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 (Figure 1) gastric bypass is the most common intervention, and has been reviewed for safety and efficacy 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).
The authors therefore decided to undertake an exploratory literature search of the available evidence to inform best practice for addressing prescribing challenges following 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.
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 refined 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 (CW) then searched for duplicates and conducted a review of the titles and abstracts for relevance to the study, using 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 2). Five of these studies were excluded after reading (Table 1).
Table 1. Excluded articles
| Author | Study type | Reason for exclusion |
|---|---|---|
| Yska et al (2016a) | Systematic review | Excluded as not relevant to the article |
| Yska et al (2016b) | Randomised controlled trial | Not applicable because it was a randomised controlled trial of behaviour of clinicians and not drug absorption |
| 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 specific, focused on gastric sleeve and only had four subjects. |
| Gómez-Ramírez et al (2018) | Non-research | Excluded because this was a non-research article on drug formulations and not related to use in bariatric surgery |
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.
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 |
It is notable that low numbers of subjects have been involved in these trials, which might be considered to be a significant 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 (Pirola et al, 2013; Fallahi at al, 2017; Hommel and Delgrange, 2017). 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 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 specific, with the most consistent evidence for reduced absorption found for cyclosporine, levothyroxine, phenytoin and rifampicin.
Sawaya et al (2012) reviewed vitamin and mineral deficiency, with emphasis on the likelihood of patients developing vitamin B12 deficiency after bariatric surgery. This led to guidance recommending routine vitamin B12 intramuscular injections for 3 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, 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 fenofibrate 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-specific 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.
Key Points
- Little is known about the impact of bariatric surgery on patients' medication burden or the absorption of drugs
- 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
- It may be pertinent to consider other drug formulations in people who have undergone surgery
CPD reflective questions
- In your experience, how often do you prescribe for people who have undergone bariatric surgery? How has this article affected your prescribing decisions?
- Using a reflective model of choice, consider how you would support a patient who is about to undergo bariatric surgery. What factors would you need to address when carrying out a consultation?
- What did you learn as a consequence of reading the article?