QTC prolongation

EPS Sedation Anticholinergic Side Effects Cardiovascular Side Effects Seizure Effects/ QTc Prolongation... 

It has been recommended to discontinue a medication associated with QTc prolongation if the interval consistently exceeds 500 msec. 

Luck, S., Kiesecker, C., Thomas, D., Kathofer, S., Niroomand, F., Kiehn, J., Kreye, V.A., Katus, H.A., Schoels, W. and Karle, C.A. (2005) QTc prolongation by grapefruit juice and its potential pharmacological basis HERG channel blockade by flavonoids. Circulation, 111, 835-838. 

Clinical evaluation of QT/QTc prolongation and proarrhythmic potential for nonantiarrhythmic drugs the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline. Journal of Clinical Pharmacology, 46, 498-507. 

XL647 is currently in phase I chnical trials [102]. The MTD has not yet been defined, although two DLTs have been observed one QTc prolongation at 3.12 mg/kg/day (ca. 220mg/day) and one grade 3 diarrhea at 7.0 mg/kg/day (ca. 500 mg/day). One partial response (NSCLC) has been observed early in the dose escalation (0.06 mg/kg or 4.2 mg/day). Twenty-three percent of patients have experienced stable disease in the trial. 

Experience so far from cUnical trials has shown these agents can be well tolerated at biologically active doses. However, cardiac toxicity, mainly QTC prolongation, and cardiac arrhythmias, including atrial fibrillation and tor-... 

Electrolyte disturbances Correct potassium or magnesium deficiency before therapy begins as these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsades de pointes. 

Cardiac effects Acute, usually reversible, EGG changes (PR and QTc prolongation QRS widening) caused by dolasetron have been observed. Dolasetron appears to prolong depolarization and, to a lesser extent, repolarization time. The magnitude and frequency of the EGG changes increased with dose. These EGG interval prolongations usually returned to baseline within 6 to 8 hours but in some patients were present at 24-hour follow up. 

Hypersensitivity to fluoroquinolones or the quinolone group tendinitis or tendon rupture associated with quinolone use patients receiving disopyramide and amiodarone or other QTc-prolonging antiarrhythmic drugs reported to cause torsade... 

Cardiac effects Telithromycin has the potential to prolong the QTc interval in some patients. QTc prolongation may lead to an increased risk for ventricular arrhythmias, including torsades de pointes. 

QTc prolongation dose-related risk of torsades de pointes and sudden death... 

A child with Tourette s disorder is treated with a daily dose of 2 mg of pimozide for tics. A family doctor treats a streptococcal pharyngitis with clarithromycin, and 24 hours later the child develops palpitations. An electrocardiogram (ECG) reveals a QTc prolongation to 0.465 milliseconds. 

Cardiovascular side effects. Ziprasidone produced a mean QTc prolongation of 21 ms at maximal blood levels achieved with typical therapeutic doses. However, in all clinical trials, the rate of QTc intervals greater than 500 ms (considered a threshold for arrhythmia risk) did not differ from the rate associated with placebo (<0.1%). The QTc effect of ziprasidone is larger than that of other atypical antipsychotics but smaller than that of thioridazine. Blood levels of ziprasidone increased about 40% when ketoconazole (a metabolic inhibitor) was coadministered, and no change in QTc duration was detected. 

Dihydroindolone Ziprasidone Perhaps less weight gain than clozapine, parenteral form available QTC prolongation... 

Haddad PM, Anderson IM Antipsychotic-related QTC prolongation, torsade de pointes and sudden death. Drugs 2002 62 1649. [PMID 12109926]... 

Erythromycin Prevents bacterial protein synthesis by binding to the 50S ribosomal subunit Bacteriostatic activity against susceptible bacteria Community-acquired pneumonia t pertussis corynebacterial, and chlamydial infections Oral, IV hepatic clearance (half-life 1.5 h) dosed every 6 h cytochrome P450 inhibitor Toxicity Gastrointestinal upset, hepatotoxicity, QTC prolongation... 

Fluoroquinolones are extremely well tolerated. The most common effects are nausea, vomiting, and diarrhea. Occasionally, headache, dizziness, insomnia, skin rash, or abnormal liver function tests develop. Photosensitivity has been reported with lomefloxacin and pefloxacin. QTC prolongation may occur with gatifloxacin, levofloxacin, gemifloxacin, and moxifloxacin, which should be avoided or used with caution in patients with known QTC interval prolongation or uncorrected... 

In view of the clinical importance of the corrected Q-T interval (QTc) prolongation in drug development, the DIDB team has created a new set of data summarizing QTc effects of drugs. In addition, 150 publications already in the database were recently reviewed to highlight the articles with QTc measurement and cases of QTc prolongation. Case reports of torsades de pointes/ventricular fibrillation were also individualized for easy access by DIDB users. 

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