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Drug Safety-related Labeling Changes (SrLC)

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VEOZAH (NDA-216578)

(FEZOLINETANT)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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12/16/2024 (SUPPL-4)

Approved Drug Label (PDF)

Boxed Warning

Newly added section

WARNING: RISKS OF HEPATOTOXICITY

Hepatotoxicity has occurred with the use of VEOZAH in the postmarketing setting (5.1).

  • Perform hepatic laboratory tests prior to initiation of treatment to evaluate for hepatic function and injury. Do not start VEOZAH if either aminotransferase is greater than or equal to 2 x the upper limit of normal (ULN) or if the total bilirubin is greater than or equal to 2 x ULN for the evaluating laboratory.
  • Perform follow-up hepatic laboratory testing monthly for the first 3 months, at 6 months, and 9 months of treatment (2.1, 5.1).
  • 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) (2.1, 5.1).
  • Discontinue VEOZAH if transaminase elevations are > 5 x ULN, or if transaminase elevations are > 3 x ULN and the total bilirubin level is > 2 x ULN.

If transaminase elevations > 3 x ULN occur, perform more frequent follow-up hepatic laboratory tests until resolution (5.1).


5 Warnings and Precautions

5.1 Hepatotoxicity

Subsection title revised

Additions and/or revisions underlined:

In three clinical trials, elevations in serum transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels  greater than or equal to 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 (greater than or equal to 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 [see Adverse Reactions (6.1)].

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 [see Adverse Reactions (6.2)].

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 greater than or equal to 2 x ULN or if the total bilirubin is greater than or equal to 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 greater than or equal to 5 x ULN.
  • transaminase elevations are  greater than or equal to 3 x ULN and total bilirubin is greater than or equal to 2 x ULN.

If transaminase elevations greater than or equal to 3 x ULN occur, perform more frequent follow-up hepatic laboratory tests until resolution.

Exclude alternative causes of hepatic laboratory test elevations.

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

In the pooled laboratory data of Trials 1, 2, and 3, elevated hepatic transaminases (greater than or equal to 3 x ULN) occurred in 25 women (2.3%, 2.7 EAIR) exposed to VEOZAH 45 mg (n=1100, 912.1 total person-years) as compared to 8 women (0.9%, 1.5 EAIR) exposed to placebo (n=952, 549.1 total person-years).

6.2 Postmarketing Experience

Additions and/or revisions underlined:

The following adverse reactions have been identified during postapproval use of VEOZAH. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatic: Cases of serious drug-induced hepatotoxicity occurred within 40 days of starting VEOZAH. Patients experienced elevated transaminases (up to 50 x ULN at peak elevation), elevated alkaline phosphatase (up to 4 x ULN at peak elevation), and bilirubin (up to 5 x ULN at peak elevation) coupled with symptoms of fatigue, nausea, pruritus, jaundice, pale feces, and dark urine. After discontinuation of VEOZAH, these abnormalities gradually resolved.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise patients to read the FDA-approved patient labeling (Patient Information).

Evaluation of Hepatic Injury During Treatment with VEOZAH

Inform patients that they will have to have a blood test to evaluate their liver function before beginning VEOZAH and while using VEOZAH monthly for the first 3 months, at 6 months, and 9 months after initialization 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 abnormalities such as new onset fatigue, decreased appetite, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or abdominal pain [see Warnings and Precautions (5.1)].

PATIENT INFORMATION

Additions and/or revisions underlined:

What is the most important information I should know about VEOZAH?

Stop VEOZAH right away and call your healthcare provider if you have the following signs or symptoms of liver problems:

  • feeling more tired than you do usually                    

  • yellowing of the eyes or skin (jaundice)

  • decreased appetite

  • pale feces

  • nausea                                                                      

  • dark urine

  • vomiting                                                                  

  • pain in the stomach (abdomen)

  • itching

See “What are the possible side effects of VEOZAH?” for more information about side effects.

What are the possible side effects of VEOZAH?

  • See “What is the most important information I should know about VEOZAH?

08/31/2024 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Hepatic Transaminase Elevation and Hepatotoxicity

Subsection title revised

Additions and/or revisions underlined:

In the postmarketing setting, a case of acute mixed hepatocellular cholestatic drug-induced liver injury with elevations of ALT, AST, alkaline phosphatase (ALP), and total bilirubin with symptoms of fatigue, nausea, pruritus, jaundice, pale feces, and dark urine occurred in a woman receiving VEOZAH. The individual’s signs and symptoms gradually resolved after discontinuation of the drug [see Adverse Reactions (6.2)].

Perform baseline hepatic laboratory tests to evaluate for hepatic function and injury [including serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum alkaline phosphatase (ALP), and serum bilirubin (total and direct)] prior to VEOZAH initiation. Do not start VEOZAH if the concentration of ALT or AST is equal to or exceeds 2 times the ULN or if the total bilirubin is elevated (for example, equal to or exceeds 2 times the ULN) for the evaluating laboratory. If baseline hepatic transaminase evaluation is less than 2 times the ULN and the total bilirubin is normal, VEOZAH can be started.

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, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or right upper quadrant pain.

Discontinue VEOZAH if:

  • transaminase elevations are greater than 5 times the ULN.

  • transaminase elevations are greater than 3 times the ULN and the total bilirubin level is greater than 2 times the ULN.

If transaminase elevations greater than 3 times the ULN occur, perform more frequent follow-up hepatic laboratory tests until resolution.

Exclude alternative causes of hepatic laboratory test elevations.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Hepatic Transaminase Elevation and Hepatotoxicity [see Warnings and Precautions (5.1)].

6.2 Postmarketing Experience

Newly added subsection:

The following adverse reactions have been identified during postapproval use of VEOZAH. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatic: A case of serious drug-induced hepatotoxicity with elevated transaminases (greater than 10 times the ULN at peak elevation), elevated alkaline phosphatase (greater than 4 times the ULN at peak elevation), and bilirubin (greater than 3 times the ULN at peak elevation) coupled with symptoms of fatigue, nausea, pruritus, jaundice, pale feces, and dark urine occurred within 40 days of starting VEOZAH. After discontinuation of VEOZAH, these abnormalities gradually resolved.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Evaluation of Hepatic Injury During Treatment with VEOZAH

Inform patients that they will have to have a blood test to evaluate their liver function before beginning VEOZAH and while using VEOZAH monthly for the first 3 months, at 6 months, and 9 months after initialization 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 abnormalities such as new onset fatigue, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or right upper quadrant pain [see Warnings and Precautions (5.1)].

Serious Adverse Reactions with VEOZAH

Inform patients of possible serious adverse reactions of VEOZAH including hepatic transaminase elevation and liver injury [see Warnings and Precautions (5.1)].

PATIENT INFORMATION

Additions and/or revisions underlined:

What are the possible side effects of VEOZAH? VEOZAH can cause serious side effects, including:

  • increased liver blood test values and liver problems. Your healthcare provider will do a blood test to check your liver before you start taking VEOZAH. Your healthcare provider will also do this blood test monthly for the first 3 months, at month 6, and month 9 after you start taking VEOZAH or if you have signs or symptoms that suggest liver problems. If your liver blood test values are elevated, your healthcare provider may advise you to stop treatment or request additional liver blood tests.

Stop VEOZAH and call your healthcare provider right away if you have the following signs or symptoms of liver problems:

  • feeling more tired than you do usually

  • nausea

  • vomiting

  • itching

  • yellowing of the eyes or skin (jaundice)

  • pale feces

  • dark urine

  • pain in the right upper stomach (abdomen)