Skip to main content

Drug Interactions between cabozantinib and rifampin

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

rifAMPin cabozantinib

Applies to: rifampin and cabozantinib

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of cabozantinib, which is a substrate of the isoenzyme. In healthy subjects, administration of the potent CYP450 3A4 inducer rifampin (600 mg daily for 31 days) decreased single-dose cabozantinib plasma exposure (AUC) by 77%. Reduced therapeutic efficacy of cabozantinib may occur. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: Chronic use of potent CYP450 3A4 inducers during treatment with cabozantinib should be avoided whenever possible. If chronic coadministration is required, the daily dosage of cabozantinib should be increased in accordance with the prescribing information for the specific product. For the treatment of progressive, metastatic medullary thyroid cancer (capsule formulation), the recommendation is to increase cabozantinib dosage by 40 mg (e.g., from 140 mg to 180 mg daily or from 100 mg to 140 mg daily) as tolerated, not to exceed 180 mg/day. For the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy (tablet formulation), the recommendation is to increase cabozantinib dosage by 20 mg (e.g., from 60 mg to 80 mg daily or from 40 mg to 60 mg daily) as tolerated, not to exceed 80 mg/day. The original dosage of cabozantinib may be resumed 2 to 3 days after discontinuation of the potent CYP450 3A4 inducer. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath.

References (2)
  1. (2012) "Product Information. Cometriq (cabozantinib)." Exelixis Inc
  2. (2016) "Product Information. Cabometyx (cabozantinib)." Exelixis Inc

Drug and food interactions

Moderate

rifAMPin food

Applies to: rifampin

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References (6)
  1. (2022) "Product Information. Rifampin (rifAMPin)." Akorn Inc
  2. (2022) "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc
  3. (2023) "Product Information. Rifadin (rifampicin)." Sanofi
  4. (2024) "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE (2024) Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/
  6. (2019) "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc.
Moderate

cabozantinib food

Applies to: cabozantinib

ADJUST DOSING INTERVAL: Food may alter the oral bioavailability of cabozantinib. When healthy subjects were given a single 140 mg oral dose with a high-fat meal, cabozantinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 41% and 57%, respectively, relative to administration under fasting conditions. In clinical studies, patients were administered cabozantinib without food.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of cabozantinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Cabozantinib should be administered at least one hour before or two hours after a meal. The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided.

References (1)
  1. (2012) "Product Information. Cometriq (cabozantinib)." Exelixis 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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer