Presentation and Status in Health Basket
90 X 140 mg
120 X 140 mg
Mantle Cell Lymphoma: The recommended dose for MCL is
560 mg (four 140 mg capsules) orally once daily.
Chronic Lymphocytic Leukemia: The recommended dose of IMBRUVICA for CLL is 420 mg (three 140 mg capsules) orally once daily.
BCL-2 Inhibitor. Venetoclax 10, 50, 100 mg. F.C. TABS.: Dosage should be ajust. individ. See lit.
Tmt. of pts. with Chron. Lymphoc. Leukem./Small Lymphoc. Lymphoma with or without 17p deletion, who have received at least one prior ther.
Acute Myeloid Leukem.: in comb. with a hypomethylating agent/comb. with low dose cytarabine is indicated for newly diagnosed pts. with AML who are ineligible for intensive chemother.
C/I: Concom. use with strong CYP3A inhib. at init. and during ramp-up phase is contraind. in pts. with CLL/SLL due to the potent. for incr. risk of tumor lysis syndr. Concom. use with St. John’s wort.
Indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This indication is based on overall response rate. An improvement in survival or disease-related symptoms has not been established.
Hemorrhage: Five percent of patients with MCL had Grade 3 or higher bleeding events (subdural hematoma, ecchymoses, gastrointestinal bleeding, and hematuria). Overall, bleeding events including bruising of any grade occurred in 48% of patients with MCL Treated with 560 mg daily. The mechanism for the bleeding events is not well understood. This drug may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies.
Consider the benefit-risk of withholding it for at least 3 to 7 days pre and postsurgery depending upon the type of surgery and the risk of bleeding.
Infections: Fatal and non-fatal infections have occurred with this therapy. At least 25% of patients With MCL had infections Grade 3 or greater NCI Common Terminology Criteria for Adverse Events (CTCAE) [See Adverse Reactions (6.1)].Monitor patients for fever and infections and evaluate promptly.
Myelosuppression: Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients with MCL. These included neutropenia (29%), thrombocytopenia (17%) and anemia (9%) in patients with MCL. Monitor complete blood counts monthly.
Renal Toxicity: Fatal and serious cases of renal failure have occurred with this therapy. Treatmentemergent increases in creatinine levels up to 1.5 times the upper limit of normal occurred in 67% of patients with MCL. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 9% of patients with MCL. Periodically monitor creatinine levels. Maintain hydration.
Second Primary Malignancies: Other malignancies have occurred in 5% of patients with MCL who have been treated with this drug. Four percent of patients with MCL had skin cancers and 1% had other carcinomas.
Embryo-Fetal Toxicity: Based on findings in animals, this drug can cause fetal harm when administered to a pregnant woman. Ibrutinib caused malformations in rats at exposures 14 times those reported in patients with MCL, receiving the ibrutinib dose of 560 mg per day. Reduced fetal weights were observed at lower exposures. Advise women to avoid becoming pregnant while taking it. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations.
The following adverse reactions are discussed in more detail in the special precaution section above:
• Renal Toxicity.
• Second Primary Malignancies.
Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice.
For full details see prescribing information.
USE IN SPECIAL POPULATION
Pediatric Use: The safety and effectiveness of this drug in pediatric patients has not been established.
Geriatric Use: Of the 111 patients treated for MCL, 63% were 65 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse events (atrial fibrillation and hypertension), infections (pneumonia and cellulitis) and gastrointestinal events (diarrhea and dehydration) occurred more frequently among elderly patients.
Renal Impairment: Less than 1% of ibrutinib is excreted renally. Ibrutinib exposure is not altered in patients with Creatinine clearance (CLcr) > 25 mL/min. There are no data in patients with severe renal impairment (CLcr < 25 mL/min) or patients on dialysis [see Clinical Pharmacology (12.3)].
Hepatic Impairment: Ibrutinib is metabolized in the liver and significant increases in exposure of ibrutinib are expected in patients with hepatic impairment. Patients with serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) were excluded from it in clinical trials. There is insufficient data to recommend a dose of IMBRUVICA in patients with baseline hepatic impairment [see Clinical Pharmacology.
Females and Males of Reproductive Potential: Advise women to avoid becoming pregnant while taking it because this drug can cause fetal harm.
Ibrutinib is primarily metabolized by cytochrome P450 enzyme 3A.
CYP3A Inhibitors: In healthy volunteers, co-administration of ketoconazole, a strong CYP3A inhibitor, increased Cmax and AUC of ibrutinib by 29- and 24-fold, respectively. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 – 1400 mg) given for 28 days with single dose AUC values of 1445 ± 869 ng ⋅ hr/mL which is approximately 50% greater than steady state exposures seen at the highest indicated dose (560 mg). Avoid concomitant administration it with strong or moderate inhibitors of CYP3A. For strong CYP3A inhibitors used short-term (e.g., antifungals and antibiotics for
7 days or less, e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin) consider interrupting dhis drug herapy during the duration of inhibitor use. Avoid strong CYP3A inhibitors that are needed chronically. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose. Patients taking concomitant strong or moderate
CYP3A4 inhibitors should be monitored more closely for signs of IMBRUVICA toxicity. Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain moderate inhibitors of CYP3A.
CYP3A Inducers: Administration of IMBRUVICA with strong inducers of CYP3A decrease ibrutinib plasma concentrations by approximately 10-fold.
Avoid concomitant use of strong CYP3A inducers (e.g., carbamazepine, rifampin, phenytoin and St. John’s Wort). Consider alternative agents with less CYP3A induction.
Pregnancy and Lactation
Pregnancy: Pregnancy Category D. Risk Summary Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. If IMBRUVICA is used during pregnancy or if the patient becomes pregnant while taking IMBRUVICA, the patient should be apprised of the potential hazard to the fetus. Animal Data Ibrutinib was administered orally to pregnant rats during the period of organogenesis at oral doses of 10, 40 and 80 mg/kg/day. Ibrutinib at a dose of 80 mg/kg/day was associated with visceral malformations (heart and major vessels) and increased post-implantation loss. The dose of 80 mg/kg/day in animals is approximately 14 times the exposure (AUC) in patients with MCL administered the dose of 560 mg daily. Ibrutinib at doses of 40 mg/kg/day or greater was associated with decreased fetal weights. The dose of 40 mg/kg/day in animals is approximately 6 times the exposure (AUC) in patients with MCL administered the dose of 560 mg daily.
Nursing Mothers: It is not known whether ibrutinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from IMBRUVICA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.