Usual Adult Dose for Lymphoma

560 mg orally once a day

Comments:

• Therapy should be continued until disease progression or unacceptable toxicity.

• For the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy
• For the treatment of adult patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy

Usual Adult Dose for Chronic Lymphocytic Leukemia

420 mg orally once a day

Comments:

• Therapy should be continued until disease progression or unacceptable toxicity.
• This drug can be administered as a single agent, in combination with rituximab or obinutuzumab, or in combination with bendamustine and rituximab.
• When administering in combination with rituximab or obinutuzumab, consider administering this drug prior to rituximab or obinutuzumab when given on the same day.

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

Usual Adult Dose for non-Hodgkin's Lymphoma

420 mg orally once a day

Comments:

• Therapy for Waldenstrom's Macroglobulinemia (WM) should be continued until disease progression or unacceptable toxicity.
• When used for WM, this drug can be administered as a single agent or in combination with rituximab.
• Therapy for cGVHD should be continued until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity

• For the treatment of adult patients with Waldenstrom's macroglobulinemia (WM)
• For the treatment of adult patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy

Usual Adult Dose for Graft Versus Host Disease

420 mg orally once a day

Comments:

• Therapy for Waldenstrom's Macroglobulinemia (WM) should be continued until disease progression or unacceptable toxicity.
• When used for WM, this drug can be administered as a single agent or in combination with rituximab.
• Therapy for cGVHD should be continued until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity

• For the treatment of adult patients with Waldenstrom's macroglobulinemia (WM)
• For the treatment of adult patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy

Renal Dose Adjustments

• Mild or moderate renal impairment (CrCl 25 mL/min or greater): No adjustment recommended.
• Severe renal impairment (CrCl less than 25 mL/min): Data not available

Liver Dose Adjustments

• Mild hepatic impairment (Child-Pugh A): 140 mg orally daily
• Moderate hepatic impairment (Child-Pugh B): 70 mg orally daily
• Severe hepatic impairment (Child-Pugh C): Not recommended.

Dose Adjustments

ADVERSE REACTIONS:

• Interrupt therapy for any Grade 3 or greater nonhematologic toxicity, Grade 3 or greater neutropenia with infection or fever, or Grade 4 hematological toxicity. -When toxicity has resolved to Grade 1 or baseline, therapy may be reinitiated at the starting dose.
• If toxicity reoccurs, reduce dose by 140 mg per day.
• A second reduction of dose by 140 mg may be considered if needed.
• If toxicity persists or recurs following 2 dose reductions, discontinue therapy.

• First occurrence of toxicity: Restart at 560 mg daily
• Second occurrence of toxicity: Restart at 420 mg daily
• Third occurrence of toxicity: Restart at 280 mg daily
• Fourth occurrence of toxicity: Discontinue therapy

• First occurrence of toxicity: Restart at 420 mg daily
• Second occurrence of toxicity: Restart at 280 mg daily
• Third occurrence of toxicity: Restart at 140 mg daily
• Fourth occurrence of toxicity: Discontinue therapy

• Concomitant administration of moderate CYP450 3A inhibitor: Administer 280 mg orally once daily; modify dose as recommended
• Voriconazole 200 mg orally twice daily or posaconazole suspension 100 mg orally once daily, 100 mg orally twice daily, or 200 mg orally twice daily: Administer 140 mg orally once daily; modify dose as recommended
• Posaconazole suspension 200 mg orally 3 times daily or 400 mg orally 2 times daily or posaconazole 300 mg IV once daily or posaconazole delayed-release tablets 300 mg orally once daily: Administer 70 mg orally once daily
• Other strong CYP450 3A inhibitors: Avoid concomitant use; if these inhibitors will be used short-term (such as anti-infectives for 7 days or less): Interrupt therapy

• Concomitant administration of moderate CYP450 3A Inhibitor: Administer usual dose (420 mg orally once a day); modify dose as recommended.
• Concomitant administration of voriconazole 200 mg orally 2 times a day or posaconazole suspension 100 mg orally once daily, 100 mg orally twice daily, or 200 mg orally twice daily: Administer 280 mg orally once daily; modify dose as recommended.
• Concomitant administration of posaconazole suspension 200 mg orally 3 times daily or 400 mg orally 2 times daily or posaconazole 300 mg IV once daily or posaconazole delayed-release tablets 300 mg orally once daily: Administer 140 mg orally once daily; interrupt dose as recommended
• Other strong CYP450 3A inhibitors: Avoid concomitant use; if these inhibitors will be used short-term (such as anti-infectives for 7 days or less): Interrupt therapy
• After discontinuation of a CYP450 3A inhibitor, resume previous dose of this drug.

Precautions

CONTRAINDICATIONS:

• None

Dialysis

Data not available

Other Comments

• Administer this drug at approximately the same time each day.
• Instruct patients to swallow capsules or tablets whole with water, and not to open, break, or chew the capsules. Do not cut, crush, or chew the tablets.
• Instruct the patient that this drug must not be taken with grapefruit juice or Seville oranges.
• Administer a missed dose as soon as possible on the same day with a return to the normal dosing schedule the following day; do not administer extra doses to make up the missed dose.

• Store drug bottles at 20C to 25C (68F to 77F); excursions are permitted between 15C and 30C (59F to 86F).
• Retain in original packaging until dispensing.

• Cardiovascular: Signs/symptoms of atrial fibrillation, atrial flutter, ventricular tachyarrhythmia, new onset hypertension or uncontrolled hypertension (during treatment)
• Embryofetal toxicity: Pregnancy status of females of reproductive potential (baseline and during treatment)
• General: Signs of bleeding (during treatment)
• Hematologic: Complete blood counts (monthly); signs/symptoms of leukostasis (during treatment)
• Hepatic: Liver function tests (during treatment)
• Infections/infestations: Fever and infections (during treatment)
• Metabolic: Signs/symptoms of tumor lysis syndrome (during treatment)
• Oncologic: Appearance of non-melanoma skin cancer (during treatment)
• Respiratory: Signs/symptoms of interstitial lung disease

• Avoid grapefruit, grapefruit juice, and Seville oranges (often used in marmalades) during therapy.
• This drug may cause side effects such as fatigue and dizziness; avoid driving or other potentially dangerous activities such as operating machinery until you know how this drug affects you.
• Inform your healthcare provider with you have symptoms of heart problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, swelling of the feet, ankles or legs, chest discomfort, or faint.

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