Opioid analgesics drug interactions

Opioid Pharmacokinetic Drug-Drug Interactions

June 29, 2014 – 10:31 pm

Pain-Topics.org News/Research UPDATES: Why Use UDT in Pain Management?

September 24, 2011

Brian R. Overholser, PharmD and David R. Foster, PharmD, FCCP

Adverse drug reactions (ADRs) are a significant problem, resulting in substantial morbidity, mortality, and healthcare expenses.1 In 2004, 1.2 million hospitalized patients experienced an ADR, 90% of which were due to a medication that was properly administered.2 Drug-drug interactions (DDIs) are an important and potentially preventable source of ADRs. DDIs can be broadly categorized as pharmacokinetic or pharmacodynamic; pharmacokinetic DDIs occur when a drug (the “precipitant drug”) causes a change in the absorption, distribution, metabolism, and/or elimination (“ADME”) of another drug (the “object drug”). These interactions can lead to either loss of efficacy or toxicity of the object drug. Pharmacodynamic DDIs result when 2 drugs are coadministered and the concentration-response curve of 1 or both drugs is altered without a change in the object drug’s pharmacokinetics.3Opioid analgesics are widely used in the treatment of both cancer-related and noncancer-related pain. In consensus guidelines, chronic opioid therapy is proposed as an option for patients with moderate to severe chronic noncancer pain, where the pain is impacting their quality of life, and the potential benefits of opioids are expected to outweigh the risks.4 Similarly, in elderly patients, consideration of opioid therapy is recommended for all patients with moderate to severe pain, pain-related functional impairment, or pain-related diminished quality of life.5

As a drug class, opioids are associated with a narrow therapeutic index, wide interindividual variability in response (eg, doses used in an opioid-tolerant patient can be fatal to an opioid-naïve patient), and potentially life-threatening toxicity. As the prevalence of opioid use has increased, serious adverse reactions and deaths associated with opioids have also increased.6 Although there have been substantial efforts to improve the safety of opioids in clinical practice, much of this effort has been directed to prevention of misuse and diversion, and management of chronic adverse effects.7 In contrast, the importance of pharmacokinetic DDIs related to opioids has received little attention. For example, in a systematic review of publications that described “opioid related problems, ” 105 publications including 156 patients were identified; of these, approximately 30% described opioid-associated DDIs.8 Moreover, in a series of analyses evaluating opioid users with chronic low back pain and osteoarthritis in a managed care database, approximately 30% of patients identified were taking opioids metabolized by the cytochrome P450 (CYP450) system and were also exposed to other CYP450 substrates, including potentially interacting drugs.9, 10 Consequences of pharmacokinetic DDIs associated with opioids can include excess opioid effects (including fatal toxicity), loss of analgesic efficacy, predisposition to other adverse effects, relapse to illicit or inappropriate drug use, and misinterpretation of opioid screening results.

Source: www.ajmc.com


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