For questions about the recent update for TAVNEOS® and what this means for you, please see our Letter to Providers
TAVNEOS® targets C5aR and blocks the complement-mediated cycle of chronic inflammation1-4
Neutrophils are primed by proinflammatory cytokines or C5a. MPO or PR3 antigens become exposed on the neutrophil surface4-6
Tethered to the vessel wall, neutrophils are activated by ANCA4,7
Activated neutrophils release more C5a and destructive mediators and eventually leads to NETosis4-6,8
C5a attracts more neutrophils to the site of inflammation and binds to their C5aRs to prime and allow activation of neutrophils4-6
The precise mechanism by which TAVNEOS® exerts a therapeutic effect in patients with severe active GPA or MPA has not been definitively established.1
C5a = complement fragment 5a; C5aR = C5a receptor; GPA = granulomatosis with polyangiitis; MAC = membrane attack complex; MOA = mechanism of action; MPA = microscopic polyangiitis; MPO = myeloperoxidase; PR3 = proteinase 3.
Serious hypersensitivity to avacopan or to any of the excipients.
Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. In the postmarketing setting, vanishing bile duct syndrome (VBDS) as a consequence of liver injury, including cases with a fatal outcome, has been reported. These events occurred predominantly in Japan in patients aged 65 years and older, but VBDS may affect patients of any age or ethnicity who are receiving TAVNEOS. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for 6 months and as clinically indicated thereafter. For patients of Japanese descent, consider more frequent laboratory testing: every 2 weeks after the start of therapy for the first 3 months, followed by laboratory testing every 4 weeks for the next 3 months of treatment, and as clinically indicated thereafter. If a patient receiving treatment with TAVNEOS presents with an elevation in alanine aminotransferase [ALT] or aspartate aminotransferase [AST] to >3 times the upper limit of normal (ULN), evaluate promptly and consider pausing treatment as clinically indicated. If AST or ALT is > 5 times the ULN, or ALT or AST > 3 times the ULN with total bilirubin > 2 times the ULN, or alkaline phosphatase ≥ 2 times the ULN, or if the patient has clinical symptoms such as jaundice or pruritus, discontinue TAVNEOS until TAVNEOS-induced liver injury is ruled out. Immediately and permanently discontinue TAVNEOS if VBDS is suspected. TAVNEOS is not recommended for patients with active, untreated, and/or uncontrolled chronic liver disease (e.g., chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risks and benefits before administering this drug to a patient with liver disease.
Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including 1 serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be readministered unless another cause has been established.
Hepatitis B Virus (HBV) Reactivation: Hepatitis B reactivation, including life-threatening hepatitis B, was observed in the clinical program. Screen patients for HBV. For patients with evidence of prior infection, consult with physicians with expertise in HBV and monitor during TAVNEOS therapy and for 6 months following. If patients develop HBV reactivation, immediately discontinue TAVNEOS and concomitant therapies associated with HBV reactivation, and consult with experts before resuming.
Serious Infections: Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. The most common serious infections reported in the TAVNEOS group were pneumonia and urinary tract infections. Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. Consider the risks and benefits before initiating TAVNEOS in patients with chronic infection, at increased risk of infection, or who have been to places where certain infections are common.
The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increased, and paresthesia.
Avoid co-administration of TAVNEOS with strong and moderate CYP3A4 enzyme inducers. Reduce TAVNEOS dose when co-administered with strong CYP3A4 enzyme inhibitors to 30 mg once daily. Consider dose reduction of CYP3A4 substrates when co-administering TAVNEOS. Co-administration of avacopan and 40 mg simvastatin increases the systemic exposure of simvastatin. While taking TAVNEOS, limit simvastatin dosage to 10 mg daily (or 20 mg daily for patients who have previously tolerated simvastatin 80 mg daily for at least one year without evidence of muscle toxicity). Consult the concomitant CYP3A4 substrate product information when considering administration of such products together with TAVNEOS.
TAVNEOS (avacopan) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use.
Please see Full Prescribing Information and Medication Guide for TAVNEOS.
To report a suspected adverse event, call 1-833-828-6367. You may report to the FDA directly by visiting www.fda.gov/medwatchor calling 1-800-332-1088.
important safety information Contraindications Serious hypersensitivity to avacopan or to any of the excipients.
Warnings and Precautions Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. In the postmarketing setting, vanishing bile duct syndrome (VBDS) as a consequence of liver injury, including cases with a fatal outcome, has been reported...
References: 1. TAVNEOS [package insert]. Cincinnati, OH: Amgen Inc. 2. Data on file, Amgen; Clinical Study Report [92070]; 2020. 3. Khan MM, Molony DA. Ann Intern Med. 2021;174(7):JC79. 4. Chen M, Jayne DRW, Zhao M-H. Nat Rev Nephrol. 2017;13(6):359-367. 5. Kitching AR, Anders H-J, Basu N, et al. Nat Rev Dis Primers. 2020;6(1):71. 6. Al-Hussain T, Hussein MH, Conca W, Al Mana H, Akhtar M. Adv Anat Pathol. 2017;24(4):226-234. 7. Jennette JC, Nachman PH. Clin J Am Soc Nephrol. 2017;12(10):1680-1691. 8. Shochet L, Holdsworth S, Kitching AR. Front Immunol. 2020;11:525. 9. Jones RB, Ferraro AJ, Chaudhry AN, et al. Arthritis Rheum. 2009;60(7):2156-2168. 10. Winkelstein A. Blood. 1973;41(2):273-284. 11. Eickenberg S, Mickholz E, Jung E, et al. Arthritis Res Ther. 2012;14(3):R110. 12. Ogino MH, Prasanna T. In: StatPearls [Internet]. StatPearls Publishing; 2023. Accessed October 3, 2023. https://www.ncbi.nlm.nih.gov/books/NBK553087/ 13. Mohammadi O, Kassim TA. In: StatPearls [Internet]. StatPearls Publishing; 2023. 14. Anders H-J, Nakazawa D. CJASN. 2021;16:1581-1583.
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