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Venclexta Dosage

Generic name: Venetoclax 10mg; Venetoclax 50mg; Venetoclax 100mg
Dosage form: tablets

Medically reviewed by Drugs.com. Last updated on Nov 29, 2018.

Recommended Dosage

Assess patient-specific factors for level of risk of tumor lysis syndrome (TLS) and provide prophylactic hydration and anti-hyperuricemics to patients prior to first dose of VENCLEXTA to reduce risk of TLS [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].

Instruct patients to take VENCLEXTA tablets with a meal and water at approximately the same time each day. VENCLEXTA tablets should be swallowed whole and not chewed, crushed, or broken prior to swallowing.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

All VENCLEXTA dose regimens begin with a 5-week ramp-up.

VENCLEXTA 5-week Dose Ramp-Up Schedule

Administer the VENCLEXTA dose according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg as shown in Table 1. The 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS.

Table 1. Dosing Schedule for Ramp-Up Phase in Patients with CLL/SLL
VENCLEXTA
Daily Dose
Week 1 20 mg
Week 2 50 mg
Week 3 100 mg
Week 4 200 mg
Week 5 and beyond 400 mg

The CLL/SLL Starting Pack provides the first 4 weeks of VENCLEXTA according to the ramp-up schedule. The 400 mg dose is achieved using 100 mg tablets supplied in bottles [see How Supplied/Storage and Handling (16)].

VENCLEXTA in Combination with Rituximab

Start rituximab administration after the patient has completed the 5-week dose ramp-up schedule with VENCLEXTA (see Table 1) and has received the 400 mg dose of VENCLEXTA for 7 days. Administer rituximab on Day 1 of each 28-day cycle for 6 cycles, with rituximab dosed at 375 mg/m2 intravenously for Cycle 1 and 500 mg/m2 intravenously for Cycles 2-6.

Patients should continue VENCLEXTA 400 mg once daily for 24 months from Cycle 1 Day 1 of rituximab.

VENCLEXTA as Monotherapy

The recommended dose of VENCLEXTA is 400 mg once daily after the patient has completed the 5-week dose ramp-up schedule. VENCLEXTA should be taken orally once daily until disease progression or unacceptable toxicity is observed.

Acute Myeloid Leukemia

The dose of VENCLEXTA depends upon the combination agent.

The VENCLEXTA dosing schedule (including ramp-up) is shown in Table 2. Initiate the azacitidine or decitabine or low-dose cytarabine on Day 1.

Table 2. Dosing Schedule for Ramp-up Phase in Patients with AML
VENCLEXTA
Daily Dose
Day 1 100 mg
Day 2 200 mg
Day 3 400 mg
Days 4 and beyond 400 mg
when dosing in combination with
azacitidine or decitabine
600 mg
when dosing in combination with
low-dose cytarabine

Continue VENCLEXTA, in combination with azacitidine or decitabine or low-dose cytarabine, until disease progression or unacceptable toxicity is observed.

Risk Assessment and Prophylaxis for Tumor Lysis Syndrome

Patients treated with VENCLEXTA may develop tumor lysis syndrome. Refer to the appropriate section below for specific details on management. Assess patient-specific factors for level of risk of tumor lysis syndrome (TLS) and provide prophylactic hydration and anti-hyperuricemics to patients prior to first dose of VENCLEXTA to reduce risk of TLS.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS in the initial 5-week ramp-up phase. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase.

The risk of TLS is a continuum based on multiple factors, including tumor burden and comorbidities. Reduced renal function (creatinine clearance [CLcr] <80 mL/min) further increases the risk. Perform tumor burden assessments, including radiographic evaluation (e.g., CT scan), assess blood chemistry (potassium, uric acid, phosphorus, calcium, and creatinine) in all patients and correct pre-existing abnormalities prior to initiation of treatment with VENCLEXTA. The risk may decrease as tumor burden decreases [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].

Table 3 below describes the recommended TLS prophylaxis and monitoring during VENCLEXTA treatment based on tumor burden determination from clinical trial data. Consider all patient comorbidities before final determination of prophylaxis and monitoring schedule.

Table 3. Recommended TLS Prophylaxis Based on Tumor Burden in Patients with CLL/SLL
Tumor Burden Prophylaxis Blood Chemistry
Monitoringc,d
Hydrationa Anti-hyperuricemics Setting and
Frequency of
Assessments
Low All LN <5 cm AND
ALC <25 x109/L
Oral
(1.5-2 L)
Allopurinolb Outpatient
  • For first dose of 20 mg and 50 mg: Pre-dose, 6 to 8 hours, 24 hours
  • For subsequent ramp-up doses: Pre-dose
Medium Any LN 5 cm to <10 cm
OR
ALC ≥25 x109/L
Oral
(1.5-2 L)
and consider additional intravenous
Allopurinol Outpatient
  • For first dose of 20 mg and 50 mg: Pre-dose, 6 to 8 hours, 24 hours
  • For subsequent ramp-up doses: Pre-dose
  • For first dose of 20 mg and 50 mg: Consider hospitalization for patients with CLcr <80ml/min; see below for monitoring in hospital
High Any LN ≥10 cm OR
ALC ≥25 x109/L AND
any LN ≥5 cm
Oral (1.5-2L)
and intravenous
(150-200 mL/hr
as tolerated)
Allopurinol; consider rasburicase if baseline uric acid is elevated In hospital
  • For first dose of 20 mg and 50 mg: Pre-dose, 4, 8, 12 and 24 hours
Outpatient
  • For subsequent ramp-up doses: Pre-dose, 6 to 8 hours, 24 hours
ALC = absolute lymphocyte count; CLcr = creatinine clearance; LN = lymph node.
aAdminister intravenous hydration for any patient who cannot tolerate oral hydration.
bStart allopurinol or xanthine oxidase inhibitor 2 to 3 days prior to initiation of VENCLEXTA.
cEvaluate blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine); review in real time.
dFor patients at risk of TLS, monitor blood chemistries at 6 to 8 hours and at 24 hours at each subsequent ramp-up dose.

Acute Myeloid Leukemia

  • All patients should have white blood cell count less than 25 × 109/L prior to initiation of VENCLEXTA. Cytoreduction prior to treatment may be required.
  • Prior to first VENCLEXTA dose, provide all patients with prophylactic measures including adequate hydration and anti-hyperuricemic agents and continue during ramp-up phase.
  • Assess blood chemistry (potassium, uric acid, phosphorus, calcium, and creatinine) and correct pre-existing abnormalities prior to initiation of treatment with VENCLEXTA.
  • Monitor blood chemistries for TLS at pre-dose, 6 to 8 hours after each new dose during ramp-up and 24 hours after reaching final dose.
  • For patients with risk factors for TLS (e.g., circulating blasts, high burden of leukemia involvement in bone marrow, elevated pretreatment lactate dehydrogenase (LDH) levels, or reduced renal function) additional measures should be considered, including increased laboratory monitoring and reducing VENCLEXTA starting dose.

Dose Modifications Based on Toxicities

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Interrupt dosing or reduce dose for toxicities. See Table 4 and Table 5 for recommended dose modifications for toxicities related to VENCLEXTA. For patients who have had a dosing interruption greater than 1 week during the first 5 weeks of ramp-up phase or greater than 2 weeks after completing the ramp-up phase, reassess for risk of TLS to determine if reinitiation with a reduced dose is necessary (e.g., all or some levels of the dose ramp-up schedule) [see Dosage and Administration (2.1, 2.2)].

Table 4. Recommended VENCLEXTA Dose Modifications for Toxicitiesa in CLL/SLL
Event Occurrence Action
Tumor Lysis Syndrome
Blood chemistry changes or symptoms suggestive of TLS Any Withhold the next day’s dose. If resolved within 24 to 48 hours of last dose, resume at the same dose.
For any blood chemistry changes requiring more than 48 hours to resolve, resume at a reduced dose (see Table 5) [see Dosage and Administration (2.2)].
For any events of clinical TLS,b resume at a reduced dose following resolution (see Table 5) [see Dosage and Administration (2.2)].
Non-Hematologic Toxicities
Grade 3 or 4 non-hematologic toxicities 1st occurrence Interrupt VENCLEXTA.
Once the toxicity has resolved to Grade 1 or baseline level, VENCLEXTA therapy may be resumed at the same dose. No dose modification is required.
2nd and subsequent occurrences Interrupt VENCLEXTA.
Follow dose reduction guidelines in Table 5 when resuming treatment with VENCLEXTA after resolution. A larger dose reduction may occur at the discretion of the physician.
Hematologic Toxicities
Grade 3 neutropenia with infection or fever; or Grade 4 hematologic toxicities (except lymphopenia) [see Warnings and Precautions (5.2)] 1st occurrence Interrupt VENCLEXTA.
To reduce the infection risks associated with neutropenia, granulocyte-colony stimulating factor (G-CSF) may be administered with VENCLEXTA if clinically indicated. Once the toxicity has resolved to Grade 1 or baseline level, VENCLEXTA therapy may be resumed at the same dose.
2nd and subsequent occurrences Interrupt VENCLEXTA.
Consider using G-CSF as clinically indicated.
Follow dose reduction guidelines in Table 5 when resuming treatment with VENCLEXTA after resolution. A larger dose reduction may occur at the discretion of the physician.
Consider discontinuing VENCLEXTA for patients who require dose reductions to less than 100 mg for more than 2 weeks.
aAdverse reactions were graded using NCI CTCAE version 4.0.
bClinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or sudden death and/or seizures [see Adverse Reactions (6.1)].
Table 5. Dose Reduction for Toxicity During VENCLEXTA Treatment in CLL/SLL
Dose at Interruption, mg Restart Dose, mga
400 300
300 200
200 100
100 50
50 20
20 10
aDuring the ramp-up phase, continue the reduced dose for 1 week before increasing the dose.

Acute Myeloid Leukemia

Monitor blood counts frequently through resolution of cytopenias. Management of some adverse reactions [see Warnings and Precautions (5.2) and Adverse Reactions (6.2)] may require dose interruptions or permanent discontinuation of VENCLEXTA. Table 6 shows the dose modification guidelines for hematologic toxicities.

Table 6. Recommended Dose Modifications for Toxicitiesa in AML
Event Occurrence Action
Hematologic Toxicities
Grade 4 neutropenia with or without fever or infection; or Grade 4 thrombocytopenia [see Warnings and Precautions (5.2)] Occurrence prior to achieving remission Transfuse blood products, administer prophylactic and treatment anti-infectives as clinically indicated.

In most instances, VENCLEXTA and azacitidine, decitabine, or low-dose cytarabine cycles should not be interrupted due to cytopenias prior to achieving remission.
First occurrence after achieving remission and lasting at least 7 days Delay subsequent treatment cycle of VENCLEXTA and azacitidine, decitabine, or low-dose cytarabine and monitor blood counts.

Administer granulocyte-colony stimulating factor (G-CSF) if clinically indicated for neutropenia. Once the toxicity has resolved to Grade 1 or 2, resume VENCLEXTA therapy at the same dose in combination with azacitidine or decitabine or low-dose cytarabine.
Subsequent occurrences in cycles after achieving remission and lasting 7 days or longer Delay subsequent treatment cycle of VENCLEXTA and azacitidine, or decitabine, or low-dose cytarabine and monitor blood counts.

Administer G-CSF if clinically indicated for neutropenia. Once the toxicity has resolved to Grade 1 or 2, resume VENCLEXTA therapy at the same dose and the duration reduced by 7 days for each subsequent cycle.
aAdverse reactions were graded using NCI CTCAE version 4.0.

Dosage Modifications for Concomitant Use with Strong or Moderate CYP3A Inhibitors or P-gp Inhibitors

Table 7 describes VENCLEXTA contraindication or dosage modification based on concomitant use with a strong or moderate CYP3A inhibitor or P-gp inhibitor [see Drug Interactions (7.1)] at initiation, during, or after the ramp-up phase.

Resume the VENCLEXTA dosage that was used prior to concomitant use of a strong or moderate CYP3A inhibitor or P-gp inhibitor 2 to 3 days after discontinuation of the inhibitor [see Dosage and Administration (2.3) and Drug Interactions (7.1)].

Table 7. Management of Potential VENCLEXTA Interactions with CYP3A and P-gp Inhibitors
Coadministered
drug
Initiation and
Ramp-Up Phase
Steady Daily Dose
(After Ramp-Up Phase)
a
Posaconazole CLL/SLL Contraindicated Reduce VENCLEXTA dose to 70 mg.
AML Day 1 – 10 mg
Day 2 – 20 mg
Day 3 – 50 mg
Day 4 – 70 mg
Other strong CYP3A
inhibitor
CLL/SLL Contraindicated Reduce VENCLEXTA dose to 100 mg.
AML Day 1 – 10 mg
Day 2 – 20 mg
Day 3 – 50 mg
Day 4 – 100 mg
Moderate CYP3A
inhibitor
Reduce the VENCLEXTA dose by at least 50%.
P-gp inhibitor
aIn patients with CLL/SLL, consider alternative medications or reduce the VENCLEXTA dose as described in Table 7.

Missed Dose

If the patient misses a dose of VENCLEXTA within 8 hours of the time it is usually taken, the patient should take the missed dose as soon as possible and resume the normal daily dosing schedule. If a patient misses a dose by more than 8 hours, the patient should not take the missed dose and should resume the usual dosing schedule the next day.

If the patient vomits following dosing, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time.

Further information

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