AHFS Class:

• Antineoplastic Agents 10:00

Brands:

• Beqalzi^®

Generic Name(s):

• Sonrotoclax

Sonrotoclax, a B-cell lymphoma 2 (BCL-2) inhibitor, is an antineoplastic agent.1

Sonrotoclax has the following uses:

Sonrotoclax is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor.1

This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1

General

Sonrotoclax is available in the following dosage form(s) and strength(s):

Tablets: 1 mg, 5 mg, 20 mg, and 80 mg.1

Dosage

Adults

Dosage and Administration

• Recommended dosage: 320 mg orally once daily following completion of a 4-week dose ramp-up schedule.1 The ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of tumor lysis syndrome (TLS).1 Continue treatment until disease progression or unacceptable toxicity.1
• Swallow tablets whole with food and water.1 Do not break, chew, or crush tablets.1
• Provide prophylaxis for TLS.1
• See Full Prescribing Information for the 4-week ramp-up schedule and recommendations for dosage modifications for adverse effects and drug interactions.1

Contraindications

• Concomitant use of sonrotoclax with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated in patients due to the potential for increased risk of tumor lysis syndrome.1

Warnings/Precautions

Tumor Lysis Syndrome

Sonrotoclax can cause serious or life-threatening tumor lysis syndrome (TLS).1 Sonrotoclax can cause rapid reduction in tumor and changes in blood chemistries consistent with TLS that require prompt management.1 This can occur as early as 4 hours after the first dose, at any dose increases, and upon restart following dosage interruption.1 Laboratory or clinical TLS occurred in 7% of the 115 patients with mantle cell lymphoma who followed the recommended dose ramp-up.1 Risk factors for TLS include higher tumor burden such as bulky lymphadenopathy or lymphocytosis and reduced renal function.1

Assess all patients for TLS risk and provide appropriate prophylaxis, including hydration and anti-hyperuricemics starting prior to the first dose of sonrotoclax.1 Correct relevant chemistry abnormalities prior to starting sonrotoclax.1 Consider hospitalization with IV hydration and monitoring and employ more frequent monitoring for patients with high TLS risk.1 Monitor blood chemistries and manage abnormalities promptly.1 Interrupt dosing if needed; when restarting sonrotoclax, follow the dose modification guidance.1

Concomitant use of sonrotoclax with strong or moderate CYP3A inhibitors increases sonrotoclax exposure, which may increase the risk of TLS at initiation and during the ramp-up phase.1

Serious Infections

Sonrotoclax can cause fatal or serious infections.1 Among patients who received sonrotoclax at the recommended dosage in the clinical trial, serious infections occurred in 14% of patients and Grade 3 or higher infections in 17%, with fatal infections in 2.6% of patients.1 The most common Grade 3 or greater infection was pneumonia (10%).1

Monitor for signs and symptoms of infection and treat appropriately.1 Consider prophylactic antimicrobials and immunoglobulins according to guidelines.1 Withhold or dose reduce sonrotoclax based on severity.1

Neutropenia

Sonrotoclax can cause serious or severe cytopenias, including neutropenia.1 Among 115 patients with mantle cell lymphoma who received sonrotoclax, new or worsening Grade 3 or 4 decrease in neutrophils developed in 18% (Grade 4, 6%).1 Febrile neutropenia occurred in 1.7% of patients.1 Monitor complete blood counts throughout treatment.1 Based on severity, reduce dose, interrupt, or permanently discontinue sonrotoclax.1

Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, sonrotoclax can cause fetal harm when administered to a pregnant woman.1 In embryo-fetal development toxicity studies conducted in pregnant mice and rabbits, oral administration of sonrotoclax during the period of organogenesis caused adverse developmental outcomes, including structural abnormalities and altered fetal growth at approximately ≥2 times the clinical exposure based on the AUC at the recommended dose in humans (320 mg/day).1

Advise patients of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with sonrotoclax and for 1 week after the last dose.1 Advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose.1

Specific Populations

Pregnancy

Based on findings in animals and its mechanism of action, sonrotoclax can cause embryo-fetal harm when administered to pregnant women.1 There are no available data on sonrotoclax use in pregnant women to evaluate for a drug-associated risk.1 In animal reproduction studies, oral administration of sonrotoclax to pregnant mice and rabbits during the period of organogenesis resulted in adverse developmental outcomes, including structural abnormalities and altered fetal growth, at maternal exposures approximately ≥2 times the human exposure (AUC) at the recommended dose of 320 mg daily.1 Advise patients of the potential risk to a fetus.1

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

Lactation

There are no data on the presence of sonrotoclax or its metabolites in human milk or the effects on the breastfed child or milk production.1 Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with sonrotoclax and for 1 week after the last dose.1

Females and Males of Reproductive Potential

Based on findings in animals and its mechanism of action, sonrotoclax can cause fetal harm when administered to pregnant women.1

Verify pregnancy status in females of reproductive potential prior to initiating sonrotoclax.1

Advise females of reproductive potential to use effective contraception during treatment with sonrotoclax and for 1 week after the last dose.1

Advise males with female partners of reproductive potential to use effective contraception during treatment with sonrotoclax and for 1 week after the last dose.1

Pediatric Use

The safety and effectiveness of sonrotoclax in pediatric patients have not been established.1

Geriatric Use

Of the 115 patients with mantle cell lymphoma who were treated with sonrotoclax, 74 (64%) were 65 years of age or older and 26 (23%) were 75 years of age or older.1 Patients 65 years of age and older experienced higher rates of serious adverse reactions (42%) compared to younger patients (29%).1 Clinical studies of sonrotoclax did not include sufficient numbers of patients to determine whether efficacy differs in patients 65 years of age or older compared to younger patients.1

Hepatic Impairment

No dose adjustments are recommended for patients with mild or moderate hepatic impairment (bilirubin ≤3 × upper limit of normal [ULN] and any aspartate aminotransferase [AST]).1 Sonrotoclax has not been studied in patients with severe hepatic impairment (bilirubin >3 × ULN and any AST).1

Renal Impairment

No dose adjustments are recommended for patients with mild or moderate renal impairment (estimated glomerular filtration rate (eGFR) ≥30 mL/min).1 Sonrotoclax has not been studied in patients with severe renal impairment (eGFR <30 mL/min).1

Common Adverse Effects

The most common adverse reactions (≥15%) are pneumonia and fatigue.1 The most common Grade 3-4 laboratory abnormalities (≥15%) are decreases in lymphocytes and neutrophils.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Strong CYP3A inhibitors: Contraindicated at initiation and during the ramp-up phase.1 Reduce target dose after ramp-up.1
• Moderate CYP3A inhibitors: Avoid concomitant use at 1 mg and 2 mg doses of sonrotoclax and reduce all other doses.1
• Strong or moderate CYP3A inducers: Avoid coadministration.1

Actions

Mechanism of Action

Sonrotoclax is an inhibitor of B-cell lymphoma 2 (BCL-2) protein.1 Overexpression of BCL-2 in various cancers mediates cell survival and has been associated with chemotherapeutic resistance.1 Sonrotoclax binds to the BCL-2 protein, displacing pro-apoptotic proteins, thereby inducing apoptosis of cells.1 In nonclinical studies, sonrotoclax demonstrated cytotoxicity in cancer cells overexpressing BCL-2, with a series of intrinsic apoptotic events, including caspase activation.1

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).1
• Advise patients of the potential risk of tumor lysis syndrome (TLS), particularly at treatment initiation, during the ramp-up phase, and with restarting the dose 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, decreased urination, unusual tiredness, muscle cramps or twitches) to their healthcare provider for evaluation.1
• Advise patients to be adequately hydrated when taking sonrotoclax to reduce the risk of TLS.1 The recommended volume is 6 to 8 glasses (approximately 1.5 to 2 liters) of water daily starting 1-2 days before taking sonrotoclax, on the day of the first dose, on any day the dose is increased until target dose is reached, and at restart, if applicable.1 Advise patients of the importance of keeping scheduled appointments for blood work or other laboratory tests.1 Advise patients that it may be necessary to take sonrotoclax in the hospital or medical office setting to allow monitoring for TLS.1
• Advise patients of the importance of keeping scheduled appointments for blood work or other laboratory tests.1 Advise patients that it may be necessary to take sonrotoclax in the hospital or medical office setting to allow monitoring for TLS.1
• Advise patients to contact their healthcare provider immediately if they develop a fever or any signs of infection.1
• Advise patients of the need for periodic monitoring of blood counts.1
• Advise patients to avoid consuming grapefruit products, Seville oranges, or star fruit during treatment with sonrotoclax.1 Sonrotoclax may interact with some drugs; therefore, advise patients to inform their healthcare provider of the use of any prescription medication, over-the-counter (OTC) drugs, vitamins, and herbal products.1
• Advise pregnant women and females of reproductive potential of the potential risk to a fetus.1 Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy.1 Advise females of reproductive potential to use effective contraception during treatment with sonrotoclax and for 1 week after the last dose.1 Advise males with female partners of reproductive potential to use effective contraception during treatment with sonrotoclax and for 1 week after the last dose.1
• Advise women not to breastfeed during treatment with sonrotoclax and for 1 week after the last dose.1
• Advise males and females of reproductive potential that sonrotoclax may impair fertility.1
• Advise patients to take sonrotoclax exactly as prescribed and not to change their dose or to stop taking the drug unless they are told to do so by their healthcare provider.1 Advise patients to take sonrotoclax orally once daily, at approximately the same time each day, according to their healthcare provider's instructions and that the tablets should be swallowed whole with a meal and a glass of water without being broken, chewed, or crushed.1
• Advise patients if sonrotoclax is missed within 8 hours, to take it as soon as possible with a meal on the same day with a return to the normal schedule the following day.1 If they miss a dose by more than 8 hours, advise patients to not take the missed dose and resume the usual dosing schedule the next day.1 Advise patients not to take any additional dose that day if they vomit after taking sonrotoclax, and to take the next dose at the usual time the following day.1
• Advise patients to contact their healthcare provider before restarting sonrotoclax after stopping treatment.1

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Only references cited for selected revisions after 1984 are available electronically.

1. BeOne Medicines. BEQALZI™ (sonrotoclax) ORAL prescribing information. 2026 May.