title: Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors.
abstract: OBJECTIVE
  To review the potential drug interactions between low-dose methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton-pump inhibitors (PPIs) given the disparity between interactions reported for high-dose and low-dose MTX to help guide clinicians.
  
  
  METHODS
  A literature search was performed in MEDLINE (1946 to September 2016), EMBASE (1974 to September 2016), and International Pharmaceutical Abstracts (1970 to January 2015) to identify reports describing potential drug interactions between LD-MTX and NSAIDS, penicillins, or PPIs. Reference lists of included articles were reviewed to find additional eligible articles.
  
  
  METHODS
  All English-language observational, randomized, and pharmacokinetic (PK) studies assessing LD-MTX interactions in humans were analyzed to determine clinical relevance in making recommendations to clinicians. Clinical case reports were assigned a Drug Interaction Probability Scale score.
  
  
  RESULTS
  A total of 32 articles were included (28 with NSAIDs, 3 with penicillins, and 2 with PPIs [1 including both PPI and NSAID]). Although there are some PK data to describe increased LD-MTX concentrations when NSAIDs are used concomitantly, the clinical relevance remains unclear. Based on the limited data on LD-MTX with penicillins and PPIs, no clinically meaningful interaction was identified.
  
  
  CONCLUSIONS
  Given the available evidence, the clinical importance of the interaction between LD-MTX and NSAIDs, penicillins, and PPIs cannot be substantiated. Health care providers should assess the benefit and risk of LD-MTX regardless of concomitant drug use, including factors known to predispose patients to MTX toxicity, and continue to monitor clinical and laboratory parameters per guideline recommendations.
authors.affiliation: 1 University of Alberta, Edmonton, AB, Canada.
authors.forename: Jill J
authors.initials: JJ
authors.lastname: Hall
authors.affiliation: 2 Alberta Health Services, Edmonton, AB, Canada.
authors.forename: Monika
authors.initials: M
authors.lastname: Bolina
authors.affiliation: 1 University of Alberta, Edmonton, AB, Canada.
authors.forename: Trish
authors.initials: T
authors.lastname: Chatterley
authors.affiliation: 1 University of Alberta, Edmonton, AB, Canada.
authors.forename: Fakhreddin
authors.initials: F
authors.lastname: Jamali
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010406:Penicillins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010406:Penicillins; D054328:Proton Pump Inhibitors; D008727:Methotrexate
keywords: arthritis; drug interactions; methotrexate; nonsteroidal anti-inflammatory agents; penicillins; proton pump inhibitors; review