Subject: In-Practice Usage and Performance (IPUP) Study of Roles20 mg tablets/ Roles –D capsule and Roles-L capsule;

Study code: IPUP/Roles /Stanlife /April 2023

Gastroesophageal reflux (GERD) is a frequent condition characterized by various clinical manifestations ranging from typical (heartburn), to many extra-esophageal disorders such as non-cardiac chest pain, respiratory disorders (chronic cough, asthma, and sleep apnea), laryngeal disorders (hoarseness, posterior laryngitis, and sub-glottic stenosis), and other ear, nose, and throat (ENT) disorders (chronic sore throat, pharyngitis, sinusitis, globus sensation, and otalgia).^I,II,III,IV

At least four factors contribute to the pathogenesis of GERD : (1) an incompetent anti-reflux barrier because of lower esophageal sphincter (LES) dysfunction, (2) esophageal irritation by the refluxate, especially acid and pepsin (3) motility disturbances of the esophagus leading to decreased clearing capacity of refluxed material; and (4) delayed gastric emptying increasing the risk of reflux. Furthermore, the resistance of esophageal tissue to reflux-induced injury also seems to play a role.

Proton pump inhibitors (PPIs) are first-line agents used in the treatment of patients with GERD. PPIs have been shown to be clinically superior to H2-receptor antagonists in terms of healing esophagitis and resolution of GERD symptoms.^VII,VIII,IX

Rabeprazole is a proton pump inhibitor. Pharmacodynamic data show rabeprazole can achieve optimal acid suppression since the first administration and can maintain this advantage in the following days of therapy. ^X

Rabeprazole has the highest pKa (~ 5.0, the pH at which a drug becomes 50% protonated), and hence the molecule can be activated at higher pH levels much faster than other PPIs.⁹

Due to its peculiar catabolic pathway, i.e., a prevalent metabolism through a non-enzymatic pathway, rabeprazole is less susceptible to the influence of genetic polymorphisms for CYP2C19, resulting in minor influences on its pharmacokinetics and pharmacodynamics.⁹

ROLES 20 mg tablets (Rabeprazole 20 mg tablets), ROLES-D capsules (Rabeprazole 20 mg enteric coated + Domperidone 10 mg immediate release and 20 mg sustained-release) and ROLES-L capsule (Rabeprazole 20 mg enteric coated + Levosulpiride 75 mg sustained-release) are marketed by the ‘Stanlife’ team of Sun Pharmaceutical Industries Ltd..

Although every product is marketed only after regulatory approval, it is important to know how it performs in day-to-day practice of individual medical practitioners. For this purpose, we have planned to conduct a prospective study to assess the real-life performance of ROLES in patients with respiratory tract infection, dental infections and skin and skin structure infections.

We invite you to participate in this study. All you need to do is to report on a standard form your experience with ROLES in these patients (to avoid any bias) in whom you prescribe this product in the normal course of your practice. Thus, this is not an experimental study because the product will be prescribed and purchased as you and your patients normally do.