BEQALZI Film-coated tablet Ref.[116693] Active ingredients: Sonrotoclax

2.1 Important Safety Information

• BEQALZI can cause tumor lysis syndrome (TLS), especially during the ramp-up phase or during restart after a dosage interruption [see Warnings and Precautions (5.1)].
• Initiate BEQALZI with a dose ramp-up. For dose interruption lasting greater than 7 days, adjust the restart BEQALZI dose as instructed [see Dosage and Administration (2.3) and (2.4)].
• Assess patient risk for TLS and whether hospitalization for monitoring is warranted.
• Initiate prophylactic hydration and anti-hyperuricemics before the first dose of BEQALZI and continue as appropriate.
• Correct pre-existing electrolyte abnormalities before the first dose.
• Monitor blood chemistries closely [see Warnings and Precautions (5.1)].

2.2 Recommended Dosage for Mantle Cell Lymphoma

BEQALZI dosing begins with a 4-week ramp-up. The ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS.

4-Week Dose Ramp-Up Schedule

Administer BEQALZI orally once daily, according to the ramp-up dosing schedule shown in Table 1.

Table 1. Dosing Schedule for 4-Week Ramp-Up Phase:

The Starter Pack provides the first 4 weeks of BEQALZI according to the ramp-up schedule [see How Supplied/Storage and Handling (16)].

Target Dose Week 5 and Beyond

After completion of the 4-week ramp-up phase, the recommended dosage of BEQALZI is 320 mg (four 80 mg tablets) taken orally once daily until disease progression or unacceptable toxicity.

Dosing after treatment interruption greater than 7 days is described in Table 3 [see Dosage Modifications for Adverse Reactions (2.3)].

2.3 Dosage Modifications for Adverse Reactions

Table 2 provides recommended BEQALZI dosage modifications for adverse reactions.

Table 3 provides temporary dose modifications upon restart after dose interruptions lasting more than 7 days.

Table 4 provides recommended modifications to the target dose after adverse reactions are resolved.

Table 2. Recommended BEQALZI Dosage Modifications for Adverse Reactions:

^a Adverse reactions were graded using NCI CTCAE version 5.0.
^b A maximum of 2 dose reductions is recommended.
^c Patients may continue taking BEQALZI for the following:
* Grade 3 gastrointestinal toxicity (i.e., nausea, vomiting, diarrhea) unless unresponsive to treatment ≥3 days.
* Asymptomatic biochemical laboratory abnormalities, other than TLS, that resolve in 7 days or less.

For patients with a dose interruption lasting 7 days or less:

• During ramp-up phase (Weeks 1 to 4): Resume BEQALZI and continue the remaining ramp-up schedule.
• During the target dose (Week 5 and beyond): Resume BEQALZI once the adverse reaction has resolved. Refer to Table 2 and Table 4 if a modified target dose is needed.

For patients with a dose interruption lasting more than 7 days:

• During ramp-up phase (Weeks 1 to 4): Restart BEQALZI at the dose shown in Table 3 based on the dose at the time of interruption, then re-escalate following the ramp-up schedule.
• During the target dose (Week 5 and beyond): Restart BEQALZI at the dose shown in Table 3 based on the dose at the time of interruption. Then, re-escalate to target dose determined per Table 4 when clinically appropriate.

Table 3. Dose to Restart BEQALZI After a Dose Interruption Greater than 7 Days:

^a The physician may restart at a lower dose than noted.
^b Resume on Day 1 of the individual restart pack. Instruct patients to follow the dosing schedule printed on the blister card starting on Day 1 (1 tablet daily on Days 1 through 3, then 2 tablets daily on Days 4 through 7).
^c Resume on Day 4 of the individual restart pack. Instruct patients to remove and dispose of single tablets labeled Days 1 through 3 and restart taking tablets labeled Day 4 (2 tablets daily) of the individual restart pack.

Table 4. Recommended Modification of Target Dose Level for Adverse Reactions:

2.4 Dosage Modifications for Drug Interactions

Strong or Moderate CYP3A Inhibitors

Concomitant strong CYP3A inhibitors are contraindicated at initiation and during ramp-up of BEQALZI. For dose adjustments after ramp-up, see Table 5. Avoid moderate CYP3A inhibitors during initiation and at the 1 mg and 2 mg dose of sonrotoclax.

Table 5. Management of Potential BEQALZI Interactions with CYP3A Inhibitors:

^a Consider alternative medicinal products or reduce the sonrotoclax dose as described in Table 6.

Resume the BEQALZI dosage that was used prior to treatment with a strong or moderate CYP3A inhibitor at least 5 days after discontinuation of the inhibitor.

Table 6. BEQALZI Dose with Moderate CYP3A Inhibitor:

2.5 Administration

Take BEQALZI tablets with a meal once a day at the same approximate time. Swallow tablets whole with a glass of water. Do not break, chew, or crush the tablets.

Missed Dose

If a dose of BEQALZI is missed within 8 hours of when it is usually taken, instruct the patient to take the missed dose as soon as possible with a meal and resume the normal daily dosing schedule. If a dose is missed by more than 8 hours, instruct the patient to not take the missed dose, and resume the usual dosing schedule the next day.

If the patient vomits following a dose, instruct the patient to not take an additional dose that day, and resume the usual dosing schedule the next day.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

Storage of blister wallets: Store tablets in the original blister package; do not transfer the tablets to a different container.