AHFS Class:

• Blood Formation, Coagulation, and Thrombosis Agents; Miscellaneous 20:92

Brands:

• Wayrilz^®

Generic Name(s):

• Rilzabrutinib

Rilzabrutinib is a kinase inhibitor.1

Rilzabrutinib has the following uses:

Rilzabrutinib is indicated for the treatment of adult patients with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.1

General

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

Tablets: 400 mg1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• See Full Prescribing Information for important recommendations prior to treatment.1
• Recommended dosage: 400 mg orally twice daily; swallow tablets whole with water, with or without food.1 Do not cut, crush, or chew tablets.1
• See Full Prescribing Information for monitoring and dose modification recommendations.1

Contraindications

None1

Warnings/Precautions

Serious Infections

An increased risk of serious infections (including bacterial, viral, or fungal) can occur in patients treated with Bruton's tyrosine kinase (BTK) inhibitors, including rilzabrutinib.1 In the LUNA-3 trial, fatal pneumonia occurred in one participant in the rilzabrutinib group.1 Other serious infections [one each (0.8%)] included COVID-19 infection, wound infection, and one patient experienced urinary tract infection and kidney abscess.1 Monitor patients for signs and symptoms of infection and treat appropriately.1

Hepatotoxicity, Including Drug-induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), can occur in patients treated with BTK inhibitors.1 In the clinical trials of rilzabrutinib in patients with ITP, elevations of liver transaminases occurred and were generally mild to moderate in severity.1 Evaluate bilirubin and transaminases at baseline and as clinically indicated during treatment with rilzabrutinib.1 For patients who develop abnormal liver tests after rilzabrutinib, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity.1 If DILI is suspected, withhold rilzabrutinib.1 Upon confirmation of DILI, discontinue rilzabrutinib.1

Embryo-fetal Toxicity

Based on findings from preliminary animal reproduction studies, rilzabrutinib may cause fetal harm when administered to a pregnant woman.1 Adverse visceral and skeletal findings occurred in rat fetuses at a maternally toxic dose at exposures 22-times the human exposure (based on AUC) at the maximum recommended human dose (MRHD), and renal visceral malformations occurred in a single rabbit fetus at 5.6-times the human exposure (based on AUC) at the MRHD.1 Verify pregnancy status of females of reproductive potential prior to initiating rilzabrutinib treatment.1 Advise females of reproductive potential to use an effective method of contraception during treatment with rilzabrutinib and for 1 week after the final dose. 1

Specific Populations

Pregnancy

Based on animal data, rilzabrutinib may cause fetal harm when administered to a pregnant woman.1 In animal reproduction studies, oral administration of rilzabrutinib to pregnant rats and rabbits during organogenesis at exposures 4- to 10-times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 400 mg twice daily did not cause adverse developmental effects.1 However, adverse visceral and skeletal findings occurred in rat fetuses at a maternally toxic dose at exposures 22-times the human exposure (based on AUC) at the MRHD.1 There are no available clinical data on the use of rilzabrutinib during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.1 Advise pregnant women of the potential risk to a fetus.1

The background risk of major birth defects and miscarriage for the indicated population is unknown.1 All pregnancies have a background risk of birth defects, loss, and other adverse outcomes.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 rilzabrutinib or its metabolites in either human or animal milk, the effects on the breastfed child, or the effects on milk production.1 Due to the potential for adverse reactions in a breastfed child from rilzabrutinib, advise lactating women not to breastfeed while taking rilzabrutinib and for at least 1 week after the final dose.1

Females and Males of Reproductive Potential

Based on preliminary animal data, rilzabrutinib may cause fetal harm when administered to pregnant women.1

Verify pregnancy status of females of reproductive potential prior to initiating rilzabrutinib treatment.1

Advise female patients of reproductive potential to use effective contraception during rilzabrutinib treatment and for 1 week after stopping treatment.1

Pediatric Use

Safety and effectiveness of rilzabrutinib have not been established in pediatric patients.1

Geriatric Use

Of the 202 patients in the LUNA-3 study, 36 (18%) patients were 65 years of age and older, and 9 (5%) patients were 75 years of age and older.1 No overall differences in safety and efficacy were observed between patients 65 years of age and older and younger adult patients. 1

Hepatic Impairment

Avoid administration of rilzabrutinib in patients with moderate or severe hepatic impairment (Child-Pugh class B-C) because of potential for increased rilzabrutinib exposures.1 Dose modification is not required for patients with mild hepatic impairment (Child-Pugh class A).1

Renal Impairment

Avoid use in patients with severe renal impairment.1 Patients with severe renal impairment were not studied.1 Dose modification is not required for patients with mild or moderate renal impairment.1

Common Adverse Effects

Most common adverse reactions (incidence ≥10%) were diarrhea, nausea, headache, abdominal pain, and COVID-19.1

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:

• CYP3A Inhibitors: Avoid co-administration with moderate or strong CYP3A inhibitors.1
• CYP3A Inducers: Avoid co-administration with moderate or strong CYP3A inducers.1
• Gastric Acid Reducing Agents: Avoid co-administration with proton pump inhibitors (PPIs).1 Rilzabrutinib should be administered at least 2 hours before taking an antacid or H2 receptor antagonist.1

Actions

Mechanism of Action

Rilzabrutinib is a small-molecule, covalent, reversible kinase inhibitor targeting Bruton's tyrosine kinase (BTK).1 Rilzabrutinib mediates its therapeutic effect in ITP through immune modulation including 1) inhibition of B cell activation, and 2) interruption of antibody-coated cell phagocytosis by Fcγ receptor (FcγR) in spleen and liver.1 In vitro , rilzabrutinib reduced autoantibody signaling mediated through the FcγR pathway, blocked B cell signaling, and decreased autoantibody generation through effects on B cell activation.1

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information).1
• Instruct patients to store rilzabrutinib at room temperature in the original package and to protect from light and moisture.1
• Instruct patients to take rilzabrutinib orally twice daily at approximately the same time each day with or without food.1 Advise patients that rilzabrutinib tablets should be swallowed whole with a glass of water, and not to cut, crush or chew the tablets.1
• Advise patients that if they miss a dose of rilzabrutinib, they should take it as soon as possible on the same day and at least 2 hours apart from the next regular scheduled dose.1
• Advise patients to inform their healthcare providers of all concomitant medications, including over-the-counter medications, vitamins, and herbal supplements.1 Advise patients to avoid eating grapefruit, starfruit, and Seville oranges and products containing these fruits with rilzabrutinib.1
• Advise patients of the possibility of serious infection, and to report any signs or symptoms.1
• Inform patients that liver problems, including severe, life-threatening, or fatal hepatitis, drug-induced liver injury (DILI) and abnormalities in liver tests, have occurred in patients treated with BTK inhibitors.1 Advise patients to contact their healthcare provider immediately if they experience abdominal discomfort, dark urine, or jaundice. 1
• Advise female patients of reproductive potential that rilzabrutinib may cause fetal harm and to inform their healthcare providers of a known or suspected pregnancy.1 Advise females of reproductive potential to use effective contraception during treatment with rilzabrutinib and for 1 week after the last dose.1
• Advise women not to breastfeed during treatment with rilzabrutinib and for at least 1 week after the final dose.1

Additional Information

AHFS first Release^™. 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.

1. Genzyme Corporation. WAYRILZ^® (rilzabrutinib) ORAL prescribing information. 2025 Aug. [Web]