Ibrutinib Dosage

Usual Adult Dose for Lymphoma

Initial dose: 560 mg orally once a day

Comment: Dose modifications may be necessary for adverse reactions.

Use: For the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

Usual Adult Dose for Chronic Lymphocytic Leukemia

Initial dose: 420 mg orally once a day

Comment: Dose modifications may be necessary for adverse reactions.

Use: The treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy or CLL with 17p deletion.

Usual Adult Dose for non-Hodgkin's Lymphoma

Initial dose: 420 mg orally once a day

Comment: Dose adjustments of this drug are not required for patients undergoing plasmapheresis; dose modifications may be necessary for adverse reactions.

Use: The treatment of patients with Waldenstrom's macroglobulinemia.

Renal Dose Adjustments

-CrCl greater than 25 mL/min: No dose adjustments recommended
-CrCl less than 25 mL/min: No data available

Liver Dose Adjustments

-Mild liver impairment (Child-Pugh class A): 140 mg orally once a day
-Moderate liver impairment (Child-Pugh class B): Use not recommended
-Severe liver impairment (Child-Pugh class C): Use not recommended

Dose Adjustments

Dose Modifications for Adverse Reactions:
-Grade 3 or greater non-hematological toxicity, Grade 3 or greater neutropenia with infection or fever, or Grade 4 hematological toxicity: Interrupt therapy
-After resolution to Grade 1 or baseline: Reinitiate at the initial dose
-If toxicity reoccurs: Reduce dose by 140 mg and consider a second 140 mg dose reduction if needed
-If toxicity persists or recurs following 2 dose reductions: Discontinue therapy

Dose Modifications for Concomitant Use with CYP450 3A4 inhibitors:
-Concomitant administration of Strong or Moderate CYP450 3A inhibitors should be avoided; alternative agents with less CYP450 3A inhibition should be considered.
-For short-term-use (7 days or less): consider interrupting ibrutinib until the CYP450 3A inhibitor is no longer needed.
-If a moderate CYP450 3A inhibitor must be used; reduce ibrutinib dose to 140 mg orally once a day.
-Increased monitoring for toxicity is recommended for patients taking concomitant strong or moderate CYP450 3A4 inhibitors.

Precautions

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

-Hemodialysis: Data not available
-Peritoneal dialysis: Data not available

Other Comments

Administration advice:
-Administer orally at approximately the same time each day.
-Swallow whole with water; do not open, break, or chew the capsules.
-Take a missed dose as soon as possible on the same day with a return to the normal schedule the following day; do not take extra capsules to make up for the missed dose.

General:
-Treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
-Accelerated FDA approval for MCL indication was granted based on overall response rate.

Monitoring:
-Patients taking concomitant strong or moderate CYP450 3A4 inhibitors should be monitored more closely for signs of toxicity.
-Monitor patients periodically for atrial fibrillation.
-Perform an ECG on patients who develop arrhythmic symptoms or new onset dyspnea.
-Monitor complete blood counts monthly.
-Monitor patients for signs and symptoms of infection, including fever and neutropenia.

Patient advice:
-Avoid grapefruit, grapefruit juice, and Seville oranges (often used in marmalades); avoid taking over-the-counter medications without checking with your health care provider as they may affect the levels of drug in your blood.
-Serious bleeding events and infections can happen during treatment; immediately contact your health care provider if you have any signs of bleeding or infection.
-Diarrhea is a common side effect of this drug; drink plenty of fluids during treatment and contact your doctor if your diarrhea does not go away.
-Avoid driving or operating machinery until you know how this drug affects you; this drug may cause fatigue, drowsiness, and asthenia.
-Women of childbearing potential should use highly effective contraceptive measures while taking this drug and for 3 months after stopping treatment.
-A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.