BY

K. TEJA KUMAR REDDY13GD1R0023

IV B-PHARMACY

PHARMACOVIGILIANCE

CHIKUR BALAJI COLLEGE OF PHARMACY

.

DEFINATION:

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

PHARMACOVIGILANCE IN INDIATests in animals are insufficiently predictive of human safetyPatients in clinical trials are selected and limited in number, the conditions of use differ from those in clinical practice and the duration of trials is limited.Information about rare but serious adverse reactions, chronic toxicity, and use in special groups (such as children, the elderly or pregnant women) or drug interactions is often incomplete or not available

ORIGINS OF PHARMACOVIGILANCE• The history of pharmacovigilance goes back more than 40 years. In 1965 the eighteenth World Health Assembly. In 1966, 1967 and 1970 the International Drug Monitoring Programme came into being.• In 2005, 78 member countries are participating in this Programme and the last decade has seen the participation of numerous developing countries. •The programme functions on the basis of national pharmacovigilance centres coordinated by the WHO Programme for International Drug Monitoring, which consists of the WHO Collaborating Centre for International Drug Monitoring, Uppsala and the Pharmacovigilance Department of WHO, Geneva. Recently, the concerns of pharmacovigilance have been widened to include herbal, traditional and complementary medicines, blood products, biologicals, medical devices and vaccines

Many other issues are also of relevance to the science of pharmacovigilance.• These include substandard medicines, medication errors, lack of efficacy, use of medicines for indications that are not approved and for which there is inadequate scientific basis, case reports of acute and chronic poisoning, assessment of medicine-related mortality, abuse and misuse of medicines, and adverse interactions medicines with chemicals, other medicines and foods and drinks.

• CURRENT PRACTICE IN STATE AND CENTRAL

The success or failure of any pharmacovigilance activity depends on the reporting of suspected adverse reactionsSpontaneous reporting The definition of spontaneous reporting is as follows: “A system whereby case reports of adverse drug events are voluntarily submitted by health professionals and pharmaceutical companies to the national pharmacovigilance centre.

•The success or failure of any pharmacovigilance activity depends on the reporting of suspected adverse reactions. •To date, the mainstay of pharmacovigilance has been spontaneous reporting by health professionals. To detect the full spectrum of complications from pharmaceutical treatment and to gain a representative picture, all sectors of the health-care system need to be involved. •This includes public and private hospitals, general practice, pharmacies, nursing homes, retail dispensaries and providers of traditional medicine.• Wherever medicines are being used, there should be a readiness to observe and report unwanted and unexpected medical events. Reports made by a health professional are an interpretation of information originally provided by a patient who has experienced the actual benefit or harm of a medicine taken .

• It may also be the result of a direct observation of the effect of a medicine. Patients who suspect they have been affected by a reaction to a medicine are normally encouraged to inform their health professionals to enable them to report to the pharmacovigilance centre.

• In a few countries the national reporting system provides some opportunity for patient reporting. This is of particular value where there are disease specific control programmes in operationOther methods of collecting safety dataThere are various other pharmacoepidemiological methods of collecting safety information. A number of countries have implemented active surveillance systems to complement spontaneous reporting. Examples of such systems are: — prescription event monitoring (PEM) in New Zealand and the United Kingdom; — record linkage; and — case-control studies.

1. Early detection of hither to unknown adverse reactions and

interactions 2. Detection of increases in frequency of (known) adverse

reactions 3. Identification of risk factors and possible mechanisms

underlying adverse reactions 4. Estimation of quantitative aspects of benefit/risk analysis

and dissemination of information needed to improve drug prescribing and regulation.

AIMS OF PHARMACOVIGILANCE

National pharmacovigilance centres: National pharmacovigilance centres are responsible for: — promoting the reporting of adverse reactions; — collecting case reports of adverse reactions; — clinically evaluating case reports; — collating, analysing and evaluating patterns of adverse reactions; — distinguishing signals of adverse reactions from “noise”; — recommending or taking regulatory action in response to findings supported by good evidence; — initiating studies to investigate significant suspect reactions; — alerting prescribers, manufacturers and the public to new risks of adverse reactions; and — sharing their reports with the WHO Programme for International Drug Monitoring.

Pharmacovigilance is the pharmacological science relating to the

detection, assessment, understanding and prevention of adverse effects, particularly long term and short term side effects of medicines.

Pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, biologicals, herbalism and traditional medicines with a view to:

Identifying new information about hazards associated with medicines

Preventing harm to the patients. The Pharmacovigilance effort in the India is coordinated by The

Indian Pharmacopoeia Commission and conducted by the Central Drugs Standard Control Organization (CDSCO).

CONCEPTS AND DEFINITIONS PHARMACOVIGILANCE

An 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 modification of physiological function.

The old term "side effect" has been used in various ways in the past, usually to describe negative (unfavourable) effects, but also positive (favourable) effects.

It is recommended that this term no longer be used and particularly should not be regarded as synonymous with adverse event or adverse reaction.

CLASSIFICATIONType A effects: Augmented pharmacologic effects - dose dependent

and predictable are those which are due to pharmacological effects

ADVERSE DRUG REACTION (ADR)

Chronic effects refer to situations where the use of a

medicine, often for unknown reasons, increases the frequency of a "spontaneous" disease.

Type C effects may be both serious and common (and include malignant tumours)

Type C effects may be coincidental and often concern long term effects; there is often no suggestive time relationship and the connection may be very difficult to prove.

Type C effects

Type B effects :Bizarre effects (or idiosyncratic) - dose independent

and unpredictable (Patient reactions) characteristically occur in only a minority of patients and display little or no dose relationship.

They are generally rare and unpredictable, and may be serious and are notoriously difficult to study.

Type B effects are either immunological or nonimmunological and occur only in patients, with - often unknown - predisposing conditions.

Type A effects tend to be fairly common, dose related (i.e. more frequent or severe with higher doses) and may often be avoided by using doses which are appropriate to the individual patient. Such effects can usually be reproduced and studied experimentally and are often already identified before marketing.

Delayed effects (dose independent) Carcinogenicity (e.g., immunosuppressants) Teratogenicity (e.g., fetal hydantoin syndrome) Type E effects End-of-treatment effectsType F effectsFailure of therapy

Type D effects

INDIVIDUAL REPORTING: Doctors are the major source of reports. Those whose practice is primarily outside hospitals tend to care

for patients for prolonged periods of time and may therefore also see the occurrence of slowly developing or delayed reactions.

Since most severe reactions are seen in hospitals, physicians who are hospital-based are often able to ascertain previous drug administration, link it to the reaction, and submit a report.

The physician, during an outpatient or inpatient examination, may decide that the patient has a recognizable syndrome of signs, symptoms, and/or laboratory findings and that this syndrome may be associated with a previously administered drug.

SOURCES OF REPORT

COMPREHENSIVE MONITORING: Comprehensive monitoring is typically performed in a hospital setting

and the input consists of abstracts of patient identification, drug administration, and patient reactions.

Specialized methods are used to ensure that this information is complete, and case reports or tabulated summary data can be supplied to the national centre.

POPULATION MONITORING : In population monitoring the records of hospital or clinic patients, or

of the entire population of a district, may be employed. Such monitoring could be effective when a large stable population is

surveyed in an organized medical care system.· As rapid advances are being made in the electronic processing of

patient documentation and records, there may be unusual opportunities to incorporate a drug monitoring element in these systems.

He / She then report this information to the centre.

INDIVIDUAL CASE SAFETY REPORT (ICSR): A document providing the most complete information related to an

individual case at a certain point of time. An individual case is the information provided by a primary

reporter to describe suspected adverse reaction(s) related to the administration of one or more medicinal products to an individual patient at a particular point of time.

It is complex and expensive, however, and the patient population may not be large enough for the detection of rare (1 in 10 000-50 000) reactions. This system would automatically record drug use and patient syndromes or events, permitting searches for associations between the two. The results of such searches may be reported to the national centre.

Spontaneous reporting is a system whereby case reports of adverse

drug events are voluntarily submitted by health professionals, pharmaceutical companies or consumers to the national pharmacovigilance centre

It is basically the reporting of a suspected adverse reaction on the initiative of the health professional who becomes aware of the problem, or on the patient’s initiative. These reports can be communicated by any means, but in countries with a well-developed pharmacovigilance system they are most often reported on the country-specific reporting card.

The key feature is that reports are initiated by the health professional (or patient) and not solicited systematically. The type of reporting described in this document so far should be considered spontaneous. However, in PHPs, reporting should be more focused and intensive.

Such reporting is sometimes referred to as intensified spontaneous reporting, or ideally, prospective

SPONTANEOUS REPORTING

As well as producing data on rates, cohort event monitoring is

particularly effective at identifying previously unrecognized and unsuspected adverse reactions and defining the associated risk factors.

A cohort is built up of all patients receiving the medicine together with demographic data. This requires a record of patients to whom the medicine is administered.

The means of recording this information will be best established when planning the PHP and may vary depending on the country the programme and the medicine being monitored.

Normally a cohort of 10 ,000 patients is sufficient to provide adequate statistical power, but larger numbers may be needed to enable adequate study of particular subgroups of interest. This method has been described as “prescription event monitoring” (PEM) .The term “PEM” is inappropriate for use in most PHPs and this method is better referred to as “cohort event monitoring”.

COHORT EVENT MONITORING

It was reported that worldwide, more than 50% of all

medicines are prescribed, dispensed, or sold inappropriately, while 50% of patients fail to take them correctly. Moreover, about one-third of the world’s population lacks access to essential medicines.

Overuse of drugs and injections: occurs as a consequence of overprescribing as well as overconsumption. It concerns particularly the use and prescription of antibiotics, anti-diarrhoeals, painkillers, injections and cough and cold preparations. Injections have long had a special connotation as particularly powerful and fast acting medicines.

IRRATIONAL DRUG COMBINATIONS

The number of drugs per prescription is often more than needed, with

an average of 2.4 up to ten drugs, while generally one or two drugs would have sufficed.

Multi-drug use is also common among consumers who purchase their drugs (over the counter drugs).

Incorrect drug use:  Involves the wrong drug for a specific condition (e.g. antibiotics or

antidiarrhoeals for childhood diarrhoea), drugs of doubtful efficacy (e.g. antimotility agents for diarrhoea), or use of drugs in the wrong dosage (which is often the case with antibiotics, ORS and antimalarials).

Incorrect drug use occurs in the sense of incorrect prescribing as well as inappropriate use by consumer

Multi-drug use or polypharmacy:

 Lack of information: Unlike many developed countries we don’t have regular facilities, which provide us with up to date, unbiased information on the currently used drugs. The majority of our practitioners rely on medical representatives. There are differences between pharmaceutical concern & the drug regulatory authorities in the interpretation of the data related to in

. Faulty & inadequate training & education of medical graduates: Lack of proper clinical training regarding writing a prescription during training period, dependency on diagnostic aid, rather than clinical diagnosis, is increasing day by day in doctors.dications & safety of drugs.

REASON FOR IRRATIONAL USE OF DRUGS

Medical practitioners & other health professional giving less time to the patient & not explaining some basic information about the use of drugs

 Lack of diagnostic facilities/Uncertainty of diagnosis: Correct diagnosis is an important step toward rational drug therapy. Doctors posted in remote areas have to face a lot of difficulty in reaching to a precise diagnosis due to non availability of diagnostic facilities. This promotes poly-pharmacy.

Demand from the patient: To satisfy the patient expectations and demand of quick relief, clinicians prescribe drugs for every single complaint. Also, there is a belief that “every ill has a pill” All these increase the tendency of polypharmacy.

 Poor communication between health professional & patient: 

Some of the public health and economic consequences of irrational use of

drugs are: Adverse, possibly lethal effects, e.g. due to antibiotic misuse or

inappropriate use of drugs in self-medication. 

Limited efficacy, e.g. in the case of under-therapeutic dosage of antibiotics, tuberculosis or leprosy drugs.

Antibiotic resistance, due to widespread overuse of antibiotics, as well as their use in under-therapeutic dosage.

Drug dependence, e.g. due to daily use of painkillers and tranquilizers. Risk of infection (due to improper use of injections): injection-related

disorders are abscesses, polio, hepatitis and AIDS. Waste of resources: Reduced availability of other vital drugs and increased

cost. Irrational drug use and its consequence- the antimicrobial misuse problem:

IMPACT OF IRRATIONAL USE OF DRUGS

The WHO says that antimicrobial resistance is one of the world’s most serious public health problems being faced. A major reason, of the irrational use of medicines according to WHO, worldwide, more than 50% of all medicines are prescribed, dispensed or sold inappropriately and 50% of patients fail to take them correctly. The consequence of this is seen directly with the misuse of antibiotics

1. Enalapril + Losartan =

Some irrational fixed dose drug combinations available in the Indian market

Combining two drugs affecting the same pathway is irrational; it doesn’t add to

2. Domperidone + Rabeprazole; Domperidone= Esomeprazole

Increased incidence of rhabdomyolysis.

3.Simvastatin + Nicotinic acid; Atorvastatin + Nicotinic acid

probability of myopathy is increased

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