REMINDER: Use of QTdrugs in Clinical Decision Support Programs

REMINDER:  The QTdrugs List includes three distinct risk categories for Torsades de Pointes (TdP) and QT prolongation but not all drugs in the List should be considered “QT prolonging”.
 

Because of the inherent complexity of drug-induced QT prolongation and the ensuing risk of developing TdP, AZCERT has sub-divided the QTdrugs List into three categories of risk of causing TdP.¹ We want to remind those who wish to use the QTdrugs List in clinical decision making of the differences between these categories and caution that the QTdrugs List should not simply be thought of as a list of “QT-prolonging drugs”… it is not.

Drugs that are in the Known Risk of TdP category have clear and compelling evidence that they can cause TdP.  By definition, they prolong the QT interval because that action is required for induction of TdP.  These drugs should be avoided in patients with known QT prolongation unless there is a compelling reason for their use. This category has been extensively evaluated and found useful in clinical decision support programs and, when used as factors in QT/TdP risk scores, has been proven to be a major contributor to the scores' accuracy for predicting increased mortality² and excessive QT prolongation.^3-5  Because of the extensive supporting data, we recommend that this category be used in clinical decision support systems for QT risk management.

Drugs in the Possible Risk of TdP category have definite evidence of QT prolongation when they are taken as intended BUT they do not, at this time, have convincing clinical evidence for risk of TdP.  In patients known to have QT prolongation, these drugs may increase TdP risk and we do not recommend their use unless clinical benefit is expected to be high.  When evaluated in clinical decision support programs, this category of drugs has not been found to contribute to the predictive accuracy⁶ of QT risk scores and we do not recommend its inclusion at this time.

Drugs in the Conditional Risk of TdP category are a complex group of drugs that have been associated with TdP BUT only under certain conditions such as drug overdose or when they are used in combination with drugs or conditions known to prolong the QT interval.  Since many of these drugs do not per se prolong the QT interval, we do not consider the Conditional Risk category be “QT-prolonging” and do not recommend that the category be used as a risk factor in clinical decision support programs.

Drugs to Avoid in Congenital Long QT Syndrome

In addition to the QTdrugs List, the CredibleMeds website offers a separate list of Drugs to Avoid in congenital long QT syndrome (cLQTS). This list includes all drugs in the QTdrugs List plus some additional non-QT-prolonging drugs that could have special risk for some patients with cLQTS.  Whereas the list is extremely useful and relevant for those with cLQTS, we do not recommend that the Drugs to Avoid in cLQTS list be used in clinical decision support programs at this time.

We hope this information is clarifying and we would be glad to answer any questions about how the QTdrugs list has been constructed and the definitions of its risk categories for QT/TdP. Contact us at info@azcert.org.

Raymond L. Woosley, MD, PhD  and C. William Heise, MD, AZCERT

Reference List

1. Woosley RL, Romero K, Heise CW, et al. Adverse Drug Event Causality Analysis (ADECA): A Process for Evaluating Evidence and Assigning Drugs to Risk Categories for Sudden Death. Drug Saf 2017;40:465-74.

2. Haugaa KH, Bos JM, Tarrell RF, Morlan BW, Caraballo PJ, Ackerman MJ. Institution-wide QT alert system identifies patients with a high risk of mortality. Mayo Clin Proc 2013;88:315-25.

3. Tisdale JE, Jaynes HA, Kingery JR, et al. Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes 2013;6:479-87.

4. Vandael E, Vandenberk B, Vandenberghe J, Spriet I, Willems R, Foulon V. Development of a risk score for QTc-prolongation: the RISQ-PATH study. Int J Clin Pharm 2017;39:424-32.

5. Bindraban AN, Rolvink J, Berger FA, et al. Development of a risk model for predicting QTc interval prolongation in patients using QTc-prolonging drugs. Int J Clin Pharm 2018;40:1372-9.

6. Vandael E, Vandenberk B, Vandenberghe J, Willems R, Foulon V. Risk factors for QTc-prolongation: systematic review of the evidence. Int J Clin Pharm 2017;39:16-25.