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Esomeprazole-prokinetic combination: A novel approach to managing GERD

Written By : Dr. Shubham Vatsya |Medically Reviewed By : Dr. Kamal Kant Kohli Published On 2021-11-27T12:03:38+05:30  |  Updated On 27 Nov 2021 3:14 PM IST
Esomeprazole-prokinetic combination: A novel approach to managing GERD
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Gastroesophageal reflux disease (GERD) is emerging as a major health concern, having a strikingly high prevalence rate of 7.6% to 33%, varying among the global population. (1) 30% of the GERD patients continue to manifest symptoms even after being treated with the standard doses of Proton Pump Inhibitors (PPI)s, a fact, well documented in researches. (2)

One- Third of Patients Fail to Respond with PPI
Besides the chief symptoms of heartburn and regurgitation, studies have demonstrated that 50% of GERD patients may have symptoms of esophageal dysmotility like epigastric discomfort or fullness, nausea, and early satiety. (3) With a multifactorial etiology, a widely variable healing rate of 60-70%, 20-30%, and 6-10% in the symptoms of GERD has been noted across different populations, in response to PPI monotherapy. (4) Specifically speaking,
one-third of patients with GERD fail to respond symptomatically to a standard dose PPI, either partially or completely (4)
. Such unpredictable results warrant the addition of prokinetic agents, along with PPIs, thus assuring an optimized management therapy of GERD.
How does a prokinetic drug help in GERD?
One of the major key factors responsible for GERD is a motor imbalance of the lower esophageal sphincter (LES), leading to slow esophageal wall contractions, abnormal esophageal clearing, delayed gastric emptying, and increased transient LES relaxation. (5, 6). Prokinetic drugs work by raising the LES basal pressure, improving esophageal peristalsis, accelerating esophageal acid clearance, and facilitating gastric emptying.
Prokinetics also improve the pharmacokinetics of PPIs, which are usually unstable in gastric acid. Rapid and consistent peristalsis facilitates in rapid transit of PPIs into the intestine, exerting a better therapeutic effect. (7)
Among the prokinetics agents available, Metoclopramide, Domperidone, Mosapride, Itopride, and Cisapride have been widely studied as an add-on to PPI therapy for GERD.(8)
4 weeks of Treatment With PPI+ Prokinetic helps
A recent comprehensive meta-analysis (9) has identified mosapride, domperidone, acotiamide, and revexepride as effective prokinetics in GERD patients when combined with PPI. The authors further elaborated that patients treated for at least 4 weeks, those receiving PPI plus prokinetics therapy were found to show a greater reduction in GERD symptoms than patients receiving PPI monotherapy, thereby suggesting that while prescribing a combination of prokinetics and PPI to patients with GERD, a treatment regimen of at least 4 weeks should be recommended.
Esomeprazole –prokinetic combination: Fighting GERD at its best
Esomeprazole, regarded as the most potent acid suppressor among all the PPIs have already proven their supreme efficacy in managing GERD. (10)
Evidence-based studies supporting esomeprazole –prokinetic combination in GERD have been summarised below.
A study by Yu Kyung Cho and team, aimed at assessing the effect of Mosapride, a prokinetic drug, with esomeprazole on the esophageal peristaltic function in patients with GERD affirmed that the combination affected esophageal peristalsis by improving esophageal contractibility and lowering IBP, that could lead to facilitating esophageal bolus transit. (11)
Another study by Biltagi and co-workers, that examined the efficacy of esomeprazole monotherapy vs its combination with domperidone, a prokinetic, in those who had GERD, concluded that a combination of domperidone and esomeprazole was more effective in improving the endoscopic reflux score. (12)
Yet another trial investigating the efficacy and safety of esomeprazole single therapy versus mosapride and esomeprazole combined therapy in patients with GERD highlighted that tendency for upper abdominal pain, belching, and total GERD symptoms scores improve more rapidly in the combination group, suggesting that esomeprazole and mosapride are useful for rapid improvement of specific GERD symptoms. (13)
A major Indian study evaluating the clinical efficacy, tolerability, and safety of a fixed-dose combination of Esomeprazole 20 mg and sustained release (SR) Domperidone 30mg administered once daily in adult Indian patients for the symptomatic relief of dyspepsia associated with GERD has concluded that the combination drug therapy was very effective and a well-tolerated therapeutic option in the management of symptomatic relief of GERD.(14)
With such a rising number of researches targeted at exploring the unique dual therapy of esomeprazole plus prokinetics, establishing its unparalleled authority in managing GERD remains only a matter of time.
What Guidelines Recommend
Acknowledging the superior efficacy of dual drug therapy in GERD, an Asia-Pacific consensus on the management of gastroesophageal reflux disease has concluded that the use of prokinetic agents as adjunctive therapy to PPIs may have a role in the treatment of GERD in Asia. (15) Current guidelines recommend the use of prokinetics in combination with PPIs in GERD patients who exhibit an insufficient response to PPI alone. (4)
Take home message for clinicians
- Evidence points out certain key facts about the combination of esomeprazole with a prokinetic, which if implemented properly can lead to adequate control of GERD-related symptoms.
ï‚· Esomeprazole-prokinetic acts best in cases of refractory GERD, or when symptoms keep relapsing despite completion of PPI monotherapy.
ï‚· Owing to the synergistic action of the two drugs together, studies have affirmed their superior success in managing GERD, specifically when advised for more than 4 weeks continuously.
ï‚· Physicians should keep themselves updated to utilize the advantages provided by the combination therapy, as and when needed.
Conclusion
With growing evidence highlighting that there has been a drastic increase in GERD prevalence since 1995, particularly in East Asia (9), it is high time to consider prokinetics as an adjunct to PPIs for successful resolution of GERD. Future studies based on empirical drug therapy of esomeprazole and prokinetic drugs targeted to treat GERD, depending on individualized needs and severity of the disease will lead the way forward in establishing the best pharmacological remedy for GERD.
References
1. Bhatia SJ, Makharia GK, Abraham P, Bhat N, Kumar A, Reddy DN, Ghoshal UC, Ahuja V, Rao GV, Devadas K, Dutta AK, Jain A, Kedia S, Dama R, Kalapala R, Alvares JF, Dadhich S, Dixit VK, Goenka MK, Goswami BD, Issar SK, Leelakrishnan V, Mallath MK, Mathew P, Mathew P, Nandwani S, Pai CG, Peter L, Prasad AVS, Singh D, Sodhi JS, Sud R, Venkataraman J, Midha V, Bapaye A, Dutta U, Jain AK, Kochhar R, Puri AS, Singh SP, Shimpi L, Sood A, Wadhwa RT. Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology. Indian J Gastroenterol. 2019 Oct;38(5):411-440. doi: 10.1007/s12664-019-00979-y. Epub 2019 Dec 5. PMID: 31802441.
2. Vedamanickam, D.R., Arunprasath, D., Vinothkumar, D.R., & Dasan, D.S. (2016). Evaluation of the efficacy, tolerability, and safety of a combination of esomeprazole and domperidone in GERD.
3. Champion MC. Prokinetic therapy in gastroesophageal reflux disease. Can J Gastroenterol. 1997 Sep;11 Suppl B:55B-65B.PMID: 9347180.
4. Kahrilas, P. J., Boeckxstaens, G., & Smout, A. J. (2013).Management of the patient with incomplete response to PPI therapy. Best practice & research. Clinical gastroenterology, 27(3),401–414. https://doi.org/10.1016/j.bpg.2013.06.005
5. De Giorgi, F., Palmiero, M., Esposito, I., Mosca, F., & Cuomo, R.(2006). Pathophysiology of gastro-oesophageal reflux disease.Acta otorhinolaryngologica Italica : organo ufficiale della Societaitaliana di otorinolaringologia e chirurgia cervico-facciale, 26(5),241–246.
6. Kawada, A., Kusano, M., Hosaka, H., Kuribayashi, S.,Shimoyama, Y., Kawamura, O., Akiyama, J., Yamada, M., &Akuzawa, M. (2017). Increase of transient lower esophageal sphincter relaxation associated with cascade stomach. Journal of clinical biochemistry and nutrition, 60(3), 211–215.https://doi.org/10.3164/jcbn.16-53
7. Ren, L. H., Chen, W. X., Qian, L. J., Li, S., Gu, M., & Shi, R. H.(2014). Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis. World journal of gastroenterology, 20(9), 2412–2419. https://doi.org/10.3748/wjg.v20.i9.2412
8. Wang, Y.-K., Hsu, W.-H., Wang, S. S. W., Lu, C.-Y., Kuo, F.-C.,Su, Y.-C., … Kuo, C.-H. (2013). Current Pharmacological Management of Gastroesophageal Reflux Disease. Gastroenterology Research and Practice, 2013, 1–12.doi:10.1155/2013/983653
9. Jung, Da Hyun & Huh, Cheal & Lee, Sang & Park, Jun Chul &Shin, Sung & Lee, Yong. (2021). A Systematic Review and Meta-analysis of Randomized Control Trials: Combination Treatment With Proton Pump Inhibitor Plus Prokinetic for Gastroesophageal Reflux Disease. Journal of neuro gastroenterology and motility. 27. 165-175. 10.5056/jnm20161.
10. Kalaitzakis, E., & Björnsson, E. (2007). A review of esomeprazole in the treatment of gastroesophageal reflux disease (GERD). Therapeutics and clinical risk management, 3(4),653–663.
11. Cho, Y.K., Choi, MG., Park, E.Y. et al. Effect of Mosapride Combined with Esomeprazole Improves Esophageal Peristaltic Function in Patients with Gastroesophageal Reflux Disease: A Study Using High-Resolution Manometry. Dig Dis Sci 58, 1035–1041 (2013). https://doi.org/10.1007/s10620-012-2430-y
12. Taghvaei, T., Kazemi, A., Hosseini, V., Hamidian, M., Tirga Fakheri, H., Hashemi, S. A., & Maleki, I. (2019). Evaluation of the Additive Effect of Domperidone on Patients with Refractory Gastroesophageal Reflux Disease; A Randomized Double Blind Clinical Trial. Middle East Journal of digestive diseases, 11(1),24–31. https://doi.org/10.15171/mejdd.2018.124
13. Lee JY, Kim SK, Cho KB, Park KS, Kwon JG, Jung JT, Kim EY, Jang BI, Lee SH; Daegu-Gyeongbuk Gastrointestinal Study Group (DGSG). A Double-blind, Randomized, Multicenter Clinical Trial Investigating the Efficacy and Safety of Esomeprazole Single Therapy Versus Mosapride and Esomeprazole Combined Therapy in Patients with Esophageal Reflux Disease. J Neurogastroenterol Motil. 2017 Apr 30;23(2):218-228. doi: 10.5056/jnm16100. Erratum in: J
Neurogastroenterol Motil. 2019 Jan 31;25(1):175. PMID: 28192647; PMCID: PMC5383116.
14. Evaluation of the efficacy, tolerability and safety of a combination of esomeprazole and domperidone in gerd. Dr. R.Vedamanickam, 2Dr. D. Arunprasath, 3 Dr. R. Vinothkumar, 4Dr.Sakthi Dasan; World Journal of Pharmaceutical Research; Volume 5, Issue 10, 857-865.
15. Fock KM, Talley NJ, Fass R, Goh KL, Katelaris P, Hunt R,Hongo M, Ang TL, Holtmann G, Nandurkar S, Lin SR, Wong BC,Chan FK, Rani AA, Bak YT, Sollano J, Ho KY, Manatsathit S.Asia-Pacific consensus on the management of gastroesophageal reflux disease: update. J Gastroenterol Hepatol. 2008 Jan;23(1):8-
22. doi: 10.1111/j.1440-1746.2007.05249.x. Erratum in: JGastroenterol Hepatol. 2008 Mar;23(3):504. Ho, Lawrence K Y [corrected to Ho, Khek Yu]. PMID: 18171339.
GERDEsomeprazoleEsomeprazole prokinetic combinationPPIProton Pump InhibitorProkinetic drugnightime gerddomperidoneacotiamiderevexepride
Dr. Shubham Vatsya
Dr. Shubham Vatsya

    Dr. Vatsya has completed three professional Degrees, a graduation degree MBBS from University College Of Medical Sciences, New Delhi, a post-graduation MD in Internal Medicine from Maulana Azad Medical College, New Delhi, and a super specialty degree DM in Gastroenterology and has been rewarded by renowned personalities for excelling vastly in this domain. He was granted the Smt. Ram Pyari Gold Medal and Shri L.N. Chugh Memorial Gold Medal for getting the first position in Medicine in MBBS. The second one was the K. Sridharan Gold Medal for his first position in Pharmacology. He also won the Young Scholar Award Gastroenterology 2017.

    Dr. Kamal Kant Kohli
    Dr. Kamal Kant Kohli

    Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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