rilzabrutinib (Wayrilz)

Indications

• treatment of immune thrombocytopenia (ITP)

Contraindications

• pregnancy

Dosage

• 400 mg twice daily

Tablets: 400 mg

Pharmacokinetics

• absolute oral bioavailability of rilzabrutinib is 4.7%
  • high fat meal diminishes bioavailability 20-30%
• metabolized by CYP3A
• 97.5% bound to plasma proteins
• volume of distribution at terminal phase after IV administration is 149 L
• median time to peak plasma concentration is ~ 2 hours after 400 mg PO

Monitor

• serum bilirubin, serum AST, serum ALT baseline& as indicated

Adverse effects

• grade 1 or 2, transient, no bleeding, thrombotic, or serious adverse events
  • urticaria, hepatotoxicity
  • most common
    • diarrhea, nausea, headache, abdominal pain, COVID-19

Drug interactions

• CYP3A inhibitors:
  • avoid co-administration with moderate or strong CYP3A inhibitors.
• CYP3A inducers:
  • avoid co-administration with moderate or strong CYP3A inducers.
• avoid co-administration with proton pump inhibitor

Mechanism of action

• reversible, covalent inhibitor of Bruton tyrosine kinase
  • inhibits phagocytosis of platelets by blocking BTK signaling in macrophages

More general terms

• small inhibitory antineoplastic agent (ib drug)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=73388818
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=90003064
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=90004027
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=73388819