Can I administer Ribociclib (ribociclib) to a patient with a prolonged QTc interval of 416 milliseconds?

From the Guidelines

Ribociclib should not be administered to a patient with a prolonged QTc interval of 416 milliseconds without careful consideration and close monitoring of the QTc interval. While this QTc value is only slightly prolonged, ribociclib is known to cause QT interval prolongation, which could potentially increase the risk of dangerous arrhythmias like torsades de pointes 1. The potential benefits of treatment with ribociclib, including improved progression-free survival and overall survival in patients with HR-positive, HER2-negative metastatic breast cancer, as seen in the MONALEESA-7 trial 2, must be weighed against the increased cardiac risk. Key considerations include:

• Close monitoring of the QTc interval with ECGs at baseline, after 14 days of treatment, at the beginning of the second cycle, and as clinically indicated thereafter
• Dose modifications may be required if QTc exceeds 480 ms during treatment
• Correction of electrolyte abnormalities, particularly potassium and magnesium, before starting therapy
• Avoidance of concomitant use of other QT-prolonging medications if possible
• Cardiology consultation if there are additional cardiac risk factors The decision to use ribociclib in this situation should prioritize the patient's overall morbidity, mortality, and quality of life, taking into account the potential benefits and risks of treatment 2.

From the FDA Drug Label

Table 4: Dose Modification and Management for QT Prolongation QTcF* prolongation | Early breast cancer | Advanced or metastatic breast cancer ----------------------------------------|--------------------------------------------------|----------------------------------------

480 ms and ≤ 500 ms | Interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms Resume at the same dose | Reduce to the next lower dose level If QTcF > 480 ms recurs, interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms, then resume at next lower dose level. 500 ms | Interrupt KISQALI treatment and wait until QTcF resolves to ≤ 480 ms, then resume at next lower dose level. | If QTcF > 500 ms recurs, discontinue KISQALI.

The patient's QTc interval of 416 milliseconds is below the threshold of 480 ms, at which dose modification or interruption is recommended. No dose adjustment is required for a QTc interval of 416 milliseconds, as it does not meet the criteria for dose modification or interruption outlined in Table 4. However, it is essential to monitor ECGs as clinically indicated, especially since the patient has a prolonged QTc interval, to ensure that it does not exceed the threshold during treatment with ribociclib 3.

From the Research

QTc Interval Prolongation and Ribociclib Administration

• The administration of Ribociclib to a patient with a prolonged QTc interval of 416 milliseconds requires careful consideration of the potential risks associated with QTc interval prolongation.
• According to a systematic review and meta-analysis of randomized controlled trials 4, the use of CDK4/6 inhibitors, including Ribociclib, is associated with an increased risk of QTc prolongation.
• A study analyzing gene expression and pharmacological data 5 suggests that Ribociclib, but not Palbociclib, may act by down-regulating the expression of KCNH2 and up-regulating SCN5A and SNTA1, which are associated with long QT syndrome.
• The risk of torsades de pointes, a potentially life-threatening arrhythmia, is associated with QTc interval prolongation, and a QT interval of at least 500 milliseconds is generally considered to correlate with a higher risk 6.
• However, a study on the comparison of QT interval readings between a smartphone heart monitor and a 12-lead ECG 7 found that a QTc of > 500 milliseconds was associated with a higher likelihood of not achieving perfect agreement between the two methods.
• Another study on QT interval prolongation and the rate of malignant ventricular dysrhythmia and cardiac arrest in adult poisoned patients 8 found that the risk of cardiac arrest remains low even in patients with prolonged QTc intervals, with an overall rate of 1.1% and 1.7% for patients with QTc > 500 ms.

Considerations for Administration

• The decision to administer Ribociclib to a patient with a prolonged QTc interval of 416 milliseconds should be based on a careful assessment of the potential benefits and risks, taking into account the patient's individual clinical characteristics and medical history.
• Close monitoring of the patient's QTc interval and cardiac function is recommended, as well as careful consideration of any concomitant medications that may also prolong the QTc interval 4, 5, 6.