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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VEOZAH (VEOZAH).
| Breastfeeding | There is no information regarding the presence of fezolinetant in human milk, effects on the breastfed infant, or effects on milk production. Fezolinetant and its metabolites are excreted in rat milk. When a drug is present in animal milk, it is likely to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for fezolinetant and any potential adverse effects on the breastfed infant from fezolinetant or from the underlying maternal condition. M/P ratio: not determined in humans. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
Known hypersensitivity; concomitant use with strong CYP3A4 inhibitors; Child-Pugh C hepatic impairment; women with history of chronic hepatitis or severe hepatic impairment.
| 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. |
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| 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. |