Received: 13 October 2021 | Revised: 14 February 2022 | Accepted: 19 March 2022

DOI: 10.1002/hsr2.605

REVIEW

Drug absorption in bariatric surgery patients:

A narrative review

Abdullah Abdulaziz Alalwan1,2 | Jeffrey Friedman3 | Osamah Alfayez1 |

2
Abraham Hartzema

1
Department of Pharmacy Practice, College of
Pharmacy, Qassim University, Qassim, Saudi Abstract
Arabia
Background: Despite the increase in the number of bariatric surgeries performed,
2
Pharmaceutical Outcomes and Policy,
College of Pharmacy, University of Florida,
little is known about the impact of the surgery on drug absorption. Unpredictability
Gainesville, Florida, USA is assumed with drugs, given the anatomical changes after surgery.
3
Department of Surgery, UF Health Bariatric Objective: To evaluate the impact of bariatric surgery on drug absorption based on
Surgery Center, University of Florida,
Gainesville, Florida, USA the type of procedure performed.
Methods: We conducted a comprehensive literature review searching PubMed/
Correspondence
Medline for published studies (from inception to December 2017) that evaluate the
Abdullah Abdulaziz Alalwan, Department of
Pharmacy Practice, College of Pharmacy, use of drugs and the assessment of drug absorption after bariatric surgery.
Qassim University, P.O. Box: 6800,
Pharmacokinetic/pharmacodynamic studies, case reports, and observational studies
Buraidah 51452, Saudi Arabia.
Email: alalwan@qu.edu.sa and were included in our review.
alalwan@ufl.edu
Results: We found 60 studies addressing drug use after bariatric surgery. Twenty‐
eight studies reported a decrease in drug absorption after bariatric surgery while
only four studies showed an increase in drug absorption. Unchanged absorption of
drugs was seen in 23 studies after the surgery.
Conclusion: The available information shows variations in drug absorption after
bariatric surgery. The unpredictability may result from factors related to the patient,
drug, and/or type of surgery. Therefore, pharmacists' involvement and close
monitoring of patients after bariatric surgery could be effective to avoid sub‐/
supratherapeutic responses.

KEYWORDS
bariatric surgery, drug absorption, drug use, pharmacotherapy, therapeutics

1 | B A R I A T R I C SU R G E R Y treatments and lifestyle modification approaches. Studies show that

bariatric surgery is more effective than pharmacological, lifestyle, and
Recent years have seen increases in the utilization of bariatric dietary interventions and can significantly improve comorbidities
surgery, often known as obesity surgery, metabolic surgery, or weight such as diabetes, sleep apnea, hypertension, and hyperlipidemia.2,3
1
loss surgery. Bariatric surgery has been attributed to long‐term Obese patients who undergo bariatric surgery are more likely to
weight loss, which is rarely achieved using pharmacological have comorbidities that require pharmacotherapy management.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any
medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.

Health Sci. Rep. 2022;5:e605. wileyonlinelibrary.com/journal/hsr2 | 1 of 8

https://doi.org/10.1002/hsr2.605
2 of 8 | ALALWAN ET AL.

The pharmacokinetic and pharmacodynamic properties of medica- comorbidities or to control postsurgery pain and adverse effects, it is
tions used in comorbidities management can be affected by the important to understand drug absorption after bariatric surgery. Available
changes resulting from bariatric surgery. These changes in pharma- evidence shows that drug absorption is more likely to decrease after
cokinetic and pharmacodynamic properties are primarily due to the bariatric surgery; however, the change in absorption is drug‐specific and
anatomical alterations caused by bariatric procedures, which are substantially affected by the type of procedure received.9,10 The decrease
restrictive, malabsorptive, or a combination of restrictive and in absorption can be due to gastric restriction caused by the surgery
4
malabsorptive. Restrictive procedures aim to decrease the amount where the stomach surface area is significantly reduced, which decreases
of food ingested, as used in sleeve gastrectomy (SG), vertical banded the amount of hydrochloric acid secreted and increases the gastric pH,
gastroplasty (VBG), adjustable gastric banding (AGB), and gastric leading to poor disintegration, dissolution, and absorption of acid‐soluble
stapling. Malabsorptive procedures reduce the absorption of nu- drugs. Similarly, bariatric procedures that involve resection or bypass of
trients from food, such as in jejunoileal bypass (JIB) and jejunocolic the absorptive areas of the duodenum and proximal jejunum affect the
bypass. Other bariatric procedures combine restrictive and malab- dissolution and absorption of drugs due to a decrease in the surface areas
sorptive techniques to achieve less food volume ingestion and less for intestinal absorption. A long section of the intestines is bypassed in
absorption of nutrients. These techniques are used in Roux‐en‐Y some bariatric procedures; thus, transporters that function as carriers of
gastric bypass (RYGB), distal gastric bypass, duodenal switch, and drug particles across the intestine lumen to the circulation lead to low
biliopancreatic diversion with duodenal switch (BPD‐DS).4,5 Conse- bioavailability of drugs. Furthermore, extended‐release dosage forms are
quently, most drugs are expected to behave differently in a bariatric designed to travel through the gastrointestinal tract to achieve adequate
population compared to a non‐bariatric population. dissolution and absorption. The bypassing of portions of the gastro-
In recent years, SG and RYGB were the most performed intestinal system gives the drug an insufficient transit time to reach full
procedures compared to other procedures, such as JIB, VBG, AGB, absorption and consequently limits the bioavailability of the administered
and BPD‐DS. In SG, a longitudinal resection is performed to create a dose.11 Other drugs, such as lipophilic drugs (i.e., phenytoin, selective
sleeve‐like structure of the stomach along the lesser curvature. serotonin receptors inhibitors, and thyroxin) depend on bile acids, which
Weight loss in SG is achieved by reducing the amount of food intake, function as surfactants to enhance the solubility of the drug molecules.
restricting caloric intake, and promoting a sensation of satiety; The secretion of the bile acids is impaired by the bypass procedure, which
however, the endocrine mechanisms and related changes after SG may lead to the incomplete dissolution and absorption of lipophilic
remain unclear.6 The other procedure discussed in this study is drugs.12 On the other hand, other studies reported an increase in drug
RYGB, which involves partial resection of the stomach to create a absorption which can be attributed to mucosal hypertrophy that causes
small pouch to limit the amount of food intake. This gastric pouch is higher absorptive capacity in the remaining part of the intestines.13
stapled and anastomosed between the pouch and jejunum to disrupt There are currently no guidelines for how to address drug use
the absorption of nutrients and restrict the amount of food after bariatric surgery. Available studies presumed that the altera-
ingested.7,8 These anatomical changes may also interfere with drugs tions in the gastrointestinal system after bariatric surgery are more
absorption, metabolism, and excretion. likely to change drug absorption compared to the non‐bariatric
population. Patient medication counseling should be provided before
hospital discharge to ensure that patients are aware of the change in
2 | M E TH O D S drug absorption after the surgery. Close monitoring of the patients'
use of drugs soon after bariatric surgery is recommended to avoid
PubMed/Medline comprehensive literature search for published adverse effects. If the levels of the drug administered can be obtained
studies (from inception to December 2017) was conducted. We via laboratory tests, it is recommended to monitor the drug levels
used combinations of the following terms “drug absorption,” “bariatric frequently. Due to the impairment of disintegration and dissolution
surgery,” “gastric bypass,” “bypass,” “gastroplasty,” “gastrectomy,” “gas- after bariatric surgery, liquid dosage forms are preferred over solid
tric banding,” “sleeve gastrectomy,” “malabsorption,” “drug use,” phar- dosage forms, if available. Additionally, enteric‐coated, film‐coated,
macodynamic,” and “pharmacokinetic.” We included pharmaco- delayed‐release, or extended‐release tablets are not recommended,
kinetic/pharmacodynamic studies, case reports, and observational and immediate‐release, crushable, or chewable tablets may have
studies in our review. We excluded results from non‐English and fewer variations in absorption after bariatric surgery. A nonoral route
animal studies. of administration, such as intravenous, intramuscular, subcutaneous,
vaginal, rectal, or nasal dosage forms, is preferred to avoid
unpredictable absorption. A limited number of studies have examined
3 | DRUG ABSORPTION AFTER the changes in drug absorption after bariatric surgery. The available
BARIATRIC SUR GERY literature that assessed the absorption of drugs reported either an
increased, decreased, or unchanged absorption after bariatric surgery
There is a paucity of literature that discusses the changes in pharmaco- (Table 1). Due to insufficient data, absorption is concluded to be
kinetics and pharmacodynamics after bariatric surgery. Because obese influenced by many factors; it is “patient‐specific” and “procedure‐
patients are likely to use one or more medications to treat obesity‐related specific,” and each patient should be managed independently.9
ALALWAN ET AL. | 3 of 8

TABLE 1 Summary of the changes in drug absorption after bariatric surgery

Drug Route (dosage form) Procedure Outcome Comments

Amoxicillin Oral (unspecified) RYGB Ineffective A case report of a 29‐year‐old pregnant woman treated with amoxicillin as
well as other orally administered antibiotics. Oral treatment regimens
failed, which could be due to interrupted absorption. IV ceftriaxone was
used to treat the infection.17

Amoxicillin/ Oral (unspecified) RYGB Ineffective A case report of a 29‐year‐old pregnant woman treated with amoxicillin/
clavulanate clavulanate as well as other orally administered antibiotics. Oral
treatment regimens failed, which could be due to interrupted
absorption. IV ceftriaxone was used to treat the infection.17

Acetaminophen Oral (tablet) JIB Unchanged A pharmacokinetic study on 8 bariatric and 15 non‐bariatric patients; pre‐
and postsurgery. Cmax and AUC were similar pre‐ and postsurgery.18

Acetaminophen and Oral (unspecified) SG Unchanged A controlled cohort study compared 24 patients who underwent bariatric
caffeine RYGB surgery and 28 non‐bariatric normal‐weight patients. A lower AUC and
Cmax in morbidly obese compared to healthy non‐bariatric patients and
bariatric patients. The bioavailability was normalized after bariatric
surgery and showed no difference between bariatric surgery patients
and normal weight patients.19

Ampicillin Oral (unspecified) JIB Decreased A pharmacokinetic study on 6 patients. Ampicillin was given as prodrug
pivampicillin and pre‐ and postsurgery ampicillin levels were obtained.
Bioavailability decreased significantly.20

Atorvastatin Oral (unspecified) RYGB Varied A pharmacokinetic study on 12 patients pre‐ and postsurgery. AUC
showed both a threefold increase and twofold decrease pre‐ and
postsurgery.21

Atorvastatin Oral (unspecified) BPD Increased A pharmacokinetic study on 10 patients pre‐ and postsurgery. AUC
showed a twofold increase in both pre‐and postoperation levels.22

Atorvastatin Oral (unspecified) RYGB Decreased A pharmacokinetic study on 12 RYGB and 10 BPD patients assessed pre‐
and BPD and postsurgery. The long‐term effect (27 months) showed a decrease
in the AUC.23

Azithromycin Oral (tablet) RYGB Decreased A pharmacokinetic study on 14 bariatric and 14 non‐bariatric patients. The
AUC was 33% lower in the treatment group.24

Caffeine Oral (powder) RYGB Unchanged A pharmacokinetic study on 18 bariatric and 18 non‐bariatric patients. Cmax
and AUC did not change; however, Tmax was shorter in the RYGB
patients.25

Citalopram Oral (unspecified) RYGB Decreased A pharmacokinetic study on 12 bariatric patients who received SRIs. Two
patients were given citalopram and showed a decrease in the AUC 1
month after surgery; however, the AUC tended to normalize 6 months
after surgery.26

Cyclosporine Oral (unspecified) JIB Decreased A pharmacokinetic study compared one bariatric patient to seven non‐
bariatric patients and showed a 50% lower concentration of cyclosporin
in the bariatric patient.27

Cyclosporine Oral (unspecified) LAGB Unchanged A case report of a patient using cyclosporine after a heart transplant.
Cyclosporine levels remained steady after the surgery.28

Dabigatran Oral (capsule) RYGB Decreased A case report of a 66‐year‐old male patient who showed a left ventricular
systolic dysfunction on transesophageal echocardiogram and abnormal
findings on magnetic resonance imaging alongside other
thromboembolic symptoms. The study indicated that anticoagulation
with dabigatran was subtherapeutic. Later, the patient's symptoms
were improved after bridged with heparin and switched to warfarin.29

Dabigatran Oral (capsule) RYGB Decreased A case report of a 67‐year‐old female patient who showed subtherapeutic
serum trough levels of dabigatran. The patient was switched to warfarin
to evade thromboembolic events.29

(Continues)
4 of 8 | ALALWAN ET AL.

TABLE 1 (Continued)

Drug Route (dosage form) Procedure Outcome Comments

Dextromethorphan Oral (syrup) RYGB Unchanged A pharmacokinetic study on 18 bariatric and 18 non‐bariatric patients. Cmax
and AUC did not change; however, Tmax was shorter in the RYGB
patients.25

Digoxin Oral (tablet) RYGB Unchanged A pharmacokinetic study on 12 bariatric patients pre‐ and postsurgery. Tmax
was lower in the RYGB patients. However, the AUC did not change.30

Digoxin Oral (tablet) JIB Unchanged A pharmacokinetic study on 7 patients pre‐ and postsurgery. The AUC
remained unchanged.31

Duloxetine Oral (unspecified) RYGB Decreased A pharmacokinetic study on 12 bariatric patients who received SRIs. One
patient was given duloxetine and showed a decrease in AUC 1 month
after surgery; however, the AUC tended to normalize at 6 months after
surgery.26

Duloxetine Oral (tablet) RYGB Decreased A case control Pharmacokinetic study on 10 bariatric and non‐bariatric
patients. Bariatric patients were exposed to 57% of the drug compared
to non‐bariatric patients. AUC and Tmax were lower, while Cmax did not
change.32

Escitalopram Oral (unspecified) RYGB Decreased A pharmacokinetic study on 12 bariatric patients who received SRIs. Two
patients were given escitalopram and showed a decrease in the AUC 1
month after surgery; however, the AUC began to normalize at 6 months
after surgery.26

Escitalopram Oral (unspecified) RYGB Decreased A pharmacokinetic study on four patients pre‐ and postsurgery.
Bioavailability decreased after the surgery.33

Ethosuximide Oral (unspecified) JIB Decreased A case report of a patient who underwent JIB surgery and showed a
decrease in ethosuximide absorption; therefore, a dose increase was
warranted.34

Furosemide Oral (tablet) RYGB Unchanged A pharmacokinetic study on 18 bariatric and 18 non‐bariatric patients. The
Cmax and AUC did not change; however, Tmax was shorter in the RYGB
patients.25

Hydrochlorothiazide Oral (unspecified) JIB Decreased A pharmacokinetic study of five patients showed a 50% lower AUC in
bariatric users compared to healthy users.35

Imatinib Oral (unspecified) SG Decreased A case report of a patient who has been treated with imatinib and had
achieved therapeutic plasma concentration levels before bariatric
surgery. After bariatric surgery, the patient had lower Cmax and AUC
levels. The plasma concentration was 60% lower after the surgery.36

Lamotrigine Oral (unspecified) RYGB Unchanged A case report of a patient who was diagnosed with epilepsy and treated
with phenytoin plus phenobarbital. The levels of these two drugs
became subtherapeutic following surgery. Phenytoin was replaced by
lamotrigine, which showed therapeutic levels.37

Levothyroxine Oral (tablet) RYGB Unchanged A pharmacokinetic study on 15 bariatric and 15 non‐bariatric patients. AUC
of the total T4, free T4, and Δ TSH had the same levels in both groups.38

Levothyroxine Oral (tablet) RYGB Decreased A case series of 4 patients who were treated with levothyroxine tablets
showed supra‐therapeutic TSH levels after the surgery compared to the
levels before the surgery. The patients were switched to levothyroxine
oral solution; the TSH levels were then in the normal range.39

Linezolid Oral (unspecified) RYGB Increased A pharmacokinetic crossover pre‐ and postsurgery study. AUC increased
and IV and clearance was decreased after the surgery, suggesting lower doses
after bariatric surgery.40

Metformin Oral (tablet) RYGB Increased A pharmacokinetic trial of 16 bariatric and 16 non‐bariatric patients
matched based on BMI and gender. The bariatric group showed 50%
higher bioavailability and 21% higher AUC.41

Methylphenidate Oral (tablet RYGB Ineffective A case report of an ADHD adult patient who reported a lack of efficacy
immediate after RYGB. Switching an immediate‐release tablet to a slow‐release
ALALWAN ET AL. | 5 of 8

TABLE 1 (Continued)

Drug Route (dosage form) Procedure Outcome Comments

release/slow‐ tablet did not improve the efficacy. A therapeutic effect was obtained
release) after switching to the transdermal dosage form.42

Midazolam Oral (unspecified) RYGB Unchanged A pharmacokinetic study on 18 bariatric and 18 non‐bariatric patients. Cmax
and IV did not change; however, there was a slightly lower AUC and shorter
Tmax in the RYGB patients.25

Midazolam Oral (tablets) RYGB Unchanged A pharmacokinetic study on 18 patients pre‐ and postsurgery.
IV (vial) Bioavailability remained unchanged, although systematic clearance
increased by 1.7‐fold.43

Midazolam Oral (solution) RYGB Unchanged A pharmacokinetic study on 12 bariatric patients; pre‐and postsurgery.
Tmax was lower in the RYGB patients. However, the AUC did not
change.30

Moxifloxacin Oral (tablet) and IV RYGB Increased A pharmacokinetic crossover study on 12 patients who showed higher Cmax
and AUC after bariatric surgery.44

Mycophenolic acid Oral (unspecified) RYGB Decreased A pharmacokinetic study compared the levels of six bariatric patients to the
levels of published levels of non‐bariatric patients. The AUC was
significantly lower in the bariatric patients.45

Nitrofurantoin Oral (unspecified) RYGB Ineffective A case report of a 29‐year‐old pregnant woman treated with nitrofurantoin
among other orally administered antibiotics. Oral treatment regimens
failed, which could be due to interrupted absorption. IV ceftriaxone was
used to treat the infection.17

Omeprazole Oral (unspecified) RYGB Unchanged A pharmacokinetic study on 18 bariatric and 18 non‐bariatric patients. Cmax
and the AUC did not change; however, Tmax was shorter in the RYGB
patients.25

Penicillin V Oral (tablet) JIB Increased A pharmacokinetic study on eight bariatric patients; pre‐and postsurgery.
Cmax and AUC were higher after surgery.18

Oral contraceptives Oral (unspecified) BPD Decreased A prospective pre‐ and postsurgery study using a questionnaire of 40
women. The study concluded that an oral contraceptive may fail when
used in bariatric patients due to a lack of absorption.46

Oral contraceptives Oral (unspecified) JIB Unchanged A pharmacokinetic study on 12 bariatric and 6 non‐bariatric patients to
compare absorption in both groups. The plasma concentration of the
drugs was similar between the groups.47

Oral contraceptives Oral (unspecified) JIB Decreased A pharmacokinetic study on six bariatric and five non‐bariatric patients
concluded that the AUC was lower in bariatric patients.48

Phenytoin Oral (unspecified) RYGB Decreased A case report of a patient who was diagnosed with epilepsy and treated
with phenytoin plus phenobarbital and never had an episode for 30
years. The patient had an episode 1 year after the surgery; phenytoin
levels were subtherapeutic.37

Phenytoin Oral (capsule) JIB Decreased A pharmacokinetic study on seven bariatric and nine non‐bariatric patients.
Absorption and AUC were lower in the bariatric group.49

Phenytoin Oral (unspecified) JIB Decreased A case report of a patient who underwent JIB reversal surgery and showed
a decrease in phenytoin absorption and was recommended to increase
the dose.50

Phenytoin Oral (unspecified) JIB Decreased A case report of a patient who underwent JIB surgery showed a decrease in
phenytoin absorption; therefore, a dose increase was warranted.34

Phenobarbital Oral (unspecified) RGYB Decreased A case report of a patient who was diagnosed with epilepsy and treated
with phenytoin plus phenobarbital and never had an episode for 30
years. The patient had an episode 1 year after the surgery, and
phenobarbital levels were subtherapeutic.37

Propylthiouracil Oral and IV JIB Unchanged A pharmacokinetic study on nine patients; pre‐ and postsurgery. Drug
levels were obtained, and approximately 80% of the drug bioavailability
did not change.20

(Continues)
6 of 8 | ALALWAN ET AL.

TABLE 1 (Continued)

Drug Route (dosage form) Procedure Outcome Comments

Ranitidine Oral (tablet) BPD Unchanged A pharmacokinetic study on seven patients who underwent bariatric
surgery showed AUC and plasma concentrations similar to those in
non‐bariatric patients.51

Ranitidine Oral (tablet) BPD Unchanged A pharmacokinetic study on 10 patients pre‐ and postsurgery and 11
patients who did not go through the surgery. Drug levels were
obtained; Cmax and AUC were similar among the presurgery,
postsurgery, and normal patients.52

Rivaroxaban Oral (tablet) RYGB Unchanged A case report of a patient who was unstable on warfarin anticoagulation
treatment. The patient was switched to rivaroxaban and showed
normal absorption of rivaroxaban.53

Sertraline Oral (unspecified) RYGB Decreased A pharmacokinetic study on 12 bariatric patients who received SRIs. Two
patients were given sertraline and showed a decrease in the AUC 1
month after the surgery; however, the AUC tended to normalize 6
months after the surgery.26

Sirolimus Oral (tablet) RYGB Decreased A pharmacokinetic study compared the levels of six bariatric patients to
published levels of non‐bariatric patients. The AUC was significantly
lower in the bariatric patients.45

Tacrolimus Oral (unspecified) RYGB Decreased A pharmacokinetic study compared the levels of six bariatric patients to the
published levels of non‐bariatric patients. The AUC was significantly
lower in the bariatric patients.45

Tamoxifen Oral (tablet) RYGB Decreased A case series of three women who showed subtherapeutic levels after
surgery.54

Temozolomide Oral (unspecified) RYGB Unchanged A case report of one patient who showed no changes in Cmax or AUC
compared to the data of non‐bariatric patients.55

Tolbutamide Oral (tablet) RYGB Unchanged A pharmacokinetic study on 18 bariatric and 18 non‐bariatric patients. Cmax
and AUC did not change; however, Tmax was shorter in the RYGB
patients.25

Venlafaxine Oral (unspecified) RYGB Decreased A pharmacokinetic study on 12 bariatric patients who received SRIs. Five
patients were given venlafaxine and showed a decrease in AUC 1
month after the surgery; however, the AUC tended to be normalized 6
months after the surgery.26

Warfarin Oral (tablet) RYGB and Resistance A case report of a patient who developed warfarin resistance after bariatric
gas- surgery despite a dose increase.56
trectomy

Warfarin Oral (tablet) RYGB Unchanged A small cohort study matched 27 bariatric surgery patients to 59 non‐
bariatric surgery patients to assess warfarin dose change. Bariatric
surgery patients showed a continuous decrease in warfarin doses
following the surgery compared to non‐bariatric patients. However, the
doses returned to those used in non‐bariatric surgery patients. The
change in INR values did not parallel the change in warfarin doses.57

Abbreviations: ADHD, attention‐deficit/hyperactivity disorder; AUC, area under the curve; BMI, body mass index; BPD, biliopancreatic diversion; Cmax,
maximum serum concentration; INR, international normalized ratio; IV, intravenous; JIB, jejunoileal bypass; LABG Laparoscopic adjustable gastric
banding; RYGB Roux‐en‐Y gastric bypass; SG sleeve gasterectomy; SRI, serotonin reuptake inhibitor; T4, thyroxin; Tmax, time to maximum
concentration; TSH, thyroid‐stimulation hormone.

Collaborations between pharmacists and surgeons can improve 4 | CONCLUSION

perioperative bariatric surgery patients' pharmaceuticals.
Additionally, due to the possible changes in drug absorption and Drug absorption shows variations after bariatric surgery. The
the expected need for drug adjustment, pharmacists' involvement in available data ascribed the variations in absorption to many factors
the drug management and drug reconciliation upon discharge can including route of administration, dosage form, patient‐specific
ensure a safe and effective transition for bariatric surgery factors, type of surgery, and pharmacokinetic/pharmacodynamic
patients.14–16 considerations. Therefore, patient‐tailored therapy with close
ALALWAN ET AL. | 7 of 8

monitoring of drugs is warranted after bariatric surgery. Prescribing 6. Rosenthal RJ. International sleeve gastrectomy expert panel
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