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Metamizole but not Ibuprofen reduces the plasma concentration of sertraline - Implications for the concurrent treatment of pain and depression/anxiety disorders.
Br J Clin Pharmacol. 2020 Jul 11 [Online ahead of print]BJ

Abstract

AIM

Comorbidity of pain and depression or anxiety is a challenging clinical phenomenon, often requiring the concurrent application of antidepressant and analgesic drugs. Growing evidence suggests that the analgesic metamizole exhibits cytochrome P450 inducing properties. In the present study, we assessed the impact of metamizole and ibuprofen on plasma concentrations of the selective serotonin reuptake inhibitor sertraline.

METHODS

Out of a therapeutic drug monitoring (TDM) database, three groups of patients were compared: patients receiving sertraline and metamizole (n=15), patients receiving sertraline and ibuprofen (n=19) and a matched control group without one of the analgesics (n=19).

RESULTS

Metamizole was associated with 67% lower median sertraline plasma concentrations compared to the control group (14 vs. 42 ng/mL; p<0.001). In contrast, differences between the ibuprofen group and the control group did not reach statistical significance (31 vs. 42 ng/mL; p=0.128). Moreover, the metamizole group demonstrated lower dose-adjusted drug concentrations than the ibuprofen group (0.10 vs. 0.26 (ng/mL)/(mg/day); p=0.008). Finally, the metamizole group exhibited a higher proportion of patients whose sertraline concentrations were below the therapeutic reference range (40 % in the metamizole group, 5 % in the ibuprofen group, 0 % in the control group; p=0.005) indicating therapeutically insufficient drug concentrations.

CONCLUSION

Our findings support preliminary evidence that metamizole acts as a potent inductor of cytochrome P450 isoenzymes CYP2B6 and CYP3A4. We observed a clinically meaningful pharmacokinetic interaction between metamizole and sertraline, leading to insufficiently low sertraline drug concentrations. Therefore, clinicians should consider alternative drug combinations or apply TDM-guided dose adjustment of sertraline.

Authors+Show Affiliations

Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. JARA - Translational Brain Medicine, Aachen, Germany.The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York. Hofstra Northwell School of Medicine, Hempstead, New York and The Feinstein Institute for Medical Research, Manhasset, New York, USA.Department of Psychiatry and Psychotherapy, Clinical Pharmacology, University of Regensburg, Regensburg, Germany. Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.Department of Psychiatry and Psychotherapy, Clinical Pharmacology, University of Regensburg, Regensburg, Germany. Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.Department of Psychiatry and Psychotherapy, Clinical Pharmacology, University of Regensburg, Regensburg, Germany. Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany.Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. JARA - Translational Brain Medicine, Aachen, Germany. Alexianer Hospital Aachen, Aachen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32652557

Citation

Gaebler, Arnim Johannes, et al. "Metamizole but Not Ibuprofen Reduces the Plasma Concentration of Sertraline - Implications for the Concurrent Treatment of Pain and Depression/anxiety Disorders." British Journal of Clinical Pharmacology, 2020.
Gaebler AJ, Schoretsanitis G, Ben Omar N, et al. Metamizole but not Ibuprofen reduces the plasma concentration of sertraline - Implications for the concurrent treatment of pain and depression/anxiety disorders. Br J Clin Pharmacol. 2020.
Gaebler, A. J., Schoretsanitis, G., Ben Omar, N., Haen, E., Endres, K., Hiemke, C., & Paulzen, M. (2020). Metamizole but not Ibuprofen reduces the plasma concentration of sertraline - Implications for the concurrent treatment of pain and depression/anxiety disorders. British Journal of Clinical Pharmacology. https://doi.org/10.1111/bcp.14471
Gaebler AJ, et al. Metamizole but Not Ibuprofen Reduces the Plasma Concentration of Sertraline - Implications for the Concurrent Treatment of Pain and Depression/anxiety Disorders. Br J Clin Pharmacol. 2020 Jul 11; PubMed PMID: 32652557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metamizole but not Ibuprofen reduces the plasma concentration of sertraline - Implications for the concurrent treatment of pain and depression/anxiety disorders. AU - Gaebler,Arnim Johannes, AU - Schoretsanitis,Georgios, AU - Ben Omar,Nagia, AU - Haen,Ekkehard, AU - Endres,Katharina, AU - Hiemke,Christoph, AU - Paulzen,Michael, Y1 - 2020/07/11/ PY - 2020/02/09/received PY - 2020/05/09/revised PY - 2020/05/14/accepted PY - 2020/7/12/entrez PY - 2020/7/12/pubmed PY - 2020/7/12/medline KW - depression KW - dipyrone KW - metamizole KW - pain KW - pharmacokinetics KW - sertraline KW - therapeutic drug monitoring JF - British journal of clinical pharmacology JO - Br J Clin Pharmacol N2 - AIM: Comorbidity of pain and depression or anxiety is a challenging clinical phenomenon, often requiring the concurrent application of antidepressant and analgesic drugs. Growing evidence suggests that the analgesic metamizole exhibits cytochrome P450 inducing properties. In the present study, we assessed the impact of metamizole and ibuprofen on plasma concentrations of the selective serotonin reuptake inhibitor sertraline. METHODS: Out of a therapeutic drug monitoring (TDM) database, three groups of patients were compared: patients receiving sertraline and metamizole (n=15), patients receiving sertraline and ibuprofen (n=19) and a matched control group without one of the analgesics (n=19). RESULTS: Metamizole was associated with 67% lower median sertraline plasma concentrations compared to the control group (14 vs. 42 ng/mL; p<0.001). In contrast, differences between the ibuprofen group and the control group did not reach statistical significance (31 vs. 42 ng/mL; p=0.128). Moreover, the metamizole group demonstrated lower dose-adjusted drug concentrations than the ibuprofen group (0.10 vs. 0.26 (ng/mL)/(mg/day); p=0.008). Finally, the metamizole group exhibited a higher proportion of patients whose sertraline concentrations were below the therapeutic reference range (40 % in the metamizole group, 5 % in the ibuprofen group, 0 % in the control group; p=0.005) indicating therapeutically insufficient drug concentrations. CONCLUSION: Our findings support preliminary evidence that metamizole acts as a potent inductor of cytochrome P450 isoenzymes CYP2B6 and CYP3A4. We observed a clinically meaningful pharmacokinetic interaction between metamizole and sertraline, leading to insufficiently low sertraline drug concentrations. Therefore, clinicians should consider alternative drug combinations or apply TDM-guided dose adjustment of sertraline. SN - 1365-2125 UR - https://www.unboundmedicine.com/medline/citation/32652557/Metamizole_but_not_Ibuprofen_reduces_the_plasma_concentration_of_sertraline_-_Implications_for_the_concurrent_treatment_of_pain_and_depression/anxiety_disorders L2 - https://doi.org/10.1111/bcp.14471 DB - PRIME DP - Unbound Medicine ER -
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