Avacopan

Source: UK SPC (eMC) for Avacopan Vifor 10 mg hard capsules, §4.2 (https://www.medicines.org.uk/emc/product/13744/smpc). Treatment should be initiated and monitored by healthcare professionals experienced in the diagnosis and treatment of GPA (granulomatosis with polyangiitis) or MPA (microscopic polyangiitis). COMBINATION REGIMEN as stated in §4.2: avacopan should be administered 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, together with glucocorticoids as clinically indicated; the SPC refers to §4.8 and §5.1 for details of doses of the concomitant agents (those sections were truncated at the fetch limit, so no numeric doses for rituximab, cyclophosphamide, azathioprine, mycophenolate or glucocorticoids are given here). 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 the missed dose is not to be taken. DOSE MANAGEMENT (§4.2) — treatment must be re-assessed clinically and TEMPORARILY STOPPED if ALT or AST is more than 3 times the upper limit of normal (ULN); treatment must be temporarily stopped if ALT or AST is above 5 x ULN, if the patient develops leukopenia (white blood cells below 2 x 10^9/L) or neutropenia (neutrophils below 1 x 10^9/L) or lymphopenia (lymphocytes below 0.2 x 10^9/L), or if the patient has an active serious infection (i.e. requiring hospitalisation or prolonged hospitalisation). Treatment may be resumed upon normalisation of values and based on an individual benefit/risk assessment, with close monitoring of hepatic transaminases and total bilirubin. PERMANENT DISCONTINUATION must be considered if ALT or AST is above 8 x ULN; or above 5 x ULN for more than 2 weeks; or above 3 x ULN with total bilirubin above 2 x ULN or INR above 1.5; or above 3 x ULN with fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (above 5%); or ALP at least 2 x ULN when the liver is the source; or clinical symptoms of vanishing bile duct syndrome (VBDS) such as jaundice or pruritus; or if an association between avacopan and hepatic dysfunction has been established. Treatment must be immediately and permanently discontinued if VBDS is suspected. PRE-TREATMENT AND MONITORING (§4.4): liver function tests including hepatic transaminases and total bilirubin must be obtained prior to initiation, and avacopan must be AVOIDED in patients with signs of liver disease such as AST, ALT, ALP or total bilirubin above 3 times ULN; liver function must be monitored at least every 2 weeks for the first 3 months, then every 4 weeks for the next 3 months, and as clinically indicated thereafter. A white blood cell count must be obtained prior to initiation, and treatment MUST NOT BE INITIATED if the WBC count is below 3.5 x 10^9/L, or neutrophils below 1.5 x 10^9/L, or lymphocytes below 0.5 x 10^9/L. Pneumocystis jirovecii pneumonia prophylaxis is recommended for adult patients with GPA or MPA during avacopan treatment, as appropriate according to local clinical practice guidelines. ELDERLY: no dose adjustment required. HEPATIC IMPAIRMENT: no dose adjustment for mild or moderate impairment; not studied in and not recommended for severe hepatic impairment (Child-Pugh C). SEVERE DISEASE MANIFESTED AS ALVEOLAR HAEMORRHAGE: avacopan has not been studied in these patients. PAEDIATRIC: safety and efficacy in adolescents 12 to 17 years have not yet been established and NO RECOMMENDATION ON A POSOLOGY CAN BE MADE; safety and efficacy below 12 years have not been established and no data are available — hence paedDose is null; verify any paediatric use against a children's formulary. GRAPEFRUIT: grapefruit and grapefruit juice are to be avoided in patients treated with avacopan. US LABELLING NOTE (not in the retrieved UK §4.2): the US label (TAVNEOS §2.3) instructs reducing the dosage to 30 mg ONCE daily when used concomitantly with strong CYP3A4 inhibitors — verify against the UK SPC before applying. NOTE ON SOURCES: eMC §4.5 was NOT captured in this bundle — interactions below are from UK §4.2/§4.4 plus §7 of the US label (TAVNEOS, ChemoCentryx, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=35c096c8-3581-4d09-b01c-d6e514e0c836, label date 2026-06-02). §4.4 and §4.8 were truncated at the fetch limit.