QTc INTERVAL AND RISK AJC 1993; 72:21B

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QTc INTERVAL AND RISK AJC 1993 7221B

• Relative Risk of Arrhythmias 1.052x
• where x msec increase/10
• above QTc 440msec
• QTc 440msec Risk 1.0520 1.0
• QTc 500msec Risk 1.0526 1.4
• QTc 640msec Risk 1.05220 2.8

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DRUGS AND QTc ISSUES

• 1. QTc prolongation and risk exponential
• 2. Magnitude of the QTc signal
• mean ?QTc range outliers
• 3. Drug effect on QTc
• a. direct e.g., sotalol, cisapride
• b. indirect (interaction)
• i) drug-drug terfenadine ketoconazole
• ii) drug-gene LQTS mutation/polymorphism

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DRUGS AND QTc Questions

• 1. Do the pre-clinical studies indicate an effect
  on ventricular repolarization?
• 2. Do clinical studies indicate a QTc signal?
• 3. What is the magnitude of the QTc signal?
• 4. Are there potential drug interactions?
• 5. Does the drug have unique characteristics?