ug, the patient should be informed of the potential hazard to a fetus.
Males
Advise men to avoid fathering a child while receiving IMBRUVICA, and for 1 month following the last dose of IMBRUVICA.
8.4 Pediatric Use
The safety and effectiveness of IMBRUVICA in pediatric patients has not been established.
8.5 Geriatric Use
Of the 905 patients in clinical studies of IMBRUVICA, 62% were ≥ 65 years of age, while 21% were ≥75 years of age. No overall differences in effectiveness were observed between younger and older patients. Anemia (all grades) and Grade 3 or higher pneumonia occurred more frequently among older patients treated with IMBRUVICA.
8.6 Hepatic Impairment
Avoid use of IMBRUVICA in patients with severe hepatic impairment (Child-Pugh class C). The safety of IMBRUVICA has not been eva luated in patients with mild to severe hepatic impairment by Child-Pugh criteria.
Dose modifications of IMBRUVICA are recommended in patients with mild or moderate hepatic impairment (Child-Pugh class A and B). Monitor patients for adverse reactions of IMBRUVICA closely [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].
8.7 Plasmapheresis
Management of hyperviscosity in WM patients may include plasmapheresis before and during treatment with IMBRUVICA. Modifications to IMBRUVICA dosing are not required.
10 OVERDOSAGE
There is no specific experience in the management of ibrutinib overdose in patients. One healthy subject experienced reversible Grade 4 hepatic enzyme increases (AST and ALT) after a dose of 1680 mg. Closely monitor patients who ingest more than the recommended dosage and provide appropriate supportive treatment.
11 DESCRIPTION
Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). It is a white to off-white solid with the empirical formula C25H24N6O2 and a molecular weight 440.50. Ibrutinib is freely soluble in dimethyl sulfoxide, soluble in methanol and practically insoluble in water.
The chemical name for ibrutinib is 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one and has the following structure:
Chemical Structure
IMBRUVICA (ibrutinib) is available as immediate-release oral capsules and immediate-release oral tablets.
IMBRUVICA (ibrutinib) capsules for oral administration are available in the following dosage strengths: 70 mg and 140 mg. Each capsule contains ibrutinib (active ingredient) and the following inactive ingredients: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate. The capsule shell contains gelatin, titanium dioxide, yellow iron oxide (70 mg capsule only), and black ink.
IMBRUVICA (ibrutinib) tablets for oral administration are available in the following dosage strengths: 140 mg, 280 mg, 420 mg, and 560 mg. Each tablet contains ibrutinib (active ingredient) and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium lauryl sulfate. The film coating for each tablet contains ferrosoferric oxide (140 mg, 280 mg, and 420 mg tablets), polyvinyl alcohol, polyethylene glycol, red iron oxide (280 mg and 560 mg tablets), talc, titanium dioxide, and yellow iron oxide (140 mg, 420 mg, and 560 mg tablets).
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Ibrutinib is a small-molecule inhibitor o |
