AVACOPAN Drug Interactions: What You Need to Know

INTERACTIONS Strong and moderate CYP3A4 enzyme inducers: Avoid use. ( 7.1 ) Strong CYP3A4 enzyme inhibitors: Reduce avacopan dose to 30 mg once daily. ( 7.2 ) CYP3A4 substrates: Consider dose reduction of CYP3A4 substrates when co-administering TAVNEOS with CYP3A4 substrates. ( 7.3 )

7.1 CYP3A4 Inducers Avacopan exposure is decreased when co-administered with strong CYP3A4 enzyme inducers such as rifampin <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Avoid coadministration of strong and moderate CYP3A4 inducers with TAVNEOS.

7.2 CYP3A4 Inhibitors Avacopan exposure is increased when co-administered with strong CYP3A4 enzyme inhibitors such as itraconazole <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Administer TAVNEOS 30 mg once daily when coadministered with strong CYP3A4 inhibitors.

7.3 CYP3A4 Substrates Avacopan is a moderate CYP3A4 inhibitor. 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). Consider dose reduction of CYP3A4 substrates when co-administering TAVNEOS with CYP3A4 substrates. Consult the concomitant CYP3A4 substrate product information when considering administration of such products together with TAVNEOS <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> .

TAVNEOS is contraindicated in patients with serious hypersensitivity reaction to avacopan or to any of the excipients [see Warnings and Precautions (5.2) ]. Serious hypersensitivity to avacopan or to any of the excipients. ( 4 )

AND PRECAUTIONS Hepatotoxicity: Increase in liver function tests occurred in clinical trials. Obtain liver function tests before initiation of therapy and monitor as clinically indicated. ( 5.1 )

Serious Hypersensitivity

Reactions: Cases of angioedema occurred in a clinical trial. Observe for signs and symptoms of angioedema and manage accordingly. ( 5.2 ) Hepatitis B Virus (HBV) Reactivation: Cases of HBV reactivation occurred in a clinical trial. Withhold TAVNEOS and institute appropriate anti-infective therapy. ( 5.3 )

Serious

Infections: Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. ( 5.4 )

5.1 Hepatotoxicity Serious cases of hepatic injury have been observed in patients taking TAVNEOS. During controlled trials, the TAVNEOS treatment group had a higher incidence of transaminase elevations and hepatobiliary events, including serious and life-threatening events <span class="opacity-50 text-xs">[see Adverse Reactions 6.1 ]</span> . Obtain liver test panel (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin) before initiating TAVNEOS, every 4 weeks after start of therapy for the first 6 months of treatment and as clinically indicated thereafter. If a patient receiving treatment with TAVNEOS presents with an elevation in ALT or AST to &gt;3 times the upper limit of normal, evaluate promptly and consider pausing treatment as clinically indicated. If AST or ALT is &gt;5 times the upper limit of normal, or if a patient develops transaminases &gt;3 times the upper limit of normal with elevation of bilirubin to &gt;2 times the upper limit of normal, discontinue TAVNEOS until TAVNEOS-induced liver injury is ruled out <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>. 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 risk and benefit before administering TAVNEOS to a patient with liver disease. Monitor patients closely for hepatic adverse reactions [ see Use in Specific Populations (8.7) ].

5.2 Hypersensitivity Reactions TAVNEOS may cause angioedema <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . In clinical trials, two cases of angioedema occurred, including one serious event requiring hospitalization. If angioedema occurs, discontinue TAVNEOS immediately, provide appropriate therapy, and monitor for airway compromise. TAVNEOS must not be re-administered unless another cause has been established. Educate patients on recognizing the signs and symptoms of a hypersensitivity reaction and to seek immediate medical care should they develop.

5.3 Hepatitis B Virus (HBV)

Reactivation

Hepatitis B virus (HBV) reactivation, including life threatening hepatitis B, was observed in the clinical program. HBV reactivation is defined as an abrupt increase in HBV replication, manifesting as a rapid increase in serum HBV DNA levels or detection of HBsAg, in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis, i.e., increase in transaminase levels. In severe cases, increase in bilirubin levels, liver failure, and death can occur. Screen patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with TAVNEOS. For patients who show evidence of prior hepatitis B infection (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during TAVNEOS treatment. Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis, or HBV reactivation during and for six months following TAVNEOS therapy. In patients who develop reactivation of HBV while on TAVNEOS, immediately discontinue TAVNEOS and any concomitant therapy associated with HBV reactivation, and institute appropriate treatment. Insufficient data exist regarding the safety of resuming TAVNEOS treatment in patients who develop HBV reactivation. Resumption of TAVNEOS treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing HBV.

5.4 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 an active, serious infection, including localized infections. Consider the risks and benefits of treatment prior to initiating TAVNEOS in patients: with chronic or recurrent infection who have been exposed to tuberculosis with a history of a serious or an opportunistic infection who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with TAVNEOS. Interrupt TAVNEOS if a patient develops a serious or opportunistic infection. A patient who develops a new infection during treatment with TAVNEOS should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient; appropriate antimicrobial therapy should be initiated, the patient should be closely monitored, and TAVNEOS should be interrupted if the patient is not responding to antimicrobial therapy. TAVNEOS may be resumed once the infection is controlled.