Discourage Use of Proton Pump Inhibitors in Children Below 1 Year of Age: Guidelines from Indian Society of Gastroenterology

The guidelines are published online in the September 2023 issue of the Indian Journal of Gastroenterology, and are formulated to rationalize the use of PPIs. This paper represents the guidelines in detail, including statements, a review of the literature, a level of evidence, and recommendations. The guideline aims to help clinicians optimize the use of PPIs in their clinical practice and, importantly, emphasize PPI stewardship.

The guideline issued strongly condemns the use of PPIs in children below one year of age as a “Strong” strength of recommendation with “good clinical practice” based level of evidence. This advice arises from considerations of age-specific dosing and associated potential risks.

Infants and younger children often require higher doses of PPIs due to faster metabolism; however, it should not exceed the higher end of the dose used in adults.

It is obligatory to exercise restraint and avoid prescribing PPIs to children below one year of age due to their developing physiological systems and limited evidence supporting their efficacy in this age group. Studies have raised concerns about potential long-term effects on bone health, altered gut microbiota, and increased risk of infections associated with PPI usage in children.

The guideline further noted that the dose-related effects of PPIs have not been validated appropriately in newborns, and certain enzymes involved in their clearance take five to six months to attain maturation of activity. Recommendations from various society guidelines re-iterate the ineffectiveness of PPI for symptoms usually attributed to GERD (Gastroesophageal Reflux Disease) in otherwise healthy infants, such as sleep disturbance, irritability, or unexplained crying. Also, evidence of supporting PPI trials for the diagnosis of extra-esophageal symptoms of GERD and use beyond the management of erosive esophagitis or acid reflux symptoms is lacking in the pediatric population.

Co-prescribing PPI with Antibiotics: Need to Be Cautious

These guidelines bring out evidence-based recommendations suggesting routine co-prescription of PPIs with antibiotics is not needed as a “Strong” strength of recommendation.

According to the guidelines, it is advised to avoid routine co-prescription of Proton Pump Inhibitors (PPIs) alongside antibiotics, except for Helicobacter pylori eradication therapy. Combining antibiotics and PPIs heightens the risk of Clostridiodes difficile infection (CDI)-related diarrhea, as substantiated in pre-clinical and clinical studies. This combination can lead to alterations in gut microbiota, further increasing the risk of CDI. A population-based study demonstrated a higher likelihood of CDI-associated diarrhea in individuals using antibiotics alongside PPIs. This depicts the need for careful consideration when combining these medications.

• Routine Use of Fixed-dose Combination Therapy of PPIs with Prokinetic Agents Not Recommended in GERD: PPIs are frequently used in combination with prokinetics to treat GERD by increasing stomach emptying, peristalsis, and lower esophageal sphincter pressure. However, it must be well-established to support the regular use of such a combination. Prokinetics may be used in addition to PPIs for symptoms similar to dysmotility and an insufficient PPI response. The recommendations of the Indian Society of Gastroenterology (ISG) and the American College of Gastroenterology (ACG) prohibit routine prokinetic use in GERD patients without objective gastroparesis evidence. Similarly, prokinetics are not suggested in GERD management guidelines for healthy children with isolated regurgitation.
• Routine Use of PPIs with Selective Serotonin Reuptake Inhibitors (SSRIs) is Not Recommended: Gastrointestinal (GI) bleeding is more prevalent when SSRIs are prescribed. In one meta-analysis, when SSRIs and NSAIDs are used together, co-prescribing acid-suppressing medicines reduces this risk, but not when SSRIs are used alone. However, recommendations regarding PPI/antisecretory medicines should be individualized due to significant interactions and potential adverse effects, particularly in individuals taking multiple medications or suffering from comorbid conditions.
• Routine Use of PPIs with Corticosteroids is Not Recommended: Routine PPI prophylaxis is not recommended with patients on short or long-term corticosteroids treatment. This is due to a lack of quality data showing PPI prophylaxis reduces the risk of GI bleeding or perforation in this patient population.
• Routine PPI Prophylaxis among NSAID users is Not Recommended: Additionally, the new guideline recommended routine PPI prophylaxis is not recommended for all patients on non-steroidal anti-inflammatory drugs. The consideration for the use of PPIs among patients taking NSAIDs is recommended based on the risk assessment for the prevention of GI complications.

Reference: Dutta, Amit Kumar et al. “Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship.” Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology, 10.1007/s12664-023-01428-7. September 12 2023, doi:10.1007/s12664-023-01428-7