Potentially Inappropriate Medicines in the Australian Setting

A list of potentially inappropriate medicines (PIMs) specific to the Australian setting has recently been published. Potentially inappropriate medicines can be defined as medications with risks that may outweigh their benefits in older adults. This includes medicines with a high risk of severe adverse effects and drug interactions, as well as an increased risk of falls.

The use of PIMs in older people should be avoided unless there is a clear therapeutic need and an absence of effective and lower-risk alternatives. Avoiding PIMs is an important part of the quality use of medicines, as demonstrated by the 2020 report Medicine Safety: Aged Care. This report showed that the use of PIMs is common, with over half of all people living in aged care facilities prescribed a PIM. Furthermore, one in five unplanned hospital admissions among this population is a result of taking a PIM. Admissions related to PIMs include falls, heart failure, confusion, constipation, and gastrointestinal bleeds. Studies suggest that PIMs also cause up to 39% of all cases of delirium.

Older patients may be more susceptible to medication-related harm due to physiological changes associated with the ageing process. A medicine’s pharmacokinetic and pharmacodynamic properties can be affected by changes in body composition and reductions in renal and hepatic function. Furthermore, older patients are more likely to have multiple comorbidities and polypharmacy, thereby increasing the risk of drug interactions.

The newly published list of Australian-specific PIMs is significant for two reasons. Firstly, it may be more relevant than international lists due to differences in medication availability and clinical practice guidelines in Australia. Secondly, this new list also includes recommendations for potentially safer alternatives.

Table 1 contains the medicines and medicine classes that achieved consensus agreement for inclusion in the Australian list of PIMs.

Table 1. PIMs and possible alternatives (adapted from Wang et al. 2024)

PIM or medicine class	Avoid these drugs in older people	Avoid this medicine or medicine class in older people with these conditions	Alternatives that may be considered
Alpha-adrenoreceptor antagonists (prazosin)	Prazosin	Risk of hypotension Taking other antihypertensive Frailty Risk of falls Initial dose adverse effects	ACE inhibitors Sartans Calcium channel blockers Silodosin Tamsulosin
Antiemetics – dopamine antagonist	Chlorpromazine Prochlorperazine	Parkinson disease Polypharmacy Lewy body dementia Neurodegenerative diseases Frailty High risk of falls	Ondansetron Domperidone
Antihypertensives, centrally acting (methyldopa, clonidine and moxonidine)	Methyldopa	Risk of hypotension Risk of falls Taking other antihypertensive Frailty	ACE inhibitors Sartans Thiazide diuretics
Antipsychotics (haloperidol, zuclopenthixol, trifluoperazine, thioridazine, periciazine and flupenthixol)	Haloperidol Zuclopenthixol Trifluoperazine Thioridazine Periciazine Flupenthixol	Risk of extrapyramidal reactions Taking anticholinergic medications Polypharmacy Frailty Neurodegenerative diseases Cognitive impairment Cardiovascular diseases Cerebrovascular diseases Risk of falls	Atypical antipsychotics (e.g. quetiapine) Risperidone Non-pharmacological strategies (e.g. yoga)
Antipsychotics (olanzapine, quetiapine, amisulpride, ziprasidone, lurasidone, risperidone, aripiprazole and paliperidone)	Olanzapine	Cardiometabolic syndrome Risk of falls Polypharmacy When a non-pharmacological option has not been adequately tried Neurodegenerative diseases Long-term use	Quetiapine Risperidone
Benzodiazepine, long-acting (clobazam, clonazepam, diazepam, flunitrazepam and nitrazepam)	Clonazepam Flunitrazepam	Dependence Other medications with sedative properties Polypharmacy Frailty Neurodegenerative diseases Cognitive impairment Poor renal function Long-term use Risk of falls	Short-acting benzodiazepine Melatonin (for indication of sleep) Non-pharmacological strategies
Benzodiazepines, medium-acting (bromazepam and lorazepam)	Bromazepam Lorazepam	Falls With other sedating medications Polypharmacy Frailty Neurodegenerative diseases Cognitive impairment
Benzodiazepines, short-acting (alprazolam, oxazepam and temazepam)	Alprazolam	Falls With other sedating medications Polypharmacy Frailty Neurodegenerative diseases Dependency Renal impairment Long-term use	Oxazepam Temazepam Melatonin (for indication of sleep) Non-pharmacological strategies
Genito-urinary anticholinergics (oxybutynin, propantheline, tolterodine and solifenacin)	Oxybutynin	With other anticholinergics Frailty Polypharmacy Risk of falls Neurodegenerative diseases Constipation Cognitive impairment	N/A
Non-selective NSAIDs, (indomethacin, diclofenac, ketorolac, piroxicam, meloxicam, ibuprofen, naproxen, ketoprofen and mefenamic acid)	Diclofenac Indomethacin Ibuprofen Ketoprofen Piroxicam Meloxicam Ketorolac	History of gastrointestinal bleeding ↑ bleeding risks Frailty Poor renal function Peptic ulcer disease Multimorbidity Chronic kidney disease Heart failure Cardiovascular diseases	Paracetamol
Selective NSAIDs (celecoxib and etoricoxib)	N/A	History of gastrointestinal bleeding ↑ bleeding risks Frailty Poor renal function Heart failure Cardiovascular disease Chronic kidney disease Long-term use Taking ACE inhibitors or diuretics	Paracetamol Celecoxib
Opioids (morphine, pethidine, fentanyl, dextropropoxyphene, hydromorphone, buprenorphine, oxycodone and codeine)	Pethidine Fentanyl Codeine Hydromorphone Dextropropoxyphene	Polypharmacy Risk of falls Frailty Poor renal function Neurodegenerative diseases Constipation Opioid dependency Long-term use Impaired cognition Chronic pain	Physiotherapy Paracetamol Oxycodone Buprenorphine
Oral anticoagulants – direct thrombin inhibitors (dabigatran)	Dabigatran	↑ bleeding risk Multimorbidity Peptic ulcer disease Frailty Risk of falls Poor blood pressure control Chronic kidney disease Poor renal function	N/A
Oral anticoagulants – Factor Xa inhibitors (apixaban and rivaroxaban)	Rivaroxaban	Peptic ulcer disease ↑ bleeding risk Risk of falls Multimorbidity Polypharmacy Poor renal function Chronic kidney disease	N/A
Sedating antihistamines	Promethazine	Taking other sedating medications Cognitive impairment Taking anticholinergics Frailty Neurodegenerative diseases Risk of falls Polypharmacy	Non-sedating antihistamines (e.g. fexofenadine)
Sulfonylureas	Glibenclamide Glimepiride	With other glucose-lowering medications High risk of falls Frailty Chronic kidney diseases Polypharmacy Multimorbidity Renal impairment Irregular diet Dehydration	Metformin Gliclazide DPP-4 inhibitors (sitagliptin, saxagliptin) SGLT2 inhibitor (dapagliflozin)
Tramadol	N/A	Multimorbidity Frailty Neurodegenerative diseases Risk of falls Polypharmacy Poor renal function Cognitive impairment Long-term use Taking antidepressant medications Epilepsy Risk of seizures	Paracetamol NSAIDs
Tricyclic antidepressants	Doxepin Dosulepin (dothiepin)	With other anticholinergics Frailty Polypharmacy Risk of falls Neurodegenerative diseases (e.g. delirium) Constipation Cognitive impairment With other sedating medications Risk of postural hypotension Benign prostatic hyperplasia	SSRIs (e.g. citalopram, paroxetine) SNRIs (e.g. duloxetine) Mirtazapine
Zolpidem and zopiclone	N/A	Dependency Taking other sedating medications Frailty Neurodegenerative diseases Risk of falls Polypharmacy Cognitive impairment Long-term use	Melatonin Nonpharmacological strategies (e.g. sleep hygiene)

Abbreviations: ACE, angiotensin converting enzyme; DPP4 inhibitor, dipeptidyl peptidase-4; SSRI, selective serotonin reuptake inhibitor; SNRIs, serotonin and noradrenaline reuptake inhibitors; NSAID, non-steroidal anti-inflammatory drug; SGLT2, sodium-glucose transport protein 2

This list of PIMs was obtained by consensus agreement of 33 experts with specialties across 15 areas. One limitation of the study is that participants were not asked to provide sources of evidence to support their recommendations. Therefore, it is possible that the recommendations reflect clinical practice rather than current scientific evidence. Other factors not considered include medication dosage, frequency, and route of administration. It is also worth highlighting that the medications suggested as potentially safer alternatives may not have the same level of evidence to support their efficacy for all indications. For example, paracetamol is suggested as an alternative to opioids and NSAIDs, although paracetamol may not be an effective alternative in all clinical scenarios.

The harm related to PIMs contributes to loss of independence and poorer quality of life for older adults. It is also responsible for a significant amount of healthcare resource utilisation. Lists of PIMs may be useful as decision-support tools when assessing the appropriateness of a medication for an older person. However, they do not replace clinical judgment in individual cases. In some cases, a PIM may be the most appropriate option for an older individual after accounting for allergies, drug interactions, and other medical conditions. Wherever a PIM is used in an older patient, regular medication review is vital to ensure the benefit continues to outweigh the potential risks.

References:

Pharmaceutical Society of Australia. Medicine safety: aged care. Canberra: PSA; 2020.
Wang KN, Etherton-Beer CD, Sanfilippo F, Page AT. Development of a list of Australian potentially inappropriate medicines using the Delphi technique. Intern Med J. 2024; 1-23.
Zhang X, Zhou S, Pan K, Li X, Zhao X, Zhou Y, et al. Potentially inappropriate medications in hospitalized older patients: a cross-sectional study using the Beers 2015 criteria versus the 2012 criteria. Clin Interv Aging. 2017; 12: 1697-1703.

Potentially Inappropriate Medicines in the Australian Setting

May 24, 2024

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