Avacopan (C5a Receptor Inhibitor — ANCA Vasculitis)

Treatment should be initiated and monitored by healthcare professionals experienced in the diagnosis and treatment of GPA or MPA. Avacopan is given IN COMBINATION with either rituximab for 4 weekly intravenous doses, or intravenous or oral cyclophosphamide for 13 or 14 weeks followed by oral azathioprine or mycophenolate mofetil — plus glucocorticoids as clinically indicated (the SPC refers to §4.8/§5.1 for the doses of the concomitant regimens). Clinical study data are limited to 52 weeks of exposure followed by 8 weeks of observation. MISSED DOSE: take as soon as possible unless within three hours of the next scheduled dose, in which case skip it. DOSE MANAGEMENT — re-assess clinically and temporarily stop if ALT or AST is more than 3 x ULN. Temporarily stop if: ALT or AST > 5 x ULN; leukopenia (white cell count < 2 x 10^9/L) or neutropenia (neutrophils < 1 x 10^9/L) or lymphopenia (lymphocytes < 0.2 x 10^9/L); or an active, serious infection requiring or prolonging hospitalisation. Treatment may be resumed on normalisation of values and after individual benefit/risk assessment, with close monitoring of hepatic transaminases and total bilirubin. CONSIDER PERMANENT DISCONTINUATION if: ALT or AST > 8 x ULN; ALT or AST > 5 x ULN for more than 2 weeks; ALT or AST > 3 x ULN with total bilirubin > 2 x ULN or INR > 1.5; ALT or AST > 3 x ULN with fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (> 5%); ALP at least 2 x ULN where the liver is the source; clinical symptoms of vanishing bile duct syndrome (VBDS) such as jaundice or pruritus; or an established association between avacopan and hepatic dysfunction. Stop immediately and permanently if VBDS is suspected. BEFORE STARTING: obtain liver function tests and a white cell count; do not initiate if WBC < 3.5 x 10^9/L, neutrophils < 1.5 x 10^9/L or lymphocytes < 0.5 x 10^9/L; avoid in patients with signs of liver disease (AST, ALT, ALP or total bilirubin > 3 x ULN). Monitor liver function at least every 2 weeks for the first 3 months, then every 4 weeks for the next 3 months, and as clinically indicated thereafter. Pneumocystis jirovecii pneumonia prophylaxis is recommended for adults with GPA or MPA during treatment, per local guidelines. HEPATIC IMPAIRMENT: no dose adjustment for mild or moderate; not studied in and not recommended for severe hepatic impairment (Child-Pugh Class C). NOT STUDIED in severe disease manifested as alveolar haemorrhage. PAEDIATRIC: safety and efficacy in adolescents 12 to 17 years have not been established and no posology recommendation can be made; in children below 12 years no data are available — no paediatric dose is stated in the source. US LABELLING CROSS-CHECK: the US label in this bundle gives the same 30 mg (three 10 mg capsules) twice daily with food, and adds a dosage modification to 30 mg ONCE daily when used with strong CYP3A4 inhibitors. SOURCE: UK SPC (eMC), Avacopan Vifor 10 mg hard capsules, §4.2 — https://www.medicines.org.uk/emc/product/13744/smpc