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  • Review
  • Open Access

Adverse drug reactions monitoring: prospects and impending challenges for pharmacovigilance

  • 1Email author,
  • 1,
  • 1,
  • 1 and
  • 1

  • Received: 6 June 2014
  • Accepted: 17 November 2014
  • Published:


Pharmacovigilance plays a consequential role in the surveillance of adverse drug reactions, which is provoked by the drugs used to cure diseases. Adverse drug reactions (ADRs) produce detrimental or undesirable effects to the body after administration of drugs. It has been reported that the number of patients dying because of contrary effects of drugs per year increased upto 2.6-fold. Moreover, rates of hospitalization of patients are increasing owing to adverse effects of drugs. Thus, it becomes challengeable for physician, health care providers, WHO and pharmaceutical industries to resolve the associated problem of ADRs. During the clinical trial of a novel drug, it is prominent to explore the dependability of drug. In this review, we documented the details required to identify the ADRs in patients along with reported banned drugs.


  • Pharmacovigilance
  • Adverse drug reactions
  • Clinical trial


World Health Organization (WHO) defines that adverse drug reactions (ADRs) are noxious and unwanted effects produced by the drug, when it is applied for the ailment of disease or diagnosis (Shukla et al.2012). The most common examples of drugs that produce ADRs include paracetamol and nimesulide (hepatotoxic effects) (Rehan et al.2002).

It is a well-known fact that no drug is completely free from side effects. The European commission proclaimed ADRs (Rishi et al.2012; Rehan et al.2002) till date are referred in Table 1.
Table 1

ADRs report according to European Commission Impact

Patient’s report

Percentage reported

Patients admitted in hospital

0.3% - 5%

Patient’s death reported


Patient’s reported with ADR during their hospital stay

1.9% -6%

Before executing any new drug in the market, its clinical trial and safety database are validated for the safety profile of the drug. In various countries, whether developed or developing, the issue of ADRs is accepted to effortlessly, and thus it becomes a prime duty to develop awareness among patients about ADRs.

When a novel drug’s safety is under process, it is being constantly supervised by pharmacovigilance centres for the identification of adverse effects of the drug, if any (Beard1992; Mishra and Kumar2013). According to WHO, pharmacovigilance is a set of practices aiming at the identification, understanding and assessment of risks associate with drugs. Moreover, they take steps to control the adverse effect of drugs. Pharmacovigilance starts from the pre-marketing of new drugs and continues through the post-marketing of drugs (Lazarou et al.1998).

There are a bunch of examples of drugs, which have been detached as well as outlawed from the European market owing to reported adverse effects of drugs. Rosiglitazone holds the first position in the market; other well-known drugs including terfenadine, cisapride, phenylpropanolamine, rofecoxib, cerivastatin, gatifloxacin, cisapride, sibutramine and tegaserod were withdrawn because of their adverse reactions. For every drug in the market, the adverse events, if any, should be inspected in detail, and the facts should be conveyed to the people or public for elucidation of the information (Hampton2005; Lisa et al.2003; Lazarou et al.1998).

In contemplation to supply the news for effective drug use in population, which includes different groups of patients, such as elderly, children and diseased patients, an adequate information regarding drug’s adverse effects is required, which is achieved by a successful pharmacovigilance programmes run on that drug (Gupta and Udupa2011; Santosh and Tragulpiankit2002).

Pharmacovigilance plays several roles such as recognition, observation, assessment and documentation of drug based problems and understanding the factors producing adverse effects (Ravi Shankar et al.2006; Rohilla et al.2012). Here we tried to summarize about ADRs, and how it can be monitored by pharmacovigilance to minimize the adverse effects of drugs. Hence, this review will provide adverse events about ADRs along with the complete information of medication errors.

Proclamations of adverse effects of drug

The USFDA data disclosed that adverse effect of drugs increased almost two times in the endmost decade. It has been noticed that significant sum of patients were pegged out because of fervent adverse effects of drugs. This report has been authenticated in the 10th issue of the Archives of Internal Medicine (Livio et al.2012; Doheny2009; Aeries1995). The number of reports per annum proliferated upto 2.6-fold from 1998 to 2005. In 1998, the numbers of adverse events proclaimed were 34,966, which increased to 89,842 by 2005.

The number of drugs in the market producing ADRs is documented in Table 2.
Table 2

List of drugs causing ADRs

Marketed drug

Type of dosage form

Patients affected

Side effects



Tablet- film coated and extended release


Constipation, nausea, somnolence, dizziness, pruritis, vomiting, sweating, asthenia, dry mouth, headache



IV , patch


Skin reactions, respiratory depression, mental changes, stroke

(Pasero2005; Mohammed2012) (Peng and Sandler1999, Prommer2009)




Cardiotoxicity, fever, chills, bodyache, flu symptoms, mouth-throat ulcers, cough, sore throat, rapid heart rate, rapid and shallow breathing.

(Cole et al.2009)




Respiratory depression, QT prolongation, lacrimation, chilling, rhinorrhea, tachycardia, cramps, anorexia, nausea, dilated pupils, fluching

(Kung et al.2008) (Minino et al.2002)




Constipation, addiction, asphyxia, respiratory depression, renal failure, slow heartbeat, increase in B.P.

(Haupt and Jeste2006)




dark urine, loss of appetite, jaundice, damage to liver and death, difficulty in breathing, swelling of face and lips

(Huismen et al.2002)


Syringe and subcutaneous injection


Injection site pain, erythema reaction, rheumatoid arthritis, vestibular neuritis

(Orlando and Perkins2002)



1.6- 1.7%

Stroke, heart failure, pneumonia, irregular heartbeat, seizure, white patches and sore in lips



Injectionand vials

0.01- 0.06%

Blurred vision, black stools, painful urination, ulcers, sores, red spots on skin, urticaria

(Orlando and Perkins2002)




Bone pain, serious ventricular arrhythmias, agitation, hallucinations, tremors, increase in muscle tone

(Thisted et al.1986)




Increased arrhythmias, abdominal pain, tenderness, or discomfort, nausea, blood while vomiting, bloody, black, or tarry stools, unexplained weight gain, swelling or water retention, fatigue or lethargy, skin rash, itching, yellowing of skin or eyes, flu-like symptoms, or unusual bruising or bleeding.

(Krumholz et al.2007)



1.2 -2.3%

Fatal bleeding, stroke, heart attack, abdominal pain, crawling, numbness, increase in menstrual flow, vaginal bleeding, paralysis, shortness of breath, diarrhea, skin blisters, hemorrhage, necrosis, purple toe syndrome

(Holbrook et al.2005)




Risk of GI ulcerations, bleeding perforations, coronary artery disorder, cellulitis, angina pectoris, deep thrombo phlebritis, myocardial infarction, pneumonia, unstable angina




37 deaths

Liver damage, loss of appetite, allergic pruritis, muscles and joint pain, tendon problems, tiredness, jaundice

(Gaudreault et al.1982)




Abortion, miscarriage, GI bleeding, multi organ failure, acute pain, haemodynamic instability, oesophageal necrosis, cardiac arrest, resuscitation efforts, birth defects

(Fu et al.1998)




Somnolence, haematuria, urticaria, asthenia, pulmonary embolism, heart failure, bradycardia, tachycardia, cardiac arryhmias, deep vein thrombosis, seizures, orthostatic hypotension, birth defects (phocomelia)

(Ito et al.2010)


Only in old patients injections subcutaneous insulin pump transdermal intranasal

Not available

Hypoglycemia (may result fatal if severe), low BP, irritability, fast heartbeat, convulsions, blurred visions





Excess acid secretion, stomach cramps, haemorrhage, bronchospasm, hepatitis interstitial, nephritis, inflammation of skin, allergic, abnormal liver functioning, clotted organs and tissues


COX 2 inhibitors


3- 3.9%

Myocardial infarction, fatal stroke, death from vascular events, hypertension, congestive heart failure, ulceration, bleeding from stomach, coronary artery blockage

(He et al.2005; Solomon et al.2004)


Tablets– extended release tablets oral suspension

0.65- 1.2%

High BP, angina, paroxysmal supraventicular tachycardia, prolonged QT interval, blood clot in brain, hepatitis, interstitial nephritis, migraine

(Carlo and Francesco1978)


Tablets, cream, ointments, injectable

Severe kidney failure, nerve damage, permanent hearing loss, agitation, stomach pain, blood in urine, chest pain, stroke, coma, hallucinations, mental changes

(Carlo and Francesco1978)



0.001% only on overdose

Slow heartbeat, abnormal heart rhythm, Low blood pressure, Inability to have an erection, hallucinations, involuntary quivering, difficult urination, nervous, confused, heart burn, diarrhea

(Delini et al.2007)


Capsules, tablets, liquids


Severe blistering, peeling and red skin rash, uneven heartbeats, tremors, overactive reflexes, hallucination and seizures

(Michael and Ma2006)



0.5% only on overdose

Neuroleptic malignant syndrome, irregular heartbeats, parkinsonism, tardive dystonia, stroke sometimes, purple patches, mental changes, tightness in chest, shortness of breath, sore throat

(Jankovic and beach1997)




Severe hypotension, bradycardia, pulmonary edema, systole, cardiac arrest, ventricular arrhythmias, respiratory acidosis, dysponea, bronchospasm

(Douketis et al.2007)

Scientific data indicated that different drugs were banned, and some were detached owing to the adverse effects in patients (Tables 3 and4).
Table 3

Records of banned drugs

Marketed drug

Dosage form

Banned date


Death occurred


Terfenadine (Seldane)


February 1998

Irregular heartbeat, stomach pain, light coloured stools, yellowing of eyes or skin, fainting, dizziness, abdominal discomfort, dry skin or itchiness, prolongation of QT interval, headache, benign prostatic hypertrophy, acute hepatitis, cholestatic hepatitis, jaundice, hepatic dysfunction


(Ito et al.2010)

Mibefradil (Posicor)


June 1998

Leg edema, hypertension, chronic angina, rhinitis, leg edema, heart stroke, headache, abdominal pain, light headedness, dyspepsia

123 death in 1 year

(Chyka et al.2007)

Astemizole (Hismanal)

Tablets, capsules

July 1999

Heart problems, death, cardiac arrest, QT prolongation, Torsades de pointes, ventricular arrhythmias, cardiac arrhythmias, bradycardia, hypotension


(Minino et al.2002)

Cisapride (Populsid)

Tablets, oral suspension, capsules, medi-melt tablets, injections

January 2000

Fast heartbeat, convulsions, irregular heartbeat, QT prolongations, torsades de pointes, cardiac arrest, sudden death renal failure, ventricular arrhythmias

80 deaths during clinical trial

(Solomon et al.2004)



November 2007

increased arrhythmias, abdominal pain, tenderness, or discomfort, nausea, blood while vomiting, bloody, black, or tarry stools, unexplained weight gain, swelling or water retention, fatigue or lethargy, skin rash, itching, yellowing of skin or eyes, flu-like symptoms, or unusual bruising or bleeding.


(He et al.2005) (Solomon et al.2004)

Table 4

Records of drugs withdrawn after ADRs observed in patient

Marketed drug

Dosage form

Withdrawn due to

Patient’s effected



Tablets, injectables

Causes hyperglycemia and liver damage


(Carlo and Francesco1978)


Microcapsules, tablets, sustained release tablets

Increased risk of stroke


(Gaudreault et al.1982)

Propoxyphene (Darvon)

Capsule, tablet film coated

Caused fatal heart rhythm abnormalities


(Delini et al.2007)



Increased cardiovascular risk





Causes increased risk of heart attack



Nimesulide (below 13 years age)

Tablets, oral suspension, gel, suppositories

Caused life threatening hepatotoxic effects


(Gaudreault et al.1982)


Tablets, oral suspension, capsules, medi-melt tablets, injections

Risk of cardiac arrhythmias


(Solomon et al.2004)



Risk of teratogenicity


(Ito et al.2010)



Caused allergic reactions and haemolyticanaemia

0.002- 0.04%

(Delini et al.2007)


Tablet- film coated,

Proved to be hepatotoxic


(Gaudreault et al.1982)

Tolrestat (Alredase)

Withdrawn not available

Proved as severe hepatotoxic agent

Not available

(Schonthal et al.2003)

Terfenadine (Seldane)

Tablet withdrawn

Caused cardiac arrhythmias


(Orlando and Perkins2002)

Mibefradil (Posicor)


Reported to cause drug interaction

123 death in 1 year




Hepatotoxic in nature

Not available

(Delini et al.2007)



Interaction with other drugs


(Holbrook et al.2005)



Showed to be hepatotoxic


(Solomon et al.2004)


Tablets, oral suspension, capsules, medi-melt tablets, injections

Caused cardiac arrhythmias

80 deaths during clinical trial

(Solomon et al.2004)


Oral tablets

Liver failure cases reported


(Ito et al.2010)



Caused rhadomyolysis

Not available

(Chyka et al.2007)

Rofecoxib (Vioxx)


Myocardial infarction were reported


(He et al.2005) (Solomon et al.2004)

Valdecoxib (Bextra)


Heart attack and stroke occurred



Tegaserod (Zelnorm)


Cardiovascular ischemic events occurred followed by heart attack and stroke




Tablets, injection

Death occurred

Not available




Cardio toxicity occurred by its use

Not available




Cardiovascular risk increases by its use


(Schonthal et al.2003)

Documentation of ADRs

The pharmacovigilance curriculum conveyed worldwide to motivate that all suspected drug-related adverse events should be outlined. It takes interests on reports of the following:
  1. (A)

    Every adverse effect suspected or occurred by new drugs and drugs of current issue.

  2. (B)

    Documentation of various drugs that caused ADRs, which include death, life-threatening conditions, disability, hospitalization and congenital abnormalities.


The significant adverse reaction of any drug should be notified within seven days. The other facts related to adverse events should be informed within eight days (Bates et al.1995; Classen et al.1997). The ADR form can be collected through any pharmacovigilance centre. The filled ADR form can be submitted to the peripheral pharmacovigilance centre. After reviewing the form, the centre forwards it to the regional centre and after that it is propelled to the zonal centre (Goldman1998; Palaian et al.2006; Ravi Shankar et al.2010). The details are then statistically inspected and forwarded to WHO-Uppsala Monitoring Committee (UMC).

Procedure for reporting ADRs

It is the first duty of any pharmacovigilance centre to report all suspected adverse events of the drug if found. Information regarding ADRs and the type of ADRs that should be reported are tabulated in Table 5.
Table 5

Details required for reporting ADR events

Elements in ADR reporting

Necessary information



What should be reported

Adverse reactions of the drug, suspected drug’s details, patient’s information

Medications overdose, pharmaceutical defect, drug interactions


Who can report

medical practitioners or health care professionals, doctors, nurses, pharmacists, assistants, pharmaceutical technicians, pharmaceutical assistants, clinical officers and other health care providers

Manufacturers, all government and private hospital’s health center

Palaian et al.2006

When it can be reported

Any adverse reactions if noticed should be reported as soon as possible.

Ravi Shankar et al.2010

How to report

Through completely filled yellow card form

Ravi Shankar et al.2010

Where it can be reported

Fully filled completely ADR form should be submitted to pharmacovigilance center

Palaian et al.2006

Monitoring of ADRs

ADR monitoring is spelled out as the practice of continuously monitoring the undesirable effects caused using any drug. Pharmacovigilance plays an imperative impersonation in monitoring ADRs (Hall et al.1995; Hornbuckle et al.1999; Juntti and Neuvoren2002).

It is inherent for pharmaceutical regulators to screen their pharmaceutical products in the market and record if any suspected adverse reactions are identified. ADRs can occur by use of various pharmaceutical products, herbal drugs, cosmetics, medical devices, biological, etc. The introducing of this monitoring procedure intends at warranting that patients receive safe and beneficial medicinal products (Karch and Lasagna1997).

If any of the adverse events are not stated it may result in noxious and serious effects of remedial products. Thus, properly conducting ADR monitoring programmes will help to reduce the harmful effects of therapeutic products (Kessler1993).

Benefits of ADR monitoring

An ADR monitoring and reporting programme can furnish following benefits:
  1. 1.

    It caters information about quality and safety of pharmaceutical products.

  2. 2.

    It initiates risk-management plans.

  3. 3.

    It prevents the predictable adverse effects and helps in measuring ADR incidence.

  4. 4.

    It instructs health care team, patients, pharmacists and nurses about adverse drug effects and creates awareness regarding ADRs.


The main objective of ADR monitoring is to disclose the quality and frequency of ADRs and to identify the risk factors that can cause the adverse reactions (Moore2001; Murphy and Frigo1993).

ADR monitoring includes different studies for the identification of adverse events

Case reports

By this method, the unpredictable (bizarre) effects i.e. TYPE-B adverse drug reactions are reported.

Anecdotal reporting

This kind of reporting comes through reports of individual doctors when a patient suffers from the particular effect.

Impulsive reporting system

This method is considered as the most efficient method. Mostly, all ADR reporting programmes follow this method. Here, the effects are recorded spontaneously. With this method, both unusual and acute ADRs can be focused on and monitored (Naranjo and Busto1981).

Intensive monitoring studies

Health care members continuously watch the patients and record all the events observed when a drug or different drugs are administered. In this, defined groups of patients are screened to detect ADRs. The main disadvantage of these studies is that the population includes the minimum patients and each patient is studied for the concise period of time. Special investigations can be performed if statistical screening is incorporated in this study method (Naranjo and Busto1981; Nebeker and Barach2008).

Contingent studies

In these studies, patients administering similar medicines are identified, and their events are recorded. Major drawbacks of this method are that minimum patients are included and no control group is present for comparison. The contingent examinations are too expensive, and these investigations are difficult to perform on newly marketed drugs (Nissen and Wolski2007).

Case–control studies (Retrospective Studies)

In these studies, patients who have illness or disease due to the use of a drug are investigated to check if they have taken the drug. These patients are then compared with a matched control group that is similar in confounding factors but do not possess the adverse events or illness. This is a useful method in determining whether the drug has caused the adverse event or not. However, by this method, new ADRs cannot be identified (Parthasarathi et al.2007).

Case cohort studies

These studies include both prospective cohort study and retrospective case–control studies; in other words, it is the combination of both the studies (Pearson et al.1994).

Record linkage

In this method, all the records such as prescription records, patient records and hospital records are studied to identify the illness with drugs.

Meta analysis

It is a quantitative examination of two or more independent studies to determine the overall effect and to describe reasons in variation of study results (Prosser and Kamysz1990).

Utilitization of resident’s statistics

If a drug-induced event is very frequent and if suspicions arise for them, case–control and experimental cohort studies shall be initiated (Rao2010).

Roles of pharmacovigilance in monitoring ADRs

Many incidents occurred that caused the need of laws and regulations regarding the safe use of drugs. After rofecoxib withdrawal from the European market, the FDA rules on post-market surveillance were criticized and a new system of pharmacovigilance was introduced that provided information on identified risks (Palaian et al.2006; Rawlins and Thompson1981; Yadav2008).

Throughout the early post-marketing period, the product might be used in different groups of people from those used in clinical trials and much larger populations might be exposed in a relatively short time. The post-marketing product is required to develop new information, which can focus on the benefits as well as risks of the product (Arnott et al.2012). Pharmacovigilance produces detailed information of marketed products to ensure their safe use.

The impressive pharmacovigilance planning can reduce the adverse events of drugs in patients. The most important method used in pharmacovigilance is to collect information on a drug when it is in the pre-marketing phase is by conducting a clinical trial. This study design is not optimum to determine the ADRs of the drug. Because in this approach limited numbers of patients participate and it is not necessary that the patients resemble the population in which the drug is to be used (Arora2008; Bahri and Tsintis2005), it becomes impossible to understand the mechanism and consequence of the drug in these groups. Some methods that can be helpful in the detection as well as the prevention of suspected ADRs are listed as follows.

Different study designs are included for proper pharmacovigilance study:
  1. a.

    Descriptive studies:

    Descriptive studies are conducted to obtain the outcome rate of drug use events in a specific population. These studies include the data of adverse events that occurred in diseased patients. Another factor included is the drug utilization study (Biswas and Biswas2007; Biswas2008). These studies provide data on the specific groups of patients such as children, elderly or patient with renal or hepatic dysfunction. With these data study rates of adverse events can be reported.

  2. b.

    Analytical studies:

    Analytical studies are performed to study related outcomes of the exposure to the drug. They can take the form of observational as well as interventional/experimental studies. There are four main types of analytical studies namely ecological, cross-sectional, cohort and case–control (Brewer and Colditz1999).

  3. c.

    Observational studies:

    Observational studies provoke aspects of drug effectiveness in patients during treatment. This is in contrast with experiments, such as randomized controlled trials, where each subject is indiscriminately allocated to a treatment group or a control group (Ciorciaro et al.1998; Jeetu and Anusha2010; Joshi and Sapatnekar2008).


Methods in pharmacovigilance for monitoring of ADR

Passive surveillance

Spontaneous reports The spontaneous reporting systems were developed after the thalidomide incident. The aim of this spontaneous reporting system is to regulate and control the safety of drugs. This system is applied in the collection of post-marketing information on safety of drugs and identification of safety signals. Consequently, this system is used in the identification of signals of new, rare and serious ADRs of drugs. This system makes it easier for physicians, patients and pharmacists to report suspected ADRs to the pharmacovigilance centre (Herdiero et al.2005; Olsson2008; Rahman et al.2007). The pharmacovigilance centre collects all these reports and informs the stakeholders about the new reported ADRs. By this method, we can monitor all drugs in the market throughout their lifecycles (Ravindra and Vishal2011); (Surendra et al.2010).

Case series The case series are applied in developing a hypothesis between post-marketing drugs and its outcome (Faich1996).

Stimulated reporting

The stimulated reporting system encourages and facilitates health professionals to report ADRs in specific situations. It is very useful in generating adverse events of drugs online (Gerritsen et al.2011). It is effective in generating spontaneous reports of adverse events of drugs identified during the post-marketing phase. This system can assist in minimizing events by linking stimulated reporting with early post-marketing phase (Gupta2010).

Active surveillance

Active surveillance includes a pre-organized process to find out more serious adverse events, including the additional efforts to find the adverse reactions. Risk management programme is followed in this process, and more detailed information on individual adverse event reports can be obtained compared with passive surveillance (Panos et al.2004; Harmark and Van Grootheest2008; Surendra et al.2010; Muthiah et al.2012; Lobo et al.2013; Kshirsagar et al.2011).

Comparative observation studies

To test a hypothesis, a study has to be performed. These are the key events to evaluate the adverse events. The study can be conducted using different methods, which can be retrospective and perspective. Major types of these studies are cross-sectional studies, case–control studies and cohort studies (Bates et al.1995). Cross-sectional studies are conducted for ecological analysis. These are helpful in examining the prevalence of any disease at one time point. These studies are helpful to provide information between exposure of the drug and outcome in the ecological analysis.

Case–control study can easily identify the adverse events of drugs. The ADRs are determined by comparing the two distinctive groups. Case–control studies are useful when they are aimed to investigate adverse event in different groups. It is helpful in determining the absolute incidence rate of the adverse events.

Cohort studies provide data that has been collected in a routine fashion. This study can also be used to examine safety issues in specific populations such as children and patients with co-morbid conditions (Gor and Desai2008; Hussein et al.1999).

Earmarked clinical examinations

After pre-approved clinical trials, if sufficient risks are identified, further clinical studies are done to find or evaluate the mechanism of action for the identified adverse reactions. Pharmacokinetic and pharmacodynamic studies are applicable in determining the particular dosing, which can cause enhanced uncertainty of adverse effects in patients. Genetic testing can also be helpful in knowing which group of patients might be at an increased risk of adverse reactions. Children, elderly and patients with renal conditions might metabolize drugs in a different manner compared with patients enrolled or included in clinical trials. By these investigations events of particular interest are focused and used to determine or quantify the magnitude of the risk (Surendra et al.2010).

Thus, all of the above steps are linked with adverse event monitoring studies. Consequently, good safety profile of drug can be established and further suspected adverse events can be minimized and prevented by incorporating the pharmacovigilance methods for adverse drug reactions.


ADRs have a perspective to provoke harmful effects in patients. Health-care workers and pharmacovigilance constrain being more conscious of perceive the ADRs in the patient. In conclusion, this study can be useful for physician to identify the ADRs in patients by applying above mentioned methods.


Authors’ Affiliations

Columbia Institute of Pharmacy, Tekari, Raipur, CG, 493111, India


  1. Aeries N: Consumer reporting of ADRs. WHO Drug Information 1995, 14: 211-215.Google Scholar
  2. Arnott J, Hesselgreaves H, Nunn AJ, Peak M, Pirmohamed M: What can we learn from parents about enhancing participation in Pharmacovigilance? British J Clin Pharmacol 2012, 78(2):312-322.Google Scholar
  3. Arora D: Pharmacovigilance obligations of the pharmaceutical companies in India. Indian J Pharmacol 2008, 40: 13-16.Google Scholar
  4. Bahri P, Tsintis P: Pharmacovigilance–related topics at the level of the International Conference on Harmonisation (ICH). Pharmacoepidemiol Drug Saf 2005, 14: 377-387. 10.1002/pds.1043View ArticleGoogle Scholar
  5. Bates DW, Cullen DJ, Laird N: Incidence of adverse drug events and potential adverse drug events. JAMA 1995, 274: 29-34. 10.1001/jama.1995.03530010043033View ArticleGoogle Scholar
  6. Beard K: Adverse reactions as a cause of hospital admission in the aged. Indian J Pharmacol 1992, 2: 356-357.Google Scholar
  7. Biswas P: Pharmacovigilance safety matters. Indian J Pharmacol 2008, 7613(40):1-3.Google Scholar
  8. Biswas P, Biswas A: Setting standards for proactive pharmacovigilance in India: The way forward. Indian J Pharmacol 2007, 39: 124-128. 10.4103/0253-7613.33431View ArticleGoogle Scholar
  9. Brewer T, Colditz GA: Postmarketing surveillance and adverse drug reactions: current perspectives and future needs. JAMA 1999, 281: 824-829. 10.1001/jama.281.9.824View ArticleGoogle Scholar
  10. Carlo T, Francesco S: Ototoxicity of tobramycin, gentamicin, amikacin and sisomicin. J Antimicrob Chemother 1978, 4: 73-83.Google Scholar
  11. Chyka PA, Erdman AR, Christianson G, Wax PM, Booze LL, Manoguerra AS, Caravati : Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol 2007, 45(2):95-131. 10.1080/15563650600907140View ArticleGoogle Scholar
  12. Ciorciaro C, Hartmann K, Kuhn M: Differences in the relative incidence of adverse drug reactions in relation to age, an evaluation of the spontaneous reporting system of SANZ. Journal Suisse de medicine 1998, 128: 254-258.Google Scholar
  13. Classen DC, Pestotnik SL, Evans RS: Adverse drug events in hospitalized patients. JAMA 1997, 277(4):301-306. 10.1001/jama.1997.03540280039031View ArticleGoogle Scholar
  14. Cole M, Proctor GB, Trigoboff E: Adverse Drug Reaction Review: Evaluation of Concomitant Medications Effecting Blood Dyscrasias Associated with Clozapine. American Society of Health-System Pharmacists, Las Vegas December 6-10; 2009.Google Scholar
  15. Delini SA, Mikkelsen H, Angst J: Therapeutic efficacy of antidepressants in agitated anxious depression–a meta-analysis of moclobemide studies. J Affect Disord 2007, 35(2):21-30.Google Scholar
  16. Doheny K: Reports of adverse drug effects up. Web MD Health News 2009, 6: 1-2.Google Scholar
  17. Douketis JD, Crowther M, Wells PS: A review on propofol and its drug and food interactions. Arch Intern Med 2007, 45(10):167-176.Google Scholar
  18. Faich GA: U.S. adverse drug reaction surveillance. Pharmacoepidemiol Drug Saf 1996, 5(6):393-398. 10.1002/(SICI)1099-1557(199611)5:6<393::AID-PDS235>3.0.CO;2-HView ArticleGoogle Scholar
  19. FDA: Early Communication about Safety of Lantus (insulin glargine). US Food and Drug Adminstration, Silver Spring, MD; 2009.Google Scholar
  20. Fu H, Darroch JE, Henshaw SK, Kolb E: Measuring the extent of abortion underreporting in the 1995. Fam Plann Perspect 1998, 30: 128-133. 138 10.2307/2991627View ArticleGoogle Scholar
  21. Gaudreault P, Temple AR, Lovejoy FH: The relative severity of acute versus chronic salicylate poisoning in children: a clinical comparison. Pediatrics 1982, 70(4):566-569.Google Scholar
  22. Gerritsen R, Faddegon H, Dijkers F, VanGrootheest K, Van Puijenbroek E: Effectiveness of pharmacovigilance training of general practitioners: a retrospective cohort study in the Netherlands comparing two methods. Drug Saf 2011, 34: 755-762. 10.2165/11592800-000000000-00000View ArticleGoogle Scholar
  23. Goldman SA: Limitations and strengths of spontaneous reports data. Clinical Therapeutic 1998, 4: 40-44.View ArticleGoogle Scholar
  24. Gor AP, Desai SV: Adverse drug reaction in the in patients of medicine department of a rural tertiary care teaching hospital and influence of pharmacovigilance in reporting ADR. Indian J Pharmacol 2008, 40(1):37-40. 10.4103/0253-7613.40488View ArticleGoogle Scholar
  25. Gupta Y: Ensuring patient safety- launching the new pharmacovigilance programme of india. Pharma Times 2010, 42(8):234-289.Google Scholar
  26. Gupta P, Udupa A: Adverse drug Reaction Reporting and pharmacovigilance: knowledge, attitudes and perceptions amongst resident doctors. J Pharm Sci Res 2011, 1459(2):1064-1069.Google Scholar
  27. Hall M, Mc Cormack P, Arthurs N, Feely J: The spontaneous reporting of ADRs by nurses. British J ClinPharmacol 1995, 3: 173-175.Google Scholar
  28. Halpern GM: COX-2 inhibitors: a story of greed, deception and death. Inflammo Pharmacology 2005, 13(4):419-425. 10.1163/156856005774415574View ArticleGoogle Scholar
  29. Hampton T: Experts point to lessons learned from controversy over rofecoxib safety. JAMA 2005, 293: 413-414.View ArticleGoogle Scholar
  30. Harmark L, Van Grootheest AC: Pharmacovigilance: methods, recent developments and future perspective. European J ClinPharmacol 2008, 64(6):743-752.View ArticleGoogle Scholar
  31. Haupt M, Jeste D: Mortality in elderly dementia patients treated with risperidone. J ClinPsychopharmacol 2006, 26(6):566-570.View ArticleGoogle Scholar
  32. He Q, Luo X, Jin W, Huang Y, Reddy MV: Celecoxib and a novel COX-2 inhibitor ON09310 up regulate death receptor 5 expression via GADD153/CHOP. Inflammo Pharmacology 2005, 13(4):419-425. 10.1163/156856005774415574View ArticleGoogle Scholar
  33. Herdiero MT, Figueiras A, Polonia J: Physians attitudes and adverse drug reaction reporting: a case control study in Portugal. Drug Saf 2005, 28(9):825-833. 10.2165/00002018-200528090-00007View ArticleGoogle Scholar
  34. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS: Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 2005, 165(10):1095-1106. 10.1001/archinte.165.10.1095View ArticleGoogle Scholar
  35. Holford NH: Clinical pharmacokinetics and pharmacodynamics of warfarin understanding the dose-effect relationship. Clin Pharmacokinet 1986, 11(6):483-504. 10.2165/00003088-198611060-00005View ArticleGoogle Scholar
  36. Hornbuckle K, Wu HH, Fung MC: Evaluation of spontaneous adverse event reports by primary reporter - a 15-year review (1983 to 1997). Drug Inf J 1999, 33: 1117-1124.Google Scholar
  37. Huismen C, Ferreira CG, Broker LE: Paclitaxel triggers cell death primarily via caspase-independent routes in the non-small cell lung cancer cell line. Clin cancer Res 2002, 8(2):596-606.Google Scholar
  38. Hussein G, Bleidt B, Belding B: Recognition evaluation and reporting of adverse drug reactions. Clin Res Regul Aff 1999, 16(3):91-107. 10.3109/10601339909007064View ArticleGoogle Scholar
  39. Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H: Identification of a primary target of thalidomide teratogenicity. Science 2010, 327(5971):1345-1350. 10.1126/science.1177319View ArticleGoogle Scholar
  40. Jankovic J, beach J: Long term effects of tetrabenazine in hyperkinetic movement disorders. Neurology 1997, 48(2):358-362. 10.1212/WNL.48.2.358View ArticleGoogle Scholar
  41. Jeetu G, Anusha G: Pharmacovigilance: a worldwide master key for drug safety monitoring. Journal Young Pharm 2010, 2(3):315-316. 10.4103/0975-1483.66802View ArticleGoogle Scholar
  42. Joshi SR, Sapatnekar SM: The importance of pharmacovigilance. Geneva: World Health Organization, Pharmacovigilance in India: how safe are the new drugs? How sure are we? J Assoc Physicians Ind 2008, 56(8):933-934.Google Scholar
  43. Juntti PL, Neuvoren PJ: Drug related deaths in a university central hospital. Eur J ClinPharmacol 2002, 58: 479-482.Google Scholar
  44. Karch FE, Lasagna L: Towards the operational identification of adverse drug reactions. Clin Pharmacol Ther 1997, 21: 247-254.Google Scholar
  45. Kessler DA: Introducing Med Watch, using FDA form 3500, a new approach to reporting medication and device adverse effects and product problems. JAMA 1993, 269: 2765-2778. 10.1001/jama.1993.03500210065033View ArticleGoogle Scholar
  46. Krumholz HM, Ross JS, Presler AH: What have we learnt from Vioxx? Br Med J 2007, 334: 120-123. 10.1136/bmj.39024.487720.68View ArticleGoogle Scholar
  47. Kshirsagar N, Ferner R, Figueroa BA, Ghalib H, Lazdin J: Pharmacovigilance methods in public health programmes: the example of miltefosine and visceral leishmaniasis. Trans R Soc Trop Med Hyg 2011, 105: 61-67. 10.1016/j.trstmh.2010.11.004View ArticleGoogle Scholar
  48. Kung HC, Hoyert DL, Xu JQ, Murphy SL: Increase in poisoning and methadone related effects; National Center for Health Statistics. Natl Vital Stat Rep 2008, 56(10):8-15.Google Scholar
  49. Lazarou J, Pomeranz BH, Corey PN: Incidence of adverse drug reactions in hospitalized patients-a meta-analysis of prospective studies. JAMA 1998, 2: 1200-1205.View ArticleGoogle Scholar
  50. Lisa A, Ladewski SM, Belknap JR, Nebeker OS: Dissemination of information on potentially fatal adverse drug reactions of drugs from 2000 to 2002: first results from the research on adverse drug events and reports project. J ClinOncol 2003, 21(20):3859-3866. 10.1200/JCO.2003.04.537View ArticleGoogle Scholar
  51. Livio F, Renard D, Buclin T: Pharmacovigilance, a review. Med Suisse 2012, 8: 116-119.Google Scholar
  52. Lobo A, Germana M, Gerley J: Adverse drug reaction monitoring; support for pharmacovigilance at a tertiary care hospital in northern Brazil. BMC Pharmacol Toxicol 2013, 78(3):1-7.Google Scholar
  53. Marx J: Rosen’s Emergency Medicine: Concepts and Clinical Practice. Mosby Inc Mosby/Elsevier, Maryland Heights, Missouri; 2006:2242.Google Scholar
  54. Michael S, Ma L: Fluoxetine and suicide rates suicide and the economy. J Pub Med 2006, 3(11):501-503.Google Scholar
  55. Minino AM, Anderson RN, Fingerhut LA, Boudreault MA, Warner M: Deaths: injuries. Natl Vital Stat Rep 2002, 54(10):1-20.Google Scholar
  56. Mishra H, Kumar V: Pharmacovigilance: current scenario in a tertiary care teaching Medical College in North India. Journal Pharmacovigilance 2013, 1(2):1-4.Google Scholar
  57. Mohammed A: Analysis of multiple risks involving the use of IV fentanyl. Patient Safe Advis 2012, 9(4):122-129.Google Scholar
  58. Moore N: The role of the clinical pharmacologist in the management of ADRs. Drug Saf 2001, 24(1):1-7. 10.2165/00002018-200124010-00001View ArticleGoogle Scholar
  59. Murphy BM, Frigo LC: Development implementation and results of a successful ultidisciplinary adverse drug reaction reporting Program in a University Teaching Hospital. Hospital Pharm 1993, 28: 1199-1240.Google Scholar
  60. Muthiah NS, Elumalai M, Murali NP: HazraRamsundar: pharmacovigilance: a tool for health safety- review article. Indian J Multidiscip Dent 2012, 2(1):374-376.Google Scholar
  61. Naranjo CA, Busto U: A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981, 30: 239-245. 10.1038/clpt.1981.154View ArticleGoogle Scholar
  62. Nebeker JR, Barach P: Clarifying adverse drug events, a clinicians view. Ann Intern Med 2008, 12: 87-112.Google Scholar
  63. Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007, 356: 2457-2471. 10.1056/NEJMoa072761View ArticleGoogle Scholar
  64. Olsson S: Pharmacovigilance training with focus on India. Ind J Pharmacol 2008, 40(7):28-30.Google Scholar
  65. Orlando M, Perkins CL: Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels. Clin cancer Res 2002, 8(2):596-606.Google Scholar
  66. Palaian S, Mishra P, Shankar PR, Dubey AK, Bista D, Almeida R: Safety monitoring of drugs- where do we stand? Kathmandu Univ Med J 2006, 4(13):119-120.Google Scholar
  67. Panos T, Sintis P, La Mache E: CIOMS and ICH initiatives in pharmacovigilance and risk management overview and implications European agency for the evaluation of medicinal products. London, United Kingdom Drug Safety 2004, 27(8):509-517.Google Scholar
  68. Parthasarathi G, Karin Nyfort H, Nahata MC: Adverse Drug Reactions. A Textbook of Clinical Pharmacy Practice Essentials Concepts and Skills, vol 76. University Press, Hyderabad; 2007:84-102.Google Scholar
  69. Pasero C: Fentanyl for acute pain management. J Perianesth Nurs 2005, 20(4):279-284. 10.1016/j.jopan.2005.03.007View ArticleGoogle Scholar
  70. Pearson TF, Pittman D, Longley JM, Grapes T, Vigliotti DJ, Mullis SR: Factors associated with preventable adverse drug reactions. Am J Hosp Pharm 1994, 51: 2268-2271.Google Scholar
  71. Peng PW, Sandler AN: A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology 1999, 90(2):576-599. 10.1097/00000542-199902000-00034View ArticleGoogle Scholar
  72. Prommer E: The role of fentanyl in cancer-related pain. J Palliat Med 2009, 12(10):947-954. 10.1089/jpm.2009.0051View ArticleGoogle Scholar
  73. Prosser TR, Kamysz PL: Multidisciplinary adverse drug reaction surveillance program. American J Hosp Pharm 1990, 47: 1334-1339.Google Scholar
  74. Purdue Pharma L.P. Stamford, CT: 06901-3431 2010 U.S. Patent Numbers 5,508,042; 6,488,963; 7,129,248; 7,674,799; 7,674,800 and 7,683,072. 2009.Google Scholar
  75. Rahman SZ, Khan RA, Gupta V, Uddin M: Pharmacoenvironmentology - a component of pharmacovigilance. Environmental Health 2007, 56(20):38-42.Google Scholar
  76. Rao HP: Reporting of adverse drug reactions by consumers: rationale and potential. Pharmbit. Am J Hosp Pharm 2010, 22(20):110.Google Scholar
  77. Ravi Shankar P, Subish P, Mishra P, Dubey AK: Teaching pharmacovigilance to medical students and doctors. Indian J Pharmacol 2006, 38(5):316-319. 10.4103/0253-7613.27698View ArticleGoogle Scholar
  78. Ravi Shankar P, Subish P, Mishra P, Dubey AK: Teaching Pharmacovigilance to Medical students and doctors. Educational Forum 2010, 38(5):37-379.Google Scholar
  79. Ravindra A, Vishal B: Pharmacovigilance: an overview. Int J Res Pharmacy Chemistry 2011, 1(40):968-969.Google Scholar
  80. Rawlins MD, Thompson JW: Mechanisms of Adverse Drug Reactions. In Textbook of Adverse Drug Reactions. 4th edition. Oxford: Oxford University press; 1981.Google Scholar
  81. Rehan HS, Vasudev K, Tripathi CD: Adverse drug reaction monitoring: knowledge, attitude and practices of medical students and prescribers. Natl Med J India 2002, 15(1):24-25.Google Scholar
  82. Rishi RK, Patel RK, Bhandari A: Opinion of physicians towards adverse drug reactions reporting results of pilot study. J Commun Nutr Health 2012, 1(1):25.Google Scholar
  83. Rohilla A, Singh N, Kumar V, Sharma MK, Dahiya A, Kushnoor A: Pharmacovigilance: needs and objectives- review article. J Adv Pharm Technol Res 2012, 2(4):201-205.Google Scholar
  84. Santosh KC, Tragulpiankit P: Pharmacovigilance: an overeview. Department of Pharmacy, Faculty of Pharmacy Mahidol University. Journal of Pharmaceutical Sciences 2002, 21: 23-146.Google Scholar
  85. Schluter G: Ciprofloxacin: toxicological evaluation of additional safety data. Am J Med 1989, 87(5):99-106.View ArticleGoogle Scholar
  86. Schonthal AH, Chen TC, Hofman FM, Louie SG, Petasis NA: Celecoxib analogs that lack. COX-2 inhibitory function: preclinical development of novel anticancer drugs. Expert Opin Investig Drugs 2003, 17(2):197-208.View ArticleGoogle Scholar
  87. Shukla SS, Gidwani B, Pandey R, Rao SP, Singh V, Vyas : A importance of pharmacovigilance in Indian pharmaceutical industry – review article. Asian Pharma Online 2012, 5: 2231-5659.Google Scholar
  88. Solomon DH, Schneeweiss S, Glynn RJ, Kiyota Y, Levin R, Mogun H, Avorn : Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. American J 2004, 109: 2068-2073.Google Scholar
  89. Surendra S, Dang A, Rataboli P: Pharmacovigilance and Pharmaco epidemiology. Indian J Pharm Sci 2010, 72(1):96-102.Google Scholar
  90. Thisted B, Krantz T, Stroom J, Sorensen M: Acute salicylate self-poisoning in 177 consecutive patients treated in ICU. Actaanaesthesiologica Scandinavica 1986, 31(4):312-316.View ArticleGoogle Scholar
  91. Yadav S: Status of adverse drug reaction monitoring and pharmacovigilance in selected countries. Indian J Pharmacol 2008, 40: 4-9.View ArticleGoogle Scholar


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