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RIPER PDIC Bulletin Peer Reviewed / Indexed in Pharmainfo.net &
Open J-Gate
ISSN 2230 – 8741
www.riperjournals.org
http://www.pharmainfo.net
/og/riper
RIPER PDIC Bulletin,
September 2011, Volume 2,
Issue 14
R I P E R P o i s o n & D r u g I n f o r m a t i o n C e n t e r ( P D I C ) , R D T H O S P I T A L ,
B a t h a l a p a l l i , A . P . & R a g h a v e n d r a I n s t i t u t e o f P h a r m a c e u t i c a l
E d u c a t i o n a n d R e s e a r c h ( R I P E R )
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2 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
RIPER PDIC Bulletin R I P E R P o i s o n & D r u g I n f o r m a t i o n C e n t e r ( P D I C ) ,
R D T H O S P I T A L , B a t h a l a p a l l i , A . P . &
Raghavendra Institute of Pharmaceutical Education and Research ((((RIPERRIPERRIPERRIPER))))
VOLUME 2, ISSUE VOLUME 2, ISSUE VOLUME 2, ISSUE VOLUME 2, ISSUE 14141414
SEPTEMBERSEPTEMBERSEPTEMBERSEPTEMBER 2011201120112011
Editorial team Page 03
Contents Page 05
Editorial Page 06
Articles Page 07
Drug News Page 26
Instruction to authors Page 28
‘RIPER’ is the premier educational institution promoted by Raghavendra Educational & Rural Development
Society. The institution is established in 2002 under the leadership of four pharmacy graduates including
Dr. Y. Padmanabha Reddy and Dr. J. Ravindra Reddy. Now the institution is offering; M. Pharm, B. Pharm,
D. Pharm, Pharm D and PharmD (PB) courses approved by AICTE, PCI and Govt. of AP. The college is
affiliated to JNT University, Anantapur (JNTUA) / SBTET, AP.
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3 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
EDITORIAL BOARDEDITORIAL BOARDEDITORIAL BOARDEDITORIAL BOARD CHIEF EDITORCHIEF EDITORCHIEF EDITORCHIEF EDITOR
Dr. Y. Padmanabha Reddy, M.Pharm, PhD, FIC, Principal, RIPER EDITOREDITOREDITOREDITOR
Mr. Dixon Thomas, Associate Professor, & Head, Dept. of Pharmacy Practice, RIPER MANAGING EDITORSMANAGING EDITORSMANAGING EDITORSMANAGING EDITORS
Mr. Vigneshwaran, M.Pharm, Asst Professor, RIPER Mr. G. Narayana, M.Pharm, Asst Professor, RIPER ASSOCIATE EDITORSASSOCIATE EDITORSASSOCIATE EDITORSASSOCIATE EDITORS
Dr. Adepu Ramesh, M.Pharm, PhD, Professor, JSS University, Mysore Dr. Gerardo Alvarez-Uria, Head, Dept. of Infectious Diseases, RDT Hospital, Anantapur Mrs. Seeba Zachariah, M.Pharm, Assoc Professor, RIPER, Anantapur Dr. S. Sriram, M.Pharm, PhD, Professor, SRIPMS, Coimbatore Dr. Roger Walker, Chief Pharmaceutical Officer, Wales, U.K. Dr. Chris Wisniewski, MUSC Drug Information Center, USA Dr. Meghana Aruru, Midwestern University, USA EDITORIAL ADVISORY BOARDEDITORIAL ADVISORY BOARDEDITORIAL ADVISORY BOARDEDITORIAL ADVISORY BOARD
Dr. M.S. Kannan, Medical Director, RDT Hospital Dr. A.N. Nagappa, M.Pharm, PhD, Professor, Manipal University, Karnataka Dr. G.P. Mohanta, M.Pharm, PhD, Professor, Annamalai Univeristy, T.N. Dr. K.G. Revikumar, M.Pharm, PhD, Principal, ASP, Amrita University, Kerala Dr. Gayathri Palat, Program Director, Palliative Access (PAX) Programme, India Dr. C. Vijaya Raghavan, M.Pharm, PhD, Vice-Principal, PSG College of Pharmacy, T.N. Dr. Molly Mathew, M.Pharm, PhD, Principal, MDCP, KUHAS, Kerala Dr. Subhash C. Mandal, M.Pharm, PhD, Assoc Professor, Jadavpur University, Kolkata Dr. Sunil K Jain, M.Pharm, PhD, Chief Pharmacist, AIIMS, New Delhi Dr. B. J. Mahendra Kumar, M.Pharm,PhD, Prof, SACCP, RGUHS University, Karnataka Dr. Gunasakaran, Clinical Head, Azidus Laboratory Ltd, T.N. Dr. S.S. Rao, Pharmacist, Canada Mr. Ali Dulfikkar, Pharmacist, Dubai Mr. Sojo Augustin, Pharmacy Technician, Ireland Dr. H. Harish, Medical Superintendent, RDT Hospital Dr. Tadepalli Durgesh, Head, Children’s Hospital, RDT Hospital Dr. Alexander Daniel Sunad, Surgeon, RDT Hospital Mr. K. Thejomoorthy, M.Pharm, Chief Pharmacist, RDT Hospital Mr. Prasanth Kumar, Data Manager, Novartis Healthcare Pvt. Ltd. Mr. Tapan Kumar Shah, Clinical Operations, Boehringer Ingelheim India Pvt. Ltd Mr. Tarun Wadhwa, M.Pharm, Asst Professor, KLE College of Pharmacy, Belgaum Dr. C. Sowmya, M.Pharm, PhD, Professor, RIPER Dr. P. Ramalingam, M.Pharm, PhD, Professor, RIPER Dr. Jyothi MV, M.Pharm, PhD, Professor, RIPER
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4 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
PUBLICATION COMMITTEEPUBLICATION COMMITTEEPUBLICATION COMMITTEEPUBLICATION COMMITTEE
CHAIRMANCHAIRMANCHAIRMANCHAIRMAN
Dr. J. Ravindra Reddy, M.Pharm, PhD, Correspondent, RIPER
REGULATORY NEWSREGULATORY NEWSREGULATORY NEWSREGULATORY NEWS
Rohit Bhavsar
D. Giri Rajasekhar
PROOF READINGPROOF READINGPROOF READINGPROOF READING
K. Balaji, M.Pharm, Asst Professor, RIPER
S.R.K. Sowmya
N. Sreelalitha
A. Srinadh
INDEXING & DISTRIBUTIONINDEXING & DISTRIBUTIONINDEXING & DISTRIBUTIONINDEXING & DISTRIBUTION
Mr. M. Jaffar, M.Pharm, Asst Professor, RIPER Seetharam C Vinay Pawar
K H Ushadevi
V. N. HariKiran
WEBSITE ADMINISTRATIONWEBSITE ADMINISTRATIONWEBSITE ADMINISTRATIONWEBSITE ADMINISTRATION
D. K. Sudheer Naik
RIPER PDIC Bulletin
Raghavendra Institute of Pharmaceutical Education and Research (RIPER)
Chiyyedu Post, Anantapur 515721, AP, India
Phone: 91-8978541693
[email protected] , www.riper.ac.in, www.riperjournals.org
Notice: For healthcare professionals only. View of authors are independent to that of editorial
team, it is highly advised for consulting other drug information sources also for your specific
needs. Publisher, editorial team or authors are not responsible for any damage happens due to
the information provided. RIPER PDIC Bulletin Published by the Principal, RIPER, Anantapur—
515721, A.P
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5 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
RIPER PDIC Bulletin
CONTENTSCONTENTSCONTENTSCONTENTS
1 Editorial Page 06
2 71st International Congress of FIP – Hyderabad,
India – S.R.K. Sowmya Page 07
3 Appropriateness of drug therapy monitoring for
immunosuppressant therapy in adult solid organ
transplant patients - Holly E. Barrier, Sarah M. Tischer,
David J. Taber, Kelli L. Garrison
Page 08
4 Clinical research in Malaysia: a new direction for
clinical trial initiative in Malaysia - Hon YK, Goh PP,
Teoh SC, Hazrah A
Page 13
5 Alzheimer’s disease - an overview - Anwar Basha, H.
Harish, C. Vijaya Raghavan, Y. Padmanabha Reddy
Page 17
6 Drug prescribing for geriatrics –a review - Alexander
Daniel Sunad, Anwar Basha, Ram Keshav Reddy
Page 21
7 Drug news – Rohit Bhavsar Page 26
8 Instruction to the authors Page 28
Page 6
6 RIPER PDIC Bulletin,
It was a dream comes
International Pharmaceutical Fed
3-8 September 2011 together wit
theme of the congress was ‘Comp
Please see the detailed news on
seminars and conferences. Next
Pharmaceutical Congress on 16-18
Sincerely yours,
Dr. Y. Padmanabha Reddy, M
Principal, RIPER & Chief Edito
First of its kind, a Semin
Pharmacy, Mysore by the leade
develop faculty and preceptors w
International Seminar on Experi
renowned experts in pharmacy fo
� Dr. Mike Rouse, Director, I
Pharmaceutical Education
� Dr. Lucinda L. Maine, Exec
Association of College of P
� Dr. Kevin G. Moores, Direc
City, USA.
� Dr. Wafa Dahdal, Associate
Clinical Pharmacy, USA.
Dr. Lucinda L. Maine, Ex
Colleges of Pharmacy said at M
continuous professional develop
The Director of Division of Drug
Iowa announced that The Iowa
institutions for the half rate of wh
Best Regards,
Mr. Dixon Thomas, M.Pharm
HOD, Pharmacy Practice, RIPERIPER PDIC Bulletin [email protected]
lletin, September 2011, Volume 2, Issue 14
Editorial
es true that the 71st International Congress o
Federation (FIP) happened in Hyderabad, India o
with Indian Pharmaceutical Association (IPA). Mai
ompromising safety and quality: A risky path’.
on next page. It is going to be a season of
ext major congress we await is 63rd Indian
18 December 2011 at Bangalore, India.
, M.Pharm, PhD, FIC
ditor, RIPER PDIC Bulletin
minar conducted on September 10-11, 2011 at
adership of Dr. B. Suresh, Vice-Chancellor of JSS
rs with excellence, it is important to have such qual
periential Education in Pharmacy Practice was
y for USA;
or, International Services, Accreditation Council of
tion, Chicago, USA.
xecutive Vice-President & CEO, American
of Pharmacy, USA.
irector, Division of Drug Information Services, Iowa
ciate Director of Professional Development, Americ
, Executive Vice President & CEO of American
t Mysore that, "there is a shortage of quality w
lopment and educational needs of pharmacy stu
rug Information Services Dr. Kevin Moores of Th
wa Drug Information Service (IDIS) will be avail
f what is mentioned in its website.
arm, M.S., M.Sc.
RIPER & Editor,
ss of
ia on
Main
at JSS College of
JSS University. To
quality programs.
as enlightened by
il of
Iowa
erican College of
can Association of
y websites for the
students in USA."
f The University of
vailable for Indian
Page 7
7 RIPER PDIC Bulletin,
71st Internationa
‘I am a pharmacist’ was
71st International Pharmaceutical
at Hyderabad from 3rd- 8th Septe
event a grand success. The FIP in
has done a great job for the smoo
The inaugural program
India, Smt. Pratibha Devi Singh Pa
pharmacy in country. Also, the go
chief minister of Andhra Pradesh,
on the present situation of pharm
competence with the global mark
very good morning from 1 million
applause.
The theme of the 71st F
path’ After the inaugural session
Buchman and the assistant direc
measures to reduce the number
where the incarnation of lord Vish
On the 4th of Septemb
representing various countries
international organizations attend
held as scheduled. On the 5th of
national organizations as well as
about their activities. Also, the po
from around the globe. The sessio
On the 6th & 7th of Se
welcome party was organized by
day which was memorable for a
paper and electronic media with
smoothly and the event was a gra
organizing committee of FIP cong
Dixon, Vigneshwaran, Sudheer, Vinay
Dr. B. Suresh, Dr. T.V. Narayana
lletin, September 2011, Volume 2, Issue 14
onal Congress of FIP – Hyderabad, I
S.R.K. Sowmya
was the feeling for any pharmacist around the glo
tical Federation (FIP) congress in India. The 6 day c
eptember was a tremendous effort of many people
P in collaboration with the Indian Pharmaceutical A
mooth running of the event.
am on the 3rd of September was addressed by t
h Patil. Her speech has given a new hope for the d
e governor of Andhra Pradesh, Sri. E.L.Narasimhan
esh, Sri. Kiran Kumar Reddy addressed the audienc
armacy in India and the need for improvement of
arket. Dr. B.Suresh, president of PCI started off hi
illion pharmacist of India” which was followed by a
1st FIP convention was ‘compromising quality and
ion an agreement was signed by the president of
irector-general of WHO Dr. Hiroki Nakatani to m
ber of TB demises in India. This was followed by
Vishnu was presented by a dance.
mber, a council meeting was held, where the co
ies and the pharmacy professionals of various
tended the meeting. Simultaneously, the scientific
of September, the exhibition was set up where in
l as the colleges in Hyderabad put up stalls and ga
e poster presentations were done by various pharm
ssions continued as scheduled in the program.
f September the sessions went as usual and in
d by the FIP for all the participants. The 8th of Se
or all the participants. A council meeting was hel
with a briefing up of the conference. Everything
a grand success. Volunteers from India thank Dr. T.
ongress.
inay & Samhitha with
yana, Dr. Padmanabha Reddy, Dr. Sten Olsson & Dr. Go
d, India
e globe to describe
ay conference held
ople for making the
al Association (IPA)
by the president of
he development of
han and honorable
ience and discussed
t of the industry for
ff his talk saying “A
by a great round of
and safety – a risky
t of FIP, Mr. Michel
o mutually take up
by cultural session
e council members
ious national and
ntific sessions were
e international and
d gave an exposure
harmacy graduates
in the evening, a
f September was a
held to report the
ing ended up very
r. T.K. Ravi and the
. Goli Divakar
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8 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Appropriateness of drug therapy monitoring for immunosuppressant
therapy in adult solid organ transplant patients
Holly E. Barrier1, Sarah M. Tischer1, David J. Taber2, Kelli L. Garrison3
1Pharmacy Resident, MUSC Drug Information Center, USA 2Clinical Liaison, MUSC Drug Information Center, USA 3Drug Information Liaison, MUSC Drug Information Center, USA
Abstract
Objective: This retrospective review was conducted to determine the appropriateness of
immunosuppressant TDM in solid organ transplant (SOT) patients, assess the appropriateness
of clinical intervention based on serum concentration results, and determine the economic
impact of current immunosuppressant drug therapy monitoring.
Methods: A retrospective chart review was performed to assess the appropriateness of
immunosuppressant therapy TDM in SOT patients from May 15, 2010, to August 15, 2010. All
SOT patients who had received cyclosporine, tacrolimus, mycophenolate mofetil,
mycophenolate sodium, and sirolimus during the time period were eligible for inclusion.
Results & Discussion: A total of 223 patient charts were identified for evaluation for inclusion.
The primary outcome of overall appropriateness of TDM was achieved in 42% (n = 347) of drug
concentrations ordered. Overall appropriateness of immunosuppressant TDM was similar
among the services (Transplant Surgery 59%, Transplant Medicine 54%, other 58%, P = 0.564).
The total cost of inappropriate drug concentration monitoring was $55,922.
Conclusion: The timing of the immunosuppresant drug concentration is the most important
contributor to inappropriate drug concentration monitoring at our institution. While the clinical
scenarios are difficult to ascertain in a retrospective review, this study should alert practitioners
to the importance of establishing whether drug concentrations are true troughs and to
determine why concentrations are not being adjusted per institutional protocols.
Key Words: TDM, immunosuppressant, transplant, cyclosporine
Introduction
Therapeutic drug monitoring (TDM) has become an integral part of immunosuppressant
drug therapy management in solid organ transplantation since the introduction of cyclosporine
in the 1980’s.1,2 Today, complex regimens utilizing immunosuppressive drugs targeting
different aspects of the immune system are important in the prevention of acute rejection and
deterioration of graft function. The immunosuppressive agents commonly used in solid organ
transplantation, including the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus, the
antimetabolite mycophenolic acid (MPA), and the mammalian target of rapamycin inhibitors
(mTORi) everolimus and sirolimus, have a narrow therapeutic index, large inter-individual
variation in pharmacokinetics and pharmacodynamics, and significant drug-drug interactions.
TDM of immunosuppressants has helped reduced toxicities, life-threatening infections, and
acute cellular rejections by ensuring that the lowest therapeutic dose is utilized.1-4 TDM is the
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9 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
standard of practice for the CNIs and the mTORis, but MPA is typically dosed at fixed doses and
controversy exists whether TDM is beneficial.4-5 Unfortunately, appropriate TDM of
immunosuppressants past the initial post-transplant period has not been well studied.5
Despite developed protocols identifying therapeutic ranges for immunosuppressant
drugs in kidney, liver, pancreas, and heart transplant recipients at our institution, there is a lack
of standardization for TDM. This retrospective review was conducted at an academic medical
center to determine the appropriateness of immunosuppressant TDM in solid organ transplant
(SOT) patients, assess the appropriateness of clinical intervention based on serum
concentration results, and determine the economic impact of current immunosuppressant drug
therapy monitoring.
Methods
A retrospective chart review was performed to assess the appropriateness of
immunosuppressant therapy TDM in SOT patients from May 15, 2010, to August 15, 2010. All
SOT patients who had received cyclosporine, tacrolimus, mycophenolate mofetil,
mycophenolate sodium, and sirolimus during the time period were eligible for inclusion.
Patients were identified from the pharmacy order entry system. Patients were excluded if they
were < 18 years of age. Outcome data were collected from electronic medical records. The
study was approved by the institutional review board.
Patient demographic data were collected, including gender, age, type of SOT, time from
transplant (≤ 3 months or > 3 months), and primary service during admission (Transplant
Surgery, Transplant Medicine, and other). Monitoring data were collected for each serum
concentration drawn during their hospital admission. Concentrations were deemed
appropriate based on the following criteria: concentration was a true trough defined as
administered within 2 hours of when the next dose was due; only one serum concentration was
drawn in a 24-hour period; a clinical intervention was made for serum concentrations out of
range; and TDM was clinically indicated. Appropriate clinical indications for TDM included the
following: first day of admission; previous concentration out of range; recent change in dosing
regimen; within 3 months of transplant; and concomitant medications that interacted with
immunosuppressant therapy. Therapeutic range of immunosuppressant drugs were based on
institutional protocols for kidney, pancreas, liver, and heart transplant recipients (Table 1).
An economic cost analysis was performed to assess cost-effectiveness of TDM. The
patient charges of serum concentrations for the individual drugs are as follows: tacrolimus
$109; sirolimus $109; cyclosporine $127; and mycophenolic acid $145. Societal cost was then
calculated using an average insurance company reimbursement rate of 64.5161% and an
estimated provider cost of $170 per hour. It was estimated that the provider would spend 15
minutes assessing and intervening on each serum concentration.
Data Analysis: A total of 223 patient charts were identified for evaluation for inclusion. Of
these patients, 8 were excluded (1 pediatric patient, 2 never admitted to hospital, 5 did not
receive immunosuppressant ordered). Thus, 215 charts of SOT patients were identified
resulting in 838 whole blood drug concentrations for analysis. Baseline characteristics are
reported in Table 2.
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10 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Table 1. Institution-Specific Goal Immunosuppressant Serum Concentrations in Solid Organ
Transplant Recipients
Table 2. Patient Characteristics (n = 215)
The primary outcome of overall
appropriateness of TDM was achieved in 42%
(n = 347) of drug concentrations ordered.
Individual criteria defining this outcome were
assessed. Frequency of adherence to the
primary outcome and its criteria are available
in Figure 1. Overall appropriateness of
immunosuppressant TDM was similar among
the services (Transplant Surgery 59%,
Transplant Medicine 54%, other 58%, P =
0.564).
The secondary objective of
appropriateness of clinical intervention based
on serum concentration results was also
evaluated. Sixty-eight percent (n = 538) of
serum concentrations were out of range and
42% of those were adjusted based on
institutional protocols.
Organ
Transplanted
Cyclosporine Tacrolimus Sirolimus Mycophenolic
Acid
Kidney
Acute
Chronic
175-275 ng/mL
70-175 ng/mL
6-12 ng/mL
4-10 ng/mL
8-12 ng/mL
8-12 ng/mL
N/A
N/A
Heart
Acute
Chronic
Minimization
with Sirolimus
250 ± 25 ng/mL
125 ± 25 ng/mL
50 ± 25 ng/mL
10-12 ng/mL
8-10 ng/mL
~4 ng/mL
5-15 ng/mL (CSA);
5-8 ng/mL (FK);
10-15 ng/mL (No CNI)
5-12 ng/mL (CSA);
5-10 ng/mL (FK)
2-4 mcg/mL
2-4 mcg/mL
Liver
Acute
Chronic
CNI sparring
175-250 ng/mL
25-200 ng/mL
150-200 ng/mL
8-12 ng/mL
6-10 ng/mL
6-8 ng/mL
8-12 ng/mL
8-12 ng/mL
8-12 ng/mL
N/A
N/A
N/A
Pancreas
Acute
Chronic
175-275 ng/mL
70-175 ng/mL
8-12 ng/mL
4-10 ng/mL
8-12 ng/mL
8-12 ng/mL
N/A
N/A
Age (y), median 57
Sex
Male 66%
Transplant Organ Type
Kidney 45%
Liver 28%
Heart 18%
Pancreas 8%
Service
Transplant Surgery 45%
Transplant Medicine 38%
Other 17%
Time from Transplant
Acute (< 3 months) 41%
Chronic (> 3 months) 59%
Length of stay (d), median 4
Monitored Immunosuppressant
Tacrolimus 80%
Cyclosporine 14%
Mycophenolic acid 4%
Sirolimus 2%
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11 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Figure 3. Adjustment of Out of Range
Concentrations by Medical Service
0
20
40
60
80
100
120
140
160
180
Transplant
Surgery
Transplant
Medicine
Other Services
Adjusted
Not Adjusted
Figure 1: Appropriateness of Immunosuppressant
Drug Concentrations
97%
42%
32%
55%
42%
Only one in 24 hours
Not in range and adjusted
In-range
True Trough
Appropriate
Clinical interventions based on
concentration results differed between
primary services (P < 0.01 across all
data points). Transplant Surgery made
a clinical dosing intervention for 50% of
the out-of-range concentrations.
Transplant Medicine made an
intervention on 30% while other
services made an intervention 27% of
the time (Figure 3 and Table 3). The total cost of inappropriate drug concentration monitoring
was $55,922.
All clinical and economic outcomes are displayed in Table 3.
There is suboptimal immunosuppressant
drug concentration monitoring in SOT
patients at our institution. Based on our
pre-specified definition of an appropriate
drug concentration, only 42% of drug
levels assessed during the study period
were deemed appropriate, mainly due to
inappropriate timing of the draw. Only
55% of all serum concentrations were
true troughs, drawn within 2 hours of the
next dose.
Table 3. Clinical and Economic Outcomes
Outcomes Percentage P value
Inappropriate (n = 838) 58%
Transplant Surgery (n = 482) 59% 0.586
Transplant Medicine (n = 244) 55%
Other (n = 112) 58%
True Trough (n = 838) 55%
In Therapeutic Range (n = 838) 32%
Transplant Surgery (n = 482) 29% 0.385
Transplant Medicine (n = 244) 34%
Other (n = 112) 38%
Not In Therapeutic Range and Adjusted (n = 572) 42%
Transplant Surgery (n = 340) 50% < 0.001
Transplant Medicine (n = 162) 30%
Other (n = 70) 27%
Only One Concentration in 24 Hours (n = 838) 97%
Total Cost of Immunosuppressant Monitoring $96,285
Cost of Inappropriate Concentration Monitoring $55,922
In analyzing whether adjustments were made to drug concentrations out of therapeutic
range per protocol, the Transplant Surgery services made adjustments to immunosuppressant
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12 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
agents based on institutional protocols more often than Transplant Medicine and other services
in the hospital. However, the Transplant Surgery group still only adjusted out of range values
50% of the time.
There was a small percentage of patients that had multiple drug concentrations drawn
during a 24-hour period. These patients usually had concentrations drawn on admission and
then again with morning labs. There are only two scenarios when drawing concentrations on
admission is necessary – when a patient may be noncompliant or if a patient appears to have
toxicity from the agent.
The economic impact of inappropriate immunosuppressant concentrations is significant.
When adjusted to 1 year, approximately $220,000 is wasted with inappropriate drug
concentrations in the SOT population at our institution. By implementing restrictions and
protocols for immunosuppressant drug concentration monitoring, there is an opportunity for
significant cost savings per year.
Conclusion
The timing of the immunosuppresant drug concentration is the most important
contributor to inappropriate drug concentration monitoring at our institution. While the clinical
scenarios are difficult to ascertain in a retrospective review, this study should alert practitioners
to the importance of establishing whether drug concentrations are true troughs and to
determine why concentrations are not being adjusted per institutional protocols. Prospective
studies are needed to assess how often immunosuppressant drug concentrations should be
monitored in order to maximize cost savings, minimize episodes of acute rejection, and prolong
graft survival.
Limitations: This was a retrospective, observational review that was reliant on appropriate
documentation and data collection by all investigators. It is likely some concentrations were
deemed inappropriate due to out of range values in which doses were not adjusted to achieve
protocol trough targets. The lack of adjustment may have been appropriate in certain clinical
situations (eg, infection, adverse effects). Some providers may adjust immunosuppression
based on their own clinical experience instead of relying on institutional protocols. Therefore,
the individual decision-making of the practitioner may differ from protocol and result in
protocol deviation.
References 1. Masuda S, Inui Ken-ichi. An up-date review on individualized dosage adjustments of calcineurin
inhibitors in organ transplant patients. Pharm Thera 2006; 112:184-198.
2. Oellerich M, Hon, Armstrong VW. The role of therapeutic drug monitoring in individualizing
immunosuppressive drug therapy: recent developments. Ther Drug Monit 2006; 28:720-725.
3. Kahan BD, Keown P, Levy GA, Johnston A. Therapeutic drug monitoring of immunosuppressant
drugs in clinical practice. Clin Thera 2002; 24:330-350.
4. De Jonge H, Naesens M, Kuypers DRJ. New insights into the pharmacokinetics and
pharmacodynamics of the calcineurin inhibitors and mycophenolic acid: possible consequences
of therapeutic drug monitoring in solid organ transplantation. Ther Drug Monit. 2009 Aug;
31(4):416-35.
5. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical
practice guideline for the care of kidney transplant recipients. American Journal of
Transplantation 2009; 9(Suppl 2): S1-S157.
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13 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Clinical research in Malaysia: a new direction for clinical trial
initiative in Malaysia
Hon YK, Goh PP, Teoh SC, Hazrah A
Clinical Research Centre, Dermatology Block, Hospital Kuala Lumpur
Abstract
Asia has 80% of the 6.4 billion world population. Malaysia, being a country within the
ASEAN region, is well-placed to achieve the status of a preferred destination for clinical trials in
the region. Coordination of public and private hospitals, clinical research organization, diverse
patient pool, low cost and qualified professionals make Malaysia as one of the favorite
destination for clinical research.
Key words: Clinical Trials, development, Malaysia, cost
Introduction
Clinical trials are important for development of new drugs in the pharmaceutical
industry. The reasons for this are many: including improving treatment of illnesses, more
innovative ways to manage diseases and to establish the clinical efficacy of new compounds as
well for registration of such drugs. The whole process of drug development is long and tedious
incurring a large investment in materials, systems, human resources and funds.1
Asia has 80% of the 6.4 billion world population and ASEAN itself, comprises more than
300 million people, thus there is a huge potential both for the scientific pursuit of clinical trials,
as well as the subsequent pharmaceutical commercialization of research & development
efforts. Sometimes, we need to know the pharmacokinetics and pharmacodynamics of drugs in
a particular genetic subset of the human race. In the drug world, the Aryans, Mongoloids,
Caucasians and Pacific islanders sometimes react differently to the same drug because of their
differing genetic make-up. Some trials are conducted specifically to register a well-known
pharmaceutical entity for use in a particularly-defined human population to ensure its safety
and efficacy within that genetically defined subset.2
Malaysia, being a country within the ASEAN region, is well-placed to achieve the status
of a preferred destination for clinical trials in the region. In view of the potential foreign
investment to the country, contract clinical research has been identified as one of the entry
point projects for the National Key Economic Areas (NKEA). The Prime Minster of Malaysia,
Dato’ Sri Mohd Najib has launched the 12 NKEAs as part of the Economic Transformation
Program (ETP) in August 2010. The ETP aims to accelerate Malaysia’s growth as a fully
developed nation with per capita income of USD 15,000 by 2020. In the healthcare NKEA,
besides Clinical Research Malaysia (CRM: www.crc.gov.my), which will focus on contract
clinical research, the other five entry point projects are Health Insurance For Foreign Workers,
Malaysian Pharmaceuticals, Diagnostic Services Nexus, Health Travel And Health Metropolis.
The details can be found at http://etp.pemandu.gov.my/Overview_of_NKEAs_-@-
Healthcare.aspx.3
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14 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Clinical Research Malaysia as one of the entry point projects was established to promote
and develop the growth of industry sponsored clinical trials in drug development. CRM’s main
task is to encourage and support the pharmaceutical industry and Clinical Research
Organizations (CRO) to select Malaysia as the preferred destination for contract clinical
research and thus gain foreign direct investment from the global drug development industry. Its
core function is to coordinate and foster greater collaboration among the Ministry of Health’s
(MOH) network of twenty-four Clinical Research Centers (CRCs) and other independent CRCs
formed in private hospitals and academic centres.4
Malaysia expended its efforts in increasing the number of high-quality clinical trials
being conducted by initially forming a One-Stop-Centre within the CRC, which acted as the main
contact point for network of CRCs to facilitate access to 137 general and district Ministry Of
Health (MOH) hospitals. These hospitals act as the referral centers for more than 4000 health
clinics as serving also as potential sites for clinical trials. Thus, the One-Stop-Centre served as
the main contact point for industry and sponsors to access the sites and investigators.5
The Health Minister Datuk Seri Liow Tiong Lai, during the opening ceremony of National
Conference for Clinical Research 2011, launched Clinical Research Malaysia (CRM) and
announced that CRM “provides a unique strategy to attract clinical trials to Malaysia.” The
embryonic OSC has now emerged as CRM, and in the transformation, been entrusted with
expanded scope and responsibilities. The new name also offers heightened branding and a
national role for global reach.4
Some of the advantages of Malaysia for Industry Sponsored Trials (IST) include:
A single point of contact and access for information through CRM
CRM will ensure better communications between potential pharmaceutical industry
sponsors and CRO’s with the MOH sites and investigators. This is made possible by mobilizing
CRM as a single point of information and referral system for both, thus facilitating the proper
matching of potential clinical trial investigators with the right subjects. Therefore, CRM will now
galvanize the pool of competent and well-trained clinical specialists within an extensive
network of 341 public and private hospitals and hundreds of clinical trial sites.4
It is neither viable nor ethical to conduct trials without adequate and equitable
healthcare. Since independence in 1957, Malaysia has built on its good foundation, not just by
building new and modern facilities, but has developed extensive training and systems
integration. The present system has been remarkable for equitable, sustainable and accessible,
at a very manageable cost, to a very high standard of care throughout the nation. The cause of
CRM is thus supported by our good logistics connections and investment in ICT infrastructure.6
Supportive research infrastructure
The establishment of supportive research infrastructure such as the National Medical
Research Register (NMRR: www.nmrr.gov.my) is an online register in which every clinical trial
conducted within the country is recorded. It serves as a database that will give the
pharmaceutical industry the access to expert clinical researchers and the number of clinical
trials (either currently being conducted or already completed) within a medical discipline.7
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15 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
The networking of Malaysia’s research institutes with others such as the National Institute of
Health in the United States is also an additional advantage, as knowledge transfer between
them will enable quick sharing of research ideas and establishing potential research ties and/or
collaborations.7
Well established patient registries
The CRC has been instrumental in establishing patient registries in more than thirty
disease area. The first was the renal dialysis registry, which was started in the early nineties and
it has been a valuable source of information on the management of patients as well as the
allocation of scarce resources for end stage renal disease sufferers. Since then, many more
registries have been set up and these are publically available on the web. Although they are not
designed as such, these registries have eventually proven to be a valuable resource for sponsors
coming to do trials in the country, as they serve as a valuable database for sponsors looking for
the patients and their doctors.8
Well trained and experienced investigators
Since 1999, Malaysia has mandated that all clinical trial investigators must receive
training in relevant research topics such as Good Clinical Practice (GCP) and Good Research
Practice (GRP), in order for them to be well-equipped with the necessary technical expertise
and administrative capabilities when conducting clinical trials. Therefore, the wide availability
of research training, in the form of seminars, hands-on workshops and didactic and interactive
forums, provides an excellent supportive platform for conduct of clinical trials in Malaysia, as
they ensure that they have been trained to comply with international standards.9
Availability of a diverse genetic pool
The multiracial and multiethnic local patient population provides an excellent
opportunity for clinical trial investigators to conduct clinical research on a widely diverse
patient population, especially pertaining to their genetic make-up. This availability of a diverse
genetic pool within a nation is unique and facilitates the conduct of clinical trials of a smaller
scale, yet able to reach a larger scale of patient population.10
It is relevant that all Malaysians have a personal identity card with photo and thumb
print on a machine readable chip, which facilitates the unique identifiable subject for
research.10
Relatively low cost incurred
There is very good transport logistics, and costs are very manageable when conducting
clinical trials in Malaysia. Besides, the administrative and other costs incurred during the
conduct of these trials in Malaysia will also be kept minimal.11
Phase 1 Established
One result of the Ministry of Health’s (MOH) effort in promoting clinical research is a
joint collaborative effort between MOH and Veeda Clinical Research, a full service global clinical
research organization (CRO) specializing in the early clinical development of pharmaceutical
compounds, in the conduct of early phase I clinical trials.12
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16 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Phase I clinical trials are conducted to investigate and to establish the safety of
potentially-viable pharmaceutical compounds for management of human diseases. Veeda
Clinical Research is a well-established organization in clinical trials, particularly in phase I and IIa
clinical trials, validated with many inspections by various regulatory bodies throughout the
world, and has also been awarded the Medicines and Healthcare products Regulatory Agency
(MHRA) Phase I Supplementary Accreditation. Thus, by setting a Phase I clinical trial unit in
Malaysia, India’s Veeda Clinical Research has joined the growing list of contract research
organizations (CRO) attracted to Malaysia.12
Conclusion
Malaysia has is enhancing its agenda in clinical research within the clinical research
ecosystem. The direction of the clinical trial initiative in Malaysia is heading on the right track.
With a conglomerate of competitive strengths in clinical research, Malaysia is well-placed to
achieve greater heights in all forms of clinical research. Greater research collaborative effort
should be fostered among the private, academic and MOH to ensure a win-win triumph for all.
This vision should be realistic and together with a team spirit and a collaborative working
culture, our Clinical Research Centers nationwide will bring the science of clinical trial initiatives
to a higher platform. All these factors highlight the prominence of Malaysia as the preferred
location for all forms of clinical research, especially industry sponsored trials, being facilitated
by Clinical Research Malaysia.4
References
1. Clinical trials in drug development,
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivi
ties/ucm121345.htm
2. Clinical trials conducted to investigate safety and efficacy in human populations within a
genetically defined subset, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684667/
3. Aims of of ETP, http://[email protected]
4. Clinical Research Malaysia, http://www.crc.gov.my/
5. One Stop Centre, http://www.phama.org.my/index.cfm?&menuid=25
6. Good logistics connections and investment in ICT infrastructure,
http://www.mastic.gov.my/portals/mastic/publications/warta/insights2008/vol8.pdf
7. NMRR, http://www.nmrr.gov.my/fwbLoginPage.jsp
8. Well-established patient registries,
http://www.crc.gov.my/20080728_patientRegistry.pdf
9. Well-trained and experienced investigators,
http://www.crc.gov.my/documents/DGspeech1.pdf
10. Multiracial and multiethnic local patient population,
http://thestar.com.my/health/story.aspfile=/2007/4/22/health/17505975@sec=health
11. Relatively low cost incurred,
http://thestar.com.my/health/story.asp?file=/2007/4/22/health/17505975&sec=health
12. Phase I clinical trials,
http://thestar.com.my/news/story.asp?file=/2009/7/27/nation/20090727123611&sec=
nation
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17 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Alzheimer’s disease - an overview
Anwar Basha1, H. Harish2, C. Vijaya Raghavan3, Y. Padmanabha Reddy4
1PharmD Candidate, RIPER, Anantapur, A.P. 2HOD, Anesthesia, RDT Hosptial, Bathalapalli, A.P. 3Vice-Principal, PSG College of Pharmacy, T.N. 4Principal, RIPER, Anantapur, A.P.
Abstract
Alzheimer disease is the most common cause of dementia in the elderly. The disease
usually becomes clinically apparent as insidious impairment of higher intellectual function, with
alterations in mood and behavior. Later, progressive disorientation, memory loss, and aphasia
indicate severe cortical dysfunction, and over the next 5 to 10 years, the patient becomes
profoundly disabled, mute, and immobile. Death usually occurs from inter-current pneumonia
or other infections. The increasing incidence with age has given rise to major medical, social,
and economic problems in countries with a growing number of elderly.
Key words: Alzheimer’s disease, aging, dementia, aphasia
Introduction
Alzheimer’s disease (AD) is an illness of the brain. It causes large numbers of nerve cells
in the brain to die. This affects ability to remember things and think clearly. It usually begins
after age 60 and nearly half of people age 85 and older may have Alzheimer’s. However, it is
not a normal part of aging. The current advances in the AD show those genes play an important
role in the development of this disease.1
In 1906's, Alois Alzheimer (1864-1915), a German Neurologist and Psychiatrist, observed
a patient who experienced progressive problems with memory, language and behavior. After
her death, from brain autopsy studies, Alzheimer found dense deposits surrounding the nerve
cells (neuritic plaques) and within the neuronal cells he observed twisted bands of fibers
(neurofibrillary tangles). In this new age of medicine, this degenerative brain disorder bears his
name and the two features he observed are said to be Hallmarks of the disease.2
Epidemiology
•Dementia among people aged 60 and older is due to Alzheimer’s disease.
• In last year’s report (World Alzheimer Report-2010) submitted by the Alzheimer’s Disease
International, it is estimated that there are 35.6 million people living with AD worldwide in
2010, increasing to 65.7 million by 2030 .
•The number of people affected will be over 115.4 million by 2050.
• In 2010, there are 3.7 million Indians with dementia.3,4
Approximately 1%-6% of all Alzheimer disease (AD) is early onset (age <60-65 years) and
approximately 60% of early-onset AD is due to familial, with 13% appearing to be inherited in
an autosomal dominant manner .5
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18 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Etiology
Cause % of Cases
Chromosomal (Down syndrome) <1%
All familial ~25%
-Late-onset familial (AD2) 15%-25%
-Early-onset familial AD (AD1, AD3, AD4) <2%
Unknown (includes genetic/environment interactions) ~75%
Pathophysiology
Plaques and Tangles: The Hallmarks of AD
• Beta-amyloid plaques are dense deposits made up of protein and cellular material that
accumulate outside and around nerve cells. These amyloid plaques are made up of aggregates
of containing 40 or 42 residues of amino acids.
• Neurofibrillary tangles are twisted fibers that build up inside the nerve cell. These deposits
are protein aggregates that result from misfolding of native proteins.6
Some signs of Alzheimer’s disease
Forget how to brush the teeth or comb hair
Trouble remembering recent events
Cannot remember the names of things such as desk, house, apple or common people and
places
Wander away from home
Trouble solving simple Mathematics problems.7
Clinical manifestations of Alzheimer’s disease � The clinical manifestation of Alzheimer disease (AD) is dementia that typically begins
with subtle and poorly recognized failure of memory and slowly becomes more severe
and, eventually, horrendous. Other common findings include confusion, poor judgment,
language disturbance, agitation, withdrawal, and hallucinations.8
� Occasionally, seizures, Parkinsonian features, increased muscle tone and mutism
occur.9
Drug treatments for Alzheimer’s disease
No drug treatments can provide a cure for Alzheimer's disease. However, drug
treatments have been developed that can improve symptoms, or temporarily slow down
their progression, in some people.10
Drugs used: There are two main types of drugs used to treat Alzheimer's disease;
� Cholinesterase inhibitors: Donepezil hydrochloride, rivastigmine, galantamine.
These drugs work principally by reducing the breakdown of acetylcholine and thus
increasing the amount of the chemical in the brain. As people with Alzheimer's disease
have lower brain levels of acetylcholine. These drugs not only by preserving the
acetylcholine from being destroyed by cholinesterase, but make the receptors more
responsive to the lower amounts of acetylcholine.11
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19 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
� N-methyl D aspartate (NMDA) antagonist: Memantine is known as N-methyl D
aspartate (NMDA) antagonist which targets a neurotransmitter in the brain known as
glutamate. Glutamate plays a vital role in learning and memory but when there is too
much of it in the brain it sticks to the neuroreceptors, allowing deposits of calcium to
travel into the brain cells and kill them off. Memantine works by preventing excess
glutamate from sticking to the neuroreceptors so stopping harmful calcium deposits
destroying brain cells.12
Side-effects
• The most frequent side-effects of donepezil hydrochloride, rivastigmine,
galantamine include nausea and vomiting, diarrhea, stomach cramps and headaches,
dizziness, fatigue, insomnia and loss of appetite, while side-effects of memantine include
dizziness, headaches, tiredness, increased blood pressure and, on rare occasions,
hallucinations and confusion.
• None of these drugs is addictive.13
Treatments currently under investigation
Researchers are also looking at other treatments, including;
• Cholesterol-lowering drugs called ‘statins’
• Anti-oxidants (vitamins) and folic acid
• Anti-inflammatory drugs (NSAIDs)
• Substances that prevent formation of beta-amyloid plaques
• Nerve growth factor to keep neurons healthy.14
Vitamin E
A large study found evidence that taking vitamin E slightly delayed the progression of
the disease and allowed patients to stay independent for longer. Researchers think vitamin E
may help slow neural cell death because it is a powerful antioxidant that may help protect
neurons from damage. Do not use vitamin E (2000 IU / day), to treat Alzheimer’s without
supervision of a physician, as the doses required are high and may interact with
other medications.15
References
1. Robbins basic pathology, 8th edition, the nervous system, degenerative disease and
dementias.
2. http://www.ahaf.org/alzheimers/about/understanding/history.html (Accessed on 13-
02-2011)
3. http://www.alzheimer.org.in/assets/report_summary.pdf (Accessed on 13-02-2011)
4. http://www.alz.co.uk/research/worldreport/ (Accessed on 13-02-2011)
5. Campion D, Dumanchin C, Hannequin Early-onset autosomal dominant Alzheimer
disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum
Genet. 1999; 65:664–70.
6. Rang and Dale PHARMACOLOGY, 6th Edition, Elsevier Publications, Pg:514,515
7. Harrison's Principles of Internal Medicine, 17 ed. McGraw-Hill, NY, 2393-2406.
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20 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
8. Bacanu SA, Chowdari KV, Sweet RA. Heritability of Psychosis in Alzheimer Disease. Am
J Geriatr Psychiatry. 2005; 13:624–7.
9. Harrison's Principles of Internal Medicine, 17 ed. McGraw-Hill, NY, pp 2393-2406.
10. http://www.nia.nih.gov/Alzheimers/Publications/medicationsfs.htm
11. Alzheimer’s society – treatment ,
http://www.alzheimer.ca/english/treatment/treatments-intro.htm
12. Guide4living-independent health information online, Alzheimer’s - Memantine drug
treatment , http://www.guide4living.com/alzheimers/namenda.htm
13. Tariot, PN et al for the Memantine Study Group (2004) Memantine treatment in
patients with moderate to severe Alzheimer disease already receiving Donepezil; A
Randomized Controlled Trial, Journal of the American Medical Association 291:317-324.
http://alzheimers.org.uk/site/scripts/documents_info.php?documentID=147.
14. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922037/ (Accessed on 13-02-2011)
15. Vitamin E Treatment for Alzheimer's,
http://alzheimers.about.com/od/treatmentoptions/a/vitamin_e_treat.htm
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21 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Drug prescribing for geriatrics –a review
Alexander Daniel Sunad1, Anwar Basha2, Ram Keshav Reddy3
1Surgeon, RDT Hosptial, Bathalapalli, A.P. 2PharmD Candidate, RIPER, Anantapur, A.P. 3HOD, General Medicine, RDT Hospital, Bathalapalli, A.P.
Abstract
Geriatric is one of the challenging populations in rational prescribing. Physical,
psychological, familial and socioeconomic features are compromised in old age. In this review
we discuss on the age related changes and safe prescribing in geriatrics. There are many
medicines which can harm this population if enough care is not taken. Even the patient
counseling is also not easy as compared to adults.
Key words: Geriatrics, prescribing, polypharmacy, patient counseling
Introduction
Age-related biologic and physiologic changes, the presence of multiple pathologic
conditions with increasing age (requiring multiple drugs with possible interactions) and several
socioeconomic considerations combine to make drug prescribing more difficult for geriatric
patients.1
Elderly people are at a high risk of experiencing problems with drug therapy due to:
• Age-related changes in the body (i.e., diminution or loss of organ function).
• Exposure to many medications due to multiple health problems.
• Social circumstances such as living alone, difficulty in visiting their primary physician and
affordability of prescription medications.
• Failure to comply with the complicated drug treatment plan and poor understanding of
the drug treatment.
• Confusion resulting from the use of multiple medications, memory problems and failing
vision leading to impaired functioning2 (and mis-dosing, ranging from omission to
automatism.)
Safe prescribing principles for the elderly
I. Before prescribing a new medication, assess the patient’s current drug regimen
(including prescriptions, OTCs), and alternative medications.
II. For medications that have no alternatives, monitor the patient closely for adverse
effects.
III. Prescribe as few drugs as possible. Consider if one drug could be prescribed to treat two
conditions.
IV. Avoid adding new drugs to treat side effects of current medications.
V. “Start low and go slow” with new medications, and increase dose only as needed.
VI. Discuss potential side effects and treatment adherence with patients and caregivers.
VII. Decide if drug therapy is needed or if a non-drug alternative exists.
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22 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
VIII. Discontinue medications without a known benefit or clinical indication.
IX. Develop systems or reminders to decrease the use of these medications.
X. Understand the side effect profile and pharmacokinetic properties of the medications
that are prescribed to elderly patients.
XI. If a patient develops a new or unexplained medical problem, consider an ADE as a
potential cause.
XII. Provide patients with written information about their medications, and ensure every
patient carries a list of their medications with them at all times.
XIII. Work as an interdisciplinary team consisting of physician, pharmacist, and nurse to
optimize patient outcomes and safety.3,4
Age-related changes relevant to pharmacology1
Pharmacologic Function Age-Related Change
Absorption
Decreased absorptive surface
Decreased splanchnic blood flow
Increased gastric pH
Altered gastrointestinal motility
Distribution
Decreased lean body mass
Decreased total body water
Decreased serum albumin
Increased fat
Altered protein binding
Hepatic metabolism
Decreased liver mass
Decreased liver blood flow
Decreased enzyme activity and
inducibility
Renal excretion
Decreased renal blood flow
Decreased glomerular filtration rate
Decreased tubular secretory function
Receptor sensitivity
Alterations in:-
Receptor number
Receptor affinity
Second messenger function
Cellular responses
Drug classes used by the elderly
The drugs most often prescribed to elderly patients are of the following classes:
• cardiovascular (21% of drugs prescribed),
• central nervous system (18%of drugs prescribed), and
• diuretics and potassium (14% of drugs prescribed).
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23 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Medications and risks in geriatrics2
(Medications listed below are to be avoided or need close monitoring)
Medications of Risk
Problems
Benzodiazepines (antianxiety),
Long acting agents
Diazepam
Flurazepam
Chlordiazepoxide
Alprazolam
Barbiturates
Confusion, sedation and falls.
Antidepressants (used to treat depression),
Amitryptiline
Doxepin
Imipramine
Confusion, sedation, hypotension, falls, and
urinary retention.
Antipsychotic Agents (used to treat mental disorders)
Chlorpromazine
Thioridazine
Haloperidol
Confusion, sedation, hypotension, falls,
urinary retention, Parkinsonism (involuntary
shaking and twitching), tardive dyskinesia
(TD).
Antihistamines (used to treat sinus problems and
allergies)
Diphenhydramine
Hydroxyzine
Confusion, sedation, hypotension, falls, and
urinary retention (inability to empty bladder),
sleep disturbance.
Antiemetics (used to relieve nausea)
Promethazine
Prochlorperazine
Thiethylperazine
Confusion, sedation, hypotension, falls,
urinary retention, Parkinsonism (involuntary
tremors and rigidity), involuntary movement
Analgesics (used to relieve pain)
Paracetamol
Diclofenac
Celecoxib
Hepatotoxicity, Peptic ulceration, increased
risk of myocardial infarction.
Antiparkinsonian (used to treat Parkinsons disease)
Carbidopa-Levodopa
Confusion, dizziness, hypotension, increase in
cardiovascular toxicity.
Cardiovascular drugs (used to treat heart and blood
vessels)
Digoxin
Warfarin
Nausea, vomiting, anorexia, weight loss. Risk
of overdose and toxicities.
Bleeding tendencies (requires close
monitoring).
Antispasmodic drugs (used to prevent or relieve
spasms)
Dicyclomine
Hyoscyamine
Pro-Banthine
Dry mouth, constipation, urinary retention,
delirium.
Urinary Incontinence drugs
Oxybutynin
Tolterodine
Dry mouth, constipation, urinary retention,
delirium, confusion.
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24 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Polypharmacy
• Polypharmacy has been recognized as a major problem in the geriatric patient. Drugs
prescribed disproportionately for the elderly, constitutes over prescribing, or
"polypharmacy" (also referred to as polymedicine).
• There is no standard definition of polypharmacy. At one time, polypharmacy was
defined only as multiple drug use, but this definition is not specific enough.
Polypharmacy is now used to indicate that a particular patient receives too many drugs,
drugs for too long a time, or drugs in exceedingly high doses.
• Multiple chronic medical problems, multiple physicians, lack of coordination of care,
vague symptoms, patient pressure to prescribe, and the use of additional medications
to treat drug-related complaints have all been implicated as major factors contributing
to polypharmacy.
• Other factors include poor prescribing; the effect of primary, secondary, and tertiary
aging; pharmacodynamic and pharmacokinetic changes in drug action with aging; poor
nutritional status; prescribing drugs according to a patient's chronologic rather than
physiologic age; lack of a match between a patient's homeostatic state and the drug
selected; and unrecognized intercurrent diseases and drugs.5
Patient counseling for geriatric patients
Check for visual or hearing impairment and dementia. Patients with affected
joints may have difficulty in opening medicine bottles. It is advisable better to do
counseling at presence of their care takers, if the old is not able to manage their medical
needs.
Try non-pharmacological approaches such as walking or regular activity or
exercise, getting adequate sleep, quitting smoking, consuming alcohol in moderation
and dietary changes toward a healthier life.
Alternatives to using hypnotics;
o Get enough sleep. Go to bed and wake up at a fixed time.
o Omit caffeine after 1:00 p.m.
o Exercise and avoid daytime napping.
o Avoid alcohol use close to bed time
Alternatives to using laxatives;
o Eat a high fiber diet.
o Drink plenty of water.
o Exercise regularly.
o Identify medications causing constipation.
Alternatives to using urinary incontinence drugs;
o Try bladder training and pelvic exercises.
o Schedule a trip to the bathroom every two hours while you are awake.
o Treatment of urinary infections with antibiotics.
o Consider other medical conditions and medications causing incontinence.2
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25 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
References
1. Western journal of Medicine, Drug prescribing for the elderly, In Geriatric Medicine.
West J Med 135:455-462, Dec 1981
2. Net wellness consumer health information,
www.netwellness.org
3. United States Pharmacopeia, 2000. "Guiding Principles for Enhancing the Likelihood of
Positive Medication Use Outcomes in Geriatric Patients."
4. Primaris, Safe Prescribing Principles for the Elderly
http://www.primaris.org/sites/default/files/resources/primaris_safe_prescribing_for_el
derly_propoxyphene.pdf
5. Drug Prescribing for the Elderly, Robert J. Michocki, PharmD; Peter P Lamy, PhD, ScD;
Frank J. Hooper, MPH, ScD; James P. Richardson, MD, arc fam med vol2/apr 1993.
www.archfammed.com
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26 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Drug news Collected by Rohit Bhavsar
Toothpastes contain cancer causing nicotine
A study by the Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR) has
found that many of the toothpaste manufacturers are adulterating toothpastes and
toothpowders with high quantity of nicotine. "Out of the 24 brands of toothpastes studied in
2011, seven brands were found to contain nicotine," said Professor S. S. Agarwal of DIPSAR,
which is affiliated to the Delhi University and is funded by the Delhi government.
"Oral ingestion of nicotine can lead to oral cancer and cancer causing agents can also get
into the lining of the stomach, esophagus and into the bladder," Dr Malhotra said. Other side-
effects of nicotine consumption include drooling. Children are particularly impacted by this, and
may even report a burning sensation in the mouth.
According to Dr R. C. Jiloha of the psychiatry department, G. B. Pant Hospital, "Nicotine
is distributed throughout the body, mostly to skeletal muscles and binds to the receptors in the
brain, where it influences the cerebral metabolism."
Reference: http://indiatoday.intoday.in/story/toothpastes-contain-cancer-causing-nicotine-
study/1/150836.html
Pioglitazone Causes Bladder-Cancer Risk
French Agency for Safety of Health Products confirmed that small increases in bladder
cancer among patients treated with diabetic drug pioglitazone. German regulators recently
announced that pioglitazone should not be started in new patients with diabetes. FDA
announces previously that label for this drug should be updated. Now FDA has updated the
label for the drug to highlight the risk of the cancer, they stated that the patient with active
bladder cancer should not use the drug. They also give alert to patients who experience blood
or see red color urine. European Medicines Agency states that the small increase in risk of
bladder cancer could be reduce by appropriate patient selection and exclusion and periodic
review of efficacy and treatment of individual patient.
Reference: http://www.medscape.com/viewarticle/747609
Abnormal heart rhythms associated with high doses of citalopram hydrobromide
FDA notified healthcare professional and patients that 40 mg of citalopram
hydrobromide should not be use for longer duration because it causes abnormal changes in
electrical activity of the heart. Changes in the electrical activity includes such as prolongation of
the QT interval of the electrocardiogram. It leads to abnormal heart rhythm which can be fatal.
There is risk of prolongation of QT interval includes underline heart condition and
predisposition to low level of potassium and magnesium in blood. Previously the citalopram
drug label stated that certain patient may require dose of 60mg per day but recent studies say
that there is no benefit in treatment of depression with higher than 40 mg per day. The
citalopram drug label has been revised to include new dosage and usage recommendation.
Reference: http://www.drugs.com/fda/celexa-citalopram-hydrobromide-safety-communication-
abnormal-heart-rhythms-associated-doses-13017.html
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27 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
Chronic Use of NSAID Doubles CV Death in Elderly
International Verapamil-Trandolapril Study (INVEST) demonstrates that older patients
with hypertension and coronary artery disease who use nonsteroidal anti-inflammatory drugs
(NSAIDs) chronically for pain are at significantly increased risk of cardiovascular events.
Dr Anthony A Bavry (University of Florida, Gainesville) found that significant increase in
adverse cardiovascular outcomes, primary driven by an increase in cardiovascular mortality. In
his observational study of INVEST the patients included were typical of those seen in internal-
medicine, geriatric, and cardiology clinics; they were older, with hypertension and clinically
stable coronary artery disease. Most of the patients are taking ibuprofen, naproxen, or
celecoxib. He suggested that by concerned with their physician, these medication should be
terminated and switch to acetaminophen or at least try to get them to reduce the dose of
NSAID or the frequency of dosing.
Reference: http://www.medscape.com/viewarticle/746380
FDA Warns: High-Dose Fluconazole in Early Pregnancy may cause birth defect.
The US Food and Drug Administration (FDA) warned that chronic use of fluconazole in
high doses (400 - 800 mg/day) during the first trimester of pregnancy may be associated with
certain birth defects in infants. The risk does not appear to be associated with a single, low dose
of fluconazole (150 mg) used to treat vaginal candidiasis (yeast infection).
The features seen in these infants include brachycephaly, abnormal facies, abnormal
calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis,
and congenital heart disease.
The FDA has changed the pregnancy category from category C to category D. Pregnancy
category D means there is positive evidence of human fetal risk based on human data but the
potential benefits from use of the drug in pregnant women with serious or life-threatening
conditions may be acceptable despite its risks but the pregnancy category for a single, low dose
of fluconazole has not changed and remains category C.
Reference: http://www.medscape.com/viewarticle/747466
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28 RIPER PDIC Bulletin, September 2011, Volume 2, Issue 14
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