Overview
11 DESCRIPTION WAYRILZ (rilzabrutinib) is a kinase inhibitor. Rilzabrutinib is a white to off-white solid, which is freely soluble in ethanol, sparingly soluble in isopropyl alcohol and practically insoluble in water. The chemical name for rilzabrutinib is 1-Piperidinepropanenitrile, 3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1 H -pyrazolo[3,4- d...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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. 12.2 Pharmacodynamics Plasma Exposure and BTK Occupancy WAYRILZ has a short duration of systemic exposure with a long duration of action on the target due to its slow dissociation from BTK.
Indications
- 1 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 )
Common Doses
- 400 mg
Dosage
2 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.
Contraindications
- 4 CONTRAINDICATIONS None None
Side Effects
- 6 ADVERSE REACTIONS The following clinically important adverse reactions are described elsewhere in the labeling: Serious Infections [see Warnings and Precautions (5.1) ] Hepatotoxicity, Including Drug-Induced Liver Injury [ see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥10%) were diarrhea, nausea, headache, abdominal pain, and COVID-19. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS CYP3A Inhibitors: Avoid co-administration with moderate or strong CYP3A inhibitors. ( 7.1 ) CYP3A Inducers: Avoid co-administration with moderate or strong CYP3A inducers. ( 7.1 ) Gastric Acid Reducing Agents: Avoid co-administration with proton pump inhibitors (PPIs). WAYRILZ should be administered at least 2 hours before taking an antacid or H2 receptor antagonist. ( 7.1 ) 7.1 Effect of Other Drugs on WAYRILZ Strong and Moderate CYP3A Inhibitors Avoid concomitant use of WAYRILZ with strong or moderate CYP3A inhibitors.