What is the recommended dosage and usage of Tavneos (avacopan) for treating ANCA-associated vasculitis?

Tavneos (Avacopan) Dosing and Usage for ANCA-Associated Vasculitis

The recommended dose of Tavneos is 30 mg (three 10 mg capsules) orally twice daily with food, used in combination with rituximab or cyclophosphamide for induction therapy in adults with severe active ANCA-associated vasculitis (GPA or MPA). 1

Standard Dosing Regimen

• Administer 30 mg twice daily with food for the treatment of severe active ANCA-associated vasculitis 1
• Capsules must be swallowed whole—do not crush, chew, or open 1
• If a dose is missed, wait until the next scheduled dose; do not double the dose 1
• Duration of therapy is up to 52 weeks based on clinical trial data, with no evidence supporting use beyond 1 year 2, 3

Combination Therapy Requirements

Avacopan does not eliminate glucocorticoid use and must be combined with standard immunosuppressive therapy. 1

• Use in combination with either rituximab or cyclophosphamide for remission induction 2
• Avacopan serves as a glucocorticoid-sparing agent, substantially reducing but not eliminating steroid exposure 2
• Patients still require some glucocorticoid therapy as part of the treatment regimen 1

Dose Modifications

Reduce avacopan to 30 mg once daily when used with strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, clarithromycin, ritonavir) 1

Patient Selection and Optimal Candidates

Avacopan should be prioritized for patients at high risk of glucocorticoid toxicity and those with active glomerulonephritis with rapidly deteriorating kidney function. 2

Ideal candidates include:

• Patients with active glomerulonephritis and declining renal function (avacopan demonstrated superior eGFR recovery compared to prednisone) 2, 3
• Patients at risk for glucocorticoid-related complications (diabetes, osteoporosis, infections, weight gain) 2
• Patients with lower baseline GFR who may benefit from greater renal function recovery 2

Mandatory Pre-Treatment Evaluations

Hepatic Assessment

• Obtain baseline liver function tests (ALT, AST, alkaline phosphatase, total bilirubin) before initiating therapy 1
• Avacopan is not recommended for patients with cirrhosis, especially Child-Pugh C 1
• Avoid in patients with active, untreated chronic liver disease (chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) 1

Hepatitis B Screening

• Screen all patients for HBV by measuring HBsAg and anti-HBc before starting avacopan 1
• For patients with evidence of prior or current HBV infection, consult hepatology regarding monitoring and antiviral therapy 1
• HBV reactivation, including life-threatening hepatitis, has been observed with avacopan 1

Monitoring Requirements During Treatment

Hepatic Monitoring

• Monitor liver function tests every 4 weeks for the first 6 months, then as clinically indicated 1
• If ALT or AST >3× upper limit of normal: evaluate promptly and consider pausing treatment 1
• If AST or ALT >5× upper limit of normal, or transaminases >3× with bilirubin >2× upper limit of normal: discontinue avacopan until drug-induced liver injury is ruled out 1

Clinical Monitoring

• Monitor for signs of hypersensitivity reactions, particularly angioedema 1
• Assess disease activity using Birmingham Vasculitis Activity Score (BVAS) 3
• Monitor renal function with serial creatinine and eGFR measurements 2, 3

Clinical Efficacy Data

Avacopan achieved non-inferior remission rates at 26 weeks (72.3% vs 70.1% with prednisone) and superior sustained remission at 52 weeks (65.7% vs 54.9% with prednisone) in the ADVOCATE trial. 3

• Glucocorticoid toxicity scores were significantly lower with avacopan compared to prednisone 2, 3
• Cumulative glucocorticoid dose was 2.3 grams lower over 1 year in the avacopan group 2
• Patients with active glomerulonephritis had greater recovery of kidney function with avacopan versus glucocorticoids 2, 4
• Serious adverse events (excluding worsening vasculitis) occurred in 37.3% with avacopan versus 39.0% with prednisone 3

Critical Limitations and Contraindications

• Contraindicated in patients with serious hypersensitivity to avacopan or any excipients 1
• No data exist for use beyond 52 weeks; longer-term use cannot be recommended 2
• Not studied in patients with GFR <15 mL/min/1.73 m² or refractory disease 2
• Safety and efficacy beyond 52 weeks have not been established 3

Role in Treatment Algorithm

Avacopan represents an alternative to standard glucocorticoid regimens rather than a replacement for all glucocorticoids, and should be considered as part of a glucocorticoid-minimization strategy. 2

• Position avacopan as a glucocorticoid-sparing agent in combination with rituximab or cyclophosphamide 2
• Reserve for patients who would derive enhanced benefit from reduced glucocorticoid exposure 2
• Continue to use standard immunosuppression (rituximab or cyclophosphamide) as the backbone of therapy 1, 3
• Transition to maintenance therapy with rituximab or azathioprine after achieving remission 2