Table. Drugs associated with adverse events in intercurrent illness .

Drug class	Drug examples	Problems arising from intercurrent illness	Potential adverse outcome
Analgesics	Hydromorphone, morphine, oxycodone, tramadol	Reduced absorption of controlled-release formulations, or deliberate cessation	Exacerbation of pain Opioid withdrawal syndrome − dysphoria, restlessness, salivation, nausea, abdominal pain and diarrhoea
	Morphine, hydromorphone	Reduced clearance in renal dysfunction, with risk of accumulation and toxicity	Opioid toxicity
Antidepressants	Venlafaxine, desvenlafaxine	Reduced absorption of controlled-release formulations, or deliberate cessation	Withdrawal syndrome − agitation, anxiety, diarrhoea, fasciculations, sensory disturbance (including shock-like syndrome, tremor, vertigo and vomiting)
Antihypertensives	Controlled-release metoprolol	Reduced absorption or deliberate cessation	Exacerbation of angina Conflicting data on association with rebound hypertension, arrhythmias3
	Renin–angiotensin inhibitors	Impaired physiological homeostasis, impairing renal perfusion	Acute kidney injury and hyperkalaemia
	Diuretics	Exacerbation of hypovolaemia and altered electrolyte excretion	Dehydration and electrolyte disequilibria
	Clonidine or moxonidine	Reduced absorption or deliberate cessation leading to withdrawal of central inhibitory effect	Tachycardia and hypertension
Drugs for parkinsonism	Levodopa with carbidopa or benserazide	Reduced absorption of controlled-release formulations, or deliberate cessation	Decline in motor function Case reports of neuroleptic malignant syndrome with acute withdrawal4 featuring fever, altered mental state, rhabdomyolysis, rigidity
Mood stabiliser	Lithium	Reduced clearance in renal dysfunction with risk of accumulation and toxicity	Lithium toxicity – nausea, confusion, muscle weakness, apathy, hyperreflexia, myoclonic jerks, dysarthria, seizures
Anticoagulants	Warfarin, rivaroxaban, apixaban, dabigatran	Reduced absorption or deliberate cessation	Reduced anticoagulant effect and elevated risk of thrombosis
	Dabigatran, rivaroxaban, apixiban	Risk of accumulation in renal dysfunction	Increased anticoagulant activity leading to bleeding complications
	Warfarin	Decreased oral intake contributing to vitamin K deficiency	Increased anticoagulant activity leading to bleeding complications
	Warfarin, rivaroxaban, apixaban	Concomitant administration of anti-infectives that reduce drug clearance e.g. erythromycin (warfarin, rivaroxaban, apixaban), ciprofloxacin (warfarin) or fluconazole (warfarin)	Increased anticoagulant activity leading to bleeding complications
Antiarrhythmics	Disopyramide, flecainide, sotalol, digoxin	Reduced absorption or deliberate cessation	Reduced antiarrhythmic activity and potentially life-threatening arrhythmias
	Sotalol, digoxin	Reduced clearance in renal dysfunction	Bradycardia (sotalol and digoxin) and hyperkalaemia (digoxin)
Antiepileptics	Carbamazepine, valproate, phenytoin, levetiracetam, topiramate	Reduced absorption or deliberate cessation	Reduction in serum concentration and increased seizure risk
Drugs for diabetes	Sodium-glucose co-transporter 2 inhibitors	Exacerbation of hypovolaemia and electrolyte loss	Dehydration and electrolyte disequilibria
	Metformin	Reduced clearance in renal dysfunction causing accumulation and toxicity	Nausea, anorexia, lactic acidosis
	Insulin, sulfonylureas	Inappropriate dose relative to intake and hormonal counterregulatory response (insulin and sulfonylureas) or reduced clearance in renal dysfunction causing accumulation and toxicity (glibenclamide, glimepiride)	Hypoglycaemia or hyperglycaemia
Oral contraceptives	Oestrogen and progestogen combinations	Reduced absorption or deliberate cessation	Contraceptive failure