Project Work On Post Marketing Surveillance of Pemazyre: For Partial Fulfilment of The Requirement For The

PROJECT WORK ON POST MARKETING
SURVEILLANCE OF PEMAZYRE
For Partial Fulfilment of the Requirement for the

Bachelor of Pharmacy
For
Dr. A.P.J. ABDUL KALAM TECHNICAL UNIVERSITY,
LUCKNOW
Through
AZAD INSTITUTE OF PHARMACY & RESEARCH,
LUCKNOW
Under the supervision of

SUBMITTED BY:
MR. NEERAJ PANDEY
MOHD SAIF SIDDIKEE SUPERVISED BY :
1819750063 NEERAJ PANDEY
BPHARM 4TH YEAR Asst. Professor
8TH SEMESTER A.I.P.R
AZAD INSTITUTE OF PHARMACY &
RESEARCH, LUCKNOW
Azad Puram, Post-Chandrawal, Via Bangla Bazar, Near CRPF
Camp, Lucknow
DECLARATION
I, MOHD SAIF SIDDIKEE certify that the work

embodied in the “Project Work on Post
Marketing Surveillance PEMAZYRE” is my own
bonafide work carried out under the supervision
of Neeraj Pandey, Azad Institute of Pharmacy &
Research, Lucknow.
MOHD SAIF SIDDIKEE
MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

AZAD INSTITUTE OF PHARMACY &
RESEARCH, LUCKNOW
Azad Puram, Post-Chandrawal, Via Bangla Bazar, Near CRPF
Camp, Lucknow
ACKNOWLEDGEMENT
I would like to express my sincere gratitude for
Neeraj Pandey, Azad Institute of Pharmacy and
Research, who inspire me and courage me with
his valuable knowledge and experience. I am very
thankful to Rizwan Ahmad& Head of Pharmacy
Department for providing me all the necessary
facilities, suggestion, support and guidance.
NEERAJ PANDEY

Table of Contents
Front Page..................................................................................................1
Declaration……………………………………………………………………………………….......2
Acknowledgement... ……………………………………………………………………………..3
Table of Content... ………………………………………………………………………….,…….4
Abstract..... ……………………………………………………………………………………........5
Background... …………………………………………………………………………………….....6
Introduction. ……………………………………………………………………………………......7
Pharmacovigilance. ……………………………………………………………………………....8
The importance of PV & Do's. ……………………………………………………………....9
Terms used in PV... ……………………………………………………………………………..10
Adverse Drug Reactions.... ………………………………………………………………….11
Classification of ADR. ………………………………………………………………………....12
ADR Knowledge... …………………………………………………………………….………...13
Reporting ADR.. ……………………………….………………………………………………..14
ADR FORM... ……………………………………………………………………………………...15
PROCLAMATIONS.. …………………………………………………………………………….16
Drug Causing ADR.. ………………………………………………………………………......17
DRUG PROFILE. …………………………………………………………………………….......18
PEMAZYRE.. ………….…………………..…………………………………………………......19
ADVERSE REACTION... …………………………………………………………….……......20
FULL PRESCRIBING INFO.. ……………………………………………………….……......21
DOSAGE MODIFICATION... …………………………………………………….………....22
DOSAGE FORMS AND STRENGTHS.... ….………………………………….…………23
ADVERSE REACTION...
…………………………………………………………….…….....24CONCLUSION..
….……………………….…………………………………………….…......30DISCUSSION……
……..………………………………………………………….………….....31
REFERENCE... ………………………………………………………………………….…….....32

ABSTRACT
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 up to 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.
Keywords: Pharmacovigilance; Adverse drug reactions;

Clinical trial

BACKGROUND
Pharmacovigilance is the science and activity relating to the

detection, assessment, understanding and prevention of
adverse events.
An adverse drug event is defined as any undesirable medical
event related to the use of medications, including any
noxious or unintended side effect or adverse drug reaction
(ADR).
Specific aims of pharmacovigilance activities are to detect
any rare or long-term adverse drug events across much larger
patient population and over longer periods than possible
during Phase I-III investigations. Harmful effects discovered
may result in warnings restricting its use for certain
indications or populations or in the event of profound safety
concerns, removal of the drug from the market entirely.The
ultimate goal of pharmacovigilance is to improve the safe and
rational use of medicines, thereby improving patient care and
public health.4,5 Adverse drug event reporting is the
cornerstone of pharmacovigilance activity. It has been
previously demonstrated that the majority of global
information related to ADRs arises from Western nations.The
nature of adverse event reporting systems and generated
data is not currently readily available for all countries.

INTRODUCTION
Safety and efficacy are the two major concerns about a drug. While
efficacy of a drug can be quantified with relative ease, the same cannot
be said about safety. This is because, the adverse effect of a drug may be
uncommon (but very serious) and many patients may be affected or
subjected to a potential risk before the relationship with the drug is
established. Adverse Drug Reactions (ADRs) are associated with a
significant morbidity and mortality. Recent estimates suggest ADRs to be
the fourth major cause of death in the Unites States of America (USA).
This gave birth to the branch of pharmacovigilance. By definition,
pharmacovigilance is, “The science and activities relating to the detection,
assessment, understanding and prevention of adverse effects or any
other drug-related problems”. Spontaneous reporting has contributed
significantly to successful pharmacovigilance. The contribution of health
professionals, in this regard, to ADRs databases is enormously significant
and has encouraged ongoing ascertainment of the benefit-risk ratio of
some drugs, as well as contributed to signal detection of unsuspected and
unusual ADRs previously undetected during the initial evaluation of a
drug. The Uppsala Monitoring centre (UMC, WHO), Sweden is
maintaining the international database of adverse drug reaction reports
(currently about 4.7 million case reports) received from several national
centres (96 member countries). However, still, it is estimated that only 6-
10% of all ADRs are reported. Although, India is participating in the
program, its contribution to UMC database is very little. This is essentially
due to the absence of a vibrant ADR monitoring system and also lack of a
reporting culture among health care workers. Many factors are
associated with ADRs under-reporting among health professionals.

PHARMACOVIGILANCE
Medicines and vaccines have transformed the prevention and

treatment of diseases. In addition to their benefits, medicinal
products may also have side effects, some of which may be
undesirable and / or unexpected. Pharmacovigilance is the
science and activities relating to the detection, assessment,
understanding and prevention of adverse effects or any other
medicine/vaccine related problem.
All medicines and vaccines undergo rigorous testing for safety

and efficacy through clinical trials before they are authorized for
use. However, the clinical trial process involves studying these
products in a relatively small number of selected individuals for
a short period of time. Certain side effects may only emerge
once these products have been used by a heterogenous
population, including people with other concurrent diseases,
and over a long period of time.

The importance of Pharmacovigilance:
We have shown a notable rise in the number of clinical trials through
the past few years, and this happening is a double-edged
weapon!Although new medicine development is essential for a large
portion of patients, the number of clinical trials may affect the
function of ethics committees and regulators, which may lead to
unethical patient practices, poor reporting of adverse effects, and
inadequate patient monitoring during the phases of clinical trials.
What does pharmacovigilance do?

The role of pharmacovigilance is to assess whether the benefits of a
drug outweigh the risks, and it doesn’t stop after the medicines are
certified. PV involves ongoing monitoring of medications to ensure
they remain safe for use, primarily since previously undetected
adverse events can occur at any time.
This position has a significant impact on improving the medicines’
safety profile, intensifying patient care and safety, and also
supporting the work of national drug regulatory authorities.

TERMS USED IN PHARMACOVILANCE
Absolute
Risk in a population of exposed persons; the probability of an event affecting
members of a particular population (e.g. 1 in 1,000). Absolute risk can be measured
over time.
AdverseEvent
Any untoward medical occurrence that may present during treatment with a
pharmaceutical product but which does not necessarily have a causal relationship
with this treatment.
synonym: adverse experience
Adverse(drug)reaction(ADR)
A response which is noxious and unintended, and which occurs at doses normally
used in humans for the prophylaxis, diagnosis, or therapy of disease, or for the
modification of physiological function. (WHO, 1972).
An adverse drug reaction, contrary to an adverse event, is characterized by the
suspicion of a causal relationship between the drug and the occurrence, i.e. judged
as being at least possibly related to treatment by the reporting or a reviewing health
professional.
Allopathy
Non-traditional, western scientific therapy, usually using synthesised ingredients, but
may also contain a purified active ingredient extracted from a plant or other natural
source; usually in opposition to the disease. Compare homeopathy.
Association
Events associated in time but not necessarily linked as cause and effect.
Attributable
Difference between the risk in an exposed population (absolute risk) and the risk in
an unexposed population (reference risk). Also referred to as excess risk.
Attributable risk is the result of an absolute comparison between outcome frequency
measurements, such as incidence.
Examples: If the exposed persons with a particular outcome are A, the exposed
persons without the outcome are B, the unexposed persons with the outcome are C
and the unexposed persons with the outcome are D, then the attributable risk is
calculated as : [A / (A+B)] - [C / (C+D)]. If, during the same time period, the
incidence of rash in a population treated with medicine X is 35/1,500=0.023, and the
incidence of rash in a population not treated with X is 5/2,000=0.0025, the
attributable risk is (35/1,500) - (5/2,000) = 0.0205.

ADVERSE DRUG REACTION
An adverse drug reaction (ADR) can be defined as ‘an appreciably

harmful or unpleasant reaction resulting from an intervention
related to the use of a medicinal product; adverse effects usually
predict hazard from future administration and warrant prevention,
or specific treatment, or alteration of the dosage regimen, or
withdrawal of the product. Since 2012, the definition has included
reactions occurring as a result of error, misuse or abuse, and to
suspected reactions to medicines that are unlicensed or being used
off-label in addition to the authorised use of a medicinal product in
normal doses. While this change potentially alters the reporting and
surveillance carried out by manufactures and medicines regulators,
in clinical practice it should not affect our approach to managing
ADRs.

CLASSIFICATION ADEVERSE DRUG REACTION
Traditionally, ADRs have been classified into two types:

Type A reactions – sometimes referred to as augmented reactions – which are
‘dose-dependent’ and predictable on the basis of the pharmacology of the
drug
Type B reactions – bizarre reactions – which are idiosyncratic and not
predictable on the basis of the pharmacology.
Although still widely quoted, this basic classification does not work for all
ADRs, such as with chronic adverse effects associated with cumulative drug
exposure (eg osteoporosis with long-term corticosteroid treatment) or
withdrawal reactions (eg rebound hypertension with centrally-acting
antihypertensive cessation). An alternative and perhaps more comprehensive
classification scheme is ‘DoTS’, which classifies reactions dependent on
the Dose of the drug, the Time course of the reaction and
relevant Susceptibility factors (such as genetic, pathological and other
biological differences).As well as classifying reactions, DoTS has the advantage
of being helpful to consider the diagnosis and prevention of ADRs in practice.

ADR Knowledge
Pharmacist knowledge of ADR terminology was assessed. Over 90%

identified the WHO description of an ADR; however, approximately 1 in 5
selected statements inconsistent with accepted ADR descriptions, in
addition to another 1 in 5 who were unable to choose. Many correctly
identified that prolonged hospitalization (78.4%) or death (65.5%)
associated with use of a medication would be categorized as a severe
ADR, but less (39.7%) did so for hospital admission to investigate a
recognized, but uncommon ADR. Most pharmacists were able to correctly
distinguish an ADR (Scenarios 1 and 3) from a medication error (Scenarios
2, 4, and 5), but approximately 10% mischaracterized or were unable to
offer an answer for each scenario.

Suspected ADR Reporting Experience
Forty-nine (42.2%) made suspected ADR reports in the past, of whom

thirty-four (29.3%) reported doing so in Qatar. Twenty-nine (85.3%) of
these reports were by hospital pharmacists, 4 (11.7%) from ambulatory
clinics and 1 from a non-direct patient care position. No community
pharmacist surveyed had ever made a suspected ADR report in Qatar.
Reporters mostly submitted their documentation to the hospital
pharmacy and therapeutics (P&T) committee (97%), but also directly to
the SCH (14.7%) or drug manufacturer (5.9%). Eighteen (53%) described
receiving some form an acknowledgement for their submission. When
asked to describe the ultimate fate of a submitted suspected ADR report
in Qatar, over half of all surveyed (54.3%) were unsure (Figure 1). If faced
with a patient experiencing a serious ADR, most respondents said they
would investigate further, including consulting the literature for
information concerning the reaction (90.5%), taking the responsibility to
alert the prescriber (97.1%), and directing the patient for further
emergent care (84.6%). The majority (90.5%) thought they would initiate
a suspected ADR report.

Suspected ADR Reporting Form

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 was 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; Doheny 2009; Aeries 1995). 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.
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: (A) Every adverse effect suspected or occurred by new
drugs and drugs of current issue. (B) Documentation of various drugs that
caused ADRs, which include death, life-threatening conditions, disability,
hospitalization and congenital abnormalities.
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.
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 Neuvoren 2002). 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.
Benefits of ADR monitoring
An ADR monitoring and reporting programme can furnish following benefits: 1.
It caters information about quality and safety of pharmaceutical products.
2. It initiates risk-management plans.
3. It prevents the predictable adverse.

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 Busto 1981).
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 Busto 1981; Nebeker and Barach 2008)

DRUG PROFILE (PEMAZYRE)
Pemazyre is a cancer medicine used to treat adults with cholangiocarcinoma

(biliary tract cancer or cancer of the bile ducts) when the cancer cells have an
abnormal form of a receptor (target) called FGFR2 on their surface. Pemazyre
is used when the cancer has spread to other parts of the body or cannot be
removed by surgery and has worsened after previous treatment with at least
one cancer medicine.
Cholangiocarcinoma is rare, and Pemazyre was designated an ‘orphan
medicine’ (a medicine used in rare diseases) on 24 August 2018.
Pemazyre contains the active substance pemigatinib.

PEMAZYRE™ (PEMIGATINIB) tablets, for oral use Initial U.S. Approval: 2020
INDICATIONS AND USAGE

PEMAZYRE is a kinase inhibitor indicated for the treatment of adults with previously
treated, unresectable locally advanced or metastatic cholangiocarcinoma with a
fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as
detected by an FDA-approved test. This indication is approved under accelerated
approval based on overall response rate and duration of response. Continued
approval for this indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial(s).
DOSAGE AND ADMINISTRATION
 Confirm the presence of an FGFR2 fusion or rearrangement prior to initiation of
treatment with PEMAZYRE.
 Recommended dose is 13.5 mg orally once daily for 14 consecutive days followed
by 7 days off therapy in 21-day cycles. Continue treatment until disease progression
or unacceptable toxicity occurs.
 Swallow tablet whole, with or without food. (2.2) DOSAGE FORMS AND STRENGTHS
_________ Tablets: 4.5 mg, 9 mg, and 13.5 mg.
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
 PEMAZYRE can cause retinal pigment epithelial detachment. Perform
ophthalmological examination including optical coherence tomography (OCT) prior
to initiation of therapy, every 2 months for the first 6 months of treatment and every
3 months thereafter, and urgently at any time for visual symptoms.
 Hyperphosphatemia: Increases in phosphate levels are a pharmacodynamic effect
of PEMAZYRE. Monitor for hyperphosphatemia and withhold, reduce the dose, or
permanently discontinue based on duration and severity of hyperphosphatemia.
 Embryo-Foetal Toxicity: Can cause foetal harm. Advise patients of reproductive
potential of the potential risk to the foetus and use effective contraception.

ADVERSE REACTIONS
The most common adverse reactions (incidence ≥ 20%) are
hyperphosphatemia, alopecia, diarrhoea, nail toxicity, fatigue, dysgeusia,
nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite,
vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry
skin.
To report SUSPECTED ADVERSE REACTIONS, contact Incyte Corporation at 1-
855-463-3463 or FDA at 1-800-FDA1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
 Strong and moderate CYP3A Inducers: Avoid concomitant use of PEMAZYRE.
 Strong and moderate- CYP3A inhibitors: Reduce the dose of PEMAZYRE, if
concomitant use cannot be avoided.
USE IN SPECIFIC POPULATIONS
 Lactation: Advise not to breastfeed.

FULL PRESCRIBING INFORMATION: PEMAZYRE
INDICATIONS AND USAGE

PEMAZYRE is indicated for the treatment of adults with previously treated,
unresectable locally advanced or metastatic cholangiocarcinoma with a
fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as
detected by an FDA-approved test.
This indication is approved under accelerated approval based on overall
response rate and duration of response [see Clinical Studies. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in a confirmatory trial(s).
DOSAGE AND ADMINISTRATION
Patient Selection
Select patients for the treatment of locally advanced or metastatic
cholangiocarcinoma with PEMAZYRE based on the presence of an FGFR2 fusion
or rearrangement as detected by an FDA-approved test [see Clinical Studies
(14.1)]. Information on FDA-approved test(s) for the detection of an FGFR2
fusion or rearrangement in cholangiocarcinoma is available at
http://www.fda.gov/CompanionDiagnostics.
Recommended Dosage
The recommended dosage of PEMAZYRE is 13.5 mg orally once daily for 14
consecutive days followed by 7 days off therapy, in 21-day cycles. Continue
treatment until disease progression or unacceptable toxicity occurs.
Take PEMAZYRE with or without food at approximately the same time every
day [see Clinical Pharmacology. Swallow tablets whole. Do not crush, chew,
split, or dissolve tablets.
If the patient misses a dose of PEMAZYRE by 4 or more hours or if vomiting
occurs, resume dosing with the next scheduled dose.

Dosage Modification for Adverse Reactions

Dosage Modification for Concomitant Use with Strong or Moderate CYP3A Inhibitors
Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. If concomitant use
with a strong or moderate CYP3A inhibitor cannot be avoided:
 Reduce PEMAZYRE dose from 13.5 mg to 9 mg.
 Reduce PEMAZYRE dose from 9 mg to 4.5 mg.
If concomitant use of a strong or moderate CYP3A inhibitor is discontinued, increase the PEMAZYRE
dose (after 3 plasma half-lives of the CYP3A inhibitor) to the dose that was used before starting the
strong inhibitor.
DOSAGE FORMS AND STRENGTHS

Tablets:
 4.5 mg: round, white to off-white tablet debossed on one side with "I" and "4.5" on the other side.
 9 mg: oval, white to off-white tablet debossed on one side with "I" and "9" on the other side.
 13.5 mg: round, white to off-white tablet debossed on one side with "I" and "13.5" on the other
side.
CONTRAINDICATIONS: None.
WARNINGS AND PRECAUTIONS
Ocular Toxicity
Retinal Pigment Epithelial Detachment (RPED)
PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or
photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical
coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of
asymptomatic RPED with PEMAZYRE is unknown.
Among 466 patients who received PEMAZYRE across clinical trials, RPED occurred in 6% of patients,
including Grade 3-4 RPED in 0.6%. The median time to first onset of RPED was 62 days. RPED led to
dose interruption of PEMAZYRE in 1.7% of patients, and dose reduction and permanent
discontinuation in 0.4% and in 0.4% of patients.
Hyperphosphatemia Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE [see

Clinical Pharmacology (12.2)]. Among 466 patients who received PEMAZYRE across clinical trials,
hyperphosphatemia was reported in 92% of patients based on laboratory values above the upper
limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169).
Phosphate lowering therapy was required in 29% of patients receiving PEMAZYRE. Monitor for
hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is > 5.5 mg/dL.
For serum phosphate levels > 7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the
dose.
Embryo-Foetal Toxicity Based on findings in an animal study and its mechanism of action,
PEMAZYRE can cause foetal harm when administered to a pregnant woman. Oral administration of
pemigatinib to pregnant rats during the period of organogenesis caused foetal malformations, foetal
growth retardation, and embryo-foetal death at maternal exposures lower than the human exposure
based on area under the curve (AUC) at the clinical dose of 13.5 mg.

ADVERSE REACTIONS
The following adverse reactions are discussed elsewhere in the labelling:
 Ocular Toxicity
 Hyperphosphatemia
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical
trials of another drug and may not reflect the rates observed in practice.
The safety of PEMAZYRE was evaluated in FIGHT-202, which included 146 patients with
previously treated, locally advanced or metastatic cholangiocarcinoma. Patients were
treated orally with PEMAZYRE 13.5 mg once daily for 14 days on followed by 7 days off
therapy until disease progression or unacceptable toxicity. The median duration of
treatment was 181 days (range: 7 to 730 days).
The median age of PEMAZYRE-treated patients was 59 years (range 26-78), 58% were
females, and 71% were White. Serious adverse reactions occurred in 45% of patients
receiving PEMAZYRE.
Serious adverse reactions in ≥ 2% of patients who received PEMAZYRE included abdominal
pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure
to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract
infection. Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive,
bile duct obstruction, cholangitis, sepsis, and pleural effusion.
Permanent discontinuation due to an adverse reaction occurred in 9% of patients who
received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥1% of
patients included intestinal obstruction and acute kidney injury.

Adverse reactions ≥ 15% in patients receiving PEMAZYRE in FIGHT-2021

Select laboratory abnormalities (≥10%) worsening from baseline in patients
receiving PEMAZYRE in FIGHT-2021

DISEASES OBSERVED AFTER PATIENT TREATED WITH PEMAZYRE
RPED was observed in patients treated

with PEMAZYRE
Advise patients to inform you of any vision changes while taking PEMAZYRE1
PEMAZYRE can cause retinal pigment epithelial detachment (RPED), which may cause
symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE
did not conduct routine monitoring including optical coherence tomography (OCT) to detect
asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is
unknown.1
Among 466 patients who received PEMAZYRE across clinical trials, RPED occurred in 6% of
patients, including Grade 3-4 RPED in 0.6%1
The median time to first onset of RPED was 62 days
RPED led to dose interruption of PEMAZYRE in 1.7% of patients
0.4% of patients required dose reduction for RPED
0.4% of patients discontinued treatment due to RPED
RPED resolved or improved to Grade 1 levels in 87.5% of patients who required dosage
modification for RPED
Perform a comprehensive ophthalmological examination including OCT prior to initiation of
PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during
treatment. For onset of visual symptoms, refer patients for ophthalmologic evaluation
urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE.
Modify the dose or permanently discontinue PEMAZYRE as recommended.
When to perform a comprehensive ophthalmological

examination, including OCT1

Hyperphosphatemia was observed in
patients treated with PEMAZYRE1
PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous
calcification, calcinosis, and non-uremic calciphylaxis1
Among 466 patients who received PEMAZYRE across clinical trials, hyperphosphatemia was
reported in 92% of patients based on laboratory values above the upper limit of normal1
֍The median time to onset of hyperphosphatemia was 8 days (range 1-169)1
Phosphate lowering therapy was used by 29% of patients during treatment with PEMAZYRE
֍No patients discontinued treatment due to hyperphosphatemia2
Recommendations for management of hyperphosphatemia1
֍Monitor for hyperphosphatemia.
֍Initiate a low phosphate diet when serum phosphate level is >5.5 mg/dL
֍For serum phosphate levels >7 mg/dL, initiate phosphate lowering therapy and withhold,
reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of
hyperphosphatemia
֍Dose modifications for hyperphosphatemia1
Severity
֍PEMAZYRE Dosage Modification

Potential for embryo-foetal toxicity
Embryo-foetal toxicity1
֍Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause
foetal harm when administered to a pregnant woman
֍Oral administration of pemigatinib to pregnant rats during the period of organogenesis
caused malformations, foetal growth retardation, and embryo-foetal death at maternal
exposures lower than the human exposure based on area under the curve (AUC) at the
clinical dose of 13.5 mg.

CONCLUSION
The study points out that the awareness about ADR reporting system, amongst
resident doctors, in the country (43%) and even in their own hospitals (49.5%)
is very low. More alarming, however, is the fact that very few resident doctors
have ever reported an adverse event to any of the national centres (2.9%) or
the ADR monitoring system of their own hospitals (22.6%) which is similar to
the result obtained by Li Qing et al. From these results we hypothesize that the
management and propaganda of ADR monitoring is not perfect and need
serious rethinking. Lack of knowledge of where ADRs should be reported
would automatically affect reporting, therefore, awareness programmes;
through publicity, would appear necessary to improve ADR reporting. Perhaps,
the undergraduate training in pharmacovigilance and medicine risk
perceptions may be either insufficient or improperly delivered to prepare the
doctors for the task of ADR monitoring and reporting in their future career.
Though it is known to the doctors that the medical professionals like doctors
and dentists can report an ADR, the awareness that even a nurse (70.7%),
pharmacist (36.9%) or a physiotherapist (32.8%) can do so is very low. Active
involvement of the paramedical staff in spontaneous reporting of ADR will go a
long way in improving the reporting rates, since they are in closer contact with
the patients for a longer duration, than the doctors. Also, it is a general
perception that ADR reporting is only for allopathic drugs and vaccines. The
knowledge that it encompasses other products like herbals, traditional
medicines, and blood products, biological and medical devices is comparatively
quite low. It is also evident that the resident doctors perceive reporting an
adverse event related to a new drug (98.7%) as the most important aspect of
pharmacovigilance. The awareness that even suspected drug interactions and
their consequences, congenital anomalies, and adverse events of which cause
is not evident, require equal vigilance and prompt reporting. This is contrasting
to the study by Li Qing et al in which 65.6% doctors were aware and willing to
report suspected ADRs. Although an overwhelming majority of the doctors
(89.5 %, 281/ 314) felt that ADR reporting is necessary and also that it is a
professional obligation (80.9%, 254/ 314). But they would be more inclined to
do it, if the reaction is to a new drug (93%, 292/ 314), is serious (88.9%, 279/
314) or unusual (82.8%, 260/ 314), which is similar to the results obtained by Li
Qing et al and Karen J Belton et al, but contrasting to that obtained by
Bateman et al. Only 22.9% (72/ 314) doctors would want to report an event if
it was an already well recognised adverse reaction as opposed to 62% doctors
who wanted to report a similar event in the study by Li Qing et al.

DISCUSSION
This study is the first to describe suspected ADR reporting by

pharmacist. Most responding pharmacists had never
submitted a report in the country, although they expressed
positive attitudes towards pharmacovigilance activity and
good knowledge of its purpose. The results indicate that
pharmacists‟ workplace exerts a strong influence on
suspected ADR reporting. National coordinated effort to
build and promote an infrastructure for pharmacovigilance
that would increase ease of suspected ADR reporting and
enhance transparency of actions taken following a report is
necessary to facilitate pharmacist participation, especially
among ambulatory-care based practitioners.

REFERENCE
1. https://hcp.pemazyre.com/safety-side-
effects
2. https://www.who.int/teams/regulation-
prequalification/regulation-and-
safety/pharmacovigilance#:~:text=Pharm
acovigilance%20is%20the%20science%2
0and,they%20are%20authorized%20for
%20use.
3. https://www.ncbi.nlm.nih.gov/pmc/article
s/PMC2964775/
4. https://www.ema.europa.eu/en/document
s/scientific-guideline/international-
conference-harmonisation-technical-
requirements-registration-
pharmaceuticals-human-use_en-25.pdf
5. https://en.wikipedia.org/wiki/Pharmacovi
gilancehttps://en.wikipedia.org/wiki/Phar
macovigilance


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PROJECT WORK ON POST MARKETING

For Partial Fulfilment of the Requirement for the

Under the supervision of

I, MOHD SAIF SIDDIKEE certify that the work

MOHD SAIF SIDDIKEE

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

Pharmacovigilance plays a consequential role in the

Keywords: Pharmacovigilance; Adverse drug reactions;

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

Pharmacovigilance is the science and activity relating to the

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

Medicines and vaccines have transformed the prevention and

All medicines and vaccines undergo rigorous testing for safety

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

What does pharmacovigilance do?

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

An adverse drug reaction (ADR) can be defined as ‘an appreciably

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

Traditionally, ADRs have been classified into two types:

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

Pharmacist knowledge of ADR terminology was assessed. Over 90%

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

Forty-nine (42.2%) made suspected ADR reports in the past, of whom

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

Pemazyre is a cancer medicine used to treat adults with cholangiocarcinoma

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

INDICATIONS AND USAGE

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

INDICATIONS AND USAGE

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

 Reduce PEMAZYRE dose from 13.5 mg to 9 mg.

 Reduce PEMAZYRE dose from 9 mg to 4.5 mg.

DOSAGE FORMS AND STRENGTHS

WARNINGS AND PRECAUTIONS

Hyperphosphatemia Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE [see

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

RPED was observed in patients treated

When to perform a comprehensive ophthalmological

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

This study is the first to describe suspected ADR reporting by

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

MOHD SAIF SIDDIKEE | 1819750063 | AZAD INSTITUTE OF PHARMACY & RESEARCH

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