Usual Adult Dose for non-Hodgkin's Lymphoma

150 mg orally 2 times a day until disease progression or unacceptable toxicity

Comments:

• This drug can be taken with or without food.
• Tablets should be swallowed whole.
• If the patient misses a dose within 6 hours of the time it is usually taken, the patient should take the missed dose as soon as possible and resume the normal dosing schedule.
• If a patient misses a dose by more than 6 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.

• In combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.
• The treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) who have received at least 2 prior systemic therapies.
• The treatment of patients with relapsed small lymphocytic lymphoma (SLL) who have received at least 2 prior systemic therapies.

Usual Adult Dose for Chronic Lymphocytic Leukemia

150 mg orally 2 times a day until disease progression or unacceptable toxicity

Comments:

• This drug can be taken with or without food.
• Tablets should be swallowed whole.
• If the patient misses a dose within 6 hours of the time it is usually taken, the patient should take the missed dose as soon as possible and resume the normal dosing schedule.
• If a patient misses a dose by more than 6 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.

• In combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.
• The treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) who have received at least 2 prior systemic therapies.
• The treatment of patients with relapsed small lymphocytic lymphoma (SLL) who have received at least 2 prior systemic therapies.

Usual Adult Dose for Lymphoma

150 mg orally 2 times a day until disease progression or unacceptable toxicity

Comments:

• This drug can be taken with or without food.
• Tablets should be swallowed whole.
• If the patient misses a dose within 6 hours of the time it is usually taken, the patient should take the missed dose as soon as possible and resume the normal dosing schedule.
• If a patient misses a dose by more than 6 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.

• In combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.
• The treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) who have received at least 2 prior systemic therapies.
• The treatment of patients with relapsed small lymphocytic lymphoma (SLL) who have received at least 2 prior systemic therapies.

Renal Dose Adjustments

No dose adjustment is necessary for patients with a CrCl greater than or equal to 15 mL/min.

Liver Dose Adjustments

• AST and/or ALT greater than 3 to 5 times the upper limit of normal (3 to 5 x ULN): Maintain dose, monitor at least weekly until less than or equal to ULN.
• AST and/or ALT greater than 5 to 20 x ULN: Withhold therapy, monitor at least weekly until less than or equal to ULN, may resume at 100 mg twice a day.
• AST and/or ALT greater than 20 x ULN: Permanently discontinue therapy.

• Bilirubin greater than 1.5 to 3 x ULN: Maintain dose, monitor at least weekly until less than or equal to ULN.
• Bilirubin greater than 3 to 10 x ULN: Withhold therapy, monitor at least weekly until less than or equal to ULN, may resume at 100 mg twice a day.
• Bilirubin greater than 10 x ULN: Permanently discontinue therapy.

Dose Adjustments

Pneumonitis:

• Discontinue therapy in patients with any severity of symptomatic pneumonitis.

• If moderate diarrhea develops during therapy (increase of 4 to 6 stools per day over baseline), maintain dose and monitor at least weekly until resolved.
• If severe diarrhea develops during therapy (increase of 7 or more stools per day over baseline), withhold therapy and monitor at least weekly until resolved, then resume therapy at 100 mg twice a day.
• If life-threatening diarrhea develops during treatment, discontinue therapy permanently.

• ANC 1 to less than 1.5 Gi/L: Maintain dose.
• ANC 0.5 to less than 1 Gi/L: Maintain dose and monitor ANC at least weeky.
• ANC less than 0.5: interrupt therapy and monitor at least weekly until ANC is 0.5 Gi/L or greater, then resume therapy at 100 mg twice a day.

• Platelets 50 to less than 75 Gi/L: Maintain dose.
• Platelets 25 to less than 50 Gi/L: Maintain dose and monitor platelet counts at least weekly.
• Platelets less than 25 Gi/L: Withhold therapy and monitor at least weekly; resume therapy at 100 mg twice a day when platelets are 25 Gi/L or greater.

• Grade 3 or higher sepsis or pneumonia: Interrupt therapy until infection has resolved.
• Evidence of CMV infection or viremia: Interrupt therapy in patients with evidence of active CMV infection of any grade or viremia (positive PCR or antigen test) until the viremia has resolved. If therapy is resumed, monitor patients by PCR or antigen test for CMV reactivation at least monthly.
• Evidence of PJP infection: Interrupt therapy in patients with suspected PJP infection of any grade. Permanently discontinue therapy if PJP infection is confirmed.

• No dose modification is required for lymphocytosis, which has been observed in some patients taking this drug. This lymphocytosis is a pharmacodynamic effect and should not be considered progressive disease in the absence of other clinical findings.

Precautions

US REMS: The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for this drug. It includes a communication plan. For additional information: www.fda.gov/REMS.

US BOXED WARNINGS:
WARNING: FATAL AND SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMONITIS, INFECTIONS, and INTESTINAL PERFORATION:

• Fatal and/or serious hepatotoxicity occurred in 16% to 18% of patients. Monitor hepatic function prior to and during therapy. Interrupt therapy and then reduce or discontinue the drug as recommended.
• Fatal and/or serious and severe diarrhea or colitis occurred in 14% to 20% of patients. Monitor for development of severe diarrhea or colitis. Interrupt therapy and then reduce or discontinue the drug as recommended.
• Fatal and/or serious pneumonitis occurred in 4% of patients. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt therapy and then reduce or discontinue the drug as recommended.
• Fatal and/or serious infections occurred in 21% to 48% of patients. Monitor for infection. Interrupt therapy if infection is suspected.
• Fatal and serious intestinal perforation can occur. Discontinue therapy for intestinal perforation.

• History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis

Dialysis

Data not available

Other Comments

Administration advice:

• Take with or without food.
• Tablets should be swallowed whole.

Frequently asked questions

• What is Zydelig used for and how does it work?