DRUG SAFETY

Nia Kurnia SholihatTunggul Adi PJurusan Farmasi Unsoed

Tujuan pembelajaran Mampu menjelaskan dampak dari Drug

Safety Mampu menjelaskan perbedaan dan

hubungan antara Adverse Event, Adverse Drug Event, Adverse Drug Reaction

Mampu menjelaskan tipe reaksi A dan B Mampu menjelaskan tool untuk

menunjukkan hubungan antara obat dan harm`

DRUGSAFE, EFFECTIVE, and ACCEPTABLE

Importance of drug safety Adverse drug reactions: Account for 5% of all hospital admissions Occur in 10 -20% of hospital inpatients Cause deaths in 0.1% of medical and 0.01% of

surgical inpatients Adversely affect patients' quality of life Cause patients to lose confidence in their doctors Increase costs of patient care Preclude use of drug in most patients, although

they may occur in only a few patients May mimic disease, resulting in unnecessary

investigations and delay in treatment

Australia 10% pasien yang masuk rumah sakit disebabkan masalah yang berkaitan dengan obat

Amerika Serikat 20% pasien masuk ke rumah sakit disebabkan kesalahan penggunaan obat.

Amerika Serikat kesalahan pengobatan pada pasien rawat inap di rumah sakit bertanggungjawab terhadap 44.000 hingga 98.000 kematian tiap tahun, jumlah yang lebih tinggi daripada kematian akibat kecelakaan kendaraan (43.458), kanker payudara (42.297) dan AIDS (16.516)

Dana yang dihabiskan oleh masyarakat Amerika pada tahun 1995 bagi mortalitas dan morbiditas akibat penggunaan obat berkisar 76 milyar US dollar per tahun atau sekitar 684 trilyun rupiah per tahunnya.

THE COST OF DRUG SAFETY

6.7% of hospital patients in the US have serious adverse drug reactions (medication error excluded) (Lazarou J. Pomeranz BH, Corey PN. JAMA 1998;279:1200-5)

The Netherlands Hospitalisations caused by adverse drug reactions (ADR)

16.6% in elderly, 4.1% in younger Cost of ADR prevention related hospital

admissions ranged from $158 million or £110 million $365 million or £256 million.

(Pharm World Sci 2002;24(2): 46-54.)

Cost Avoidance of Adverse Drug Reactions Prevention in Outpatient Pharmacy Department Ramathibodi Hospital, Thailand

The estimated cost avoidance generated during 2013 was 750,286 THB to 1,619,576 THB. (1 THB = 392 IDR)

(Sholihat NK, Chimsawat W, Poncharoensuk P)

Definitions

Patient safety: “freedom from accidental injury; ensuring patient safety involves the establishment of operational systems and processes that minimize the likelihood of errors and maximize the likelihood of intercepting them when they occur”

An adverse drug event (ADE) is “an injury resulting from the use of a drug”.

An adverse drug reaction (ADR) is a “response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function.” (Edwards and Aronson, Lancet, 2000; 356(9237):1255-9) INTRINSIC TOXICITY

A medication error (ME) is defined as “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient or consumer” EXTRINSIC TOXICITY

ADE, ADR, and, ME relationship

ADVERSE DRUG REACTION(INTRINSIC TOXICITY)

Classifications of ADR

ABCDE classification DoTS classification

WHO Classification on type of ADR (ABCDE classification)

Type A reactions (drug actions)

the result of an exaggerated but otherwise usual pharmacological effect of the drug dose-related, predictable, less serious,

common patients receiving more drug than customarily

required, a conventional amount but metabolize or excrete the drug unusually slowly, on an additional drug which interferes with excretion or metabolism, or are overly sensitive to the drug

In principle, these factors all are predictable and thereby potentially preventable

These complications could all be considered medication errors

Different types of adverse events

Type A effects (‘drug actions’):

• due to pharmacological effects,• fairly common, • dose related (i.e. more frequent or severe with high

doses) and may often be avoided by using doses which are appropriate to the individual patient,

• can usually be reproduced and studied experimentally and are often already identified before marketing.

Drug interactions - may be classified as Type A effects, although they are restricted to a defined sub-population of patients, i.e. those taking interacting drugs

Risks Associated With the Use of Drugs

Type B reactions are aberrant effects Uncommon, not related to dose, potentially more

serious, but unpredictable May be due to hypersensitivity reactions or

immunologic reactions, or some other idiosyncratic reaction to the drug, either due to some inherited susceptibility or some other factor

Most difficult to predict Yet, historically have represented the major focus of

commercial and regulatory interest, and thereby the major focus of pharmacoepidemiology studies of adverse drug reactions

Different types of adverse events

Type B effects (‘patient reactions’):

occur in only a minority of predisposed, intolerant patients,

little or no dose relationship,generally rare and unpredictable, sometimes serious,difficult to study

Examples of Type B effects (‘patient reactions’):

Drug intolerance:toxic reactions, not related to overdose or diminished elimination. Some drug intolerances are known to result from genetic variants of drug metabolism, example: liver failure after normal dose of acetaminophen

Drug idiosyncrasy:genetically determined abnormal reaction to the drug that may be related to metabolic or enzyme deficiency. Example: hemolytic anemia in a patient with G6PD deficiency after primaquine therapy

Drug allergy:immunologically meditated reaction that is characterised by specificity, involvement of antibodies or lymphocytes and re-occurence in case of new contact with the drug

Pseudoallergic reactions:the same clinical symptoms as allergic reaction but without immunological specificity, example: anaphylactoid reaction after radiocontrast media

DoTS classification

Dose relatedness Time relatedness Susceptibility

BMJ 2003;327:1222–5

DoTS classification

Causality categories

Other algorithm: Roussel Uclaf Causality Assessment Method (RUCAM)

ADR CAUSALITY ALGORITHM

The burden of ADR

Admission (6.5%)

In patients (14.7%)

Emergency room (2.5%)

Primary care (25%)

MEDICATION ERROR (EXTRINSIC TOXICITY)

Medication Error

> 7000 deaths per year from medication error in the USATo Err is Human: Building a Safer Health System. National Academy Press, 1999

Medication Use Process and ME

Diagnosis Prescribing Dispensing Administration Ingestion Monitoring and

control

Medication errors are mishaps that occur during prescribing, transcribing, dispensing, administering, adherence, or monitoring a drug.

Examples of medication errors include misreading or miswriting a prescription.

Medication errors that are stopped before harm can occur are sometimes called “near misses” or “close calls” or more formally, a potential adverse drug event.

Not all prescribing errors lead to adverse outcomes. Some do not cause harm, while others are caught before harm can occur (“near-misses”)