Rabeprazole is a proton-pump inhibitor (PPI) that lowers the amount of acid produced in the stomach. This substituted benzimidazole PPI belongs to the class of antisecretory compounds. ^[1] 

Pharmacological Class: Proton Pump Inhibitor (PPI)

It is indicated^[2];

(a) In pediatric patients 1 to 11 years of age

• To treat gastroesophageal reflux disease (GERD) 

(b) In adults for:

• Treatment of symptomatic GERD and heartburn
• Healing and relief of duodenal ulcers
• Healing and symptomatic relief of erosive or ulcerative GERD
• Helicobacter pylori (H. pylori) elimination to lower recurrence risk of duodenal ulcer
• Maintenance of healing of erosive or ulcerative GERD
• Treating pathological hypersecretory conditions, including Zollinger-Ellison Syndrome

(b) In adolescent patients 12 years of age and older for:

• Short-term treatment of symptomatic GERD

Rabeprazole inhibits the secretion of gastric acid by suppressing the gastric H+ , K+ ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. However, this gastric proton-pump inhibitor does not demonstrate anticholinergic or histamine H2-receptor antagonist properties. It hinders the final step of secretion of gastric acid. In the parietal cells, rabeprazole is protonated, accumulates, and is potentially transformed to an active sulfenamide. ^[3]

Absorption

Absolute bioavailability is about 52%.

Volume of distribution

0.34 L/kg*

Protein binding

96.3% bound to human plasma proteins

Metabolism

Rabeprazole is metabolized to the active metabolite of rabeprazole

Route of elimination

After a single 20 mg oral dose of 14C-labeled rabeprazole, about 90% of rabeprazole was excreted via urine, primarily as thioether carboxylic acid; its glucuronide, and mercapturic acid metabolites. The remainder dose was recovered in stools.

Half-life

1-2 hours (in plasma)

Clearance^[3]

Not Available 

History of hypersensitivity to rabeprazole^[2]

• Rabeprazole may lower plasma levels of atazanavir
• Rabeprazole has been demonstrated to lower cyclosporine metabolism in vitro
• Rabeprazole may elevate serum levels of methotrexate
• Elevated International normalized ratio (INR) and prothrombin times have been noted with concomitant usage with warfarin
• Rabeprazole impedes gastric acid secretion and may hinder the absorption of drugs where gastric pH is a vital determinant of bioavailability (like ketoconazole, mycophenolate mofetil, iron salts, and digoxin)^2]

• Diarrhea
• Headache
• Increased risk of fractures of hip, spine, or wrist
• Pain, pharyngitis, flatulence, infection
• Cyanocobalamin/Vitamin B12 deficiency 
• Abdominal pain
• Acute interstitial nephritis
• Low magnesium levels
• Sore throat^[2]

• Should be avoided in pregnant females as it may cause fetal harm
• Should not be used to treat GERD in pediatric patients younger than one year of age^[2]

Rabeprazole has comparable H. pylori elimination rates as omeprazole ^[4]

A study demonstrated that in acid-peptic disorder patients having H. pylori infection, rabeprazole has comparable H. pylori elimination rates in comparison with omeprazole when co-administered with the antibiotics like clarithromycin and amoxicillin for about two weeks.

A study was carried to investigate the efficacy of rabeprazole (20 mg) vs. omeprazole (40 mg) in the triple therapy regimen. Overall, 100 H. pylori-infected patients who gave their consent for trial participation were incorporated. In total, 50 subjects were given omeprazole-based triple treatment and the other 50 subjects were given rabeprazole-based triple treatment. Following two weeks of triple therapy and four weeks of proton pump inhibitor therapy, H. pylori antigen was tested in stools.

A substantial correlation was noted between nausea, epigastric pain, and water brash with a p-value, 0.001. Similarly, the p-value was < 0.05 between bile reflux, hiatus hernia, and reflux and the p-value was < 0.001 among hiatus hernia and reflux. In the follow-up assessment, after triple therapy, H. pylori antigen tests were found to be negative in about 94% of the trial population, who were administered rabeprazole which displayed similarity to omeprazole-recipients (92%). Both rabeprazole and omeprazole have comparable H. pylori elimination rates when co-administered with antibiotics like clarithromycin and amoxicillin for two weeks.

Triple therapy containing rabeprazole is effective to treat H. pylori infection ^[5]

A study illustrated that a 14-day course has superior efficacy in comparison with the 10-day course of triple therapy (rabeprazole, amoxicillin, and clarithromycin) as a first-line for eliminating H. pylori infection. A double-blinded, prospective, randomized clinical trial was carried to investigate the efficacy of a 10-day vs a 14-day course of triple therapy to treat H. pylori infection.

Overall, 75 participants were randomly allocated to receive triple therapy as 20 mg rabeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin twice daily for 14 days (n=38) or 10 days plus four days placebo (n=37). Elimination was determined with a urea breath test at least four weeks after completion of the therapy. The elimination rate for the 10-day cohort and the 14-day cohort in the intention-to-treat analysis and the per-protocol analysis is shown in the following table:

Table 1: Comparison of H. pylori elimination rate

Adverse events were not considerably different between the two cohorts. Thus, the 14-day course is superior compared to a 10-day course triple therapy to eliminate H. pylori.

1. Available online from: https://www.drugs.com/mtm/rabeprazole.html#:~:text=Rabeprazole%20is%20a%20proton%20pump,at%20least%201%20year%20old.  [Last accessed on: 30 Jan 2021]
2. Available online from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020973s035204736s005lbl.pdf [Last accessed on: 30 Jan 2021]
3. Available online from: https://go.drugbank.com/drugs/DB01129  [Last accessed on: 30 Jan 2021]
4. Sukh Bahadur Gurung, Shiva Raj Kc, Purnima Gyawali, Gyanendra Lal Amatya. Comparative Study on Effect of Rabeprazole Versus Omeprazole in Acid-peptic Disorder with Helicobacter pylori Infection. J Nepal Health Res Counc. 2020 Jan 21;17(4):479-484
5. Ryan Herardi, Ari Fahrial Syam, Marcellus Simadibrata, Siti Setiati, Nikko Darnindro, Murdani Abdullah et al. Comparison of 10-Day Course of Triple Therapy Versus 14-Day Course for Eradication of Helicobacter pylori Infection in an Indonesian Population: Double-Blinded Randomized Clinical Trial. Asian Pac J Cancer Prev. 2020 Jan 1;21(1):19-24. *Swan Hoyumpa Merritt. Review article: the pharmacokinetics of rabeprazole in health and disease. 

*Swan Hoyumpa Merritt. Review article: the pharmacokinetics of rabeprazole in health and disease. Alimentary Pharmacology and Therapeutics. Volume 13, Issues 3 August 1999 Pages 11-17.