Evaluation of the concentrations of psychotropic drugs in HIV-infected versus HIV-negative patients: Potential implications for clinical practice

Cattaneo, Dario; Baldelli, Sara; Resnati, Chiara; Giacomelli, Andrea; Meraviglia, Paola; Minisci, Davide; Astuti, Noemi; Ridolfo, Annalisa; Socio, Giuseppe Vittorio De; Clementi, Emilio; Galli, Massimo; Gervasoni, Cristina

doi:10.1080/15622975.2018.1500032

Cited by 9 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recently published study demonstrated that clinicians tend to overestimate the impact of the inhibitory effect of ritonavir/cobicistat, resulting in the use of too low doses of psychotropic drugs in PLWH due to fear of DDIs . While ARTs are indeed among therapeutic agents with the highest potential for DDIs, they did not appear to affect escitalopram exposure, confirming previous observations .…”

Section: Discussionsupporting

confidence: 86%

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

Courlet

Guidi

Glatard

et al. 2019

Brit J Clinical Pharma

View full text Add to dashboard Cite

Aims The aims of this study were to characterize escitalopram pharmacokinetic profile, to identify factors influencing drug exposure, notably drug–drug interactions with antiretrovirals, and to simulate expected exposure under standard dosage regimen. Methods A population pharmacokinetic analysis was performed using NONMEM. A total of 159 plasma concentration measurements were obtained from 39 human immunodeficiency virus (HIV)‐infected and 71 uninfected psychiatric patients. The influence of age, weight, sex, HIV and psychiatric cohorts, racemic citalopram treatment, and comedications on oral clearance was examined. Simulations served to calculate the percentage of patients expected to be under‐ or over‐exposed, considering established therapeutic targets (15–80 ng/mL). Results A 1‐compartment model with first‐order absorption and elimination described the data adequately. The average escitalopram clearance and volume of distribution were 23.1 L/h (interindividual variability 51%), and 920 L, respectively. Escitalopram disposition did not differ between HIV‐infected and uninfected patients, and was not affected by antiretroviral treatments. Coadministration of at least 1 proton‐pump inhibitor (CYP2C19 inhibitor) modestly influenced escitalopram elimination (clearance decreased by 19%), with limited clinical relevance. Model‐based simulations showed that, under a standard regimen of 10 mg once daily, a significant proportion of patients (56%) might be under‐exposed. Conclusion The variability in escitalopram disposition is large and poorly explained by demographic, clinical and environmental covariates, thus suggesting a role for dosage individualization based on therapeutic drug monitoring in case of poor clinical response. Escitalopram disposition is modestly impacted by comedications and therefore no a priori dosage adjustments are needed in patients receiving antiretroviral treatments, including boosted regimens.

show abstract

Section: Discussionsupporting

confidence: 86%

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

Courlet

Guidi

Glatard

et al. 2019

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…A misunderstanding of these concepts and of the different DDI of each antiretroviral drugs can lead to an overestimation of the risk of DDI leading consequently to sub-optimal treatment. This issue has been reported for antidepressants since a larger proportion of PLWH were shown to have sub-therapeutic antidepressants levels compared to uninfected individuals suggestive of a deliberate lower dosing as clinicians fear DDIs with antiretroviral drugs [118]. It should be highlighted that most antidepressants are metabolized by several cytochromes and therefore the magnitude of DDIs with boosted regimens tend to be mitigated.…”

Section: Current Issues When Managing Drug-drug Interactionsmentioning

confidence: 96%

The challenge of HIV treatment in an era of polypharmacy

2020

View full text Add to dashboard Cite

Introduction The availability of potent antiretroviral therapy has transformed HIV infection into a chronic disease such that people living with HIV (PLWH) have a near normal life expectancy. However, there are continuing challenges in managing HIV infection, particularly in older patients, who often experience age‐related comorbidities resulting in complex polypharmacy and an increased risk for drug‐drug interactions. Furthermore, age‐related physiological changes may affect the pharmacokinetics and pharmacodynamics of both antiretrovirals and comedications thereby predisposing elderly to adverse drug reactions. This review provides an overview of the therapeutic challenges when treating elderly PLWH (i.e. >65 years). Particular emphasis is placed on drug‐drug interactions and other common prescribing issues (i.e. inappropriate drug use, prescribing cascade, drug‐disease interaction) encountered in elderly PLWH. Discussion Prescribing issues are common in elderly PLWH due to the presence of age‐related comorbidities, organ dysfunction and physiological changes leading to a higher risk for drug‐drug interactions, drugs dosage errors and inappropriate drug use. Conclusions The high prevalence of prescribing issues in elderly PLWH highlights the need for ongoing education on prescribing principles and the optimal management of individual patients. The knowledge of adverse health outcomes associated with polypharmacy and inappropriate prescribing should ensure that there are interventions to prevent harm including medication reconciliation, medication review and medication prioritization according to the risks/benefits for each patient.

show abstract

“…antidepressants, and antiepileptic drug trough concentrations in our laboratory, we assessed the distribution of plasma trough CNS drug concentrations in both PLWH and HIV-negative patients using the reference ranges provided by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guidelines. 81,82 Interestingly, we found that 64 % and 55 % of PLWH concomitantly receiving an antiretroviral and antipsychotic or antidepressant drug treatment versus 26 % and 25 % of HIV-negative patients had sub-therapeutic plasma psychotropic drug concentrations (Figure 3, difference statistically significant). Conversely, only 30 % and 28 % of PLWH and HIV-negative patients, respectively, had antiepileptic concentrations below the therapeutic targets (difference not statistically significant).…”

Section: A C C E P T E Dmentioning

confidence: 83%

“…Shaded lines represent the minimum effective atazanavir trough concentration (set at 150 ng/mL). Distribution of trough antipsychotic, antidepressant, and antiepileptic drug concentrations below, within, and above the reference ranges of the AGNP consensus guidelines 81,82 in PLWH versus HIV-negative patients.…”

Section: Discussionmentioning

confidence: 99%

Impact of Therapeutic Drug Monitoring of Antiretroviral Drugs in Routine Clinical Management of People Living With HIV: A Narrative Review

Cattaneo

Baldelli

Cozzi

et al. 2020

Therapeutic Drug Monitoring

Self Cite

View full text Add to dashboard Cite

Purpose:The treatment of human immunodeficiency virus (HIV) infection has evolved significantly since the advent of highly active antiretroviral therapy. As a result, a response rate of 90-95 % now represents a realistically achievable target. Given this background, it is difficult to imagine the additional benefits that therapeutic drug monitoring (TDM) could provide in the management of HIV infection.Methods: This article is not intended to provide a systematic literature review on TDM of antiretroviral agents; rather, the authors aim to discuss the potential added value of TDM in the optimal management of people living with HIV (PLWH) in selected real-life clinical scenarios based on data collected over 10 years by their TDM service.Results: Some clinical situations, in which the selection of the optimal antiretroviral therapy is challenging, have been identified. These include poorly compliant patients, sub-optimal antiretroviral therapies (in terms of both efficacy and toxicity), polypharmacy with a high risk of drug-drug interactions (DDIs), and different patient populations, such as pregnant women. Conclusions:The transformation of HIV infection from a near universally fatal illness to a lifelong chronic disease has resulted in an HIV population that is growing and aging, placing new and increasing demands on public programs and health services. Increasingly, the management of comorbidities, polypharmacy, and DDIs and their impact on antiretroviral therapy will have to be undertaken. These clinical settings represent some of the new frontiers for the use of TDM with the goal of achieving optimal prescription and outcome for PLWH.

show abstract

Evaluation of the concentrations of psychotropic drugs in HIV-infected versus HIV-negative patients: Potential implications for clinical practice

Abstract: A higher rate of sub-therapeutic antidepressant and/or antipsychotic drugs concentrations were found in HIV-infected patients. The creation of multidiscliplinary specialist teams may contribute to improving the management of such complex patients.

Cited by 9 publications

References 24 publications

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

The challenge of HIV treatment in an era of polypharmacy

Impact of Therapeutic Drug Monitoring of Antiretroviral Drugs in Routine Clinical Management of People Living With HIV: A Narrative Review

Contact Info

Product

Resources

About