CONSENSUS STATEMENT FOR DECREASING THE RISK OF TORSADES DE POINTES IN PATIENTS ON QT-PROLONGING COVID-19 ANTI-VIRAL DRUGS (Chloroquine, Hydroxychloroquine, Azithromycin, Lopinavir/Ritonavir)

1. The risk for the development of Torsades de Pointes must not rely solely on the QTc measurement but should rather be an overall risk-benefit assessment of the patient’s risk based on the general clinical

2. Avoid, correct, and control other factors that can potentially enhance the risk of Torsades de Pointes of these QT-prolonging anti-viral drugs^1,2,3.
   • Advance Age
   • Female gender
   • Heart failure (ejection fraction <20%)
   • Renal insufficiency
   • Concomitant non-essential QT prolonging medications
   • Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia)
   • Use of diuretics
   • Bradycardia
   • Ischemia/infarction
   • Left ventricular hypertrophy
   • History of Congenital or Acquired Long QT Syndrome

3. Corrected QT (QTc) Measurement (see illustrations)

• A rhythm strip, preferably Lead II, may be sufficient for serial
• Use Bazett’s Formula: QTa/RR^1/2 for the computation of the
• The actual QT interval (QTa) is measured from the start of the QRS complex to the end of the T wave. The RR measurement is taken from the RR interval preceding the measured actual QT
• If the end of the T wave cannot be determined due to an abnormal TU morphology, the tangent method is used to define the end of the T wave⁴ (see illustration⁴ below):

• Actual QT measurement in the presence of intraventricular conduction delay (QRS > 120 msec)

e.g. right bundle branch block (RBBB), and left bundle brank block (LBBB) is the same (see 3.3).

• For Sinus rhythm: take an average of at least 3 cycles
• For Atrial fibrillation1, either:
  • Calculate the average QTc of measurement made from QTa of the shortest and the longest RR interval in the entire rhythm strip (see illustration1 below), OR
  • Average of 10 QTc measurements

4. QTc Monitoring

• Measure QTc immediately prior to each dose of the anti-viral drug
• Monitor QTc two hours (or at the estimated peak levels) after the 1^st two doses of the drug (e.g. post 1^st 2 doses of 400 mg of hydroxychloroquine)
• Monitor QTc twice a day and more frequently if it is noted to be prolonging

5. Recommended QTc threshold for NOT starting and dose reduction and/or discontinuation of QT- prolonging anti-viral drug

• QTc > 500 msec for Narrow QRS
• QTc > 550 msec for Wide QRS (more than 120 msec QRS duration)
• QTc > 60 msec absolute increase from prior QTc^{2, 3,}

6. Do not give essential QT-prolonging anti-viral drugs at the same Schedule according to the estimated peak plasma values of individual drugs.

7. Correct electrolytes prior to starting any QT-prolonging anti-viral drug and do aggressive electrolyte correction to maintain at high normal values (potassium >5 mEq/L, Magnesium > 2.0 mEq/L).

8. Follow anti-viral drug dose adjustment according to renal

9. Discontinue non-essential potential QT prolonging medications and/or find non-QT prolonging

References:

¹ Al-Khatib, Sana, Allen LaPointe, Nancy et al, Journal of the American Medical Association 2003; Vol 28 No. 16

² Drugs and Therapeutics Bulletin, British Medical Journal 2016; 353: i2732

³ Tisdale, James E. Canadian Pharmacist Journal 2016; Vol. XX No. X

⁴ Vink, Arja Suzanne, Neumann, Benjamin, Lieve, Krystien, Wilde, Arthur, Postema, Circulation 2018; 138: 2345-2