NEWS & INSIGHTS

MAY/JUNE 2015

87 percent of ICU patients at

SGH experience drug-drug
interactions

NEWS

DRUG PROFILE

Attenuated sunitinib
regimen better for
Asians with late-stage
kidney cancer

Sofosbuvir for hepatitis

C virus infection

BUSINESS

CLINICAL
PHARMACY

New headquarters
to help Sigma-Aldrich
support AsiaPac clients

Imatinib may be a
novel treatment option
for colon cancer

MAY-JUNE 2015 N E W S 2

87 percent of ICU patients at SGH

experience drug-drug interactions
RADHA CHITALE

ighty-seven percent of patients in the intensive care unit (ICU) of Singapore General

Hospital (SGH) experienced drug-drug interactions (DDI); about a third were major or contraindicated drug interactions with significant adverse effects such as major bleeding.
In our study, with every increase in the number of drug interactions, the risk of adverse drug
reactions [ADR] for our patients increased by

interactions. One-third were major or contraindi-

1.2 percent, said Ms. Jasmine Ong, a pharma-

cated DDIs.

cist at SGH, speaking at the SGH 21st Annual

Scientific Meeting, held recently in Singapore.
For an average ICU patient with a mean of
eight drug interactions per patient, this will be at
least a 10 percent risk.

Polypharmacy is common in ICUs, Ong noted,

but the clinical consequences are poorly understood, and they can vary between institutions depending on prescribing practices.
During the follow-up period, there were 14

The prospective observational cohort study

cases of ADR due to DDIs, the most common of

included 91 adults admitted to the SGH ICU

which were major bleeding. Bleeding was likely

(mean age 62 years, 59 percent male) in May

due to concurrent use of antiplatelet combina-

2014 who were followed up for their entire ICU

tions of aspirin, clopidogrel, ticagrelor, enoxapa-

stay or until the end of the 1-month study pe-

rin, warfarin, or amiodarone.

riod. The median length of ICU stay was 6 days

Strategies need to be developed to reduce

and the median length of hospital stay was 21

this risk of bleeding, Ong said. For example...

days. Twenty-five percent of the cohort died

determine the baseline bleeding risk of ICU pa-

during the study.

tients and if it is high, consider using alternative

The researchers reported a total of 794 DDIs.

Eighty-seven percent of patients had at least one

medications or totally avoiding the drug interaction.

DDI, for a mean 8.6 DDIs per patient or 147 DDIs

Nephrotoxicity, peripheral necrosis, hepato-

per 100 patient days. The majority of these were

toxicity, QTc prolongation and hypotension also

a result of pharmacodynamic drug interactions,

occurred.

as opposed to pharmacokinetic or other types of

ADRs warranted drug discontinuation in 10

MAY-JUNE 2015 N E W S 3

patients along with some additional measures

cludes consultation, laboratory test, and proce-

such as dialysis for nephrotoxicity.

dure fees at SGH.

Patients with more DDIs had a higher risk of

Ong said the reported incidence of DDIs and

ADRs. Patients with ADRs had an average of 10

corresponding high rate of ADRs in the SGH

DDIs per patient compared with 6.5 DDIs in pa-

ICU population was higher than those reported

tients without ADRs.

in other studies, likely because their study in-

Patients with ADRs also stayed longer in the

ICU, an average of 15 days compared with 5
days for patients without ADRs.

cluded patient data from two databases as well

as a literature search.
The study was limited by the follow-up period,

Other factors associated with longer hospital

which may not have captured patients who expe-

stays ICU mortality, 28-day mortality were

rienced an ADR after discharge, and by the tool

not associated with ADR.

for evaluating how likely an adverse reaction is the

The longer ICU stay and additional monitoring and management required by patients

result of a drug, which is meant to address reactions to single drugs only.

who develop ADR also led to a sharp increase

This highlights the role of the pharmacist in

in costs, Ong said. If they experience an ADR,

the active surveillance for DDI and the streamlin-

patients can pay an additional S$9,000 on top

ing of medication regimens and monitoring for

of the average cost of S$910/day which ex-

potential ADRs, Ong said.

MAY-JUNE 2015 N E W S 4

MIMS rolls out new identity,

purpose

eading medical and drug information

macy,Oncology,Cardiology,

provider MIMS has rolled out a major re-

Endocrinology, Hepatology, Gastroenterol-

brand initiative to better engage healthcare

ogy, Neurology, Psychiatry and Obstetrics &

communities and provide healthcare profes-

Gynaecology and Paediatrics) on its website

sionals with unified multichannel information

www.mims.com and MIMS mobile app.

they can put into practice.

Respirology,

Were going beyond just providing infor-

All MIMS publications Medical Tribune,

mation, said Ms Diana Edwards, managing

Oncology Tribune, Pharmacy Today, and JPOG

director, MIMS Hong Kong and Singapore.

were renamed MIMS Doctor, MIMS Oncol-

To build and sustain thriving communities,

ogy, MIMS Pharmacy and MIMS JPOG, re-

we need to engage and connect people. We

spectively. The publication titles now carry the

hope our news and insights, eLearning pro-

new red logo to mirror the companys renewed

grams, congress coverage and other servic-

commitment to connect and engage people.

es will facilitate knowledge-sharing and build

Mr Ben Yeo, managing director of MIMS

such communities.

Asia Pacific, recognized the importance of

MIMS, a subsidiary of AXIO Data Group,

communicating the companys new identity

with presence across 13 countries, has been

and purpose across a global platform.

the source of clinical news and drug infor-

We see MIMS as the link that brings to-

mation for health care professionals in Asia.

gether healthcare communities, helping

With MIMS integrated multichannel content,

them to obtain and exchange knowledge

information becomes even more accessible

to improve patient outcomes through better

on print, online and mobile, said Ms Sher-

care, he said.

lynn Tan, deputy director, MIMS Marketing.

To further support clinicians treatment

This allows MIMS to grow its registered user

decisions, MIMS introduced 12 disease

base to over 2 million and to generate an av-

specialty channels (Multispecialty, Phar-

erage of 30,000 new users each month.

MAY-JUNE 2015 FO R U M 5

NCDs and the need for policy

solutions, effective interventions
Excerpted from a speech by Dr Margaret Chan, WHO director general, during a
dialogue on non-communicable diseases held recently in Geneva, Switzerland.

oncommunicable diseases (NCDs) have

overtaken infectious diseases as the lead-

ing cause of mortality worldwide. WHO estimates that 80 percent of the burden from NCDs
now falls on low- and middle-income countries,
where people develop these diseases earlier,
fall sicker, and unfortunately die sooner than
their counterparts in wealthy nations. WHO estimates that NCDs are responsible for 14 million
premature deaths in the developing world each

doors? For the millions of people living in so-

year.

called urban food deserts, healthy eating is

In some developing countries in Asia, the

simply not an option.

number of deaths from cardiovascular disease

This is the first big challenge. The evidence,

before the age of 55 is twice that in wealthy

statistics, and arguments you put forward for

countries. The reference to type 2 diabetes as

international cooperation must stress the need

adult onset diabetes is no longer apt as so

for policy solutions that shape social environ-

many children are now being diagnosed with

ments. These solutions must be supported at

this disease.

the highest level of government, and they need

The responsibility for the rise in NCDs does

not fall on individuals who choose to eat,

to be put in place through a whole-of-government approach.

smoke, and drink too much or opt for a sed-

A second big challenge is competition. With

entary lifestyle. The responsibility falls on the

17 goals and 169 targets currently proposed

environments in which these choices are made.

for the post-2015 development agenda, this is

Can children be blamed for an addiction to

competition for a sliver or some crumbs from

nicotine when single cigarettes are sold at the

the pie, not a piece.

gates of their schoolhouse? Can parents be

You are being asked to sharpen the evidence

blamed for their overweight children when cit-

showing the two-way links between NCDs and

ies have no green spaces or the crime rate is

poverty. You are being asked to make a stron-

so high that children are not safe playing out-

ger case for viewing the prevention and control

MAY-JUNE 2015 FO R U M 6

of NCDs as an explicit poverty-reduction strat-

how strongly prevention and control depend on

egy.

the engagement of multiple non-health sectors.

You are being asked to provide an inventory

To guide work, we have an action plan

of international agencies that have integrated

through 2020, a monitoring framework with

NCDs into their development policies and ex-

nine global targets, and a set of effective and

tract the lessons learned. We want to hear your

affordable interventions, known as best buys,

proposals about how official development as-

that can make a difference in any resource set-

sistance can be used to strengthen prevention

ting.

and control, yet without compromising funding

for other health priorities.
We ask you to do all of these things because
of your expertise, knowledge, and experience.
A third big challenge is the opposition. This
is opposition from powerful economic opera-

As the root causes of NCDs lie beyond the

direct purview and responsibility of the health
sector, combatting these diseases is a complex task involving multiple sectors. Here, too,
we have support from the Global Coordination
Mechanism and a UN Interagency Task Force.

tors who strongly oppose any regulatory con-

There are two points made in the discus-

trol or restrictions on their marketing of health-

sion paper prepared for this meeting. First, the

harming products.

UN General Assemblys 2014 progress review

This is a formidable obstacle to prevention.

found no lack of high-level government commit-

Economic power readily translates into politi-

ment to NCDs. But it witnessed, in far too many

cal power. We rely on civil society for support

countries, a lack of capacity to act, largely be-

in many areas, but most especially in this one.

cause of insufficient national expertise in low-

The public health community has some

and middle-income countries. International co-

tools in hand to respond to these challenges.

operation can provide this expertise. Second,

The 2011 UN Political Declaration on NCDs

efforts to prevent and control NCDs depend on

sets out some compelling arguments. It posi-

a well-functioning health system, ideally one

tions these diseases as one of the major chal-

that aims to reach universal health coverage.

lenges for development in the 21st century. It

Any look at the interactions between NCDs

points out their threat to economies and their

and poverty must also look at ways to increase

contribution to inequalities. It gives the primary

access to care and reduce the catastrophic

role and responsibility of responding to these

medical bills that push so many millions of fam-

challenges to governments. And it underscores

ilies below the poverty line each year.

MAY-JUNE 2015 N E W S 7

Attenuated sunitinib regimen

better for Asians with late-stage
kidney cancer
RADHA CHITALE

n attenuated regimen of the first-line metastatic renal cell carcinoma (mRCC) treat-

ment sunitinib had similar efficacy to the conventional regimen but significantly reduced
toxic side effects among Asian patients, said
researchers from the National Cancer Centre
Singapore (NCCS).
Compared with the standard 50 mg/day
in a 4-weeks on, 2-weeks off treatment cycle,
a 37.5 mg/day dose of sunitinib for the same

vere side effects of grade 3 or higher with the

6-week treatment cycle resulted in fewer se-

conventional dosing, Tan said. Our immediate

vere toxicities (59 percent attenuated vs 85

response was to refine the treatment protocol to

percent conventional, p=0.0088), dose delays

improve patients quality of life.

(24 percent attenuated vs 58 percent conven-

The attenuated regimen also lowers the cost

tional, p=0.0004), and dose reductions (35

of treatment with sunitinib by about S$1,350 per

percent attenuated vs 70 percent conven-

month from the average cost of conventional

tional, p=0.0005). [Clin Genitourin Cancer

treatment, which is about S$5,400 per month,

2014;pii:S1558-7673(14)00255-9. doi:10.1016/j.

Tan said.

clgc.2014.11.004]

Sunitinib is a targeted therapy for use in

Just 3 years into the 7-year study, which be-

mRCC and the 50 mg/day 6-week cycle regi-

gan in 2007, oncologists around Singapore ad-

men is the US Food and Drug Administration-

opted the attenuated regimen for their mRCC

(FDA) approved dosing, determined safe and

patients and it has now become the standard

efficacious, with acceptable toxicity, through a

of care, said lead researcher Dr. Tan Min Han,

number of studies in Western populations.

a member of the genitourinary oncology team

However, studies in Asian populations

and visiting consultant in the Division of Medical

showed that many had to stop treatment or

Oncology at NCCS.

lower their dose due to grade 3-4 toxicities in-

Many of the patients were experiencing se-

cluding neutropaenia, thrombocytopaenia, and

MAY-JUNE 2015 N E W S 8

hand-foot syndrome.
One alternative was to lower the dose to 37.5
mg/day for continuous once-daily dosing (CDD)

regimen and compared to mRCC patients

around Singapore who were treated with the
conventional sunitinib regimen.

but a retrospective analysis in Asian vs non-Asian

Overall survival (OS) from treatment initiation

patients showed Asian patients continued to have

(18.3 vs 16.5 months; p=0.54), total OS (27.4

a higher frequency of grade 3-4 toxicities, al-

vs 21.8 months, p=0.45), and progression-free

though the antitumour effect remained. [Ann On-

survival (6.7 vs 7.9 months, p=0.64), were simi-

col. 2010;21(Suppl. 8):913P]

lar between the conventionally and attenuated

Other than the CDD regimen, there is lim-

dosed groups, respectively. There was a lower

ited data on alternative sunitinib regimens, the

rate of adverse outcomes in the attenuated

researchers said.

group during treatment real world results that

In the current study, 127 mRCC patients at

the NCCS were treated with the attenuated

the researchers said is evidence for such a regimen in the absence of a randomized trial.

Light-based assay could swiftly

identify treatment for XDR bacteria
RADHA CHITALE

light-based assay could help identify the

best antibiotic combinations for combating

extremely drug resistant (XDR) bacteria.

Combination therapy is highly strain-spe-

cases occurring at SGH. Such infections can require strong antibiotic treatments used in combination, which can be toxic to patients.
While there are a number of treatment options available, swiftly determining optimal
treatment can be challenging.

cific, which means that one combination may

Traditional efficacy testing using the viable

be effective against one strain but not another,

plate count method is sensitive and specific but

said Ms. Jocelyn Teo, a pharmacist at Singa-

requires a lot of manpower to plate cells and

pore General Hospital, during a presentation

compare the effects of various drug combina-

at the SGH 21st Annual Scientific Meeting, held

tions, Teo said, and can take over 2 days.

recently in Singapore.
But which antibiotic combina-tions to use?
There is no assay for this.
XDR bacterial infections are an increasingly
common clinical scenario, Teo said, with weekly

Teo and colleagues capitalized on the presence of the intracellular energy molecule adenosine triphosphate (ATP), present in all living
cells, as a surrogate marker for viable bacteria
count.

MAY-JUNE 2015 N E W S 9

Applying the light-emitting compound lucif-

low which the drug combination was no longer

erin to ATP allowed Teo to measure the amount

inhibiting bacterial growth. Prospective valida-

of ATP as a function of bioluminescence.

tion using additional strains showed the meth-

Teo and her team used 100 randomly selected XDR isolates with a variety of bacteria covering many different resistance mechanisms.

od to be robust.
We identified individual cut offs for each
species combination, Teo said.

Each isolate was tested against single and

The bioluminescence assay proved sensitive

two-drug combinations of the most appropriate

and specific at determining optimal drug com-

set of antibiotics. For example, Klebsiella pneu-

binations effective against XDR bacterial infec-

moniae was tested against tigecycline, rifampi-

tions, reduced the testing time to 24 hours, and

cin, polymyxin B, levofloxacin, and meropenem.

was easy to perform.

Results were available within 24 hours.

The researchers then analysed for sensitivity
and specificity, determining the cut-off point be-

Teo said further testing on more bacterial

strains and drug combinations to assess the
clinical utility of the test would be necessary.

Solution-focused conversations help

motivate patients to change
RADHA CHITALE

solution-focused approach is more likely to

ate in situations such as diagnosis, prescribing

treatment and information counselling. However, this approach can be flawed.

help clinicians engage with their patients

We work in hospitals, we are very accus-

and motivate them to change their behaviours

tomed to the medical model, and there is a ten-

than a problem-solving approach, said Ms.

dency to perceive our clients in terms of their

Cheryl Ng, a senior Speech-Language therapist

deficits and as problems to be solved, Ng said.

in the Department of Speech Therapy at Sin-

For example, an overweight patient who

gapore General Hospital (SGH).Rather than

wants to lose weight might be told what they

focusing on whats wrong, [a solution-focused

should and should not do as far as diet and ex-

approach] focuses on what works, said Ng,

ercise.

during a presentation at the SGH 21st Annual

Scientific Meeting, held recently in Singapore.

But this reinforces the clinicians as experts,

clients are disempowered, and they dont have

Clinicians often adopt a problem-solving ap-

ownership of the solution. We shouldnt be sur-

proach to patients, Ng said, which is appropri-

prised when the client comes back not having

MAY-JUNE 2015 N E W S 10

lost any weight.

In addition, the pressure to constantly solve
patient problems can increase the rate of clinician burnout.

vising them to buy a pill box or create reminders

in their calendar.
Since the solutions come from the patients
frame of reference and not ours, they have a

Solution-focused brief therapy (SFBT) was

much higher chance of fitting naturally in their

developed in the 1970s as a therapeutic ap-

lives and a much higher chance to be effective

proach that favours how change happens over

and complied with, Ng said.

how problems develop, focusing on patient

A review of 43 controlled-outcome SFBT

knowledge and resources. It is used most often

studies showed that 74 percent reported sig-

in the context of palliative care, cancer care, de-

nificant positive benefit from the approach and

pression, fatigue, and pain management.

23 percent reported positive trends. Other re-

The overarching principles guiding the pa-

views generally support SFBT for non-severe

tient-clinician interaction are that they should

presenting problems, although they have not-

be patient-led, future-oriented, and strength-

ed problems with SFBT study methodology

focused. Conversations should re-frame nega-

such as concurrent therapies and a wide vari-

tive feelings and transition to asking for stories

ety of subjects included. [Research on Social

where patients created solutions. Positive feed-

Work Practice 2013,23:266-283; J Child Psy-

back is also critical.

chol Psychiatry 2013,54:707-723; Fam Process

For example, asking a patient who forgets

2000,39:477-498]

to take medicine to recall times when they did

Clinicians themselves may balk at engag-

remember to take it and identify helpful behav-

ing with patients this way because they lack the

iours such as putting it in a convenient place

confidence or skills for such interactions.

like the kitchen counter is more helpful than

However, they should remember that the

asking why they forget to take the medicine, tell-

knowledge and experience of patients is a valu-

ing them the risks of not taking medicine, or ad-

able resource, Ng said

MAY-JUNE 2015 N E W S 11

Tabalumab no better than placebo

for RA
ELVIRA MANZANO

structurally efficacious in patients with moderate-to-severe RA taking MTX, said lead inves-

n investigational anti-B-cell activating fac-

tigator Professor Josef Smolen of the Medical

tor (BAFF) monoclonal antibody is no bet-

University of Vienna in Vienna, Austria.

ter than placebo in achieving clinical response

The study included 1,041 patients with mod-

in patients with rheumatoid arthritis (RA) who

erate-to-severe RA (6 months duration) who

had not responded to methotrexate (MTX), a

had inadequate responses to MTX therapy, ran-

phase III study has shown.

domized to tabalumab 120 mg every 4 weeks

There was no difference in ACR20 (American

or 90 mg every 2 weeks or placebo. Median

College of Cardiology 20 percent) response

CD20+ B-cell counts increased at week 1 in the

score at week 24 the primary endpoint of

tabalumab groups, but decreased from week

the study or change in mTSS (modified To-

4 to 52. The differences in absolute and rela-

tal Sharp Score) from baseline at week 52 be-

tive CD20+ B-cell-level changes from baseline

tween patients treated with tabalumab and

to week 52 were significant in both tabalum-

placebo. Nearly 30 percent of patients treated

ab groups compared with the placebo group

with tabalumab 120 mg every 4 weeks and 32.8

(p<0.001). Numerically more serious infections

percent of those assigned to tabalumab 90 mg

were seen with tabalumab groups (1.7 and 0.6

every 2 weeks achieved ACR20 compared with

percent vs 0.3 percent for placebo).

25.1 percent for placebo. There were also no

significant differences between the tabalumab

The study was terminated early due to insufficient efficacy.

and placebo groups in the percentage of pa-

BAFF blockade alone does not appear to

tients achieving ACR50 and ACR70 responses

provide sufficient interference with the immuno-

at the end of treatment. [Ann Rheum Dis 2015;

pathogenesis of RA, said the researchers.

doi:10.1136/annrheumdis-2014-207090]

Tabalumab is the third anti-BAFF monoclo-

Despite changes in CD20+ B cells, RF

nal antibody to fail in RA studies. Earlier, belim-

rheumatoid factor, and immunoglobulins follow-

umab and atacicept also failed to achieve signif-

ing tabalumab treatment, BAFF inhibition with

icant responses in RA patients on background

tabalumab was not clinically, functionally, or

MTX.

MAY-JUNE 2015 N E W S 12

First WHO guidelines on hep B take

public health approach
SARAS RAMIYA

he first-ever WHO guidelines on hepatitis

B take a public health approach. This will

simplify and standardize approaches, to ensure

every person has access to treatment, says
Dr. Gottfried Hirnschall, director, department of
HIV/AIDS, WHO, Geneva, Switzerland, at the official launch of the guidelines.
The evidence-based guidelines, which target

the most advanced stage of liver disease;

national programme managers, are intended for

the use of two safe and highly effective medi-

low- and middle-income countries (LMICs) that

cines, tenofovir (TDF) or entecavir (ETV), for

have poor access to liver biopsy and HBV DNA

the treatment of chronic hepatitis B; and

testing. [2015 WHO Guidelines for the preven-

regular monitoring using simple tests for ear-

tion, care and treatment of persons with chronic

ly detection of liver cancer, to assess wheth-

hepatitis B infection. Available at: www.who.int/

er treatment is working, and if treatment can

hiv/pub/hepatitis/hepatitis-b-guidelines/en/ Ac-

be stopped.

cessed on 16 March]

Source: WHO. Available at: www.who.int/

The guidelines aim to strike a balance between implementing the best-proven standard

mediacentre/news/releases/2015/hepatitis-bguideline/en/

of care and what is feasible on a large scale in

The WHO guidelines offer opportunities to

resource-limited settings, said Dr. Philippa East-

Asia through massive price reductions for TDF

erbrook, department of HIV/AIDS, WHO.

and ETV. These reductions have been achieved

Priority for treatment is given to those most

through negotiation among governments, the

in need, and treatment is provided in an envi-

pharmaceutical industry and NGOs, said Pro-

ronment free of stigma and discrimination, she

fessor Ji-Dong Jia, Liver Research Center, Bei-

added.

jing Friendship Hospital, China. He noted that

Key recommendations include:

the use of a few simple non-invasive tests
to assess the stage of liver disease to help
identify who needs treatment;
prioritizing treatment for those with cirrhosis

there are both voluntary and compulsory licenses, and tiered pricing eg, US$0.50 per day for
TDF in Thailand.
Furthermore, there is a need for Asian countries to establish long-term follow up systems

MAY-JUNE 2015 N E W S 13

to monitor and evaluate patients in relation to

[It] certainly simplifies treatment and resources

efficacy and safety of treatment, treatment com-

to prioritize those in greatest need of treatment,

pliance and disease progression, he added.

which will reduce the health cost disparity and

Documenting disease burden of hepatitis B

is a challenge in sub-Saharan Africa, said Pro-

contribute to the regional control of hepatitis B

infection, said Lesi.

fessor Olufunmilayo Lesi, Gastroenterology and

These guidelines are an important step to-

Hepatology Unit, department of medicine, Col-

wards making sure that governments have

lege of Medicine, University of Lagos, Nigeria.

treatment programs for hepatitis B, and get re-

Although hepatitis B screening is done rou-

imbursement for the best drugs, said Charles

tinely in blood transfusion services, antenatal

Gore, president, World Hepatitis Alliance, Lon-

care (in some hospitals) and health screening,

don, UK.

there are no clear guidelines for population

At the same time, we need help from the

screening. Assessment of liver disease is most-

governments to outlaw stigma. Too many coun-

ly done in specialist and referral and private

tries have allowed testing and then exclusion of

hospital settings. Most chronically infected per-

people with hepatitis B from education or em-

sons are unaware and undiagnosed, she said.

ployment. And that again is not acceptable. We

So, these guidelines provide an opportunity

for a paradigm shift in hepatitis management

have to make sure the guidelines are put into

practice by all countries, he said.

Fish oil consumption may induce

chemoresistance
JENNY NG

onsuming fish oil has been shown to induce chemo-resistance in mice, leading

experts to advise avoiding fish and fish oil supplements when undergoing chemotherapy.
Patients with cancer often adopt lifestyle
changes such as taking dietary supplements
with the intention to influence and improve their
health. However, mice studies showed that add-

cisplatin chemotherapy substantially reduced

ing the fatty acid fish oil component 16:4(n-3) to

the drugs effect on tumour suppression.

MAY-JUNE 2015 N E W S 14

A 95.5 mm3 difference in tumour volume was

prolonged elevation of plasma 16:4(n-3).

seen in mice treated with 16:4(n-3) plus cispla-

Healthy volunteers who ate 100 g of herring

tin vs cisplatin alone (p=0.04), while cisplatin

and mackerel also showed increased plasma

alone effectively reduced tumour volume by

levels of 16:4(n-3). However, the level of plasma

142.4 mm3. [JAMA 2015, doi:10.1001/jamaon-

16:4(n-3) was highly dependent upon the levels

col.2015.0388]

of 16:4(n-3) in the fish. Tuna, which contained

Similar chemoresistant effects of 16:4(n-

the smallest amount of 16:4(n-3), had no effect

3) were seen with irinotecan and oxaliplatin

on plasma 16:4(n-3) while salmon led to a small

(p<0.05 for both).

and short-lived spike.

Our results add to the growing awareness

In dose-response analyses, as little as 1 L

that not all dietary supplements are beneficial or

of 16:4(n-3) added to cisplatin was enough to

harmless some may interfere with treatment

induce chemoresistance in tumours. According

outcomes, the researchers wrote.

to the researchers, the equivalent intake of 3

In a survey of 118 patients undergoing cancer treatment, the researchers identified regular

mL of fish oil in an average-sized adult is much

lower than the recommended daily intake.

supplement use in 30 percent, and regular use

All six commercially available fish oils test-

of omega-3 fatty acids in 11 percent of patients.

ed were found to contain substantial levels of

Consuming the recommended daily amount

16:4(n-3), ranging from 0.2 to 5.7 M. Moreover,

of fish oil (10 mL) was shown to rapidly increase

the data suggest that other fatty acids in fish oil

plasma levels of 16:4(n-3), up to 20 times base-

may be metabolized in the body to form 16:4(n-

line levels, in healthy volunteers. Different com-

3), with the potential to interfere with chemo-

mercially available fish oils containing varied

therapy.

amounts of 16:4(n-3) were found to induce similar spikes in plasma 16:4(n-3).

Based on our findings, until further data become available, we advise patients to temporarily

16:4(n-3) levels peaked around 4 hours and

avoid fish and fish oil from the day before chemo-

normalized after 8 hours of intake. However, in-

therapy until the day thereafter, the researchers

gesting a high dose of fish oil (50 mL) led to a

concluded.

MAY-JUNE 2015 N E W S 15

FDA to assist pharma in developing

abuse-deterrent opioids
CHRISTINA LAU

he US FDA is to assist the pharmaceutical industry in developing abuse-deterrent

opioids and in making these safer formulations

available sooner, according to a final guidance
document issued on 1 April 2015.
These safer opioids are to be formulated in
ways that make it more difficult to inhale or in-

of the Society of Hospital Pharmacists of Hong

ject the medications.

Kong. In Victoria, a 21-fold increase was seen

The document, titled Abuse-Deterrent Opi-

in the detection of oxycodone in deaths reported

oids Evaluation and Labelling Guidance for

to the Coroner between 2000 and 2009. Almost

Industry, is part of the FDAs efforts to curb

54 percent of the cases of death were the result

the escalating misuse or abuse of prescrip-

of drug toxicity. [Inj Prev 2011;17:254-259]

tion opioids in the US, which has become a

Diversion of prescription opioids to drug

public health concern. [http://www.fda.gov/

abusers or dealers is very common in Austra-

downloads/Drugs/GuidanceComplianceReg-

lia. To curb the opioid epidemic, a formulation

ulatoryInformation/Guidances/UCM334743.

of hydromorphone is enteric-coated with a hard

pdf; Addiction 2014;109:177-181; Addiction

substance to prevent abuse through injection,

2014;109:185-186]

he told MIMS. Furthermore, community phar-

The science of abuse-deterrent medication is

macists actively provide counselling and moni-

still relatively new and rapidly evolving. The FDA

toring for patients on opioid therapy through a

is eager to engage with manufacturers to sup-

government-run programme.

port advancements in this area and make these

In the rest of Asia Pacific, little data is pub-

medications available as quickly as possible,

lished on the prevalence of opioid diversion,

said FDA Commissioner, Dr. Margaret Hamburg.

he continued. In Hong Kong, opioid diversion

In the Asia-Pacific region, Australia takes the

is uncommon because these analgesics are

lead in the opioid epidemic and the develop-

generally underused except in oncology set-

ment of measures against abuse.

tings. Also, our choice of opioid analgesics is

The prescription of oxycodone and tramadol in Australia saw dramatic increases between
1992 and 2007, said William Chui, President

limited, and no abuse-deterrent opioids are currently available on the Hong Kong market.
Although the development of abuse-de-

MAY-JUNE 2015 N E W S 16

terrent opioids can help reduce diversion and

orative care with physicians in cases of misuse,

abuse, Chui said pharmacists also play impor-

abuse or diversion, he suggested.

tant roles in ensuring appropriate use of these

In Hong Kong, opioid registries should be

medications. Their roles include opioid pre-

implemented and made mandatory for all pre-

scription monitoring, identification and referral

scribers, including those in the private sector,

of patients at risk of opioid abuse, and collab-

he added.

Tenofovir safe, effective in pregnant

women with hep B refractory to
lamivudine or telbivudine
LIANNE COWIE

enofovir monotherapy appears to be both

safe and effective for treating pregnant women

with chronic hepatitis B refractory to lamivudine or

telbivudine, according to a recent study in China.
In the retrospective study, clinical data were

termined the effects of tenofovir on maternal and

evaluated from 17 pregnant women (median age

perinatal outcomes, foetal growth and develop-

30.6 [range 2345] years) with chronic hepatitis B

ment, and neonatal prognosis.

resistant to lamivudine or telbivudine therapy who

At the time of delivery, HBV levels were signifi-

were subsequently treated with tenofovir mono-

cantly reduced to <500 copies/ml in 14 women

therapy. [World J Gastroenterol 2015;21:2504-

(82.4 percent; p<0.0001). Moreover, serum ALT

2509]

levels had normalized in the 10 women who had

The median level of hepatitis B virus (HBV) DNA

elevated levels at baseline (p=0.0003). All of

among the women was 5.9 (range 4.27.2) log10

the infants had good Apgar scores with normal

copies/mL at baseline. Ten women also had ab-

growth and development. There was no evidence

normal levels of alanine aminotransferase (ALT).

of vertical transmission among the 11 infants who

All of the women were treated with tenofovir 300

completed HBV vaccination.

mg/day initiated at a median gestational age of 15

Although these findings are promising, the re-

(range 028) weeks and continued for a median

searchers cautioned that larger studies are need-

of 24.4 (range 1240) weeks. The researchers de-

ed for confirmation.

Essential Clinical
Practice Tool
On-The-Go

The FREE MIMS app delivers critical prescribing information, medical news
and CME articles as well as clinical calculators essential to physicians daily
practice needs.
With MIMS available across multiple platforms and devices, you can now easily
and conveniently find the most up-to-date and relevant drug information you
need anytime, anywhere.

Join over a million MIMS members who have incorporated MIMS

into their daily workflow. Connect with MIMS today.
www.mims.com

MIMS mobile/tablet app

facebook.com/mimscom

MAY-JUNE 2015 D R U G P R O F I L E 17

Sofosbuvir for hepatitis C virus

infection
Hepatitis C virus (HCV) infection is a major global public health issue and chronic
infections can lead to cirrhosis and end-stage liver disease or hepatocellular carcinoma.
Existing drug regimens have been limited by poor response in some patient subgroups
as well as a lack of efficacy across the range of HCV genotypes. Sofosbuvir (Sovaldi,
Gilead), a nucleotide polymerase inhibitor, terminates HCV RNA synthesis and leads
to sustained virological response across a number of HCV genotypes.
NAOMI ADAM
MSc (Med), Category 1
Accredited Education Provider
(Royal Australian College of General Practitioners)
Introduction
Hepatitis C virus (HCV) infection is emerging
as a major public health issue worldwide. Acute
infection is the cause of over 54,000 deaths an-

(Brunei, Japan, South Korea, Singapore) 1.4 per-

nually. However the major burden of disease is

cent. [Hepatology 2013;57:1333-42]

due to the adverse consequences of chronic in-

With the rising prevalence and serious con-

fection. About 20 percent of patients with HCV

sequences of HCV infection, there is an urgent

eventually develop cirrhosis and die due to end-

need for effective and safe therapies. The first

stage liver disease or hepatocellular carcinoma.

treatment used was interferon alfa-2b introduced

It is estimated that there are 3-4 million new HCV

in the early 1990s, followed a few years later by

infections each year and 170 million people with

interferon alfa-2a. Combination therapy with the

chronic infection. [Hepatology 2013;57:1333-42]

antiviral ribavirin was introduced in 1998.

The prevalence of HCV is relatively high in

More recently, the protease inhibitors telapre-

some parts of Asia: in East Asia (China, Hong

vir and bocepravir have become a third compo-

Kong, Macau, North Korea, Taiwan) 3.7 percent

nent of standard care for HCV. With this approach,

and South Asia (Afghanistan, Bangladesh, Bhu-

a subgroup of patients are able to achieve a sus-

tan, India, Nepal, Pakistan) 3.8 percent. Preva-

tained virological response (defined as complete

lence is lower in Southeast Asia (including Ma-

eradication of the virus) and enjoy an excellent

laysia, Philippines, Thailand, Vietnam) at 2.0

benefit in terms of reversal of liver fibrosis and re-

percent and high-income Asia-Pacific nations

duction in long-term adverse hepatic outcomes.

MAY-JUNE 2015 D R U G P R O F I L E 18

A significant proportion of patients, however, do

lication. GS-461203 is highly specific to its viral

not respond. Furthermore, many patients experi-

target and has no affinity for human RNA or DNA

ence intolerable side effects from interferon. In

polymerases. [Pharmacogenom Personal Med

others, interferon cannot be commenced due to

2014;7:387-398; Product Monograph, SOVAL-

contraindications or an unwillingness to take the

DI (sofosbuvir). Gilead Sciences Inc.]

therapy.

Sofosbuvir is rapidly absorbed orally, with

Another limitation of available therapies arises

plasma levels peaking within 0.5-2 hours. Ab-

from the fact that HCV exists in at least six distinct

sorption is slowed by the presence of food,

genotypes. The protease inhibitors are effective

however overall exposure remains the same. It

in patients infected with HCV genotype 1 (the

is readily taken up by hepatocytes from the plas-

more commonly occurring genotype) and 2, but

ma, where a number of activation steps occur.

have no or limited efficacy in other genotypes.

The triphosphate metabolite has a long intracel-

This has stimulated interest in alternative thera-

lular half-life of 17.8 hours. Eventually dephos-

peutic strategies and interferon-free regimens.

phorylation produces inactive metabolites that

[Digestive Liver Dis 2014;46:S174-S178; Ther

are mainly cleared by the kidney.

Adv Chronic Dis 2015;6:414] The emerging class

of nucleotide polymerase inhibitors has been the

Clinical efficacy

subject of intense research in recent years, with

The phase II ELECTRON study of sofosbu-

15 candidate drugs investigated. To date, only

vir (with and without ribavirin) provided prom-

one of these sofosbuvir has been approved

ising proof of concept that the oral nucleoside

for clinical use. [Phamacogenom Personal Med

polymerase inhibitor could produce a sustained

2014;7:387-98]

virological response in HCV, without the need

for interferon. This prompted phase III investi-

Pharmacology and pharmacokinetics

gations. Five trials (FISSION, POSITRON, FU-

Sofosbuvir is a prodrug that undergoes in-

SION, NEUTRINO and VALENCE, n = 1724)

tracellular metabolism in the liver to form GS-

studied the effects of sofosbuvir in combination

461203 a triphosphate analogue of uridine

with ribavirin or pegylated interferon plus ribavi-

nucleotides, modified by the addition of methyl

rin, mostly in treatment-nave but also in previ-

and fluoro groups. During replication of HCV,

ously treated patients with chronic HCV. Many of

GS-461203 competes with naturally occurring

the subjects (16-34 percent) had cirrhosis. The

uridine and is incorporated into the growing RNA

PHOTON-1 study enrolled subjects that were

strand in a process mediated by NS5B protein

co-infected with HCV and HIV-1, while a further

an RNA-dependent RNA polymerase. The struc-

study was conducted in patients awaiting liver

tural modifications introduced into the strand

transplantation. The clinical trials program pro-

limit elongation and lead to premature termina-

vided sufficient data for product registration and

tion of RNA synthesis, thereby stopping viral rep-

clearly demonstrated that sofosbuvir represents

MAY-JUNE 2015 D R U G P R O F I L E 19

a major advance in the treatment of HCV. Sus-

(genotypes 1 and 4) or ribavirin alone (geno-

tained virological response rates were 89-90 per-

types 2 and 3). The recommended dose is one

cent among patients with genotypes 1, 4, 5 and

400 mg tablet daily, with or without food. Treat-

6 treated with pegylated interferon, ribavirin and

ment is given for 12 weeks in patients infected

sofosbuvir for 12 weeks.

with HCV genotypes 1, 2 and 4; treatment du-

Sofosbuvir targets the highly conserved active

ration is extended to 24 weeks in patients with

site of the HCV polymerase and this results in an-

genotype 3. Sofosbuvir is also indicated in pa-

tiviral activity across the spectrum of HCV geno-

tients with hepatocellular carcinoma awaiting

types albeit with some variations in potency.

liver transplantation to prevent post-transplant

The drug also has a high barrier to the develop-

re-infection. In this setting treatment is given in

ment of acquired resistance. Some intrinsic re-

combination with ribavirin for 48 weeks or until

sistance to sofosbuvir exists in the NS5B S282T

transplantation occurs, whichever occurs first.

mutation, however this mutant has reduced re-

No dose adjustment is needed in elderly patients

productive fitness compared to wild-type virus

or those with mild or moderate renal impairment.

and is also susceptible to ribavirin.

[Product Monograph, SOVALDI (sofosbuvir).

Gilead Sciences Inc.]

Safety and tolerability

Pooled analysis of phase III trials found that

Future directions

permanent treatment discontinuations due to

The management of chronic HCV infection is

adverse events occurred in 4 percent of patients

moving away from immune-modifying therapy

receiving placebo, 1 percent for subjects receiv-

with modest efficacy and a high side effect bur-

ing sofosbuvir plus ribavirin for 12 weeks, <1

den towards new regimens combining direct an-

percent for subjects receiving sofosbuvir plus

tiviral agents with high efficacy and good tolera-

ribavirin for 24 weeks, 11 percent for subjects

bility. Currently sofosbuvir-based, interferon-free

receiving peginterferon alfa plus ribavirin for 24

regimens are only recommended in genotypes

weeks and 2 percent for subjects receiving so-

2 and 3, but this approach is likely to soon be

fosbuvir plus peginterferon alfa plus ribavirin for

possible across all HCV genotypes. Sofosbuvir

12 weeks. No adverse drug reactions specific to

is emerging as the new backbone of therapeu-

sofosbuvir have been identified. [Product Mono-

tic regimens that combine direct antiviral agents

graph, SOVALDI (sofosbuvir). Gilead Sciences

from other classes. Several studies of sofosbuvir

Inc.]

in conjunction with second-generation protease

inhibitors (simeprevir, daclatasvir and ledipasvir)

Dose and administration

have yielded highly positive initial results and this

Sofosbuvir is indicated for the treatment of

line of investigation is ongoing. [Digestive Liver

chronic HCV infection as part of a combination

Dis 2014;46:S174-S178; Ther Adv Chronic Dis

regimen with pegylated interferon plus ribavirin

2015;6:414]

MAY-JUNE 2015 B U S I N E SS 20

New headquarters to help SigmaAldrich support AsiaPac clients

RADHA CHITALE

ife science and biotechnology firmSigmaAldrich opened a new regional business

headquarters at Singapores Biopolis Research

Park in April, consolidating existing laboratories
and offices to become a supply hub for pharmaceutical manufacturers in the Asia Pacific
region.
The new facility also houses the companys

Mr. Kevin Lai (center) with executives from SigmaAldrich at the launch of the Cell Culture Technical
Center at Biopolis Research Park. Photo courtesy of
Sigma-Aldrich.

Cell Culture Technical Center, the first such center in the region, which will focus on developing

global pharmaceutical companies have a

and optimizing cell culture media for clients.

presence in Singapore across manufacturing,

Mr. Jason Apter, vice president at Sigma-

headquarters and R&D operations is testimo-

Aldrich and the Asia Pacific managing director,

ny to the continued growth of our pharmaceu-

noted the ease of reaching out to regional clients

tical industry, said Mr. Kevin Lai, executive

in Tokyo, Shanghai, Bangalore, and elsewhere,

director of Biomedical Sciences and Con-

from Singapore, as well as the significant front

sumer Businesses of the Singapore Econom-

and back ecosystems here of talent that can com-

ic Development Board. We welcome Sigma-

municate across the region.

Aldrichs new investment and are confident

[This headquarters] is the only place from

that this will further strengthen our supporting

which we can technically support customers in

ecosystem for biopharmaceutical manufac-

Asia, Apter said.

turing and R&D.

The company also plans on completing a re-

The overall goals of consolidating and ex-

gional distribution center in Tuas by the end of the

panding operations are to improve efficiency

year.

and profits, reduce risk, and accelerate speed-

Sigma-Aldrich is one of several biomedical

to-market for products from the many biotech

sciences companies, including Amgen, Novar-

companies in the region, from those well es-

tis, and GlaxoSmithKline, that are capitalizing

tablished companies in Korea, for example, to

on Singapores strategic location and business

smaller start-ups in China. Apter said the rate of

infrastructure to grow their Asia operations.

growth in the biotech sector will be twice what it

Today, the fact that nine of the top 10

has been in the US.

MAY-JUNE 2015 B U S I N E SS 21

Novel radiation-free test to aid

diagnosis of gastroparesis
KAVITHA G. SHEKAR

he US Food and Drug Administration (FDA)

has approved gastric emptying breath test

(GEBT) to aid the diagnosis of gastroparesis.

GEBT measures carbon-13, a naturally existing non-radioactive form of carbon-12, in a patients breath. Gastric scintingraphy, the standard
diagnostic test for gastroparesis, uses radioactive
material and requires specialist training.
[GEBT] can be performed in any clinical setting since it does not require the health care professionals administering the test to undergo spe-

carbon-13 enriched meal containing scrambled

cial training or to take special precautions related

egg-mix and Spirulina platensis. GEBT and scin-

to radiation emitting compounds, as no radioac-

tigraphy results agreed 73-97 percent of the time.

tive materials are used said Dr. Alberto Gutierrez,

Gastroparesis interferes with normal diges-

director of the Office of In Vitro Diagnostics and

tion causing severe nausea and vomiting, dehy-

Radiological Health in the FDAs Center for De-

dration, and malnutrition. Diabetes is the most

vices and Radiological Health.

common cause of gastroparesis. Other causes

The approval is based on a study of 115 par-

include infections, internal surgery, neurological

ticipants who underwent both GEBT and gastric

disease like Parkinsons disease, and endocrine

scintigraphy. Performed over a 4-hour period fol-

disorders like hypothyroidism.

lowing an overnight fast, GEBT measured the ra-

GEBT is not advisable for patients with an al-

tio of carbon-13 to carbon-12 in breath samples

lergy to Spirulina, egg, milk, wheat, or certain

at multiple points, which is then compared to

lung diseases or conditions that cause small

the baseline measure. Participants consumed a

bowel malabsorption.

MAY-JUNE 2015 B U S I N E SS 22

First home-use EEG device for

autism launched in Singapore
ELVIRA MANZANO

novel neurofeedback device designed to

reduce overactive brain waves in children

with autism has been rolled out in Singapore.

MenteTM, touted as the first portable homeuse electroencephalogram (EEG) device for autism, uses neurofeedback to help mentally relax
patients with autism, allowing them to focus better and engage positively with the environment.

reduced delta wave peaks and increased and

Children with autism spectrum disorder

wave peaks in children (age 6-18) with ASD,

[ASD] process sensory information sights and

allowing them to be more relaxed over time.

sounds in particular differently from children

Parents reported that their children had fewer

without autism, said Dr. Adrian Attard Trev-

tantrums and were able to concentrate more. [J

isan, founder and managing director of AAT Re-

Neural Discord 2013;1:4]

search, which makes Mente. They have higher

These led to longer attention spans, en-

levels of delta waves in the brain even during

hanced relaxation and improved communi-

daytime and low levels of alpha [] and beta []

cation skills for most patients, said Trevisan.

waves. This causes many of the symptoms and

The device was originally developed to help a

distractions patients experience.

friends son who had Aspergers syndrome, a

The device comprises an EEG headband

and a software application that creates tailor-

form of autism that affects language and behavioral development in children.

made binaural beats to level the brainwaves ac-

I spent time observing him, watching him

cording to a patients mental state. All it takes is

carefully, trying to figure out how I could help.

40 minutes of use every morning and the effects

Through this neurofeedback technology, chil-

last the rest of the day until the child goes back

dren like him with autism can focus and better

to sleep, Trevisan said. With sleep, the delta

engage with the world.

waves naturally increase so the process must

Mente is FDA-registered and has been given

be repeated daily. Depending on the childs

the CE Medical mark of approval as a medical

symptoms, this treatment must be used for 4 to

device in April. It is easy to set up and doesnt

8 weeks to start seeing positive results.

require specialist supervision, making it ideal

In one study, the use of Mente significantly

for home use, said Trevisan.

MAY-JUNE 2015 C L I N I C A L P H A R M AC Y 23

Imatinib may be a novel treatment

option for colon cancer
RADHA CHITALE

matinib halves colon tumour growth and may

be a novel method for preventing or control-

ling colon cancer, according to Singaporean

and Swedish researchers.
In mice with human colon cancer, imatinib
was shown to prolong survival, said Dr. Parag
Kundu, senior research fellow at Nanyang Technological Universitys (NTU) Lee Kong Chian
School of Medicine, Singapore. The drug was

performed similarly to the mouse model.

also effective in increasing the survival of mice

Although there are side effects associated

with late-stage tumours and rectal bleeding.

with long-term imatinib use cardiotoxicity and

[Sci Transl Med 2015;7:281ra44]

oedema are the most serious these could be

Imatinib targeted and blocked cell receptors of EphB proteins, which control growth and
movement of intestinal stem cells and progenitor cells.

attenuated by administering treatment in short,

intermittent bursts, the researchers said.
Our work has important clinical implications, since imatinib is a potentially novel drug

Importantly, while imatinib blocked EphB re-

for the prevention and treatment of colorectal

ceptors, it did not affect EphB itself, which acts

cancer, said senior principal investigator Pro-

to prevent progression to invasive carcinoma.

fessor Sven Pettersson of the Lee Kong Chian

When administered in vitro to cancerous cells

taken from humans with colon cancer, imatinib

School of Medicine, Singapore and Karolinska

Institute in Solna, Sweden.

MAY-JUNE 2015 C L I N I C A L P H A R M AC Y 24

Paracetamol study highlights risks

of long-term use

new study shows paracetamol, the worlds

most commonly used and recommended

painkiller, is not as benign as once thought.

prescribing paracetamol for long-term use.

Based upon the data presented above, we
believe the true risk of paracetamol prescription

Until recently, paracetamol was perceived

to be higher than that currently perceived in the

as relatively safe, but new research shows pa-

clinical community. Given its high usage and

tients with chronic pain on long-term, highdose

availability as an over-the-counter analgesic,

paracetamol are increasing their risk of kidney,

a systematic review of paracetamols efficacy

intestinal and heart problems, and also death.

and tolerability in individual conditions is war-

In a systematic review of paracetamol safety

ranted, the researchers say.

studies, UK researchers selected eight obser-

However, the industry body for over-the-

vational studies to analyse. [Ann Rheum Dis; 2

counter medicines is pointing to the long his-

March early online publication]

tory of use and well-established safety profile of

Two studies showed an increase in mortality

paracetamol.

of up to 63 percent for longterm paracetamol

The study only looked at people on prescrip-

users, compared with those not prescribed

tions for paracetamol, but, in a press release,

it. Four showed a higher risk of kidney dam-

Self Medication Industry executive director Tim

age and another four reported cardiovascular

Roper says the maximum recommended dose

events increasing by between 19 to 68 per-

for people over 12 years is 4000mg in a 24-hour

cent.

period, and people should consult a medical

Gastrointestinal problems also increased in

one study. Generally, the higher the dose, the
higher the risk, researchers found.
The researchers acknowledged their results
may be affected by the study populations often

professional if they want more.

Arthritis New Zealand chief executive Sandra
Kirby says the study is a timely reminder that all
medications have side effects, but urged people not to be alarmed.

being on other drugs to treat multiple comor-

This latest study is another of the ongoing

bidities, and also that paracetamols benefits

challenges chronic pain sufferers face of bal-

may still outweigh its risks for many people.

ancing pain relief with potential adverse effects.

However, given that recent studies have

The internet is full of information about

called into question the efficacy of paracetamol

adverse effects from painkillers, including

for treating osteoarthritis joint pain and acute

paracetamol, but often pain relief will allow

low back pain, they wanted health profession-

people to participate in everyday activities, in-

als to think carefully before recommending or

cluding exercise, which in turn helps with ar-

MAY-JUNE 2015 C L I N I C A L P H A R M AC Y 25

Pharmacists can really add value by looking

thritis, Kirby says.

Pharmacists should reassure people that

at the patients whole picture, finding out what

as long as they take their paracetamol as pre-

other pain management they are using, includ-

scribed and have regular check-ups, the ben-

ing complementary medicine, and looking for

efits usually outweigh the risks.

drug interactions.

Pharmacists can also talk to people about

Pharmaceutical Society clinical advisor Bob

other ways of managing their pain, such as

Buckham says the standard advice following

through exercise, joint support, relaxation

studies such as this, is people shouldnt just

techniques, and hot and cold packs. There

stop taking their medication without discussing

is also good evidence for acupuncture, mas-

it with their doctor first. Unichem Hillpark Phar-

sage, capsaicin cream and transcutaneous

macy owner Kathy Maxwell says she has not

electrical nerve stimulation (TENS), which

had any customer queries following the release

uses electricity to stimulate the nerves, Kirby

of

says.

have to consider what the alternatives to

Directing people to the Arthritis New Zealand

helpline is another good option, she says.

the

study,

but

says

patients

would

paracetamol are and how their safety profiles

compare.

PTNZ

JPOG

News & CME

Stay up-to-date on the latest

medical trends and developments,
wherever you may be.
You can now enjoy MIMS Journal of Paediatrics, Obstetrics & Gynaecology (JPOG)
through MIMS.com and the MIMS tablet and mobile applications. Log on to
www.mims.com today for instant access to news and CME articles covering the
latest trends and developments in paediatrics, obstetrics and gynaecology.

Join over a million MIMS members who have incorporated MIMS into their daily workflow. Connect with MIMS today.

www.mims.com

MIMS mobile/tablet app

facebook.com/mimscom

MAY-JUNE 2015 P H A R M AC Y P R AC T I C E 26

Pharmacists can help to ease chronic

pain patients off opioids

harmacists have a vital role to play in iden-

opposed to whats recommended, James says.

tifying and referring patients with chronic

The more that pharmacists can ask sensible

pain, according to pain specialists.

About 17 percent of the population has
chronic pain, which lasts for longer than three

questions and give quality advice, the better, because there are a lot of people living with chronic pain, she says.

to six months, New Zealand Pain Society presi-

New Zealand Pain Society president and pain

dent-elect and chronic pain clinical psychologist

medicine specialist Brigitte Gertoberens agrees

Frances James says.

many patients self-medicate and take pain med-

Thats one person in five, and certainly not

all of them are making it to a specialist, James
says.

ications incorrectly.
There are heaps of patients, especially headache patients, who self-medicate and it would

In acute cases, pain is useful because it alerts

be helpful if pharmacists help them, because

the patient to an injury and encourages them to

you see them before we do, Gertoberens says.

look after the injured area, she says.

But chronic pain is like an alarm that sounds
and then cant be turned off, James explains.

Medication over-use headaches, or rebound

headaches, are caused by taking too much pain
medication. They are the third most common

Pain doesnt always mean that somethings

type of headache, after migraine and tension-

wrong, but were programmed to believe it is,

type headaches, according to the Healthcare

and thats what people are often very frightened

Handbook 2014 (pp8889).

of.
Pain clinics help patients with chronic pain
live with that pain and maximise quality of life.
In most cases, it is important to keep moving,
and the likes of physiotherapy or acupuncture
can help, James says.

Patients can become addicted to pain medications and can suffer from adverse effects, and
pharmacists need to educate them about this,
Gertoberens says.
Pharmacists should advise patients with ongoing pain to consult their GP, and ask for a re-

Patients who are coming into the pharmacy

ferral to a pain service, if necessary. It is impor-

to buy a lot of overthe-counter (OTC) pain medi-

tant to rule out anything sinister that could be

cation should be referred to a doctor, and should

causing the pain.

be checked to see if they are taking the recommended doses, she says.

Medications play a minor role

We commonly find people who are really sore

In a pain clinic, medications play a minor role

will take a handful of Panadol [paracetamol], as

in the management of chronic pain, Gertobe-

MAY-JUNE 2015 P H A R M AC Y P R AC T I C E 27

rens says.
They can be useful, but are never curative,
and patients often show adverse reactions.

he says.
Gulbransen encourages pharmacists to ring
the doctor with any queries, especially for opioid

Tricyclic antidepressants are one treatment

prescriptions. Pharmacists should also look out

option, and can be useful if the patient is also

for drug-seeker red flags, including frequent ap-

suffering a mental health condition, she says.

pearances, scripts in different names or scripts

Other options for long-term use include epi-

that have been changed.

lepsy medication gabapentin.

Opioids are not considered useful for non-

Pharmacies have a role to play

cancer chronic pain, Gertoberens says. Pa-

Pharmacists can play a big role in the man-

tients who have been taking opioids should be

agement of chronic pain, according to Welling-

weaned off them, but this needs to be done as

tons Miramar pharmacist Ann Privett.

part of a team, she says.

Customers who are frequently buying strong

OTC pain relievers, such as codeine-containing

The movement against opioids

An Auckland GP who specialises in addic-

medicines or diclofenac, are queried, Privett

says.

tion, Graham Gulbransen, agrees doctors and

Its very easy for us to see, on our LOTS com-

pain services are very much against the use of

puter system, their history of OTC purchases, all

opioids. People build up a tolerance and need

we have to do is put their name in, she says.

bigger and bigger doses. On the other hand,

That often opens the door for us to say we

people like me, and a lot of GPs, see people

notice that youre buying quite a lot of these, do

who arent getting adequate pain relief unless

you want to talk to us about it?

they do take adequate doses of opioids.

Pharmacies can help patients manage their

Controlled dispensing is one way to control

pain, such as by suggesting glucosamine and

opioid use, reducing the risk of overdose or di-

chondroitin if the person has arthritic pain, or re-

version, Gulbransen says.

ferring the patient to physiotherapy or acupunc-

Referring patients to a pain service is another

option, but the waiting lists can be as long as
nine months, he says.

ture, Privett says.

Its important to find out exactly what the pain
is, so you can have a chat with them about it.

Other medications like tricyclic antidepres-

If we notice that their usage rate is not ap-

sant amitriptyline and anticonvulsant gabapen-

propriate, we will not sell [an OTC product] to

tin should be considered, Gulbransen says.

them, and will refer them to a doctor.

They are less likely to be diverted to other

people, [patients are] less likely to build up a tol-

Long-term help needed

erance, and they are most likely to be safer, but

Privett also works with her local general prac-

some people will have intolerable side effects,

tice to assist patients suffering from chronic pain

MAY-JUNE 2015 P H A R M AC Y P R AC T I C E 28

who have been taking opioid pain medications

for years.
At the request of GPs, and in consultation
with them, she helps these patients manage
their medications, in a service similar to a medicines therapy assessment.
Privett initially meets with patients weekly to
discuss their medications, then monthly.

Privett also refers patients to pain clinics,

when available, and encourages patients to distract themselves from the pain, with a number
taking up crochet.
While the patients are registered with the
Long Term Conditions service, Privett admits
this is not enough funding to cover the cost of
the service.

Some are on horrendous doses, she says.

Its what the doctors want, and, ethically, you

Usually we look at ways of reducing the co-

cant turn these patients away. Plus it is really

deine and tramadol, and anti-inflammatories, in

rewarding, she says.

PTNZ

a very, very slow and structured regimen, and

increasing other medication, like amitriptyline
and gabapentin.

KEY POINTS:
About 17% of people suffer from chronic pain.

If a patient is being taken off opioids, it is im-

Pharmacies play a key role in identifying and refer-

portant they are not left in pain and have some

ring patients who use too many OTC pain reliev-

sort of other pain relief, Privett says.

ers.

Once the process starts, we usually find

weve got good acceptance because the patient
doesnt want to be on these drugs.

Pharmacists can help patients come off opioids

with intense one-on-one care.

www.mims.com

MIMS mobile/tablet app

facebook.com/mimscom

MAY-JUNE 2015 I N F O C U S 29

Irritable bowel syndrome patients

need guidance, support
With as many as 20 percent of people having irritable bowel syndrome, many customers
are looking for help to manage their symptoms.

rritable bowel syndrome (IBS) is a common

gastrointestinal disease.
Symptoms typically include abdominal bloat-

ing and pain, diarrhoea with occasional periods

of constipation, and mucus in the stools, according to the Healthcare Handbook 2014.
Symptoms can range from minor and occasional, to severe and disabling.
When it comes to health, IBS patients have
similar quality of life to those with diabetes and
end-stage renal patients (Pharmacy Today, September 2013).
There are not a lot of New Zealand data indi-

toms.
Irritable bowel syndrome does not do any
long-term damage even if untreated, Gearry
says.

cating how frequent IBS is, aside from a Dunedin

However, it is important for patients to get a

population-based study which estimated 20 per-

proper diagnosis to rule out anything else in-

cent of the population has the syndrome, Christ-

cluding cancer, inflammatory bowel disease like

church gastroenterologist Richard Gearry says.

Crohns and ulcerative colitis, or coeliac disease.

I usually say about one in six women and

Pains that are not specific require clinical

one in nine men have irritable bowel syndrome,

tests, and they may require faecal tests or blood

and most of my colleagues would agree, Gearry

tests to be sure, Gearry says.

says.

And then, if a diagnosis has been made, it

There are a number of theories as to why the

comes down to what symptoms annoy people

syndrome is more common in women, including

the most if its constipation, look at agents for

a possibility of it being related to endometriosis

that, if its diarrhoea there are agents for that.

or hormones, or more reporting by women, he

says.

Greenhithe pharmacist Samit Patel, who specialises in natural treatments to manage bowel

The causes of IBS are currently unknown and

conditions, agrees a proper diagnosis is essen-

are not defined anatomically or biochemically. Di-

tial. Youre looking for all the red flags, including

agnosis is based on chronic and relapsing symp-

how long they have had symptoms, if there is a

MAY-JUNE 2015 I N FO C U S 30

lot of mucus in the stools. Blood in the stools always needs to be checked out.
People who have been diagnosed with IBS
will know all about it, but some patients know

adds.
I always emphasis a bit more care, rather
than just giving a product thats pharmacys
point of difference.

nothing about the condition, Patel says.

People frequently coming into the pharmacy
for products for diarrhoea or constipation should
be encouraged to see their doctor.
For some patients, diagnosis is a process, as
it can take years to eliminate everything.

Diet is key to managing IBS

Managing diet is important in managing IBS,
as different foods can often trigger symptoms,
Gearry says.
There are a million different diets recommend-

These patients still need support, and can be

ed for IBS but the only one clinically proven to

treated as if they have some sort of inflammatory

help is the low-Fodmap (fermentable oligosac-

bowel condition, Patel says.

charides, disaccharides, monosaccharides and

polyols) diet.

Manage flare-ups first

Studies replicated in Australia, New Zealand

Managing primary symptoms is one of the

and the UK show 75 percent of patients will get a

first steps in managing IBS, particularly if they are

significant improvement in abdominal pain, diar-

suffering from bad diarrhoea, Patel says.

rhoea and bloating with a low-Fodmap diet, he

Over-the-counter medicines can help with

symptoms.

says.
Gearry outlines Fodmaps in a Pharmacy To-

Peppermint in oil or tea form can help get

day How to Manage feature (September 2013).

rid of bloating, and aloe vera can help soothe the

Oligosaccharides are shortchain carbohy-

stomach. A good probiotic is also worth recom-

drates found in large amounts in wheat, barley,

mending, he says.

rye and some vegetables like onions and cab-

An Auckland dietitian recommended by gastroenterologists, Nikki Talacek, agrees probiotics

are good for people with unhappy guts.
But it is important they do not contain

bage.
Disaccharides include lactose, with high-lactose foods including cows milk yoghurt and icecream.

fructo-oligosaccharides (FOS) as they are

Monosaccharides include fruits with high fruc-

usually not tolerated by people with IBS,

tose-to-glucose ratio, such as pears, apples and

Talacek says.

watermelon.

Other products, including turmeric, Boswellia

Polyols are sugar alcohols found in stone fruit,

and essential amino acid glutamine, can also

some vegetables and some sugar-free products.

help with inflammation, Patel says. It is important

As the low-Fodmap diet is so exclusionary,

to encourage the patient to come back and give

patients need to consult a Fodmap-trained dieti-

feedback about whether the products work, he

tian, to make sure they do not become deficient

MAY-JUNE 2015 I N FO C U S 31

in nutrients, Talacek says.

erywhere else in the body. Everything around us

Information is power

has an effect on the gut.

Patel agrees a proper low-Fodmap diet

Reducing caffeine and alcohol is also impor-

which involves reducing all Fodmap foods then

tant, as is getting adequate sleep, and drinking

slowly reintroducing them is very involved and

water.

requires someone to offer the patient guidance.

He offers one-hour clinical sessions, which his
patients pay for, or a dietitian is another option.
But pharmacies can always better inform their
patients, including talking about the low-Fodmap
diet, Patel says.
There are information sheets available to hand
out to patients and even a Fodmap app, he says.

Antidepressants an option
Antidepressants are another treatment for IBS,
with both tricyclic antidepressants and selective
serotonin reuptake inhibitors (SSRIs) shown to
be effective, Gearry says.
Antispasmodics, such as meberverine, have
also been shown to be effective for the management of abdominal pain due to spasm.

As people are told fruit and vegetables are

However, not all patients want to be on these

healthy to eat, they may not realise they could be

medications, and lifestyle changes should be

causing them problems, he adds.

tried first, he says.

IBS is a lifestyle disorder so, if you can man-

Start simple in pharmacy

age it with lifestyle, thats a much better approach

Rather than telling patients what they should

than putting someone on a drug long term. While

be eliminating, Patel prefers to suggest things

there are data that they work, many patients

that they can eat.

wouldnt want to go on an antidepressant.

Rice with fish or chicken is a simple dish that

The gut is hypersensitive, so any stimulus

is easily digestible. Vegetables like carrots are

will cause symptoms at a much lower threshold

good, and cooked foods are easier to digest

than people without IBS. You can reduce sensi-

than raw foods, he says.

tivity with drugs or you can reduce the triggers

Its about keeping the food a little bit bland

[through diet].

PTNZ

and allowing the bowel to heal up, he says.

Another option is a soup or bone broth, with
vegetables added then strained out, giving good
nutrition, but not too much fibre.

KEY POINTS:
Patients

with

assessment

IBS
to

symptoms

rule

out

need

anything

GP
more

sinister.

Stress also needs addressing

Stress is another trigger that also needs to be
reduced, Gearry says.
Ms Talacek agrees, saying food alone isnt the
answer. The gut has got more nerves than ev-

OTC products can help manage symptoms as a

first step.
A low-irritant diet and stress reduction are key for
longterm management of IBS.

PUBLISHER

Ben Yeo
MANAFING EDITOR

Elvira Manzano
DEPUTY MANAFING EDITOR

Radha Chitale
CONTRIBUTING EDITORS

Saras Ramiya, Pank Jit Sin, Dr Joslyn Ngu

(Malaysia)
BUSINESS MANAGER

Carrie Ong, Josephine Cheong,

Melanie Nyam
DESIGNERS

Razli Rahman, Anson Suen,

Joseph Nacpil, Agnes Chieng,
Cindy Ang, Ryan R.A. Baranda,
PRODUCTION

Jasmine Chay
C I R C U L AT I O N E X E C U T I V E

Christine Chok

EDITORIAL ADVISORY BOARD

SINGAPORE
Associate Professor Chui Wai Keung
Head of Department of Pharmacy,
Faculty of Science
National University of Singapore (NUS)

Assistant Professor Lita Chew

Chief Pharmacist,
Ministry of Health,
Singapore Registrar,
Singapore Pharmacy Council
Head, Pharmacy Department,
National Cancer Center Singapore
Assistant Professor,
Department of Pharmacy, NUS

Associate Professor Alexandre Chan

Department of Pharmacy, NUS
Associate Consultant Clinical Pharmacist,
Department of Pharmacy
National Cancer Center Singapore

ACCOUNTING MANAGER

Minty Kwan
A D V E RT I S I N G C O O R D I N AT O R

Angeline Chua
PUBLISHED BY

MIMS Pte Ltd

6 Shenton Way, #15-08
OUE Downtown 2,
Singapore 068809
Tel: (65) 6290 7400
Fax: (65) 6290 7401
Email: enquiry.mimspharmacy@mims.com

Dr. Joyce Yu-Chia Lee

Assistant Professor of Clinical Pharmacy
Department of Pharmacy, NUS
Principal Clinical Pharmacist,
National Healthcare Group Polyclinics

MIMS Pharmacy is published 6 times a year by MIMS Pte Ltd. MIMS Pharmacy is on controlled circulation
publication to pharmacists in Singapore. It is also available on subscription to members of allied professions.
The price per annum is US$48 (surface mail) and US$60 (overseas airmail); back issues at US$5 per copy.
Editorial matter published herein has been prepared by professional editorial staff. Articles ending with PTNZ
have been adapted from Pharmacy Today New Zealand. Views expressed are not necessarily those of MIMS
Pte Ltd. Although great effort has been made in compiling and checking the information given in this publication
to ensure that it is accurate, the authors, the publisher and their agents shall not be responsible or in any
way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this
publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom.
The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either
generally or in any particular field or fields. The information contained within should not be relied upon solely for
final treatment decisions.
2015 MIMS Pte Ltd. All rights reserved. No part of this publication may be reproduced in any language, stored
in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical,
photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint
must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence
on editorial content or presentation. MIMS Pte Ltd does not guarantee, directly or indirectly, the quality or efficacy
of any product or service described in the advertisements or other material which is commercial in nature.
Printed by KHL Printing Co Pte Ltd, 57 Loyang Drive, Singapore 508968.

ISSN 2382-6487