PHARMACOVIGILANCE

ASHUTOSH MISHRA, M.Pharm, (P’COLOGY)

KSOP

WHAT IS PHARMACOVIGILANCE (PV)

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problems -

Pharmaco - Vigilance

• Pharmaco = medicine• Vigilare = to watch

– alert watchfulness– forbearance of sleep; wakefulness– watchfulness in respect of danger; care;

caution; circumspection– the process of paying close and continuous

attention

Pharmacovigilance Aims

• Early detection of unknown safety problems

• Detection of increases in frequency• Identification of risk factors• Quantifying risks• Preventing patients from being affected

unnecessarily

Objectives of Pharmacovigilance

• To improve patient care and safety• To improve public health and safety• To contribute to the assessment of benefit,

harm, effectiveness and risk of medicines• To promote understanding, education and

clinical training

Scope of Pharmacovigilance• Improve patient care and safety in relation to the use of

medicines, and all medical and paramedical interventions,

• Improve public health and safety in relation to the use of medicines,

• Contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe, rational and more effective (including cost-effective) use, and

• Promote understanding, education and clinical training in pharmacovigilance and its effective communication to the public

• ADVERSE Drug Events- ADE, harm caused by the drug (ADR & overdoses) and harm from the use of the drug (including dose reductions & discontinuations of drug therapy).

• ADVERSE Drug Reactions- A response to drug which is noxious & unintended which occurs at doses at normally used in man for the prophylaxis, diagnosis or therapy of disease. There is causal link between a drug & an adverse drug reaction.

• SIDE Effect- is an expected & known effect of a drug that is not the intended therapeutic outcome.

Adverse Reactions:Possible Causes• INTRENSIC FACTORS OF THE DRUG -P’COLOGICAL -IDIOSYNCRATIC -CARCINOGENICITY, MUTAGENICITY -TERATOGENICITY

• EXTRENSIC FACTORS -ADULTERANTS -CONTAMINATION

• UNDERLYING MEDICAL CONDITIONS• INTERACTION

NEED FOR PVReason 1: • Humanitarian concern –

– Insufficient evidence of safety from clinical trials

– Animal experiments– Phase 1 – 3 studies prior to marketing

authorization

CONT…

Reason 2• Medicines are supposed to save lives

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

• UK It has been suggested that ADRs may cause

5700 deaths per year in UK• UK ADRs were 4th-6th commonest cause of

death in the US in 1994

Reason 3: ADRs are expensive !!

• Cost £446 million per annum

• 6.5% of admissions are due to ADRs• Seven 800-bed hospitals are occupied by

ADR patients

Reason 4:Promoting rational use of medicines and

adherence

Reason 5: Ensuring public confidence

If something can go wrong, it will – Murphy's law

Reason 6: Ethics

To know of something that is harmful to another person who does not know, and not telling, is unethical

WHY PV IS NEEDED

Why Pharmacovigilance?

• Post-marketing Topics Unexpected adverse reactions Interactions Dependence Long-term efficacy, Resistance Risk factors Quality (Counterfeit) Cost assessment

Why Pharmacovigilance?

• Adverse Drug Reactions are the 4th to 6th largest cause of mortality in the US

• The percentage of hospital admissionsdue to drug related events in some countries is

about or more than 10%.

Some Examples

Medicine ADRThalidomide Congenital malformations

Amidopyrine Agranulocytosis

Clioquinol Myeloneuropathy (SMON)

Statins Rhabdomyolyis

Oral Contraceptives Thromboembolism

NEED OF PV IN INDIA

• INDIA RATES BELOW 1% OF PV WHILE WORLD 5% DUE TO IGNORANCE OF SUBJECT AND LACK OF TRAINING

• PROBLAM OF A LARGE POPULATION THAT IS PREDOMINENT RURAL AND EXTENT USE OF TRADITIONAL MEDICINE

• LACK OF PHYCISIAN AND CONSUMER AWAIRNESS PROGRAM

Pharmacovigilance in WHO• Exchange of Information• Policies, guidelines, normative activities• Country support• Collaborations

CURRENT SCENARIO

• Increased awareness and interest amongst doctors and pharmacists to report ADRS as they have seen some benefit in reporting

• GCP training for investigators served to increase

awareness of SAE and ADR reporting amongst health care professionals and the industry

CONT…..

• More hospitals and companies using on-line reporting system – less hassle than submitting hard copy reports

• Increasing involvement by hospital pharmacists in pharmacovigilance – during clinical ward rounds and when counseling patients

Who are the partners?• Government• Industry• Hospitals and academia• Medical and pharmaceutical associations• Poisons information centres• Health professionals• Patients• Consumers• Media• WHO

WHAT TO REPORT?

SERIOUS ADRS• A serious adverse event (experience) or reaction is any untoward

medical occurrence that at any dose:– results in death,– is life-threatening,– requires inpatient hospitalization of prolongation of existing

hospitalization,– is a congenital anomaly/birth defect.NOTE: The term “life-threatening” in the definition of “serious”

refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it was more severe.

WHAT SHOULD BE REPORTED

• New drugs– Report all suspected reactions including minor

ones• For established or well known drugs

– All serious, unexpected, unusual ADRs• Change in frequency of a given reaction• ADRs to generics not seen with innovator

products• ADRs to traditional medicines

WHAT SHOUD BE REPORTED

• All suspected drug-drug, drug-food, drug-food supplement interactions– Statement highlighting marine source of supplements

such as glucosamine so that can be avoided by those with allergy to sea food

• ADRs associated with drug withdrawals• ADRs due to medication errors

– eg vincristine given IT • ADRs due to lack of efficacy or suspected

pharmaceutical defects

INNOVATOR PRODUCTS

– Limited information available at time when drug is first marketed

– Minimal information on use in Asian population, interactions with indigenous medicines

– Conduct intensive monitoring to identify new, unlabeled adverse reactions, monitor for “rare” reactions

– Provide updates to prescribers on new findings, labelling changes, safety issues

NON-PRESCRIPTION MEDICATIONS

• Quality defects can also lead to ADRs e.g. Pan Pharmaceuticals (Australia) case

• Patients can develop ADRs to food supplements, “health products”

• Overuse of supplements• Current issue of dioxin contamination in Cod Liver Oil

preparations resulting in product withdrawals in UK

TRADITIONAL & COMPLEMENTARY MEDICINES• Minimal information available on traditional medicines

– ADRs– Drug interactions– At risk groups e.g. alfalfa and exacerbation of SLE

• Misnomer of “because it is natural, it is safe– Association of Black Cohosh with liver problems

• Health professionals should try to get as much information as possible– Name of product– Indication– Place of purchase (esp for unregistered products)

PREGNANCY– Very little information available on outcome

data for drugs used in pregnancy• Current issue of association between lamotrigine use

and cleft palate syndrome• ACE Inhibitors and congenital anomalies

– Should follow-up cases where drugs are prescribed intentionally or have been used inadvertently to monitor outcome of pregnancy, effect to the foetus/baby

ACTIVE INGREDIENTS WITHDRAWN

– THALIDOMIDE (1961) Congenital limb defects– BENOXAPROFEN (1982) Hepatotoxicity– PHENFORMIN (1982) Lactic acidosis– FENFLURAMINE (1997) Heart-valve abnormalities– ASTEMIZOLE Many drug interactions– PHENYLPROPANOLAMINE(2000) Haemorragic stroke– KAVA KAVA Liver abnormalities– CERIVASTATIN Rhabdomyolysis– CISAPRIDE Cardiac arrythmias– ROFECOXIB (2004) Cardiovascular events– VALDECOXIB (2005) Cardiovascular events,

serious skin reactions– COMFREY, SENECIO Nephrotoxicity – TEGASEROD (2007) Cardiovascular events– CLOBUTINOL (2007) Cardiac arrhythmia

COMMUNICATING THE OUTCOME OF PV

• Product Alerts – National Health Authorities• Media statements - National Health

Authorities/Pharmacovigilance Centres• Newsletters – National Pharmacovigilance Centres

and WHO• Feedback to reporters – National Pharmacovigilance

Centres

SO….WHAT IS OUR ROLE?

• SEND NOT ONLY QUANTITY BUT….

QUALITY REPORTS

HOW?

• Monitor clinical status of patients• Identify the correct ADRs not side effects• Get more information• Investigate at hospital level• Help doctors to fill-up the forms• Keep patient’s record if more information

needed

REFERANCE

• WHO Safety of medicines. A guide to detecting and reporting adverse drug Reaction. Geneva WHO 2002

• DRUG ALERT,volume1, issue 1 nov 2005 regional pv centre (south) JIPMER, Pondicherry INDIA

• http://cdsco.nic.in/pharmacovigilance_intro.htm#Programme Communications

• PROTOCOL FOR NATIONAL PV PROGRAM, CDSCO Ministry of health &family walfare, gov of INDIA 2004