Cardiovascular Side Effects of Atomoxetine and Its Interactions with Inhibitors of the Cytochrome P450 System

Kasi, Pashtoon Murtaza; Mounzer, Rawad; Gleeson, George H.

doi:10.1155/2011/952584

Cited by 15 publications

(12 citation statements)

References 9 publications

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“…Although the therapeutic index of atomoxetine is known to be wide, there are several reports on the adverse events related to increased plasma concentration of atomoxetine. There have been case reports of QT interval prolongation with the use of atomoxetine (Barker et al 2004;Sawant et al 2004), which may lead to life-threatening arrhythmias and may account for the cases of sudden cardiac death reported with the use of the drug (Kasi et al 2011). The atomoxetine apparently inhibits human Ether-à-Go-Go-Related Gene (hERG) potassium channels, leading to prolongation of the QT interval (Scherer et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Effects of the CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites

Byeon

Kim

et al. 2015

Arch. Pharm. Res.

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To investigate the effect of the variant CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites, 4-hydroxyatomoxetine (4-HAT) and N-desmethylatomoxetine (NAT), in healthy subjects, a single oral dose of atomoxetine was administered to 62 subjects with a CYP2D6*wt/*wt (*wt = *1 or *2, n = 22), CYP2D6*wt/*10 (n = 22) or CYP2D6*10/*10 (n = 18) genotype. Plasma samples were then collected for 24 h after atomoxetine administration. The concentrations of atomoxetine and its metabolites were assayed using LC-MS/MS. For atomoxetine, the Cmax, AUC0-∞, t1/2 and CL/F showed genotype-dependent differences. The CYP2D6*10/*10 and CYP2D6*wt/*10 groups showed 1.74- and 1.15-fold higher Cmax, 3.40- and 1.33-fold higher AUC0-∞, and 69.7 and 24.6 % lower CL/F, compared to those of the CYP2D6*wt/*wt group, respectively. The Cmax and t1/2 for 4-HAT were lower and longer in the CYP2D6*10/*10 group than those in the CYP2D6*wt/*wt group, but the AUC0-∞ was not different between these groups. The Cmax, AUC0-∞ and t1/2 for NAT were profoundly greater in the CYP2D6*10/*10 group than they were in the CYP2D6*wt/*wt group. The concentration of active moieties of atomoxetine (atomoxetine + 4-HAT) in the CYP2D6*10/*10 group was 3.32-fold higher than that in the CYP2D6*wt/*wt group. The mean exposure to active moieties of atomoxetine was markedly higher in subjects with the CYP2D6*10/*10 genotype compared to that in those with the CYP2D6*wt/*wt genotype. The higher systemic exposure of the active atomoxetine moieties in CYP2D6*10/*10 individuals may increase the risk of concentration-related adverse events of atomoxetine, although this has not yet been clinically confirmed.

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Section: Discussionmentioning

confidence: 99%

Effects of the CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites

Byeon

Kim

et al. 2015

Arch. Pharm. Res.

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“…Specifically, the MPH could increase mean heart rate, mean blood pressure, or skin conductance level indicating increased sympathetic activity (45)(46). Despite the fact that increased noradrenergic neurotransmission in the prefrontal cortex -due to atomoxetine as a specific noradrenaline reuptake inhibitor -could elevate blood pressure and heart rate (47,48), the cardiovascular effects of atomoxetine were minimal in ADHD patients (49,50). However, to best of our knowledge, the effect of atomoxetine on skin conductance is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Potential Effect of Pharmacotherapy on Sympathetic Arousal in Autism

Bujnakova

Ondrejka

Mestanik

et al. 2017

Acta Medica Martiniana

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Background: Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder associated with autonomic nervous system (ANS) abnormalities. Moreover, at least 50% of children with ASD suffer from other comorbid diseases such as anxiety, depression, and attention deficit hyperactivity disorder (ADHD) associated with receiving psychotropic medication. From this context we aimed to evaluate changes in sympathetic arousal using analysis of electrodermal activity (EDA) as an index of sympathetic cholinergic activity in treated and non-treated autistic children under resting conditions. Methods: We examined 23 children with ASD and 14 healthy age- and gender-matched children at the age of 7–15 years. The ASD patients were divided into ASD non-treated group (n=12) and ASD treated group (n=11). The EDA was continuously monitored during resting phase in a supine position. The EDA amplitude (μS) was computed as an average of 5 min baseline period. Results: We found significantly lower EDA in ASD non-treated subgroup compared to controls indicating subtle abnormalities in the regulation of the sympathetic nervous system. Although no significant differences were found between the ASD treated and non-treated subgroups the ASD treated group showed comparable sympathetic activity relative to controls indicating a potential ameliorated treatment effect on sympathetic arousal in ASD. Conclusions: These findings could help to determine differences in sympathetic arousal in treated and non-treated children with ASD, which is important for assessment of autism-linked cardiovascular risk depending on pharmacotherapy.

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“…Side effects of atomoxetine include headache, abdominal pain, nausea, vomiting, decreased appetite, weight loss, irritability, insomnia, and sedation. Common cardiovascular side effects include increase in heart rate, sinus tachycardia, increase in SBP in adults, and palpitations …”

Section: Atomoxetine In Ohmentioning

confidence: 99%

“…Common cardiovascular side effects include increase in heart rate, sinus tachycardia, increase in SBP in adults, and palpitations. 20 The Table 1 summarizes the literature surrounding atomoxetine in OH. When compared with placebo in a randomized, single-blind, crossover study of 21 patients, atomoxetine in extremely low doses induced hypertension in patients with central autonomic failure, with an increase of 54 (±26) mm Hg in seated SBP and 45 (±23) mm Hg in standing SBP.…”

Section: Atomoxe Tine In Ohmentioning

confidence: 99%

Evaluating the effectiveness of atomoxetine for the treatment of primary orthostatic hypotension in adults

Patel

Simpson

Palevoda

et al. 2018

J of Clinical Hypertension

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Cardiovascular Side Effects of Atomoxetine and Its Interactions with Inhibitors of the Cytochrome P450 System

Cited by 15 publications

References 9 publications

Effects of the CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites

Effects of the CYP2D6*10 allele on the pharmacokinetics of atomoxetine and its metabolites

Potential Effect of Pharmacotherapy on Sympathetic Arousal in Autism

Evaluating the effectiveness of atomoxetine for the treatment of primary orthostatic hypotension in adults

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