Usual Adult Dose for Chronic Lymphocytic Leukemia

25 mg orally 2 times a day in 28-day cycles until unacceptable toxicity or progressive disease

Comments:

• If a dose is missed by fewer than 6 hours, take the missed dose right away

and take the next dose as usual. If a dose is missed by more than 6 hours, wait
and take the next dose at the usual time.

• Provide prophylaxis for Pneumocystis jirovecii (PJP) during therapy with this drug.
• Withhold therapy in patients with suspected PJP of any Grade and discontinue if PJP is confirmed.
• Consider prophylactic antivirals during therapy to prevent cytomegalovirus

(CMV) infection/reactivation.

Uses: For the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least 2 prior therapies

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

No adjustment recommended.

Dose Adjustments

DOSE MODIFICATION LEVELS:

• Initial dose: 25 mg orally 2 times a day
• Dose reduction: 15 mg orally 2 times a day
• Subsequent dose modification: Discontinue therapy if patient is unable to tolerate 15 mg orally 2 times a day.

Nonhematologic Adverse Reactions:
INFECTION:

• Grade 3 or greater infection: Withhold therapy until resolved; resume at the same or reduced dose.
• CMV infection or viremia (positive PCR or antigen test): Withhold therapy until resolved; resume at the same or reduced dose; if therapy is resumed, monitor for CMV reactivation (by PCR or antigen test) monthly.
• Pneumocystis jiroveci pneumonia (PJP): For suspected PJP, withhold therapy until evaluated; for confirmed PJP, discontinue therapy.

NON-INFECTIOUS DIARRHEA OR COLITIS:

• Mild/moderate diarrhea (Grade 1 or 2, up to 6 stools per day over baseline) and

responsive to antidiarrheal agents, OR asymptomatic (Grade 1) colitis: Maintain current dose; initiate antidiarrheals if needed; monitor weekly until resolved.

• Mild/moderate diarrhea (Grade 1 or 2, up to 6 stools per day over baseline) and

unresponsive to antidiarrheals: Withhold therapy until resolved; initiate enteric acting steroids (e.g., budesonide); monitor weekly until resolved; resume at reduced dose.

• Abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs, OR severe diarrhea (Grade 3, greater than 6 stools per day over baseline): Withhold therapy until resolved; initiate enteric acting steroids (e.g., budesonide) or systemic steroids; monitor weekly until resolved; resume at reduced dose. For life-threatening recurrent Grade 3 diarrhea or recurrent colitis of any Grade, discontinue therapy.

CUTANEOUS REACTIONS:

• Grade 1 to 2: Maintain dose; initiate emollients, antihistamines, or topical steroids; monitor closely.
• Grade 3: Withhold therapy until resolved; initiate emollients, antihistamines, or topical steroids; monitor weekly until resolved; resume at reduced dose. If severe cutaneous reaction does not improve, worsens, recurs, or becomes life-threatening, discontinue therapy.
• SJS, TEN, DRESS (any Grade): Discontinue therapy.

PNEUMONITIS WITHOUT SUSPECTED INFECTIOUS CAUSE:

• Moderate (Grade 2) symptomatic pneumonitis: Withhold therapy; initiate systemic steroids; if pneumonitis recovers to Grade 0 or 1, resume therapy at reduced dose; if non-infectious pneumonitis recurs or patient does not respond to steroid therapy, discontinue this drug.
• Severe (Grade 3) or life-threatening pneumonitis: Discontinue therapy; initiate systemic steroids.

ALT/AST ELEVATION:

• Grade 2 (3 to 5 x upper limit of normal [ULN]): Maintain dose; monitor weekly until recovery to less than 3 x ULN.
• Grade 3 (greater than 5 to 20 x ULN: Withhold therapy and monitor weekly until recovery to less than 3 x ULN; resume at same dose (first occurrence) or reduce dose for subsequent occurrences.
• Grade 4 (greater than 20 x ULN: Discontinue therapy.

Hematologic Adverse Reactions:
NEUTROPENIA:

• Absolute neutrophil count (ANC) 0.5 to 1 Gi/L: Maintain dose; monitor ANC weekly.
• ANC less than 0.5 Gi/L: Withhold therapy; monitor ANC until greater than 0.5 Gi/L; resume at same dose (first occurrence) or reduce dose for subsequent occurrences.

THROMBOCYTOPENIA:

• Grade 3 (platelet count 25 to less than 50 Gi/L with Grade 1 bleeding: Maintain dose; monitor platelet counts weekly.
• Grade 3 (platelet count 25 to less than 50 Gi/L with Grade 2 bleeding or Grade 4 (platelet count less than 25 Gi/L): Withhold therapy; monitor platelet count until 25 Gi/L or greater and resolution of bleeding; resume at same dose (first occurrence) or reduce dose for subsequent occurrences.

Dose Modification for Concomitant Use with CYP450 3A4 Inhibitors:

• When given with strong CYP450 3A4 inhibitors (e.g., ketoconazole), reduce the dose of this drug to 15 mg orally 2 times a day.

Precautions

US BOXED WARNINGS:
SERIOUS AND/OR FATAL TOXICITIES:
Infections:

• Serious and/or fatal infections occurred in 31% of patients. Monitor for infection. Withhold therapy if infection is suspected.

Diarrhea/Colitis:

• Serious and/or fatal diarrhea or colitis occurred in 18% of patients. Monitor

for severe diarrhea or colitis and withhold therapy.
Cutaneous Reactions:

• Serious and/or fatal cutaneous reactions occurred in 5% of patients. Withhold therapy for these reactions.

Pneumonitis:

• Serious and/or fatal 5% of patients. Monitor for pulmonary symptoms and interstitial infiltrates. Withhold therapy for these reactions.

CONTRAINDICATIONS:

• None

This drug is not recommended for use in children.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug may be taken with or without food.
• Capsules should be swallowed whole, not opened, broken, or chewed.

Storage requirements:

• Store at 20C to 25C (68F to 77F), with excursions permitted at 15C to 30C (59F to 86F).
• Retain in original package until dispensing.
• Dispense blister packs in original container.

Monitoring:

• Monitor hepatic function.
• Neutropenia: Monitor blood counts.

Patient advice:

• Read patient labeling for the initial prescription and for all refills.
• This drug can cause serious infections that may be fatal; immediately report symptoms of infection (e.g., fever, chills).
• This drug can cause serious diarrhea or colitis (inflammation of the gut) that may be fatal. Immediately report new or worsening diarrhea, stool with mucus or blood, or abdominal pain.
• This drug can cause a serious skin rash that may be fatal; immediately report new or worsening skin rash.
• This drug can cause pneumonitis (inflammation of the lungs) that may

be fatal; immediately report new or worsening respiratory symptoms such as cough or difficulty breathing.

• Immediately report jaundice (yellow eyes or skin), abdominal pain, bruising, bleeding, or fever.
• Do not become pregnant or breastfeed while taking this drug.
• Males with female partners of reproductive potential should use effective contraception during therapy and for at least one month after the last dose.

Frequently asked questions

• What type of drug is Copiktra?