Drug Interactions between Coxanto and regorafenib
This report displays the potential drug interactions for the following 2 drugs:
- Coxanto (oxaprozin)
- regorafenib
Interactions between your drugs
oxaprozin regorafenib
Applies to: Coxanto (oxaprozin) and regorafenib
MONITOR CLOSELY: Coadministration of regorafenib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Treatment with regorafenib is associated with a high frequency of hemorrhage and thrombocytopenia. In one study, the overall incidence of hemorrhage (grades 1 to 5) was 21% in regorafenib-treated patients compared to 8% in placebo-treated patients, and the incidence of thrombocytopenia was 41% versus 17%. Fatal hemorrhage occurred in 4 of 500 (0.8%) patients receiving regorafenib and involved the respiratory, gastrointestinal, or genitourinary tracts.
GENERALLY AVOID: Coadministration of regorafenib with strong UGT1A9 inhibitors such as mefenamic acid or diflunisal may theoretically increase systemic exposure to regorafenib.
MANAGEMENT: Concomitant use of other medications that interfere with platelet function or coagulation should be considered cautiously in patients treated with regorafenib. Close clinical and laboratory observation for bleeding complications is recommended during therapy. The INR should be monitored more frequently during coadministration of warfarin. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools. According to European labeling, concomitant use of regorafenib with mefenamic acid or diflunisal should be avoided.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
- (2012) "Product Information. Stivarga (regorafenib)." Bayer Pharmaceutical Inc
Drug and food interactions
regorafenib food
Applies to: 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
- (2012) "Product Information. Stivarga (regorafenib)." Bayer Pharmaceutical Inc
oxaprozin food
Applies to: Coxanto (oxaprozin)
GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.
MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.
References
- (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn
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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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