Propafenone for the Prevention of Atrial Tachyarrhythmias After Cardiac Surgery: A Randomized, Double-blind Placebo-controlled Trial

Mörike, Klaus; Kivistö, Kari T.; Schaeffeler, Elke; Jägle, Christine; Igel, Svitlana; Drescher, Siegfried; Fux, Richard; Marx, Claudia; Hofmann, Ute; Engel, Corinna; Wagner, F.; Delabar, Ursula; Meisner, C; Bail, DH; Böhm, J; Ch, Gleiter; Ziemer, Gerhard; Rein, JG; Hellberg, KD; Eichelbaum, Michel; Schwab, Matthias

doi:10.1038/sj.clpt.6100473

Cited by 18 publications

(14 citation statements)

References 26 publications

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“…This indicates that even CF patients, who are carriers of functionally relevant CYP2D6 variants, may profit from a doseadjusted amitriptyline therapy. In principle low doses of amitriptyline have been successfully administered for patients with major depression, fibromyalgia and irritable bowel syndrome [13] and, thus, such a treatment option might be also applied for CF patients. A further concern to use amitriptyline in CF patients, infected chronically with P. aeruginosa or other bacterial pathogens, is the fact that amitriptyline would prevent the acute increase of ceramide levels in the respiratory tract observed after P. aeruginosa infections, which seems to be part of the host defence [12].…”

Section: Discussionmentioning

confidence: 99%

“…Because mutations of cytochrome P450 (CYP2D6) may reduce the hepatic metabolism of amitriptyline, patients were excluded if they were homozygous or compound heterozygous for the CYP2D6 alleles *4,*5,*6,*9,*10,*41, since these individuals may have a higher sensitivity to amitriptyline. Genotyping was performed as previously described [13]. Glaucoma, seizures, heart failure, major depression, clinical instability, pregnancy or involvement in other clinical studies were further exclusion criteria.…”

Section: Pilot Studymentioning

confidence: 99%

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Therapeutic Efficacy and Safety of Amitriptyline in Patients with Cystic Fibrosis

Riethmüller¹,

Anthonysamy

Serra

et al. 2009

Cell Physiol Biochem

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Amitriptyline, a blocker of acid sphingomyelinase and acid ceramidase, significantly reduces Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) mice with concurrent increase of survival. Our aim was to establish whether amitriptyline is safe and effective in the treatment of CF patients. In a randomised, double-blinded, placebo-controlled, cross-over pilot study, 4 adult CF patients received 37.5 mg of amitriptyline or placebo twice daily for 14 days. Subsequently in a phase II study 19 adult CF patients were randomly allocated to three treatment groups receiving amitriptyline once daily for 28 days at doses of 25 mg (n=7), 50 mg (n=8), or 75 mg (n=8) or placebo (n=13). The primary outcome was the difference of forced expiratory volume in 1 sec (FEV₁) at day 14 between amitriptyline and placebo. Primary endpoint measures improved significantly in three of four patients in the pilot study after amitriptyline treatment vs placebo (relative FEV₁: 14.7±5%; p = 0.006) and in the 25 mg treatment group of the phase II study (relative FEV₁: 4.0±7%; p = 0.048). Amitriptyline was well tolerated in both studies and 96% of the patients completed the studies. Amitriptyline as a novel therapeutic option in patients with CF is safe and seems to be efficacious.

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Section: Discussionmentioning

confidence: 99%

Section: Pilot Studymentioning

confidence: 99%

Therapeutic Efficacy and Safety of Amitriptyline in Patients with Cystic Fibrosis

Riethmüller¹,

Anthonysamy

Serra

et al. 2009

Cell Physiol Biochem

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“…The drug label approved by FDA for propafenone recommends the dosing regimen is the same for all patients (CYP2D6 PMs and NMs) (Rouini and Afshar, 2017). The DPWG guidelines recommend, “CYP2D6 PMs receive a 70% reduction in initial dose, plus electrocardiogram and plasma concentration monitoring.” For CYP2D6 IMs and UMs, the guideline states that data which calculates the dose adjustment is insufficient and recommends that, “the drug dose adjustment should be based on plasma concentration and the electrocardiogram, or it is encouraged to choose alternative drugs, such as sotalol, quinidine, disopyramide, or amiodarone” (Mörike et al, 2008).…”

Section: Pharmacogenomics Of Commonly Used Icu Medicationsmentioning

confidence: 99%

Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit

et al. 2018

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In the intensive care unit (ICU) setting, where highly variable and insufficient drug efficacies, as well as frequent and unpredictable adverse drug reactions (ADRs) occur, pharmacogenomics (PGx) offers an opportunity to improve health outcomes. However, PGx has not been fully evaluated in the ICU, partly due to lack of knowledge of how genetic markers may affect drug therapy. To fill in this gap, we conducted a review to summarize the PGx information for the medications commonly encountered in the ICU.

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“…Antiarrhythmic efficacy. At low doses of propafenone, CYP2D6*4 carriers have greater reduction in exercise-or isoproterenol-induced HR compared to noncarriers (143), although not with higher doses or without the "stress" of exercise/isoproterenol (140,142,143). Further, CYP2D6*4 carriers have enhanced suppression of atrial and ventricular arrhythmias compared to noncarriers in some studies (141,144), although not in all (140,142) Therefore, there are insufficient data to make any conclusions regarding CYP2D6 genotype and antiarrhythmic efficacy.…”

Section: Antiarrhythmic Drugsmentioning

confidence: 99%

Clinical Application of Cardiovascular Pharmacogenetics

Voora

Ginsburg

2012

Journal of the American College of Cardiology

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Pharmacogenetics primarily uses genetic variation to identify subgroups of patients who may respond differently to a certain medication. Since its first description, the field of pharmacogenetics has expanded to study a broad range of cardiovascular drugs and has become a mainstream research discipline. Three principle classes of pharmacogenetic markers have emerged: 1) pharmacokinetic; 2) pharmacodynamic; and 3) underlying disease mechanism. In the realm of cardiovascular pharmacogenetics, significant advances have identified markers in each class for a variety of therapeutics, some with a potential for improving patient outcomes. While ongoing clinical trials will determine if routine use of pharmacogenetic testing may be beneficial, the data today support pharmacogenetic testing for certain variants on an individualized, case-by-case basis. Our primary goal is to review the association data for the major pharmacogenetic variants associated with commonly used cardiovascular medications: antiplatelet agents, warfarin, statins, beta-blockers, diuretics, and antiarrhythmic drugs. In addition, we highlight which variants and in which contexts pharmacogenetic testing can be implemented by practicing clinicians. The pace of genetic discovery has outstripped the generation of the evidence justifying its clinical adoption. Until the evidentiary gaps are filled, however, clinicians may choose to target therapeutics to individual patients whose genetic background indicates that they stand to benefit the most from pharmacogenetic testing.

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Propafenone for the Prevention of Atrial Tachyarrhythmias After Cardiac Surgery: A Randomized, Double-blind Placebo-controlled Trial

Cited by 18 publications

References 26 publications

Therapeutic Efficacy and Safety of Amitriptyline in Patients with Cystic Fibrosis

Therapeutic Efficacy and Safety of Amitriptyline in Patients with Cystic Fibrosis

Pharmacogenomics of Medications Commonly Used in the Intensive Care Unit

Clinical Application of Cardiovascular Pharmacogenetics

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