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C5a Receptor Inhibitor (ANCA Vasculitis) Pregnancy: Avoid — insufficient human data. Not recommended in pregnancy. Effective contraception required during and for at least 1 week after treatment.

Avacopan

Brand names: Tavneos

Adult dose

Dose: 30 mg twice daily
Route: Oral
Frequency: Twice daily with food
Max: 60 mg/day
ANCA-associated vasculitis (granulomatosis with polyangiitis, GPA; microscopic polyangiitis, MPA). Used in combination with rituximab or cyclophosphamide. Continue for 52 weeks. Must be taken with food (significant food effect on absorption). Source: BNF 90; MHRA SPC Tavneos.

Paediatric dose

Dose: Not licensed under 18 years N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not licensed for paediatric ANCA vasculitis.

Dose adjustments

Renal

No dose adjustment required. Avacopan is not renally excreted; studied in patients with eGFR as low as 8 mL/min. Safe across all levels of renal impairment.

Hepatic

Moderate hepatic impairment (Child-Pugh B): reduce dose to 30 mg once daily. Severe (Child-Pugh C): avoid — significantly increased exposure.

Paediatric weight-based calculator

Not licensed for paediatric ANCA vasculitis.

Clinical pearls

  • ADVOCATE trial (NEJM 2021): avacopan non-inferior to high-dose prednisolone for remission at week 26, AND superior at week 52 for sustained remission (65.7% vs 54.9%). Critically, avacopan group had significantly less glucocorticoid toxicity — weight, diabetes, bone density, infection rate all improved. First ANCA vasculitis drug that allows steroid dose reduction.
  • Mechanism — C5a receptor blockade: ANCA vasculitis is complement-driven. C5a recruits and activates neutrophils at vascular endothelium → necrotising vasculitis. Avacopan blocks C5a receptor (C5aR1) on neutrophils and macrophages, interrupting this loop. Unlike eculizumab (blocks C5 cleavage — inhibits both C5a and C5b-9), avacopan is selective for C5a pathway without affecting MAC formation.
  • Steroid-sparing: ADVOCATE used avacopan + rituximab/cyclophosphamide WITH a reduced-dose prednisolone taper (vs standard high-dose taper in control group). It does NOT completely replace steroids in induction — helps reduce cumulative steroid dose and steroid-related morbidity.
  • Hepatotoxicity monitoring critical: ALT/AST must be checked before starting, monthly for 6 months, then every 3 months. If ALT >3× ULN: withhold and investigate. Serious DILI reported — early detection is key.
  • ANCA screening before treatment: confirm positive ANCA (MPO-ANCA or PR3-ANCA) before initiating. Screen for TB (IGRA), HBV (HBsAg, anti-HBc), HIV. Consider PCP prophylaxis if on cyclophosphamide concurrently. Source: BNF 90; Jayne et al. NEJM 2021 (ADVOCATE); MHRA SPC Tavneos.

Contraindications

  • Active serious infection including TB and hepatitis B (screen before starting)
  • Severe hepatic impairment (Child-Pugh C)
  • Hypersensitivity to avacopan
  • Live vaccines during treatment

Side effects

  • Nausea, vomiting, diarrhoea (most common — up to 30%)
  • Upper respiratory tract infections, nasopharyngitis
  • Headache
  • Elevated liver enzymes (ALT, AST) — monitor; dose reduce or stop if significant elevation
  • Hepatotoxicity (rare but serious — including serious drug-induced liver injury)
  • Herpes zoster reactivation (complement suppression)

Interactions

  • Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole): increase avacopan exposure — avoid or reduce to 30 mg once daily
  • Strong CYP3A4 inducers (rifampicin, carbamazepine, St John's Wort): reduce avacopan concentrations — avoid
  • Live vaccines: contraindicated during treatment

Monitoring

  • Liver function tests (ALT, AST) at baseline, monthly for 6 months, then every 3 months
  • eGFR and urinary sediment (ANCA vasculitis renal activity)
  • ANCA titres (PR3 or MPO) — correlate with disease activity
  • Signs of infection throughout
  • CRP/ESR for disease activity monitoring
  • Blood pressure (often elevated in ANCA nephritis)

Reference: BNFc; BNF 90; Jayne et al. NEJM 2021 (ADVOCATE trial); MHRA SPC Tavneos; NICE TA757 (avacopan for GPA/MPA). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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