What is the patient's indication for Venetoclax?
What is the patient's assigned Tumor Lysis Syndrome (TLS) risk category with cancer type?
What is the patient's largest lymph node size?
What is the patient's absolute lymphocyte count (ALC)?
Before beginning therapy, what is the patient's WBC?
Risk Levels CLL/SLL:
Low Risk, CLL/SLL
- Hydration: Oral (1.5-2 L/day) beginning 2-3 days prior to first dose
- Anti-hyperuricemics: Begin allopurinol 2-3 days prior to first dose
- TLS Lab Monitoring: Monitor blood chemistries, including potassium, uric acid, phosphorous, calcium, and creatinine, pre-dose for each dose of the ramp-up series. For the first dose of 20 mg and 50 mg, obtain additional lab work 6-8 hours after the first dose, as well as 24 hours after the first dose.
- Screen for drug-drug interactions - click for link to CLL Dose Modification During Ramp Up with CYP3A Inhibitors chart
Medium Risk, CLL/SLL
- Hydration: Oral (1.5-2 L/day) beginning 2-3 days prior to first dose
- Anti-hyperuricemics: Begin allopurinol 2-3 days prior to first dose
- TLS Lab Monitoring: Monitor blood chemistries, including potassium, uric acid, phosphorous, calcium, and creatinine, pre-dose for each dose of the ramp-up series. For the first dose of 20 mg and 50 mg, obtain additional lab work 6-8 hours after the first dose, as well as 24 hours after the first dose.
- Screen for drug-drug interactions - click for link to CLL Dose Modification During Ramp Up with CYP3A Inhibitors chart
- Consider hospitalization for patients with CrCl < 80mL/min at first dose of 20mg and 50mg
High Risk, CLL/SLL
- Hydration: Oral (1.5-2 L/day) beginning 2-3 days prior to first dose and IV (150-200 mL/hr) as tolerated.
- Anti-hyperuricemics: Begin allopurinol 2-3 days prior to first dose. Consider rasburicase if elevated baseline uric acid.
- TLS Lab Monitoring: Monitor blood chemistries, including potassium, uric acid, phosphorous, calcium, and creatinine. For the first dose of 20 mg and 50 mg, which should be given in the hospital on two separate admissions, obtain lab work pre-dose as well as 4, 8, 12, and 24 hours after administration of the dose. Ensure inpatient staff is aware of the lab orders and the frequency so that labs are not seen as "duplicates" and inadvertently cancelled. For subsequent ramp-up doses, which can be given outpatient, obtain lab work pre-dose as well as 6-8 hours and 24 hours after administration. All labs should be reviewed in "real time" for early detection of TLS.
- Screen for drug-drug interactions - click for link to CLL Dose Modification During Ramp Up with CYP3A Inhibitors chart
Links to CLL Dosing Tables:
CLL Monotherapy Dosing
CLL Ven + G Dosing
CLL Ven + R Dosing
CLL Dose Modification During Ramp Up with CYP3A Inhibitors
CLL Monotherapy Dosing
CLL Monotherapy Dosing
CLL Ven + G Dosing
CLL Ven + R Dosing
CLL Dose Modification During Ramp Up with CYP3A Inhibitors
| VENETOCLAX Monotherapy | |
|---|---|
| Week 1 | 20mg QD |
| Week 2 | 50mg QD |
| Week 3 | 100mg QD |
| Week 4 | 200mg QD |
| Week 5 | 400mg QD |
| After week 5, continue with 400mg QD until disease progression or unacceptable toxicity | |
CLL VEN + G Dosing
| VENETOCLAX + OBINUTUZUMAB 1st line | |
|---|---|
| Week 1 (Cycle 1, Day 22) | 20mg QD |
| Week 2 | 50mg QD |
| Week 3 | 100mg QD |
| Week 4 | 200mg QD |
| Week 5 (Cycle 3, Day 1) | 400mg QD (Continue through Cycle 12) |
| Obinutuzumab Cycle 1, Day 1 for a total of 6 cycles - refer to package insert for additional information | |
CLL VEN + R Dosing
| VENETOCLAX + RITUXIMAB R/R | |
|---|---|
| Week 1 | 20mg QD |
| Week 2 | 50mg QD |
| Week 3 | 100mg QD |
| Week 4 | 200mg QD |
| Week 5 | 400mg QD |
| Begin Rituximab after patient has completed the 5 week ramp up schedule above - refer to package insert for additional information. 400mg QD Ven dose continues for 24 months from Cycle 1 Day 1 of Rituximab | |
CLL Dose Modification During Ramp Up with CYP3A Inhibitors
| CLL DOSE MODIFICATION DURING RAMP UP WITH MODERATE CYP3A INHIBITORS | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
Moderate CYP3A Inhibitors include but are not limited to the following:
|
Week 1 | 10mg | |||||||||
| Week 2 | 20mg | ||||||||||
| Week 3 | 50mg | ||||||||||
| Week 4 | 100mg | ||||||||||
| Week 5 | 200mg | ||||||||||
| If initiating Moderate CYP3A Inhibitor treatment during Venetoclax treatment, dose reduce Venetoclax by at least 50%, with steady state dosing at 200mg or less. | |||||||||||
| CLL DOSE MODIFICATION DURING RAMP UP WITH MODERATE CYP3A INHIBITORS | |||||||||||
Strong CYP3A Inhibitors include but are not limited to the following:
|
Contraindicated during ramp up of Venetoclax. If use of both Venetoclax and Strong CYP3A is warranted, consider dose interruption/pause of CYP3A treatment during ramp up phase, with final Venetoclax steady state dose of 100mg (complete ramp up at week 4 and continue dosing at 100mg daily for treatment dose). Restart CYP3A treatment once at steady state Venetoclax dose and monitor. For concomitant Posaconazole, reduce week 4 ramp up Venetoclax dosing from 100mg to 70mg, with 70mg daily as final steady state Venetoclax treatment dose. |
||||||||||
| If the use of a Strong CYP3A Inhibitor is warranted during Venetoclax treatment, consider dose interruption/pause of Venetoclax treatment for course of Strong CYP3A Inhibitor, then resume Venetoclax dose 2-3 days after discontinuation of Strong CYP3A Inhibitor. | |||||||||||
AML - with WBC < 25 x 109/L
In patients with WBC < 25 x 109/L, prophylactic measures below should start 1-2 days prior to treatment:- Ensure patient is adequately hydrated (oral hydration for all patients should include 1.5-2 L/day), beginning 1-3 days prior to treatment
- Premedicate with allopurinol 1-2 days prior to therapy and continue if needed, based on uric acid levels
- Monitor potassium, calcium, phosphorous, uric acid levels and CrCL to ensure adequate baseline levels prior to start of first dose
- Once all measures above are taken into consideration, check for drug-drug interactions and modify as needed using chart below - click for link to table
- Bone marrow assessment recommended at the end of Cycle 1 to measure response
AML - with WBC ≥ 25 x 109/L
In any AML patient with WBC ≥ 25 x 109/L, cytoreduction prior to treatment may be required. Please see package insert for more information on cytoreduction.- In any AML patient with WBC ≥ 25 x 109/L, cytoreduction prior to treatment may be required. Once the patient has WBC < 25 x 109/L, please proceed with treatment in the next steps.
- Ensure patient is adequately hydrated (oral hydration for all patients should include 1.5-2 L/day), beginning 1-3 days prior to treatment
- Premedicate with allopurinol 1-2 days prior to therapy and continue if needed, based on uric acid levels
- Monitor potassium, calcium, phosphorous, uric acid levels and CrCL to ensure adequate baseline levels prior to start of first dose
- Once all measures above are taken into consideration, check for drug-drug interactions and modify as needed using chart below - click for link to table
- Bone marrow assessment recommended at the end of Cycle 1 to measure response
Links to AML Dosing Tables:
AML Ven + AZA or DEC
AML Ven + LDAC
AML ramp up dose modifications for drug interactions
AML Dosing Chart for DECitibine or AZAcitidine regimens
AML Ven + AZA or DEC
AML Ven + LDAC
AML ramp up dose modifications for drug interactions
| VENETOCLAX Dosing with DECitabine1 or AZAcitidine2 | |
|---|---|
| Day 1 | 100mg |
| Day 2 | 200mg |
| Days 3-28 | 400mg |
1DECitabine regimens will include 20mg/m2 IV on Days 1-5 of Venetoclax treatment
2AZAcitidine regimens will include 75mg/m2 IV/SQ on Days 1-7 of Venetoclax treatment
AML Dosing Chart for LDAC regimens
| VENETOCLAX + LDAC1 | |
|---|---|
| Day 1 | 100mg |
| Day 2 | 200mg |
| Day 3 | 400mg |
| Days 4-28 | 600mg |
1LDAC – Low dose cytarabine regimens will include 20mg/m2 SQ on Days 1-10 of Venetoclax treatment
AML Ramp up Dose Modifications for Drug Interactions
| Drug (s) | Dose Reduction Recommended |
|---|---|
| Posaconazole | Reduce Ramp up as follows: Day 1: 10mg Day 2: 20mg Day 3: 50mg Day 4: 70mg 70mg Continuous Daily Dose |
| Strong CYP3A Inhibitors: Clarithromycin Conivaptan Indinavir Itraconazole Ketoconazole Lopinavir Ritonavir Telaprevir Voriconazole |
Reduce Ramp up as follows: Day 1: 10mg Day 2: 20mg Day 3: 50mg Day 4: 100mg 100mg Continuous Daily Dose |
| Moderate CYP3A Inhibitors: Ciprofloxacin Diltiazem Dronedarone Erythromycin Fluconazole Verapamil |
Reduce VEN dose by at least 50% for VEN + AZA/DEC regimens: Day 1: 50mg Day 2: 100mg Day 3: 200mg 200mg Continuous Daily Dose |
The drugs listed above are not all inclusive. Please refer to the Package Insert for more information.
Ramp up Dose Modifications for Drug Interactions
| Drug(s) | Dose Reduction Recommended |
|---|---|
| Posaconazole | Reduce Ramp up as follows: Day 1: 10mg Day 2: 20mg Day 3: 50mg Day 4: 70mg 70mg Continuous Daily Dose |
| Strong CYP3A Inhibitors: Clarithromycin Conivaptan Indinavir Itraconazole Ketoconazole Lopinavir Ritonavir Telaprevir Voriconazole |
Reduce Ramp up as follows: Day 1: 10mg Day 2: 20mg Day 3: 50mg Day 4: 100mg 100mg Continuous Daily Dose |
| Moderate CYP3A Inhibitors: Ciprofloxacin Diltiazem Dronedarone Erythromycin Fluconazole Verapamil |
Reduce VEN dose by at least 50% for VEN + AZA/DEC regimens: Day 1: 50mg Day 2: 100mg Day 3: 200mg 200mg Continuous Daily Dose |
To save this tool report, please click 'Print' below. The option to save as a PDF file can then be selected.