adverse drug reaction monitoring and reporting

ADVERSE DRUG REACTION MONITORING AND REPORTING

THUSHARA C1ST YEAR MPHARMGRACE COLLEGE OF PHARMACY

Any response to a drug which is noxious andunintended, and which occurs at dosesnormally used in man for prophylaxis,diagnosis, or therapy of disease, or for themodification of physiological function

DEFINITION

Classification of ADRs Type A (Augmented) Type B (Bizarre) Type C (Chemical) Type D (Delayed) Type E (Exit/End of treatment) Type F (Familial) Type G (Genotoxicity) Type H (Hypersensitivity) Type U (Un classified)

• Reactions which can be predicted from the known pharmacology of the drug

• Dose dependent, • Can be alleviated by a dose reduction

E.g. • Anticoagulants Bleeding, • Beta blockers Bradycardia, • Nitrates Headache,• Prazosin Postural hypotension.

Type A (Augmented) reactionsTYPE A (AUGMENTED)

• Cannot be predicted from the pharmacology of the drug

• Not dose dependent, • Host dependent factors important in

predisposition

E.g. • Penicillin Anaphylaxis,• Anticonvulsant Hypersensitivity

TYPE B (BIZZARE) REACTIONS

• Biological characteristics can be predicted from the chemical structure of the drug/metabolite

E.g.• Paracetamol Hepatotoxicity

TYPE C (CHEMICAL) REACTIONSTYPE C (CHEMICAL REACTIONS

TYPE D (DELAYED) REACTIONS

• Occur after many years of treatment. • Can be due to accumulation.

E.g. • Chemotherapy Secondary tumours• Phenytoin during pregnancy Teratogenic

effects• Antipsychotics Tardive dyskinesia• Analgesics Nephropathy

TYPE D (DELAYED) REACTIONS

TYPE E (END OF TREATMENT) REACTIONS

• Occur on withdrawal especially when drug is stopped abruptly

E.g. • Phenytoin withdrawal Seizures, • Steroid withdrawal Adrenocortical insufficiency.

TYPE D (END OF TREATMENT ) REACTIONS

PREDISPOSING FACTORS

POLY PHARMACY :

Patients on multiple drug therapy are more prone to develop an ADR

Alteration of drug effect through interaction mechanism or by synergism

Risk increases with increase in the no: of drugs administered

Increased risk due to multiple drugs use for their diseses

Impaired hepatic and renal status are also at high risk of developing an ADR

Patient with decreased renal function treated with aminoglycosides increased risk of nephrotoxicity

MULTIPLE AND INTERCURRENT DISEASES

AGE Elderly and pediatric patients are more

vulnerable to ADRs In elderly patients physiological changes Eg: nitrate or ACE inhibitor induce postural

hypotension In neonates drug handling capacity differ

compared to adults Eg: grey baby syndrome with

chloramphenicol

DRUG CHARACTERISTICS:

Some drugs are highly toxic in nature Eg: cytotoxic drugs result in nausea and

vomiting Narrow therapeutic range drugs like

digoxin and gentamicin slight increase in concentration may result in toxicity

GENDER

Womens are more susceptible to ADRs than males,

reasons are physiological, pharmacokinetic, pharmacodynamic and hormonal.

Eg: chloramphenicol induced aplastic anaemia and phenylbutazone induced agranulocytosis are twice and thrice as common in women as in man,respectivley

RACE AND GENETIC FACTORS

ADRs are more common in genetically predispose individuals

Eg : G6PD deficient patient high risk of devoleping heamolysis due to primaquine

DETECTION OF ADRS

1. pre- marketing studies2. Post –marketing surveillance3. Under reporting4. Communicating ADRs

Identifying adverse drug reaction (ADR). Assessing causality between drug and suspected reaction by using various

algorithms. Documentation of ADR in patient’s

medical records. Reporting serious ADRs to

pharmacovigilance centers /ADR regulating authorities

STEPS INVOLVE ADR MONITORING

During the development of new medicines, their safety is tested in animal models.

Specific animal studies for carcinogenicity, teratogenicity and mutagenicity are also available

Clinical trials are carried out in 3 different phases prior to the submission of a marketing authorization application

Clinical trials normally identifies ADRs of frequency greater that .5-1.0%

PREMARKETING STUDIES

Pharmavigilance methodologies are used for detection of risk and for the collection of risk information

Powerful and cost effective system for the identification of unknown drug-related risk is spontaneous adverse drug reactions reporting

Health care practitioner should see it as a part of professional duty report ADR result in a patient under his care

Concerned identifying product defect, intoxicants and abuse and unexpected lack of therapeutic effect

POST MARKETING SURVEILLANCE

Two epidemiological methods are most commonly used are

1. Cohort studies2. Control studies

Cohort studies: Patient exposed to a particular drug are followed up actively and systematically and ADR frequencies are compared to an unexposed control population

control studies : Individuals affected by the adverse event

being studied are identified . Each case is matched with several disease – free control patients randomly recruited from the study base.

Both cases and controls are investigated their exposure to possible causative agents prior to occurrence of the event.

The odd ratio calculated on the basis of exposure data

The health care professionals should be very vigilant in detecting ADRs.

ADR may be detected during ward rounds with medical team

ADRs detected during review of patient chart , patient counseling, medication history review, communicating with other health professionals

ROLE OF HEALTHCARE PROFESSIONALS

To assist ADR health care professionals should closely monitor patients who are at high risk include

1. Patients with renal or hepatic impairment

2. Patients taking drugs which have potential to cause ADR . Eg: DIGITOXIN

3. Patient who have had previous allergic reactions

4. Patient taking multiple drugs5. Pregnant and breast feeding women

First step in the detection of ADRs is collection of data.

Data collected includes ,1. patients demographic information2. Presenting complaints3. Past medication history4. Drug therapy details including over the

counter, current medications , medication on admission

5. Lab data such as hematological, liver and renal function test.

The information can be obtained from the following sources

1. Patient’s case note and treatment chart2. Patient interview3. Laboratory data sources4. Communication with healthcare

professionals

Under reporting

Under reporting varies with no: of factors1. Reporting higher for new drugs than for old2. Serious reactions are reported to a higher

degree3. Type B reactions are reported more

commonly than their share of events in practice

4. Reporting is affected by promotional claims of the drug sponsor.

5. Reporting is affected by general publicity around the ADR reporting scheme.

The reasons more often by health professionals for not reporting are:

1. Lack of time2. Lack of knowledge on what, how or where to

report3. The drug-reaction association is uncertain4. The reaction is already well known5. Guilt or fear of litigation6. Belief that all registered medicines are safe7. Non-availability of reporting forms

Activities that may increase the reporting rate include

1. Ease of reporting, improve the design of reporting form, using online reporting

2. Providing feedback to clinicians in the form of articles in journals, ADR bulletins, news letters

3. Participate in pre and post graduate education programmes

4. Collaboration with local Drug and Therapeutics committees

5. Integrating pharmacovigilance in public healthcare programmes

Knowledge about rational and safe use of medicines needs to be provided,

1. During basic training of health professionals2. Through continuous education programmes

to health professionals.3. By specially designated drug information

centers.4. Through packaged inserts and patient

counseling

COMMUNICATING ADRs

REFERENCE

Text book of clinical pharmacy practice – G Parthasarathy . Page no: 105-118