Drug-drug:
- Strong CYP3A inhibitors, including clarithromycin, cobicistat, conivaptan, diltiazem, idelalisib, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, and ritonavir, significantly ↑ levels and risk of toxicity; avoid concurrent use. If short-term use of strong CYP3A inhibitors is necessary, ibrutinib may be temporarily interrupted.
- Moderate CYP3A inhibitors, including aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, or verapamil, ↑ levels and the risk of toxicity; if concurrent therapy is necessary, ↓ ibrutinib dose in patients with mantle cell lymphoma, marginal zone lymphoma, CLL/small lymphocytic leukemia, or Waldenström’s macroglobulinemia; in patients with chronic graft-versus-host disease, ibrutinib dose may be modified if adverse reactions develop.
- Posaconazole and voriconazole↑ levels and the risk of toxicity; if voriconazole is necessary, ↓ ibrutinib dose; if posaconazole is necessary, dose of ibrutinib may need to be ↓ based on dose of posaconazole used.
- Strong CYP3A inducers, including carbamazepine, enzalutamide, phenytoin, and rifampin, significantly ↓ levels and effectiveness; avoid concurrent use.
- Concurrent use of antiplatelet agents or anticoagulants↑ risk of bleeding.
Natural-Natural Products:
Natural-Food Products:
- Grapefruit juice or Seville oranges↑ levels and the risk of toxicity, avoid concurrent ingestion.
Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia or Waldenström’s Macroglobulinemia
- PO (Adults ): 420 mg once daily until disease progression or unacceptable toxicity; if given with rituximab or obinutuzumab, administer ibrutinib before the rituximab or obinutuzumab when given on the same day; Concurrent use of moderate CYP3A inhibitors: 280 mg once daily until disease progression or unacceptable toxicity; Concurrent use of posaconazole suspension (100 mg once daily, 100 mg twice daily, or 200 mg twice daily), or voriconazole 200 mg twice daily: 140 mg once daily until disease progression or unacceptable toxicity; Concurrent use of posaconazole suspension (200 mg 3 times daily or 400 mg twice daily), posaconazole IV 300 mg once daily, or posaconazole delayed-release tablets 300 mg once daily: 70 mg once daily until disease progression or unacceptable toxicity;Concurrent use of other strong CYP3A inhibitors: Avoid concurrent use.
Hepatic Impairment
- PO (Adults ): Mild hepatic impairment: 140 mg once daily. Moderate hepatic impairment: 70 mg once daily.
Chronic Graft-Versus-Host Disease
- PO (Adults and Children ≥12 yr): 420 mg once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity; Concurrent use of moderate CYP3A inhibitors: 420 mg once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity; Concurrent use of posaconazole suspension (100 mg once daily, 100 mg twice daily, or 200 mg twice daily) or voriconazole 200 mg twice daily: 280 mg once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity; Concurrent use of posaconazole suspension (200 mg 3 times daily or 400 mg twice daily), posaconazole IV 300 mg once daily, or posaconazole delayed-release tablets 300 mg once daily: 140 mg once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity;Concurrent use of other strong CYP3A inhibitors: Avoid concurrent use.
- PO (Children 1–11 yr): 240 mg/m2 (max = 420 mg) once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity (oral suspension should be used if body surface area [BSA] ≤0.7 m2; capsule, tablets, or oral suspension can be used if BSA >0.7 m2); Concurrent use of moderate CYP3A inhibitors: 240 mg/m2 (max = 420 mg) once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity (oral suspension should be used if BSA ≤0.7 m2; capsule, tablets, or oral suspension can be used if BSA >0.7 m2); Concurrent use of voriconazole suspension 9 mg/kg twice daily: 160 mg/m2 once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity (oral suspension should be used if BSA ≤0.7 m2; capsule, tablets, or oral suspension can be used if BSA >0.7 m2); Concurrent use of posaconazole: 80 mg/m2 once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity (oral suspension should be used if BSA ≤0.7 m2; capsule, tablets, or oral suspension can be used if BSA >0.7 m2);Concurrent use of other strong CYP3A inhibitors: Avoid concurrent use.
Hepatic Impairment
- PO (Adults and Children ≥12 yr): Total bilirubin level 1.51–3 times ULN (unless due to nonhepatic cause or Gilbert's syndrome): 140 mg once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity; Total bilirubin level >3 times ULN (unless due to nonhepatic cause or Gilbert's syndrome): Avoid use.
Hepatic Impairment
- (Children 1–11 yr): Total bilirubin level 1.51–3 times ULN (unless due to nonhepatic cause or Gilbert's syndrome): 80 mg/m2 once daily until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity; Total bilirubin level >3 times ULN (unless due to nonhepatic cause or Gilbert's syndrome): Avoid use.
Therapeutic Classification: antineoplastics
Pharmacologic Classification: kinase inhibitors
Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: 97.3%
Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A isoenzymes. One minor metabolite has antineoplastic activity. Metabolites are mostly eliminated in feces (80%), <10% excreted in urine.
Half-Life: 4–6 hr.
