Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin

Furst, Benjamin A.; Champion, Katherine; Pierre, Joseph M.; Wirshing, Donna A.; Wirshing, William C.

doi:10.1016/s0006-3223(01)01333-6

Cited by 41 publications

(24 citation statements)

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“…Coadministration of quetiapine and lovastatin was associated with QTc interval prolongation in a 46-year-old woman with schizophrenia initially receiving quetiapine, 800 mg/day, and sertraline, 100 mg/day. 51 A screening lipid profile revealed mildly elevated cholesterol and triglycerides. The patient was given lovastatin, 10 mg/day.…”

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confidence: 99%

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New Generation Antipsychotic Drugs and QTc Interval Prolongation

Vieweg

2003

Prim. Care Companion CNS Disord.

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Background: Recent regulatory and clinical concerns have brought into sharp focus antipsychotic drug-induced QTc interval prolongation, torsades de pointes, and sudden cardiac death. Several new generation (atypical) antipsychotic drugs have either been withdrawn from clinical use or delayed in reaching the marketplace due to these concerns. Because torsades de pointes is rarely found, QTc interval prolongation serves as a surrogate marker for this potentially life-threatening arrhythmia. Current methods of calculating this electrocardiographic parameter have limitations. The primary care physician is a key member of the team managing a patient who requires administration of antipsychotic drugs. This article focuses on new generation antipsychotic drugs and principles useful to both the primary care physician and the psychiatrist.Method: PubMed was searched in September 2002 using the terms antipsychotic drug and QT interval. References were examined from review articles describing antipsychotic drugs and the QT interval. The author's files gathered over the past 20 years on the QT interval were also reviewed.Results: Nine cases were available in which druginduced QTc interval prolongation was associated with new generation antipsychotic drug administration. Eight cases were taken from the literature, and the author added one additional report. The newer agents involved were risperidone, quetiapine, and ziprasidone. In at least 8 cases, there was evidence of other risk factors associated with QTc interval prolongation. In one case frequently referenced in the literature, the authors misunderstood their own data showing that QTc interval prolongation did not relate to delayed ventricular repolarization. In another instance, 2 authors reported on the same patient, with important information missing from both articles. No evidence of torsades de pointes appeared in any of the 9 cases.Conclusions: No evidence is currently available in the literature implicating new generation antipsychotic drugs in the production of torsades de pointes. However, the absence of such evidence does not prove that newer antipsychotic drugs do not cause torsades de pointes. Among patients free of risk factors for QTc interval prolongation and torsades de pointes, current literature does not dictate any specific consultative or laboratory intervention before administering new generation antipsychotic drugs. When risk factors are present, evaluation and intervention specific to those risk factors should dictate the clinician's course of action. More specific guidelines for monitoring the QT interval and risk of torsades de pointes await improved methods of measuring the QTc interval relevant to each patient.(Primary Care Companion J Clin Psychiatry 2003;5:205-215)

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“…Commentary. To explain QTc interval prolongation in their case, Furst et al 51 postulated that lovastatin inhibited the metabolism of quetiapine, thereby increasing the plasma concentration of the newer antipsychotic drug to cardiotoxic levels. The authors offer no information about the patient's heart rate, and recovery was uneventful.…”

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confidence: 99%

New Generation Antipsychotic Drugs and QTc Interval Prolongation

Vieweg

2003

Prim. Care Companion CNS Disord.

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“…Case 3, 2002 [Furst et al 2002] 'Possible association of QTc interval prolongation with coadministration of quetiapine and lovastatin'…”

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Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports

Hasnain

Vieweg

Howland

et al. 2013

Therapeutic Advances in Psychopharmacology

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Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes (TdP) when using this drug within the approved labeling. We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an 'outlier' manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.

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“…In der im Zusammenhang mit der klinischen Prüfung von Ziprasidon durchgeführten Vergleichsstudie, betrug die mittlere Verlängerung des QTcIntervalls im Steady-state 14,5 ms und war damit stärker ausgeprägt als unter Risperidon, Olanzapin und Haloperidol [16]. Einzelne Fälle von abnormer QT-Verlän-gerung unter Quetiapin liegen vor [35][36][37]. Experimentelle Untersuchungen belegen eine konzentrationsabhängige Blockade von I Kr [38].…”

Section: Risperidonunclassified

Antipsychotikainduzierte QT-Verlängerung

Haverkamp

Deuschle

2006

Nervenarzt

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Prolongation of myocardial repolarisation, i.e. lengthening of the QT interval on surface electrocardiogram, has been recognised as a side effect of many drugs, including antipsychotics. In predisposed individuals, abnormal excessive QT prolongation and severe ventricular arrhythmias (the ventricular tachycardia type 'torsade de pointes', or TdP) may occur. In almost all cases, additional factors are present that increase the propensity of patients to develop TdP, such as serum hypokalemia, the combination of drugs prolonging repolarisation, overdosing, intoxication, and factors interfering with drug metabolism and excretion. Serum hypokalemia and/or bradycardia may induce TdP alone, in the absence of drugs prolonging the QT interval. Experimental studies demonstrate that prolongation of myocardial repolarisation is a class effect of neuroleptics. Clinically, the extent to which individual drugs prolong the QT interval varies. Among the antipsychotics, thioridazine has the greatest propensity to induce abnormal QT prolongations and TdP. Case reports of TdP with other antipsychotics have been published. Physicians prescribing physicians these drugs must be aware that they can induce proarrhythmia in individual cases. They should also be aware of the circumstances which are necessary for abnormal QT prolongation and TdP to develop. Patients should be monitored with regard to these risk factors before and during drug treatment.

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Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin

Cited by 41 publications

References 8 publications

New Generation Antipsychotic Drugs and QTc Interval Prolongation

New Generation Antipsychotic Drugs and QTc Interval Prolongation

Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports

Antipsychotikainduzierte QT-Verlängerung

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