Intelligent Polypharmacy Professor Colin P Bradley Department of General Practice University College Cork
Polypharmacy No standard definition 2005 review the use of medications that are not clinically indicated 2010 Swedish study - > 5 medicines defined as polypharmacy and > 10 excessive polypharmacy
Problems of polypharmacy Increased risk & prevalence of drugdrug interactions Increased risk & prevalence of adverse effects Increased risk & prevalence of nonadherence Increased risk & prevalence of medication errors Increased cost
Risk of type C* interactions related to number of drugs (Astrand et.al., 2007) * Interactions which are correctable by dosage adjustment (usually less serious)
Risk of type D* interactions related to number of drugs (Astrand et.al., 2007) * Interactions which may have serious clinical consequences
Factors determining risk of adverse effects of medications Patient age, gender, ethnicity Renal and hepatic function Co-morbities which increase ADR risks e.g. peptic ulcer disease or heart disease and NSAIDs Therapeutic index of the medicine
Factors determining risk of nonadherence Experience of adverse effects Experience of interactions Complexity of medication regimen Cognitive function Drug aversion
Factors related to risk of medication error Number of medicines prescribed Complexity of medication regimen SALADs sound alike, look alike drugs e.g. penicillin & penicillamine Cognitive function of doctor, pharmacist, patient and/or carers Care setting hospital, home etc.
Costs of polypharmacy Costs of medicines Costs of mechanisms to reduce error Costs of strategies to compensate for cognitive function decline Costs of non-adherence (waste)
Benefits of polypharmacy = benefits of pharmacotherapy Reduction in adverse events prophylactic medicines medicines to counter possible ADRs Improvement in clinical conditions reduction in complication rates reduction in symptoms control of disease progression Savings to health system if used appropriately
What is intelligent polypharmacy? Use of multiple medicines in patients where the benefits of the medicines taken still outweigh the risks intrinsic to each medicine plus the risks associated with the combination of medicines.
An example of intelligent polypharmacy? the polypill Proposed originally in 2003 by Wald & Law Combination of statin, thiazide, betablocker, ACE inhibitor, folic acid and aspirin Estimated to reduce risk of cardiovascular disease by 80% in unselected population aged over 55 years ADR rate estimated at 8-15% Has been trialed in India
Other examples H. Pylori eradication regimens HAART for HIV infection Multi-drug regimens for TB treatment Treatment of type 2 diabetes usually involves metformin, other glucose lowering drugs plus drugs for hypertension (esp ACEI) and lipid lowering drugs
Implementing intelligent polypharmacy in practice Systematic review of patients on multiple medicines Key drugs to review drugs with narrow therapeutic index e.g. Warfarin, digoxin etc. drugs with known detectable ADRs e.g. Immunosuppresants watch out for the prescribing cascade (Feely) Key conditions to review Renal disease hepatic disease Key patient group - elderly
SAIL and TIDE SAIL Simple as possible Adverse reactions look out for them Indication to be checked for each medicine List all the medicines in the notes and provide copy to the patient TIDE Time set aside to review medicines Individual responses need to gauged Drug-drug interactions need to be checked Educate the patient about their medicines
STOPP/ START Screening Tool of Older People s potentially inappropriate Prescriptions Screening Tool to Alert doctors to Right (i.e. appropriate, indicated) Treatment
Which are the problem drugs? Cardiovascular CNS and psychotropics Gastrointestinal Respiratory Musculoskeletal Urogenital Endocrine
The problem drugs - cardiovascular Digoxin Loop diuretics Thiazide diuretics Beta-blockers Calcium channel blockers Vasodilators Dipyridamole Aspirin Clopidrogrel Warfarin
The problem drugs - CNS Tricyclic anti-depressants Benzodiazepines Neuroleptics Phenothiazines Anti-cholinergics SSRIs First generation anti-histamines Opiates
The problem drugs gastrointestinal Diphenoxylate Loperamide Codeine phosphate Prochlorperazine PPIs Anti-cholinergic anti-spasmodics
The problem drugs respiratory system Theophylline Systemic corticosteroids Nebulised ipratropium
The problem drugs musculoskeletal system NSAIDs Corticosteroids Colchicine
The problem drugs urogenital system Bladder anti-muscarinics Alpha-blockers
The problem drugs endocrine system Glibenclamide Chlorpromamide Oetrogens
Other issues Duplicate drugs same class or same therapeutic effect Complex regimens more than twice per day or other special requirements for taking the drug Multiple tablets to be taken simultaneously Look-alike tablets Difficult formulations Slow accumulation of medical problems (and, hence, associated medications) Prevention v therapy
Medications sometimes denied inappropriately Warfarin Aspirin Clopidrogrel Statins ACE inhibitors Beta-blockers Beta-agonists Inhaled corticosteroids L-DOPA Antidepresants PPIs Fibre supplements DMARDs Bisphosphonates Calcium and vit D Metformin
Reducing the risk Avoid prescribing where appropriate Start low and go slow Robust repeat prescribing system Clinical pharmacy ICT solutions Interaction alerts Drug disease contraindication alerts Dosage alerts including paediatric alerts
Case 1 66 year old man with a history of hypertension x 10yrs; angina x 3 yrs and osteoarthritis x 1 yr Atenolol 100mg daily x 30 Lisinopril 5mg daily x 30 Imdur (isosorbide mononitrate) 60mg daily x 30 Nuseals aspirin 75mg x 30 Lipostat 20mg nocte x 30 Voltarol 25mg tds x 90
Case 2 72 year old woman with 12yr history of type II diabetes, 6 yr history of hypertension history of ankle oedema (of uncertain cause and duration). Daonil 5mg daily x 30 Frusemide 20mg daily x 30 Tritace 10mg daily x 30 Dalmane 30mg nocte x 30
Case 3 58 year old woman with a 9 month history of hypertension Adalat LA 20mg daily x 30 Innovace 10mg daily x 30 Moducren ii daily x 30 (combination of hydrochlorthiazide 25mg; amiloride 2.5mg and timolol maleate 10mg)
Case 4 64 year old woman with a history of recurrent depression was found on screening 3 years ago to have osteoporosis Fosamax i weekly x 8 Lexapro 10mg daily x 30 Zopiclone 7.5mg nocte x30 Nexium 20mg daily x 30 Ixprim ii prn x 100
Case 5 62 year old man with a 4 year history of atrial fibrillation recently presented with a first episode of gout Digoxin.625mg od x 30 Warfarin 4mg daily (INR check 8 weekly, last reading 6 weeks ago was 2.3) Centyl K i daily x 30 Indomethacin 50mg tds x 14 days
Case 6 77 year old woman with 5 year history of angina, 1 year history of polymyalgia rheumatica recently presented with indigestion Atenolol 50mg daily x 30 Adalat 10mg three times daily x 90 GTN spray as needed x 1 Syndol i or ii as needed x 50 Prednisolone 5mg daily x 30 Gaviscon Advance 10mls as needed Pariet 10mg daily x 30