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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 )

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.


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


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

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Phone: 91-8978541693

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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


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

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

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

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ntific sessions were

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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


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


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.


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%


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


Other (n = 112) 38%

Not In Therapeutic Range and Adjusted (n = 572) 42%

Transplant Surgery (n = 340) 50% < 0.001


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


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.


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


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


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


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


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


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


� 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.


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


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.


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).


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.


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


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


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


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.


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.



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RIPER PDIC Bulletin - · PDF fileMrs. Seeba Zachariah, M.Pharm, Assoc Professor, ... RIPER PDIC Bulletin Published by the Principal, ... Goh PP, Teoh SC, Hazrah A