Medication-related harm accounts for half of all preventable harm in healthcare. A recent systematic review found that the prevalence of medication-related harm globally is 1 in 20, where one fourth of the harm was potentially serious or life threatening.8 The majority of harm, 53% occurs at the ordering/ prescribing stage and 36% at the monitoring/ reporting stage, with 80% of the avoidable harm arising at the ordering/ prescribing stage.8 At least a quarter of this preventable harm was found to range from severe to potentially life threatening. The highest prevalence rate was found in the older person with high comorbidities and polypharmacy. This was greatest in medicines affecting the central nervous system and the cardiovascular system.
High-risk medicines are those that have an increased risk of causing significant harm or death if they are misused or used in error.23,24 Errors with these medicines are not necessarily more common than with other medicines, but the consequences can be more devastating.23,24 Medicines considered ‘high-risk’ vary between hospitals and other healthcare settings, such as primary and care of the elderly, and depend on the context and the clinical conditions treated.23,24
The acronym ‘A-PINCHS’ is used for example in hospital settings, to highlight specific medicines in the categories known to cause harm in the organisation or setting.24
Most common classes of medicines causing harm in the hospital setting
A Anti-infectives
P Potassium and other electrolytes
I Insulin and other hypoglycaemic agents
N Narcotics and other sedatives
C Chemotherapeutic agents
H Heparin and anticoagulants
S Systems
Many of the medicines above will be recognised as high risk regardless of the setting such as opioids and insulin. However, many medicines in common usage, when taken together with other medicines, or due to a change of physiology for the individual e.g. impaired kidney function, are responsible for the potential adverse effects. In these scenarios the potential benefits should be considered against the potential adverse effects.
The sections below contain a list of common medications that have the potential to cause harm and factors to consider. The list is not exhaustive, and further detail is provided in Detail by therapeutic area based on amalgamated medication assessment tools.
*adapted from Komagamine,33 Agrawal,34 Pirmohamed29 and Osanlou10
(Reproduced with permission from Polypharmacy and Deprescribing: Pharmacovigilance and Drug Safety in Clinical Practice)
Examples of individual medications
Ramipril, enalapril, captopril, lisinopril, perindopril, irbesartan, losartan
Issues/ important areas to consider 25,26
The indication for ACEI and ARB and the evidence base for their use
Kidney function before starting and while titrating the dosage
Can also cause a drop in BP and cause dizziness and falls
Examples of individual medications
Cephalosporins (e.g. cefalexin), penicillins (e.g. amoxicillin), quinolones (e.g. ciprofloxacin), macrolides (e.g. azithromycin)
Issues/ important areas to consider 25,26
Use antibiotics only when indicated and avoid prophylactic use in care homes
Commonly used antibiotics, such as cephalosporins, fluoroquinolones and amoxicillin with clavulanic acid increase the risk of C. diff and antimicrobial resistance
Examples of individual medications
Selective serotonin reuptake inhibitors (e.g. fluoxetine, paroxetine, citalopram)
Tricyclic antidepressants (e.g. amitriptyline, dosulepin)
Serotonin-norepinephrine reuptake inhibitor (e.g. venlafaxine)
Issues/ important areas to consider 25,26
Antidepressants have been implicated in causing falls
Tricyclic antidepressants have more anticholinergic and cardiotoxic effects than other antidepressants and should be used with caution in those with cardiovascular or cognitive comorbidities
Examples of individual medications
Antiplatelet agents (e.g. aspirin, clopidogrel)
Oral anticoagulants (warfarin and direct oral anticoagulants [DOACs] e.g. dabigatran, edoxaban rivaroxaban, apixaban)
Issues/ important areas to consider 25,26
Consider kidney function. Kidney function declines as people age, which has an impact on the dose and suitability of DOACs
Individual factors can contribute to increased risk of bleeding, such as age, previous bleeding or stroke, raised blood pressure, reduced kidney/liver function and drug-drug interactions.
Review dual antiplatelet therapy and its intended duration, due to the risk of gastro-intestinal haemorrhage
Examples of individual medications
Atenolol, propranolol, sotalol, bisoprolol, metoprolol, carvedilol
Issues/ important areas to consider 25,26
Adverse effects such as bradycardia and fatigue can be exacerbated with age, frailty and by drug-drug interactions
Examples of individual medications
There are various agents that fall into this category
Issues/ important areas to consider 25,26
Neutropenic sepsis, sepsis, constipation, deranged electrolytes, rash, thrombocytopenia
Examples of individual medications
Digoxin
Issues/ important areas to consider 25,26
Kidney function, electrolytes and digoxin serum concentration require monitoring
Drug-drug interactions can impact on digoxin clearance and increase toxicity
Examples of individual medications
Furosemide, bendroflumethiazide, bumetanide, spironolactone
Issues/ important areas to consider 25,26
Potent diuretics, useful for symptomatic management (e.g. of heart failure), require regular review due to risk of hypotension and electrolyte disturbances
Examples of individual medications
Insulin, sulfonylureas (e.g. glibenclamide, glipizide)
Issues/ important areas to consider 25,26
Intensive glycaemic control strategies markedly increase the risk of hypoglycaemia, associated with increased mortality, cardiovascular events, falls, and accidents,27 especially sulfonylureas in over 75-year-old persons
Examples of individual medications
Montelukast
Issues/ important areas to consider 25,26
Risk of neuropsychiatric reactions, including new or worsening changes in mood, sleep, or behaviour. Discontinue use if individuals develop new or worsening neuropsychiatric symptoms28
Examples of individual medications
Lithium
Issues/ important areas to consider 25,26
Lithium concentrations require regular monitoring, especially when other medicines are added or withdrawn, or with changes to the patient’s clinical conditions (e.g. kidney impairment, dehydration)
Adverse effects can develop over time and require dosage adjustment
Examples of individual medications
Diclofenac, ibuprofen, celecoxib, ketoprofen, naproxen
Issues/ important areas to consider 25,26
NSAIDs and antiplatelet agents was the leading cause of drug-related hospital admissions, accounting for approximately a third of all drug-related admissions and half of drug-related deaths.29 This is exacerbated with a history of peptic ulcer disease and the use of several medicines, including antiplatelets, anticoagulants, corticosteroids, and selective serotonin reuptake inhibitors
In those at highest risk of GI bleeding, if treatment with NSAID is unavoidable, consider gastroprotection (usually with a proton pump inhibitor)
Cardiovascular risk associated with many of the NSAIDs
Examples of individual medications
Morphine, oxycodone dihydrocodeine, codeine (± paracetamol) tramadol, fentanyl
Issues/ important areas to consider 25,26
There is little evidence for the long-term use of opioids in long-term, non-malignant pain
Adverse effects such as respiratory and cognitive dysfunction are exacerbated with drug-drug interactions and altered pharmacodynamics in older person
Examples of individual medications
Diazepam, nitrazepam, temazepam, zopiclone
Issues/ important areas to consider 25,26
Long-term use of hypnotics and anxiolytics in general practice is not appropriate, maximum duration for most people is three to four weeks30
Long-term use is associated with numerous risks, including drowsiness and falls, forgetfulness, confusion, depression, irritability, aggression, impulsivity, digestive problems, and dependence
Examples of individual medications
Olanzapine, clozapine, quetiapine
Issues/ important areas to consider 25,26
Antipsychotics are not recommended but frequently used to reduce symptoms of stress and distress in people with dementia. These drugs have (time) limited benefits, and older patients are particularly vulnerable to their adverse effects.31 They should therefore be used as the last resource
Long-term use is associated with cerebrovascular events and death in people with dementia32
Examples of individual medications
Lansoprazole, omeprazole, esomeprazole, pantoprazole
Issues/ important areas to consider 25,26
Hypomagnesaemia, hyponatraemia, Clostridioides difficile
Examples of individual medications
Various Inhaled Corticosteroid (ICS)
Issues/ important areas to consider 25,26
Pneumonia, oral thrush
Examples of individual medications
Prednisolone
Issues/ important areas to consider 25,26
Require ongoing review to wean or use the lowest, effective dose
Adverse effects with long-term use necessitate management, such as osteoporosis and glaucoma
Consider adrenal suppression with prolonged use, increases susceptibility to infections
Polypharmacy guidance: Appropriate prescribing making medicines safe, effective and sustainable 2026-2029