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Drug Interactions between ibrutinib and radium 223 dichloride

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

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Interactions between your drugs

Major

radium Ra 223 dichloride ibrutinib

Applies to: radium 223 dichloride and ibrutinib

MONITOR CLOSELY: Coadministration of radium Ra 223 dichloride (Ra-223 dichloride) with other agents that can cause bone marrow suppression or myelosuppression may result in additive toxicity. Ra-223 dichloride alone is associated with thrombocytopenia, neutropenia, pancytopenia, and leukopenia; death from bone marrow failure has also been reported. In a randomized clinical trial in patients with metastatic castration-resistant prostate cancer with bone metastases, 2% of the patients on Ra-223 dichloride experienced bone marrow failure or ongoing pancytopenia compared to no patients in the placebo group. Grade 3-4 adverse reactions of thrombocytopenia and neutropenia were more commonly reported in patients who had received prior docetaxel. However, data from clinical drug interaction studies are lacking.

MANAGEMENT: Caution and close monitoring for additive hematologic toxicity are recommended if concomitant use of Ra-223 dichloride with other agents that can cause bone marrow suppression or myelosuppression is required. The manufacturer advises that Ra-223 dichloride be discontinued in patients requiring administration of chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy. If concomitant use is required, the manufacturer's product labeling should be consulted for specific hematologic monitoring and dose adjustment recommendations. Some authorities recommend not initiating subsequent systemic cancer treatment for at least 30 days after the last administration of Ra-223 dichloride. Patients should be advised to contact their physician if they develop signs or symptoms of myelosuppression or infection including but not limited to pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, fever, chills, sore throat, body aches, and/or other influenza-like symptoms.

References (4)
  1. (2019) "Product Information. Xofigo (radium Ra 223 dichloride)." Bayer Pharmaceutical Inc
  2. (2022) "Product Information. Xofigo (radium (Ra-223) dichloride)." Bayer Plc
  3. (2019) "Product Information. Xofigo (radium (223Ra) dichloride)." Bayer Australia Limited
  4. Bayer Inc. (2023) Product monograph xofigo radium Ra 223 dichloride solution for injection 1100 kBq/mL (29.7 microcurie/mL) radium-223 dichloride https://pdf.hres.ca/dpd_pm/00052465.PDF

Drug and food interactions

Major

ibrutinib food

Applies to: ibrutinib

GENERALLY AVOID: Coadministration with grapefruit, grapefruit juice, or Seville oranges may significantly increase the plasma concentrations of ibrutinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Pharmacokinetic modeling suggests that other moderate CYP450 3A4 inhibitors such as diltiazem and erythromycin may increase ibrutinib systemic exposure (AUC) by 6- to 9-fold under fasting condition. The safety and efficacy of these exposures are unknown. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 to 1400 mg) given for 28 days, which yielded single dose AUC values that were approximately 50% greater than steady-state exposures seen at the highest indicated dose of 560 mg.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ibrutinib. The mechanism of interaction is unknown. According to the product labeling, administration with food increases ibrutinib exposure approximately 2-fold compared to administration after overnight fasting.

MANAGEMENT: Patients treated with ibrutinib should avoid consumption of Seville oranges, grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ibrutinib should be taken once daily at approximately the same time each day.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Imbruvica (ibrutinib)." Pharmacyclics 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.


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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.