Guiding dose adjustment of amlodipine after co-administration with ritonavir containing regimens using a physiologically-based pharmacokinetic/pharmacodynamic model

Mukherjee, Dwaipayan; Zha, Jiuhong; Menon, Rajeev; Shebley, Mohamad

doi:10.1007/s10928-018-9574-0

Cited by 19 publications

(22 citation statements)

References 44 publications

(66 reference statements)

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“…Boosted ARVs increase the exposure of calcium channel inhibitors due to inhibition of CYPs and thereby the hypotensive effect Start at a lower dose and titrate based on blood pressure response. Consider a 50% dose reduction for amlodipine and diltiazem Lercanidipine: contraindicated …”

Section: Discussionmentioning

confidence: 99%

The challenge of HIV treatment in an era of polypharmacy

2020

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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.

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Section: Discussionmentioning

confidence: 99%

The challenge of HIV treatment in an era of polypharmacy

2020

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“…A physiologically based pharmacokinetic (PBPK) model study showed that a 50% reduced dose of amlodipine given with RTV was enough to maintain the same plasma level of amlodipine as with its full dose without RTV. The full dose of amlodipine can be resumed either immediately after stopping RTV or 5 days later under clinical monitoring [59].…”

Section: Lopinavir/ritonavir + Calcium Channel Blockersmentioning

confidence: 99%

“…Nifedipine [56,57], Amlodipine [58,59], Lacidipine , Cilnidipine, Diltiazem [58], Verapamil [63] Lercanidipine [61,39] Antiarrhythmic agents…”

Section: Calcium Channel Blockersmentioning

confidence: 99%

Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications

Agarwal

2020

Cardiovasc Drugs Ther

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Lopinavir-ritonavir combination is being used for the treatment of SARS-CoV-2 infection. A low dose of ritonavir is added to other protease inhibitors to take advantage of potent inhibition of cytochrome (CYP) P450 3A4, thereby significantly increasing the plasma concentration of coadministered lopinavir. Ritonavir also inhibits CYP2D6 and induces CYP2B6, CYP2C19, CYP2C9, and CYP1A2. This potent, time-dependent interference of major hepatic drug-metabolizing enzymes by ritonavir leads to several clinically important drug-drug interactions. A number of patients presenting with acute coronary syndrome and acute heart failure may have SARS-CoV-2 infection simultaneously. Lopinavir-ritonavir is added to their prescription of multiple cardiac medications leading to potential drug-drug interactions. Many cardiology, pulmonology, and intensivist physicians have never been exposed to clinical scenarios requiring co-prescription of cardiac and antiviral therapies. Therefore, it is essential to enumerate these drug-drug interactions, to avoid any serious drug toxicity, to consider alternate and safer drugs, and to ensure better patient care.

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“…Then, the established nifedipine PBPK model was used to predict multiple dosing of nifedipine when co-administered with RTV-containing regimens. Since RTV is the only clinical inhibitor and inducer of CYP3A4 within the regimen, only RTV was simulated as a surrogate for the RTV-containing regimens [35]. In addition, the PBPK model of RTV has been already verified by simulating its inhibition effects on the PK profiles of CYP3A4 substrates [36].…”

Section: Nifedipine-rtv Ddi Predictionmentioning

confidence: 99%

“…In addition, it takes days of wash-out after RTV withdrawal to allow the nifedipine concentration to drop down to a safe level when patient taking nifedipine. These results are the important hints for patients taking the nifedipine treatment.The PBPK/PD analysis was once used to investigate dose adjustment recommendations for amlodipine during and after co-administration of RTV by Mukherjee, et al[35]. The analysis suggested that resuming a full dose of amlodipine…”

mentioning

confidence: 99%

Investigation on the interaction between nifedipine and ritonavir containing antivirus regimens: a physiologically-based pharmacokinetic/pharmacodynamic analysis

Niu

Jin

et al. 2020

Preprint

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Background and Objective Hypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Those patients are often treated with commonly used antiviral and antihypertensive agents concomitantly, such as ritonavir-containing regimens and nifedipine. Since ritonavir is a strong inhibitor of CYP3A, when nifedipine is combined with ritonavir-containing antiviral drugs, there is a potential risk of drug-drug interaction. This study aimed to provide guidance on nifedipine treatment during and after co-administration with ritonavir-containing regimens using a physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) analysis. Methods A PBPK/PD model was developed for nifedipine by the software of Simcyp, and the model was verified using published data. The effects of ritonavir on nifedipine exposures and systolic blood pressure were assessed for instant-release, sustained-release and controlled-release formulations. Moreover, various nifedipine regimens were investigated when co-administrated with and withdrawing ritonavir. Results PBPK/PD models for three formulations of nifedipine were successfully established. The model predicted pharmacokinetic profiles of nifedipine were comparable to the published data. Ratios of predicted versus observed AUCDDI/AUCNifedipine of nifedipine were within 0.70- to 1.83-fold. Model simulations showed that the inhibitory effect of ritonavir on CYP3A4 increased the Cmax of nifedipine by 9.82-34.35 times and the AUC by 44.94-50.77 times at steady state. Moreover, nifedipine dose reduced to 1/16 of the regular dose during ritonavir co-administration could lead to severe hypotension. Conclusions Ritonavir had a pronounced influence on the pharmacokinetics and antihypertensive effect of nifedipine. It is not recommended for patients to take nifedipine and ritonavir-containing regimens simultaneously.

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Guiding dose adjustment of amlodipine after co-administration with ritonavir containing regimens using a physiologically-based pharmacokinetic/pharmacodynamic model

Cited by 19 publications

References 44 publications

The challenge of HIV treatment in an era of polypharmacy

The challenge of HIV treatment in an era of polypharmacy

Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications

Investigation on the interaction between nifedipine and ritonavir containing antivirus regimens: a physiologically-based pharmacokinetic/pharmacodynamic analysis

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