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By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a fixed-dose combination, rifabutin-based (RFB) regimen to treat Helicobacter pylori infection. RFB is combined with amoxicillin (AMX), an antibiotic, along with omeprazole (OMEP), a proton pump inhibitor.
This regimen is designed to address clarithromycin-resistant H. pylori. It received a Qualified Infectious Disease Product designation and a priority review. The combination will be distributed by RedHill Biopharma as Talicia.
OMEP/AMX/RFB is indicated for the treatment of H. pylori infection in adults.1
The recommended dose is four capsules every eight hours (120 mg OMEP, 3 g AMX, 150 mg RFB) with food for 14 days. It should not be taken with alcohol. Each delayed-release capsule contains OMEP magnesium 10.3 mg (the equivalent of 10 mg of OMEP), AMX 250 mg, and RFB 12.5 mg.
Worldwide H. pylori antibacterial resistance to RFB is low compared to other antibacterials.2 Rifabutin-based triple therapy with a lower dose of AMX and OMEP (2 g AMX and 80 mg of OMEP) has been shown to be effective in patients with triple-resistant (clarithromycin, metronidazole, and levofloxacin) H. pylori, achieving an 83% cure rate.3
RFB is an inducer of and substrate for CYP3A isoenzymes, and OMEP is a substrate and inhibitor for CYP2C19 and a substrate for CYP3A4.1 Clinically important drug-drug interactions may occur with concomitant treatment. Avoid concomitant use with 2C19 and 3A4 inducers and inhibitors. The most frequently reported (vs. placebo) adverse reactions were diarrhea (10-14% vs. 10%), headache (8-16% vs. 10%), and chromaturia (13% vs. 2%).1
The approval of OMEP/AMX/RFB was based, in part, on two phase III studies: one with an active control arm to confirm the added benefit of RFB and the other a placebo-controlled study.1 Participants were treatment-naïve, H. pylori-positive adult patients with complaints of epigastric pain/discomfort. Infection was confirmed with 13C urea breath test and follow-up upper endoscopy.
In study 1, participants were randomized to OMEP/AMX/RFB or AMX (3 g) and OMEP (120 mg) daily for 14 days. Treatment eradication/success was confirmed with a negative 13C urea breath test or fecal antigen test conducted ≥ 28 days post-therapy. Eradication rates were 83.8% for OMEP/AMX/RFB (n = 228) vs. 57.7% (n = 227) for OMEP/AMX. In study 2, the eradication/success rates for OMEP/AMX/RFB (n = 77) vs. placebo (n = 41) were 76.6% and 2.4%, respectively.
H. pylori infection is a common (usually lifelong) infection. The prevalence of the infection is much higher outside of North America (79.1% in Africa, 63.4% in Latin America and the Caribbean).4 In North America, the prevalence is 37.1% and varies with socioeconomic status and race/ethnicity.4,5 The World Health Organization classifies H. pylori as a group 1 carcinogen leading to gastric adenocarcinoma.5 Worldwide H. pylori antibacterial resistance has increased for clarithromycin and metronidazole, with higher prevalence in women vs. men.2 In vitro effectiveness for RFB against multidrug-resistance has been reported in 76% of isolates tested (n = 33).5
Currently, the American College of Gastroenterology recommends clarithromycin-based triple therapy (clarithromycin, a proton pump inhibitor, and AMX or metronidazole) for 14 days where H. pylori clarithromycin resistance is less than 15%.6 For patients with high levels of clarithromycin resistance or history of macrolide use, bismuth-based quadruple therapy (bismuth, proton pump inhibitor, tetracycline, nitroimidazole) for 10-14 days is recommended.6,7 OMEP/AMX/RFB provides an effective alternative to first-line therapy for drug-resistant H. pylori infections. The product is expected to be available in the first quarter of 2020.
Financial Disclosure: Internal Medicine Alert’s Physician Editor Stephen Brunton, MD, is a retained consultant for Abbott, Acadia, Allergan, AstraZeneca, Avadel, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Mylan, and Salix; he serves on the speakers bureau of AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, and Novo Nordisk. Peer Reviewer Gerald Roberts, MD; Editor Jonathan Springston; Editor Jason Schneider; Editorial Group Manager Leslie Coplin; and Accreditations Manager Amy M. Johnson, MSN, RN, CPN, report no financial relationships relevant to this field of study.