DANICOPAN TAB
Clinical Criteria Summary
Document 634
Exclusion Criteria
- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
Inclusion Criteria
- Prescribed by a REMS registered VA or VA Community Care hematologist, oncologist, immunologist or genetic specialist
- Laboratory-confirmed diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH), as evidenced by detectable GPI-deficient hematopoietic clones (Type III PNH red blood cells (RBC)) via Flow Cytometry
- Evidence of clinically significant hemolysis (e.g., Hemoglobin <10g/dL) despite 6 months of stable therapy with anti-C5 inhibitor (e.g., ravulizumab or eculizumab)
- Complete or update vaccination for encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis at least 2 weeks prior to the first dose of therapy according to current Advisory Committee on Immunization Practices (ACIP)
Document 644
Indication & Patient Population
- Add-on therapy to ravulizumab or eculizumab for treatment of extravascular hemolysis in adults with Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Adults with confirmed PNH and clinically significant extravascular hemolysis (e.g., Hgb <9.5) despite stable anti-C5 treatment
Dosage & Administration
- 150mg to 200mg three times daily
- Available as 50mg and 100mg oral tablets
Contraindications
- Hypersensitivity to danicopan
- Unresolved serious infection caused by encapsulated bacteria (Strep. Pneumoniae, Neisseria meningitidis, or H. influenzae type B)
Warnings & Monitoring
- Risk of serious infections caused by encapsulated bacteria; complete or update vaccination at least 2 weeks prior to first dose unless risks of delaying therapy outweigh infection risk
- Not recommended in severe hepatic impairment (Child-Pugh class C)
- Insufficient data regarding risk of birth defects in pregnancy
- Cessation of breastfeeding recommended during treatment and for 3 days after final dose
- Hepatic enzyme elevations reported; baseline screening and monitoring recommended
- Monitor for hemolysis after cessation of therapy
Drug Interactions
- BCRP inhibitor: May increase plasma concentrations of BCRP substrates
- P-glycoprotein inhibitor: May increase plasma concentrations of P-gp substrates
- Rosuvastatin: Exposure significantly increased; dose should not exceed 10mg/day when used concomitantly
Adverse Reactions
- Headache (11%), vomiting (7%), pyrexia (7%), ALT increase (5%), hypertension (5%)