2010 International Conference on Pharmacovigilance and Drug Safety

Strategies to Promote Drug Safety and Effectiveness

Thomas Y.K. ChanDivision of Clinical Pharmacology

Department of Medicine and Therapeutics, and

Centre for Food and Drug Safety, Faculty of MedicineThe Chinese University of Hong Kong

30 November 2010

Drugs Used Only if Needed andThe Right Drug for the Right Problem

Quality use of medicines

• Quality use of medicines – a joint effort

• Benefits of appropriate use of medicines

• Problem of incorrect use of medicines

• Rational use of medicines

• Prescribing to the elderly as an example

• Towards rational prescribing

• How to measure appropriateness of prescribing

• Education and training for junior doctors

Quality use of medicines A joint effort and a shared responsibility

• Patients – use medicines safely, appropriately• Health care professionals – prescribe, dispense

and administer the medicines, provide education and skills to patients and monitor the responses, education and training, research

• Providers of health services – policies, systems and processes

• Pharmaceutical industry – suitable information, education and promotion about medicines

• Governments – public policies, health systems, regulation and education

Benefits of appropriate use of medicines(Prescribing, dispensing, administration)

• Clinically significant improvement is achieved in several common diseases by appropriate drug treatment, for example:

Hypertension (thiazides in elderly patients)

Post-myocardial infarction (aspirin, blockers)

CHF (ACEI, ARB, blockers)

Hypercholesterolaemia (statins)

Diabetic nephropathy (ACEI, ARB)

• Alzheimer’s disease – drug’s cost-effectiveness

• Medicines are investments if used appropriately

Examples of incorrect use of medicines

• Use of drugs when no drug therapy is needed

• Use of wrong drugs

• Use of drugs with doubtful efficacy

• Use of drugs with uncertain safety status

• Incorrect administration, dosages or duration

• Polypharmacy and duplications

• Overuse of antibiotics and injections

• Inappropriate self-medications

• Not following evidence-based guidelines

Consequences of incorrect use of medicines

• Adverse drug reactions

• Drug-drug and drug-disease interactions

• Medication errors

• Treatment failure

• Drug overdose and poisoning

• Antimicrobial resistance

• Eroded patient confidence

Rational use of medicines (WHO, 1987)Correct, proper and appropriate use of medicines

When patients receive drugs that are:

• Appropriate to their clinical needs

• In dosages that meet their own individual requirements

• For an adequate period of time

• At the lowest cost to the individuals and the community

"Drugs used only if needed" and

"The right drug for the right problem"

The process of rational prescribing

• Diagnosis

• Goals of treatment (curative, symptom control or preventive)

• Treatment options (drug or non-drug)

• Choosing a drug (drug factors, patient factors or prescriber factors)

• Prescription

• Follow up and review (clinical response and adverse effects, drug to be continued or not)

Prescribing is a complex task

Requiring an understanding of: • The disease to be treated and goals of treatment• The drugs of choices• The principles of clinical pharmacology• Appreciation of risks, cost-effectiveness• Reasons for adverse drug reactions (ADRs)• Reasons for non-compliance• High risk drugs and high-risk situations• Potential problems – ADRs, inappropriate use

and under-treatment

ADRs in the elderly ADRs in the elderly – the facts the facts

• Age-related in the incidence of ADRs 10% elderly admissions are due to ADRs • ADRs are usually type A (predictable, dose-

dependent) hence, largely preventable• 15% of hospitalised elderly experience ADRs

• ADR frequency in proportion to use frequency

Cardiovascular – diuretics and digoxin

Aspirin and NSAIDs

Psychotropic (antipsychotics antidepressants benzodiazepines)

ADRs in the elderly – contributory factor 1ADRs in the elderly – contributory factor 1Inadequate clinical assessment

Such as inaccurate diagnosis and uncritical assessment of the need for treatment

• Non-specific symptoms (e.g. dizziness) will require meticulous history-taking and examination to make a diagnosis, but tendency to treat only the symptom

• Dependent oedema due to physical immobility, but diuretics are given, causing urinary incontinence

• Dizziness due to impaired postural control, but prochlorperazine is given, causing acute confusion and postural hypotension

ADRs in the elderly – contributory factor 2ADRs in the elderly – contributory factor 2Excessive prescribing

• Pressure on doctors to prescribe because of patient's expectations

• Therapeutic enthusiasm

• Over-energetic treatment

• Inappropriate prescribing

• Polypharmacy

ADRs in the elderly – contributory factor 3ADRs in the elderly – contributory factor 3Inadequate supervision of long-term drugs

Drugs for an acute illness may no longer be required

Drug therapy may be continued unnecessarily if:

• Failure to review the drug history

• Failure to question the need for drugs to be continued

• Patients receive drugs from more than one doctor

• Other factors

ADRs in the elderly – contributory factor 4ADRs in the elderly – contributory factor 4Physiological changes affecting drug handling

Changes May affect

Gastric acid output and pH Absorption

Gastric emptying First-pass metabolismSplanchnic blood flow

Body fat , body H2O , lean body mass Distribution

Serum albumin , liver size/blood flow Protein binding/liver clearance

GFR & renal plasma flow/tubular function Renal excretion*

*Many elderly patients thus excrete drugs slowly and are highly susceptible to nephrotoxic drugs.

ADRs in the elderly – contributory factor 5ADRs in the elderly – contributory factor 5Physiological changes affecting drug responses

• Age-related impairment of homeostatic mechanisms – postural control, orthostatic circulatory responses, thermoregulation and cognitive function

• Age-related changes in specific receptor and target organ responses, resulting in sensitivity to drugs or sensitivity to drugs

• Elderly patients are more sensitive to the CNS and respiration depressant effects of all narcotics

• Cognitive impairment with anticholinergic drugs

• Benzodiazepines impair balance falls

ADRs in the elderly – contributory factor 6ADRs in the elderly – contributory factor 6Polypharmacy

• Possible causes – multiple diseases, treatment from more than one doctor, failure to review drugs, over-energetic treatment, self-medications

• The risk of drug-drug interactions and ADRs steeply with the number of drugs given

• Reducing the number of drugs prescribed has been shown to decrease the likelihood of ADRs

ADRs in the elderly – contributory factor 7ADRs in the elderly – contributory factor 7Non-compliance with drug treatment - 1

Incidence and significance

• Hospital- and community-based studies have shown that as many as 75% of elderly patients make errors in their compliance to prescriptions, 25% of which are potentially dangerous (J R Coll Physicians Lond 1984)

• Non-compliance & ADRs account for 11.4 & 16.8% of elderly hospital admissions* (Arch Intern Med 1990)

• Risk factors* - poor recall of drug regimen, seeing several doctors, female gender, medium income, polypharmacy, opinion that drugs are expensive

ADRs in the elderly – contributory factor 7ADRs in the elderly – contributory factor 7Non-compliance with drug treatment - 2

Over-use of medications

• During self-treatment of an acute illness in the mistaken belief that a greater dose will speed up their recovery, e.g. COPD exacerbation

• Unintentional overuse because of forgetfulness or confusion

• Deliberate overdose

ADRs in the elderly – contributory factor 7ADRs in the elderly – contributory factor 7Non-compliance with drug treatment - 3

Under-use of medications

• Forget to take a drug, e.g. in polypharmacy

• Mistaken belief that the drug is unnecessary

• Mistaken belief that the drug can be stopped or can now be taken prn since patients feel better

• Previous experience or occurrence of ADRs

• Cannot afford to pay or difficulty in opening the containers

ADRs in the elderly – contributory factor 7ADRs in the elderly – contributory factor 7Non-compliance with drug treatment - 4

Over-use or under-use of medications

• Frequent changes in the drug regimen

• Inaccurately-labelled containers

• Lack of supervision – the role of caregivers

ADRs in the elderly – contributory factor 7ADRs in the elderly – contributory factor 7Risk factors for non-compliance with drug treatment

• Compliance with drug regimens in the elderly is dependent on knowledge of drug usage

• Non-compliance with the number of drugs

• Dosage errors 15-fold when the number of drugs is increased from 1 to 4

• Compliance from 84% for once or twice daily dosing to 59% for 3 or more doses daily

• The correct knowledge of drug from 75% to 40% when the number of drug from 1 to 4

ADRs in the elderly – contributory factor 7ADRs in the elderly – contributory factor 7Non-compliance with drug treatment - 5

Techniques to improve medication compliance

• Drug regimen

• Patient instruction and counselling

• Written instructions

• Containers

• Labelling

• Memory aids, e.g. the use of calendar packs

• Long-term supervision, review, communication

ADRs in the elderly – contributory factor 8ADRs in the elderly – contributory factor 8Inappropriate prescribingnappropriate prescribing

Prescribing of drugs that are

• Contraindicated

• Potentially interacting with other drugs

• Previously causing ADRs

• Unnecessary

The frequency of ADRs can be by as much as 50% if inappropriate drugs are not prescribed and drugs are not repeated unnecessarily

Examples of drugs posing special risks in elderlyExamples of drugs posing special risks in elderlyCardiovascular and antihypertensive drugs

Thiazides

• Hypokalaemia, hyponatraemia (delirium), gout and impaired glucose tolerance

• Higher risk of hyponatraemia if a potassium-sparing diuretic is also used

• Use low dose (e.g. hydrochlorothiazide 12.5 mg daily, bendrofluazide 2.5 mg daily)

Examples of drugs posing special risks in elderlyExamples of drugs posing special risks in elderlyWarfarin therapy – some suggestions

• Determine the risk-benefit and target range of INR

• Educate the patient with regular review

• Avoid interacting drugs (e.g. NSAIDs), herbs and large variations in dietary vitamin K intake (which can cause large fluctuations in INR)

• Be aware - poor vitamin K intake especially among institutionalised elderly resulting in sensitivity to warfarin (Tse SLS et al. Asia Pacific J Clin Nutr 2002; 11: 62-5) and other patient factors (e.g. disease states) causing unstable control (Chan TYK. HK Pract 1999; 21: 11-6)

Drugs posing special risks in the elderlyDrugs posing special risks in the elderlyTheophylline (elderly may take extra doses)

• Consider the risk-benefit, but its use has much

• ADRs (e.g. nausea and vomiting) and major toxic effects (cardiac arrhythmias and seizure) seen more frequently in the elderly

dose (hepatic clearance 15-30% because of cytochrome P450 activity), especially in the presence of heart failure or liver dysfunction

• Drug interactions, e.g. quinolones, macrolides

• Monitor blood levels if necessary

Examples of drugs posing special risks in elderlyExamples of drugs posing special risks in elderlyLong-acting sulphonylureas

• Prolonged severe hypoglycaemia due to prolonged half-life of the parent drug (chlorpropamide) or its metabolite (glibenclamide), particularly in the presence of renal failure

• Use with caution, always consider metformin as an alternative

• Avoid long-acting sulphonylureas in elderly patients

Towards rational pharmacotherapy

To promote rational use of medicines:

• Continuing medical education

• Drug information

• Producing, implementing evidence-based clinical guidelines

• Individual or practice-based feedbacks

• Family physicians as a target group

• National or multi-national programmes

Principles of prescribingPrinciples of prescribingChecklist for clinicians - 1

• Is drug therapy required?

• If drug treatment is necessary, which drug is appropriate?

• Is the patient being asked to take more drugs than are tolerable or manageable?

• Which type of preparation should be used?

• Should the standard dosage or dosage schedule be modified?

Principles of prescribingPrinciples of prescribingChecklist for clinicians - 2

• Which ADRs are likely to occur and which drugs should be avoided if possible?

• Should the drug be specially packaged and labelled?

• Can the patient living at home manage self medication?

• Is there is need for continued medication?

Indicators to measure irrational drug useWHO/International Network for the Rational Use of Drugs (1)

Prescribing indicators:

• Average number of drugs per encounter (<2)

• Percentage of drugs prescribed by generic name (close to 100%)

• Percentage of encounters with an antibiotic prescribed (<30%)

• Percentage of encounters with an injection prescribed (<10%)

• Percentage of drugs prescribed from EDL or formulary (close to 100%)

Indicators to measure irrational drug useWHO/International Network for the Rational Use of Drugs (2)

Patient care indicators:• Average consultation time• Average dispensing time• Percentage of drugs actually dispensed (100%)• Percentage of drugs adequately labelled (100%)• Patients’ knowledge of correct dosage (100%)

Facility indicators:• Availability of copy of WHO’s Essential Drug

List (EDL) or formulary (100%)• Availability of key drugs (100%)

To measure appropriateness of prescribingMedication appropriateness index (1)

• Is there an indication for the drug?*• Is the medication effective for the condition?*• Is the dosage correct?‡• Are the directions correct? ‡• Are the directions practical? ‡• Are there clinically significant drug–drug

interactions?‡

Weighting of *3 and ‡2 on a 3-point scale

Question 2 should be given more weighting

To measure appropriateness of prescribingMedication appropriateness index (2)

• Are there clinically significant drug–disease interactions?*

• Is there unnecessary duplication with other drugs?*

• Is the duration of therapy acceptable?*

• Is the drug the least expensive alternative compared to others of equal utility?*

Weighting of *1 on a 3-point scale

To measure appropriateness of prescribingOther criteria commonly used

• Drug-drug interactions

• Drug duplications (drugs in the same

class)

• Drug-disease interactions