Prescribing challenges following bariatric surgery

Abstract

Obesity is an increasing problem in the UK, with over half of the population being overweight or obese. The use of gastric surgery is increasing, with a 5% increase in 2016/17 compared to 2015/16. However, little is known about ideal drug formulations after bariatric surgery. An exploratory literature search of research databases was carried out to address this. The authors found that there was a dearth of high-quality primary studies available, with many studies using low numbers of participants. The major finding was of the need for increased vigilance and monitoring of patients after surgery.

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RESEARCH
© 2019 MA Healthcare Ltd
The statistics surrounding obesity in the UK
are concerning. The prevalence of people
who are overweight or obese was 57% for
women and 66% for men in 2016 (NHS
Digital, 2017). The prevalence of obesity alone
has increased from 15% of the population in 1993
to 27% by 2015 (NHS Digital, 2017). This is an
increasing trend worldwide, with the UK currently
having the dubious value of being near the top
of the league table for obesity prevalence; ranked
sixth out of 34 countries (NHS Digital, 2018).
The same statistics reveal that 617 000 admissions
to hospital in 2016/17 were related to obesity, an
increase of 18% on the previous year. There was a
5% increase in admissions for bariatric surgery in
2016/17 compared to 2015/16 from 6000 to 6760,
although the total number has not reached the
peak seen in 2011/12 (NHS Digital, 2018).
The four most common surgical interventions
for the management of obesity are Roux-en-Y
gastric bypass, sleeve gastrectomy, laparoscopic
gastric band and biliopancreatic diversion with
duodenal switch. The Roux-en-Y gastric bypass
is the most common intervention, and has
been reviewed for safety and efcacy of surgical
procedures (Guller et al, 2009). A meta-analysis
showed that the Roux-en–Y bypass was superior
to alternative surgical options in obtaining weight
loss (Zhang et al, 2014). While there has been
some controversy surrounding which approach
is best, the likely superiority of the Roux-en-Y
approach was upheld by Ettleson et al (2017).
The Roux-en Y bypass involves reducing the
volume of the stomach by approximately 98%. The
normal volume of the stomach is 1,500 ml, but
this is reduced to approximately 30 ml after the
procedure. In addition, a shortened length of the
small intestine is attached to the smaller pouch of
the stomach, thus reducing absorption through the
small intestine and affecting the body’s ability to
absorb minerals and drugs.
Managing long-term conditions after major
surgery is potentially complex. Therefore, it is
opportune to review the available literature on
absorption of drugs post bariatric surgery.
Little is known about the impact of bariatric
surgery on patients’ medication burden or the
absorption of drugs (Azran et al, 2017).
We therefore decided to undertake an
exploratory literature search of the available
evidence to inform best practice for addressing
prescribing challenges after bariatric surgery. We
conducted a literature review with assistance
from the university librarian. We noted the
relative dearth of primary sourced evidence on
drug absorption and concluded that enhanced
monitoring in regards to drug management is a key
need post surgery.
Prescribing challenges after
bariatric surgery
Colin Waldock and David Bedford
Abstract
Obesity is an increasing problem in the UK, with over half the population being
overweight or obese. The use of gastric surgery is increasing, with a 5% increase
in 2016/17 compared to 2015/16. However, little is known about ideal drug
formulations after bariatric surgery. An exploratory literature search of research
databases was carried out to address this. We found that there was a dearth
of high-quality primary studies available, with many studies using low numbers
of participants. The major finding was of the need for increased vigilance and
monitoring of patients after surgery.
Key words: bariatric surgery | obesity | safe practice | drug formulation
Colin Waldock
Lecturer, Medway School of Pharmacy,
Universities of Kent and Greenwich
David Bedford
Librarian, University of Greenwich
c.waldock-551@kent.ac.uk
D.d.Bedford@greenwich.ac.uk
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Method
Assistance was sought from the university library to
conduct an exploratory literature search for relevant
articles in English using the following terms: bariatric
surgery, weight loss surgery, prescribing, prescriber,
prescribers, prescribe, dosage form, dosage forms,
pharmacotherapy, pharmacotherapeutic, formulation,
absorb, absorption and absorbance.
The search databases Cinahl and Medline
were used, yielding a high number of results
unconnected with the question. The search was
further rened by adding the following terms to
focus the results on postoperative management:
after, following, postoperative, post-operative,
postsurgical, post-surgical.
The records retrieved were screened to ensure
inclusion only of English language research articles
relevant to the question (eg, to remove articles
relating to absorption of food or comparisons of
weight-loss surgery to pharmacotherapy).
The principal author then searched for duplicates
and conducted a review of the titles and abstracts
for relevance to the study, utilising the Critical
Appraisal Skills Programme (CASP) tool to aid in
decision-making as to relevance. This process led
to the exclusion of a further 41 articles, leaving 53
to be reviewed (Figure 1). Five of these studies were
excluded after reading (Table 1).
Discussion
The 48 articles in the review covered a variety of
topics and used several types of study methods
(Table 2). It is clear from these numbers that there
is a dearth of literature using controlled trials to
investigate absorption and issues affecting drug
formulation after bariatric surgery.
It is notable that low numbers of subjects have
been involved in these trials, which might be
considered to be a signicant limitation.
Mischler et al (2018) studied 14 subjects to
investigate what type of iron formulation to
recommend after bariatric surgery. In the largest
study, Ring Madsen et al (2018) studied 39 subjects
to assess the effectiveness of calcium citrate
versus calcium carbonate on elevated parathyroid
hormone after Roux-en-Y gastric bypass. The
lowest number of subjects was eight (Rocha
et al, 2019). There is a requirement for large,
high-quality randomised controlled trials to be
developed in order to inform practice.
There are also some case reports in the literature.
Three of these studied liquid levothyroxine as an
alternative to the tablet formulation after bariatric
surgery (Fallahi at al, 2017; Hommel and Delgrange,
2017; Pirola et al, 2013). While the use of liquid
formulations appears to be supported by these
reports, it is worth considering the cost of liquid and
soft gel formulations. Levothyroxine 100 microgram
tablets cost 4p per day, whereas the equivalent liquid
formulation is £5.72 per day (100 microgram/5 ml)
(Joint Formulary Committee, 2018).
Azran et al (2017) presented a case of a patient
who had a lower absorption of oral methylphenidate
after bariatric surgery. They discussed a second case
(Ludvigsson and Haenni, 2016) where the patient
suffered methylphenidate toxicity after surgery. The
contradictory effects in these two cases suggest that
methylphenidate absorption is unpredictable post
surgery. Further work is clearly needed and patients
should be closely monitored in order to avoid under-
or overdose of methylphenidate.
Darwich et al (2012) used simulation models to
assess the likely pharmacokinetic effects on a range
of drugs after bariatric surgery. They found that
adverse effects on absorption were dependent on a
range of factors and made recommendations to use
Table 1. Excluded articles
Author Study type Reason for exclusion
Yska et al (2016b) Randomised
controlled trial
Not applicable because it was
a randomised controlled trial of
behaviour of clinicians and not
drug absorption
Yska et al (2016a) Systematic review Excluded as not relevant to the
article
Macgregor and Boggs
(1996)
Literature review Excluded as article superseded by
recent developments
Muzard et al (2017) Case series Excluded as area of study too
specic, focused on gastric sleeve
and only had four subjects.
Gomez-Ramirez et al
(2018)
Non research Excluded because this was a
non research article on drug
formulations and not related to use
in bariatric surgery
Table 2. Types of articles reviewed
The 48 articles included in the review covered a variety of topics and used
several methods
Type Number of articles
Review 28
Cohort study 2
Controlled trial 6
Crossover trial 1
Case reports 4
Single dose pharmacokinetic study 4
Qualitative 2
Simulation model based 1
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best evidence from these models to predict required
dosage adjustments.
In our review, no further published material was
found that used simulation models.
In vitro models showed that 10 out of 22
psychotropic medicines have altered absorption,
while cyclosporin, phenytoin and thyroxine also have
changes in absorption (Seaman et al, 2005).
The majority of articles in this literature review
were themselves reviews, with the majority arguing
for close monitoring of patients after surgery. Padwal
et al (2010) stated that the effects post surgery appear
to be drug specic, with the most consistent evidence
for reduced absorption found for cyclosporine,
levothyroxine, phenytoin and rifampicin.
Sawaya et al (2012) reviewed vitamin and
mineral deciency, with emphasis on the likelihood
of patients developing vitamin B12 deciency
after bariatric surgery. This led to guidance
recommending routine vitamin B12 intramuscular
injections for three months post-operatively
(O’Kane et al, 2014).
Stein et al (2014) concluded that life-long
monitoring of patients was essential, echoed in
a review of levothyroxine dosage by Azran et al
(2019). Yska et al (2013) noted the dearth of high-
quality studies on dosage and formulations, while
Schlatter (2017) highlighted the need for more
research into oral contraception after bariatric
surgery.
In a review of anticoagulation, Martin et al
(2017) argued for the increased role of pharmacists
in post-surgical management. Greenblatt and
Greenblatt (2015) supported this, and noted that
any alteration in drug behaviour could be due to
a range of factors, including the surgery itself and
subsequent weight change.
Titus et al (2013) mentioned the lack of large
trials, but noted the relatively larger number of
small case studies and individual reports, again
calling for more work of high calibre, which was
echoed by other authors (Mitchell at al, 2013;
Azran at al, 2016).
A small number of single-dose pharmacokinetic
studies have shown that venlafaxine extended
release is unaffected by bariatric surgery (Krieger et
al, 2017). However, azithromycin is affected, with
a reduction of up to 30% in peak concentration in
patients undergoing bariatric surgery compared with
age-matched controls (Padwal et al, 2012).
Chan et al (2015) conducted a single-dose
pharmacokinetic study on midazolam and digoxin,
Figure 1. Selection process
Identication Records identied after database searching
n=112
Records after duplicates removed
n=94
Screening Records screened
n=94
Records excluded
n=41
Eligibility Full text articles assessed for eligibility
n=53
Full text excluded with reasons
n=5
Included Studies included
n=48
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and showed an increase in drug absorption rate
but no effect on overall exposure of the drug to the
individual. In a similar study design, Gesquiere et
al (2016) looked at fenobrate and posaconazole.
They found a marked reduction in the absorption
of posaconazole, highlighting the potential for early
treatment failure and the need for close monitoring.
Conclusion
The number of bariatric surgery procedures is
increasing. This surgery has the potential to reduce
prescribing for a wide range of drugs, including
insulins, oral diabetes medications, beta-blockers,
statins, NSAIDs and antidepressants, and reduce the
indicdence of hypertension and type 2 diabetes (Yska
et al, 2013; Bland et al, 2016).
There is a lack of high-quality, long-term large
studies. The current literature recommends close
monitoring of the patient for an extended time after
bariatric surgery.
Drug-specic changes have been reported in
single-dose pharmacokinetic studies (Padwal et al,
2012; Chan et al 2015; Gesquiere et al, 2016; Krieger
et al, 2017). There is potential for the use of drug
simulation models (Darwich et al, 2012). Liquid
formulations of levothyroxine have been promoted,
but the effect on costs needs to be considered.
Individual attention to patient needs and a patient-
centred model of care is recommended to best meet
the needs of this complex cohort. Pharmacists could
have an increased role to play in the post-operative
management phase. JPrP
Acknowledgements: Denise Rabbette and Teresa
Benniman, Medway School of Pharmacy Universities of
Kent and Greenwich, for peer review prior to submission
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