FEZOLINETANT Drug Interactions: What You Need to Know

INTERACTIONS

7.1 Effect of Other Drugs on VEOZAH CYP1A2 Inhibitors VEOZAH is a substrate of CYP1A2. Concomitant use of VEOZAH with drugs that are weak, moderate, or strong CYP1A2 inhibitors, increase the plasma C max and AUC of VEOZAH <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> . VEOZAH is contraindicated in individuals using CYP1A2 inhibitors.

VEOZAH is contraindicated in women with any of the following conditions:

• Known cirrhosis [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.7 ), and Clinical Pharmacology ( 12.3 )] .
• Severe renal impairment or end-stage renal disease [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] .
• Concomitant use with CYP1A2 inhibitors [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] .
• Known cirrhosis ( 4 , 5.1 )
• Severe renal impairment or end-stage renal disease ( 4 , 8.6 )
• Concomitant use with CYP1A2 inhibitors ( 4 , 7.1 )

AND PRECAUTIONS Hepatotoxicity: Cases of hepatotoxicity and jaundice have been reported in the postmarketing setting. Perform hepatic laboratory tests prior to initiation of VEOZAH to evaluate for hepatic function and injury. Perform follow-up hepatic laboratory tests monthly for the first 3 months, at 6 months, and 9 months after initiation of therapy. Advise patients to discontinue VEOZAH immediately and seek medical attention including hepatic laboratory tests if they experience signs or symptoms that may suggest liver injury (new onset fatigue, decreased appetite, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or abdominal pain). ( 5.1 )

5.1 Hepatotoxicity In three clinical trials, elevations in serum transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels &gt; 3 x the upper limit of normal (ULN) occurred in 2.3% [exposure adjusted incidence rate (EAIR) of 2.7 per 100 person-years] of women receiving VEOZAH and 0.9% (EAIR of 1.5 per 100 person-years) of women receiving placebo. No elevations in serum total bilirubin (&gt; 2 x ULN) occurred. Women with ALT or AST elevations were generally asymptomatic. Transaminase levels returned to pretreatment levels (or close to these) without sequelae with dose continuation, and upon dose interruption, or discontinuation. Women with cirrhosis were not studied <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . In the postmarketing setting, cases of drug-induced liver injury with elevations of ALT, AST, alkaline phosphatase (ALP), and total bilirubin occurred within 40 days of starting VEOZAH. Patients reported a general sense of feeling unwell and symptoms of fatigue, nausea, pruritus, jaundice, pale feces, and dark urine. The patients’ signs and symptoms gradually resolved after discontinuation of VEOZAH <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 )]</span>. Perform baseline hepatic laboratory tests to evaluate for hepatic function and injury [including serum ALT, serum AST, serum ALP, and serum bilirubin (total and direct)] prior to VEOZAH initiation. Do not start VEOZAH if ALT or AST is ≥ 2 x ULN or if the total bilirubin is ≥ 2 x ULN for the evaluating laboratory. Perform follow-up hepatic laboratory tests monthly for the first 3 months, at 6 months, and 9 months after initiation of therapy. Advise patients to discontinue VEOZAH immediately and seek medical attention including hepatic laboratory tests if they experience signs or symptoms that may suggest liver injury:

• new onset fatigue, decreased appetite, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or abdominal pain. Discontinue VEOZAH if:
• transaminase elevations are > 5 x ULN.
• transaminase elevations are > 3 x ULN and total bilirubin is > 2 x ULN. If transaminase elevations > 3 x ULN occur, perform more frequent follow-up hepatic laboratory tests until resolution. Exclude alternative causes of hepatic laboratory test elevations.