ia
IMBRUVICA is indicated for the treatment of adult patients with Waldenström’s macroglobulinemia (WM).
1.5 Marginal Zone Lymphoma
IMBRUVICA is indicated for the treatment of adult patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for this indication based on overall response rate [see Clinical Studies (14.4)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
1.6 Chronic Graft versus Host Disease
IMBRUVICA is indicated for the treatment of adult patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Guidelines
Administer IMBRUVICA orally once daily at approximately the same time each day. The dose should be taken orally with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets.
2.2 Recommended Dosage
Mantle Cell Lymphoma and Marginal Zone Lymphoma
The recommended dose of IMBRUVICA for MCL and MZL is 560 mg orally once daily until disease progression or unacceptable toxicity.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Waldenström's Macroglobulinemia
The recommended dose of IMBRUVICA for CLL/SLL and WM is 420 mg orally once daily until disease progression or unacceptable toxicity.
The recommended dose of IMBRUVICA for CLL/SLL when used in combination with bendamustine and rituximab (administered every 28 days for up to 6 cycles) is 420 mg orally once daily until disease progression or unacceptable toxicity.
Chronic Graft versus Host Disease
The recommended dose of IMBRUVICA for cGVHD is 420 mg orally once daily 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.
2.3 Dose Modifications for Adverse Reactions
Interrupt IMBRUVICA therapy for any Grade 3 or greater non-hematological toxicities, Grade 3 or greater neutropenia with infection or fever, or Grade 4 hematological toxicities. Once the symptoms of the toxicity have resolved to Grade 1 or baseline (recovery), IMBRUVICA therapy may be reinitiated at the starting dose. If the toxicity reoccurs, reduce dose by 140 mg per day. A second reduction of dose by 140 mg may be considered as needed. If these toxicities persist or recur following two dose reductions, discontinue IMBRUVICA.
Recommended dose modifications are described below:
Toxicity Occurrence Dose Modification for MCL and MZL After Recovery
Starting Dose = 560 mg Dose Modification for CLL/SLL, WM, and cGVHD After Recovery
Starting Dose = 420 mg
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 IMBRUVICA Discontinue IMBRUVICA
2.4 Dose Modifications for Use with CYP3A Inhibitors
Recommended dose modifications are described below [see Drug Interactions (7.1)]:
Patient Population Coadministered Drug Recommended IMBRUVICA Dose
B-Cell Malignancies
Moderat |
