Drug Detail:Imbruvica (Ibrutinib)
Generic Name: IBRUTINIB 70mg
Dosage Form: capsule
Drug Class: BTK inhibitors
2.1 Recommended Dosage
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Waldenström’s Macroglobulinemia
The recommended dosage of IMBRUVICA for CLL/SLL and WM is 420 mg orally once daily until disease progression or unacceptable toxicity.
For CLL/SLL, IMBRUVICA can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR).
For WM, IMBRUVICA can be administered as a single agent or in combination with rituximab.
When administering IMBRUVICA in combination with rituximab or obinutuzumab, consider administering IMBRUVICA prior to rituximab or obinutuzumab when given on the same day.
Chronic Graft versus Host Disease
The recommended dosage of IMBRUVICA for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2 orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity. When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA should be discontinued considering the medical assessment of the individual patient.
| Recommended dose to achieve 240 mg/m2 | ||
| BSA* (m2) Range | Dose (mg) of IMBRUVICA Capsules/Tablets to Administer | Volume (mL) of IMBRUVICA Oral Suspension (70 mg/mL) to Administer |
| > 0.3 to 0.4 | - | 1.2 mL |
| > 0.4 to 0.5 | - | 1.5 mL |
| > 0.5 to 0.6 | - | 1.9 mL |
| > 0.6 to 0.7 | - | 2.2 mL |
| > 0.7 to 0.8 | 210 mg | 2.6 mL |
| > 0.8 to 0.9 | 210 mg | 2.9 mL |
| > 0.9 to 1.0 | 210 mg | 3.3 mL |
| > 1.0 to 1.1 | 280 mg | 3.6 mL |
| > 1.1 to 1.2 | 280 mg | 4 mL |
| > 1.2 to 1.3 | 280 mg | 4.3 mL |
| > 1.3 to 1.4 | 350 mg | 4.6 mL |
| > 1.4 to 1.5 | 350 mg | 5 mL |
| > 1.5 to 1.6 | 350 mg | 5.3 mL |
| > 1.6 | 420 mg | 6 mL |
*BSA = body surface area.
Administration
Administer IMBRUVICA at approximately the same time each day.
Swallow tablets or capsules whole with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets.
Follow Instructions for Use for further administration details of IMBRUVICA oral suspension.
If a dose of IMBRUVICA 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. Do not take extra doses of IMBRUVICA to make up for the missed dose.
2.2 Dosage Modifications for Adverse Reactions
For adverse reactions listed in Table 2, interrupt IMBRUVICA therapy. Once the adverse reaction has improved to Grade 1 or baseline (recovery), follow the recommended dosage modifications (see Table 2).
| Adverse Reactiona,b | Occurrence | Dose Modification for CLL/SLL, WM, and Patients 12 Years or older with cGVHD After Recovery Starting Dose = 420 mg |
Dose Modification for Patients 1 Year to less than 12 Years with cGVHD After Recovery Starting Dose = 240 mg/m2 |
| Grade 2 cardiac failure | First | Restart at 280 mg dailyc | Restart at 160 mg/m2 dailyc |
| Second | Restart at 140 mg dailyc | Restart at 80 mg/m2 dailyc | |
| Third | Discontinue IMBRUVICA | Discontinue IMBRUVICA | |
| Grade 3 cardiac arrhythmias | First | Restart at 280 mg dailyc | Restart at 160 mg/m2 dailyc |
| Second | Discontinue IMBRUVICA | Discontinue IMBRUVICA | |
| Grade 3 or 4 cardiac failure Grade 4 cardiac arrhythmias |
First | Discontinue IMBRUVICA | Discontinue IMBRUVICA |
| Other Grade 3 or 4 non-hematological toxicitiesd Grade 3 or 4 neutropenia with infection or fever Grade 4 hematological toxicities |
First | Restart at 280 mg daily | Restart at 160 mg/m2 dailyc |
| Second | Restart at 140 mg daily | Restart at 80 mg/m2 dailyc | |
| Third | Discontinue IMBRUVICA | Discontinue IMBRUVICA |
a [see Warnings and Precautions (5)].
b 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.
c Evaluate the benefit-risk before resuming treatment.
d For Grade 4 non-hematologic toxicities, evaluate the benefit-risk before resuming treatment.
| Recommended dose to achieve 160 mg/m2 | Recommended dose to achieve 80 mg/m2 | |||
| BSA* (m2) Range | Dose (mg) of IMBRUVICA Capsules/Tablets to Administer | Volume (mL) of IMBRUVICA Oral Suspension (70 mg/mL) to Administer | Dose (mg) of IMBRUVICA Capsules/Tablets to Administer | Volume (mL) of IMBRUVICA Oral Suspension (70 mg/mL) to Administer |
| > 0.3 to 0.4 | - | 0.8 mL | - | 0.4 mL |
| > 0.4 to 0.5 | - | 1 mL | - | 0.5 mL |
| > 0.5 to 0.6 | - | 1.3 mL | - | 0.6 mL |
| > 0.6 to 0.7 | - | 1.5 mL | - | 0.7 mL |
| > 0.7 to 0.8 | 140 mg | 1.7 mL | 70 mg | 0.9 mL |
| > 0.8 to 0.9 | 140 mg | 1.9 mL | 70 mg | 1 mL |
| > 0.9 to 1.0 | 140 mg | 2.2 mL | 70 mg | 1.1 mL |
| > 1.0 to 1.1 | 140 mg | 2.4 mL | 70 mg | 1.2 mL |
| > 1.1 to 1.2 | 210 mg | 2.6 mL | - | 1.3 mL |
| > 1.2 to 1.3 | 210 mg | 2.9 mL | - | 1.4 mL |
| > 1.3 to 1.4 | 210 mg | 3.1 mL | - | 1.5 mL |
| > 1.4 to 1.5 | 210 mg | 3.3 mL | 140 mg | 1.7 mL |
| > 1.5 to 1.6 | 280 mg | 3.5 mL | 140 mg | 1.8 mL |
| > 1.6 | 280 mg | 4 mL | 140 mg | 2 mL |
*BSA = body surface area.
2.3 Dosage Modifications for Use with CYP3A Inhibitors
Recommended dosage modifications are described below [see Drug Interactions (7.1)]:
| Patient Population | Coadministered Drug | Recommended IMBRUVICA Dosage |
| B-cell Malignancies |
|
280 mg once daily Modify dose as recommended [see Dosage and Administration (2.2)]. |
|
140 mg once daily Modify dose as recommended [see Dosage and Administration (2.2)]. |
|
|
70 mg once daily Interrupt dose as recommended [see Dosage and Administration (2.2)]. |
|
|
Avoid concomitant use. If these inhibitors will be used short-term (such as anti-infectives for seven days or less), interrupt IMBRUVICA. |
|
| Patients 12 years and older with cGVHD |
|
420 mg once daily Modify dose as recommended [see Dosage and Administration (2.2)]. |
|
280 mg once daily Modify dose as recommended [see Dosage and Administration (2.2)]. |
|
|
140 mg once daily Interrupt dose as recommended [see Dosage and Administration (2.2)]. |
|
|
Avoid concomitant use. If these inhibitors will be used short-term (such as anti-infectives for seven days or less), interrupt IMBRUVICA. |
|
| Patients 1 year to less than 12 years of age with cGVHD |
|
240 mg/m2 once daily Modify dose as recommended [see Dosage and Administration (2.2)]. |
|
160 mg/m2 once daily | |
|
80 mg/m2 once daily | |
|
Avoid concomitant use. If these inhibitors will be used short-term (such as anti-infectives for seven days or less), interrupt IMBRUVICA. |
After discontinuation of a CYP3A inhibitor, resume previous dose of IMBRUVICA [see Dosage and Administration (2.1), Drug Interactions (7.1)].
2.4 Dosage Modifications for Use in Hepatic Impairment
Adult Patients with B-cell Malignancies
The recommended dosage is 140 mg daily for patients with mild hepatic impairment (Child-Pugh class A).
The recommended dosage is 70 mg daily for patients with moderate hepatic impairment (Child-Pugh class B).
Avoid the use of IMBRUVICA in patients with severe hepatic impairment (Child-Pugh class C) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Patients with cGVHD
The recommended dosage is 140 mg daily for patients 12 years of age and older with total bilirubin level >1.5 to 3 x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilbert’s syndrome).
The recommended dosage is 80 mg/m2 daily for patients 1 to less than 12 years of age with total bilirubin level >1.5 to 3 x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome).
Avoid the use of IMBRUVICA in these patients with total bilirubin level > 3 x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
