Drug Interactions

Spina, Edoardo; Italiano, Domenico

doi:10.1002/9781118936979.ch25

Cited by 4 publications

(6 citation statements)

References 81 publications

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“…Information on the drug‐metabolizing enzymes, in particular the human CYP system, and their substrates, inhibitors and inducers may be of great value for rational prescribing and may help clinicians to anticipate and eventually avoid potential interactions . In fact, co‐administration of two substrates of the same enzyme, or co‐administration of a substrate with an inhibitor or an inducer, involves the risk of a DDI.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, not all theoretically possible DDIs that are predicted from in vitro studies will occur in vivo, and some may not be clinically important. A variety of drug‐related (ie potency and concentration/dose of the inhibitor/inducer, therapeutic index of the substrate, extent of metabolism of the substrate through the affected enzyme, presence of active metabolites), patient‐related (ie age, genetic predisposition) and epidemiological factors (ie probability of concurrent use) must be taken into account when evaluating the potential occurrence and clinical relevance of a PK DDI . As shown in Tables and , most statin and antidepressants are extensively metabolized, primarily via CYPs.…”

Section: Resultsmentioning

confidence: 99%

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Clinically relevant drug interactions between statins and antidepressants

et al. 2019

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What is known and objective Statins, also known as 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibitors, and antidepressant drugs are frequently used in combination due to the high and growing incidence of cardiovascular diseases and psychiatric disorders worldwide. Several aspects on management, the risk of adverse events (AEs) occurrence and the potential clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) drug‐drug interactions (DDIs) between these two classes have not been well investigated. The aim of the present review was to describe the PK and PD interactions, of clinical relevance, between statins and antidepressant drugs and provide a comprehensive overview of their pharmacological features for appropriate multiple drug regimens. Methods Relevant studies were identified through a literature search of PubMed and the Cochrane databases focusing on clinically relevant DDIs between statins and antidepressants. Only papers in English were included in the search. Results and discussion Pharmacodynamic (PD) drug‐drug interactions (DDIs) are unlikely to occur as statins are highly selective inhibitors of HMG‐CoA reductase with no relevant effect on other enzymes or receptor systems. Despite the numerous PK studies on individual drugs belonging to statins and antidepressant agents, only a few case reports regarding specific DDIs are present in the literature and no clinical studies have been performed. PK data allow to speculate on potential DDIs, comparing the metabolic pathways, intestinal and liver transporters and elimination routes. Overall, second‐generation antidepressants, in particular citalopram, escitalopram, mirtazapine, reboxetine and venlafaxine, have weak inhibitory effects on various cytochrome (CYP) isozymes and seem to have a more advantageous DDIs profile in vivo. Conversely, nefazodone, fluoxetine, paroxetine and fluvoxamine influence considerably CYPs activity with potential effects on statins plasma levels, although pravastatin, pitavastatin and rosuvastatin are not susceptible to inhibition by any CYP. Albeit no studies have been performed on P‐glycoprotein (P‐gp), interactions of clinical relevance are unlikely. What is new and conclusion Although DDIs with antidepressants are potentially, but rarely clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. An evaluation on DDIs between these drugs can be useful for future PK/PD studies on drug‐drug interaction to provide clinicians with more data for appropriate multiple drug regimens.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Clinically relevant drug interactions between statins and antidepressants

et al. 2019

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“…The main clinically significant PK DIs between atypical antipsychotics and anti-infective agents occur at a metabolic level and result from enzyme inhibition or induction. Available knowledge of substrates, inhibitors, and inducers of the major drug-metabolizing enzymes has greatly improved the possibility of predicting and eventually avoiding potential DIs [1]. In principle, concomitant treatment with drugs metabolized by the same enzyme or coadministration of a drug with another medication acting as an inhibitor or inducer involves a DI risk.…”

Section: Pk Dismentioning

confidence: 99%

“…In principle, concomitant treatment with drugs metabolized by the same enzyme or coadministration of a drug with another medication acting as an inhibitor or inducer involves a DI risk. A variety of drug-related (i.e., potency and concentration/dose of the inhibitor/inducer, therapeutic index of the substrate, extent of metabolism of the substrate through the affected enzyme, presence of active metabolites), patient-related (i.e., age, genetic predisposition) and epidemiological factors (i.e., probability of concurrent use) must be taken into account when evaluating the potential occurrence, magnitude and clinical relevance of a metabolic DI [1].…”

Section: Pk Dismentioning

confidence: 99%

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Clinically Relevant Interactions between Atypical Antipsychotics and Anti-Infective Agents

2020

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This is a comprehensive review of the literature on drug interactions (DIs) between atypical antipsychotics and anti-infective agents that focuses on those DIs with the potential to be clinically relevant and classifies them as pharmacokinetic (PK) or pharmacodynamic (PD) DIs. PubMed searches were conducted for each of the atypical antipsychotics and most commonly used anti-infective agents (13 atypical antipsychotics by 61 anti-infective agents/classes leading to 793 individual searches). Additional relevant articles were obtained from citations and from prior review articles written by the authors. Based on prior DI articles and our current understanding of PK and PD mechanism, we developed tables with practical recommendations for clinicians for: antibiotic DIs, antitubercular DIs, antifungal DIs, antiviral DIs, and other anti-infective DIs. Another table reflects that in clinical practice, DIs between atypical antipsychotics and anti-infective agents occur in patients also suffering an infection that may also influence the PK and PD mechanisms of both drugs (the atypical antipsychotic and the anti-infective agent(s)). These tables reflect the currently available literature and our current knowledge of the field and will need to be updated as new DI information becomes available.

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