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Drug Interactions between sorafenib and sunitinib

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

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Interactions between your drugs

Moderate

SORAfenib SUNItinib

Applies to: sorafenib and sunitinib

MONITOR: Sorafenib has the potential to prolong QT interval of the electrocardiogram. 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 multicenter, open-label, nonrandomized trial consisting of 53 patients with advanced cancer, no large changes in the mean QTc interval (i.e., greater than 20 msec) from baseline were detected during treatment with sorafenib 400 mg twice daily. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 msec was observed at 6 hours postdose on day 1 of cycle 2. In another study, QT/QTc measurements were recorded in 31 cancer patients at baseline and posttreatment. Following one 28-day treatment cycle with sorafenib 400 mg twice a day, QTcF was prolonged by 9 +/-18 msec at the time of maximum concentration of sorafenib, as compared to placebo treatment at baseline. 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). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is recommended if sorafenib is used in combination with cumulative high-dose anthracycline therapy or other drugs that can prolong the QT interval. ECG and serum electrolytes, including potassium, magnesium and calcium, should be monitored before starting sorafenib therapy and periodically during treatment. 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.

References

  1. "Product Information. Nexavar (sorafenib)." Bayer Pharmaceutical Inc (2005):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  4. Cerner Multum, Inc. "Australian Product Information." O 0
View all 4 references

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Drug and food interactions

Moderate

SORAfenib food

Applies to: sorafenib

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of sorafenib. According to the product labeling, sorafenib bioavailability was reduced by 29% when administered with a high-fat meal compared to administration in the fasted state. When given with a moderate-fat meal, bioavailability was similar to that in the fasted state.

MANAGEMENT: To ensure maximal and consistent oral absorption, sorafenib should be taken at least one hour before or two hours after eating.

References

  1. "Product Information. Nexavar (sorafenib)." Bayer Pharmaceutical Inc (2005):

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Moderate

SUNItinib food

Applies to: sunitinib

GENERALLY AVOID: Consumption of grapefruit or grapefruit juice during sunitinib therapy may increase the plasma concentrations of sunitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of large amounts of grapefruit or grapefruit juice during sunitinib therapy.

References

  1. "Product Information. Sutent (sunitinib)." Pfizer U.S. Pharmaceuticals Group (2006):

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Vegf/vegfr inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'VEGF/VEGFR inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'VEGF/VEGFR inhibitors' category:

  • sorafenib
  • sunitinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

Duplication

Multikinase inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

  • sorafenib
  • sunitinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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.