High risk medicines in the community: identifying and managing risk Rohan Elliott Centre for Medicine Use and Safety, Faculty of Pharmacy & Pharmaceutical Sciences, Monash University Pharmacy Department, Austin Health
Outline 1. High risk medicines Which medicines should we be most concerned about? 2. Adherence to medicines What is adequate adherence? How can we identify poor adherence? How can we improve adherence? 3. Polypharmacy How can we reduce the number of medicines?
Benefits & risks of medicines Benefits:» Symptom management, reduced mortality When prescribed, taken and monitored appropriately Risks:» Adverse drug reactions (ADR) (~20% of older people with chronic disease)» Medication-related hospitalisations (~30% of admissions for older people)» Death (~3% of deaths are cause by ADR, more common in older people) Sometimes unpredictable, unavoidable Often predictable & preventable (~50% of cases)» Prescribing, dispensing or administration errors» Inadequate monitoring & review» Patient errors or non-adherence
1. High risk medicines Not all medicines are the same when it comes to risk of adverse drug events Medicines with greatest risk are those with: narrow therapeutic window (e.g. warfarin, phenytoin); serious toxicities in overdose (e.g. paracetamol); and/or complicated dosing schedules (e.g. methotrexate, oral chemo)
Therapeutic window Drug concentration vs time Drug
Examples of high risk medicines Anticoagulants, e.g: warfarin low molecular weight heparins» enoxaparin (Clexane)» dalteparin (Fragmin) new oral anticoagulants:» apixaban (Eliquis)» dabigatrin (Pradaxa)» rivaroxaban (Xarelto)
Warfarin
Examples of high risk medicines Oral chemotherapy, e.g: cyclophosphamide everolimus imatinib lenalidomide mercaptopurine hydroxyurea temozolamide thalidomide tretinoin
Examples of high risk medicines Immunosuppressants, e.g: azathioprine cyclosporin leflunomide methotrexate tacrolimus Insulins lithium potent opiates (e.g. fentanyl)
Examples of moderate risk medicines antiepileptics antipsychotics corticosteroids digoxin non-steroidal anti-inflammatory drugs (eg. celecoxib, ibuprofen) potent diuretics (e.g. frusemide) some oral hypoglycaemic agents (e.g. glibenclamide) sedative drugs (e.g. diazepam, nitrazepam)
Medicine-related hospitalisation & deaths Commons causes: ADRs» Acute renal failure» Haemorrhage» Falls & fractures» Delirium Non-adherence / errors» CCF» COPD» Falls & fractures (osteoporosis)» CVA
Medicine-related hospitalisation & deaths Most commonly implicated drugs: cardiovascular & diuretics (due to high prevalence of prescribing) psychotropics (antidepressants, antipsychotics, anxiolytics, sedatives) anticoagulants hypoglycemics (especially insulin) opiates (e.g. fentanyl, oxycodone) non-steroidal anti-inflammatory drugs potassium supplements cytotoxic and immunosuppressive drugs (e.g. cancer therapies) corticosteroids - anti-epileptics - antibiotics - antiplatelet drugs
Assessing risk Can t judge risk based on the type of medicine only Also need to consider factors such as: Medication factors:» dose & indication» duration & stability of drug therapy (& clinical condition) Patient factors» level of understanding of the therapy / complexity of regimen» motivation» history of non-adherence or errors» cognitive function» supports in place
2. Adherence (compliance) to medicines The extent to which medicine-taking coincides with the prescribed treatment. What is adequate adherence? Depends on the type of medicine 100% adherence is not necessary, and is probably unachievable!!! 80-120% is acceptable for most medicines (some exceptions) 70% is probably adequate for many medicines 60% is generally inadequate Cramer et al. Value in Health 2008; 11: 44-47
Risk factors for poor adherence Polypharmacy (especially 8 or more medicines) Complex treatment regimen Recent medication changes Cognitive impairment Poor motivation Poor understanding of medicines Financial difficulties Depression
How can we identify poor adherence? Ask the patient (&/or carer) carefully worded questioning can elicit honest answers Review clinical parameters & outcomes (e.g. BP, BSL, INR, drug levels) Ask the patient s pharmacy (with consent) only helpful if they use 1 pharmacy Nb. dispensing taking! Inspect the medicines when were they dispensed? have doses been taken from the packs? Look around the home (e.g. are there medicine stockpiles?)
When should we worry about poor adherence? High risk medicines need to avoid over-adherence & errors, to minimise toxicity Medicines prescribed for serious/acute medical problems e.g. infection, cancer, thromboembolism, CCF need to avoid under-adherence to maximise effectiveness Frail or cognitively impaired patients need to avoid over-adherence & errors, to minimise toxicity Patients with recent medication changes increased risk of errors Patients whose adherence is <80% or >120%
How can we improve adherence? First, identify the reasons / causes! The appropriate strategy(s) to improve adherence will depend on the underlying cause Two main categories: Intentional (e.g. poor motivation, financial difficulties) Unintentional (e.g. confusion, forgetfulness, poor knowledge) (may be both)
How can we improve adherence? Weak evidence for most commonly used adherence strategies (when used alone): Patient counselling and education Medicine lists / charts / calendars Tailoring regimens (routinisation) Reminder alarms Dosing aids (Webster packs, Dosett boxes, Medi-sachets, etc) Self-medication training programs (in hospital)
How can we improve adherence? Strongest evidence is for: Regimen simplification 1 Multi-component interventions 2» patient education & counselling plus other strategies (e.g. medication list, reminders, dosing aid, etc) 1. Haynes, et al. Cochrane Database Syst Rev 2008;(2): CD000011. 2. George J et al, Drugs Aging 2008; 25: 307-24.
Dosing aids May improve medicine-taking for some people Not suitable for all patients. many limitations and potential problems» they don t address intentional non-adherence, poor motivation, forgetfulness» many medicines cannot be packed» reduces patients medication knowledge & autonomy» increases medicine wastage and cost to patient» requires adequate cognition, eye sight & dexterity many patients have difficulty using them» makes care transitions more complex» unintended discrepancies are common (10%)
Dosing aids Recent Cochrane review: 1 No evidence in older people using multiple medicines Limited evidence in patients with single disease» average 11% increase in adherence» small improvements in BP and HbA1C Recent NICE review: 2 evidence not strong enough to recommend widespread use should only be used to overcome practical problems if there is a specific need. Careful patient selection, and awareness of the limitations of dosing aids, is vital for ensuring appropriate and safe use. 1. Mahtani KR, et al. Cochrane Database Syst Rev 2011 CD005025 2. Nunes V, et al. National Collaborating Centre for Primary Care and Royal College of General Practitioners. 2009
Regimen simplification Regimens can often be simplified, without changing the therapeutics of the regimen 1,2 1. Elliott RA, et al. J Pharm Pract Res 2011; 41: 21-5. 2. Elliott RA. J Clin Pharm Ther Published online 21 May 2012 (DOI: 10.1111/j.1365-2710.2012.01356.x)
What determines regimen complexity? Number of medications Number of dose-times
% compliance Dose-frequency & adherence 100 90 80 70 60 50 40 30 20 10 0 D BD TDS QID Dose-frequency Based on: Richter A et al. Clin Ther 2003; 25: 2307-2335
What determines regimen complexity? Number of medications Number of dose-times Number of dose-units Complex dose-forms Specific dietary or time requirements
How can we simplify a regimen? Number of medications review & remove unnecessary meds use one medicine for two problems Number of dose-times switch to longer-acting formulations consolidate dose-times Number of dose-units change strength or formulation Complex dose-forms switch to simpler dose-form (e.g. GTN tab vs. patch) Specific dietary or time requirements switch to simpler doseform
3. Polypharmacy Now the standard of care for many diseases» e.g. CCF, COPD, hypertension, osteoporosis Polypharmacy is the norm in elderly patients 1 e.g. Austin Health:» Mean 10 medications on discharge (range 1-21) May not be avoidable! Therefore the goal is to minimise & manage polypharmacy
Minimising polypharmacy Avoid recommending or prescribing drugs for minor, nonspecific or self-limiting complaints Encourage non-drug approaches where possible e.g. for insomnia, constipation, dementia/bpsd Be alert to atypical presentation of ADRs which can result in a prescribing cascade e.g. incontinence, confusion/behaviour change, falls Consider any new symptom to be a potential ADR Review all medicines regularly cease any that are not essential ( de-prescribing )
Minimising polypharmacy: de-prescribing Challenging! Requires patient agreement Usually 1 medicine at a time (prioritise highest risk medicines) Some medicines need to be weaned to minimise withdrawal effects, e.g.: sedatives some antidepressants anti-epileptics corticosteroids
Managing polypharmacy Simplify regimen choose once- or twice-daily drugs where possible reduce total number of doses & dose-times Ensure patient has a medication routine Provide medication aids Medication list Reminder devices Dosing aid (if appropriate) Refer for a pharmacist medication management review
Pharmacist medication management review Home medicines review (HMR) GP referral to community pharmacy GP referral directly to accredited pharmacist Hospital-initiated HMR (commencing 2013) Hospital outreach medication review (HOMR) some hospitals only (HARP) Residential care medication review (RMMR) RACFs only MedsCheck In pharmacy only; No referral required Focus is on education & adherence (not a thorough med review)
Pharmacist medication management review Can help to: Obtain an accurate medication history (prescribed & non-prescribed) Identify unnecessary & high-risk medicines» assist with de-prescribing Identify non-adherence Simplify the medicine regimen / routine Provide patient education & counselling Provide/up-date medication list Assess suitability for dosing aids
Summary Not all medicines have equal risk Be aware of which ones to look out for» Also consider other factors, e.g. dose, clinical status Adherence is important.. but 80-120% is usually OK (some exceptions) Explore reasons for non-adherence before deciding what to do Non-adherence usually requires a multi-pronged approach» Dosing aids are not always the answer Polypharmacy can be minimised & managed Regimen simplification & medication review are important