rilzabrutinib 400 MG Oral Tablet

INDICATIONS AND USAGE WAYRILZ 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. WAYRILZ is a kinase inhibitor 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 )

DOSAGE AND ADMINISTRATION See Full Prescribing Information for important recommendations prior to treatment. ( 2.1 , 2.3 ) Recommended dosage: 400 mg orally twice daily; swallow whole with water, with or without food. Do not cut, crush, or chew tablets. ( 2.2 ) 2.1 Recommended Testing Before Initiating WAYRILZ Verify pregnancy status of females of reproductive potential prior to initiating WAYRILZ treatment [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1 , 8.3) ] . 2.2 Recommended Dosage The recommended dosage of WAYRILZ is 400 mg taken orally twice daily. WAYRILZ can be taken at approximately the same time each day with or without food. In patients who experience gastrointestinal symptoms, taking WAYRILZ with food may improve tolerability. Advise patients to swallow tablets whole with a glass of water. Advise patients not to cut, crush or chew the tablets. If a dose is missed, patients should take the missed dose of WAYRILZ as soon as possible on the same day and at least 2 hours apart from the next regular scheduled dose. If taking antacid or histamine H2 receptor antagonist, administer the dose of WAYRILZ at least 2 hours before the antacid or histamine H2 receptor antagonist. 2.3 Monitoring and Dose Modifications for Hepatotoxicity Evaluate bilirubin and transaminases at baseline and as clinically indicated during treatment with WAYRILZ. For patients who develop abnormal liver tests after WAYRILZ, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If Drug-Induced Liver Injury (DILI) is suspected, withhold WAYRILZ. Upon confirmation of DILI, discontinue WAYRILZ.

WARNINGS AND PRECAUTIONS Serious Infections: Monitor patients for signs and symptoms of infection, evaluate promptly, and treat. ( 5.1 ) Hepatotoxicity, Including Drug-Induced Liver Injury: Evaluate bilirubin and transaminases at baseline and as clinically indicated during treatment. ( 5.2 ) Embryo-Fetal Toxicity: Based on preliminary animal data, WAYRILZ may cause fetal harm. Advise females of reproductive potential of the potential risk and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 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 WAYRILZ. In the LUNA-3 trial, fatal pneumonia occurred in one participant in the WAYRILZ group. Other serious infections [one each (0.8%)] included COVID-19 infection, wound infection, and one patient experienced urinary tract infection and kidney abscess. Monitor patients for signs and symptoms of infection and treat appropriately. 5.2 Hepatotoxicity, Including Drug-Induced Liver Injury Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of DILI, can occur in patients treated with BTK inhibitors. In the clinical trials of WAYRILZ in patients with ITP, elevations of liver transaminases occurred and were generally mild to moderate in severity. Evaluate bilirubin and transaminases at baseline and as clinically indicated during treatment with WAYRILZ. For patients who develop abnormal liver tests after WAYRILZ, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold WAYRILZ. Upon confirmation of DILI, discontinue WAYRILZ. 5.3 Embryo-Fetal Toxicity Based on findings from preliminary animal reproduction studies, WAYRILZ may cause fetal harm when administered to a pregnant woman. Adverse visceral and skeletal findings occurred in rat fetuses at a maternally toxic dose at exposures 22-times the human exposure [based on area under the curve (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. Verify pregnancy status of females of reproductive potential prior to initiating WAYRILZ treatment. Advise females of reproductive potential to use an effective method of contraception during treatment with WAYRILZ and for 1 week after the final dose [see Use in Specific Populations (8.1 , 8.3) ] .

CONTRAINDICATIONS None None

Mechanism of Action Rilzabrutinib is a small-molecule, covalent, reversible kinase inhibitor targeting Bruton's tyrosine kinase (BTK). 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. 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.