QT Prolongation - All Kinase Inhibitors

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Kinase Inhibitor QT-interval prolongation?
 (Yes/ No)
Recommendations on how DDIs can be managed
Afatinib No  
Axitinib No  
Bosutinib No

Bosutinib should be administered with caution to patients with a history of or predisposition for QT prolongation, uncontrolled or significant cardiac disease including recent MI, CHF, unstable angina or clinically significant bradycardia, or taking medicinal products known to prolong the QT interval

Monitoring is advisable and a baseline ECG is recommended prior to initiating therapy and as clinically indicated

Hypokalemia or hypomagnesemia must be corrected prior to bosutinib administration and should be monitored periodically during therapy

Cabozantinib No

Cabozantinib should be used with caution in patients with a history of QT interval prolongation, those taking antiarrhythmics, or those with relevant pre-existing cardiac disease, bradycardia, or electrolyte disturbances

When using cabozantinib, periodic monitoring with on-treatment ECGs and electrolytes (serum calcium, potassium, and magnesium) should be considered

Ceritinib Yes

Avoid use in patients with congenital long QT syndrome

Conduct periodic monitoring with ECGs and elecotrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities or taking medications that prolong the QT interval

Withhold in patients who develop a QT interval greater than 500 msec on at least 2 separate ECGs until the QT interval is less than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then resume at a reduced dose. Permanently discontinue in patients who develop QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia

Crizotinib Yes

Monitor with ECGs and electrolytes in patients who have a history of or predisposition for QT prolongation, or who are taking medications that prolong QT

Temporarily suspend (Grade 3 QTc prolongation), dose reduce, or permanently discontinue (Grade 4 QTc prolongation) crizotinib

Dabrafenib Yes

Treatment with dabrafenib is not recommended in patients with uncorrectable electrolyte abnormalities (including magnesium), long QT syndrome or those taking medicines known to prolong QT interval

ECG and electrolytes must be monitored in all patients before treatment, after 1 month of treatment, and after dose modification

Further monthly monitoring is recommended in patients with moderate to severe hepatic impairment during the first 3 months of treatment, followed by every 3 months thereafter

If QTc exceeds 500 msec, dabrafenib should be temporarily interrupted, electrolyte abnormalities corrected, and cardiac risk factors for QT prolongation (e.g. CHF, bradyarrhythmias) controlled

Permanent discontinuation of dabrafenib is recommended if QTc >500 msec and there is a >60 msec change from pre-treatment values

Dasatinib No

Dasatinib should be used with caution in patients who have or may develop prolongation of the QT interval, including patients with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy

Correct hypokalemia or hypomagnesemia prior to dasatinib initiation

Erlotinib No  
Gefitinib Yes  
Ibrutinib Yes Clinicians are cautioned to use clinical judgment when assessing whether to prescribe ibrutinib to patients at risk from further shortening QTc duration (e.g., congenital short QT syndrome or a family history of the syndrome)
Idelalisib Yes Concurrent administration of salmeterol and idelalisib is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation.
Imatinib No  
Lapatinib Yes

Lapatinib should be administered with caution to patients who have or may develop prolongation of QTc (e.g., hypokalemia, hypomagnesemia, congenital long QT syndrome, co-administration of anti-arrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy)

Hypokalemia or hypomagnesemia should be corrected prior to lapatinib administration

ECG and electrolyte monitoring should be considered

Lenvatinib Yes

Withhold lenvatinib for the development of Grade 3 or greater QT interval prolongation

Resume lenvatinib at a reduced dose when QT prolongation resolves to Grade 0 or 1 or baseline.

Nilotinib Yes

Prior to nilotinib administration and periodically, patients should be monitored for hypokalemia or hypomagnesemia and deficiencies corrected

ECGs should be obtained at baseline, 7 days after initiation, and periodically thereafter, and following any dose adjustments

Nilotinib should not be administered to patients with hypokalemia, hypomagnesemia, or long QT syndrome

Concomitant use of drugs known to prolong the QT interval should be avoided

Nintedanib No Caution should be exercised when administering nintedanib in patients who may develop QTc prolongation
Pazopanib Yes

Pazopanib should be used with caution in patients with a history of QT interval prolongation, in those taking antiarrhythmics or other medications that may prolong QT interval, and those with relevant pre-existing cardiac disease

Baseline and periodic monitoring of ECGs and maintenance of electrolytes (e.g., calcium, magnesium, potassium) within the normal range should be performed

Ponatinib No  
Regorafenib No  
Ruxolitinib No  
Sorafenib Yes

If a drug is indicated which also prolongs the QTc interval, an ECG should be obtained 24-48 hours before and 1 week after initiating the concomitant therapy.

Pharmacists should also routinely check for concomitant use of such QT prolonging drugs such as 5HT3 antagonists, antibiotics, antifungals and over the counter drugs such as domperidone

Sunitinib Yes

Sunitinib should not be administered with QTc interval-prolonging drugs (e.g. 5HT3 antagonists, antibiotics, antifungals and over-the-counter drugs (e.g. domperidone)

If co-administration of QTc interval-prolonging drugs is necessary, an ECG should be obtained 24-48 hours before, and 1 week after, the start of treatment

Trametinib No  
Vandetanib Yes

Concomitant administration with products known to prolong the QT interval should be avoided

Co-administration with ondasetron has a small additive effect on prolongation of the QTc interval

Vemurafenib Yes  

For more information on the most-commonly used kinase inhibitors, please click on each agent below to find out more on drug-drug interactions associated with QT prolongators.

References

  1. Food and Drug Administration. 2015. (last accessed July 2015)
  2. European Medicines Agency. 2015. (last accessed July 2015)
Last update: 21 July 2015