventing or resolving diuretic-related problems.^17, 18

The pharmacist conducting the medicines review can assess and consider:

• if the diuretic is still needed (see Box 1)
• pathology results, including electrolyte and renal, and further monitoring required
• potential drug-drug or drug-disease interactions of concern
• compliance and knowledge issues, and the patient’s ability to manage their medicines, including their diuretic medicines on sick days and during hot weather.¹⁸

Detailed information about a Residential Medication Management Review (RMMR) under item number 903 and a Home Medicines Review (HMR) under item number 900 is available at: www9.health.gov.au/mbs/fullDisplay.cfm?type=item&q=900&qt=ItemID

More frequent monitoring, dose adjustment or temporarily stopping the diuretic may be needed:

When starting medicines that can interact with a diuretic

Drug-drug interactions are more common among older patients, often because they have underlying factors contributing to greater vulnerability which include pathophysiological changes associated with aging and a high number of medicines used to treat multimorbidity.²⁵

Table 2. Examples of medicines commonly used by DVA patients that can interact with diuretics
Medicine combination	Potential adverse effects	Considerations
A loop diuretic or a thiazide diuretic with an ACE inhibitor or ARB10	Renal impairment Hypotension Hypokalaemia10	Start, titrate and stop loop diuretics only to manage congestion in heart failure patients.13, 26 To avoid symptomatic hypotension, consider withholding the loop diuretic or reducing the dose for 24 hours before starting an ACE inhibitor or ARB.10, 27 When treating patients with heart failure, prioritise use of medicines that decrease mortality, including ACE inhibitors and ARBs over the use of loop or thiazide diuretics.13, 26 Consider reducing the dose or stopping the diuretic before making any adjustments to the ACE inhibitor or ARB to avoid renal impairment or symptomatic hypotension.27 Avoid NSAIDs (and advise patients to avoid over the counter NSAIDs) when using a loop diuretic together with an ACE inhibitor or ARB as use of these medicines together substantially increases the risk of acute kidney injury.12 Monitor renal function, electrolytes and fluid status closely.10
A loop diuretic, potassium sparing diuretic or a thiazide diuretic with NSAIDs, particularly indometacin27	Renal impairment27 Hyperkalaemia10 Reduced diuretic effect8, 27, 28	NSAIDs can cause renal impairment, especially in dehydrated or elderly patients.27 People most at risk of adverse effects include older patients with liver cirrhosis, heart failure and renal impairment.27 Monitor renal function, electrolytes and fluid status closely.10
Loop diuretic with a thiazide diuretic10	Renal impairment Increased diuresis Electrolyte disturbances10	Avoid combination, unless advised by other medical specialists. Check renal function within 5 days of starting, then every 5–14 days, depending on the patient’s stability.12 Monitor fluid status closely. Once stable, check at re-prescription or 3–6 monthly unless there is a change in dose, an intercurrent illness or worsening renal function.12
A loop diuretic with a peripheral alpha-1 blocker28	Urinary incontinence in older women28	Avoid combination where possible.28
A selective serotonin re-uptake inhibitor or carbamazepine with a thiazide diuretic29	Hyponatraemia, especially in elderly women29	Check electrolytes within two weeks of starting.29

During episodes of acute illness, such as diarrhoea, vomiting or fever

During episodes of acute illness, such as diarrhoea, vomiting or fever, volume depletion, renal impairment and electrolyte disturbances can be made worse with diuretic use.³⁰

• Monitor patients closely, especially those with heart failure, during episodes of acute illness where there is risk of volume depletion and acute kidney injury. Consider reducing the dose or temporarily withholding the diuretic until the patient is eating and drinking normally again.^12, 30 Check renal function if symptoms persist beyond two days.¹²

• Gastroenteritis is a common illness in residents in aged care facilities and is associated with high morbidity and mortality.^32, 33 Be aware of diuretic use (especially loop diuretics) in residents during episodes of gastroenteritis or other acute illnesses where there is risk of volume depletion and acute kidney injury.³⁰ Ensure staff have clear instructions about diuretic use during this time, particularly if diuretics are included in a dose administration aid, or a fixed-dose combination product, where the diuretic can be overlooked or the dose cannot be adjusted.^2, 34
• An individualised sick day card may be helpful for patients managing their own medicines at home during episodes of fever, diarrhoea or vomiting. Consider including sick day instructions for diuretic use in a General Practitioner Management Plan. To see an example of a Medicine Sick Day Rules card (NHS Scotland and Scottish Patient Safety Program), go to: https://ihub.scot/media/1398/20180424-medicine-sick-day-rules-patient-leaflet-print-v20.pdf

During hot weather

In the presence of comorbidities and polypharmacy, the risk of dehydration and heat-related illness during hot weather is significantly increased for many older people.^5, 35

A retrospective analysis of 6,700 Australian veterans with an average age of 85 years found that in the year after starting:

• a diuretic, they were almost two times more likely to be hospitalised for dehydration or a heat-related illness during hot weather, compared to the year before starting the medicine (see Figure 1)⁵
• a diuretic together with an ACE inhibitor, they were almost three times more likely to be admitted to hospital for dehydration or a heat-related illness than the year before starting this combination of medicines (see Figure 1).⁵

Where appropriate, consider reducing the dose of the diuretic or temporarily withholding the diuretic on hot days, or devise an individualised plan for patients who are able to adjust their own diuretic dose. Ensure patients have a good understanding of how to stay hydrated and well during hot weather, and encourage them to make an appointment to see their doctor within a few days if they adjust their diuretic dose.³⁶

For information on managing other medicines during hot weather, refer to the Veterans’ MATES topic, Medicines and hot weather: Reducing the risk of dehydration and heat-related illness, at: www.veteransmates.net.au/topic-40-therapeutic-brief

References

1. Roush G, Kaur R, Ernst M. Diuretics: a review and update. J Cardiovasc Pharmacol Ther. 2014; 19: 5-13.
2. Wehling M. Morbus diureticus in the elderly: epidemic overuse of a widely applied group of drugs. J Am Med Dir Assoc. 2013; 14: 437-442.
3. Sica D. Diuretic-related side effects: development and treatment. Journal of Clinical Hypertension. 2004; 6(9): 532-540.
4. Jennings E, Murphy K, Gallagher P, O'Mahony D. In-hospital adverse drug reactions in older adults; prevalence, presentation and associated drugs - a systematic review and meta-analysis. Age Ageing. 2020; 49: 948-958.
5. Kalisch Ellett L, Pratt N, Le Blanc V, Westaway K, Roughead E. Increased risk of hospital admission for dehydration or heat-related illness after initiation of medicines: a sequence symmetry analysis. J Clin Pharm Ther. 2016; 41: 503-507.
6. Pirmohamed M et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients. BMJ. 2004; 329: 15-19.
7. Therapeutic Guidelines. Melbourne. Therapeutic Guidelines Limited. 2021. Available at: http://online.tg.org.au/ip/desktop/index.htm [Accessed June 2021].
8. BPAC. Drug monitoring. Monitoring diuretics in primary care. 2009. Available at: https://bpac.org.nz/BT/2009/March/monitoring.aspx [Accessed May 2021].
9. Australian Government Department of Veterans' Affairs DVA Health Claims Database. University of South Australia. QUMPRC. [Accessed June 2021].
10. Australian Medicines Handbook. Adelaide. Australian Medicines Handbook Pty Ltd. 2021.
11. Makam A, Boscardin W, Miao Y, Steinman M. Risk of thiazide-induced metabolic adverse events in older adults. J Am Geriatr Soc. 2014; 62: 1039-1045.
12. Specialist Pharmacy Service. Suggestions for drug monitoring in adults in primary care. September 2017. National Health Service. Available at: www.southstaffordshirejointformulary.nhs.uk/docs/apg/UKMi%20Guidance%20-%20Suggestions%20for%20Drug%20Monitoring%20in%20Adults%20in%20Primary%20Care.pdf [Accessed May 2021].
13. Atherton J et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: guidelines for the prevention, detection, and management of heart failure in Australia. Heart Lung Circ. 2018; 27: 1123-1208.
14. Woodward M et al. Diagnosis and management of hyponatraemia in the older patient. Intern Med J. 2018; 48 Suppl 1: 5-12.
15. Renneboog B, Musch W, Vandemergel X, Manto M, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006; 119:71 e71-78.
16. Australian Medicines Handbook Aged Care Companion. Australian Medicines Handbook Pty Ltd. Adelaide. 2018.
17. Gilbert A, Roughead E, Beilby J, Mott K, Barratt J. Collaborative medication management services: improving patient care. MJA. 2002; 177: 189-192.
18. Kardachi G et al. Guidelines for comprehensive medication management reviews. 2020. Pharmaceutical Society of Australia. ACT, Australia.
19. Okada K et al. Reduction of diuretics and analysis of water and muscle volumes to prevent falls and fall-related fractures in older adults. Geriatr Gerontol Int. 2017; 17: 262-269.
20. International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2016 consensus document of the International Society of Lymphology. Lymphology. 2016; 49: 170-184.
21. Savage R et al. Evaluation of a common prescribing cascade of calcium channel blockers and diuretics in older adults with hypertension. JAMA Intern Med. 2020; 180: 643-651.
22. Buckley L, Alsarraf E. Cardiovascular safety of gabapentinoids. Current Emergency and Hospital Medicine Reports. 2019; 7: 48-52.
23. Vaismoradi M, Amaniyan S, Jordan S. Patient safety and pro re nata prescription and administration: a systematic review. Pharmacy (Basel). 2018; 6.
24. Picton L et al. Rates of PRN medication administration in Australian residential aged care. J Am Med Dir Assoc. 2021; 22: 117-123 e111.
25. Royal Australian College of General Practice. RACGP aged care clinical guide (Silver book) 5^th edn, Part B. Principles of medication management. Available at: www.racgp.org.au/getattachment/90a42a07-8e54-49a1-aaaf-210473f457bc/principles-of-medication-management.aspx [Accessed March 2021].
26. NPSMedicineWise. MedicineWise News. Up-titrating heart failure medicines - a practical guide. 2021. Available at: www.nps.org.au/news/up-titrating-heart-failure-medicines [Accessed July 2021].
27. Preston C et al. Stockley's Drug Interactions Pocket Companion. Pharmaceutical Press. London. 2016.
28. American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019; 67: 674-694.
29. Rosner M. Severe hyponatremia associated with the combined use of thiazide diuretics and selective serotonin reuptake inhibitors. Am J Med Sci. 2004; 327: 109-111.
30. Lea-Henry T, Baird-Gunning J, Petzel E, Roberts D. Medication management on sick days. Australian Prescriber. 2016; 39: 168-173.
31. Dinsdale C, Wani M, Steward J, O'Mahony M. Tolerability of spironolactone as adjunctive treatment for heart failure in patients over 75 years of age. Age Ageing. 2005; 34: 392-395.
32. The National Centre for Immunisation Research and Surveillance. Review of infection control practices in residential aged care in Australia. Australian Government Australian Aged Care Quality Agency. 2018.
33. Trivedi T et al. Hospitalizations and mortality associated with norovirus outbreaks in nursing homes, 2009-2010. JAMA. 2012; 308: 1668-1675.
34. Godman B et al. Fixed dose drug combinations - are they pharmacoeconomically sound? Findings and implications especially for lower and middle-income countries. Expert Rev Pharmacoecon Outcomes Res. 2020; 20: 1-26.
35. Zhang Y, Nitschke M, Bi P. Risk factors for direct heat-related hospitalization during the 2009 Adelaide heatwave: a case crossover study. Sci Total Environ. 2013; 442: 1-5.
36. Westaway K et al. Medicines can affect thermoregulation and accentuate the risk of dehydration and heat-related illness during hot weather. J Clin Pharm Ther. 2015; 40: 363-367.
37. Chung M et al. Hyponatremia and increased risk of dementia: a population-based retrospective cohort study. PLoS One. 2017; 12:e0178977.
38. Murthy K et al. The effects of hyponatremia on bone density and fractures: a systematic review and meta-analysis. Endocr Pract. 2019; 25: 366-378.

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