DOI: https://dx.doi.org/10.18203/2349-3291.ijcp20222434
Published: 2022-09-26

Ranitidine use in pediatrics: current evidence-based review and recommendations

Uday A. Pai, Dhanasekhar Kesavelu, Abhay K. Shah, Arun K. Manglik, Arun Wadhwa, Bhaswati Acharya, Deepak Goyal, Lalit Bharadia, Lalit Verma, Nithya Franklyn, Raju C. Shah, Somashekara H. R., Subhashish Bhattacharyya

Abstract


Ranitidine plays a pivotal role in routine pediatric practice. The multi-dimensional use and safety of ranitidine are not supported by any practical guidelines, which led to recommendations convened by a group of experts based on evidence and the clinical experience of experts. A group of general pediatricians and pediatric gastroenterologists from India were part of this panel. This group of experts reviewed the literature on topics that were unanimously agreed upon, for which no recommendations were available. The Delphi method was implemented to reach unified decisions, which led to the development of evidence-based recommendations. Gastritis and gastroesophageal reflux disease (GERD) are common conditions seen in pediatric practice. Ranitidine has a rapid onset of action compared to proton pump inhibitors (PPIs). It is a preferred drug for on-demand use for gastritis and managing stress-induced gastric lesions in critically ill pediatric patients. Ranitidine has an established role in the management of GERD, and it also prevents nocturnal acid reflux effectively. It helps in reducing gastric fluid volume when used as preoperative prophylaxis. Also, ranitidine has a better safety profile in comparison to PPIs. Recommendations on the use and safety of ranitidine in pediatrics were developed which will be a guiding tool for all practicing clinicians, highlighting the strength and benefits of ranitidine as a better and safe alternative to PPIs in short-term acid suppression for multiple indications.


Keywords


Ranitidine, GERD, Gastritis, Nocturnal acid reflux, PPI, H2RA

Full Text:

PDF

References


Leung AKC, Hon KL. Gastroesophageal reflux in children: an updated review. Drugs in Context. 2019;8:212591.

Poddar U. Diagnosis and management of gastroesophageal reflux disease (GERD): An Indian perspective. Indian Pediatr. 2013;50(1):119-26.

Zaterka S, Marion SB, Roveda F, Perrotti MA, Chinzon D. Historical perspective of gastroesophageal reflux disease clinical treatment. Arq Gastroenterol. 2019;56(2):202-8.

Orenstein SR, Blumer JL, Faessel HM, McGuire JA, Fung K, Li BUK, et al. Ranitidine, 75 mg, over-the-counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux: Ranitidine, 75 mg, in children. Aliment Pharmacol Ther. 2002;16(5):899-907.

Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66(3):516-54.

Kothari S, Nelson SP, Wu EQ, Beaulieu N, McHale JM, Dabbous OH. Healthcare costs of GERD and acid-related conditions in pediatric patients, with comparison between histamine-2 receptor antagonists and proton pump inhibitors. Curr Med Res Opin. 2009;25(11):27039.

Dalkey NC. Delphi. RAND Corporation. 1967. Available at: https://www.rand.org/pubs/papers/ P3704.html. Accessed on 02 May 2022.

Singh S, Sharma B, Bairwa M, Gothi D, Desai U, Joshi J, et al. Management of interstitial lung diseases: A consensus statement of the Indian Chest Society (ICS) and National College of Chest Physicians (NCCP). Lung India. 2020;37(4):359-78.

de Martino M, Chiarugi A, Boner A, Montini G, de’ Angelis GL. Working Towards an Appropriate Use of Ibuprofen in Children: An Evidence-Based Appraisal. Drugs. 2017;77(12):1295-311.

Autret-Leca É, Bensouda-Grimaldi L, Maurage C, Jonville-Bera AP. Upper Gastrointestinal Complications associated with NSAIDs in Children. Therapies. 2007;62(2):173-6.

Mohan N, Matthai J, Bolia R, Agarwal J, Shrivastava R, Borkar VV, et al. Diagnosis and Management of Gastroesophageal Reflux Disease in Children: Recommendations of Pediatric Gastroenterology Chapter of Indian Academy of Pediatrics, Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN). Indian Pediatr. 2021;58(12):1163-70.

Sachs G, Shin JM, Howden CW. Review article: the clinical pharmacology of proton pump inhibitors. Aliment Pharmacol Ther. 2006;23(2):2-8.

Hatlebakk JG, Berstad A. Pharmacokinetic Optimisation in the Treatment of Gastro- Oesophageal Reflux Disease: Clin Pharmacokinet 1996;31(5):386-406.

Abu El-Ella SS, Said El-Mekkawy M, Mohamed Selim A. Stress ulcer prophylaxis for critically ill children: Routine use needs to be re-examined. Anales de Pediatría. 2022;96(5):402-9.

Lugo RA, Harrison AM, Cash J, Sweeley J, Vernon DD. Pharmacokinetics and pharmacodynamics of ranitidine in critically ill children: Crit Care Med. 2001;29(4):759-64.

Kuusela AL, Ruuska T, Karikoski R, Laippala P, Ikonen RS, Janas M, et al. A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients: Crit Care Med. 1997;25(2):346-51.

López-Herce J, Dorao P, Elola P, Delgado MA, Ruza F, S RM. Frequency and prophylaxis of upper gastrointestinal hemorrhage in critically ill children: A prospective study comparing the efficacy of almagate, ranitidine, and sucralfate. Crit Care Med. 1992;20(8):1082-9.

Frykholm P, Disma N, Andersson H, Beck C, Bouvet L, Cercueil E, et al. Pre-operative fasting in children: A guideline from the European Society of Anaesthesiology and Intensive Care. Eur J Anaesthesiol. 2022;39(1):4-25.

Gombar S, Dureja J, Kiran S, Gombar K, Chhabra B. The effect of pre-operative intake of oral water and ranitidine on gastric fluid volume and pH in children undergoing elective surgery. J Indian Med Assoc. 1997;95(6):166-8.

Sandhar BK, Goresky GV, Maltby JR, Shaffer EA. Effect of Oral Liquids and Ranitidine on Gastric Fluid Volume and pH in Children Undergoing Outpatient Surgery. Anesthesiology. 1989;71(3):327-30.

Peghini PL, Katz PO, Bracy NA, Castell DO. Nocturnal Recovery of Gastric Acid Secretion With Twice-Daily Dosing of Proton Pump Inhibitors. Am J Gastroenterol. 1998;93(5):763-7.

Pfefferkorn MD, Croffie JM, Gupta SK, Molleston JP, Eckert GJ, Corkins MR, et al. Nocturnal Acid Breakthrough in Children with Reflux Esophagitis Taking Proton Pump Inhibitors. J Pediatr Gastroenterol Nutr. 2006;42(2):160-5.

Dipasquale V, Cicala G, Spina E, Romano C. A Narrative Review on Efficacy and Safety of Proton Pump Inhibitors in Children. Front Pharmacol. 2022;13:839972.

Cohen S, Bueno de Mesquita M, Mimouni FB. Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review. Br J Clin Pharmacol. 2015;80(2):200-8.

De Bruyne P, Ito S. Toxicity of long-term use of proton pump inhibitors in children. Arch Dis Child. 2018;103(1):78-82.

Li J, Xie X, Liu W, Gu F, Zhang K, Su Z, et al. Acid-Suppressive Drugs and Risk of Fracture in Children and Young Adults: A Meta-Analysis of Observational Studies. Front Pharmacol. 2021;12:712939.

Yang J, Zhou TJ, Yang J, Bao DN. Use of acid-suppressive drugs and risk of fracture in children and young adults: a meta-analysis of observational studies. Eur J Clin Pharmacol. 2022;78(3):365-373.

Wang YH, Wintzell V, Ludvigsson JF, Svanström H, Pasternak B. Association Between Proton Pump Inhibitor Use and Risk of Fracture in Children. JAMA Pediatr. 2020;174(6):543-51.

Wang YH, Wintzell V, Ludvigsson JF, Svanström H, Pasternak B. Association Between Proton Pump Inhibitor Use and Risk of Asthma in Children. JAMA Pediatr. 2021;175(4):394-403.

Levy EI, Hoang DM, Vandenplas Y. The effects of proton pump inhibitors on the microbiome in young children. Acta Paediatr. 2020;109(8):1531-8.

Anjewierden S, Han Z, Foster CB, Pant C, Deshpande A. Risk factors for Clostridium difficile infection in pediatric inpatients: A meta-analysis and systematic review. Infect Control Hosp Epidemiol. 2019;40(4):420-6.

Chang TH, Hsu WY, Yang TI, Lu CY, Hsueh PR, Chen JM, et al. Increased age and proton pump inhibitors are associated with severe Clostridium difficile infections in children. J Microbiol Immunol Infect. 2020;53(4):578-84.

Holbrook JT, Wise RA, Gold BD, Blake K, Brown ED, Castro M, et al. Lansoprazole for children with poorly controlled asthma: A randomized controlled trial. JAMA. 2012;307(4):373-80.

McCrory BE, Harper HN, McPhail GL. Use and incidence of adverse effects of proton pump inhibitors in patients with cystic fibrosis. Pharmacotherapy. 2018;38(7):725-9.

Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z. Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD. JASN. 2016;27(10):3153-63.

Xu X, Nie S, Zhang A, Mao J, Liu HP, Xia H, et al. Acute Kidney Injury among Hospitalized Children in China. Clin J Am Soc Nephrol. 2018;13(12):1791-800.

Li Y, Xiong M, Yang M, Wang L, Nie S, Liu D, et al. Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children. Ann Transl Med. 2020;8(21):1438.

Pappa KA, Williams BO, Payne JE, Buaron KS, et al. A double blind, placebo-controlled study of the efficacy and safety of non-prescription ranitidine 75 mg in the prevention of meal-induced heartburn. Aliment Pharmacol Ther. 1999;13:467-73.

Nugent CC, Falkson SR, Terrell JM. H2 Blockers. Treasure Island (FL): StatPearls Publishing. 2022.

Sasaran MO, Melit LE, Mocan S, Ghiga DV, et al. Pediatric gastritis and its impact on hematologic parameters. Medicine (Baltimore). 2020;99(35):21985.

Tutuian R, Castell DO. Nocturnal Acid Breakthrough - Approach to Management. Med Gen Med. 2004;6(4):11.

Shim YK, Kim N. The Effect of H2 Receptor Antagonist in Acid Inhibition and Its Clinical Efficacy. Korean J Gastroenterol. 2017;70(1):4-12.

Dipasquale V, Cicala G, Spina E, Romano C. A narrative review on efficacy and safety of proton pump inhibitors in children. Front Pharmacol. 2022;13:8399725.