Veozah Drug Information
Generic name: FEZOLINETANT
Neurokinin 3 Receptor Antagonist [EPC]
Uses of Veozah
VEOZAH ® is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.
Dosage & Administration of Veozah
Recommended Dosage Take a single 45 mg
VEOZAH tablet orally once daily with or without food. Take VEOZAH with liquids and swallow whole. Do not cut, crush, or chew tablets.
Administer VEOZAH orally at about the same time each day. If a dose of VEOZAH is missed or not taken at the usual time, administer the missed dose as soon as possible, unless there is less than 12 hours before the next scheduled dose. Return to the regular schedule the following day.
Perform baseline hepatic laboratory tests to evaluate for hepatic function and injury before initiating treatment with VEOZAH. 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. While using VEOZAH, 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.
Side Effects of Veozah
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of VEOZAH was evaluated in three 52-week clinical trials. Across the three clinical trials, a total of 1100 women received VEOZAH.
Trials 1 and 2 were placebo-controlled for the first 12 weeks, followed by re-randomization of women previously receiving placebo to VEOZAH (women on VEOZAH remained on VEOZAH) for an additional 40 weeks of uncontrolled treatment. Trial 3 was a randomized, placebo-controlled, double-blind safety study evaluating the safety of VEOZAH for 52 weeks. 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.
| Adverse Reaction | VEOZAH 45 mg (n=609) Total Person-Years=504.2 n (%, EAIR EAIR = Number of individuals experiencing an adverse event divided by exposure time (total person-years) x 100. ) | Placebo (n=610) Total Person-Years=475.0 n (%, EAIR ) |
|---|---|---|
| Abdominal pain Abdominal pain (including Abdominal pain, Abdominal pain lower, Abdominal pain upper). | 26 (4.3%, 5.2) | 13 (2.1%, 2.7) |
| Diarrhea | 24 (3.9%, 4.8) | 16 (2.6%, 3.4) |
| Insomnia | 24 (3.9%, 4.8) | 11 (1.8%, 2.3) |
| Back pain | 18 (3.0%, 3.6) | 13 (2.1%, 2.7) |
| Hot flush | 15 (2.5%, 3.0) | 10 (1.6%, 2.1) |
| Hepatic transaminase elevation Hepatic transaminase elevations (including Alanine aminotransferase abnormal, Alanine aminotransferase increased, Aspartate aminotransferase abnormal, Aspartate aminotransferase increased). | 14 (2.3%, 2.8) | 5 (0.8%, 1.1) |
Warnings & Cautions for Veozah
Hepatotoxicity
In three clinical trials, elevations in serum transaminase levels > 3 x the upper limit of normal (ULN) occurred in 2.3% 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 (> 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. 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. Perform baseline hepatic laboratory tests to evaluate for hepatic function and injury 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.
Drug Interactions with Veozah
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. VEOZAH is contraindicated in individuals using CYP1A2 inhibitors.
Pregnancy Safety for Veozah
Pregnancy Risk Summary There are no data on VEOZAH use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In embryo-fetal toxicity animal studies with fezolinetant, embryo-lethality occurred at high doses above the human therapeutic dose in rats and rabbits, but no teratogenicity was observed. In the pre- and post-natal development animal study, delayed parturition and embryo-lethality occurred at high doses above the human therapeutic dose in rats.
Additionally, in the male offspring delayed male reproductive maturation was observed, characterized by incomplete preputial separation, which affected male fertility at doses above the human therapeutic dose in rats. In the U.S. general population, the estimated background risk of major birth defects or miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Data Animal Data In embryo-fetal development toxicity studies in rats and rabbits, embryo-lethality was noted at the highest doses (128- and 174-fold the human AUC 24 at the human therapeutic dose for rats and rabbits, respectively).
The no observed adverse effect level (NOAEL) for embryo-fetal development was 50 mg/kg/day in rats and 45 mg/kg/day in rabbits (62- and 16‑fold the human AUC 24 at the human therapeutic dose for rats and rabbits, respectively). Fezolinetant showed no effects on fertility and early embryonic development in rats. In the pre- and post-natal development study in rats, the NOAEL for maternal and fetal toxicity was 30 mg/kg/day (36‑fold the human AUC 24 at the human therapeutic dose) based on delayed parturition and embryo-lethality at 100 mg/kg/day.
The F 1 male showed delayed male reproductive maturation, characterized as incomplete balanopreputial separation at time of mating, at doses of greater than or equal to 30 mg/kg/day (36-fold the human AUC 24 at the human therapeutic dose), which affected male fertility.
Pediatric Use of Veozah
Pediatric Use The efficacy and safety of VEOZAH in individuals less than 18 years of age have not been established.
Contraindications for Veozah
- VEOZAH is contraindicated in women with any of the following conditions:
- Known cirrhosis.
- Severe renal impairment or end-stage renal disease.
- Concomitant use with CYP1A2 inhibitors.
- Known cirrhosis
Overdosage Information for Veozah
Treatment of overdose consists of discontinuation of VEOZAH therapy with institution of appropriate symptomatic care.
Clinical Studies of Veozah
Effects on Vasomotor Symptoms in Postmenopausal Women
The efficacy of VEOZAH for the treatment of moderate to severe vasomotor symptoms due to menopause was evaluated in the first 12-week, randomized, placebo-controlled, double-blind portion of each of two phase 3 clinical trials. In each of these two trials, after the first 12 weeks, women on placebo were then re-randomized to VEOZAH for a 40-week extension to evaluate safety for up to 52 weeks total exposure. Randomization was stratified by smoking status.
The mean age of the postmenopausal women was 54 years. The study population included menopausal women with one or more of the following: prior hysterectomy (32.1%), prior oophorectomy (21.6%), or prior hormone therapy use (19.9%). Those who were on prior hormone therapy underwent a wash-out period prior to trial participation.
The co-primary efficacy endpoints for both trials were the mean change from baseline in moderate to severe vasomotor symptoms frequency and severity to Weeks 4 and 12. Data from each trial also demonstrated a statistically significant reduction from baseline in the severity of moderate to severe vasomotor symptoms (over 24 hours) at Weeks 4 and 12 for VEOZAH 45 mg compared to placebo. Table 2: Mean Baseline and Change from Baseline to Weeks 4 and 12 for Mean Frequency of Moderate to Severe Vasomotor Symptoms over 24 Hours in Women Treated with VEOZAH in Trials Statistically significantly superior compared to placebo at the 0.05 level with multiplicity adjustment.
LS Mean: Least Squares Mean estimated from a mixed model for repeated measures analysis of covariance; SD: Standard Deviation; SE: Standard Error. -3.3 -- -- -- -- Change from Baseline to Week 12 LS Mean (SE) Difference vs Placebo (95% CI) P-value -- -- -- -- Results of the co-primary endpoint for change from baseline to Weeks 4 and 12 in mean severity of moderate to severe vasomotor symptoms over 24 hours from Trials 1 and 2 are shown in Table 3.
Effects on Endometrium in Postmenopausal Women In the VEOZAH 45 mg dose group across Trials 1, 2, and 3, endometrial biopsy assessments identified one case of endometrial hyperplasia and one case of endometrial malignancy.
| Parameter | Trial 1 | Trial 2 | ||
|---|---|---|---|---|
| VEOZAH 45 mg (n=174) | Placebo (n=175) | VEOZAH 45 mg (n=167) | Placebo (n=167) | |
| Baseline Mean (SD) | 10.4 (3.92) | 10.5 (3.79) | 11.8 (8.26) | 11.6 (5.02) |
| Change from Baseline to Week 4 LS Mean (SE) Difference vs Placebo (95% CI) P-value | -5.4 (0.30) -2.1 (-2.9, -1.3) < 0.001 Statistically significantly superior compared to placebo at the 0.05 level with multiplicity adjustment. LS Mean: Least Squares Mean estimated from a mixed model for repeated measures analysis of covariance; SD: Standard Deviation; SE: Standard Error. | -3.3 (0.29) -- -- | -6.3 (0.33) -2.6 (-3.5, -1.6) < 0.001 | -3.7 (0.33) -- -- |
| Change from Baseline to Week 12 LS Mean (SE) Difference vs Placebo (95% CI) P-value | -6.4 (0.31) -2.6 (-3.4, -1.7) < 0.001 | -3.9 (0.31) -- -- | -7.5 (0.39) -2.5 (-3.6, -1.5) < 0.001 | -5.0 (0.39) -- -- |
| Parameter | Trial 1 | Trial 2 | ||
|---|---|---|---|---|
| VEOZAH 45 mg (n=174) | Placebo (n=175) | VEOZAH 45 mg (n=167) | Placebo (n=167) | |
| Baseline Mean (SD) | 2.4 (0.35) | 2.4 (0.35) | 2.4 (0.34) | 2.4 (0.32) |
| Change from Baseline to Week 4 LS Mean (SE) Difference vs Placebo (95% CI) P-value | -0.5 (0.04) -0.2 (-0.3, -0.1) 0.002 Statistically significantly superior compared to placebo at the 0.05 level with multiplicity adjustment. LS Mean: Least Squares Mean estimated from a mixed model for repeated measures analysis of covariance; SD: Standard Deviation; SE: Standard Error. | -0.3 (0.04) -- -- | -0.6 (0.05) -0.3 (-0.4, -0.2) < 0.001 | -0.3 (0.05) -- -- |
| Change from Baseline to Week 12 LS Mean (SE) Difference vs Placebo (95% CI) P-value | -0.6 (0.05) -0.2 (-0.4, -0.1) 0.007 | -0.4 (0.05) -- -- | -0.8 (0.06) -0.3 (-0.5, -0.1) < 0.001 | -0.5 (0.06) -- -- |
| Final Diagnosis | VEOZAH 45 mg (n=350) | Placebo (n=186) |
|---|---|---|
| Endometrial Hyperplasia and Carcinoma, n (%) One-sided upper limit of 95% CI - Simple hyperplasia without atypia - Endometrial adenocarcinoma | 2 (0.6%) 1.8% 1 1 | 0 1.6% 0 0 |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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