Post on 06-Nov-2015
description
MAY/JUNE 2015NEWS & INSIGHTS
87 percent of ICU patients at SGH experience drug-drug interactions
CLINICAL PHARMACY
Imatinib may be a novel treatment option for colon cancer
NEWS
Attenuated sunitinib regimen better for Asians with late-stage kidney cancer
DRUG PROFILE
Sofosbuvir for hepatitis C virus infection
BUSINESS
New headquarters to help Sigma-Aldrich support AsiaPac clients
87 percent of ICU patients at SGH experience drug-drug interactionsRADHA CHITALE
Eighty-seven percent of patients in the inten-sive care unit (ICU) of Singapore General Hospital (SGH) experienced drug-drug interac-
tions (DDI); about a third were major or contra-
indicated drug interactions with significant ad-
verse effects such as major bleeding.
In our study, with every increase in the num-
ber of drug interactions, the risk of adverse drug
reactions [ADR] for our patients increased by
1.2 percent, said Ms. Jasmine Ong, a pharma-
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.
The prospective observational cohort study
included 91 adults admitted to the SGH ICU
(mean age 62 years, 59 percent male) in May
2014 who were followed up for their entire ICU
stay or until the end of the 1-month study pe-
riod. The median length of ICU stay was 6 days
and the median length of hospital stay was 21
days. Twenty-five percent of the cohort died
during the study.
The researchers reported a total of 794 DDIs.
Eighty-seven percent of patients had at least one
DDI, for a mean 8.6 DDIs per patient or 147 DDIs
per 100 patient days. The majority of these were
a result of pharmacodynamic drug interactions,
as opposed to pharmacokinetic or other types of
interactions. One-third were major or contraindi-
cated DDIs.
Polypharmacy is common in ICUs, Ong noted,
but the clinical consequences are poorly under-
stood, and they can vary between institutions de-
pending on prescribing practices.
During the follow-up period, there were 14
cases of ADR due to DDIs, the most common of
which were major bleeding. Bleeding was likely
due to concurrent use of antiplatelet combina-
tions of aspirin, clopidogrel, ticagrelor, enoxapa-
rin, warfarin, or amiodarone.
Strategies need to be developed to reduce
this risk of bleeding, Ong said. For example...
determine the baseline bleeding risk of ICU pa-
tients and if it is high, consider using alternative
medications or totally avoiding the drug interac-
tion.
Nephrotoxicity, peripheral necrosis, hepato-
toxicity, QTc prolongation and hypotension also
occurred.
ADRs warranted drug discontinuation in 10
MAY-JUNE 2015 NEWS 2
patients along with some additional measures
such as dialysis for nephrotoxicity.
Patients with more DDIs had a higher risk of
ADRs. Patients with ADRs had an average of 10
DDIs per patient compared with 6.5 DDIs in pa-
tients without ADRs.
Patients with ADRs also stayed longer in the
ICU, an average of 15 days compared with 5
days for patients without ADRs.
Other factors associated with longer hospital
stays ICU mortality, 28-day mortality were
not associated with ADR.
The longer ICU stay and additional moni-
toring and management required by patients
who develop ADR also led to a sharp increase
in costs, Ong said. If they experience an ADR,
patients can pay an additional S$9,000 on top
of the average cost of S$910/day which ex-
cludes consultation, laboratory test, and proce-
dure fees at SGH.
Ong said the reported incidence of DDIs and
corresponding high rate of ADRs in the SGH
ICU population was higher than those reported
in other studies, likely because their study in-
cluded patient data from two databases as well
as a literature search.
The study was limited by the follow-up period,
which may not have captured patients who expe-
rienced an ADR after discharge, and by the tool
for evaluating how likely an adverse reaction is the
result of a drug, which is meant to address reac-
tions to single drugs only.
This highlights the role of the pharmacist in
the active surveillance for DDI and the streamlin-
ing of medication regimens and monitoring for
potential ADRs, Ong said.
MAY-JUNE 2015 NEWS 3
MIMS rolls out new identity, purpose
Leading medical and drug information provider MIMS has rolled out a major re-brand initiative to better engage healthcare
communities and provide healthcare profes-
sionals with unified multichannel information
they can put into practice.
All MIMS publications Medical Tribune,
Oncology Tribune, Pharmacy Today, and JPOG
were renamed MIMS Doctor, MIMS Oncol-
ogy, MIMS Pharmacy and MIMS JPOG, re-
spectively. The publication titles now carry the
new red logo to mirror the companys renewed
commitment to connect and engage people.
Mr Ben Yeo, managing director of MIMS
Asia Pacific, recognized the importance of
communicating the companys new identity
and purpose across a global platform.
We see MIMS as the link that brings to-
gether healthcare communities, helping
them to obtain and exchange knowledge
to improve patient outcomes through better
care, he said.
To further support clinicians treatment
decisions, MIMS introduced 12 disease
specialty channels (Multispecialty, Phar-
macy, Oncology, Cardiology, Respirology,
Endocrinology, Hepatology, Gastroenterol-
ogy, Neurology, Psychiatry and Obstetrics &
Gynaecology and Paediatrics) on its website
www.mims.com and MIMS mobile app.
Were going beyond just providing infor-
mation, said Ms Diana Edwards, managing
director, MIMS Hong Kong and Singapore.
To build and sustain thriving communities,
we need to engage and connect people. We
hope our news and insights, eLearning pro-
grams, congress coverage and other servic-
es will facilitate knowledge-sharing and build
such communities.
MIMS, a subsidiary of AXIO Data Group,
with presence across 13 countries, has been
the source of clinical news and drug infor-
mation for health care professionals in Asia.
With MIMS integrated multichannel content,
information becomes even more accessible
on print, online and mobile, said Ms Sher-
lynn Tan, deputy director, MIMS Marketing.
This allows MIMS to grow its registered user
base to over 2 million and to generate an av-
erage of 30,000 new users each month.
MAY-JUNE 2015 NEWS 4
MAY-JUNE 2015 FORUM 5
NCDs and the need for policy solutions, effective interventionsExcerpted from a speech by Dr Margaret Chan, WHO director general, during a
dialogue on non-communicable diseases held recently in Geneva, Switzerland.
Noncommunicable diseases (NCDs) have overtaken infectious diseases as the lead-ing cause of mortality worldwide. WHO esti-
mates 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 es-
timates that NCDs are responsible for 14 million
premature deaths in the developing world each
year.
In some developing countries in Asia, the
number of deaths from cardiovascular disease
before the age of 55 is twice that in wealthy
countries. The reference to type 2 diabetes as
adult onset diabetes is no longer apt as so
many children are now being diagnosed with
this disease.
The responsibility for the rise in NCDs does
not fall on individuals who choose to eat,
smoke, and drink too much or opt for a sed-
entary lifestyle. The responsibility falls on the
environments in which these choices are made.
Can children be blamed for an addiction to
nicotine when single cigarettes are sold at the
gates of their schoolhouse? Can parents be
blamed for their overweight children when cit-
ies have no green spaces or the crime rate is
so high that children are not safe playing out-
doors? For the millions of people living in so-
called urban food deserts, healthy eating is
simply not an option.
This is the first big challenge. The evidence,
statistics, and arguments you put forward for
international cooperation must stress the need
for policy solutions that shape social environ-
ments. These solutions must be supported at
the highest level of government, and they need
to be put in place through a whole-of-govern-
ment approach.
A second big challenge is competition. With
17 goals and 169 targets currently proposed
for the post-2015 development agenda, this is
competition for a sliver or some crumbs from
the pie, not a piece.
You are being asked to sharpen the evidence
showing the two-way links between NCDs and
poverty. You are being asked to make a stron-
ger case for viewing the prevention and control
MAY-JUNE 2015 FORUM 6
of NCDs as an explicit poverty-reduction strat-
egy.
You are being asked to provide an inventory
of international agencies that have integrated
NCDs into their development policies and ex-
tract the lessons learned. We want to hear your
proposals about how official development as-
sistance can be used to strengthen prevention
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-
tors who strongly oppose any regulatory con-
trol or restrictions on their marketing of health-
harming products.
This is a formidable obstacle to prevention.
Economic power readily translates into politi-
cal power. We rely on civil society for support
in many areas, but most especially in this one.
The public health community has some
tools in hand to respond to these challenges.
The 2011 UN Political Declaration on NCDs
sets out some compelling arguments. It posi-
tions these diseases as one of the major chal-
lenges for development in the 21st century. It
points out their threat to economies and their
contribution to inequalities. It gives the primary
role and responsibility of responding to these
challenges to governments. And it underscores
how strongly prevention and control depend on
the engagement of multiple non-health sectors.
To guide work, we have an action plan
through 2020, a monitoring framework with
nine global targets, and a set of effective and
affordable interventions, known as best buys,
that can make a difference in any resource set-
ting.
As the root causes of NCDs lie beyond the
direct purview and responsibility of the health
sector, combatting these diseases is a com-
plex task involving multiple sectors. Here, too,
we have support from the Global Coordination
Mechanism and a UN Interagency Task Force.
There are two points made in the discus-
sion paper prepared for this meeting. First, the
UN General Assemblys 2014 progress review
found no lack of high-level government commit-
ment to NCDs. But it witnessed, in far too many
countries, a lack of capacity to act, largely be-
cause of insufficient national expertise in low-
and middle-income countries. International co-
operation can provide this expertise. Second,
efforts to prevent and control NCDs depend on
a well-functioning health system, ideally one
that aims to reach universal health coverage.
Any look at the interactions between NCDs
and poverty must also look at ways to increase
access to care and reduce the catastrophic
medical bills that push so many millions of fam-
ilies below the poverty line each year.
Attenuated sunitinib regimen better for Asians with late-stage kidney cancerRADHA CHITALE
An attenuated regimen of the first-line meta-static renal cell carcinoma (mRCC) treat-ment sunitinib had similar efficacy to the con-
ventional 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
6-week treatment cycle resulted in fewer se-
vere toxicities (59 percent attenuated vs 85
percent conventional, p=0.0088), dose delays
(24 percent attenuated vs 58 percent conven-
tional, p=0.0004), and dose reductions (35
percent attenuated vs 70 percent conven-
tional, p=0.0005). [Clin Genitourin Cancer
2014;pii:S1558-7673(14)00255-9. doi:10.1016/j.
clgc.2014.11.004]
Just 3 years into the 7-year study, which be-
gan in 2007, oncologists around Singapore ad-
opted the attenuated regimen for their mRCC
patients and it has now become the standard
of care, said lead researcher Dr. Tan Min Han,
a member of the genitourinary oncology team
and visiting consultant in the Division of Medical
Oncology at NCCS.
Many of the patients were experiencing se-
vere side effects of grade 3 or higher with the
conventional dosing, Tan said. Our immediate
response was to refine the treatment protocol to
improve patients quality of life.
The attenuated regimen also lowers the cost
of treatment with sunitinib by about S$1,350 per
month from the average cost of conventional
treatment, which is about S$5,400 per month,
Tan said.
Sunitinib is a targeted therapy for use in
mRCC and the 50 mg/day 6-week cycle regi-
men is the US Food and Drug Administration-
(FDA) approved dosing, determined safe and
efficacious, with acceptable toxicity, through a
number of studies in Western populations.
However, studies in Asian populations
showed that many had to stop treatment or
lower their dose due to grade 3-4 toxicities in-
cluding neutropaenia, thrombocytopaenia, and
MAY-JUNE 2015 NEWS 7
hand-foot syndrome.
One alternative was to lower the dose to 37.5
mg/day for continuous once-daily dosing (CDD)
but a retrospective analysis in Asian vs non-Asian
patients showed Asian patients continued to have
a higher frequency of grade 3-4 toxicities, al-
though the antitumour effect remained. [Ann On-
col. 2010;21(Suppl. 8):913P]
Other than the CDD regimen, there is lim-
ited data on alternative sunitinib regimens, the
researchers said.
In the current study, 127 mRCC patients at
the NCCS were treated with the attenuated
regimen and compared to mRCC patients
around Singapore who were treated with the
conventional sunitinib regimen.
Overall survival (OS) from treatment initiation
(18.3 vs 16.5 months; p=0.54), total OS (27.4
vs 21.8 months, p=0.45), and progression-free
survival (6.7 vs 7.9 months, p=0.64), were simi-
lar between the conventionally and attenuated
dosed groups, respectively. There was a lower
rate of adverse outcomes in the attenuated
group during treatment real world results that
the researchers said is evidence for such a regi-
men in the absence of a randomized trial.
Light-based assay could swiftly identify treatment for XDR bacteriaRADHA CHITALE
A light-based assay could help identify the best antibiotic combinations for combating extremely drug resistant (XDR) bacteria.
Combination therapy is highly strain-spe-
cific, which means that one combination may
be effective against one strain but not another,
said Ms. Jocelyn Teo, a pharmacist at Singa-
pore General Hospital, during a presentation
at the SGH 21st Annual Scientific Meeting, held
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
cases occurring at SGH. Such infections can re-
quire strong antibiotic treatments used in com-
bination, which can be toxic to patients.
While there are a number of treatment op-
tions available, swiftly determining optimal
treatment can be challenging.
Traditional efficacy testing using the viable
plate count method is sensitive and specific but
requires a lot of manpower to plate cells and
compare the effects of various drug combina-
tions, Teo said, and can take over 2 days.
Teo and colleagues capitalized on the pres-
ence of the intracellular energy molecule ade-
nosine triphosphate (ATP), present in all living
cells, as a surrogate marker for viable bacteria
count.
MAY-JUNE 2015 NEWS 8
Applying the light-emitting compound lucif-
erin to ATP allowed Teo to measure the amount
of ATP as a function of bioluminescence.
Teo and her team used 100 randomly select-
ed XDR isolates with a variety of bacteria cov-
ering many different resistance mechanisms.
Each isolate was tested against single and
two-drug combinations of the most appropriate
set of antibiotics. For example, Klebsiella pneu-
moniae was tested against tigecycline, rifampi-
cin, polymyxin B, levofloxacin, and meropenem.
Results were available within 24 hours.
The researchers then analysed for sensitivity
and specificity, determining the cut-off point be-
low which the drug combination was no longer
inhibiting bacterial growth. Prospective valida-
tion using additional strains showed the meth-
od to be robust.
We identified individual cut offs for each
species combination, Teo said.
The bioluminescence assay proved sensitive
and specific at determining optimal drug com-
binations effective against XDR bacterial infec-
tions, reduced the testing time to 24 hours, and
was easy to perform.
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 changeRADHA CHITALE
A solution-focused approach is more likely to help clinicians engage with their patients and motivate them to change their behaviours
than a problem-solving approach, said Ms.
Cheryl Ng, a senior Speech-Language therapist
in the Department of Speech Therapy at Sin-
gapore General Hospital (SGH).Rather than
focusing on whats wrong, [a solution-focused
approach] focuses on what works, said Ng,
during a presentation at the SGH 21st Annual
Scientific Meeting, held recently in Singapore.
Clinicians often adopt a problem-solving ap-
proach to patients, Ng said, which is appropri-
ate in situations such as diagnosis, prescribing
treatment and information counselling. Howev-
er, this approach can be flawed.
We work in hospitals, we are very accus-
tomed to the medical model, and there is a ten-
dency to perceive our clients in terms of their
deficits and as problems to be solved, Ng said.
For example, an overweight patient who
wants to lose weight might be told what they
should and should not do as far as diet and ex-
ercise.
But this reinforces the clinicians as experts,
clients are disempowered, and they dont have
ownership of the solution. We shouldnt be sur-
prised when the client comes back not having
MAY-JUNE 2015 NEWS 9
lost any weight.
In addition, the pressure to constantly solve
patient problems can increase the rate of clini-
cian burnout.
Solution-focused brief therapy (SFBT) was
developed in the 1970s as a therapeutic ap-
proach that favours how change happens over
how problems develop, focusing on patient
knowledge and resources. It is used most often
in the context of palliative care, cancer care, de-
pression, fatigue, and pain management.
The overarching principles guiding the pa-
tient-clinician interaction are that they should
be patient-led, future-oriented, and strength-
focused. Conversations should re-frame nega-
tive feelings and transition to asking for stories
where patients created solutions. Positive feed-
back is also critical.
For example, asking a patient who forgets
to take medicine to recall times when they did
remember to take it and identify helpful behav-
iours such as putting it in a convenient place
like the kitchen counter is more helpful than
asking why they forget to take the medicine, tell-
ing them the risks of not taking medicine, or ad-
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
much higher chance of fitting naturally in their
lives and a much higher chance to be effective
and complied with, Ng said.
A review of 43 controlled-outcome SFBT
studies showed that 74 percent reported sig-
nificant positive benefit from the approach and
23 percent reported positive trends. Other re-
views generally support SFBT for non-severe
presenting problems, although they have not-
ed problems with SFBT study methodology
such as concurrent therapies and a wide vari-
ety of subjects included. [Research on Social
Work Practice 2013,23:266-283; J Child Psy-
chol Psychiatry 2013,54:707-723; Fam Process
2000,39:477-498]
Clinicians themselves may balk at engag-
ing with patients this way because they lack the
confidence or skills for such interactions.
However, they should remember that the
knowledge and experience of patients is a valu-
able resource, Ng said
MAY-JUNE 2015 NEWS 10
Tabalumab no better than placebo for RAELVIRA MANZANO
An investigational anti-B-cell activating fac-tor (BAFF) monoclonal antibody is no bet-ter than placebo in achieving clinical response
in patients with rheumatoid arthritis (RA) who
had not responded to methotrexate (MTX), a
phase III study has shown.
There was no difference in ACR20 (American
College of Cardiology 20 percent) response
score at week 24 the primary endpoint of
the study or change in mTSS (modified To-
tal Sharp Score) from baseline at week 52 be-
tween patients treated with tabalumab and
placebo. Nearly 30 percent of patients treated
with tabalumab 120 mg every 4 weeks and 32.8
percent of those assigned to tabalumab 90 mg
every 2 weeks achieved ACR20 compared with
25.1 percent for placebo. There were also no
significant differences between the tabalumab
and placebo groups in the percentage of pa-
tients achieving ACR50 and ACR70 responses
at the end of treatment. [Ann Rheum Dis 2015;
doi:10.1136/annrheumdis-2014-207090]
Despite changes in CD20+ B cells, RF
rheumatoid factor, and immunoglobulins follow-
ing tabalumab treatment, BAFF inhibition with
tabalumab was not clinically, functionally, or
structurally efficacious in patients with moder-
ate-to-severe RA taking MTX, said lead inves-
tigator Professor Josef Smolen of the Medical
University of Vienna in Vienna, Austria.
The study included 1,041 patients with mod-
erate-to-severe RA (6 months duration) who
had inadequate responses to MTX therapy, ran-
domized to tabalumab 120 mg every 4 weeks
or 90 mg every 2 weeks or placebo. Median
CD20+ B-cell counts increased at week 1 in the
tabalumab groups, but decreased from week
4 to 52. The differences in absolute and rela-
tive CD20+ B-cell-level changes from baseline
to week 52 were significant in both tabalum-
ab groups compared with the placebo group
(p
First WHO guidelines on hep B take public health approachSARAS RAMIYA
The 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 of-
ficial launch of the guidelines.
The evidence-based guidelines, which target
national programme managers, are intended for
low- and middle-income countries (LMICs) that
have poor access to liver biopsy and HBV DNA
testing. [2015 WHO Guidelines for the preven-
tion, care and treatment of persons with chronic
hepatitis B infection. Available at: www.who.int/
hiv/pub/hepatitis/hepatitis-b-guidelines/en/ Ac-
cessed on 16 March]
The guidelines aim to strike a balance be-
tween implementing the best-proven standard
of care and what is feasible on a large scale in
resource-limited settings, said Dr. Philippa East-
erbrook, department of HIV/AIDS, WHO.
Priority for treatment is given to those most
in need, and treatment is provided in an envi-
ronment free of stigma and discrimination, she
added.
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
the most advanced stage of liver disease;
the use of two safe and highly effective medi-
cines, tenofovir (TDF) or entecavir (ETV), for
the treatment of chronic hepatitis B; and
regular monitoring using simple tests for ear-
ly detection of liver cancer, to assess wheth-
er treatment is working, and if treatment can
be stopped.
Source: WHO. Available at: www.who.int/
mediacentre/news/releases/2015/hepatitis-b-
guideline/en/
The WHO guidelines offer opportunities to
Asia through massive price reductions for TDF
and ETV. These reductions have been achieved
through negotiation among governments, the
pharmaceutical industry and NGOs, said Pro-
fessor Ji-Dong Jia, Liver Research Center, Bei-
jing Friendship Hospital, China. He noted that
there are both voluntary and compulsory licens-
es, and tiered pricing eg, US$0.50 per day for
TDF in Thailand.
Furthermore, there is a need for Asian coun-
tries to establish long-term follow up systems
MAY-JUNE 2015 NEWS 12
to monitor and evaluate patients in relation to
efficacy and safety of treatment, treatment com-
pliance and disease progression, he added.
Documenting disease burden of hepatitis B
is a challenge in sub-Saharan Africa, said Pro-
fessor Olufunmilayo Lesi, Gastroenterology and
Hepatology Unit, department of medicine, Col-
lege of Medicine, University of Lagos, Nigeria.
Although hepatitis B screening is done rou-
tinely in blood transfusion services, antenatal
care (in some hospitals) and health screening,
there are no clear guidelines for population
screening. Assessment of liver disease is most-
ly done in specialist and referral and private
hospital settings. Most chronically infected per-
sons are unaware and undiagnosed, she said.
So, these guidelines provide an opportunity
for a paradigm shift in hepatitis management
[It] certainly simplifies treatment and resources
to prioritize those in greatest need of treatment,
which will reduce the health cost disparity and
contribute to the regional control of hepatitis B
infection, said Lesi.
These guidelines are an important step to-
wards making sure that governments have
treatment programs for hepatitis B, and get re-
imbursement for the best drugs, said Charles
Gore, president, World Hepatitis Alliance, Lon-
don, UK.
At the same time, we need help from the
governments to outlaw stigma. Too many coun-
tries have allowed testing and then exclusion of
people with hepatitis B from education or em-
ployment. And that again is not acceptable. We
have to make sure the guidelines are put into
practice by all countries, he said.
Fish oil consumption may induce chemoresistanceJENNY NG
Consuming fish oil has been shown to in-duce chemo-resistance in mice, leading experts to advise avoiding fish and fish oil sup-
plements 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-
ing the fatty acid fish oil component 16:4(n-3) to
cisplatin chemotherapy substantially reduced
the drugs effect on tumour suppression.
MAY-JUNE 2015 NEWS 13
A 95.5 mm3 difference in tumour volume was
seen in mice treated with 16:4(n-3) plus cispla-
tin vs cisplatin alone (p=0.04), while cisplatin
alone effectively reduced tumour volume by
142.4 mm3. [JAMA 2015, doi:10.1001/jamaon-
col.2015.0388]
Similar chemoresistant effects of 16:4(n-
3) were seen with irinotecan and oxaliplatin
(p
FDA to assist pharma in developing abuse-deterrent opioidsCHRISTINA LAU
The US FDA is to assist the pharmaceuti-cal 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-
ject the medications.
The document, titled Abuse-Deterrent Opi-
oids Evaluation and Labelling Guidance for
Industry, is part of the FDAs efforts to curb
the escalating misuse or abuse of prescrip-
tion opioids in the US, which has become a
public health concern. [http://www.fda.gov/
downloads/Drugs/GuidanceComplianceReg-
ulatoryInformation/Guidances/UCM334743.
pdf; Addiction 2014;109:177-181; Addiction
2014;109:185-186]
The science of abuse-deterrent medication is
still relatively new and rapidly evolving. The FDA
is eager to engage with manufacturers to sup-
port advancements in this area and make these
medications available as quickly as possible,
said FDA Commissioner, Dr. Margaret Hamburg.
In the Asia-Pacific region, Australia takes the
lead in the opioid epidemic and the develop-
ment of measures against abuse.
The prescription of oxycodone and tramad-
ol in Australia saw dramatic increases between
1992 and 2007, said William Chui, President
of the Society of Hospital Pharmacists of Hong
Kong. In Victoria, a 21-fold increase was seen
in the detection of oxycodone in deaths reported
to the Coroner between 2000 and 2009. Almost
54 percent of the cases of death were the result
of drug toxicity. [Inj Prev 2011;17:254-259]
Diversion of prescription opioids to drug
abusers or dealers is very common in Austra-
lia. To curb the opioid epidemic, a formulation
of hydromorphone is enteric-coated with a hard
substance to prevent abuse through injection,
he told MIMS. Furthermore, community phar-
macists actively provide counselling and moni-
toring for patients on opioid therapy through a
government-run programme.
In the rest of Asia Pacific, little data is pub-
lished on the prevalence of opioid diversion,
he continued. In Hong Kong, opioid diversion
is uncommon because these analgesics are
generally underused except in oncology set-
tings. Also, our choice of opioid analgesics is
limited, and no abuse-deterrent opioids are cur-
rently available on the Hong Kong market.
Although the development of abuse-de-
MAY-JUNE 2015 NEWS 15
terrent opioids can help reduce diversion and
abuse, Chui said pharmacists also play impor-
tant roles in ensuring appropriate use of these
medications. Their roles include opioid pre-
scription monitoring, identification and referral
of patients at risk of opioid abuse, and collab-
orative care with physicians in cases of misuse,
abuse or diversion, he suggested.
In Hong Kong, opioid registries should be
implemented and made mandatory for all pre-
scribers, including those in the private sector,
he added.
Tenofovir safe, effective in pregnant women with hep B refractory to lamivudine or telbivudineLIANNE COWIE
Tenofovir 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
evaluated from 17 pregnant women (median age
30.6 [range 2345] years) with chronic hepatitis B
resistant to lamivudine or telbivudine therapy who
were subsequently treated with tenofovir mono-
therapy. [World J Gastroenterol 2015;21:2504-
2509]
The median level of hepatitis B virus (HBV) DNA
among the women was 5.9 (range 4.27.2) log10
copies/mL at baseline. Ten women also had ab-
normal levels of alanine aminotransferase (ALT).
All of the women were treated with tenofovir 300
mg/day initiated at a median gestational age of 15
(range 028) weeks and continued for a median
of 24.4 (range 1240) weeks. The researchers de-
termined the effects of tenofovir on maternal and
perinatal outcomes, foetal growth and develop-
ment, and neonatal prognosis.
At the time of delivery, HBV levels were signifi-
cantly reduced to
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 fi nd 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 workfl ow. Connect with MIMS today.
facebook.com/mimscomwww.mims.com MIMS mobile/tablet app
2015-MIMS-IOS_156x216_NewLogo.indd 1 6/4/15 6:02 pm
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.
Sofosbuvir for hepatitis C virus infection
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-
nually. However the major burden of disease is
due to the adverse consequences of chronic in-
fection. About 20 percent of patients with HCV
eventually develop cirrhosis and die due to end-
stage liver disease or hepatocellular carcinoma.
It is estimated that there are 3-4 million new HCV
infections each year and 170 million people with
chronic infection. [Hepatology 2013;57:1333-42]
The prevalence of HCV is relatively high in
some parts of Asia: in East Asia (China, Hong
Kong, Macau, North Korea, Taiwan) 3.7 percent
and South Asia (Afghanistan, Bangladesh, Bhu-
tan, India, Nepal, Pakistan) 3.8 percent. Preva-
lence is lower in Southeast Asia (including Ma-
laysia, Philippines, Thailand, Vietnam) at 2.0
percent and high-income Asia-Pacific nations
(Brunei, Japan, South Korea, Singapore) 1.4 per-
cent. [Hepatology 2013;57:1333-42]
With the rising prevalence and serious con-
sequences of HCV infection, there is an urgent
need for effective and safe therapies. The first
treatment used was interferon alfa-2b introduced
in the early 1990s, followed a few years later by
interferon alfa-2a. Combination therapy with the
antiviral ribavirin was introduced in 1998.
More recently, the protease inhibitors telapre-
vir and bocepravir have become a third compo-
nent of standard care for HCV. With this approach,
a subgroup of patients are able to achieve a sus-
tained virological response (defined as complete
eradication of the virus) and enjoy an excellent
benefit in terms of reversal of liver fibrosis and re-
duction in long-term adverse hepatic outcomes.
MAY-JUNE 2015 DRUG PROFILE 17
A significant proportion of patients, however, do
not respond. Furthermore, many patients experi-
ence intolerable side effects from interferon. In
others, interferon cannot be commenced due to
contraindications or an unwillingness to take the
therapy.
Another limitation of available therapies arises
from the fact that HCV exists in at least six distinct
genotypes. The protease inhibitors are effective
in patients infected with HCV genotype 1 (the
more commonly occurring genotype) and 2, but
have no or limited efficacy in other genotypes.
This has stimulated interest in alternative thera-
peutic strategies and interferon-free regimens.
[Digestive Liver Dis 2014;46:S174-S178; Ther
Adv Chronic Dis 2015;6:414] The emerging class
of nucleotide polymerase inhibitors has been the
subject of intense research in recent years, with
15 candidate drugs investigated. To date, only
one of these sofosbuvir has been approved
for clinical use. [Phamacogenom Personal Med
2014;7:387-98]
Pharmacology and pharmacokinetics
Sofosbuvir is a prodrug that undergoes in-
tracellular metabolism in the liver to form GS-
461203 a triphosphate analogue of uridine
nucleotides, modified by the addition of methyl
and fluoro groups. During replication of HCV,
GS-461203 competes with naturally occurring
uridine and is incorporated into the growing RNA
strand in a process mediated by NS5B protein
an RNA-dependent RNA polymerase. The struc-
tural modifications introduced into the strand
limit elongation and lead to premature termina-
tion of RNA synthesis, thereby stopping viral rep-
lication. GS-461203 is highly specific to its viral
target and has no affinity for human RNA or DNA
polymerases. [Pharmacogenom Personal Med
2014;7:387-398; Product Monograph, SOVAL-
DI (sofosbuvir). Gilead Sciences Inc.]
Sofosbuvir is rapidly absorbed orally, with
plasma levels peaking within 0.5-2 hours. Ab-
sorption is slowed by the presence of food,
however overall exposure remains the same. It
is readily taken up by hepatocytes from the plas-
ma, where a number of activation steps occur.
The triphosphate metabolite has a long intracel-
lular half-life of 17.8 hours. Eventually dephos-
phorylation produces inactive metabolites that
are mainly cleared by the kidney.
Clinical efficacy
The phase II ELECTRON study of sofosbu-
vir (with and without ribavirin) provided prom-
ising proof of concept that the oral nucleoside
polymerase inhibitor could produce a sustained
virological response in HCV, without the need
for interferon. This prompted phase III investi-
gations. Five trials (FISSION, POSITRON, FU-
SION, NEUTRINO and VALENCE, n = 1724)
studied the effects of sofosbuvir in combination
with ribavirin or pegylated interferon plus ribavi-
rin, mostly in treatment-nave but also in previ-
ously treated patients with chronic HCV. Many of
the subjects (16-34 percent) had cirrhosis. The
PHOTON-1 study enrolled subjects that were
co-infected with HCV and HIV-1, while a further
study was conducted in patients awaiting liver
transplantation. The clinical trials program pro-
vided sufficient data for product registration and
clearly demonstrated that sofosbuvir represents
MAY-JUNE 2015 DRUG PROFILE 18
a major advance in the treatment of HCV. Sus-
tained virological response rates were 89-90 per-
cent among patients with genotypes 1, 4, 5 and
6 treated with pegylated interferon, ribavirin and
sofosbuvir for 12 weeks.
Sofosbuvir targets the highly conserved active
site of the HCV polymerase and this results in an-
tiviral activity across the spectrum of HCV geno-
types albeit with some variations in potency.
The drug also has a high barrier to the develop-
ment of acquired resistance. Some intrinsic re-
sistance to sofosbuvir exists in the NS5B S282T
mutation, however this mutant has reduced re-
productive fitness compared to wild-type virus
and is also susceptible to ribavirin.
Safety and tolerability
Pooled analysis of phase III trials found that
permanent treatment discontinuations due to
adverse events occurred in 4 percent of patients
receiving placebo, 1 percent for subjects receiv-
ing sofosbuvir plus ribavirin for 12 weeks,
MAY-JUNE 2015 BUSINESS 20
New headquarters to help Sigma-Aldrich support AsiaPac clientsRADHA CHITALE
Life science and biotechnology firm Sigma-Aldrich opened a new regional business headquarters at Singapores Biopolis Research
Park in April, consolidating existing laboratories
and offices to become a supply hub for phar-
maceutical manufacturers in the Asia Pacific
region.
The new facility also houses the companys
Cell Culture Technical Center, the first such cen-
ter in the region, which will focus on developing
and optimizing cell culture media for clients.
Mr. Jason Apter, vice president at Sigma-
Aldrich and the Asia Pacific managing director,
noted the ease of reaching out to regional clients
in Tokyo, Shanghai, Bangalore, and elsewhere,
from Singapore, as well as the significant front
and back ecosystems here of talent that can com-
municate across the region.
[This headquarters] is the only place from
which we can technically support customers in
Asia, Apter said.
The company also plans on completing a re-
gional distribution center in Tuas by the end of the
year.
Sigma-Aldrich is one of several biomedical
sciences companies, including Amgen, Novar-
tis, and GlaxoSmithKline, that are capitalizing
on Singapores strategic location and business
infrastructure to grow their Asia operations.
Today, the fact that nine of the top 10
Mr. Kevin Lai (center) with executives from Sigma-Aldrich at the launch of the Cell Culture Technical Center at Biopolis Research Park. Photo courtesy of Sigma-Aldrich.
global pharmaceutical companies have a
presence in Singapore across manufacturing,
headquarters and R&D operations is testimo-
ny to the continued growth of our pharmaceu-
tical industry, said Mr. Kevin Lai, executive
director of Biomedical Sciences and Con-
sumer Businesses of the Singapore Econom-
ic Development Board. We welcome Sigma-
Aldrichs new investment and are confident
that this will further strengthen our supporting
ecosystem for biopharmaceutical manufac-
turing and R&D.
The overall goals of consolidating and ex-
panding operations are to improve efficiency
and profits, reduce risk, and accelerate speed-
to-market for products from the many biotech
companies in the region, from those well es-
tablished companies in Korea, for example, to
smaller start-ups in China. Apter said the rate of
growth in the biotech sector will be twice what it
has been in the US.
MAY-JUNE 2015 BUSINESS 21
Novel radiation-free test to aid diagnosis of gastroparesis
KAVITHA G. SHEKAR
The 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 exist-
ing non-radioactive form of carbon-12, in a pa-
tients breath. Gastric scintingraphy, the standard
diagnostic test for gastroparesis, uses radioactive
material and requires specialist training.
[GEBT] can be performed in any clinical set-
ting since it does not require the health care pro-
fessionals administering the test to undergo spe-
cial training or to take special precautions related
to radiation emitting compounds, as no radioac-
tive materials are used said Dr. Alberto Gutierrez,
director of the Office of In Vitro Diagnostics and
Radiological Health in the FDAs Center for De-
vices and Radiological Health.
The approval is based on a study of 115 par-
ticipants who underwent both GEBT and gastric
scintigraphy. Performed over a 4-hour period fol-
lowing an overnight fast, GEBT measured the ra-
tio of carbon-13 to carbon-12 in breath samples
at multiple points, which is then compared to
the baseline measure. Participants consumed a
carbon-13 enriched meal containing scrambled
egg-mix and Spirulina platensis. GEBT and scin-
tigraphy results agreed 73-97 percent of the time.
Gastroparesis interferes with normal diges-
tion causing severe nausea and vomiting, dehy-
dration, and malnutrition. Diabetes is the most
common cause of gastroparesis. Other causes
include infections, internal surgery, neurological
disease like Parkinsons disease, and endocrine
disorders like hypothyroidism.
GEBT is not advisable for patients with an al-
lergy to Spirulina, egg, milk, wheat, or certain
lung diseases or conditions that cause small
bowel malabsorption.
MAY-JUNE 2015 BUSINESS 22
First home-use EEG device for autism launched in SingaporeELVIRA MANZANO
A 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 home-
use electroencephalogram (EEG) device for au-
tism, uses neurofeedback to help mentally relax
patients with autism, allowing them to focus bet-
ter and engage positively with the environment.
Children with autism spectrum disorder
[ASD] process sensory information sights and
sounds in particular differently from children
without autism, said Dr. Adrian Attard Trev-
isan, founder and managing director of AAT Re-
search, which makes Mente. They have higher
levels of delta waves in the brain even during
daytime and low levels of alpha [] and beta []
waves. This causes many of the symptoms and
distractions patients experience.
The device comprises an EEG headband
and a software application that creates tailor-
made binaural beats to level the brainwaves ac-
cording to a patients mental state. All it takes is
40 minutes of use every morning and the effects
last the rest of the day until the child goes back
to sleep, Trevisan said. With sleep, the delta
waves naturally increase so the process must
be repeated daily. Depending on the childs
symptoms, this treatment must be used for 4 to
8 weeks to start seeing positive results.
In one study, the use of Mente significantly
reduced delta wave peaks and increased and
wave peaks in children (age 6-18) with ASD,
allowing them to be more relaxed over time.
Parents reported that their children had fewer
tantrums and were able to concentrate more. [J
Neural Discord 2013;1:4]
These led to longer attention spans, en-
hanced relaxation and improved communi-
cation skills for most patients, said Trevisan.
The device was originally developed to help a
friends son who had Aspergers syndrome, a
form of autism that affects language and behav-
ioral development in children.
I spent time observing him, watching him
carefully, trying to figure out how I could help.
Through this neurofeedback technology, chil-
dren like him with autism can focus and better
engage with the world.
Mente is FDA-registered and has been given
the CE Medical mark of approval as a medical
device in April. It is easy to set up and doesnt
require specialist supervision, making it ideal
for home use, said Trevisan.
MAY-JUNE 2015 CLINICAL PHARMACY 23
Imatinib may be a novel treatment option for colon cancerRADHA CHITALE
Imatinib 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 Tech-
nological Universitys (NTU) Lee Kong Chian
School of Medicine, Singapore. The drug was
also effective in increasing the survival of mice
with late-stage tumours and rectal bleeding.
[Sci Transl Med 2015;7:281ra44]
Imatinib targeted and blocked cell recep-
tors of EphB proteins, which control growth and
movement of intestinal stem cells and progeni-
tor cells.
Importantly, while imatinib blocked EphB re-
ceptors, it did not affect EphB itself, which acts
to prevent progression to invasive carcinoma.
When administered in vitro to cancerous cells
taken from humans with colon cancer, imatinib
performed similarly to the mouse model.
Although there are side effects associated
with long-term imatinib use cardiotoxicity and
oedema are the most serious these could be
attenuated by administering treatment in short,
intermittent bursts, the researchers said.
Our work has important clinical implica-
tions, since imatinib is a potentially novel drug
for the prevention and treatment of colorectal
cancer, said senior principal investigator Pro-
fessor Sven Pettersson of the Lee Kong Chian
School of Medicine, Singapore and Karolinska
Institute in Solna, Sweden.
MAY-JUNE 2015 CLINICAL PHARMACY 24
Paracetamol study highlights risks of long-term use
A new study shows paracetamol, the worlds most commonly used and recommended painkiller, is not as benign as once thought.
Until recently, paracetamol was perceived
as relatively safe, but new research shows pa-
tients with chronic pain on long-term, highdose
paracetamol are increasing their risk of kidney,
intestinal and heart problems, and also death.
In a systematic review of paracetamol safety
studies, UK researchers selected eight obser-
vational studies to analyse. [Ann Rheum Dis; 2
March early online publication]
Two studies showed an increase in mortality
of up to 63 percent for longterm paracetamol
users, compared with those not prescribed
it. Four showed a higher risk of kidney dam-
age and another four reported cardiovascular
events increasing by between 19 to 68 per-
cent.
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
being on other drugs to treat multiple comor-
bidities, and also that paracetamols benefits
may still outweigh its risks for many people.
However, given that recent studies have
called into question the efficacy of paracetamol
for treating osteoarthritis joint pain and acute
low back pain, they wanted health profession-
als to think carefully before recommending or
prescribing paracetamol for long-term use.
Based upon the data presented above, we
believe the true risk of paracetamol prescription
to be higher than that currently perceived in the
clinical community. Given its high usage and
availability as an over-the-counter analgesic,
a systematic review of paracetamols efficacy
and tolerability in individual conditions is war-
ranted, the researchers say.
However, the industry body for over-the-
counter medicines is pointing to the long his-
tory of use and well-established safety profile of
paracetamol.
The study only looked at people on prescrip-
tions for paracetamol, but, in a press release,
Self Medication Industry executive director Tim
Roper says the maximum recommended dose
for people over 12 years is 4000mg in a 24-hour
period, and people should consult a medical
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 peo-
ple not to be alarmed.
This latest study is another of the ongoing
challenges chronic pain sufferers face of bal-
ancing pain relief with potential adverse effects.
The internet is full of information about
adverse effects from painkillers, including
paracetamol, but often pain relief will allow
people to participate in everyday activities, in-
cluding exercise, which in turn helps with ar-
MAY-JUNE 2015 CLINICAL PHARMACY 25
thritis, Kirby says.
Pharmacists should reassure people that
as long as they take their paracetamol as pre-
scribed and have regular check-ups, the ben-
efits usually outweigh the risks.
Pharmacists can also talk to people about
other ways of managing their pain, such as
through exercise, joint support, relaxation
techniques, and hot and cold packs. There
is also good evidence for acupuncture, mas-
sage, capsaicin cream and transcutaneous
electrical nerve stimulation (TENS), which
uses electricity to stimulate the nerves, Kirby
says.
Directing people to the Arthritis New Zealand
helpline is another good option, she says.
Pharmacists can really add value by looking
at the patients whole picture, finding out what
other pain management they are using, includ-
ing complementary medicine, and looking for
drug interactions.
Pharmaceutical Society clinical advisor Bob
Buckham says the standard advice following
studies such as this, is people shouldnt just
stop taking their medication without discussing
it with their doctor first. Unichem Hillpark Phar-
macy owner Kathy Maxwell says she has not
had any customer queries following the release
of the study, but says patients would
have to consider what the alternatives to
paracetamol are and how their safety profiles
compare. PTNZ
News & CME
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.
Stay up-to-date on the latestmedical trends and developments,
wherever you may be.
JPOG
www.mims.com facebook.com/mimscomMIMS mobile/tablet app
2015-JPOG-thru-MIMS_NewLogo.pdf 2 9/4/15 10:07 am
Pharmacists can help to ease chronic pain patients off opioids
Pharmacists have a vital role to play in iden-tifying and referring patients with chronic pain, according to pain specialists.
About 17 percent of the population has
chronic pain, which lasts for longer than three
to six months, New Zealand Pain Society presi-
dent-elect and chronic pain clinical psychologist
Frances James says.
Thats one person in five, and certainly not
all of them are making it to a specialist, James
says.
In acute cases, pain is useful because it alerts
the patient to an injury and encourages them to
look after the injured area, she says.
But chronic pain is like an alarm that sounds
and then cant be turned off, James explains.
Pain doesnt always mean that somethings
wrong, but were programmed to believe it is,
and thats what people are often very frightened
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 who are coming into the pharmacy
to buy a lot of overthe-counter (OTC) pain medi-
cation should be referred to a doctor, and should
be checked to see if they are taking the recom-
mended doses, she says.
We commonly find people who are really sore
will take a handful of Panadol [paracetamol], as
opposed to whats recommended, James says.
The more that pharmacists can ask sensible
questions and give quality advice, the better, be-
cause there are a lot of people living with chron-
ic pain, she says.
New Zealand Pain Society president and pain
medicine specialist Brigitte Gertoberens agrees
many patients self-medicate and take pain med-
ications incorrectly.
There are heaps of patients, especially head-
ache patients, who self-medicate and it would
be helpful if pharmacists help them, because
you see them before we do, Gertoberens says.
Medication over-use headaches, or rebound
headaches, are caused by taking too much pain
medication. They are the third most common
type of headache, after migraine and tension-
type headaches, according to the Healthcare
Handbook 2014 (pp8889).
Patients can become addicted to pain medi-
cations and can suffer from adverse effects, and
pharmacists need to educate them about this,
Gertoberens says.
Pharmacists should advise patients with on-
going pain to consult their GP, and ask for a re-
ferral to a pain service, if necessary. It is impor-
tant to rule out anything sinister that could be
causing the pain.
Medications play a minor role
In a pain clinic, medications play a minor role
in the management of chronic pain, Gertobe-
MAY-JUNE 2015 PHARMACY PRACTICE 26
rens says.
They can be useful, but are never curative,
and patients often show adverse reactions.
Tricyclic antidepressants are one treatment
option, and can be useful if the patient is also
suffering a mental health condition, she says.
Other options for long-term use include epi-
lepsy medication gabapentin.
Opioids are not considered useful for non-
cancer chronic pain, Gertoberens says. Pa-
tients who have been taking opioids should be
weaned off them, but this needs to be done as
part of a team, she says.
The movement against opioids
An Auckland GP who specialises in addic-
tion, Graham Gulbransen, agrees doctors and
pain services are very much against the use of
opioids. People build up a tolerance and need
bigger and bigger doses. On the other hand,
people like me, and a lot of GPs, see people
who arent getting adequate pain relief unless
they do take adequate doses of opioids.
Controlled dispensing is one way to control
opioid use, reducing the risk of overdose or di-
version, Gulbransen says.
Referring patients to a pain service is another
option, but the waiting lists can be as long as
nine months, he says.
Other medications like tricyclic antidepres-
sant amitriptyline and anticonvulsant gabapen-
tin should be considered, Gulbransen says.
They are less likely to be diverted to other
people, [patients are] less likely to build up a tol-
erance, and they are most likely to be safer, but
some people will have intolerable side effects,
he says.
Gulbransen encourages pharmacists to ring
the doctor with any queries, especially for opioid
prescriptions. Pharmacists should also look out
for drug-seeker red flags, including frequent ap-
pearances, scripts in different names or scripts
that have been changed.
Pharmacies have a role to play
Pharmacists can play a big role in the man-
agement of chronic pain, according to Welling-
tons Miramar pharmacist Ann Privett.
Customers who are frequently buying strong
OTC pain relievers, such as codeine-containing
medicines or diclofenac, are queried, Privett
says.
Its very easy for us to see, on our LOTS com-
puter system, their history of OTC purchases, all
we have to do is put their name in, she says.
That often opens the door for us to say we
notice that youre buying quite a lot of these, do
you want to talk to us about it?
Pharmacies can help patients manage their
pain, such as by suggesting glucosamine and
chondroitin if the person has arthritic pain, or re-
ferring the patient to physiotherapy or acupunc-
ture, Privett says.
Its important to find out exactly what the pain
is, so you can have a chat with them about it.
If we notice that their usage rate is not ap-
propriate, we will not sell [an OTC product] to
them, and will refer them to a doctor.
Long-term help needed
Privett also works with her local general prac-
tice to assist patients suffering from chronic pain
MAY-JUNE 2015 PHARMACY PRACTICE 27
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 medi-
cines therapy assessment.
Privett initially meets with patients weekly to
discuss their medications, then monthly.
Some are on horrendous doses, she says.
Usually we look at ways of reducing the co-
deine and tramadol, and anti-inflammatories, in
a very, very slow and structured regimen, and
increasing other medication, like amitriptyline
and gabapentin.
If a patient is being taken off opioids, it is im-
portant they are not left in pain and have some
sort of other pain relief, Privett says.
Once the process starts, we usually find
weve got good acceptance because the patient
doesnt want to be on these drugs.
KEY POINTS: About 17% of people suffer from chronic pain.
Pharmacies play a key role in identifying and refer-
ring patients who use too many OTC pain reliev-
ers.
Pharmacists can help patients come off opioids
with intense one-on-one care.
Privett also refers patients to pain clinics,
when available, and encourages patients to dis-
tract 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.
Its what the doctors want, and, ethically, you
cant turn these patients away. Plus it is really
rewarding, she says. PTNZ
MAY-JUNE 2015 PHARMACY PRACTICE 28
facebook.com/mimscomwww.mims.com MIMS mobile/tablet app
2015-MIMSmobileapp156x216_NewLogo.indd 1 27/4/15 9:50 am
MAY-JUNE 2015 IN FOCUS 29
Irritable bowel syndrome patients need guidance, supportWith as many as 20 percent of people having irritable bowel syndrome, many customers
are looking for help to manage their symptoms.
Irritable 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, accord-
ing to the Healthcare Handbook 2014.
Symptoms can range from minor and occa-
sional, 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, Sep-
tember 2013).
There are not a lot of New Zealand data indi-
cating how frequent IBS is, aside from a Dunedin
population-based study which estimated 20 per-
cent of the population has the syndrome, Christ-
church gastroenterologist Richard Gearry says.
I usually say about one in six women and
one in nine men have irritable bowel syndrome,
and most of my colleagues would agree, Gearry
says.
There are a number of theories as to why the
syndrome is more common in women, including
a possibility of it being related to endometriosis
or hormones, or more reporting by women, he
says.
The causes of IBS are currently unknown and
are not defined anatomically or biochemically. Di-
agnosis is based on chronic and relapsing symp-
toms.
Irritable bowel syndrome does not do any
long-term damage even if untreated, Gearry
says.
However, it is important for patients to get a
proper diagnosis to rule out anything else in-
cluding cancer, inflammatory bowel disease like
Crohns and ulcerative colitis, or coeliac disease.
Pains that are not specific require clinical
tests, and they may require faecal tests or blood
tests to be sure, Gearry says.
And then, if a diagnosis has been made, it
comes down to what symptoms annoy people
the most if its constipation, look at agents for
that, if its diarrhoea there are agents for that.
Greenhithe pharmacist Samit Patel, who spe-
cialises in natural treatments to manage bowel
conditions, agrees a proper diagnosis is essen-
tial. Youre looking for all the red flags, including
how long they have had symptoms, if there is a
MAY-JUNE 2015 IN FOCUS 30
lot of mucus in the stools. Blood in the stools al-
ways needs to be checked out.
People who have been diagnosed with IBS
will know all about it, but some patients know
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.
These patients still need support, and can be
treated as if they have some sort of inflammatory
bowel condition, Patel says.
Manage flare-ups first
Managing primary symptoms is one of the
first steps in managing IBS, particularly if they are
suffering from bad diarrhoea, Patel says.
Over-the-counter medicines can help with
symptoms.
Peppermint in oil or tea form can help get
rid of bloating, and aloe vera can help soothe the
stomach. A good probiotic is also worth recom-
mending, he says.
An Auckland dietitian recommended by gas-
troenterologists, Nikki Talacek, agrees probiotics
are good for people with unhappy guts.
But it is important they do not contain
fructo-oligosaccharides (FOS) as they are
usually not tolerated by people with IBS,
Talacek says.
Other products, including turmeric, Boswellia
and essential amino acid glutamine, can also
help with inflammation, Patel says. It is important
to encourage the patient to come back and give
feedback about whether the products work, he
adds.
I always emphasis a bit more care, rather
than just giving a product thats pharmacys
point of difference.
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-
ed for IBS but the only one clinically proven to
help is the low-Fodmap (fermentable oligosac-
charides, disaccharides, monosaccharides and
polyols) diet.
Studies replicated in Australia, New Zealand
and the UK show 75 percent of patients will get a
significant improvement in abdominal pain, diar-
rhoea and bloating with a low-Fodmap diet, he
says.
Gearry outlines Fodmaps in a Pharmacy To-
day How to Manage feature (September 2013).
Oligosaccharides are shortchain carbohy-
drates found in large amounts in wheat, barley,
rye and some vegetables like onions and cab-
bage.
Disaccharides include lactose, with high-lac-
tose foods including cows milk yoghurt and ice-
cream.
Monosaccharides include fruits with high fruc-
tose-to-glucose ratio, such as pears, apples and
watermelon.
Polyols are sugar alcohols found in stone fruit,
some vegetables and some sugar-free products.
As the low-Fodmap diet is so exclusionary,
patients need to consult a Fodmap-trained dieti-
tian, to make sure they do not become deficient
MAY-JUNE 2015 IN FOCUS 31
in nutrients, Talacek says.
Information is power
Patel agrees a proper low-Fodmap diet
which involves reducing all Fodmap foods then
slowly reintroducing them is very involved and
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.
As people are told fruit and vegetables are
healthy to eat, they may not realise they could be
causing them problems, he adds.
Start simple in pharmacy
Rather than telling patients what they should
be eliminating, Patel prefers to suggest things
that they can eat.
Rice with fish or chicken is a simple dish that
is easily digestible. Vegetables like carrots are
good, and cooked foods are easier to digest
than raw foods, he says.
Its about keeping the food a little bit bland
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.
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-
erywhere else in the body. Everything around us
has an effect on the gut.
Reducing caffeine and alcohol is also impor-
tant, as is getting adequate sleep, and drinking
water.
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 manage-
ment of abdominal pain due to spasm.
However, not all patients want to be on these
medications, and lifestyle changes should be
tried first, he says.
IBS is a lifestyle disorder so, if you can man-
age it with lifestyle, thats a much better approach
than putting someone on a drug long term. While
there are data that they work, many patients
wouldnt want to go on an antidepressant.
The gut is hypersensitive, so any stimulus
will cause symptoms at a much lower threshold
than people without IBS. You can reduce sensi-
tivity with drugs or you can reduce the triggers
[through diet]. PTNZ
KEY POINTS: Patients with IBS symptoms need a GP
assessment to rule out anything more
sinister.
OTC products can help manage symptoms as a
first step.
A low-irritant diet and stress reduction are key for
longterm management of IBS.
ISSN 2382-6487
EDITORIAL ADVISORY BOARD S INGAPORE
Associate Professor Chui Wai KeungHead of Department of Pharmacy, Faculty of Science National University of Singapore (NUS)
Assistant Professor Lita ChewChief 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
Dr. Joyce Yu-Chia LeeAssistant Professor of Clinical Pharmacy Department of Pharmacy, NUS Principal Clinical Pharmacist, National Healthcare Group Polyclinics
P U B L I S H E R
Ben Yeo
M A N A F I N G E D I T O R
Elvira Manzano
D E P U T Y M A N A F I N G E D I T O R
Radha Chitale
C O N T R I B U T I N G E D I T O R S
Saras Ramiya, Pank Jit Sin, Dr Joslyn Ngu (Malaysia)
B U S I N E S S M A N A G E R
Carrie Ong, Josephine Cheong, Melanie Nyam
D E S I G N E R S
Razli Rahman, Anson Suen, Joseph Nacpil, Agnes Chieng, Cindy Ang, Ryan R.A. Baranda,
P R O D U C T I O N
Jasmine Chay
C I R C U L A T I O N E X E C U T I V E
Christine Chok
A C C O U N T I N G M A N A G E R
Minty Kwan
A D V E R T I S I N G C O O R D I N A T O R
Angeline Chua
P U B L I S H E D B Y
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
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.