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Drug Interactions between Fensolvi and vandetanib

This report displays the potential drug interactions for the following 2 drugs:

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Major

leuprolide vandetanib

Applies to: Fensolvi (leuprolide) and vandetanib

GENERALLY AVOID: Vandetanib can cause concentration-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a phase 3 clinical trial where 231 medullary thyroid cancer patients were randomized to receive vandetanib 300 mg once daily, mean change in QTcF (Fridericia-corrected QT interval) from baseline based on the exposure-response relationship was 35 ms for the 300 mg dose. The QTcF increase remained above 30 ms for the duration of the trial (up to 2 years). In addition, 36% of patients experienced greater than 60 ms QTcF increases from baseline and 4.3% had QTcF greater than 500 ms. Vandetanib treatment alone has been associated with reported cases of torsade de pointes, ventricular tachycardia, and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of vandetanib with other drugs that can prolong the QT interval should generally be avoided. Should treatment with other QT-prolonging drugs be required, the manufacturer recommends more frequent monitoring of the ECG as well as serum potassium, magnesium, and calcium levels. Given vandetanib's half-life of 19 days, ECGs and serum electrolytes should typically be obtained at baseline, at 2 to 4 weeks and 8 to 12 weeks after starting treatment, and every 3 months thereafter. Vandetanib should not be started if baseline QTcF is greater than 450 ms, and treatment should be interrupted if QTcF is greater than 500 ms. Treatment may resume when QTcF returns to less than 450 ms, but at a reduced dosage. In addition, hypokalemia, hypomagnesemia, and/or hypocalcemia must be corrected prior to vandetanib administration. Since diarrhea is a common side effect of vandetanib and may cause electrolyte imbalances, ECG and electrolyte levels should also be monitored more frequently when diarrhea develops. Vandetanib treatment should be stopped in the presence of severe diarrhea. Treatment may resume when diarrhea improves, but at a reduced dosage. Following any dosage reduction, or any interruption of treatment greater than 2 weeks, QT assessment and serum electrolytes should be conducted as described previously. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Because of the drug's long half-life, adverse reactions including a prolonged QT interval may not resolve quickly, thus appropriate monitoring is necessary.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2011) "Product Information. Vandetanib (vandetanib)." Astra-Zeneca Pharmaceuticals
View all 4 references

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Drug and food interactions

No alcohol/food interactions were found. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.