Lucivenet is a BCL-2 inhibitor indicated:

· For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

· In combination with Azacitidine, or Decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

Tumor Lysis Syndrome (TLS): Anticipate TLS; assess risk in all patients. Pre-medicate with anti-hyperuricemias and ensure adequate hydration. Employ more intensive measures (intravenous hydration, frequent monitoring, hospitalization) as overall risk increases.

Neutropenia: Monitor blood counts. Interrupt dosing and resume at same or reduced dose. Consider supportive care measures.

Infections: Monitor for signs and symptoms of infection and treat promptly. Withhold for Grade 3 and 4 infection until resolution and resume at same or reduced dose.

Immunization: Do not administer live attenuated vaccines prior to, during, or after treatment with Lucivenet until B-cell recovery.

Embryo-Fetal Toxicity: May cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

Treatment of patients with multiple myeloma with Lucivenet in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials.

It is indicated for the treatment of adult patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).

It is indicated in combination with Azacitidine, or Decitabine, or low-dose Cytarabine for the treatment of newly diagnosed Acute Myeloid Leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL and AML cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Lucivenet helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases. In nonclinical studies, Venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2.

Maximum plasma concentration of Venetoclax was reached 5 to 8 hours following multiple oral administration under fed conditions. 

5-week ramp-up dosing schedule

Week 1: Lucivenet 20mg once daily

Week 2: Lucivenet 50mg once daily

Week 3: Lucivenet 100mg once daily

Week 4: Lucivenet 200mg once daily

Week 5: Lucivenet 400mg once daily

The recommended dosage of Lucivenet is 400 mg once daily after completion of the 5-week ramp-up dosing schedule. Continue Lucivenet until disease progression or unacceptable toxicity.

Take Lucivenet with a meal and water.

Take Lucivenet at approximately the same time each day. 

Swallow Lucivenet tablets whole. Do not chew, crush, or break tablets prior to swallowing.

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your healthcare provider will do tests to check your risk of getting TLS before you start taking Lucivenet . You will receive other medicines before starting and during treatment with Lucivenet to help reduce your risk of TLS.

You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start treatment and during treatment with Lucivenet . It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you have any symptoms of TLS during treatment with Lucivenet , including:

Fever

Chills

Nausea

Vomiting

Confusion

Shortness of breath

Seizures

Irregular heartbeat

Dark or cloudy urine

Unusual tiredness

Muscle or joint pain

Venetoclax is continued, in combination with Azacitidine or Decitabine or low-dose Cytarabine, until disease progression or unacceptable toxicity.

Venetoclax contraindication or dosage modification based on concomitant use with a strong or moderate CYP3A inhibitor or a P-gp inhibitor at initiation, during, or after the ramp-up phase.

Resume the Lucivenet dosage that was used prior to concomitant use of a strong or moderate CYP3A inhibitor or a P-gp inhibitor 2 to 3 days after discontinuation of the inhibitor.

Parconazole - Reduce Venetoclax dose to 70 mg.

Other strong CYP3A inhibitor - Reduce Lucivenet dose to 100 mg.

Moderate CYP3A inhibitor / P-gp inhibitor - Reduce the Venetoclax dose by at least 50%.

In patients with CLL/SLL, consider alternative medications or reduce the Venetoclax dose.

Reduce the Venetoclax once daily dose by 50% for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more closely for adverse reactions.

Concomitant use of Venetoclax with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome.

No clinically significant differences in Venetoclax pharmacokinetics were observed when co-administered with Azacitidine, Azithromycin, Cytarabine, Decitabine, gastric acid reducing agents, Obinutuzumab, or Rituximab.

Store in a dry place and store at 20°C to 25°C.

The recommended dosage of Lucivenet may be delivered using any of the approved tablet strengths (e.g., patients can take 2 x 50 mg tablets or 10 x 10 mg tablets instead of 1 x 100 mg tablet as needed).

If the patient misses a dose of Lucivenet within 8 hours of the time it is usually taken, instruct the patient to 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, instruct the patient not to take the missed dose and resume the usual dosing schedule the next day.

If the patient vomits following dosing, instruct the patient to not take an additional dose that day and to take the next prescribed dose at the usual time.

Advise patients of the potential risk of TLS, particularly at treatment initiation, during the ramp-up phase, and with resumption after an interruption and to immediately report any signs and symptoms associated with this event (fever, chills, nausea, vomiting, confusion, shortness of breath, seizure, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle pain, and/or joint discomfort) to their health care provider (HCP) for evaluation.

Advise patients to be adequately hydrated every day when taking Lucivenet to reduce the risk of TLS. The recommended volume is 6 to 8 glasses (approximately 56 ounces total) of water each day. Patients should drink water starting 2 days before and on the day of the first dose, and every time the dose is increased.

Advise patients of the importance of keeping scheduled appointments for blood work or other laboratory tests.