Ibrutinib Dosage

Medically reviewed by Drugs.com. Last updated on Sep 5, 2023.

Usual Adult Dose for Chronic Lymphocytic Leukemia

420 mg orally once a day
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• This drug can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab.
• If use in combination with rituximab or obinutuzumab: Administration of this drug before rituximab or obinutuzumab should be considered when given on the same day.

Uses:

• For the treatment of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
• For the treatment of patients with CLL/SLL with 17p deletion

Usual Adult Dose for Waldenstrom's Macroglobulinemia

420 mg orally once a day
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• This drug can be administered as a single agent or in combination with rituximab.
• If used in combination with rituximab: Administration of this drug before rituximab should be considered when given on the same day.
• Management of hyperviscosity may include plasmapheresis before and during therapy with this drug; dosing modifications are not needed.

Use: For the treatment of patients with Waldenstrom's macroglobulinemia (WM)

Usual Adult Dose for Graft Versus Host Disease

420 mg orally once a day
Duration of therapy: Until progression of chronic graft-versus-host disease (cGVHD), recurrence of an underlying malignancy, or unacceptable toxicity

Comments:

• When patients no longer require treatment for cGVHD, this drug should be discontinued considering the medical assessment of the individual patient.

Use: For the treatment of patients with cGVHD after failure of 1 or more lines of systemic therapy

Usual Pediatric Dose for Graft Versus Host Disease

1 to less than 12 years: 240 mg/m2 orally once a day

• Maximum dose: 420 mg/dose

Oral Suspension:
Dosage based on BSA (to achieve 240 mg/m2):

• BSA greater than 0.3 to 0.4 m2: 84 mg orally once a day
• BSA greater than 0.4 to 0.5 m2: 105 mg orally once a day
• BSA greater than 0.5 to 0.6 m2: 133 mg orally once a day
• BSA greater than 0.6 to 0.7 m2: 154 mg orally once a day
• BSA greater than 0.7 to 0.8 m2: 182 mg orally once a day
• BSA greater than 0.8 to 0.9 m2: 203 mg orally once a day
• BSA greater than 0.9 to 1 m2: 231 mg orally once a day
• BSA greater than 1 to 1.1 m2: 252 mg orally once a day
• BSA greater than 1.1 to 1.2 m2: 280 mg orally once a day
• BSA greater than 1.2 to 1.3 m2: 301 mg orally once a day
• BSA greater than 1.3 to 1.4 m2: 322 mg orally once a day
• BSA greater than 1.4 to 1.5 m2: 350 mg orally once a day
• BSA greater than 1.5 to 1.6 m2: 371 mg orally once a day
• BSA greater than 1.6 m2: 420 mg orally once a day

Capsules/Tablets:
Dosage based on BSA (to achieve 240 mg/m2):

• BSA greater than 0.7 to 1 m2: 210 mg orally once a day
• BSA greater than 1 to 1.3 m2: 280 mg orally once a day
• BSA greater than 1.3 to 1.6 m2: 350 mg orally once a day
• BSA greater than 1.6 m2: 420 mg orally once a day

12 years and older: 420 mg orally once a day

Duration of Therapy: Until progression of cGVHD, recurrence of an underlying malignancy, or unacceptable toxicity

Comments:

• When patients no longer require treatment for cGVHD, this drug should be discontinued considering the medical assessment of the individual patient.

Use: For the treatment of patients with cGVHD after failure of 1 or more lines of systemic therapy

Renal Dose Adjustments

Mild and moderate renal dysfunction (CrCl greater than 25 mL/min): No adjustment recommended
Severe renal dysfunction (CrCl less than 25 mL/min): Data not available

Comments:

• CrCl as estimated by Cockcroft-Gault equation

Liver Dose Adjustments

Adult patients with B-cell malignancies:

• Mild liver dysfunction (Child-Pugh A): 140 mg orally once a day
• Moderate liver dysfunction (Child-Pugh B): 70 mg orally once a day
• Severe liver dysfunction (Child-Pugh C): Not recommended

Patients with cGVHD:

• Total bilirubin greater than 1.5 to 3 times the upper limit of normal (1.5 to 3 x ULN), unless of nonhepatic origin or due to Gilbert's syndrome:
• Patients 12 years and older: 140 mg orally once a day
• Patients 1 to less than 12 years: 80 mg/m2 orally once a day
• Total bilirubin greater than 3 x ULN, unless of nonhepatic origin or due to Gilbert's syndrome: Not recommended

Comments:

• Adult patients with B-cell malignancies:
• Safety has not been evaluated in patients with mild to severe liver dysfunction by Child-Pugh criteria.
• Patients with mild or moderate liver dysfunction (Child-Pugh A and B) should be monitored more frequently for adverse reactions.

Dose Adjustments

DOSAGE MODIFICATIONS FOR ADVERSE REACTIONS:
This drug should be interrupted for the adverse reactions listed below. Once the adverse reaction has improved to grade 1 or baseline (recovery), the recommended dosage modifications should be followed.

Dose Modification for CLL/SLL, WM, and Patients 12 Years and Older with cGVHD After Recovery (Starting Dose = 420 mg):
Cardiac arrhythmias:

• Grade 3:
• First occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 280 mg orally once a day
• Second occurrence: This drug should be discontinued.
• Grade 4: This drug should be discontinued.

Cardiac failure:

• Grade 2:
• First occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 280 mg orally once a day
• Second occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 140 mg orally once a day
• Third occurrence: This drug should be discontinued.
• Grade 3 or 4: This drug should be discontinued.

Hematological toxicities:

• Grade 4:
• First occurrence: Should restart at 280 mg orally once a day
• Second occurrence: Should restart at 140 mg orally once a day
• Third occurrence: This drug should be discontinued.

Neutropenia with infection or fever:

• Grade 3 or 4:
• First occurrence: Should restart at 280 mg orally once a day
• Second occurrence: Should restart at 140 mg orally once a day
• Third occurrence: This drug should be discontinued.

Other nonhematological toxicities:

• Grade 3:
• First occurrence: Should restart at 280 mg orally once a day
• Second occurrence: Should restart at 140 mg orally once a day
• Third occurrence: This drug should be discontinued.
• Grade 4:
• First occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 280 mg orally once a day
• Second occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 140 mg orally once a day
• Third occurrence: This drug should be discontinued.

Dose Modification for Patients 1 to Less Than 12 Years with cGVHD After Recovery (Starting Dose = 240 mg/m2):
Cardiac arrhythmias:

• Grade 3:
• First occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 160 mg/m2 orally once a day
• Second occurrence: This drug should be discontinued.
• Grade 4: This drug should be discontinued.

Cardiac failure:

• Grade 2:
• First occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 160 mg/m2 orally once a day
• Second occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 80 mg/m2 orally once a day
• Third occurrence: This drug should be discontinued.
• Grade 3 or 4: This drug should be discontinued.

Hematological toxicities:

• Grade 4:
• First occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 160 mg/m2 orally once a day
• Second occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 80 mg/m2 orally once a day
• Third occurrence: This drug should be discontinued.

Neutropenia with infection or fever:

• Grade 3 or 4:
• First occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 160 mg/m2 orally once a day
• Second occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 80 mg/m2 orally once a day
• Third occurrence: This drug should be discontinued.

Other nonhematological toxicities:

• Grade 3 or 4:
• First occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 160 mg/m2 orally once a day
• Second occurrence: The benefit-risk should be evaluated before resuming therapy; should restart at 80 mg/m2 orally once a day
• Third occurrence: This drug should be discontinued.

Oral Suspension:
Dosage based on BSA (to achieve 160 mg/m2):

• BSA greater than 0.3 to 0.4 m2: 56 mg orally once a day
• BSA greater than 0.4 to 0.5 m2: 70 mg orally once a day
• BSA greater than 0.5 to 0.6 m2: 91 mg orally once a day
• BSA greater than 0.6 to 0.7 m2: 105 mg orally once a day
• BSA greater than 0.7 to 0.8 m2: 119 mg orally once a day
• BSA greater than 0.8 to 0.9 m2: 133 mg orally once a day
• BSA greater than 0.9 to 1 m2: 154 mg orally once a day
• BSA greater than 1 to 1.1 m2: 168 mg orally once a day
• BSA greater than 1.1 to 1.2 m2: 182 mg orally once a day
• BSA greater than 1.2 to 1.3 m2: 203 mg orally once a day
• BSA greater than 1.3 to 1.4 m2: 217 mg orally once a day
• BSA greater than 1.4 to 1.5 m2: 231 mg orally once a day
• BSA greater than 1.5 to 1.6 m2: 245 mg orally once a day
• BSA greater than 1.6 m2: 280 mg orally once a day

Capsules/Tablets:
Dosage based on BSA (to achieve 160 mg/m2):

• BSA greater than 0.7 to 1.1 m2: 140 mg orally once a day
• BSA greater than 1.1 to 1.5 m2: 210 mg orally once a day
• BSA greater than 1.5 m2: 280 mg orally once a day

Oral Suspension:
Dosage based on BSA (to achieve 80 mg/m2):

• BSA greater than 0.3 to 0.4 m2: 38 mg orally once a day
• BSA greater than 0.4 to 0.5 m2: 35 mg orally once a day
• BSA greater than 0.5 to 0.6 m2: 42 mg orally once a day
• BSA greater than 0.6 to 0.7 m2: 49 mg orally once a day
• BSA greater than 0.7 to 0.8 m2: 63 mg orally once a day
• BSA greater than 0.8 to 0.9 m2: 70 mg orally once a day
• BSA greater than 0.9 to 1 m2: 77 mg orally once a day
• BSA greater than 1 to 1.1 m2: 84 mg orally once a day
• BSA greater than 1.1 to 1.2 m2: 91 mg orally once a day
• BSA greater than 1.2 to 1.3 m2: 98 mg orally once a day
• BSA greater than 1.3 to 1.4 m2: 105 mg orally once a day
• BSA greater than 1.4 to 1.5 m2: 119 mg orally once a day
• BSA greater than 1.5 to 1.6 m2: 126 mg orally once a day
• BSA greater than 1.6 m2: 140 mg orally once a day

Capsules/Tablets:
Dosage based on BSA (to achieve 80 mg/m2):

• BSA greater than 0.7 to 1.1 m2: 70 mg orally once a day
• BSA greater than 1.1 to 1.4 m2: The oral suspension should be used.
• BSA greater than 1.4 m2: 140 mg orally once a day

DOSAGE MODIFICATIONS FOR USE WITH CYP450 3A INHIBITORS:
Patients with B-cell malignancies:

• If coadministered with a moderate CYP450 3A inhibitor: 280 mg orally once a day
• Dose should be modified as recommended for adverse reactions.
• If coadministered with voriconazole (200 mg twice a day) or posaconazole suspension (100 mg once a day, 100 mg twice a day, or 200 mg twice a day): 140 mg orally once a day
• Dose should be modified as recommended for adverse reactions.
• If coadministered with posaconazole suspension (200 mg 3 times a day or 400 mg twice a day), posaconazole IV (300 mg once a day), or posaconazole delayed-release tablets (300 mg once a day): 70 mg orally once a day
• Dose should be interrupted as recommended for adverse reactions.
• If coadministered with other strong CYP450 3A inhibitors: Concomitant use should be avoided.
• If these inhibitors will be used short-term (e.g., anti-infectives for up to 7 days), this drug should be interrupted.

Patients 12 years and older with cGVHD:

• If coadministered with a moderate CYP450 3A inhibitor: 420 mg orally once a day
• Dose should be modified as recommended for adverse reactions.
• If coadministered with voriconazole (200 mg twice a day) or posaconazole suspension (100 mg once a day, 100 mg twice a day, or 200 mg twice a day): 280 mg orally once a day
• Dose should be modified as recommended for adverse reactions.
• If coadministered with posaconazole suspension (200 mg 3 times a day or 400 mg twice a day), posaconazole IV (300 mg once a day), or posaconazole delayed-release tablets (300 mg once a day): 140 mg orally once a day
• Dose should be interrupted as recommended for adverse reactions.
• If coadministered with other strong CYP450 3A inhibitors: Concomitant use should be avoided.
• If these inhibitors will be used short-term (e.g., anti-infectives for up to 7 days), this drug should be interrupted.

Patients 1 to less than 12 years with cGVHD:

• If coadministered with moderate CYP450 3A inhibitors: 240 mg/m2 orally once a day
• Dose should be modified as recommended for adverse reactions.
• If coadministered with voriconazole for suspension (9 mg/kg twice a day; maximum dose: 350 mg): 160 mg/m2 orally once a day
• If coadministered with posaconazole (at any dosage): 80 mg/m2 orally once a day
• If coadministered with other strong CYP450 3A inhibitors: Concomitant use should be avoided.
• If these inhibitors will be used short-term (e.g., anti-infectives for up to 7 days), this drug should be interrupted.

After discontinuation of a CYP450 3A inhibitor, the previous dose of this drug should be resumed.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established for cGVHD in patients younger than 1 year. Safety and efficacy have not been established in patients younger than 18 years with CLL/SLL, CLL/SLL with 17p deletion, or WM.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer at about the same time each day.
• Swallow capsules or tablets whole with a glass of water.
• Do not open, break, or chew the capsules.
• Do not cut, crush, or chew the tablets.
• Discard any remaining oral suspension 60 days after first opening the bottle.
• Avoid grapefruit and Seville oranges during therapy.

Storage requirements:

• Capsules: Store bottles at 20C to 25C (68C to 77F); brief exposure to 15C to 30C (59F to 86F) permitted. Keep in original package until dispensing.
• Oral suspension: Store bottle at 2C to 25C (36F to 77F); do not freeze. Dispense in original sealed container.
• Tablets: Store in original packaging at 20C to 25C (68C to 77F); brief exposure to 15C to 30C (59F to 86F) permitted.

Reconstitution/preparation techniques:

• Oral suspension: The manufacturer product information (Instructions for Use) should be consulted for further administration details.

Monitoring:

• Cardiovascular: Cardiac history and function (at baseline); for cardiac arrhythmias and cardiac function; blood pressure
• Hematologic: For signs/symptoms of bleeding; CBC (monthly)
• Infections/Infestations: For infections and fever
• Metabolism: For tumor lysis syndrome

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• Report any signs/symptoms of bleeding (e.g., severe headache, blood in stools/urine, prolonged/uncontrolled bleeding).
• Report any signs/symptoms suggestive of infection (e.g., fever, chills, weakness, confusion).
• Report any signs of palpitations, lightheadedness, dizziness, fainting, shortness of breath, chest discomfort, or edema.
• Report any signs/symptoms associated with tumor lysis syndrome to your health care provider for evaluation.
• Patients of childbearing potential: Inform health care provider of a known/suspected pregnancy; use effective contraception during therapy and for 1 month after the last dose.
• Male patients with female partners of childbearing potential: Use effective contraception during therapy and for 1 month after the last dose.
• Do not breastfeed during therapy and for 1 week after the last dose.
• Loose stools or diarrhea may occur; contact physician if diarrhea persists. Maintain adequate hydration.
• If a dose is not taken at the scheduled time, take it as soon as possible on the same day and return to the normal schedule the following day; do not take extra doses to make up for the missed dose.

Frequently asked questions

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Further information

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