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      Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review

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          Opioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug–drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines.


          To identify studies that report clinically significant drug–drug interactions involving opioids used for pain treatment in adult cancer patients.

          Design and data sources

          Systematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980) through January 2014. In addition, reference lists of relevant full-text papers were hand-searched.


          Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug–drug interactions involving opioids were grouped as follows: 1) sedation and respiratory depression, 2) other central nervous system symptoms, 3) impairment of pain control and/or opioid withdrawal, and 4) other symptoms. The most common mechanisms eliciting drug–drug interactions were alteration of opioid metabolism by inhibiting the activity of cytochrome P450 3A4 and pharmacodynamic interactions due to the combined effect on opioid, dopaminergic, cholinergic, and serotonergic activity in the central nervous system.


          Evidence for drug–drug interactions associated with opioids used for pain treatment in cancer patients is very limited. Still, the cases identified in this systematic review give some important suggestions for clinical practice. Physicians prescribing opioids should recognize the risk of drug–drug interactions and if possible avoid polypharmacy.

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          Most cited references 64

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          Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC.

          Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co-authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review.

            Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area.
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              Cancer pain relief: with a guide to opioid availability


                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                16 September 2015
                : 9
                : 5255-5267
                [1 ]Palliative Medicine Chair and Department, University Hospital of the Lord’s Transfiguration, Karol Marcinkowski University of Medical Sciences, Poznan, Poland
                [2 ]European Palliative Care Research Centre, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
                [3 ]Department of Anaesthesiology and Intensive Care Medicine, St Olavs Hospital, Trondheim, Norway
                [4 ]Regional Centre of Excellence for Palliative Care, Haukeland University Hospital, Bergen, Norway
                [5 ]Department of Clinical Medicine K1, University of Bergen, Bergen, Norway
                [6 ]Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
                Author notes
                Correspondence: Aleksandra Kotlinska-Lemieszek, Osiedle Rusa 55, 61-245 Poznan, Poland, Tel +48 60 807 9698, Fax +48 61 873 8303, Email alemieszek@ 123456ump.edu.pl
                © 2015 Kotlinska-Lemieszek et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.


                Pharmacology & Pharmaceutical medicine

                drug–drug interactions, cancer patients, pain, opioids


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