Forensic Pharmacovigilance: New Dimension of Drug Safety

Review
Forensic pharmacovigilance: Newer dimension of pharmacovigilance
Rakesh K. Sewal, Vikas K. Saini, Bikash Medhi*
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
a r t i c l e i n f o
Article history:
Received 4 October 2014
Received in revised form
25 March 2015
Accepted 29 May 2015
Available online 6 June 2015
Keywords:
Pharmacovigilance
Forensic science
Medicolegal
Adverse drug reaction
a b s t r a c t
Drug safety for the patients is of paramount importance for a medical professional. Pharmacovigilance
attempts to ensure the safety of patients by keeping a close vigil on the pattern of adverse events sec-
ondary to drug use. Number of medicolegal cases is at rise since last few years. Forensic sciences and
pharmacovigilance need to work hand in hand to unlock the mystery of many criminal and civil pro-
ceedings. Pharmacovigilance offers its wide scope in forensic sciences by putting forward its expertise on
adverse profile of drugs which may be instrumental in solving the cases and bringing the justice forth. It
may range from as simple affairs as defining the adverse drug reaction on one hand to putting expert
advice in critical criminal cases on the other one. Pharmacovigilance experts have to abide by the ethics
of the practice while executing their duties as expert else it may tarnish the justice and loosen its
dependability. As a budding discipline of science, it is confronted with several hurdles and challenges
which include reluctance of medical professionals for being involved in court proceedings, extrapolations
of facts and data and variations in law across the globe etc. These challenges and hurdles call the medical
fraternity come forward to work towards the momentous application of pharmacovigilance in the
forensic sciences. Evidence based practice e.g. testing the biological samples for the presence of drugs
may prove to be pivotal in the success of this collaboration of sciences.
© 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
1. Introduction
Pharmacovigilance has witnessed an exponential growth in last
few decades owing to the increasing awareness amongst healthcare
professionals. Pharmacovigilance is the science and activities relating
to the detection, assessment, understanding and prevention of
adverse effects or any other drug-related problem.1
The various
components of pharmacovigilance ranging from detection to pre-
vention of adverse drug reactions (ADR's) lay a strong foundation for
the solution of medicolegal cases. A medicolegal case is where a
person is injured or harmed in any way and needs medical attention
for it. Medicolegal cases comprise of detection and collection of ev-
idences in accidents, suicides and homicides. In this contemporary
world of medicine, medicolegal issues are emerging out at an
alarming rate.2
This is worthwhile to mention that law and medical
professionals need to work hand in hand for the sake of betterment
and rehabilitation of the victims of medicolegal cases.3
Forensic sci-
ences and pharmacovigilance offer collaborative services to each
other for the benefit of stakeholders. They can exchange the knowl-
edge with each other to complement the information. This symbiotic
relationship of two vital components of healthcare system gives birth
to a new discipline known as “Forensic Pharmacovigilance”.
2. Scope of pharmacovigilance in forensic medicine
2.1. Illicit drug use
Illicit drug use cases seek the expert opinion on drugs and their
possible adverse events. The illegal drugs use is on rise since few
decades. The number of intentional and unintentional deaths from
prescription drugs overdose is now greater than the deaths from
heroin and cocaine combined. A large part of the problem is the use
of pain-killers without a prescription, or misusing a prescribed drug
to get “high.” Improving the way prescription painkillers are pre-
scribed can reduce the number of people who misuse, abuse or
overdose these drugs, while making sure patients have access to
safe and effective treatment. In 2011, legislation to create a Pre-
scription Drug Monitoring Program was passed in Maryland to
make comprehensive information on prescribed and dispensed
Controlled Dangerous Substances available to doctors, pharmacists
and other healthcare providers.4
* Corresponding author. Department of Pharmacology, Postgraduate Institute of
Medical Education & Research, Chandigarh, India. Tel.: þ91 172 2755250 (O),
þ91 9815409652 (M); fax: þ91 1722744401, þ91 1722745078.
E-mail address: drbikashus@yahoo.com (B. Medhi).
Contents lists available at ScienceDirect
Journal of Forensic and Legal Medicine
journal homepage: www.elsevier.com/locate/jflm
http://dx.doi.org/10.1016/j.jflm.2015.05.015
1752-928X/© 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Journal of Forensic and Legal Medicine 34 (2015) 113e118

2.2. Role in solving civil or criminal cases
During the criminal proceedings, involvement of drugs in a case
may seek the expert advice of pharmacovigilance to solve the case.5
Examples of such cases include death due to overdose toxicity of
drugs like sedatives being used for sleep disorders or opiates used
for pain management. Under few circumstances, apart from the
involvement of toxicological effects of drugs; there are certain
adverse drug reactions which can be attributed responsible for
occurrence of the legal case. The fact that suicidal tendencies sec-
ondary to the use of antidepressants are the known adverse effects
of these drugs may be useful in mining/unleashing the cause of
death of a person treated by these drugs and who commits a suicide
leaving a mystery behind.6
Table 1 enlists the examples of drugs and their forensic signifi-
cance which illustrates the relevance of drugs’ knowledge in
forensic concerns.
2.3. Differentiation between adverse drug reaction and adverse
event
Any untoward medical occurrence that may appear during
treatment with a pharmaceutical product but which does not
necessarily have a causal relationship with the treatment is called
Table 1
Examples of drugs explain their possible ADR's of forensic significance.
S. No. Drug Class/Use ADR Forensic significance Reference
1 Citalopram Selective serotonin
reuptake inhibitors
QTc interval prolongation May cause adverse drug reactions of serious outcomes 7,8
2 Dextropropoxyphene Opioid analgesic QTc interval prolongation May cause adverse drug reactions of serious outcomes 9e11
3 Flunitrazepam Intermediate acting
benzodiazepine
QTc interval prolongation May cause adverse drug reactions of serious outcomes 12
4 Methadone Opioid analgesic QT Prolongation
Respiratory depression
Respiratory arrest 13,14
5 Varenicline Nicotinic acetylcholine
receptor agonist
Manic episodes induced
Suicidal Ideation
Death involving a suspicion of suicide committed
by a person taking varenicline
15,16
6 Digoxin Cardiac glycoside Arrhythmia ST depression,Ventricular fibrillation leading to fatal
or other serious outcome
17
7 Fentanyl Opioid analgesic Respiratory depression Overdose toxicity may result in death. 18
8 Heroin Opiate Mast cell degradation Cardiac failure which may be an explanation of death 19,20
9 Cefuroxime Cephalosporin Disulfiram-like reaction Unexpected death 21
10 Morphine Opioid analgesic Respiratory depression
leading to death in
severe cases
Intentional or accidental overdose results in death.
Medication error or suicidal events should be
differentiated.
22
11 Aldicarb Acetylcholinestearse
inhibitor
CNS depression Death due to an aldicarb acute intoxication. 23,24
12 Trazodone Antidepressant, anxiolytic,
and hypnotic
Suicidal ideation While mining the evidences in death of such cases
suicidal ideation may be considered.
25,26
13 Atracurium Nondepolarizing skeletal
muscle relaxant
Hypertension and tachycardia
and hypotension and bradycardia
Overdose toxicity for Suicidal intention 27
14 Cyclizine Antihistaminic CNS depression, hypertension Overdose toxicity may result in death 28,29
15 Zopiclone Nonbenzodiazepine
hypnotic agent
Amnesia, palpitation,
hallucination
Suicidal attempt results in fatality 30
16 Fluoxetine Selective serotonin
reuptake inhibitor
Development of akathisia
related to the development
of suicidal ideation.
Suicidal ideation information may be instrumental
in solving mysterious death cases
31
17 Imipramine Tricyclic
antidepressant
Depresses automaticity Complete atrio-ventricular heart block resulting in
sudden death
17
18 Mephedrone CNS stimulant Delirium Impaired judgement may cause accidental death 32
19 Quinidine Anti arrhythmic QT prolongation Rapid ventricular arrhythmia results in death. Reason
of death may be explained.
17
20 Clozapine Atypical
antidepressant
Myocarditis Myocarditis induced death due to overdose 33,34
21 Thioridazine Antipsychotic Arrhythmia Arrhythmogenic sudden cardiac death 35
22 Dextromethorphan Antitussive Tachycardia, hypertension,
and respiratory depression
Death from respiratory failure 36
23 Acetamenophen NSAID/Antipyretic Hepatotoxicity Fulminant hepatic failure 37
24 Ceftriaxone Cephalosporin Auto eimmune
hemolytic anemia
Hemolytic anemia induced cardio-respiratory arrest,
Acute renal failure
38,39
25 Tetracycline Antibiotic Jaundice Hepatotoxicity 40
26 Thyroxine Congenital
hypothyroidism
Progressive bradycardia Cardiac Arrest 41
27 Azathioprine Immunosuppresant Bone marrow suppression,
hematological toxicity,
pancreatitis
Serious pancytopenia due to the accumulation
of cytotoxic metabolites
42e44
28 Doxorubicin Cytotoxic Cardiotoxicity Cardiomyopathy or cardiac failure 45,46
29 Rifampicin/Isoniazide/
Ethambutol/Pyrazinamide
Antitubercular FDC Hepatotoxicity Acute liver failure due to hepatic encephalopathy 47
30 Enalapril ACE inhibitor Hepatotoxicity Hepatic failure 41
31 Propofol Anaesthetic Pulmonary oedema and
haemorrhagic pancreatitis,
respiratory depression,
bronchospasm
and chest wall rigidity
Death occurred due to pulmonary oedema as patient
did not receive ventilation
48
R.K. Sewal et al. / Journal of Forensic and Legal Medicine 34 (2015) 113e118114

as adverse event. According to WHO, adverse drug reaction is
defined as “A response to a drug which is noxious and unintended;
and occurs at doses normally used in man for the prophylaxis;
diagnosis or therapy of disease, or for modification of physiological
function.49
Thus, every adverse drug reaction is an adverse event
but not vice versa. Keeping this point in view, it is pertinent to
cautiously identify these two aspects of unintended experiences
after the use of drugs. “Causality assessment” is the tool to put
scientific evidence forth to determine the accurate nature of
adverse experience after a drug use. If there is any stronger or
weaker correlation of administration of drug with the occurrence of
adverse event then it is known as adverse drug reaction. There are
several causality assessment scales adopted by the pharmacovigi-
lance experts to assign the level of correlation. Naranjos's scale,
WHO's causality assessment scale and Bayesian scale are few to
name.50,51
Different degrees of association are described by these
scales e.g. certain, probable, possible and unlikely are the levels
mentioned by the WHO's scale for causality assessment.52,53
2.4. Discrimination between serious and severe ADR's
There is a thin line of demarcation between serious and severe
drug reactions which are misunderstood many a times. Court
proceedings may be in a need to judge the gravity of problem in
terms of seriousness and severity. Severe reactions should never be
confused with serious reactions. For instance, in any drug related
injury in clinical trials compensation is granted to the victim for
which judiciary needs to ascertain whether the injury was serious
or not.
There is a criterion almost universally accepted for determining
the seriousness of drug reaction. If the ADR falls in to the bracket of
that criterion then it should be designated as serious event. A re-
action is said to be serious if it 1) results in death, 2) is life-
threatening, 3) requires inpatient hospitalization or prolongation of
existing hospitalization, 4) results in persistent or significant
disability/incapacity, 5) results in congenital abnormality, and 6) is
any other medically important condition.
Severity of the ADR's deals with the intensity of the reaction
graded as mild, moderate, severe.49
Severe is never synonymous
with serious e.g. headache may be severe in grade but not of great
medical significance for seriousness.
2.5. Identification of counterfeit and substandard drugs
Pharmacovigilance data can generate the signal for some spe-
cific drug and/or its formulations; under some instances. Forensic
pharmacovigilance is useful when counterfeit or substandard drugs
cause the adverse events. Standard pharmacovigilance methods of
registration, analysis and investigation are able in indentifying the
substandard drugs or formulations which have caused the adverse
events. Thousands of adverse reactions in USA which are secondary
to administration of contaminated heparin in 2009 is an example of
adverse events occurred due to contaminated or counterfeit drugs
which generates the signal for taking corrective action as it
happened in case of the present example. Market authorization
holder had to recall all heparin due to alarming figure of ADR's
including hundreds of fatalities.54
Few areas of scope of forensic pharmacovigilance are depicted
in Fig. 1.
3. Forensic pharmacovigilance as another bud of
pharmacovigilance
Though birth of pharmacovigilance owes back to the occurrence
of a disaster known popularly as thalidomide tragedy but it has
attained a proliferative growth in last few decades.55
Pharmacovi-
gilance has gained a pace to expand its applications in other
streams of science. Ecopharmacovigilance, which is defined as
science and activities concerning detection, assessment, under-
standing, and prevention of adverse effects or other problems
related to the presence of pharmaceuticals in the environment,
which affect human and other animal species is a recent develop-
ment of pharmacovigilance proving its relevance in environmental
sciences.56
Haemovigilance, materiovigilance, biovigilance are few
more examples which are transformed facet of pharmacovigilance.
For example, in Indian context, haemovigilance is covered under
pharmacovigilance program of India as blood or blood products are
governed by drug regulatory authorities in India treating them as
a drug.57
On the same pattern we have recently seen a newer
budding branch of pharmacovigilance i.e Forensic Pharmacovigi-
lance which is instrumental in solving the legal issues raised
on involvement of any drug. Forensic pharmacovigilance i.e
Fig. 1. Scope of forensic pharmacovigilance.
R.K. Sewal et al. / Journal of Forensic and Legal Medicine 34 (2015) 113e118 115

implementation of pharmacovigilance expertise for forensic pur-
pose may be used to answer the following questions:
Could the drug under question (or chemical) have caused the
adverse effect in the victim ?
Did it cause the effect either ‘beyond all reasonable doubt?’
(criminal case) or ‘as a balance of probabilities (civil case)?3
4. Challenges and hurdles in forensic pharmacovigilance
4.1. Reluctance of medical professionals
Reluctance of medical professionals in playing their role as an
expert for forensic purposes is one of the sturdiest challenges to be
met. Causes contributing to the medical professional's reluctance
include fear of litigation, loss of productivity, fear of being twisted
by lawyers etc.58
Despite of these challenges medical professionals
should undertake the civic duties by contributing their expertise in
resolving the forensic issues.
4.2. Extrapolation of a data does not always produce
the real figures
Extrapolation of data generated through previous studies or
experiences cannot always be practised. Competitiveness and
quality of epidemiological studies in medicine always lies under
question mark making it difficult to accept their conclusion for
making decisions in some forensic issues.59
4.3. Uniformity vs non uniformity
Medical Sciences have similar foundation across the globe but
law varies across the borders. Medical profession is not open to
public rather it depends upon the subjective opinion of the pro-
fessionals whereas in contrast law is open at mass levels and has a
strong foundation of defined rules. Though in forensic pharmaco-
vigilance both the disciplines need to work hand in hand but there
are certain conflictions. Medicine discipline is challenged by the
law often during the trials.
4.4. Ethics in forensic pharmacovigilance
Judiciary has to rely more upon the opinion of the expert in a
case involving the drug. They rely more upon the testimony of
forensic experts. Therefore, an ethical obligation always lies upon
expert to put the truth forward and not to mislead the judiciary,
defense, or the state when testifying before the court, or when
preparing their reports relating to their analyses of forensic evi-
dence. We still lack any universally applicable guidelines on ethical
code for the forensic sciences. Though there are few professional
bodies catering to the needs of forensic analysts on ethics in
forensic sciences. American Board of Criminalistics (ABC) and the
American Academy of Forensic Science are two professional bodies
useful for forensic scientists in United States of America.60
In a
study conducted by Brandon L. Garrett and Peter J. Neufeld in 2009
six types of invalid testimony could be identified which are enlisted
as below.61
▪ Evidence that was non-probative presented as probative
▪ Discounting exculpatory evidence
▪ Conclusion of evidence originating from the defendant without
supporting empirical data
▪ Non-statistical statements made without supporting empirical
data
▪ Inaccurate presentation of statistics or frequency
▪ Providing statistics without supporting empirical data
An expert needs to be unbiased and fair enough in his/her
obligations. The prime obligation of an expert must be to
contribute towards the justice. Legal, scientific, and ethical values
can become snarled during the court proceedings. It becomes a
responsibility of an expert to keep his opinion after a competent,
unbiased and probative work. The causes behind practising un-
ethical acts include avarice, zeal of power or over ambitions of
promotion, status or personal welfare. Sometimes even casual
behaviour of experts towards professional duties also makes their
acts unethical. Living with guilt of that a guilty person escapes
and or an impeccant person gets punished based on the advice or
comments submitted by the pharmacovigilance expert may
restrain him or her from unethical acts. Professional bodies and
organizations should put the efforts forward to ensure ethical
practice, veracity of testimony among individuals engaged as
expert for forensic purpose. It is pertinent to devise a code of
conduct for such professionals to keep the benchmark of ethics in
forensic sciences.
5. Key points for an effective forensic pharmacovigilance
5.1. Forensic pharmacokinetics
Forensic pharmacokinetics should be honoured while giving the
opinion or report on medico legal case involving the drugs. If
possible, biological samples should be collected to assess them for
the presence of drugs or their metabolites which further can be
correlated with the adverse events related to the forensic concerns.
Claims of adverse drug reactions may be supported by data of
pharmacokinetics.2
Pharmacokinetics/Pharmacodynamics (PK/PD)
studies are gaining the popularity at various levels of research
which may be a tool for the effective implementation of pharma-
covigilance in forensic sciences.
5.2. Temporal relationship
Temporal relationship of occurrence of adverse event and
administration of drug should be taken into consideration while
preparing the report for forensic purposes. The time lag between
administration of drug and occurrence of ADR defines the time
course of a reaction which is of six types:
Rapid: toxic reactions
First-dose: hypersensitivity reactions
Early: collateral reactions
Intermediate ecollateral or hyper sensitivity reactions
Late ecollateral reactions
Delayed ecollateral reactions62
Temporal relationship lays a strong foundation for the causality
assessment of the case and also plays a vital role for the judgement
purposes e.g. immediate reactions showing a close temporal
relationship-between the adverse event and administration of dose
makes judiciary more convinced. Sometimes, when a far temporal
association lies between the administration of drug and event and
there is any scientific fact explaining that gap, an advice of experts
in pharmacovigilance or pharmacology must be sought because
there are certain drugs which causes the adverse events only after
accumulation of the drug or its metabolite in the body e.g.
morphine. But, there are certain exceptions in classification cited
here e.g. hypersensitivity reaction is usually immediate reactions
but may be delayed in few instances. Stevens Johnson Syndrome
secondary to paracetamol after chronic use may be an example of
such delayed immune mediated reaction.

5.3. Causality assessment of the case
Causality assessment determines the degree of probability of
correlation of administration of a drug and occurrence of adverse
event. It must be exercised cautiously and tested rigorously before
putting a report before the bench of a court. Several scales are being
used for causality assessment like Naranjo's scale, WHO's Scale for
causality assessment and Probability algorithm. A pharmacovigi-
lance expert should cautiously use the scale of causality assessment
and it should be specified in the report submitted to the judiciary.52
5.4. Cautious extrapolation of facts to every case
Exaggerated extrapolation of the case to some fact or data may
tarnish the proceedings of the forensic cases. It may entirely
mislead the verdict of the criminal or civil cases. Cautious extrap-
olation is warranted to avoid such misleading judgements based
upon inaccurate data.
5.5. Challenges of pharmacovigilance
Though pharmacovigilance is set to offer its application in
forensic sciences but there are few challenges before the pharma-
covigilance to be met. Increased globalization of drugs, exponential
rise in volume of drugs used and polypharmacy are few elements
which make the pharmacovigilance a complex discipline. Under
the light of these challenges, pharmacovigilance now should be
understood beyond merely reporting the harms; rather it should be
a rigorous risk benefit assessment. Few standards of quality in
pharmacovigilance have been set and good pharmacovigilance
practices (GVP) is a citable example of that.63
It is imperative to
adhere to such standards while implementing pharmacovigilance
in forensic areas.
5.6. Presenting evidence for the court
Proper presentation of the evidences by the medical or phar-
macovigilance expert may illuminate the case. A report for the
forensic purposes should be written clearly and should not include
the comments from the area which is beyond the expertise who is
submitting the report. A clear statement should be made in report if
some additional advice of another expert is needed. Scientifics
evidences, facts and observation should be presented in a manner
that can easily be understood by judges to make them arrive at a
verdict with reasonably fair understanding of the case.58
6. Conclusions
In the light of increasing medicolegal cases, there is a substantial
need of contribution of drug expertise in solving the criminal and
civil cases involving the drugs at one or other stages. Pharmacovi-
gilance is the science of detection, assessment, understanding,
prevention of adverse events associated with the use of drugs.
Pharmacovigilance can cater to the needs of legal framework to
mine the cases involving the drugs by differentiating the serious
and non serious reactions, establishing the causal relationship be-
tween drug and adverse event. Proliferating role of pharmacovi-
gilance has now sprawled over the arena of legal medicine giving
birth to newer branch of science known as forensic pharmacovi-
gilance which offers a wide range of its scope and application and
warrants a cautious execution of this exercise else it may deviate
from the intended use.
Conflict of interest
None declared.
Funding
None declared.
Ethical approval
None declared.
References
1. World Health Organization Collaborating Centre for International Drug Moni-
toring. The importance of pharmacovigilance safety monitoring of medicinal
products. Geneva: World Health Organization; 2002.
2. Medhi B, Singh PK, Bansal YS, Setia P. Forensic pharmacokinetics: a new
dimension for drug related medico legal cases. J Forensic Res 2011;2:128. http://
dx.doi.org/10.4172/2157-7145.1000128.
3. Edwards IR, Body D. Forensic pharmacovigilance. Int J Risk Saf Med 2012;12:
241e2.
4. Drug induced deaths. Maryland: Department of Mental Health and Hygiene;
2012.
5. Aronson JK, Hauben M. Anecdotes that provide definitive evidence. BMJ
2006;333:1267e9.
6. Kielholz P, Battegay R. Behandlung depressiver Zustandsbilder, unter spezieller
Berücksichtigung von Tofranil, einem neuen Antidepressivum. Schweiz Med
Wochenschr 1958;88:763e7.
7. Catalano G, Catalano MC, Epstein MA, Tsambiras PE. QTc interval prolongation
associated with citalopram overdose: a case report and literature review. Clin
Neuropharmacol 2001;24(3):158e62.
8. Jonasson B, Saldeen T. Citalopram in fatal poisoning cases. Forensic Sci Int
2002;126(1):1e6.
9. Carson DJL, Carson ED. Fatal dextropropoxyphene poisoning in Northern
Ireland: review of 30 cases. Lancet 1977;309(8017):894e7.
10. Lawson AAH, Northridge DB. Dextropropoxyphene overdose. Med Toxicol
Adverse Drug Exp 1987;2(6):430e44.
11. Hawton K, Simkin S, Deeks J. Co-proxamol and suicide: a study of national
mortality statistics and local non-fatal self poisonings. BMJ 2003;326(7397):
1006.
12. Barnett JM, Broad RM. Flunitrazepam used in a case of poisoning. J Clin Forensic
Med 2003;10(2):89e91.
13. Modesto-Lowe V, Brooks D, Petry N. Methadone deaths: risk factors in pain and
addicted populations. J Gen Intern Med 2010;25(4):305e9.
14. Andrews CM, Krantz MJ, Wedam EF, Marcuson MJ, Capacchione JF,
Haigney MC. Methadone-induced mortality in the treatment of chronic pain:
role of QT prolongation. Cardiol J 2009;16(3):210e7.
15. Kintz P, Evans J, Villain M, Cirimele V. Smoking cessation with varenicline: a
suicidal fatality. J Anal Toxicol 2009;33(2):118e20.
16. Stove CP, Els A, Piette MH, Lambert WE. Fatality following a suicidal overdose
with varenicline. Int J Leg Med 2013;127(1):85e91.
17. Bigger JT, Weld FM. Drugs and sudden cardiac death. Ann N Y Acad Sci
1982;382(1):229e37.
18. Algren DA, Monteilh CP, Punja M, Schier JG, Belson M, Hepler BR, et al.
Fentanyl-associated fatalities among illicit drug users in Wayne county,
Michigan (July 2005eMay 2006). J Med Toxicol 2013;9(1):106e15.
19. Edston E, Hage-Hamsten MV, Edston E. Anaphylactoid shockea common cause
of death in heroin addicts? Allergy 1997;52(9):950e4.
20. Darke S, Zador D. Fatal heroin ‘overdose’: a review. Addiction 1996;91(12):
1765e72.
21. Dong H, Zhang J, Ren L, Liu Q, Zhu S. Unexpected death due to cefuroxime-
induced disulfiram-like reaction. Indian J Pharmacol 2013;45(4):399.
22. Centers for Disease Control and Prevention. CDC grand rounds: prescription
drug overdoses-a US epidemic. Morb Mortal Wkly Rep 2012;61(1):10.
23. Proença P, Teixeira H, de Mendonca MC, Castanheira F, Marques EP, Corte-
Real F, et al. Aldicarb poisoning: one case report. Forensic Sci Int 2004;146:
S79e81.
24. Ragouc-Sengler C, Tracqui A, Chavonnet A, Daijardin JB, Simonetti M, Kintz P,
et al. Aldicarb poisoning. Hum Exp Toxicol 2000;19(12):657e62.
25. Martínez MA, Ballesteros S, de la Torre CS, Almarza E. Investigation of a fatality
due to trazodone poisoning: case report and literature review. J Anal Toxicol
2005;29(4):262e8.
26. Gamble DE, Peterson LG. Trazodone overdose: four years of experience from
voluntary reports. J Clin Psychiatry 1986;47(11):544e6.
27. Martínez MA, Ballesteros S, Almarza E. Anesthesiologist suicide with atracu-
rium. J Anal Toxicol 2006;30(2):120.
28. Arnestad M, Eldor KBB, Stray-Pedersen A, Bachs L, Karinen R. Suicide due to
cyclizine overdose. J Anal Toxicol 2014;38:110e2.
29. Backer RC, McFeeley P, Wohlenberg N. Fatality resulting from cyclizine over-
dose. J Anal Toxicol 1989;13(5):308e9.
30. Meatherall RC. Zopiclone fatality in a hospitalized patient. J Forensic Sci
1997;42(2):340e3.
31. Creaney W, Murray I, Healy D. Antidepressant induced suicidal ideation.
J Psychopharmacol 1992;6(1):120.
32. Corkery JM, Schifano F, Ghodse AH. Mephedrone-related fatalities in the United
Kingdom: contextual, clinical and practical issues. Pharmacology 2012;17:
355e80.
R.K. Sewal et al. / Journal of Forensic and Legal Medicine 34 (2015) 113e118 117

33. De Berardis D, Serroni N, Campanella D, Olivieri L, Ferri F, Carano A, et al.
Update on the adverse effects of clozapine: focus on myocarditis. Curr Drug Saf
2012;7(1):55e62.
34. Fineschi V, Ner M, Riezzo I, Turillazzi E. Sudden cardiac death due to hyper-
sensitivity myocarditis during clozapine treatment. Int J Leg Med 2004;118(5):
307e9.
35. Killeen DMJ. Antipsychotic-induced sudden cardiac death: examination of an
atypical reaction. Expert Opin Drug Saf 2009;8(3):249e52.
36. Burns JM, Boyer EW. Antitussives and substance abuse. Subst Abuse Rehabili-
tation 2013;4:75e82. http://dx.doi.org/10.2147/SAR.S36761.
37. McCormick PA, Treanor D, McCormack G. Farrell M. Early death from para-
cetamol (acetaminophen) induced fulminant hepatic failure without cerebral
oedema. J Hepatol 2003;39(4):547e51.
38. Garratty G, Postoway N, Schwellenbach J, McMahill PC. A fatal case of ceftri-
axone (Rocephin)-induced hemolytic anaemia associated with intravascular
immune hemolysis. Transfusion 1991;31:176e9.
39. Kapur G, Valentini RP, Mattoo TK, Warrier I, Imam AA. Ceftriaxone induced
hemolysis complicated by acute renal failure. Pediatr Blood Cancer 2008;50(1):
139e42.
40. Hanson GC. A death from tetracycline. Postgrad Med J 1968;44:870e4. http://
dx.doi.org/10.1136/pgmj.44.517.870.
41. Cheng K, Masters S, Stephenson T, Cooke R, Ferner R, Ashworth M, et al.
Identiﬁcation of suspected fatal adverse drug reactions by paediatricians: a UK
surveillance study. Arch Dis Child 2008;93:609e11.
42. Breen DP, Marinaki AM, Arenas M, Hayes PC. Pharmacogeneticassociation with
adverse drug reactions to azathioprine immunosuppressive therapy following
liver transplantation. Liver Transpl 2005;11(7):826e33.
43. Andersen V, Sonne J, Andersen M. Spontaneous reports on drug-induced pancre-
atitis in Denmark from 1968 to 1999. Eur J ClinPharmacol 2001;57(6e7):517e21.
44. Gastal GR, Moreira S, Noble CF, Ferreira LE, França PH, Pinho M. Toxicity of
azathioprine: why and when: analysis of the prevalence of polymorphism in
Joinville, SC, Brazil. Arq Gastroenterol 2012;49(2):130e4.
45. Clarkson A, Choonara I. Surveillance for fatal suspected adverse drug reactions
in the UK. Arch Dis Child 2002;87:462e7.
46. Ichikawa Y, Ghanefar M, Bayeva1 M, Wu R, Khechaduri A, Sathyamangla V,
et al. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron
accumulation. J Clin Invest 2014;124(2):617e30.
47. Tost JR, Vidal R, Cayla J, Díaz-Cabanela D, Jimenez A, Broquetas JM. Severe
hepatotoxicity due to anti-tuberculosis drugs in Spain. Int J Tuberc Lung Dis
2005;9(5):534e40.
48. Roussin A, Mirepoix M, Lassabe G, Dumestre-Toulet V, Gardette V,
Montastruc JL, et al. Death related to a recreational abuse of propofol at
therapeutic dose range. Br J Anaesth 2006;97(2):268.
49. [Internet] Glossary of terms used in pharmacovigilance. 2011 March [cited 2014
Feb 22]. Available from:, http://who-umc.org/Graphics/24729.pdf.
50. Agbabiaka TB, Savovic J, Ernst E. Methods for causality assessment of adverse
drug reactions a systematic review. Drug Saf 2008;31(1):21e37.
51. Edwards IR. Considerations on causality in pharmacovigilance. Int J Risk Saf Med
2012:2441e54. http://dx.doi.org/10.3233/JRS-2012-0552.
52. Zaki SA. Adverse drug reaction and causality assessment scales. Lung India
2011;28:152e3.
53. [Internet] The use of the WHO-UMC system for standardised case causality
assessment. 2012 April 17 [cited 2014 Mar27]. Available from:, http://who-
umc.org/Graphics/24734.pdf.
54. Labadie J. Forensic pharmacovigilance and substandard or counterfeit drugs. Int
J Risk Saf Med 2012;24:2437e9.
55. Grootheest KV. The dawn of Pharmacovigilance: an historical prospective. Int J
Pharm Med 2003;17:195e200.
56. Medhi B, Sewal RK. Ecopharmacovigilance: an issue urgently to be addressed.
Indian J Pharmacol 2012;44(5):547e9.
57. Bisht A, Singh S, Marwah N. Hemovigilance Programme-India. Asian J Transfus
Sci 2013;7:73e4.
58. Hartigan-Go Kenneth. Presenting evidence for the court. Int J Risk Saf Med
2012;24:59e63.
59. Persaud N, Healy D. Epidemiological evidence in forensic pharmacovigilance.
Int J Risk Saf Med 2012;24:31e5.
60. Dutelle AW. Ethics and forensic science. Mar-Apr Evid Technol Mag 2011;9(2):
24e5.
61. Barnett Peter D. Ethics in forensic science: professional standards for the practice
of criminalistics. Boca Raton, FL: CRC Press; 2001.
62. Aronson JK, Ferner RE. Clariﬁcation of terminology in drug safety. Drug Saf
2005;28(10):851e70.
63. Jeetu G, Anusha G. Pharmacovigilance: a worldwide master key for drug safety
monitoring. J Young Pharm 2010;2(3):315e20.

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