Drug-Induced QT Prolongation: A Stepwise Approach

Full update August 2022

 

When a clinical scenario presents itself in which drug-induced QT prolongation/torsades de pointes is a concern, consider a stepwise approach to gather data to inform decision-making and mitigate risk. Use clinical judgment; specific recommendations based on high-level data are lacking.

1. Assess drug risk.

  • Consult product information or www.crediblemeds.org regarding risk of torsades de pointes. Drugs may have one of the following levels of risk:
    • known risk (clearly associated with torsades).
    • possible risk (can cause QT prolongation, but unclear torsades risk when used as directed).
    • conditional risk (i.e., poses risk only in certain patients or clinical situations [e.g., electrolyte disturbance, long QT syndrome, high dose, drug interaction]).4
  • Screen for drug-drug interactions that could increase risk.2
  • Assess risk of QT prolongation/torsades de pointes of alternative medications.2

2. Assess patient risk.

  • Does the patient have long QT syndrome or a history of torsades de pointes?1
  • Does the patient have structural heart disease (e.g., heart failure with reduced ejection fraction, left ventricular hypertrophy), recent myocardial infarction, a family history of long QT syndrome or sudden death, or a personal history of symptoms suggestive of torsades de pointes (e.g., palpitations, syncope)?1-4
  • Does the patient have impaired kidney or liver function, or untreated thyroid disease?2
  • Does the patient have potentially modifiable risk factors for QT prolongation (e.g., hypokalemia, hypomagnesemia, hypocalcemia, bradycardia)?2
  • Does the patient have demographic risk factors for QT prolongation (e.g., female sex, age >65 years)?2
  • Consider use of a risk score:2

3. Mitigate risk.

  • Avoid QT prolonging drugs if the patient has long QT syndrome or a history of torsades de pointes.1,2,4
    • Also consider alternatives for patients with higher risk (e.g., Tisdale score ≥7; ≥2 QT-prolonging drug plus a risk factor; one QT-prolonging drug plus multiple risk factors).4
  • Correct modifiable risk factors:
    • Correct potassium, magnesium, and calcium to normal or toward the upper limit of normal (e.g., potassium >4 mEq [mmol]/L; magnesium 2 mg/dL [0.822 mmol/L]).2-4
    • If appropriate, stop or reduce the dose of medications that can cause bradycardia or electrolyte loss (e.g., diuretics).2
  • Dose QT-prolonging medications appropriately.
    • adjust dose for kidney and liver function.3
    • use lowest effective dose.1
    • adhere to dosing recommendations to reduce risk (e.g., citalopram, escitalopram, ondansetron).1,5
    • administer intravenous QT-prolonging drugs at the recommended rate.4
  • Manage drug-drug interactions.
    • Avoid drugs that inhibit the metabolism of the patient’s QT prolonging medication(s).3
    • Avoid, if possible, concomitant use of more than one QT-prolonging medication.4
  • Consider ECG monitoring in higher risk patients (e.g., Tisdale score ≥7; ≥2 QT-prolonging drugs plus a risk factor; one QT-prolonging drug plus multiple risk factors), or in the event of symptoms.2,4
    • Consider ECG at baseline, then when the drug reaches steady state (i.e., four to five half-lives after initiation or dosage increase), and then in the event of symptoms.2
      • Also consider ECG periodically (e.g., every three to six months) in high-risk patients (e.g., high-risk druga plus additional QT prolonging drug or risk factors).2,3
      • In hospitalized patients, consider monitoring every eight to 12 hours after starting or increasing the dose.4
    • Weigh the risks and benefit of adding a QT-prolonging medication if the QTc interval is >450 ms for males or >460 ms for females.1,4 Generally stop the drug if the QTc interval increases by >60 ms compared to baseline or exceeds 500 ms.1,4
      • Be aware of limitations of automated QT interval reports (e.g., in patients with bundle branch block or ventricular rhythm); manually calculate as appropriate (e.g., with Bazett’s formula).6
  • Educate all patients prescribed a potentially QT-prolonging drug to report symptoms (e.g., palpitations, syncope, lightheadedness, dizziness).2
  1. A high-risk drug could be considered one with drug with a QT caution, warning, or contraindication in the product labeling.2

Abbreviations: ms = millisecond; QTc = QT interval corrected for heart rate.

References

  1. Grindrod KA, Nagge J. Simplifying QT prolongation for busy clinicians. Can Fam Physician. 2019 Apr;65(4):268-270.
  2. Khatib R, Sabir FRN, Omari C, et al. Managing drug-induced QT prolongation in clinical practice. Postgrad Med J. 2021 Jul;97(1149):452-458.
  3. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation. 2020 Oct 13;142(15):e214-e233.
  4. Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016 May;149(3):139-52.
  5. Clinical Pharmacology powered by Clinical Key. Tampa, FL: Elsevier; 2022. http://www.clinicalkey.com. (Accessed July 20, 2022).
  6. Noel ZR, See VY, Flannery AH. Walk the Line-The Importance of Well-Informed Interpretation of QT Prolongation. Ann Pharmacother. 2021 Jan;55(1):123-126.

Cite this document as follows: Clinical Resource, Drug-Induced QT Prolongation: A Stepwise Approach. Pharmacist’s Letter/Prescriber’s Letter. August 2022. [380804]

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