When many high-risk medicines are prescribed the effects of these can accumulate. The sections below summarises work that has been undertaken in a modified Delphi to get consensus on the harm and action to be taken. High-risk medicines combinations are also addressed in the hot topics section Risks with combinations of high-risk medications. An unabridged version of the Cumulative Toxicity Table is available as a supporting document to the guidance.
The sections below summarises common adverse effects and the groups of medication which cause these. The frequency is based on the BNF definitions as follows:
Note: less frequent effects are not included below but cannot be excluded
Abbreviations: ACE inhibitor: angiotensin-converting enzyme inhibitor, ARB: angiotensin II receptor blocker, CCB: calcium channel blocker, DOAC: direct-acting oral anticoagulants, GLP-1RA: glucagon-like peptide-1 receptor agonists, NSAID: non-steroidal anti-inflammatory drugs, PPI: proton pump inhibitors, SGLT-2 inhibitor: sodium-glucose co-transporter 2 inhibitors, SNRI: serotonin norepinephrine reuptake inhibitors, SSRI: selective serotonin reuptake inhibitors, TCA: tricyclic antidepressant
*Falls and fractures and anticholinergic effect: it is not possible to determine the frequency of these as the adverse effect is caused by multiple factors 84, 85, 86
ACE inhibitor/ARB
Alpha blockers for urinary symptoms
Antimuscarinics e.g. oxybutynin
Antipsychotics
Benzodiazepines and z-drugs
Beta-blocker
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Digoxin
Diuretics
Gabapentinoids
NSAIDs
Opioids
Sedative antihistamines
SSRI and SNRI
TCA
*87,88
(see anticholinergic burden table)
Antimuscarinics, e.g. oxybutynin
Antipsychotics
Benzodiazepines and z-drugs
Digoxin
Metformin
Opioids
PPI
Prochlorperazine
Sedative antihistamines
SSRI and SNRI
TCA
ACE inhibitor/ARB
Alpha blockers for urinary symptoms
Amiodarone
Antimuscarinics, e.g. oxybutynin
Antiplatelets
Antipsychotics
Benzodiazepines and z-drugs
Beta-blockers
Bisphosphonates
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Centrally acting antihypertensives
DOAC
Gabapentinoids
Gliptin
GLP-1RA
Laxatives
Metformin
NSAIDs
Opioids
Penicillins
PPI
Prochlorperazine
Sedative antihistamines
SGLT-2 inhibitor
SSRI and SNRI
Statins
Steroids
Sulfonylurea
TCA
Antimuscarinics, e.g. oxybutynin
Antiplatelets
Antipsychotics
Benzodiazepines and z-drugs
Beta-blocker
Bisphosphonates
CCB (dihydropyridine)
DOAC
Gabapentinoid
Gliptin
GLP-1RA
Metformin
NSAIDs
Opioids
PPI
SSRI and SNRI
Statin
Steroids
ACE inhibitor/ARB
ACE inhibitor/ARB
Amiodarone
Antimuscarinics, e.g. oxybutynin
Antiplatelets
Antipsychotics
Beta-blocker
Bisphosphonates
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Centrally acting antihypertensives
Diuretics
Gabapentinoids
GLP-1RA
Metformin
Opioids
PPI
SSRI and SNRI
Statin
TCAs
ACE inhibitor/ARB
Antimuscarinics, e.g. oxybutynin
Antiplatelets
Antipsychotics
Benzodiazepines and z-drugs
Beta-blocker
Bisphosphonates
CCB (dihydropyridine)
Digoxin
Diuretics
DOAC
Gabapentinoids
Gliptin
GLP-1RA
Laxatives
Metformin
Metoclopramide
NSAIDs
Penicillins
PPI
SSRI and SNRI
Statin
Steroids
Sulfonylurea
TCAs
CCB (verapamil/diltiazem)
Antiplatelets
DOAC
SSRI and SNRI
Warfarin
Steroids
Beta-blocker
Antimuscarinics, e.g. oxybutynin
NSAIDs
Steroids
TCAs
ACE inhibitor/ARB
Amiodarone
Antimuscarinics, e.g. oxybutynin
Antipsychotics
Benzodiazepines and z-drugs
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Digoxin
Gabapentinoids
Opioids
SSRI and SNRI
TCAs
Alpha blockers for urinary symptoms
Bisphosphonates
Gabapentinoids
GLP-1RA
NSAIDs
ACE inhibitor/ARB
Alpha blockers for urinary symptoms
Antimuscarinics, e.g. oxybutynin
Antiplatelets
Antipsychotics
Benzodiazepines and z-drugs
Beta-blocker
Bisphosphonates
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Centrally acting antihypertensives
DOAC
Gabapentinoids
Gliptin
GLP-1RA
NSAIDs
Opioids
PPI
Sedative antihistamines
SGLT-2 inhibitor
SSRI and SNRI
Statin
TCAs
Laxatives
Sulfonylurea
ACE inhibitor/ARB
Antiplatelets
Antipsychotics
Beta-blocker
Alpha blockers for urinary symptoms
Bisphosphonates
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Gabapentinoids
Opioids
SGLT-2 inhibitor
SSRI and SNRI
ACE inhibitor/ARB
Amiodarone
Antiplatelets
Antipsychotics
Benzodiazepines and z-drugs
Beta-blockers
Gabapentinoids
Opioids
Pioglitazone
Bisphosphonate
CCB (dihydropyridine)
NSAIDs
SSRI and SNRI
Steroids
ACE inhibitor/ARB
Alpha blockers for urinary symptoms
Antimuscarinics, e.g. oxybutynin
Antiplatelets
Antipsychotics
Benzodiazepines and z-drugs
Beta-blockers
Bisphosphonates
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Centrally acting antihypertensives
Diuretics
DOAC
Gabapentinoids
Gliptin
NSAIDs
Opioids
PPI
SSRI and SNRI
Steroids
TCA
GLP-1RA
Pioglitazone
ACE inhibitor/ARB
Alpha blockers for urinary symptoms
Antimuscarinics, e.g. oxybutynin
Antiplatelets
Bisphosphonates
Gabapentinoids
Opioids
Diuretics
PPI
Steroids
ACE inhibitor/ARB
Antimuscarinics, e.g. oxybutynin
Antipsychotics
Benzodiazepines and z-drugs
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Diuretics
Gabapentinoids
Metoclopramide
Opioids
Sedative antihistamines
SSRI and SNRI
TCA
Alpha blockers for urinary symptoms
NSAIDs
PPI
Sulfonylurea
Antiplatelets
Benzodiazepines and z-drugs
Beta-blockers
Gabapentinoids
Opioids
SSRI and SNRI
TCA
Steroids
Antimuscarinics, e.g. oxybutynin
ACE inhibitor/ARB
Antipsychotics
Diuretics
Metoclopramide
PPI
Antipsychotics
Benzodiazepines and z-drugs
Beta-blockers
Centrally acting antihypertensives
Gabapentinoids
Metoclopramide
TCA
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Digoxin
PPI
Antimuscarinics, e.g. oxybutynin
Antipsychotics
Benzodiazepines and z-drugs
CCB (dihydropyridine)
Digoxin
Gabapentinoids
Pioglitazone
Sedative antihistamines
SSRI and SNRI
ACE inhibitor/ARB
Alpha blockers for urinary symptoms
Bisphosphonates
NSAIDs
Opioids
PPI
Statins
Steroids
Sulfonylurea
Antipsychotics
Benzodiazepines and z-drugs
Gabapentinoids
Metoclopramide
Prochlorperazine
Amiodarone
GLP-1RA
SGLT-2 inhibitor
Gliptin
Sulfonylurea
ACE inhibitor/ARB
Gabapentinoids
Statins
ACE inhibitor/ARB
Antiplatelets
Bisphosphonates
Diuretics
Steroids
Antipsychotics
Laxatives
NSAIDs
SGLT-2 inhibitor
ACE inhibitor/ARB
Bisphosphonates
GLP-1RA
SGLT-2 inhibitor
Antimuscarinics, e.g. oxybutynin
Antipsychotics
NSAIDs
Opioids
TCA
CCB (dihydropyridine)
Gabapentinoids
SSRI and SNRI
Amiodarone
Antipsychotics
DOAC
Gabapentinoids
Penicillins
Prochlorperazine
Statins
ACE inhibitor/ARB
Diuretics
NSAIDs
PPI
Steroids
ACE inhibitor/ARB
Amiodarone
Antimuscarinics, e.g. oxybutynin
Antiplatelets
Antipsychotics
Beta-blockers
Bisphosphonates
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Digoxin
Diuretics
Gabapentinoids
Gliptin
GLP-1RA
NSAIDs
Penicillins
PPI
Prochlorperazine
SGLT-2 inhibitor
SSRI and SNRI
Steroids
TCA
Alpha blockers for urinary symptoms
Benzodiazepines and z-drugs
Centrally acting antihypertensives
DOAC
Statins
ACE inhibitor/ARB
Bisphosphonates
Diuretics
Gabapentinoids
SSRI and SNRI
Statins
Antipsychotics
Beta-blockers
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
NSAIDs
PPI
Polypharmacy guidance: Appropriate prescribing making medicines safe, effective and sustainable 2026-2029
