IMBRUVICA Hard capsule Ref.[8478] Active ingredients: Ibrutinib

Treatment with this medicinal product should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.

Posology

MCL

Treatment of adult patients with previously untreated MCL

The recommended dose for the treatment of previously untreated MCL is ibrutinib 560 mg (four capsules) once daily (see Table 1).

Table 1. IMBRUVICA dosing schedule for previously untreated MCL:

R-CHOP = rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; R-DHAP = rituximab, dexamethasone, cytarabine, cisplatin
^* 6 cycles; each cycle is 21 days.
^§ See the Summary of Product Characteristics (SmPC) for dosing information for each medicinal product.
^# Interchangeable with R-DHAOx (rituximab, dexamethasone, cytarabine, oxaliplatin)^§.
^± Treatment should start after recovery of peripheral blood counts. Rituximab may be added as per national treatment guidelines.

Treatment of adult patients with relapsed or refractory MCL

The recommended dose for the treatment of previously treated MCL is ibrutinib 560 mg (four capsules) once daily as a single agent. Treatment with IMBRUVICA as a single agent should continue until disease progression or no longer tolerated by the patient.

CLL and WM

The recommended dose for the treatment of CLL and WM, either as a single agent or in combination, is 420 mg (three capsules) once daily (for details of the combination regimens, see section 5.1).

Treatment with IMBRUVICA as a single agent or in combination with anti-CD20 therapy should continue until disease progression or no longer tolerated by the patient. In combination with venetoclax for the treatment of CLL, IMBRUVICA should be administered as a single agent for 3 cycles (1 cycle is 28 days), followed by 12 cycles of IMBRUVICA plus venetoclax. See the venetoclax Summary of Product Characteristics (SmPC) for full venetoclax dosing information.

When administering IMBRUVICA in combination with anti-CD20 therapy, it is recommended to administer IMBRUVICA prior to anti-CD20 therapy when given on the same day.

Dose adjustments

Moderate and strong CYP3A4 inhibitors increase the exposure of ibrutinib (see sections 4.4 and 4.5).

The dose of ibrutinib should be reduced to 280 mg once daily (two capsules) when used concomitantly with moderate CYP3A4 inhibitors.

The dose of ibrutinib should be reduced to 140 mg once daily (one capsule) or withheld for up to 7 days when it is used concomitantly with strong CYP3A4 inhibitors.

IMBRUVICA 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 IMBRUVICA therapy at the recommended dose as per the tables below.

Recommended dose modifications for non-cardiac events are described below:

^† 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:

^† Evaluate the benefit-risk before resuming treatment.

Missed dose

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.

Special populations

Elderly

No specific dose adjustment is required for elderly patients (aged ≥65 years).

Renal impairment

No specific clinical studies have been conducted in patients with renal impairment. Patients with mild or moderate renal impairment were treated in IMBRUVICA clinical studies. No dose adjustment is needed for patients with mild or moderate renal impairment (greater than 30 mL/min creatinine clearance). Hydration should be maintained and serum creatinine levels monitored periodically. Administer IMBRUVICA to patients with severe renal impairment (<30 mL/min creatinine clearance) only if the benefit outweighs the risk and monitor patients closely for signs of toxicity. There are no data in patients with severe renal impairment or patients on dialysis (see section 5.2).

Hepatic impairment

Ibrutinib is metabolised in the liver. In a hepatic impairment study, data showed an increase in ibrutinib exposure (see section 5.2). For patients with mild liver impairment (Child-Pugh class A), the recommended dose is 280 mg daily (two capsules). For patients with moderate liver impairment (Child-Pugh class B), the recommended dose is 140 mg daily (one capsule). Monitor patients for signs of IMBRUVICA toxicity and follow dose modification guidance as needed. It is not recommended to administer IMBRUVICA to patients with severe hepatic impairment (Child-Pugh class C).

Severe cardiac disease

Patients with severe cardiovascular disease were excluded from IMBRUVICA clinical studies.

Paediatric population

IMBRUVICA is not recommended for use in children and adolescents aged 0 to 18 years as efficacy has not been established. Currently available data in patients with mature B-cell non-Hodgkin lymphoma are described in sections 4.8, 5.1 and 5.2.

Method of administration

IMBRUVICA should be administered orally once daily with a glass of water approximately at the same time each day. The capsules should be swallowed whole with water and should not be opened, broken, or chewed. IMBRUVICA must not be taken with grapefruit juice or Seville oranges (see section 4.5).

There are limited data on the effects of IMBRUVICA overdose. No maximum tolerated dose was reached in the phase 1 study in which patients received up to 12.5 mg/kg/day (1 400 mg/day). In a separate study, one healthy subject who received a dose of 1 680 mg experienced reversible grade 4 hepatic enzyme increases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. There is no specific antidote for IMBRUVICA. Patients who ingested more than the recommended dose should be closely monitored and given appropriate supportive treatment.

3 years.

This medicinal product does not require any special storage conditions.

HDPE bottles with a child-resistant polypropylene closure.

Each carton contains one bottle of either 90 or 120 hard capsules.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.