BY: Ahmed Nouri

Clinical Pharmacist, internal medicine and cardiology

Pharmacovigilance

OutlinesWhat is Pharmacovigilance?

Drug Related Problems and ADRs

Why do we need Pharmacovigilance?

The concept of Pharmacovigilance system

Pharmacovigilance in KSA

What is Pharmacovigilance?Pharmakon (Greek) – Medicine Vigilare (Latin) – To keep watch

The science and activities relating to the detection, assessment, andprevention of adverse drug reactions and other drug relatedproblems in humansa type of continual monitoring of unwanted effects and safetyrelated to drugs post marketing.The Importance of Pharmacovigilance, World Health Organization 2002

Aims of Pharmacovigilance• Improve patient safety in relation to medications use.

• Encouraging the safe, rational and cost-effective use of drugs

• Detection of drug related problems at early stages.

• Promotion of understanding and education toward drug safety.

Pharmacovigilance

Safety Drug Related Problems

Drug Related Problems

• An event or circumstance involving drug therapy thatactually or potentially interferes with desired healthoutcomes.

• In 1990, classified the DTPs into different categoriesaccording to: indication, effectiveness, safety, compliance.

Introduction to Health Care Delivery: A Primer for Pharmacists Strand et al1990

Drug Related Problems1. Abuse/Misuse of medications

A. Unnecessary drug therapy.Patient taking unneeded medications for his condition.

B. Wrong drug. Patient taking medication that does not treat the patient's condition.

C. Additional drug therapy needed.Patient needs more medication to treat his condition

D. DosingSub-therapeutic dose , over-dose , dosage adjustment

Drug Related Problems cont.

2. Inappropriate adherence or compliance.

3. Medication ErrorsManufacturing or compounding, prescribing, transcribing, dispensing, or drug administration.

4. Lack of efficacy

5. Adverse reactions.

ADR vs AE vs SE

• Adverse eventHarmful and undesirable effect to patients with nodirect causal relationship which may be related tomedications (by medication error, incorrect dosing oran allergic reaction) or may result from otherinterventions such as surgery or procedure.

ADR vs AE vs SE

• Adverse drug reactionAny noxious and un-intended unexpected response to adrug occurring with a direct causal relationshipbetween the event and the drug.

ADR vs AE vs SE

• Side effectImprecise term usually used to describe drug’sunintended and expected effects within thetherapeutic range related to the pharmacologicalproperties.e.g. antihistamines producing sedation

Side Effect Adverse Effect

can be both therapeutic or harmful. Harmful and undesirable.

Expected usually Not expected.

Do NOT hinder the main effect of the drug.

can hinder the treatment and lead to more complications

mild and self-resolving more severe and life threatening

CLASSIFICATION OF ADRS (RAWLIN AND THOMPSON CLASSIFICATION)

Type A Augmented Dose related – expected pharmacological effects e.g. respiratory depression with opioids and bleeding with warfarin

Type B Bizarre Non dose related – more serious – non expectede.g. anaphylaxis with beta-lactam antibiotics

Type C Continuing Dose and time related – related to cumulative drug usee.g. osteonecrosis of the jaw with bisphosphonates

Type D Delayed After the use of a medicine e.g. Teratogenicity

Type E End of use Due to withdrawale.g. Addisonian crisi after steroid withdrawal

Type F Failure Failure of therapy

Adverse Events

Medications Errors

Adverse drug reactions

Medication errors that cause events that are not ADRs

Medication errors that do not cause adverse events

ADRs from medication

Errors

Why do we need Pharmacovigilance?

Historical Background: Thalidomide Disaster• 1956, Thalidomide was launched to the market.

• Prevention of nausea in pregnancy, hypnotic, morning sickness

• 1960, Reports of fetal abnormalities (>20,000 cases )ᴥ Severe birth defects in children of women who had been

prescribed this medicine during pregnancy. Phocomelia.

Phocomelia

Results of the tragedyChange in drug regulations

• The disaster made many countries to introduce tougher rules for the testing and licensing of drugs

• By 1965, thalidomide had been removed from the market.

1. Insufficient safety evidence from clinical trials

2. Protect patients from avoidable harm

• Studies found that of all ADRs, 70% are preventable

• Patients experienced ADRs (19%)(59%) were avoidable

3. To reduce healthcare expenses

• Costs related to the ADRs exceeded the cost of the medications themselves in some countries.

• Patients with ADRs were hospitalized for an average 8 – 12 days longer than other patients.

• Permanent disability may occur in 9.7% of patients with ADRs.

• Cost due to ADRs in EU: € 79 billions/yearRef: Press Release from Brussels, 10 Dec 2008.

The Concept of Pharmacovigilance

System

1. Detection

• New drugs: report ALL suspected reactions including minor ones• Well known drugs: report all serious, unexpected, unusual reactions.• ADRs with generics that are not experienced with innovator products• All suspected drug-drug, drug-food interactions• ADRs associated with drug withdrawals• ADRs due to medication errors• ADRs due to lack of efficacy

2. Reporting

Patients Healthcare Professionals

Pharmaceutical industries

Regulatory Authorities (SFDA)

2. Reporting

A. Small scale • any suspected ADR, DTP shall be reported.• ADR reporting form (SSH-2056) in Saad Specialist Hospital

B. Large scalePharmaceutical companies play an important role in gathering ADR reports on their own products.

3. Investigations• Proper History is required

• Establishing time relationship : Some response are quick / delayed.

• Thorough physical examination with appropriate laboratory investigations.

• Search literature for medicine suspected causing the ADR

4. Actions

• Setting guidelines

• Package inserts

• Warnings

• Drug withdrawal from market

Drug withdrawal from marketDrug Year ReasonLumiracoxib 2008 HepatotoxicityAprotinin 2008 Kidney and cardiovascular toxicityTegaserod 2007 Cardiovascular ischemic eventsXimelagatran 2006 HepatotoxicityValdecoxib 2005 Dermatology adverse eventsPemoline 2005 HepatotoxicityRofecoxib 2004 Thrombotic cardiovascular eventsLevomethadyl 2003 Fatal ArrhytmiaRapacuronium 2001 Risk of fatal bronchospasmCerivastatin 2001 RhabdomyolosisTrovafloxacin 2001 HepatotoxicityAmineptine 2000 Hepatotoxicity, dermatological side effects, abuse potentialCisapride 2000 Cardiac arrhythmiasTroglitazone 2000 Hepatotoxicity

Regulatory Authorities

WHO program for international drug monitoring

• 1968, after the thalidomide disaster, the WHO set up its International Drug Monitoring Program

• 1978 , Uppsala Monitoring Centre (UMC) in Sweden responsible

for the collection of data about ADRs from around the world• Members submit reports of adverse reactions associated

with medicinal products to the WHO global database, VigiBase

124 countries have joined the WHO Program for International Drug Monitoring(May 2016)

Yellow card scheme• The main ADR reporting scheme in the UK collecting information on

suspected adverse drug reactions (ADRs).

• Introduced in 1964 after the thalidomide tragedy.

• It receives more than 20,000 reports of possible side effects each year.

• In July 2015 a Yellow Card smartphone app was launched for iOS and Android, allowing patients and healthcare workers to report adverse reactions to medications.

Sentinel Initiative

• In May 2008, the U.S. Department of Health and Human Services (HHS) and the U.S. Food and Drug Administration (FDA) announced the launch of FDA’s Sentinel Initiative.

• A long-term program designed to build and implement a national electronic system for monitoring the safety of FDA-approved drugs and other medical products.

Pharmacovigilance in KSA

Saudi Vigilance

• Saudi Food & Drug Authority (SFDA) established National Pharmacoviglance Center (NPC)

• (NPC) was announced to be functioning in March 2009.

• Contribute in protection of public health by:- Monitoring of the safety and quality of medicines - Ensure healthcare professionals and patients have accessto up to date safety information about medicines

UMC membership

Reports facts

Total number of reports received 1296 100%

ADRs 1126 87%

Herbals 17 1%

Cosmetics 14 1%

Medication Errors 39 3%

Product Quality 100 8%

Saudi Vigilance, 2014

• “Dying from a disease is sometimes unavoidable; dying from a medicine is unacceptable.” Lepakhin V. Geneva 2005

• “First, Do no harm” Hippocrates (460 –377 B.C.)

• PV improves patient care and drug safety.

• If you suspect an ADR..Do not assume someone else will report it!

unacceptable

Thank You .. Questions?

Ahmed Nouri