Avacopan

Avacopan is an orally administered small molecule C5a receptor antagonist that selectively blocks the effect of C5a via the C5a receptor (C5aR, also known as CD88). The active substance is used to treat certain forms of ANCA-associated vasculitis. The common feature of ANCA-associated vasculitis (including: granulomatosis with polyangiitis/GPA; microscopic polyangiitis/MPA; eosinophilic granulomatosis with polyangiitis/E-GPA; special form: drug-induced ANCA-positive vasculitis) is the presence of the anti-neutrophil cytoplasmic autoantibody (ANCA).

Avacopan is a selective antagonist of the human complement 5a receptor(C5aR1/CD88) and competitively inhibits the interaction between C5aR1 and the anaphylatoxin C5a. The specific and selective blockade of C5aR1 by avacopan reduces the pro-inflammatory effects of C5a, which include activation, migration and adherence of neutrophils to inflammatory sites of small blood vessels, retraction and permeability of vascular endothelial cells.

Avacopan (Tavneos) is indicated in combination with rituximab or cyclophosphamide for the treatment of adult patients with ANCA-associated vasculitis:

• Severe active granulomatosis with polyangiitis (Wegener's granulomatosis)
• Microscopic polyangiitis (MPA)

There are no data available on the use of Avacopan in pregnant women. Reproductive toxicity has been demonstrated in animal experiments. Avacopan should not be used during pregnancy and in women of childbearing age who are not using contraception.

Lactation: Avacopan has not been detected in the milk of lactating animals, but has been detected in the plasma of offspring of lactating animals with no apparent effects on them. A risk cannot be excluded.

The recommended dose of Avacopan is 30 mg (3 hard capsules of 10 mg each) taken twice daily, morning and evening, with a meal. It is recommended to use Avacopan in combination with a rituximab or cyclophosphamide regimen:

4-weekly intravenous doses of rituximab or

intravenous or oral cyclophosphamide for 13 or 14 weeks, followed by oral azathioprine or mycophenolate mofetil, and

Glucocorticoids as clinically indicated

The most commonly reported side effects in clinical trials were:

• Nausea (23.5%)
• Headache (20.5%)
• leukopenia (18.7%)
• Upper respiratory tract infection (14.5%)
• Diarrhea (15.1%)
• Vomiting (15.1%)
• Nasopharyngitis (15.1%)

The most common serious side effects are

• Liver dysfunction (5.4%) and
• pneumonia (4.8%).

Avacopan is a substrate of CYP3A4, therefore the concomitant use of inducers or inhibitors of this enzyme may affect the pharmacokinetics of avacopan. In addition, avacopan is a weak inhibitor of CYP3A4 and may therefore increase the plasma exposure of concomitantly administered drugs that are CYP3A4 substrates. Caution is therefore advised, especially with CYP3A4 substrates with a low therapeutic range, such as alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, sirolimus and tacrolimus.

Avacopan must not be used in cases of known hypersensitivity to the active substance or any of the other ingredients of the medicinal product.

^Tavneos®

Tavneos 10 mg hard capsules

Avacopan is intended for oral use. Eating grapefruit or drinking grapefruit juice should be avoided when using Avacopan.

1. Alihosseini C et al. (2023) Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Ann Pharmacother 57:1449-1454.
2. Jayne DRW et al (2024) ADVOCATE Study Group. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med 384599-609.
3. Kataoka H et al. (2023) Gradual increase of avacopan dose with concomitant ursodeoxycholic acid use may help avoid the risk of C5a receptor inhibitor-induced liver injury in antineutrophil cytoplasmic antibody-associated vasculitis. Mod Rheumatol Case Rep 7: 444-447.