Imbruvica Dosage/Direction for Use

Treatment with this medicinal product should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
Posology: Mantle cell lymphoma: The recommended dose for the treatment of MCL is 560 mg once daily.
Chronic lymphocytic leukaemia: The recommended dose for the treatment of CLL, either as a single agent or in combination, is 420 mg once daily (for details of the combination regimen, see Pharmacology: Pharmacodynamics under Actions).
Waldenström's macroglobulinaemia: The recommended dose for the treatment of WM, either as a single agent or in combination, is 420 mg once daily (for details of the combination regimen, see Pharmacology: Pharmacodynamics under Actions).
Treatment should continue until disease progression or no longer tolerated by the patient.
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.
Chronic graft versus host disease (cGVHD): 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.
Dose adjustments: Moderate and strong CYP3A4 inhibitors increase the exposure of ibrutinib (see Precautions and Interactions).
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.
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 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 as follows: (See Table 14.)

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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 Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: Ibrutinib is metabolised in the liver. In a hepatic impairment study, data showed an increase in ibrutinib exposure (see Pharmacology: Pharmacokinetics under Actions). For patients with mild liver impairment (Child-Pugh class A), the recommended dose is 280 mg daily. For patients with moderate liver impairment (Child-Pugh class B), the recommended dose is 140 mg daily. 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 Interactions).