Imbruvica
(Ibrutinib)Dosage & Administration
Tablets or capsules should be taken orally with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets. See full prescribing information for oral suspension administration instructions (
The recommended dosage of IMBRUVICA for CLL/SLL and WM is 420 mg orally once daily until disease progression or unacceptable toxicity.
For CLL/SLL, IMBRUVICA can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR).
For WM, IMBRUVICA can be administered as a single agent or in combination with rituximab.
When administering IMBRUVICA in combination with rituximab or obinutuzumab, consider administering IMBRUVICA prior to rituximab or obinutuzumab when given on the same day.
The recommended dosage of IMBRUVICA for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity. When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA should be discontinued considering the medical assessment of the individual patient.
Recommended dose to achieve 240 mg/m 2 | ||
BSA* (m 2 ) Range | Dose (mg) of IMBRUVICA Capsules/Tablets to Administer | Volume (mL) of IMBRUVICA Oral Suspension (70 mg/mL) to Administer |
| > 0.3 to 0.4 | - | 1.2 mL |
| > 0.4 to 0.5 | - | 1.5 mL |
| > 0.5 to 0.6 | - | 1.9 mL |
| > 0.6 to 0.7 | - | 2.2 mL |
| > 0.7 to 0.8 | 210 mg | 2.6 mL |
| > 0.8 to 0.9 | 210 mg | 2.9 mL |
| > 0.9 to 1 | 210 mg | 3.3 mL |
| > 1 to 1.1 | 280 mg | 3.6 mL |
| > 1.1 to 1.2 | 280 mg | 4 mL |
| > 1.2 to 1.3 | 280 mg | 4.3 mL |
| > 1.3 to 1.4 | 350 mg | 4.6 mL |
| > 1.4 to 1.5 | 350 mg | 5 mL |
| > 1.5 to 1.6 | 350 mg | 5.3 mL |
| > 1.6 | 420 mg | 6 mL |
*BSA = body surface area.
Administer IMBRUVICA at approximately the same time each day.
Swallow tablets or capsules whole with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets.
Follow Instructions for Use for further administration details of IMBRUVICA oral suspension.
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. Do not take extra doses of IMBRUVICA to make up for the missed dose.
By using PrescriberAI, you agree to the AI Terms of Use.
Imbruvica Prescribing Information
IMBRUVICA is a kinase inhibitor indicated for the treatment of:
- Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) ().1.1Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
- Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion ().1.000000000000000e+002Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with 17p deletion
IMBRUVICA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with 17p deletion.
- Adult patients with Waldenström’s macroglobulinemia (WM) ().1.000000000000000e+003Waldenström’s Macroglobulinemia
IMBRUVICA is indicated for the treatment of adult patients with Waldenström’s macroglobulinemia (WM).
- Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy ().1.000000000000000e+004Chronic Graft versus Host Disease
IMBRUVICA is indicated for the treatment of adult and pediatric patients age 1 year and older with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.
- CLL/SLL and WM: 420 mg taken orally once daily ().2.1Recommended DosageChronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Waldenström’s Macroglobulinemia
The recommended dosage of IMBRUVICA for CLL/SLL and WM is 420 mg orally once daily until disease progression or unacceptable toxicity.
For CLL/SLL, IMBRUVICA can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR).
For WM, IMBRUVICA can be administered as a single agent or in combination with rituximab.
When administering IMBRUVICA in combination with rituximab or obinutuzumab, consider administering IMBRUVICA prior to rituximab or obinutuzumab when given on the same day.
Chronic Graft versus Host DiseaseThe recommended dosage of IMBRUVICA for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity. When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA should be discontinued considering the medical assessment of the individual patient.
Table 1: Recommended dosage based on body surface area (BSA) for patients 1 to less than 12 years of age using either IMBRUVICA capsules/tablets or oral suspension Recommended dose to achieve 240 mg/m2BSA* (m2) RangeDose (mg) of IMBRUVICA Capsules/Tablets to AdministerVolume (mL) of IMBRUVICA Oral Suspension (70 mg/mL) to Administer> 0.3 to 0.4 - 1.2 mL > 0.4 to 0.5 - 1.5 mL > 0.5 to 0.6 - 1.9 mL > 0.6 to 0.7 - 2.2 mL > 0.7 to 0.8 210 mg 2.6 mL > 0.8 to 0.9 210 mg 2.9 mL > 0.9 to 1 210 mg 3.3 mL > 1 to 1.1 280 mg 3.6 mL > 1.1 to 1.2 280 mg 4 mL > 1.2 to 1.3 280 mg 4.3 mL > 1.3 to 1.4 350 mg 4.6 mL > 1.4 to 1.5 350 mg 5 mL > 1.5 to 1.6 350 mg 5.3 mL > 1.6 420 mg 6 mL *BSA = body surface area.
AdministrationAdminister IMBRUVICA at approximately the same time each day.
Swallow tablets or capsules whole with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets.
Follow Instructions for Use for further administration details of IMBRUVICA oral suspension.
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. Do not take extra doses of IMBRUVICA to make up for the missed dose.
- cGVHD:
◦ Patients 12 years and older: 420 mg taken orally once daily ().2.1Recommended DosageChronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Waldenström’s MacroglobulinemiaThe recommended dosage of IMBRUVICA for CLL/SLL and WM is 420 mg orally once daily until disease progression or unacceptable toxicity.
For CLL/SLL, IMBRUVICA can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR).
For WM, IMBRUVICA can be administered as a single agent or in combination with rituximab.
When administering IMBRUVICA in combination with rituximab or obinutuzumab, consider administering IMBRUVICA prior to rituximab or obinutuzumab when given on the same day.
Chronic Graft versus Host DiseaseThe recommended dosage of IMBRUVICA for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity. When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA should be discontinued considering the medical assessment of the individual patient.
Table 1: Recommended dosage based on body surface area (BSA) for patients 1 to less than 12 years of age using either IMBRUVICA capsules/tablets or oral suspension Recommended dose to achieve 240 mg/m2BSA* (m2) RangeDose (mg) of IMBRUVICA Capsules/Tablets to AdministerVolume (mL) of IMBRUVICA Oral Suspension (70 mg/mL) to Administer> 0.3 to 0.4 - 1.2 mL > 0.4 to 0.5 - 1.5 mL > 0.5 to 0.6 - 1.9 mL > 0.6 to 0.7 - 2.2 mL > 0.7 to 0.8 210 mg 2.6 mL > 0.8 to 0.9 210 mg 2.9 mL > 0.9 to 1 210 mg 3.3 mL > 1 to 1.1 280 mg 3.6 mL > 1.1 to 1.2 280 mg 4 mL > 1.2 to 1.3 280 mg 4.3 mL > 1.3 to 1.4 350 mg 4.6 mL > 1.4 to 1.5 350 mg 5 mL > 1.5 to 1.6 350 mg 5.3 mL > 1.6 420 mg 6 mL *BSA = body surface area.
AdministrationAdminister IMBRUVICA at approximately the same time each day.
Swallow tablets or capsules whole with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets.
Follow Instructions for Use for further administration details of IMBRUVICA oral suspension.
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. Do not take extra doses of IMBRUVICA to make up for the missed dose.
◦ Patients 1 to less than 12 years of age: 240 mg/m2 taken orally once daily (up to a dose of 420 mg) ().2.1Recommended DosageChronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Waldenström’s MacroglobulinemiaThe recommended dosage of IMBRUVICA for CLL/SLL and WM is 420 mg orally once daily until disease progression or unacceptable toxicity.
For CLL/SLL, IMBRUVICA can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR).
For WM, IMBRUVICA can be administered as a single agent or in combination with rituximab.
When administering IMBRUVICA in combination with rituximab or obinutuzumab, consider administering IMBRUVICA prior to rituximab or obinutuzumab when given on the same day.
Chronic Graft versus Host DiseaseThe recommended dosage of IMBRUVICA for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity. When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA should be discontinued considering the medical assessment of the individual patient.
Table 1: Recommended dosage based on body surface area (BSA) for patients 1 to less than 12 years of age using either IMBRUVICA capsules/tablets or oral suspension Recommended dose to achieve 240 mg/m2BSA* (m2) RangeDose (mg) of IMBRUVICA Capsules/Tablets to AdministerVolume (mL) of IMBRUVICA Oral Suspension (70 mg/mL) to Administer> 0.3 to 0.4 - 1.2 mL > 0.4 to 0.5 - 1.5 mL > 0.5 to 0.6 - 1.9 mL > 0.6 to 0.7 - 2.2 mL > 0.7 to 0.8 210 mg 2.6 mL > 0.8 to 0.9 210 mg 2.9 mL > 0.9 to 1 210 mg 3.3 mL > 1 to 1.1 280 mg 3.6 mL > 1.1 to 1.2 280 mg 4 mL > 1.2 to 1.3 280 mg 4.3 mL > 1.3 to 1.4 350 mg 4.6 mL > 1.4 to 1.5 350 mg 5 mL > 1.5 to 1.6 350 mg 5.3 mL > 1.6 420 mg 6 mL *BSA = body surface area.
AdministrationAdminister IMBRUVICA at approximately the same time each day.
Swallow tablets or capsules whole with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets.
Follow Instructions for Use for further administration details of IMBRUVICA oral suspension.
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. Do not take extra doses of IMBRUVICA to make up for the missed dose.
Tablets or capsules should be taken orally with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets. See full prescribing information for oral suspension administration instructions (
The recommended dosage of IMBRUVICA for CLL/SLL and WM is 420 mg orally once daily until disease progression or unacceptable toxicity.
For CLL/SLL, IMBRUVICA can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR).
For WM, IMBRUVICA can be administered as a single agent or in combination with rituximab.
When administering IMBRUVICA in combination with rituximab or obinutuzumab, consider administering IMBRUVICA prior to rituximab or obinutuzumab when given on the same day.
The recommended dosage of IMBRUVICA for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m2orally once daily (up to a dose of 420 mg), until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity. When a patient no longer requires therapy for the treatment of cGVHD, IMBRUVICA should be discontinued considering the medical assessment of the individual patient.
Recommended dose to achieve 240 mg/m 2 | ||
BSA* (m 2 ) Range | Dose (mg) of IMBRUVICA Capsules/Tablets to Administer | Volume (mL) of IMBRUVICA Oral Suspension (70 mg/mL) to Administer |
| > 0.3 to 0.4 | - | 1.2 mL |
| > 0.4 to 0.5 | - | 1.5 mL |
| > 0.5 to 0.6 | - | 1.9 mL |
| > 0.6 to 0.7 | - | 2.2 mL |
| > 0.7 to 0.8 | 210 mg | 2.6 mL |
| > 0.8 to 0.9 | 210 mg | 2.9 mL |
| > 0.9 to 1 | 210 mg | 3.3 mL |
| > 1 to 1.1 | 280 mg | 3.6 mL |
| > 1.1 to 1.2 | 280 mg | 4 mL |
| > 1.2 to 1.3 | 280 mg | 4.3 mL |
| > 1.3 to 1.4 | 350 mg | 4.6 mL |
| > 1.4 to 1.5 | 350 mg | 5 mL |
| > 1.5 to 1.6 | 350 mg | 5.3 mL |
| > 1.6 | 420 mg | 6 mL |
*BSA = body surface area.
Administer IMBRUVICA at approximately the same time each day.
Swallow tablets or capsules whole with a glass of water. Do not open, break, or chew the capsules. Do not cut, crush, or chew the tablets.
Follow Instructions for Use for further administration details of IMBRUVICA oral suspension.
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. Do not take extra doses of IMBRUVICA to make up for the missed dose.
Each 70 mg capsule is a yellow, opaque capsule marked with “ibr 70 mg” in black ink.
Each 140 mg capsule is a white, opaque capsule marked with “ibr 140 mg” in black ink.
Each 140 mg tablet is a yellow green to green round tablet debossed with “ibr” on one side and “140” on the other side.
Each 280 mg tablet is a purple oblong tablet debossed with “ibr” on one side and “280” on the other side.
Each 420 mg tablet is a yellow green to green oblong tablet debossed with “ibr” on one side and “420” on the other side.
70 mg/mL, white to off-white suspension.
- Lactation: Advise not to breastfeed ().8.2LactationRisk Summary
There is no information regarding the presence of ibrutinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with IMBRUVICA and for 1 week after the last dose.
- Hepatic Impairment: Avoid use of IMBRUVICA in patients with severe hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA dose (,2.4Dosage Modifications for Use in Hepatic ImpairmentAdult Patients with B-cell Malignancies
The recommended dosage is 140 mg daily for patients with mild hepatic impairment (Child-Pugh class A).
The recommended dosage is 70 mg daily for patients with moderate hepatic impairment (Child-Pugh class B).
Avoid the use of IMBRUVICA in patients with severe hepatic impairment (Child-Pugh class C)
[see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].Patients with cGVHDThe recommended dosage is 140 mg daily for patients 12 years of age and older with total bilirubin level >1.5 to 3 x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilbert’s syndrome).
The recommended dosage is 80 mg/m2daily for patients 1 to less than 12 years of age with total bilirubin level >1.5 to 3 x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome).
Avoid the use of IMBRUVICA in these patients with total bilirubin level > 3 x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome)
[see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].).8.6Hepatic ImpairmentAdult Patients with B-cell MalignanciesAvoid use of IMBRUVICA in patients with severe hepatic impairment (Child-Pugh class C). The safety of IMBRUVICA has not been evaluated in patients with mild to severe hepatic impairment by Child-Pugh criteria.
Reduce the recommended dose when administering IMBRUVICA to patients with mild or moderate hepatic impairment (Child-Pugh class A and B). Monitor patients more frequently for adverse reactions of IMBRUVICA
[see Dosage and Administration (2.4), Clinical Pharmacology (12.3)].Patients with cGVHDAvoid use of IMBRUVICA in patients with total bilirubin level > 3 x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome). Reduce recommended dose when administering IMBRUVICA to patients with total bilirubin level > 1.5 to 3 x ULN (unless of non-hepatic origin or due to Gilbert’s syndrome)
[see Dosage and Administration (2.4)].
None
- Hemorrhage: Monitor for bleeding and manage ().5.1Hemorrhage
Fatal bleeding events have occurred in patients who received IMBRUVICA. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA in 27 clinical trials. Bleeding events of any grade including bruising and petechiae occurred in 39%, and excluding bruising and petechiae occurred in 23% of patients who received IMBRUVICA, respectively
[see Adverse Reactions (6.1)].The mechanism for the bleeding events is not well understood.
Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA increases the risk of major hemorrhage. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA. Monitor for signs and symptoms of bleeding.
Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding
[seeClinical Studies (14)]. - Infections: Monitor patients for fever and infections, evaluate promptly, and treat ().5.2Infections
Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 21% of 1,476 patients with B-cell malignancies who received IMBRUVICA in clinical trials
[see Adverse Reactions (6.1,6.2)]. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Monitor and evaluate patients for fever and infections and treat appropriately. - Cardiac Arrhythmias,Cardiac Failure, and Sudden Death: Monitor for symptoms of arrhythmias and cardiac failure and manage ().5.3Cardiac Arrhythmias, Cardiac Failure, and Sudden Death
Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA. Deaths due to cardiac causes or sudden deaths occurred in 1% of 4,896 patients who received IMBRUVICA in clinical trials, including in patients who received IMBRUVICA in unapproved monotherapy or combination regimens. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities. Patients with cardiac comorbidities may be at greater risk of these events.
Grade 3 or greater ventricular tachyarrhythmias were reported in 0.2%, Grade 3 or greater atrial fibrillation and atrial flutter were reported in 3.7%, and Grade 3 or greater cardiac failure was reported in 1.3% of 4,896 patients who received IMBRUVICA in clinical trials, including in patients who received IMBRUVICA in unapproved monotherapy or combination regimens. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections
[see Adverse Reactions (6.1)].Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines
[see Dosage and Administration (2.2)], and consider the risks and benefits of continued IMBRUVICA treatment. - Hypertension: Monitor blood pressure and treat ().5.4Hypertension
Hypertension occurred in 19% of 1,476 patients with B-cell malignancies who received IMBRUVICA in clinical trials. Grade 3 or greater hypertension occurred in 8% of patients
[see Adverse Reactions (6.1)]. Based on data from a subset of these patients (N=1,124), the median time to onset was 5.9 months (range, 0 to 24 months). In a long-term safety analysis over 5 years of 1,284 patients with B-cell malignancies treated for a median of 36 months (range, 0 to 98 months), the cumulative rate of hypertension increased over time. The prevalence for Grade 3 or greater hypertension was 4% (year 0-1), 7% (year 1-2), 9% (year 2-3), 9% (year 3-4), and 9% (year 4-5); the overall incidence for the 5-year period was 11%.Monitor blood pressure in patients treated with IMBRUVICA, initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension
[see Dosage and Administration (2.2)]. - Cytopenias: Check complete blood counts monthly ().5.5Cytopenias
In 645 patients with B-cell malignancies who received IMBRUVICA as a single agent, grade 3 or 4 neutropenia occurred in 23% of patients, grade 3 or 4 thrombocytopenia in 8% and grade 3 or 4 anemia in 2.8%, based on laboratory measurements
[see Adverse Reactions (6.1)].Monitor complete blood counts monthly.
- Second Primary Malignancies: Other malignancies have occurred in patients, including skin cancers, and other carcinomas ().5.6Second Primary Malignancies
Other malignancies (10%), including non-skin carcinomas (3.9%), occurred among the 1,476 patients with B-cell malignancies who received IMBRUVICA in clinical trials
[see Adverse Reactions (6.1)]. The most frequent second primary malignancy was non-melanoma skin cancer (6%). - Hepatotoxicity, Including Drug-Induced Liver Injury: Monitor hepatic function throughout treatment ().5.7Hepatotoxicity, Including Drug-Induced Liver Injury
Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including IMBRUVICA.
Evaluate bilirubin and transaminases at baseline and throughout treatment with IMBRUVICA. For patients who develop abnormal liver tests after IMBRUVICA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold IMBRUVICA. Upon confirmation of DILI, discontinue IMBRUVICA.
- Tumor Lysis Syndrome (TLS): Assess baseline risk and take precautions. Monitor and treat for TLS ().5.000000000000000e+008Tumor Lysis Syndrome
Tumor lysis syndrome has been infrequently reported with IMBRUVICA
[see Adverse Reactions (6.2)]. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate. - Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception (,5.000000000000000e+009Embryo-Fetal Toxicity
Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 3-20 times higher than those reported in patients with hematologic malignancies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA and for 1 month after the last dose.
[see Use in Specific Populations (8.1)].,8.1PregnancyRisk SummaryIMBRUVICA can cause fetal harm based on findings from animal studies. There are no available data on IMBRUVICA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis at exposures up to 3-20 times the clinical dose of 420 mg daily produced embryofetal toxicity including structural abnormalities
(see Data). Advise pregnant women of the potential risk to a fetus.All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
DataAnimal DataIbrutinib was administered orally to pregnant rats during the period of organogenesis at 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 resorptions and post-implantation loss. The dose of 80 mg/kg/day in rats is approximately 20 times the exposure in patients with CLL/SLL or WM administered a dose of 420 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 rats is approximately 8 times the exposure (AUC) in patients administered a dose of 420 mg daily.
Ibrutinib was also administered orally to pregnant rabbits during the period of organogenesis at doses of 5, 15, and 45 mg/kg/day. Ibrutinib at a dose of 15 mg/kg/day or greater was associated with skeletal variations (fused sternebrae) and ibrutinib at a dose of 45 mg/kg/day was associated with increased resorptions and post-implantation loss. The dose of 15 mg/kg/day in rabbits is approximately 2.8 times the exposure in patients with CLL/SLL or WM administered a dose of 420 mg daily.
).8.3Females and Males of Reproductive PotentialIMBRUVICA can cause fetal harm when administered to pregnant women
[see Use in Specific Populations (8.1)].Pregnancy TestingVerify pregnancy status in females of reproductive potential prior to initiating IMBRUVICA.
ContraceptionFemalesAdvise females of reproductive potential to use effective contraception during treatment with IMBRUVICA and for 1 month after the last dose.
MalesAdvise males with female partners of reproductive potential to use effective contraception during treatment with IMBRUVICA and for 1 month following the last dose.