Pharmacogenovigilance: A Potential Tool in Pharmacovigilance

Abstract

Pharmacogenovigilance is a program which can be developed by integrating pharmacogenomics into a pharmacovigilance studies. The fact that genes play a vital role in variability in response to medicines makes pharmacogenomic of adverse drug reactions (ADRs) very essential program. Genetic variations have significantly affected the drug action in many patients, and a time predisposes patient to uncommon ADRs that are not seen in other patients. Pharmacogenetics provides greener path to individualized use of medicines, drug safety and efficacy studies due to genetic polymorphism. In order to explore these potential benefits, integration of pharmacogenovigilance in to clinical practice and public health system has become necessary. It is imperative for every medical practitioner to consider genetic factors in order to prescribe the best medication to his patients. Literature search using terms genetic biomarkers, application of pharmacogenetics and pharmacogenomics, and influence of pharmacogenetics on pharmacovigilance was done using PubMed, PhamaKG, US FDA and WHO websites. Several challenges facing drug safety and pharmacovigilance were highlighted and proposed pharmacogenomics approaches in solving them. The purpose of this article is to justify pharmacogenovigilance as an essential tool for drug safety and efficacy while providing the most feasible way for its successful integration in to the cycle of patients care. In conclusion, considerable progresses have been recorded on the potentials of pharmacogenovigilance in drug safety and efficacy study during post-marketing surveillance, and based on the provided evidences, the right time for pharmacogenovigilance is now.

Full text

Research J. Pharm. and Tech. 7(12): December 2014
1476
ISSN 0974-3618 www.rjptonline.org
REVIEW ARTICLE
Pharmacogenovigilance: A Potential Tool in Pharmacovigilance
Adamu Yau1, Nordin Bin Simbak2, Mainul Haque3*
1Masters Student, Unit of Pharmacology, Faculty of Medicine and Health Sciences (FPSK), Universiti Sultan
Zainal Abidin (UniSZA), 20400 Kuala Terengganu, Terengganu, Malaysia.
2Professor and Dean, FPSK, UniSZA, Kampus Kota, Jalan Sultan Mahmud 20400, Kuala Terengganu, Malaysia.
3Professor, Head of the Unit of Pharmacology, FPSK, UniSZA, 20400 Kuala Terengganu, Terengganu,
Malaysia.
*Corresponding Author E-mail: runurono@gmail.com
ABSTRACT:
Pharmacogenovigilance is a program which can be developed by integrating pharmacogenomics into a
pharmacovigilance studies. The fact that genes play a vital role in variability in response to medicines makes
pharmacogenomic of adverse drug reactions (ADRs) very essential program. Genetic variations have significantly
affected the drug action in many patients, and a time predisposes patient to uncommon ADRs that are not seen in other
patients. Pharmacogenetics provides greener path to individualized use of medicines, drug safety and efficacy studies
due to genetic polymorphism. In order to explore these potential benefits, integration of pharmacogenovigilance in to
clinical practice and public health system has become necessary. It is imperative for every medical practitioner to
consider genetic factors in order to prescribe the best medication to his patients. Literature search using terms genetic
biomarkers, application of pharmacogenetics and pharmacogenomics, and influence of pharmacogenetics on
pharmacovigilance was done using PubMed, PhamaKG, US FDA and WHO websites. Several challenges facing drug
safety and pharmacovigilance were highlighted and proposed pharmacogenomics approaches in solving them. The
purpose of this article is to justify pharmacogenovigilance as an essential tool for drug safety and efficacy while
providing the most feasible way for its successful integration in to the cycle of patients care. In conclusion,
considerable progresses have been recorded on the potentials of pharmacogenovigilance in drug safety and efficacy
study during post-marketing surveillance, and based on the provided evidences, the right time for
pharmacogenovigilance is now.
KEYWORDS: Pharmacogenovigilance, Pharmacovigilance, Pharmacogenetics, Pharmacogenomics, Drug-safety,
Drug-Efficacy.
INTRODUCTION:
The advancement made in technology of drug development
has led to availability of large number of new medicines
which also increases possibilities of ADRs [1]. These have
justified the setting up of systems for safety monitoring of
medicines called pharmacovigilance. The major
components of pharmacovigilance system are facing
problems of serious under reporting. Pharmacogenomics is
a discipline that deals mainly with the study of drug-
metabolizing enzymes, pharmacogenetics of ADRs,
identification of genetic biomarkers, diagnostic tests for
pharmacogenetic decision, guidelines for gene/drug pairs,
and individualized use of medicines, as well as drug safety
and efficacy studies[2-4].
Received on 12.10.2014 Modified on 22.10.2014
Accepted on 21.11.2014 © RJPT All right reserved
Research J. Pharm. and Tech. 7(12): Dec. 2014; Page 1476-1482
Pharmacogenomics based practice has been adopted in
many developed countries, however, this development has
pose challenges to medical professionals as health care
service providers[5]. The main purpose of this article is to
review pharmacovigilance issues related to
pharmacogenomic biomarkers, and to relate between
pharmacogenetics and pharmacovigilance for better drug
safety and efficacy.
PHARMACOGENOMICS:
Pharmacogenomics is the study of how genetic factors
relate to inter-individual variability of drug response[6].
Pharmacogenomics involve the application of whole
genome technologies for the prediction of the sensitivity or
resistance of an individual’s disease to a single drug or
group of drugs[7]. Many clinicians may not be familiar with
the background and terminology used in the
pharmacogenomic literature [6].

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1477
PHARMACOGENETICS:
Pharmacogenetics can be described as the science of drug
pharmacological response and its modification by
hereditary influence; pharmacogenetics study encompasses
both drug efficacy and toxicity[7]. Similarly, it deal with the
genetic basis which underlies variable drug response in
individual patients, it develops an individualized approach
to the drug therapy, where optimally effective drugs are
matched to a patient's unique genetic profile[7] .
Pharmacogenetics provides insight into the molecular level
of drug function and consequently offers the potential of
individualized drug therapy; thus it can help in optimizing
drug efficacy and minimizing adverse drug reactions[7]. The
terms ″pharmacogenomics″and ″pharmacogenetics″can be
used synonymously, pharmacogenetics study an
unexpected drug response and try to find a genetic cause,
while pharmacogenomics study genetic differences within a
population that explain certain observed responses to a drug
or susceptibility to a health problem[8].
What is Genomic Biomarker?
A measurable DNA and/or RNA characteristic that is an
indicator of normal biologic processes, pathogenic
processes, and/or response to therapeutic or other
interventions[9].WHO in coordination with the United
Nations and the International Labour Organization, has
defined a biomarker (biological marker) as “any substance,
structure, or process that can be measured in the body or its
products that influence or predict the incidence of outcome
or disease”[10]. In a broader definition, it takes into account
of the effects of treatments, interventions, and even
unintended environmental exposure, such as to chemicals or
nutrients[10]. In their report on the validity of biomarkers in
environment risk assessment, the WHO has stated that a
true definition of biomarkers includes “almost any
measurement reflecting an interaction between a biological
system and a potential hazard, which may be chemical,
physical, or biological [10]. However, research seeks to
increase our understanding of the causes of diseases, but
there is also hope that the recognition of new risk factors
will lead to improved methods for identifying persons who
are in the early stages of, or at high risk for, the diseases of
concern[11].
Drug Safety Challenges:
Globally, ADRs is a major problem for every stakeholder.
The WHO defined ADRs as any response to a drug that is
noxious and unintended, and that occurs at doses used in
humans for prophylaxis, diagnosis, or therapy, excluding
failure to accomplish the intended purpose[12]. Due to
challenges of ADRs faced by health care professionals,
international drug monitoring program was set up after the
thalidomide-disaster in 1960s [13]. ADRs are responsible for
a significant number of hospital admissions ranging from
0.3% to 11% [12]. Adverse drug reaction was also
established as the 4th leading cause of death in USA, and
up to 20% increase in healthcare budget spent on drug
complications [14]. The consequences of ADRs may lead to
short-term hospitalization, long-term hospitalization and
even mortality. Each year, approximately 100,000
Americans die of ADRs to medicine and approximately 2
million are hospitalized [15]. According to research
conducted, ADRs and medication errors causes 2.3% of
inpatient stays in UK, 4.8% in Germany and 7.3% of
USA[16]. Studies have shown that prescription drugs are
responsible for 20-25% of deaths, and in almost all the
cases the death was preventable [17].It was established that
up to 50% of newly approved medicine possess serious
ADRs that were detected at post-marketing stage but
unfortunately only 5%were reported [18]. Ethnic background
is believed to be controlled by genetic factors which are
responsible for genetic polymorphism; individual
differences in enzyme ability to metabolize drugs;
differences in drug receptors and transporters[8].
Occurrence of ADRs differs from one population of
patients to another due to genetic differences[8]. In a
cohort study to investigate factors that predisposes
patient to ADRs by angiotensin converting enzyme
(ACE) inhibitors using 2225 people where 19% dropped
out due ADRs, it was found that African-American are
more susceptible to ACE-related angioedema than other
ethnic groups[8]. Research has shown that black people had
higher risk of intracranial hemorrhage and also had 3.0
relative risk of angioedema compared to non-black people.
Patient from East-Asia have three times risk of
developing cough with ACE inhibitors than white
patients[8]. Patients suffering from Parkinson disease who
have UDP-glucuronosyltransferase 1A9 genotype are
more susceptible to ADRs when treated with catechol-
O-methyltransferase inhibitors[8]. Current research
indicated that patient that developed ADRs have higher
CYP1A2, low allele combinations (8/12; 67%) and lower
CYP1A2-mRNA than patient that do not developed
ADRs (6/22; 27%, p = 0.019)[8].
Pharmacovigilance:
Pharmacovigilance is a part of patient care safety studies
that ensures the best use of medicines. According to WHO,
pharmacovigilance is the science and activities relating to
the detection, assessment, understanding and prevention of
ADRs [12].Therefore, pharmacovigilance is an integral parts
of a quality management system spanning the whole cycle
of healthcare delivery services. It includes making the
diagnosis; choice of treatment; process of prescription,
dispensing, administration and outcomes assessment.
Meanwhile, outcomes assessments include evaluation of the
benefits as well as monitoring harmful effect of the
treatment[19]. The current pharmacovigilance system
depends largely on spontaneous reporting of ADRs as one
of the key mechanisms that allow the detection of new and
rare problems [20]. However, this operating
pharmacovigilance is facing some challenges and barriers.
Challenges of Current Pharmacovigilance:
One of the major challenges in the pharmacovigilance
program is under-reporting which is up to 95%[21]. The
reason for under-reporting includes uncertainty regarding
the types of reaction to report; lack of awareness of function
and purpose of the national ADR reporting scheme[22]. In
addition, causality assessment and mechanisms of ADRs

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reports are complicated [20]. Therefore, preparing of ADRs
reports take long time. It is difficult to extrapolate a genuine
ADRs signal detected in particular locations to a larger
population[23]. The factors contributing to variability in drug
responses include: age, medication error, concomitant drug,
concomitant diseases, products quality, diet, compliance,
gender, weight and genetic factors[8].Patient genotype is
currently neglected in prescribing of medicines. Several
studies related to pharmacovigilance and ADRs monitoring
were conducted, and despite the developments made in the
field of pharmacogenomics, little attention has been paid to
its integration in to the healthcare services[24-25]. The
effectiveness and success of any pharmacovigilance system
depends on identifications of ADRs and cooperation
between health care professionals. Studies indicated that
inadequate knowledge and lack of awareness about ADR
reporting, pharmacovigilance and pharmacogenomics
among healthcare professionals are associated with under-
reporting and low performance of pharmacovigilance
program[5, 26].
Pharmacogenovigilance:
Pharmacogenovigilance can be described as
pharmacovigilance activities that deal with
pharmacogenomics analyses and pharmacogenomics
tests [27]. Pharmacogenovigilance can also be defined the act
and science involving the knowledge of genetic variations
in whole cycle of healthcare delivery and patient care.
These include diagnosis, the choice of treatment, process of
prescriptions, dispensing, counseling, administration and
outcomes assessment. The assessment of the outcomes
should include evaluating and monitoring of the benefits,
examining and managing unwanted or harmful effects.
Justification of Pharmacogenovigilance:
There are increased number of incidences of drug related
problems that are genetically bound leading to the delayed
detection and under-reporting of ADRs [27]. Recent
evidences suggested that most prescribed medications are
significantly associated with ADRs which often leads to
hospitalization [28]. Over five decades, it was discovered that
genetic variations significantly influences pharmacokinetics
and pharmacodynamics [2]. A range of pharmacogenetics
tests have been developed and made available in medical
practice to safeguard patients from ADRs [29]. Furthermore,
drugs frequently associated with ADR are known to be
metabolised by enzyme with genetic polymorphism; when a
safety signal is observed in a patient who are ultra-rapid
metabolizers of CYP2D6, then it would be logical to study
that population for prevalence of CYP2D6 [2]. In new drug
candidates, where early phase clinical trial data suggest
toxicity due to CYP2D6 ultra-rapid metabolizers, phase 4
clinical trials can be focused more on the mentioned
enzyme [2].Research carried out revealed the need for
inclusion of genetic information in labeling certain drugs
e.g. abacavir, warfarin, clopidogrel, irinotecan, maraviroc,
cetuximab; therefore, pharmacogenovigilance studies are
essential part of drug approval [29]. Both
pharmacogenomics and pharmacovigilance aim to
understand the inter-relationships between drug therapeutic
efficacy and safety but unfortunately these two related
fields yet do not work together[30]. Pharmacogenomics
based clinical practice have been successfully recognized
by many developed countries in order to enhance quality
health care [5]. Several efforts made in individualizing use of
medicine were further advanced by the sequencing
technologies and human genome projects [31]. The major
barriers in pharmacogenomics practice are acknowledge
gaps and limited awareness among healthcare providers [5].
Further Evidence:
Early detection and assessment of ADRs is very important
in order to optimally protect patients. Individual genetics
composition plays a major role in variability of drug
responses; the developments made in the field of
pharmacogenomics have greatly improved drug safety and
efficacy. Evidence that further justified the need for
inclusion of pharmacogenovigilance study in clinical
practice is the discovery of genetic biomarkers.
Genetic Factors/Biomarkers:
Genetic biomarkers provide chances for prediction of drug
related events with respect to individual genetic makeup
prior to drug exposures. Using the microarray technologies,
the discovery of biomarkers has been achieved at
productive rates. Based on the affected parameters they can
be grouped in to the following:
a. Genetic Biomarkers associated with
Pharmacokinetics and Pharmacodynamics:
Genetic polymorphism of drug metabolizing enzymes
(DME) involves gene copy number variation such as gene
amplification and deletion, small insertions and deletions,
and single-nucleotide polymorphisms (SNPs)in DNA
sequence[32]. Most of phase I and phase II drug metabolizing
enzymes are polymorphic; consequently, this genetic
polymorphism is responsible for individual variations in
response to a drug or its metabolites, as well as drug related
problems[33]. In recent years, there is an increased in
understanding of clinical significant of genetic variations
and several data bases on pharmacogenomic information of
drug metabolizing enzymes are available[32]. In addition,
study on global and local SNP profiles in 283 DMEs as well
as transporter genes across 62 worldwide ethnic groups
indicated that there was positive selection on variation of
DME genes which contributes to population heterogeneity
in drug response [33]. Polymorphisms of DME genes are
important determinants of drug response, and genetic
biomarkers recognized by US FDA were reviewed and
explained which revealed that majority of pharmacogenetic
drug labels refer to genes encoding phase I and II of
DME[33]. These genetic biomarkers have influenced the
exposure level of drug or its metabolite(s) and thereby
affecting drug pharmacokinetics and pharmacodynamics[32].
The roles of drug metabolizing enzymes (DME) and
transporter proteins relevant to drug pharmacokinetics and
pharmacodynamics have been studied. The post-marketing
identification of a PK genomic biomarker with clinical
impact on 123 benefit risk of a medicine, the case of
CYP2C19 and the use of clopidogrel, a prodrug used for
prevention of athero-thrombotic events in coronary artery

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and 125 cerebrovascular disease or after stent implantation
which is metabolized mainly by CYP2C19 to produce the
126 active metabolite that inhibits platelet aggregation have
been investigated[34]. Similar effects have been postulated to
occur when clopidogrel was used with 138 CYP2C19
inhibitors (e.g. proton pump inhibitors);furthermore, the
impact of pharmacogenetic variants in drug
pharmacokinetics exist and scientific evidence has been
generated in the post-approval phase of the life-cycle of
medicines[6,32,35-38]. The impact of vitamin K epoxide
reductase (VKORC1) polymorphisms and the use of
warfarin is another example of a pharmacodynamic-related
genomic variant identified after drug approval by FDA [39].
The Table 1 provides a summary of how genetic
biomarkers influence pharmacokinetics and
pharmacodynamics[6, 32, 35-38]. Similarly, the US Food and
Drug Administration (FDA), the European Medicines
Agency (EMEA) and Canadians pharmacogenomics
Networks for Drug Safety highlighted such variations in
specific guidelines in clinical pharmacology in order to link
pharmacogenomics and pharmacovigilance[39].
Table 1: Summary of Genetic Biomarkers hat Affect Pharmacokinetics and Pharmacodynamics
S/N Biomarkers Drug name Clinical outcomes Types of study
1. CYP2D6(Various) Codeine Non-response/CNS toxicity GWA
2. CYP2C9* and *3 Warfarin Bleeding GWA
3. CYP2C19*2, *3, *17 Clopidogrel S. Thrombosis and Bleeding GWA
4. CYP2D6(Various) Tamoxifen Breast cancer recurrence GWA
5. CYP3A5*3 Tacrolimus Graft rejection GWA
6. CYP2D6(various) Antidepressants Non-response GWA
7. CYP2C19*17 Escitalopram Non-response
8. CYP2C9*2 and *3 NSAIDs Gasto-intestinal bleeding GWA
9. UGT1A1*28 Irinotecan Myelotoxicity GWA
10. TPMT*2, TPMT*3A, *3C 6-MP and AZA Myelotoxicity GWA
11. CYP2B6 NNRTI CNS changes GWA
NSAIDs=Non-Steroidal Anti-Inflammatory Drug, NNRTI=Non-Nucleoside Reverse Transcriptase Inhibitors
Table 2. Genetic Biomarkers that are Associated with Drug Induced Toxicity Risk Status
No. Biomarkers Drug name Clinical outcomes Types of study
1. B*57:01 Abacavir Hypersensitivity Candidate gene
2. DRB1*15:01-DQB1*06:02
A*02:01
Amoxy-clavlnate Liver injury Candidate gene
3. DRB1*07*01-DQA*02:01 Ximelagatran Liver injury GWA
4. A*33:03 Ticlopidine Liver injury GWA
5. B*57:01 Flucloxacillin Liver injury GWA
6. DRB1*15:01-DQB1*06:02 Limiracoxib Liver injury GWA
7. DQA1*02:01 Lapatinib Liver injury GW and Candidate
8. DRB1*01 Nevirapine Liver injury Candidate gene
9 B*15:02 Carbamazepine SJS and TEN Candidate gene
10 A*31:01 Carbamazepine Various skin reactions GWA
11 B*58:01 Allopurinol Various skin reactions Candidate gene
12 B*35:05 Nevirapine Skin reactions GW and Candidate
13 Cw*8 Nevirapine Skin reactions GW and Candidate
14 Cw*04 Nevirapine Skin reactions Candidate gene
15 CYP2B6 Carbamazepine Skin rashes Candidate gene
16 NAT2 Isoniazid DI Liver injury Candidate gene
17 UGT1A Tolcapone DI Liver injury Candidate gene
18 UGT2B7 Diclofenac DI Liver injury Candidate gene
19 UGT1A Various drug DI Liver injury GWA
20 IL4, C-590A Diclofenac DI Liver injury Candidate gene
21 IL6, intron Tacrine DI Liver injury Candidate gene
22 IL10, C-627A Diclofenac DI Liver injury Candidate gene
23 UGT1A6*4 Diclofenac Cardiac toxicity and HF
24 NOS3 rS1799983 Vincristine Neurotoxicity
25 TPMT Cisplatine Ototoxicity, Neurotoxicity and
Nephrotoxicity
26 SLCO1B1 Simvastatins Myopathy GWA
27 ABCB11 Various drugs DI Liver injury Candidate gene
28 ABCC2 Diclfenac DI Liver injury Candidate gene
29 SLC22A1(OCT1) Metformin,Opoid, and
odensetron
Hepatotoxicity Candidate gene
30 SLCC28A3 Anthracycline Cardiotoxicity
DI=Drug-Induced, SJS= Steven Johnson Syndrome, TEN=Toxic Epidermal Necrosis

Research J. Pharm. and Tech. 7(12): December 2014
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b. Genetic Biomarkers Non-Associated with
Pharmacokinetics and Pharmacodynamics:
These are serious adverse drug events that involved drug-
induced toxicity [3]. Some serious and unwanted
consequences of drug exposure depend on patient risk
status which genetic biomarker is one of them. Over thirty
years, it was observed that Human Leukocyte Antigen
(HLA) is a predictor of risk for certain ADRs [3] which can
be grouped in to the following:
1. Genetic Biomarker associated with Drug-Induced
Liver Injury:
Many drugs currently in use may cause serious ADRs
through the roles of human leukocyte antigen (HLA) genes
in susceptible individuals[32]. For Drug-induced liver injury
(DILI), the first reports linking HLA and genetic
susceptibility involved the use of anaesthetic halothane, an
important cause of idiosyncratic hepatitis which was used
widely up to the 1980s; association between the HLA class
II serotype DR2 was reported by a study based in Japan [40].
A large study of a number of different drugs was associated
with class I serotype HLA-A11 for DILI induced by
tricyclic antidepressants and Diclofenac, and for class II
serotype HLA-DR6 in relation to DILI was due to
chlorpromazine[3, 41]. More recently, HLA associations with
DILI have been studied directly by genotyping rather than
serotype determination [3]. The first HLA genotyping study
was gene association with amoxicillin-clavulanate-related
DILI. Though this form of DILI does not generally show
classical immune-related features, two independent gene
association studies reported an identical association with the
HLADRB1*15:01 allele which corresponds to some DR2
serotype[32]. Similarly, this form of DILI was predominantly
related to the clavulanic acid component of the drug [42].
Subsequent genetic studies on DILI using both candidate
gene and GWA methods have resulted in the identification
of a number of different HLA class I and II associations
(Table 2) [6, 32, 35-38]. The effect sizes observed vary
considerably, with odds ratios of between 2 and 80 reported
for different drugs; the strongest HLA association reported
for DILI was related to reactions with flucloxacillin[32]. A
GWA study showed a very strong association (odds ratio
80) with the class I HLA allele B*57:01 which had been
previously demonstrated to be a strong risk factor for
hypersensitivity reactions to abacavir (Table 2) [6, 32, 35-38].
2. Genetic biomarkers associated with hypersensitivity
reactions affecting the skin:
Serious ADRs affecting the skin involving drug-induced
hypersensitivity can be divided into HLA genetic associated
and Non-HLA genetic associated [3]. There was a recent
study showing the role of T-cell reactions in drug-induced
skin rash and HLA associations with this reaction had been
reported[43]. A candidate gene study involving genotyping
for HLA alleles and a range of polymorphisms in
cytochromes P450 in Taiwanese cases of Carbamazepine-
induced SJS found a very strong association with adverse
drug reaction with the class I allele B*15:02(Table 2)[6, 32,
35-38]. Genotyping for B*15:02 is now recommended in
individuals from Han Chinese, Thai, Malaysian,
Indonesian, Philippino and south Indian ethnicity prior to
Carbamazepine prescription[44], but the association does not
extend to most other ethnic groups, probably because of the
low frequency of B*15:02 among them. HLA allele
B*15:02 does not appear to be a risk factor for more
common mild skin reactions induced by Carbamazepine[44].
A combination of candidate gene and GWA studies has led
to the identification of a number of HLA associations with
ADRs affecting skin[6, 32, 35-38]. Table 2 summarizes current
data of genetic biomarkers associated with inert immunity,
cardiac toxicity and other idiosyncratic drug
reactions[6, 32, 35-38].
DISCUSSION AND CONCLUSION:
Pharmacovigilance enhances patient care and safety and
supports public health programs while pharmacogenomics
plays an important role in optimizing drug safety. Although
pharmacovigilance centres are well-established and play
crucial in ensuring drug safety, despite the important roles
of pharmacogenomics, it was wrongly perceived as an
expensive discipline resulting in poor funding from
government especially in developing countries. In the
current pharmacovigilance system, healthcare providers
detect and report adverse reactions to the medicines that
have been in the market for a long time without
consideration on the individual variability in drug response
due genetic differences. It was established that no
medicines are universally fit for all; therefore, it has become
necessary to evaluate and monitor drugs based on
individual genetic biomarkers. In general,
pharmacogenomics is not seen as an essential tool in drug
safety; therefore, it is yet to be incorporated in
pharmacovigilance. This is due to misunderstanding of the
meaning and the objectives of the two disciplines, as well as
paucity of knowledge and awareness among healthcare
providers. Finally, the developments made in the field of
pharmacogenomics, if properly explore will go a long way
in solving drug related problems. At the end of 2010, 134
countries were part of the WHO pharmacovigilance
program, therefore to successfully integrate
pharmacogenomics into public heath, linking
pharmacogenomics with pharmacovigilance study would
provide fastest and the simplest way to bridge the existing
gap in knowledge and awareness.
LIMITATION OF THE STUDY:
Many articles were included in this study but yet some of
the full texts were not accessible. Due to continuous
research in the field of pharmacogenomics and
pharmacovigilance this articles covers limited number of
biomarkers within its scope and due to time factor.
ACKNOWLEDGEMENT:
Authors are much grateful to the authority of Universiti
Sultan Zainal Abidin, Kuala Terengganu, Malaysia. This
study obtained no funding. Authors possess no conflict of
interest.

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