Deprescribing Guidelines

The following classes and medications are excluded in this guideline.

Medication Class/ Medications	Rationale for non-inclusion
Analgesia	Usually indicated for symptom management. Discontinue if no longer required / ineffective.
Hypnotics /   Benzodiazepines
Antihistamines
Laxatives
Antidepressants	Multiple indications such as treatment of depression, neuropathic pain and to enhance appetite. May still be required as antidepressant. Consider consult with specialist if needed.
Antipsychotics	Consider consult with specialist.
Antibiotics	Generally single course. Consult specialist if use is intended for long term prophylaxis.
Steroids /   Immunosuppressants	Consider consult with specialist.
Combination of anti-Parkinson agent and decarboxylase inhibitor/COMT inhibitor, dopamine agonist, MAO Type B inhibitor	Consider consult with specialist if used for Parkinson’s disease. [Note : the same agents can also be used to treat restless legs syndrome]
Antiepileptics	Multiple indications such as epilepsy, chronic pain. Consider consult with specialist.
Antiarrhythmic agents	Consider consult with specialist.
Inhalers	Not commonly encountered.
Drugs that are contraindicated or inefficacious in end stage renal failure e,g,: Metformin, glibenclamide, glimepiride, SGLT-2 inhibitors, meglitinides, hydrochlorothiazide, bisphosphonates, NSAIDs, direct oral anticoagulants, enoxaparin	Not used or use should be avoided.
Thiazolidinedione (eg: rosiglitazone, pioglitazone)	Rarely used in practice.

COMT: catechol-o-methyltransferase; MAO:monoamine oxidase inhibitor; SGLT-2: sodium-glucose co-transporter-2; NSAID: nonsteroidal anti-inflammatory

Definition:

Deprescribing can be defined as “the systematic process of identifying and discontinuing drugs in instances in which existing or potential harms outweigh existing or potential benefits within the context of an individual patient’s care goals, current level of functioning, life expectancy, values, and preferences.”¹

Polypharmacy is usually defined as taking five or more medications². 

Communicating deprescribing using the acronym FRAME³

• Fortify trust
• Recognise enablers or barriers to deprescribing
• Align deprescribing recommendations with goals of care
• Manage cognitive dissonance
• Empower patients and caregivers to continue the conversation
  
  

Less Likely to Deprescribe	Factors of Consideration (not in order of importance)	More Likely to Deprescribe
Prefer(s) to continue medication	Patient and/or caregiver preferences	Prefer(s) not to continue medication
Aligned	Goals of care	Misaligned
Young	Age	Elderly
Fit	Frailty	Frail
Absent	Cognitive impairment	Present
Long	Prognosis	Short
Good	Medication adherence	Poor
Good	Ability to swallow / administer medication	Poor
Low	Pill burden	High
Secondary / tertiary prevention Symptomatic management	Indication	Primary prevention, no indication
Shorter than prognosis	Time to benefit from medication	Longer than prognosis
Greater benefit than risk	Benefit: Risk ratio	Greater risk than benefit
Weak	Strength of evidence to deprescribe	Strong
Absent	Adverse event(s)	Present
Absent	Drug interactions	Present
Present	Social support	Absent
Inexpensive	Cost	Beyond financial means with available schemes/ subsidies/insurance

Drug Class	Medications (e.g.)	Common Indication(s)6	Factor(s) in favour of deprescribing	Factor(s) against deprescribing	Suggested Deprescribing Strategy
Antiplatelet7	Aspirin Clopidogrel Ticagrelor Prasugrel	1. Primary prophylaxis 2. Secondary prophylaxis (prior cardiovascular event such as stroke, myocardial infarction)	Aspirin 1. High risk of gastrointestinal bleeding (e.g. elderly, renal dysfunction, alcohol users, smokers, on other medications that may induce GI bleed such as corticosteroids, another antiplatelet or anticoagulant) 2. Advanced age/ limited life expectancy 3. Prior gastrointestinal pathology such as gastric ulcer, erosions 4. Low cardiovascular risk (i.e. primary prophylaxis8); no risk calculator available for patients >80 years old 5. Recurrent minor bleeding (e.g. bruises, gum bleeds) that negatively impacted quality of life	Aspirin 1. High cardiovascular risk (usually secondary prophylaxis or recent acute coronary syndromes 2. Concurrent use of PPIs or other gastric acid suppressant for prevention of gastrointestinal bleed.	1. Stop aspirin if patient does not have a history of recent acute coronary, cerebral or peripheral vascular disease symptoms/ events. 2. Review and stop second antiplatelet if intended duration has been completed (e.g. total duration of 12 months after acute cardiac syndromes). Consider earlier cessation in patients with high bleeding risk, limited prognosis.
Anticoagulant	Warfarin	Prophylaxis and treatment of: 1. thromboembolic disorders 2. embolic complications due to atrial fibrillation or cardiac valve replacement	AF only 1. Controversial benefits of anticoagulation in ESKD9 2. Life expectancy ≤ 6 months10 3. High bleeding risk10 4. Poor oral intake10 5. Poor adherence10 6. Inability to monitor9	[Opinion] 1. High thromboembolic risk e.g. high CHA2D2SVaSC score C: Congestive heart failure/ left ventricle dysfunction (1 point) H: Hypertension (1 point) Age: 65-74 years old (1 point), ≥75 years old (2 points) D: Diabetes (1 point) S: History of stroke, transient ischemic attack or thromboembolism (2 points) V: History of myocardial infarction, peripheral vascular disease aortic artherosclerosis (1 point) Sex: Female (1 point), male (0 point)	Can be discontinued without tapering
Statins	Atorvastatin Lovastatin Pravastatin Rosuvastatin Simvastatin Fluvastatin	1. Hypercholestrolemia 2. Primary or secondary prophylaxis of cardiovascular events	1. Low cardiovascular risk (i.e. primary prophylaxis) 11,12 2. Limited life expectancy 11,12 e.g. prognosis less than one year 3. Poor overall functional status11 4. Preexisting liver disease11 5. Presence of diabetic risk factors11 6. Presence of interacting medications such as fibrates, macrolides, diltiazem, verapamil11 7. Presence of suspected adverse effect such as non-specific muscular pains, issues with cognition or lethargy11,12 8. Secondary prophylaxis: patient had >5 years of treatment, low total cholesterol and no further thromboembolic events12 9. High pill burden12	1. Recent stroke (past 2 years) for plaque stablisation12 2. Actively treating peripheral vascular disease where symptoms improve on statin12 3. High risk of recurrent events (recent event, coexisting poorly controlled diabetes who are less than 85 years old)11	1. Consider a trial of cessation in patients with reduced life expectancy, relatively low risk of cardiovascular events or experiencing possible adverse effects.11 2. Stop statins in patients with limited prognosis11 3. Use minimum dose to minimise side effects11 Statins may be discontinued without tapering.
Antilipemic agent	Fenofibrate Gemfibrozil	Hypercholestrolemia Hypertriglyceridemia	[Opinion] 1. Poor oral intake 2. Hypolipidemia	[Opinion] Pancreatitis	[Opinion] Can be discontinued without tapering
	Omega-3	Hypertriglyceridemia		None
	Ezetimibe	1. Hypercholestrolemia 2. Secondary prophylaxis of atherosclerotic cardiovascular events after acute coronary syndrome
Anti-hypertensive 1. Alpha blocker 2. Beta blocker 3. Calcium channel blocker 4. Vasodilators 5. Central acting agent	Terazosin, prazosin, doxazosin Bisoprolol, carvedilol, atenolol, metoprolol, propranolol Nifedipine LA, amlodipine, diltiazem (IR or SR) Hydralazine Methyldopa	1. Hypertension 2. Heart failure 3. Atrial fibrillation and other arrhythmias 4. Angina 5. Benign prostate hyperplasia (BPH)	1. Advanced age/ frail patients13 2. High falls risk12,13 3. Postural hypotension12,13 4. Low cardiovascular risk13 and blood pressure (BP) <target 5. Unclear benefits of treating hypertension in >85 years old13 6. BP is consistently <target	1. Agents are used for other indications such as beta blockers for heart failure, atrial fibrillation or ischemic heart disease12,13 2. Multiple cardiovascular risk factors such as diabetes, renal dysfunction, high lipids, prior cardiovascular disease such as stroke, ischemic heart disease13 3. Good functional status e.g. ECOG grade 1-213 4. BP consistently >target without treatment12	Determine patient’s BP target. Avoid SBP <130 and/or DBP <65 in the frail12,14, SBP up to 150mmHg may be appropriate in the very old or frail12 Consider goal BP<150/90 (diabetic and ESKD or moderate-to-severe cognitive impairment or 2+ ADL dependencies)15 Avoid agents such as methyldopa and vasodilators where possible. Reduce dose or stop agent, one at a time. Withdrawal should be gradual.13 Taper at approximately 25% every month over 3-4 months13 or even over 3-6 months12 Reduce or stop heart rate limiting medications if heart rate <60.
Nitrates	1. Isosorbide mononitrate 2. Isosorbide dinitrate	1. Angina 2. Heart failure	[Opinion] 1. Reduced physical activity 2. Symptomatic hypotension/ orthostatic hypotension	[Opinion] 1. Frequent angina 2. Mobile 3. BP≥150/90 4. For heart failure	[Opinion] Reduce dose to the next available dosage form or frequency on a weekly basis then discontinue.
Oral hypoglycemic agents 1. Sulphonylureas 2. Dipeptidyl peptidase -4 inhibitor 3. Alpha-glucosidase inhibitor	Tolbutamide, glipizide, gliclazide (IR or MR) Linagliptin, sitagliptin Acarbose	Type 1 and Type 2 diabetes mellitus	1. Frailty16 2. Reduced food intake17 3. Increased falls risk16 4. HbA1c ≤ 6.5%16 5. Hypoglycemia history17 6. Pain or discomfort caused by treatment15 7. Caregiver stress from treatment complexity15	1. Hyperglycemic symptoms such as thirst, polyuria16 2. Comorbid cardiovascular risk factors16 3. Relatively young with high BMI16	Determine HbA1c target; interpret with caution as concurrent anaemia may lead to a falsely low HbA1c. HbA1c <8.5% and blood glucose <12mmol/L may be acceptable16 Blood glucose <15mmol/L may be acceptable near end-of-life.16,17 Aim no glucose level <6mmol/L.17 Fasting glucose of 5.6-10.0mmol/L and bedtime glucose of 6.1-11.1mmol/L may be considered. 15 For those on insulin: Type 1: insulin should not be stopped unless prognosis is in days or short weeks and oral intake is poor. General principles 1. Reduce dose or stop agent most likely to cause hypoglycemia such as sulphonylurea, insulin.16 2. Switch to an agent with lower risk of hypoglycemia such as a non-sulphonylurea; neutral protamine hagedorn (NPH) or mixed insulin to detemir or glargine to reduce nocturnal hypoglycemia.16 3. Reduce doses of renally eliminated antihyperglycemics. 4. Monitor daily for 1-2 weeks for signs of hyperglycemia or hypoglycemia. Repeat above steps if hypoglycemia and/or adverse effects persist. Lower doses every 1-4 weeks. Return to previous dose or consider alternative drug with lower risk of hypoglycemia if symptomatic hyperglycemia or blood glucose exceeds individual target.16
Insulin	Actrapid Insulatard Lantus Levemir Mixed insulins (eg Mixtard, Novomix)
Proton pump inhibitors (PPI)	Omeprazole Esomeprazole Lansoprazole Dexlansoprazole Pantoprazole Rabeprazole	Peptic ulcer disease Esophagitis Reflux Prophylaxis	1. Symptoms no longer evident12,18 2. Mild esophagitis or intermittent symptoms12,18 3. Cessation of potentially ulcerogenic medications such as antiplatelet and corticosteroids8,12,18 4. Completed treatment of GORD12 5. Peptic ulcer disease with known underlying cause (e.g. NSAIDs, H.pylori) removed/ treated12	1. Presence of hiatus hernia, Barrett's osephagus, severe oesophagitis, oesophageal stricture and/or oesophageal scleroderma12,18 2. Previous bleeding gastric ulcers12,18 3. Ongoing symptoms for GORD requiring treatment18 4. Ongoing use of gastrointestinal irritant such as antiplatelet, anticoagulant18	Step down to lower and then to lowest dose or cease if already at the lowest dose.18 Review at 4-6 weeks.18 For patients with no or minimal symptoms: intermittent treatment or use PPI, H2 antagonists or antacids as needed18 For patients with significant symptoms relapse: consider test and treat for H.pylori and consider return to previous dose for 4-8 weeks18
H2 antagonists	Famotidine Ranitidine	GORD Peptic ulcer disease	[Opinion] 1. Absence of GORD symptoms 2. Cessation of potentially ulcerogenic medications 3. Completion of treatment for GORD or peptic ulcer disease	[Opinion] 1. Ongoing symptoms or recurrence of symptoms at cessation	[Opinion] Use lowest dose and/or frequency possible
Xanthine oxidase inhibitor	Allopurinol	Treatment of gout	1. Improved/ reduced dietary intake of purine-rich food or alcohol intake19 2. Low dose allopurinol19 3. Low risk of gout relapse19 4. Gout attack more than 12 months ago and serum uric acid in the normal range19	1. Recurrent/ recent gout attacks less than 12 months ago and serum uric acid is high19 2. Presence of tophi19 3. Evidence of uric acid nephropathy or urolithiasis19	Reduce to lower dose or cease if already at lowest possible dose.
	Febuxostat		[Opinion] Similar considerations to use of allopurinol	[Opinion] Similar considerations to use of allopurinol.	[Opinion] Similar to deprescribing of allopurinol.
Acetylcholinesterase inhibitors20	Donepezil Rivastigmine Galantamine	1. Alzheimer's dementia 2. Dementia of Parkinson disease 3. Lewy body dementia 4. Dementia of vascular disease	1. Has been on it for at least 12 months and:20,21 • Has severe Alzheimer's dementia • Has no benefit from treatment • Cognition and/or function has worsened significantly in the past 6 months 2. Significant vascular disease20 3. Presence of asthma, urinary incontinence, bradycardia or gastrointestinal disorders20 4. Frailty20 5. Severe agitation/psychomotor restlessness20,21	1. Mild or moderate Alzheimer’s dementia20 2. Good initial response to starting doses of acetylcholinesterase inhibitors20 3. Good functional status20 4. Improvement in behavioral and/or functional symptoms20	Halve dose every 4 weeks to lowest available dose and maintain for 4 weeks before discontinuation.20 If severe symptoms such as agitation, aggression, hallucination or reduced consciousness occur at less than one week after dose reduction/ withdrawal, restart the previous dose immediately as this is possibly an adverse withdrawal event.21 If cognition, behavioral, psychological symptoms or function worsen at 2 weeks to 6 weeks after dose reduction/ withdrawal, consider restarting previous dose as this is possibly a re-emergence of symptoms that were treated by acetylcholinesterase inhibitor21 If cognition, behavioral, psychological symptoms or function worsen at 6 weeks to 3 months after dose reduction/ withdrawal, evaluate for re-emergence of symptoms that were treated by acetylcholinesterase inhibitor or progression of condition21
N-Methyl-D-Aspartate (NMDA) receptor antagonist21	Memantine	1. Alzheimer's dementia 2. Dementia of Parkinson disease 3. Lewy body
Beta-3 agonist	Mirabegron	Overactive bladder	[Opinion] On long term urinary catheter/ diapers	[Opinion] Adequate control of symptoms	[Opinion] Can be discontinued without tapering
Supplements/ Vitamins	Renal vitamin Ascorbic acid Multivitamin	Supplementation	1. Lack of benefit8 2. High pill burden	Existing deficiencies	[Opinion] Stop if deficiency has been corrected. Tapering is not required.
	Neurobion Princi-B forte	1. Supplementation 2. Neuropathy
	Glucosamine	Osteoarthritis
	Thiamine	1. Deficiency 2. Treatment or prophylaxis of Wernicke encephalopathy	[Opinion] No more heavy alcohol intake and maintaining good dietary intake	[Opinion] Patient is still drinking alcohol
	Mecobalamin Folic acid	Correction of deficiencies	[Opinion] 1. High pill burden 2. Deficiencies have been corrected	[Opinion] Existing deficiencies	[Opinion] Stop if deficiency has been corrected. Tapering is not required.
Phosphate binders22	1. Calcium carbonate 2. Calcium acetate	Hyperphosphatemia	1. Hypophosphatemia 2. Poor oral intake 3. Low iPTH and/or ALP 4. High pill burden	1. Concomitant hypocalcemia 2. Previous parathyroidectomy requiring calcium replacement	Avoid symptomatic hypo-/hypercalcemia and hypophosphatemia. Stop or reduce dose/ frequency. Tapering is not required.
	Lanthanum Sevelamer			None
Vitamin D analogues22	Alfacalcidol Calcitriol	Mineral and bone disorder	1. Hyperphosphatemia 2. Hypercalcemia 3. Low iPTH and/or ALP	1. Previous parathyroidectomy 2. Hypocalcemia
Vitamin D	Cholecalciferol Ergocalciferol	Vitamin D deficiency	1. Hyperphosphatemia 2. Hypercalcemia 3. Adequate serum 25-hydroxyvitamin D levels 4. Wheelchair- or bed-bound	[Opinion] Inadequate vitamin D levels with good functional status.	[Opinion] Stop or reduce dose and/or frequency. Tapering is not required.
Iron supplementation	1. Sangobion 2. Iron polymaltose	1. Iron deficiency 2. Anaemia of chronic kidney disease	1. Iron overload 2. Absence of symptomatic anaemia 3. Pill burden 4. Unacceptable side effects from oral iron	[Opinion] Symptomatic anaemia and patient is unwilling/unable to have IV iron administered.	[Opinion] Consider IV Ferinject 500-1000mg to reduce pill burden if patient is willing to accept IV replacement. PO iron may be discontinued without tapering.
Erythropoiesis-stimulating agents23	1. Recormon 2. Mircera	1. Anaemia of chronic kidney disease 2. Anaemia due to chemotherapy 3. Myelodysplastic syndrome	1. Hb≥13g/dL	Symptomatic anaemia and patient is not a candidate for blood transfusion.	Balance of symptomatic anaemia and patient's desire to stop further injections.
Alkalinizing agent	Sodium bicarbonate	Metabolic acidosis	1. Pill burden 2. Serum bicarbonate level >26.0mmol/L	[Opinion] Serum bicarbonate level <20.0mmol/L	[Opinion] Stop or reduce dose and/or frequency. Tapering is not required.
Potassium binder	1. Sodium polystyrene sulfonate 2. Sodium zirconium cyclosilicate	Correction of hyperkalemia	1. Unable to tolerate 2. Hypokalemia	[Opinion] Hyperkalemia of ≥5.5mmol/l	[Opinion] Stop or reduce dose and/or frequency. Tapering is not required.
Glaucoma eye drops24	1. Latanoprost 0.005% 2. Brimonidine 0.1% 3. Brinzolamide 1% 4. Timolol 0.5%	Glaucoma	1. Mild glaucoma 2. Difficulty with administration	1. Advanced glaucoma with symptomatic vision loss or visual field defect 2. Vision loss in one eye from glaucoma already 3. Markedly elevated intraocular pressure (>35mmHg) 4. Maintaining visual ability is important for patient.	If the patient is not at risk of severe vision loss from discontinuation, eye drops may be discontinued. Consider consult with ophthalmologist if needed.
Antimuscarinic25	Oxybutynin Tolterodine Solifenacin	Overactive bladder	1. No indication 2. Presence or risk of adverse effects e.g. delirium, blurred vision, increased thirst, dry skin. 3. Drug/disease-drug interaction 4. Poor adherence	1. Urinary incontinence has improved 2. Adverse effects are not apparent or significant to the patient	Reduce dose by 25-50% of the daily dose each week to month. Withdrawal symptoms (irritability, anxiety, insomnia, sweating, GI effect such as nausea) may occur within 1-3 days of dose reduction and can last up to 6-8 weeks. If no withdrawal symptoms occur, continue to wean then stop. If severe withdrawal symptoms (severe anxiety, tachycardia, orthostatic hypotension, severe insomnia, worsening confusion) occur, restart at the previous dose. Recurrence of previous or new symptoms may occur within 1-2 weeks of dose reduction. In cases with withdrawal/ recurrent symptoms, recommence weaning 6-12 weeks later at a slower weaning (e.g. 5-12.5% of daily dose each month). End treatment 2-4 weeks after administering the lowest dose. Alternate day dosing may be considered to aid weaning.
Diuretics	Furosemide Bumetanide Metolazone	Fluid overload	[Opinion] 1. Poor fluid intake 2. Clinically dry or euvolemic	[Opinion] 1. Fluid overloaded	[Opinion] Stop or reduce dose and/or frequency. Tapering is not required.

Abbreviations: SBP= systolic blood pressure; DBP= diastolic blood pressure; ECOG= Eastern Cooperative Oncology Group; ADL= activities of daily living; IR=immediate release; MR=modified release; GORD=gastro-oesophageal reflux disease; iPTH= intact parathyroid hormone; ALP= alkaline phosphatase

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19. Tenni, P., & Dunbabin, D. (2019, May). A Guide to Deprescribing Allopurinol. Retrieved from https://www.primaryhealthtas.com.au/wp-content/uploads/2018/09/A-Guide-to-Deprescribing-Allopurinol-2019.pdf

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