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

The recommended dose for the treatment of MCL is 560 mg (four capsules) once daily.

CLL and WM

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

The recommended dose for the treatment of WM is 420 mg (three capsules) once daily.

Treatment should continue until disease progression or no longer tolerated by the patient.

When administering IMBRUVICA in combination with anti-CD20 therapies, it is recommended to administer IMBRUVICA prior to rituximab or obinutuzumab 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 ≥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), IMBRUVICA therapy may be reinitiated at the starting dose. If the toxicity reoccurs, the once daily dose should be reduced by one capsule (140 mg). A second reduction of dose by 140 mg may be considered as needed. If these toxicities persist or recur following two dose reductions, discontinue the medicinal product.

Recommended dose modifications are described below:

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

The safety and efficacy of IMBRUVICA in children and adolescents aged 0 to 18 years have not been established. No data are available.

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.

Shelf life: 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.