Adverse Drug Reaction Monitoring

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Adverse Drug Reaction Monitoring

Anantha Naik Nagappa and Uday Venkat Mateti

Manipal College of Pharmaceutical Sciences, Manipal University, Manipal-576104.

Explain Adverse Drug Reaction?

The patients while using drugs are likely to feel all together uneasy discomfort which is also called as side effects. The side effects which occurs at regular dose affecting the quality of life of a patient is described as ADR. However according to World Healthcare Organization (WHO) adverse drug reaction (ADR) can be defined as "any 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 physiological function."

What are Adverse Drug Events?

The drugs being intensive in physiological/pharmacological actions are capable of causing an injury in some suitable patients in the usual course of treatment and may not happen on all patients like ADRs. Adverse drug events are injuries resulting from the medical management. It can occur in any health care setting, including: inpatient, outpatient and long-term care settings.

What are side effects?

Side effects are due to pharmacological interactions with living system in general. The drugs are usually administered to the whole of the body making pharmacological reactions to happen. Suppose the drug is used to relief headache shall also interact on gastric mucosa to secrete more acid similarly the drug may damage kidney. Unless the drugs are administered in a targeted delivery system, the side effects shall cause pharmacological actions on intended target leading to side effects. Side effects are the unwanted effects of a drug that are extension of pharmacological effects and are seen with the therapeutic dose of the drug.

Explain Pharmacovigilance?

All drugs are capable of producing multiple effects ranging from week to strong, slow to rapid and harmless to toxic effects. The usual course of drug development it is not possible to explore and predict the ill effects of the drugs. It is mandatory to observe the changes the drug can bring on health over a year of usage. In order to keep the observation active and regular the pharmacovigilance was initiated which is looking for strange signals while using drugs in the society. The word "pharmacovigilance" are: pharmakon (Greek for drug) and vigilare (Latin for to keep watch). Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961.

What are aims of Pharmacovigilance program?

The aim of the pharmacovigilance is to gather evidence and establish the sever ADR resulting from using of drugs for example the drug Nimesulide was approved by regulatory agencies as safe medication for use in management of RA and Analgesic. Soon it was realized the patients succumb to heart failures and kidney diseases. The drug was recommended for banning the marketing in India. Similarly several drugs were identified as dangerous in Pharmacovigilance programs leading to banning of harmful drugs. This is essential to upheld and practice patient safety.

Why the number of adverse drug reactions is are increasing day by day?

The ADRs are the signs appearing in the population while using the medicine in the initial stage soon after clinical trials. The marketing rights are given with a condition that the drug is safe and efficacious but when it is tested on large number of population. The ADRs are observed. The pharmacovigilance program has developed a system of reporting and documenting ADR on the level of national and global. It is not true that ADRs are increasing but they are detected due to systematic approach of pharmacovigilance.

Classify adverse drug reactions?

According to Rawlins ADRs can be classified into Type A and Type B. Type A ADRs are dose dependent and predictable from the known pharmacology of the drug. Whereas Type B reactions are not dose dependent and unpredictable. The classification has gradually been extended to Type A-F. Type A: Augmented pharmacologic effects, Type B: Bizarre effects (or idiosyncratic), Type C: Chemical effects, Type D: Delayed effects, Type E: End-of-treatment effects, and Type F: Failure of therapy.

Why adverse drug reactions are needed to be monitored?

The ADRs effect may have a consequence extending to future human generation by changing the genetic properties. The ADRs are of no use for therapeutic purpose. However the ADR monitoring can give an insight into other possible applications and drug development leading to new drug discovery. The off-label use of medicines can be a useful hint for extending the drug use after getting the approval for the off-label use by regulatory authorities.

Who can report the adverse drug reactions?

As per the pharmacovigilance program all Health professionals working in the field of delivering the health care (both conventional and unconventional) like physicians, dentists, nurses, pharmacists, can report suspected adverse drug reactions by letter, phone, fax, e-mail, or by personal contact to any of the five adverse drug reaction monitoring centers located across the country.

Whom to report the adverse drug reactions?

The ADRs are of public interest and there is a system of collection, documenting and reporting. The matters of ADRs are of detrimental for a pharmaceutical industry prospect of marketing. Hence an independent public funded national and international pharmacovigilance centers are established. These centers receive the reports of ADRs in format designed by the pharmacovigilance program.

What are the scales to assess the adverse drug reactions?

The adverse drug reaction scales are to establish a causal relationship between the drug and the adverse event. The Naranjo ADR probability scale, WHO- Uppsala Monitoring Centre causality categories and Severity of reported ADRs by Modified Hartwig and Siegel scale are used to assess the ADRs.

What is the role of Pharmacist in adverse drug reaction monitoring?

The pharmacist being in the field of clinical, community and hospital settings is likely to get to know about an ADR event the pharmacist are also considered as expert professionals who are consulted for drug information about an ADR management. The pharmacist are to participate in ADR reporting as a professional obligation and responsibility in the capacity of stakeholders for patient safety.

How to prevent and manage the adverse drug reactions?

The information of ADR available in data bases should be consulted before initiating a treatment. The best treatment for ADR is to identify the drug causing ADR and removing that drug from patient treatment. This will prevent further aggravation of the ADR related suffering and death event. The specific treatment if any indicated in the data base should be administered by the treatment team.

What is the role of Uppsala Monitoring Centre in adverse drug reactions monitoring?

The Uppsala Monitoring Centre is the global pharmacovigilance center promoted by WHO. The Uppsala Monitoring Centre is the final destination for ADR reports which arrives from different countries and is reviewed for signals of ADRs. Uppsala Centre also conducts training programs and helps the establishment of country, regional and local ADR reporting centers. They also train human resources in the area of software applications for ADR monitoring.

What are the benefits of adverse drug reactions monitoring?

The ADR monitoring is a gate way to identify the risks due to use of drugs and also an opportunity to re-evaluate the risk-benefit analysis serving as updated guidelines for prescription writing. If ADR is sever than there can be a revival of licensing for the drug this becomes as a countonius engagement for the industry who is involved in sale of the drugs. There is a regulatory reform even in India to run, collect and submit periodical reports of pharmacovigilance on selected products in order to continue with licensing of further sale of drug. So many industries are engaged in pharmacovigilance and ADR monitoring of their products.

What are the terminologies used to code the adverse drug reactions?

MedDRA is fully implemented in the WHO global safety database allowing entry and retrieval of information in either MedDRA or WHO- Adverse Reactions Terminology is used to code the ADRs. The structure of MedDRA is System organ class (SOC), High level group term (HLGT), High level term (HLT), Preferred term (PT) and Lowest level term (LLT). SOC is the highest level of the terminology, and distinguished by anatomical or physiological system, etiology, or purpose. HLGT is subordinate to SOC, superordinate descriptor for one or more HLTs. HLT is subordinate to HLGT, superordinate descriptor for one or more PTs. PT is represents a single medical concept. LLT is the lowest level of the terminology, related to a single PT as a synonym, lexical variant, or quasisynonym.

What is the role of post marketing surveillance?

The post marketing surveillance is program run by pharmaceutical marketing division of an industry. The post marketing surveillance along with ADR monitoring, it also engaged in collecting data and information on its effects on combination with other drugs and also the off-label use of medicines in the market. The post marketing surveillance is not a regulatory program and its aim is to identify the trends and market penetration of a drug in the market.

What is off-label prescribing?

The medicines are approved for a therapeutic indication after the company submits the clinical trial data establishing the safety and efficacy of the drug for example the Sildenafil was approved for male erectile dysfunction. During its usage it was found out that it has profound effect on pulmonary hypertension. Hence the doctors experimented themselves on patients to treat pulmonary hypertensive crisis much before it was approved for the use. Hence any use of medicines other than approval when used for any condition is called Off-Label use of that medicine.

What are the causes for not detecting ADR signals in early drug development?

The drug development program begins with preclinical study on animals. The first phase of clinical study is done on healthy voluntaries of a small number. The phase two clinical trials has an actual patients again with limited number of subjects. Phase 3 involves large number of patients. The Phase 4 includes very large number of patient the ADR of the drugs probably goes undetected as number of ADRs appears in 10-12 incidence in a population of 10, 000 or more. Hence the ADRs are identification during clinical trials is not possible.

Are there any ADRs due to Drug-Drug and Drug-Food Interactions?

The drugs are highly potential in interacting with human beings on their own. If two or more drugs are administered together there can be addition or synergism effect but in case action of the drugs are antagonistic in nature, opposing each other action. There is a possibility of reduced efficacy leading to poor safety of the patients. For example administering steroids in infections along with antibiotics. The food may contains various binding agents and chelating agents with may seriously hampered the absorption of the drug its self, for example administration of Azithromycin with food may lead to un controlled bacterial growth as Azithromycin blood concentration as remain below the minimum effective concentration due to poor absorption of the drug.


ASHP Guidelines on Adverse Drug Reaction Monitoring and Reporting.

Rawlins MD. Clinical pharmacology. Adverse reactions to drugs. Br Med J (Clin Res Ed). 1981 Mar 21; 282(6268):974-6.

Rawlins MD, Thompson JW. Pathogenesis of adverse drug reactions. In: Davies DM, ed. Textbook of adverse drug reactions. Oxford: Oxford University Press, 1977: 10

Ronson JK. Drug therapy. In: Haslett C, Chilvers ER, Boon NA, Colledge NR, Hunter JAA, eds. Davidson's principles and practice of medicine 19th ed. Edinburgh: Elsevier Science, 2002: 147-63.

Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 Aug; 30(2):239-45.

The use of the WHO-UMC system for standardized case causality assessment. Accessed from:

Introductory Guide MedDRA Version 14.0. Available from:

About the Author

Anantha Naik Nagappa's picture

I am professor, intrested in developing the community pharmacy services in India, We have an association called ASSOCIATION OF COMMUNITY PHARMACISITS OF iNDIA. CHECK AT for further detials

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