Indian Experts Opinion on Proton Pump Inhibitors in Pediatrics: Too much of a good thing!
Proton Pump Inhibitors (PPIs) have been widely used to treat acid peptic diseases for around three decades but have been under the scanner with reference to their safety from time to time. Despite the emergence of PPIs, H2 receptor antagonists (H2RAs), like ranitidine, have gained and sustained popularity among Pediatricians, owing to their effectiveness and better long-term safety profile. Since its introduction in the mid-1970s, Ranitidine has played a key role in the pharmacotherapy of gastrointestinal conditions in adults and children. (1,2)
With a peak incidence of 60–70% among infants, gastroesophageal reflux disease (GERD) is one of the most commonly diagnosed illnesses among children. Due to the vulnerability of Pediatric patients, safety becomes as important as efficacy while selecting pharmacotherapy for the management of GERD, and Pediatricians require guidelines and recommendations for this purpose. (1)
The gap in recommendations about the clinical applicability of Ranitidine in children prompted thirteen Indian Pediatricians and Pediatric Gastroenterologists to come together from across the country and review Ranitidine against PPIs on parameters of efficacy, tolerability, and safety. This national evidence-based review has been published in the recent edition of ‘The International Journal of Contemporary Pediatrics. (1)
Acid suppression therapies are used frequently and for longer duration; hence the consideration for long-term safety is of critical importance while selecting a specific agent.
The review made the following recommendations-
1. “The incidence of gastrointestinal and non-gastrointestinal side-effects with long-term use of PPIs is higher than ranitidine”.
2. “The long-term use of ranitidine therapy for acid suppression has a reduced risk of fracture in comparison to PPI use”.
3. “The risk of dysbiosis, Clostridium difficile, and respiratory infections is higher with PPIs as compared to ranitidine”.
4. “The risk of acute kidney injury is higher with the use of PPI as compared to ranitidine”.
Speaking to Medical Dialogues on the issue of adverse effects of PPIs and Ranitidine, Dr. Arun Kumar Manglik, Senior Consultant Pediatrician, Ankur Clinic, Kolkata, said- “As we all know, no drug is free of side effects, and the same applies to PPIs. The long-term use of PPIs is known to play a role in developing kidney disorders, bone health disturbances, lung issues, and asthma in some cases.”
“Ranitidine, per se, is a safer alternative for PPIs. Ranitidine can be given even in infancy. One would use PPIs cautiously in young children, particularly infants or neonates. Ranitidine can even be used in newborns.” he added.
In addition to tolerability and safety, the review also highlighted the ease of metabolization of Ranitidine in the body compared to PPIs, making it a better choice for treating gastrointestinal conditions in children. (3)
Medical Dialogues spoke to Dr. Subhashish Bhattacharyya, HOD & Prof. Dept. of Pediatrics, CSS College Obstetrics, and Gynaecology and Child Health Kolkata. He explained- “Multiple studies have revealed the association between chronic use of PPIs and acute renal disease and its recurrent episodes, which may lead to chronic renal disease, with a possible mechanism of PPI causing hypomagnesemia. Ranitidine scores better in this respect, with fewer reports in such cases.”
“The quick onset of action of Ranitidine and multiple morbidities associated with the long-term use of PPIs favors Ranitidine use in children even with no renal disease history”, he noted.
Besides the tolerability of Ranitidine, the review also reflected the pediatricians’ concerns that revolved around the continually rising incidence of poor bone health along with poor mineral absorption from the gut in children.
On the connection between PPIs and the bone health of children, Dr. Lalit Verma, Consultant Paediatric Gastroenterologist & Hepatologist at Wockhardt and Global Hospital, Mumbai opined-
“PPIs hamper the absorption of calcium and essential minerals, and long-term use of PPIs is tied with a higher risk of fracture; Reportedly, the risk increases among those who used PPIs for more than three months. This is not seen with the long-term use of Ranitidine, making it the safer alternative.”
“It is important to monitor the Vitamin D serum level while using either of the drugs” he added.
Further, PPIs are linked with an increased risk of dysbiosis, and Clostridium difficile and respiratory infections Four weeks of PPI therapy modifies the microbiome of the mouth, gut, and lungs by inhibiting gastric acid secretion, causing PPI-associated dysbiosis, which is a prodrome of the gut and respiratory infections. Additionally, reduced gastric mucus viscosity and leucocyte activity due to the administration of PPIs raised the risk of Clostridium difficile infections. (1)
Explaining PPI-associated dysbiosis, Dr. Nithya Franklyn, Senior Consultant Pediatrician & Neonatologist, Vijaya Group of Hospitals, Vihaa Hospitals Chennai, said-
“Dysbiosis plays multiple roles in infantile colic and in many functional GI disorders, functional dyspepsia, functional constipation in newborns, and decreasing immunity in children. Dysbiosis, gastroenteritis, and gut-brain axis play an essential role in the development of allergies in children.”
“The quicker onset of action, desirable effect and no undesirable side effects, ease of delivery where most PPIs are not available in syrup form, better tolerance, less renal impairment, less drastic fall in pH, and lesser resultant bacterial infection risk makes Ranitidine score over PPIs”, she added.
In children, the situation could be more threatening because dysbiosis makes them prone to respiratory tract infections (RTIs) and asthma exacerbations.
The panellists unanimously opined that in light of such robust evidence, Ranitidine represents a better and safer choice for use among infants and children who present with gastrointestinal problems.
Reference:
1. Pai UA, Kesavelu D, Shah AK, Manglik AK, Wadhwa A, Acharya B, et al. Ranitidine use in pediatrics: current evidence-based review and recommendations. Int J Contemp Pediatr 2022;9:987-97.
2. Marchetti F, Gerarduzzi T, Ventura A. Proton pump inhibitors in children: a review. Dig Liver Dis. 2003 Oct;35(10):738-46. doi: 10.1016/s1590-8658(03)00420-1. PMID: 14620626.
3. McColl KE, Kennerley P. Proton pump inhibitors--differences emerge in hepatic metabolism. Dig Liver Dis. 2002 Jul;34(7):461-7. doi: 10.1016/s1590-8658(02)80102-5. PMID: 12236477.
