VEOZAH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VEOZAH (VEOZAH).
Selective antagonist of the neurokinin 3 (NK3) receptor, which modulates gonadotropin-releasing hormone (GnRH) secretion and reduces luteinizing hormone (LH) pulses.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2C19 and CYP2D6. |
| Excretion | Primarily fecal (approximately 72% of the administered dose recovered in feces) and renal (approximately 16% in urine), with the majority as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is approximately 40–50 hours, supporting once-daily dosing. |
| Protein binding | Approximately 99% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | 95 L (corresponding to approximately 1.2 L/kg assuming 80 kg), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 30% (due to first-pass metabolism); administration with a high-fat meal reduces Cmax and AUC by approximately 65% and 55%, respectively, so consistent dosing relative to meals is recommended. |
| Onset of Action | Reduction in moderate-to-severe vasomotor symptoms (VMS) frequency is observed within 4 weeks of oral administration. |
| Duration of Action | Clinical effect persists throughout the 24-hour dosing interval; sustained efficacy with continued use. |
| Molecular Weight | 329.4 |
45 mg orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Not recommended for severe renal impairment (eGFR <30 mL/min) or ESRD. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce to 45 mg every other day. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required based on age; monitor renal function as elderly may have decreased clearance. |
| 1st trimester | Limited human data; animal studies show no teratogenicity at clinically relevant doses. Avoid use unless benefit outweighs risk. |
| 2nd trimester | Limited human data; no known fetal risk. Use caution. |
| 3rd trimester | Limited human data; no known neonatal effects. Use caution during labor. |
Clinical note
Comprehensive clinical and safety monograph for VEOZAH (VEOZAH).
| Placental transfer | Expected to cross placenta based on molecular weight and lipophilicity; no specific human data. |
| Breastfeeding | No human data on excretion in breast milk. Animal studies indicate low levels. Consider developmental benefits of breastfeeding vs maternal need for drug. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Concomitant use with strong CYP1A2 inhibitorsHistory of hypersensitivity to fezolinetant or excipients
| Precautions | Hepatic impairment (contraindicated in Child-Pugh C; not recommended in moderate to severe hepatic impairment); increases in transaminases and bilirubin; potential for drug interactions with strong CYP3A4 inhibitors/inducers. |
| Food/Dietary | Grapefruit juice may inhibit CYP1A2 and increase fezolinetant levels; avoid concurrent intake. No other dietary restrictions. Can be taken with or without food. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | Based on US prescribing information, no adequate and well-controlled studies in pregnant women. In animal reproduction studies, oral administration of fezolinetant to pregnant rats and rabbits during organogenesis produced no clear evidence of teratogenicity at exposures up to 7 times (rat) and 38 times (rabbit) the maximum recommended human dose (MRHD). However, in a rat pre- and postnatal development study, decreased pup survival and growth were observed at maternally toxic doses. Because animal studies are not always predictive of human response, fezolinetant should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. First trimester: risk cannot be ruled out; second and third trimesters: limited data. |
| Fetal Monitoring | No specific monitoring recommendations for maternal or fetal effects during pregnancy are provided in the labeling. If used in pregnancy, standard prenatal care and fetal monitoring as clinically indicated should be followed. Liver function tests are recommended before initiation of therapy and as clinically indicated during treatment due to risk of elevated transaminases. |
| Fertility Effects | Based on animal studies, fezolinetant did not affect fertility or reproductive performance in male or female rats at exposures up to 14 times (male) and 8 times (female) the MRHD. No human data on fertility effects are available. |
| VEOZAH (fezolinetant) is a neurokinin 3 receptor antagonist for vasomotor symptoms due to menopause. Titrate dose carefully: start at 45 mg once daily; may reduce to 30 mg if tolerability issues. Avoid in patients with cirrhosis or severe renal impairment (CrCl <30 mL/min). Monitor LFTs at baseline and periodically; discontinue if ALT/AST >3x ULN or bilirubin >2x ULN. CYP1A2 substrate; co-administration with strong CYP1A2 inhibitors (e.g., fluvoxamine) increases fezolinetant exposure; consider dose reduction. No food effect on absorption; can take with or without food. |
| Patient Advice | Take VEOZAH exactly as prescribed, at the same time each day. · Swallow tablet whole with liquid; do not crush or split. · Common side effects include headache and insomnia; report any signs of liver issues (yellowing skin/eyes, dark urine, abdominal pain). · Avoid drinking grapefruit juice or eating grapefruit while on VEOZAH. · This medication does not contain hormones and is not for prevention of osteoporosis or heart disease. · If you miss a dose, skip it and take the next dose at the regular time; do not double up. |