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Complement C5a Receptor Antagonist (Oral Biologic) Pregnancy: Avoid — no adequate human data; animal studies suggest potential harm; use contraception during treatment.

Avacopan (C5a Receptor Inhibitor — ANCA Vasculitis)

Brand names: Tavneos

Adult dose

Dose: 30 mg oral twice daily
Route: Oral (capsule)
Frequency: Twice daily (with or without food)
Max: 30 mg twice daily
Selective C5aR1 antagonist — blocks the complement C5a-driven neutrophil activation that causes ANCA-mediated vessel destruction. Used in combination with rituximab or cyclophosphamide for induction of remission in GPA and MPA. MHRA approved 2022. Glucocorticoid-sparing — designed to allow high-dose steroid avoidance/rapid tapering.

Paediatric dose

Route:
Not licensed in paediatrics.

Dose adjustments

Renal

No dose adjustment required for eGFR ≥15 mL/min. Insufficient data for eGFR <15 — use with caution.

Hepatic

Avoid in severe hepatic impairment (Child-Pugh C) — hepatotoxicity risk and impaired metabolism.

Clinical pearls

  • ADVOCATE trial (Jayne et al. NEJM 2021): avacopan + rituximab/cyclophosphamide vs prednisone + rituximab/cyclophosphamide in GPA/MPA — avacopan non-inferior at week 26 and significantly superior at week 52 (65.7% vs 54.9% sustained remission); achieved comparable remission WITHOUT high-dose glucocorticoids — landmark for steroid-sparing ANCA therapy
  • Glucocorticoid-sparing significance: ANCA vasculitis patients on high-dose steroids have severe morbidity (infection, bone loss, metabolic syndrome, adrenal suppression). Avacopan replaces not just steroids but fundamentally targets the C5a-driven innate immune neutrophil activation — a different mechanistic approach to all prior therapies
  • Hepatotoxicity monitoring: MHRA post-marketing: monthly LFTs mandatory (ALT/AST). Suspend avacopan if ALT/AST >5× ULN or if associated with jaundice/hepatitis symptoms. Fatal hepatic failure reported — prescribers must follow MHRA monitoring protocol

Contraindications

  • Severe hepatic impairment
  • Active serious infection (defer initiation)
  • Concurrent strong CYP3A4 inducers (rifampicin, carbamazepine — significantly reduce avacopan levels)

Side effects

  • Hepatotoxicity (significant — ALT/AST elevated ≥3× ULN in 7% in ADVOCATE; fatal hepatic failure case reported post-marketing; MHRA warning: monitor LFTs monthly)
  • Nausea and vomiting
  • Headache
  • Hypertension
  • Infection (immunosuppression context)
  • Rash

Interactions

  • Strong CYP3A4 inhibitors (itraconazole, clarithromycin — increase avacopan levels; use with caution and monitor for side effects)
  • Strong CYP3A4 inducers (rifampicin, phenytoin — dramatically reduce avacopan levels — avoid)
  • Statin interaction (avacopan inhibits OATP1B1/1B3 — increases rosuvastatin, pitavastatin exposure; monitor for myopathy)

Monitoring

  • LFTs monthly (MHRA mandatory — hepatotoxicity surveillance)
  • ANCA titres (PR3-ANCA and MPO-ANCA — disease activity markers)
  • Urinalysis (haematuria, proteinuria — renal vasculitis monitoring)
  • eGFR
  • BP (hypertension monitoring)
  • Signs of infection

Reference: BNFc; BNF 90; Jayne et al. NEJM 2021 (ADVOCATE trial); MHRA Approval Tavneos 2022; MHRA Drug Safety Update 2023 (hepatotoxicity); NICE appraisal pending. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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