CHICAGO – posing a distinct danger of unwelcome drug-drug interactions affecting the rate and extent of absorption of selected oral antirheumatic drugs, Nicholas Jones, PharmD, said at the annual meeting of the American College of Rheumatology.
Of particular interest is the fact that the oral Janus kinase inhibitors – a drug class that’s a red hot research topic now in rheumatology – are weak bases whose absorption can be greatly affected by pH-dependent solubility, according to Dr. Jones, a research scientist at Genentech in South San Francisco.
Other commonly prescribed oral antirheumatic drugs whose solubility is affected by the level of stomach acidity include azathioprine, methotrexate, mycophenolate mofetil, and sulfasalazine. On the other hand, solubility is not pH-dependent for apremilast, chloroquine, cyclophosphamide, cyclosporine, hydroxychloroquine, leflunomide, or tacrolimus.
Dr. Jones presented a retrospective analysis of proton pump inhibitor (PPI) utilization patterns during 2012-2015 in 77,034 rheumatoid arthritis and 2,224 systemic lupus erythematosus (SLE) patients included in the national Truven Health MarketScan database.
Thirty-five percent of the rheumatoid arthritis patients and 34% of SLE patients were chronic users of PPIs as defined by continuous daily use for more than a month during 2 years of follow-up. Among the SLE cohort, chronic utilization of PPIs increased stepwise with disease severity: The rate was 27% in those with mild SLE, 39% with moderate disease, and 54% among those with severe SLE.
Omeprazole was far and away the most widely used PPI. It was the one used by 53% of the RA patients who were chronic users of PPIs, followed by pantoprazole at 20% and esomeprazole at 15%. The PPI distribution pattern closely followed suit in SLE patients who were chronic users.
Esomeprazole is 60% more potent and pantoprazole 77% less potent than omeprazole, Dr. Jones noted. The pharmacokinetic clearance routes for omeprazole and esomeprazole involve CYP2C19 and CYP3A4. Clearance of pantoprazole is by those two mechanisms as well as by CYP2D6 and CYP2C9.
Dr. Jones recommended that physicians who treat rheumatoid arthritis and SLE patients be sure to ask them about concomitant use of PPIs, including OTC formulations. And clinical trialists need to be attentive to PPI usage in potential study participants.
Genentech sponsored the study.
SOURCE: Keebler D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 228