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Drug Interactions between rosuvastatin and Stivarga

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

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Interactions between your drugs

Major

rosuvastatin regorafenib

Applies to: rosuvastatin and Stivarga (regorafenib)

ADJUST DOSE: Coadministration with regorafenib may significantly increase the plasma concentrations of rosuvastatin. The proposed mechanism is inhibition of intestinal and/or hepatic breast cancer resistance protein (BCRP) efflux transporter by regorafenib and its active metabolites, resulting in increased oral bioavailability and possibly reduced hepatic clearance of rosuvastatin. When a single 5 mg dose of rosuvastatin was administered following regorafenib 160 mg daily for 14 days, mean rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 4.6- and 3.8-fold, respectively, compared to administration of rosuvastatin alone. High levels of HMG-CoA reductase inhibitory activity in plasma may be associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

MANAGEMENT: The dosage of rosuvastatin should start at 5 mg and not exceed 10 mg once daily when used in combination with regorafenib. Alternatively, a different statin that is not expected to be significantly affected by BCRP inhibition such as pitavastatin or pravastatin may be considered. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References (6)
  1. (2024) "Product Information. Rosuvastatin Calcium (rosuvastatin)." Torrent Pharma, Inc.
  2. (2020) "Product Information. Stivarga (regorafenib)." Bayer HealthCare Pharmaceuticals Inc.
  3. (2023) "Product Information. Stivarga (regorafenib)." Bayer Plc
  4. (2024) "Product Information. Rosuvastatin (rosuvastatin)." Sun Pharma UK Ltd
  5. (2024) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pty Ltd
  6. (2024) "Product Information. Ag-Rosuvastatin (rosuvastatin)." Angita Pharma Inc.

Drug and food interactions

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

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

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