Enhancing the Efficacy and Safety of Methotrexate Treatment: A Focus on Drug Interactions (Review)
INTRODUCTION. Methotrexate (MTX) is the main disease-modifying antirheumatic drug (DMARD) and the gold standard for the safety and efficacy evaluation of biologicals and targeted small molecules. However, its narrow therapeutic range, interpatient variability in pharmacokinetics and pharmacodynamics...
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| Format: | Article |
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Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»
2024-10-01
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| Series: | Безопасность и риск фармакотерапии |
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| Online Access: | https://www.risksafety.ru/jour/article/view/416 |
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| author | S. A. Doktorova Yu. Yu. Grabovetskaya M. Stefanov V. V. Rafalskiy |
| author_facet | S. A. Doktorova Yu. Yu. Grabovetskaya M. Stefanov V. V. Rafalskiy |
| author_sort | S. A. Doktorova |
| collection | DOAJ |
| description | INTRODUCTION. Methotrexate (MTX) is the main disease-modifying antirheumatic drug (DMARD) and the gold standard for the safety and efficacy evaluation of biologicals and targeted small molecules. However, its narrow therapeutic range, interpatient variability in pharmacokinetics and pharmacodynamics, and potential clinically relevant drug–drug interactions (DDIs) may lead to treatment failure and increase the risk of adverse drug reactions (ADRs).AIM. The study aimed to describe the main clinically significant DDIs associated with MTX used in rheumatic disease therapy and determine possible approaches to addressing this issue based on a literature review.DISCUSSION. MTX is characterised by pharmacokinetic DDIs during absorption, cell penetration, and elimination. Some non-steroidal anti-inflammatory drugs (NSAIDs), theophylline, sulfasalazine, antibacterial agents, and proton pump inhibitors (PPIs) affect MTX elimination and therapeutic effects. The main ADRs associated with MTX include haematotoxicity, hepatotoxicity, lung tissue damage (interstitial pneumonitis and pulmonary fibrosis), and renal dysfunction. The severity of these ADRs depends on the dose, comorbidities, and concomitant therapy. The toxicity of MTX may be increased by the concomitant administration of medicinal products that exhibit haematotoxicity and affect renal function (impair the elimination of medicines). When co-administering MTX and medicines having clinically significant DDIs described in the literature, healthcare providers should consider the risk factors for each individual patient. The most significant risk factors include moderate to severe renal and hepatic impairment, older age, polypharmacy, and hypoalbuminemia.CONCLUSIONS. This article describes potential clinically significant interactions between MTX and certain NSAIDs, antibacterial agents, and PPIs that depend on individual patient characteristics and may increase the toxicity or decrease the effectiveness of MTX. MTX deprescribing, short-term withdrawal, and dosing optimisation may be considered as approaches to DDI risk mitigation. |
| format | Article |
| id | doaj-art-c90034379d744cd1a76784042e2f9437 |
| institution | Kabale University |
| issn | 2312-7821 2619-1164 |
| language | Russian |
| publishDate | 2024-10-01 |
| publisher | Ministry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» |
| record_format | Article |
| series | Безопасность и риск фармакотерапии |
| spelling | doaj-art-c90034379d744cd1a76784042e2f94372025-08-20T03:56:38ZrusMinistry of Health of the Russian Federation, Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products»Безопасность и риск фармакотерапии2312-78212619-11642024-10-0112328529810.30895/2312-7821-2024-416338Enhancing the Efficacy and Safety of Methotrexate Treatment: A Focus on Drug Interactions (Review)S. A. Doktorova0Yu. Yu. Grabovetskaya1M. Stefanov2V. V. Rafalskiy3Immanuel Kant Baltic Federal UniversityImmanuel Kant Baltic Federal University; Clinical and Diagnostic Outpatient Clinic of the Regional Clinical Hospital of the Kaliningrad RegionImmanuel Kant Baltic Federal UniversityImmanuel Kant Baltic Federal UniversityINTRODUCTION. Methotrexate (MTX) is the main disease-modifying antirheumatic drug (DMARD) and the gold standard for the safety and efficacy evaluation of biologicals and targeted small molecules. However, its narrow therapeutic range, interpatient variability in pharmacokinetics and pharmacodynamics, and potential clinically relevant drug–drug interactions (DDIs) may lead to treatment failure and increase the risk of adverse drug reactions (ADRs).AIM. The study aimed to describe the main clinically significant DDIs associated with MTX used in rheumatic disease therapy and determine possible approaches to addressing this issue based on a literature review.DISCUSSION. MTX is characterised by pharmacokinetic DDIs during absorption, cell penetration, and elimination. Some non-steroidal anti-inflammatory drugs (NSAIDs), theophylline, sulfasalazine, antibacterial agents, and proton pump inhibitors (PPIs) affect MTX elimination and therapeutic effects. The main ADRs associated with MTX include haematotoxicity, hepatotoxicity, lung tissue damage (interstitial pneumonitis and pulmonary fibrosis), and renal dysfunction. The severity of these ADRs depends on the dose, comorbidities, and concomitant therapy. The toxicity of MTX may be increased by the concomitant administration of medicinal products that exhibit haematotoxicity and affect renal function (impair the elimination of medicines). When co-administering MTX and medicines having clinically significant DDIs described in the literature, healthcare providers should consider the risk factors for each individual patient. The most significant risk factors include moderate to severe renal and hepatic impairment, older age, polypharmacy, and hypoalbuminemia.CONCLUSIONS. This article describes potential clinically significant interactions between MTX and certain NSAIDs, antibacterial agents, and PPIs that depend on individual patient characteristics and may increase the toxicity or decrease the effectiveness of MTX. MTX deprescribing, short-term withdrawal, and dosing optimisation may be considered as approaches to DDI risk mitigation.https://www.risksafety.ru/jour/article/view/416methotrexatedrug interactionsadverse drug reactionspharmacokineticspharmacodynamicssafetyrheumatoid arthritisdisease-modifying antirheumatic drugsbiologicalsproton pump inhibitorsnon-steroidal anti-inflammatory drugs |
| spellingShingle | S. A. Doktorova Yu. Yu. Grabovetskaya M. Stefanov V. V. Rafalskiy Enhancing the Efficacy and Safety of Methotrexate Treatment: A Focus on Drug Interactions (Review) Безопасность и риск фармакотерапии methotrexate drug interactions adverse drug reactions pharmacokinetics pharmacodynamics safety rheumatoid arthritis disease-modifying antirheumatic drugs biologicals proton pump inhibitors non-steroidal anti-inflammatory drugs |
| title | Enhancing the Efficacy and Safety of Methotrexate Treatment: A Focus on Drug Interactions (Review) |
| title_full | Enhancing the Efficacy and Safety of Methotrexate Treatment: A Focus on Drug Interactions (Review) |
| title_fullStr | Enhancing the Efficacy and Safety of Methotrexate Treatment: A Focus on Drug Interactions (Review) |
| title_full_unstemmed | Enhancing the Efficacy and Safety of Methotrexate Treatment: A Focus on Drug Interactions (Review) |
| title_short | Enhancing the Efficacy and Safety of Methotrexate Treatment: A Focus on Drug Interactions (Review) |
| title_sort | enhancing the efficacy and safety of methotrexate treatment a focus on drug interactions review |
| topic | methotrexate drug interactions adverse drug reactions pharmacokinetics pharmacodynamics safety rheumatoid arthritis disease-modifying antirheumatic drugs biologicals proton pump inhibitors non-steroidal anti-inflammatory drugs |
| url | https://www.risksafety.ru/jour/article/view/416 |
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