A new ‘Potentially inappropriate medicines’ (PIMs) list unveiled 16 high-risk medicines or medicine classes that could result in negative clinical outcomes, including hospitalisation and death in older patients.
The medicines span a range of different classes, from antiemetics such as chlorpromazine and metoclopramide, to centrally active antihypertensives such as clonidine and methyldopa, and ‘Z drugs’ such as zolpidem and zopiclone, says PIMs list co-author Dr Amy Page FPS, Senior Research Fellow at the University of Western Australia’s School of Allied Health, Pharmacy and President of the PSA Victorian Branch.
‘Some antipsychotics, short, long and medium-acting benzodiazepines, non-steroidal anti-inflammatories (NSAIDs), anticholinergics for incontinence, opioids, tricyclic antidepressants and oral anticoagulants were also included,’ Dr Page said.
The below table details the potentially high-risk medicines (tilt screen in mobile view to see full table).
| PIM or medicine class group | Avoid these drugs in older people | Avoid this medicine or medicine class in older people with these conditions | Instead of prescribing this medicine or class of medicines for older people, consider these alternatives |
|---|---|---|---|
| Alpha-adrenorecepror antagonists (prazosin) | Prazosin | Risk of hypotension Taking other antihypertensive medications Frailty Risk of falls Initial dose adverse effects | ACE inhibitors (e.g. enalapril and lisinopril) Angiotensin II receptor blockers (e.g. candesartan and irbesartan) Calcium channel blockers (e.g. amlodipine and diltiazem Silodosin Tamsulosin |
| Antiemetics – dopamine antagonist (chlorpromazine, domperidone, metoclopramide and prochlorperazine) | Chlorpromazine Prochlorperazine | Parkinson disease Polypharmacy Lewy body dementia Neurodegenerative diseases (e.g. alzheimer disease and cognitive impairment) Frailty High risk of falls | Ondansetron Domperidone |
| Antihypertensives, centrally acting (methyldopa, clonidine and moxonidine) | Methyldopa | Risk of hypotension Risk of falls Taking other antihypertensive medications Frailty | ACE inhibitors (e.g. enalapril and lisinopril) Angiotensin II receptor blockers (e.g. candesartan and irbesartan) Thiazide diuretics (e.g. hydrochlorothiazide) |
| Antipsychotics (haloperidol, zuclopenthixol, trifluoperazine, thioridazine, periciazine and flupenthixol) | Haloperidol Zuclopenthixol Trifluoperazine Thioridazine Periciazine Flupenthixol | At risk of extrapyramidal reactions Taking anticholinergic medications Polypharmacy Frailty Neurodegenerative diseases (e.g. delirium) Cognitive impairment Cardiovascular diseases Cerebrovascular diseases Risk of falls | Atypical antipsychotics (e.g. quetiapine) Risperidone Nonpharmacological strategies (e.g. yoga) |
| Antipsychotics (olanzapine, quetiapine, amisulpride, ziprasidone, lurasidone, risperidone, aripiprazole and paliperidone) | Olanzapine | Cardiometabolic syndrome (e.g. high blood pressure, high blood sugar) Risk of falls Polypharmacy When a nonpharmacological method has not been tried adequately Neurodegenerative diseases (e.g. delirium) 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 (e.g. delirium) Cognitive impairment Poor renal function Long-term use Risk of falls | Short-acting benzodiazepine (e.g. oxazepam) Melatonin (for indication of sleep) Nonpharmacological strategies (e.g. yoga) |
| Benzodiazepines, medium-acting (bromazepam and lorazepam) | Bromazepam Lorazepam | Falls With other medications with sedative properties Polypharmacy Frailty Neurodegenerative diseases (e.g. delirium) Cognitive impairment | Short-acting benzodiazepine Melatonin (for indication of sleep) Nonpharmacological strategies (e.g. yoga) |
| Benzodiazepines, short-acting (alprazolam, oxazepam and temazepam) | Alprazolam | Falls With other medications with sedative properties Polypharmacy Frailty Neurodegenerative diseases (e.g. delirium) Dependency Renal impairment Long-term use | Oxazepam Temazepam Melatonin (for indication of sleep) Nonpharmacological strategies (e.g. yoga) |
| Genito-urinary anticholinergics (oxybutynin, propantheline, tolterodine and solifenacin) | Oxybutynin | With other anticholinergics Frailty Polypharmacy Risk of falls Neurodegenerative diseases (e.g. delirium) Constipation Cognitive impairment | N/A |
| NSAIDs, nonselective (indomethacin, diclofenac, ketorolac, piroxicam, meloxicam, ibuprofen, naproxen, ketoprofen and mefenamic acid) | Diclofenac Indomethacin Ibuprofen Ketoprofen Piroxicam Meloxicam Ketorolac | History of gastrointestinal bleeding Increased bleeding risks Frailty Poor renal function Peptic ulcer disease Multimorbidity Chronic kidney disease Heart failure Cardiovascular diseases | Paracetamol |
| NSAIDs, selective (celecoxib and etoricoxib) | N/A | History of gastrointestinal bleeding Increased 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 (e.g. delirium) Constipation Opioid dependency Long-term use Impaired cognition Chronic pain | Physiotherapy Paracetamol Oxycodone Buprenorphine |
| Oral anticoagulants – direct thrombin inhibitors (dabigatran) | Dabigatran | Increased risk of bleeding 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 Increased bleeding risk Risk of falls Multimorbidity Polypharmacy Poor renal function Chronic kidney disease | N/A |
| Sedating antihistamines (diphenhydramine, doxylamine, dexchlorpheniramine, pheniramine, promethazine, cyclizine, chlorpheniramine and cyproheptadine) | Promethazine | Taking other medications with sedative properties Cognitive impairment Taking anticholinergics Frailty Neurodegenerative diseases (e.g. delirium) Risk of falls Polypharmacy | Nonsedating antihistamines (e.g. fexofenadine) |
| Sulfonylureas (glibenclamide, glipizide, gliclazide and glimepiride) | Glibenclamide Glimepiride | With other glucose-lowering medications High risk of falls Frailty Chronic kidney diseases Polypharmacy Multimobidity Renal impairment Irregular diet Dehydration | Metformin Gliclazide Dipeptidyl peptidase-4 inhibitors (sitagliptin and saxagliptin) Sodium-glucose transport protein 2 inhibitor (dapagliflozin) |
| Tramadol | N/A | Multimorbidity Frailty Neurodegenerative diseases (e.g. delirium) Risk of falls Polypharmacy Poor renal function Cognitive impairment Long-term use Taking antidepressant medications Epilepsy Risk of seizures | Paracetamol NSAIDs |
| Tricyclic antidepressants (imipramine, clomipramine, amitriptyline, nortriptyline, doxepin and dosulepin [dothiepin]) | Doxepin Dosulepin (dothiepin) | With other anticholinergics Frailty Polypharmacy Risk of falls Neurodegenerative diseases (e.g. delirium) Constipation Cognitive impairment With other medications with sedative properties Risk of postural hypotension Benign prostatic hyperplasia | Selective serotonin reuptake inhibitors (e.g. citalopram and paroxetine) Serotonin and norepinephrine reuptake inhibitors (e.g. duloxetine) Mirtazapine |
| Z-drugs (zolpidem and zopiclone) | N/A | Dependency Taking other medications with sedative properties Frailty Neurodegenerative diseases (e.g. delirium) Risk of falls Polypharmacy Cognitive impairment Long-term use | Melatonin Nonpharmacological strategies (e.g. sleep hygiene) |
The updated list was developed to account for new medicines available in Australia since the last iteration was developed 15 years ago, says the researchers. Another key point of difference is the inclusion of specific conditions that make the medicines particularly risky, along with suggested, safer alternatives.
With older Australians often needing to use multiple medicines to manage chronic conditions, between 20–70% are prescribed at least one PIM on the new list.
Here, Dr Page explains how pharmacists from all areas of practice can use the PIM list for risk assessment and to identify alternative therapy approaches for older Australians.
How was the new list compiled?
To come up with the list of medicines that were potentially inappropriate for older Australians the researchers looked at all the existing lists of PIMs available internationally, said Dr Page.
‘We identified that out of 645 unique PIMs, only 416 were available in Australia, with even less (262) subsidised by the Pharmaceutical Benefits Scheme.’
A multidisciplinary expert panel comprising 33 clinicians and researchers specialising in geriatrics, pharmacy, clinical pharmacology, general practice and epidemiology identified 16 medicines and medicine classes that are potentially inappropriate for patients aged 65 and older.
Why some high-risk medicines are not included
While the new list contains medicines that may be risky to use, that doesn’t mean all high-risk medicines are included in the list.
‘It could be that a high-risk medicine carries a similar risk whether the patient is 20, 40 or 80,’ she said. ‘For example, insulin, while highly beneficial for anyone who has diabetes, has a similar risk profile for different age groups.’
Risk assessment and alternative therapies
To further assess the risks of PIM-listed medicines to older people, each medicine or class is tabled against chronic conditions, or other concurrently used medicines – which could make use particularly dangerous.
Up to 19 medicines or medicine classes had specific conditions that make them more likely to be inappropriate.
‘For example, [it’s recommended] that short-acting benzodiazepines are particularly avoided if patients are particularly frail, prone to falls, or use other medicines with sedative properties,’ said Dr Page.
‘With NSAIDs, the experts [warned] people who had a history of gastrointestinal bleeding or increased bleeding risk, frailty, poor renal function, peptic ulcer disease, multimorbidity, chronic kidney disease, heart failure, or cardiovascular disease were at higher risk.’
Where medicines are potentially inappropriate for older patients, pharmacists can refer to the suggested alternative treatment pathways included in the PIM list.
Of note, among all available short-acting benzodiazepines, alprazolam was considered the most inappropriate.
Alprazolam has increased morbidity and mortality in overdose with possible increased toxicity. It also doesn’t appear to have additional therapeutic benefits when compared with any other benzodiazepines.
While the first-line treatment alternative is non-pharmacological strategies, melatonin could be a safer option, when used for indication of sleep.
‘If a patient actually needed to use a medicine in this class [for example, for short-term management of insomnia or anxiety], temazepam and oxazepam are considered safer alternatives,’ said Dr Page, provided the indication is appropriate.
Use in practice
When conducting Home Medicine Reviews, credentialed pharmacists and those working in general practice, aged care or Aboriginal Community Controlled Health Organisations can also assess whether a PIM might be high risk for a patient with specific chronic conditions, or using other potentially contraindicated medicines.
‘While the PIM may at times be appropriate for an individual, pharmacists should consider if there is a safer alternative, or if the medicine is actually necessary,’ she said.
‘It’s also potentially useful for MedsChecks, or for community or hospital pharmacists when dispensing or reviewing medicines lists.’
For governance-level QUM activities in residential aged care facilities, on-site pharmacists can conduct audits to identify how many residents are using PIMs so there’s a baseline to measure against.
‘A similar approach would be beneficial in GP practice,’ said Dr Page. ‘GP clinics usually have regular staff and clinical meetings that pharmacists attend, making the process a lot easier when there’s direct access to prescribers.’
New downloadable PIM-list tables
For eases of access, pharmacists can now download tables for use in practice that outline medicines or medicine classes to be avoided in older patients, along with suggested alternatives:
