IMBRUVICA FILM-COATED TABLETS 420MG [SIN16220P]

Product Info

IMBRUVICA FILM-COATED TABLETS 420MG

[SIN16220P]

Indications
Mantle Cell Lymphoma (MCL)
IMBRUVICA® is indicated for the treatment of adult patients with MCL who have received at least one prior therapy. In the clinical study, efficacy was demonstrated based on overall response rate. Improvements in survival or disease-related symptoms have not been established.

Chronic lymphocytic leukemia / Small lymphocytic lymphoma (CLL/SLL)
IMBRUVICA® as a single agent, or in combination with rituximab or obinutuzumab or venetoclax, is indicated for the treatment of adult patients with previously untreated CLL/SLL.
IMBRUVICA® as a single agent, or in combination with bendamustine and rituximab, is indicated for the treatment of patients with CLL/SLL who have received at least one prior therapy.

Waldenström’s macroglobulinemia (WM)
IMBRUVICA® as a single agent, or in combination with rituximab, is indicated for the treatment of patients with WM.

Dosage and Administration
Dosage
IMBRUVICA® should be administered orally once daily with a glass of water at approximately the same time each day. The tablets should be swallowed whole with water. Do not break or chew the tablets. IMBRUVICA® must not be taken with grapefruit juice.

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

Mantle Cell Lymphoma
The recommended dose of IMBRUVICA® for MCL is 560 mg once daily until disease progression or no longer tolerated by the patient.

Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL) and Waldenström’s macroglobulinemia (WM)
The recommended dose of IMBRUVICA® for CLL/SLL or WM is 420 mg once daily. For CLL/SLL, IMBRUVICA® can be administered until disease progression or is no longer tolerated by the patient as a single agent or in combination with anti-CD20 therapy (rituximab or obinutuzumab), or in combination with bendamustine and rituximab (BR). In combination with venetoclax, IMBRUVICA® should be administered as a single agent for 3 cycles (1 cycle is 28 days), followed by 12 cycles of IMBRUVICA® plus venetoclax.

For WM, IMBRUVICA® can be administered until disease progression or no longer tolerated as a single agent or in combination with rituximab. For additional information concerning rituximab, BR, ventoclax or obinutuzumab see the corresponding local rituximab, bendamustine, venetoclax or obinutuzumab prescribing 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 modification guidelines
The concomitant use of moderate and strong CYP3A inhibitors can increase the exposure of ibrutinib (see Interactions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Avoid co-administration with strong or moderate CYP3A inhibitors and consider alternative agents with less CYP3A inhibition.

Concomitant use of strong CYP3A inhibitors which would be taken chronically (e.g. ketoconazole, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin, itraconazole, nefazodone, cobicistat) is not recommended. For short-term use (treatment for 7 days or less) of strong CYP3A inhibitors (e.g. antifungals and antibiotics), consider interrupting IMBRUVICA® therapy until the CYP3A inhibitor is no longer needed.

See recommended dose modifications in the “interactions” section if a moderate CYP3A inhibitor must be used (e.g. fluconazole, erythromycin, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, diltiazem, fosamprenavir, imatinib, verapamil, amiodarone, dronedarone) (see Interactions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Patients taking concomitant strong or moderate CYP3A inhibitors should be monitored more closely for signs of IMBRUVICA® toxicity.

IMBRUVICA® therapy should be withheld for any new onset or worsening Grade 2 cardiac failure, Grade 3 cardiac arrhythmias, Grade ≥ 3 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), resume IMBRUVICA® therapy at the recommended dose as per the tables below.

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

Recommended dose modifications for events of cardiac failure or cardiac arrhythmias are described below:

Missed dose
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. The patient should not take extra doses to make up the missed dose.

Special populations
Pediatrics (18 years of age and younger)
The safety and efficacy of IMBRUVICA® in children have not yet been evaluated.

Renal impairment
Ibrutinib has minimal renal clearance. 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. There are no data in patients with severe renal impairment or patients on dialysis (see Pharmacokinetic Properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment
Ibrutinib is metabolized in the liver. In a hepatic impairment study, data showed an increase in ibrutinib exposure (see Pharmacokinetic Properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). For patients with mild liver impairment (Child-Pugh classes A), 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 moderate and severe hepatic impairment (Child-Pugh classes B and C).

Contraindications
IMBRUVICA® is contraindicated in patients who have known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to ibrutinib or to the excipients in its formulation.