Active Ingredient: Ibrutinib
Ibrutinib as a single agent is indicated for the treatment of adult patients with Waldenström's macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. Ibrutinib in combination with rituximab is indicated for the treatment of adult patients with WM.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 420 milligrams ibrutinib, once daily.
The recommended dose for the treatment of WM, either as a single agent or in combination, is 420 mg once daily.
Treatment with ibrutinib as a single agent or in combination with anti-CD20 therapy should continue until disease progression or no longer tolerated by the patient.
When administering ibrutinib in combination with anti-CD20 therapy, it is recommended to administer ibrutinib prior to anti-CD20 therapy when given on the same day.
Moderate and strong CYP3A4 inhibitors increase the exposure of ibrutinib.
The dose of ibrutinib should be reduced to 280 mg once daily when used concomitantly with moderate CYP3A4 inhibitors.
The dose of ibrutinib should be reduced to 140 mg once daily or withheld for up to 7 days when it is used concomitantly with strong CYP3A4 inhibitors.
Ibrutinib therapy should be withheld for any new onset or worsening grade 2 cardiac failure, grade 3 cardiac arrhythmias, grade ≥3 non-haematological toxicity, grade 3 or greater neutropenia with infection or fever, or grade 4 haematological toxicities. Once the symptoms of the toxicity have resolved to grade 1 or baseline (recovery), resume ibrutinib therapy at the recommended dose as per the tables below.
Recommended dose modifications for non-cardiac events are described below:
| Events† | Toxicity occurrence | MCL dose modification after recovery | WM dose modification after recovery |
|---|---|---|---|
| Grade 3 or 4 non-haematological toxicities Grade 3 or 4 neutropenia with infection or fever Grade 4 haematological toxicities | First* | restart at 560 mg daily | restart at 420 mg daily |
| Second | restart at 420 mg daily | restart at 280 mg daily | |
| Third | restart at 280 mg daily | restart at 140 mg daily | |
| Fourth | discontinue ibrutinib | discontinue ibrutinib |
† Grading based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria, or International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for hematologic toxicities in CLL/SLL.
* When resuming treatment, restart at the same or lower dose based on benefit-risk evaluation. If the toxicity reoccurs, reduce daily dose by 140 mg.
Recommended dose modifications for events of cardiac failure or cardiac arrhythmias are described below:
| Events | Toxicity occurrence | WM dose modification after recovery |
|---|---|---|
| Grade 2 cardiac failure | First | restart at 280 mg daily |
| Second | restart at 140 mg daily | |
| Third | discontinue ibrutinib | |
| Grade 3 cardiac arrhythmias | First | restart at 280 mg daily† |
| Second | discontinue ibrutinib | |
| Grade 3 or 4 cardiac failure Grade 4 cardiac arrhythmias | discontinue ibrutinib |
† Evaluate the benefit-risk before resuming treatment.
If a dose is not taken at the scheduled time, it can be taken as soon as possible on the same day with a return to the normal schedule the following day. The patient should not take extra capsules to make up the missed dose.
Ibrutinib must not be taken with grapefruit juice or Seville oranges.
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