A and 9.0 months for patients in the control arm), the incidence of ventricular tachyarrhythmias (ventricular extrasystoles, ventricular arrhythmias, ventricular fibrillation, ventricular flutter, and ventricular tachycardia) of any grade was 1.0% versus 0.2% and of Grade 3 or greater was 0.2% versus 0% in patients treated with IMBRUVICA compared to patients in the control arm. In addition, the incidence of atrial fibrillation and atrial flutter of any grade was 7% versus 1.5% and for Grade 3 or greater was 2.8% versus 0.3% in patients treated with IMBRUVICA compared to patients in the control arm.
Diarrhea
Diarrhea of any grade occurred at a rate of 43% (range, 36% to 59%) of patients treated with IMBRUVICA. Grade 2 diarrhea occurred in 9% (range, 3% to 14%) and Grade 3 in 3% (range, 0 to 5%) of patients treated with IMBRUVICA. The median time to first onset of any grade diarrhea was 10 days (range, 0 to 627), of Grade 2 was 39 days (range, 1 to 719) and of Grade 3 was 74 days (range, 3 to 627). Of the patients who reported diarrhea, 82% had complete resolution, 1% had partial improvement and 17% had no reported improvement at time of analysis. The median time from onset to resolution or improvement of any grade diarrhea was 5 days (range, 1 to 418), and was similar for Grades 2 and 3. Less than 1% of patients discontinued IMBRUVICA due to diarrhea.
Visual Disturbance
Blurred vision and decreased visual acuity of any grade occurred in 10% of patients treated with IMBRUVICA (9% Grade 1, 2% Grade 2). The median time to first onset was 85 days (range, 1 to 414 days). Of the patients with visual disturbance, 61% had complete resolution and 38% had no reported improvement at time of analysis. The median time from onset to resolution or improvement was 29 days (range, 1 to 335 days).
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of IMBRUVICA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hepatobiliary disorders: hepatic failure
Respiratory disorders: interstitial lung disease
Metabolic and nutrition disorders: tumor lysis syndrome [see Warnings & Precautions (5.7)]
Immune system disorders: anaphylactic shock, angioedema, urticaria
Skin and subcutaneous tissue disorders: Stevens-Johnson Syndrome (SJS), onychoclasis
Infections: hepatitis B reactivation
7 DRUG INTERACTIONS
7.1 Effect of CYP3A Inhibitors on Ibrutinib
The coadministration of IMBRUVICA with a strong or moderate CYP3A inhibitor may increase ibrutinib plasma concentrations [see Clinical Pharmacology (12.3)]. Increased ibrutinib concentrations may increase the risk of drug-related toxicity.
Dose modifications of IMBRUVICA are recommended when used concomitantly with posaconazole, voriconazole and moderate CYP3A inhibitors [see Dosage and Administration (2.4)].
Avoid concomitant use of other strong CYP3A inhibitors. Interrupt IMBRUVICA if these inhibitors will be used short-term (such as anti-infectives for seven days or less) [see Dosage and Administration (2.4)].
Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain strong or moderate inhibitors of CYP3A.
7.2 Effect of CYP3A Inducers on Ibrutinib
The coadministration of IMBRUVICA with strong CYP3A inducers may decrease ibrutinib concentrations. Avoid coadmi |
