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Drug Interactions between deferasirox and Stivarga

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

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Interactions between your drugs

Major

deferasirox regorafenib

Applies to: deferasirox and Stivarga (regorafenib)

MONITOR CLOSELY: Coadministration with drugs that have known ulcerogenic or hemorrhagic potential may increase the risk of gastrointestinal bleeding associated with the use of deferasirox. Fatal gastrointestinal hemorrhages have been reported during deferasirox therapy, especially in elderly patients with advanced hematologic malignancies and/or low platelet counts. Nonfatal upper gastrointestinal irritation, ulceration, and hemorrhage have also been reported, including in children and adolescents.

MANAGEMENT: Caution is advised if deferasirox is prescribed with drugs that have known ulcerogenic or hemorrhagic potential, including but not limited to NSAIDs, salicylates, corticosteroids, oral bisphosphonates, platelet inhibitors, anticoagulants, thrombolytic agents, or agents that commonly cause thrombocytopenia. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, bloating, dizziness, lightheadedness, hematemesis, anorexia, and/or black, tarry stools.

References

  1. "Product Information. Exjade (deferasirox)." Novartis Pharmaceuticals (2005):

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Drug and food interactions

Moderate

deferasirox food

Applies to: deferasirox

ADJUST DOSING INTERVAL: According to product labeling, the bioavailability of deferasirox was variably increased when taken with a meal.

MANAGEMENT: To ensure consistent plasma drug levels, deferasirox should be taken on an empty stomach 30 minutes before eating preferably at the same time everyday.

References

  1. "Product Information. Exjade (deferasirox)." Novartis Pharmaceuticals (2005):

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Moderate

regorafenib food

Applies to: Stivarga (regorafenib)

ADJUST DOSING INTERVAL: Depending on the amount of fat, food may enhance the oral bioavailability of both regorafenib and its active metabolites, M-2 and M-5. In 24 healthy male subjects, administration of regorafenib with a high-fat meal (945 calories; 54.6 g fat) increased the mean systemic exposure (AUC) of regorafenib by 48% but decreased the mean AUC of M-2 and M-5 by 20% and 51%, respectively, compared to administration under the fasted state. In contrast, administration with a low-fat meal (319 calories; 8.2 g fat) increased the mean AUC of regorafenib, M-2 and M-5 by 36%, 40% and 23%, respectively, compared to administration during fasting.

GENERALLY AVOID: Coadministration with grapefruit juice may alter the pharmacokinetics of regorafenib and its active metabolites. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. The interaction has not been studied specifically with grapefruit juice, but has been reported with the potent CYP450 3A4 inhibitor, ketoconazole. In 18 healthy male study subjects, administration of a single 160 mg dose of regorafenib on day 5 of treatment with ketoconazole (400 mg daily for 18 days) resulted in a 33% increase in mean regorafenib systemic exposure (AUC) compared to administration of regorafenib alone. Additionally, there was a 93% decrease each in the mean AUC of the M-2 and M-5 metabolites. Both have been shown to have similar in vitro pharmacological activity and steady-state concentrations as regorafenib, thus the net clinical effect of these pharmacokinetic changes is unknown.

MANAGEMENT: To ensure optimal oral absorption, regorafenib should be administered with a low-fat breakfast that contains less than 30% fat. Examples of a low-fat breakfast include: 2 slices of white toast with 1 tablespoon of low-fat margarine and 1 tablespoon of jelly, plus 8 ounces of skim milk (319 calories; 8.2 g fat); or 1 cup of cereal, 8 ounces of skim milk, 1 slice of toast with jam, apple juice, and 1 cup of coffee or tea (520 calories; 2 g fat). Patients should be advised to avoid consuming grapefruit or grapefruit juice during treatment with regorafenib.

References

  1. "Product Information. Stivarga (regorafenib)." Bayer Pharmaceutical Inc (2012):

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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.

See also

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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.

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