fezolinetant

Acts as a neurokinin 3 receptor antagonist that blocks neurokinin B binding on the kisspeptin/neurokinin B/dynorphin neuron to regulate neuronal activity in the thermoregulatory center.

Therapeutic effects:

Reduction in frequency and severity of vasomotor symptoms due to menopause.

Pharmacokinetics ⬆ ⬇

Absorption: Extent of absorption unknown.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP1A2 isoenzyme, with some metabolism by the CYP2C9 and CYP2C19 isoenzymes. Primarily excreted in the urine (77%; 1% as unchanged drug), with 15% excreted in the feces (<1% as unchanged drug).

Half-Life: 9.6 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Cirrhosis;
Severe renal impairment or end-stage renal disease;
AST, ALT, or total bilirubin ≥2 times upper limit of normal (ULN)
;
Concurrent use with CYP1A2 inhibitors.

Use Cautiously in:

None.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: hot flush

GI: ↑liver enzymes, abdominal pain, diarrhea, HEPATOTOXICITY

MS: back pain

Neuro: insomnia

Interactions ⬆ ⬇

Drug-drug:

CYP1A2 inhibitors, including fluvoxamine, mexiletine, and cimetidine, may ↑ levels and risk of toxicity; concurrent use contraindicated.

Route/Dosage ⬆ ⬇

PO (Adults ): 45 mg once daily.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Assess vasomotor symptoms (feelings of warmth in the face, neck, and chest) or sudden intense feelings of heat and sweating (hot flashes or hot flushes) before starting and periodically during therapy.
Assess for signs and symptoms of hepatotoxicity (new onset fatigue, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, right upper quadrant pain).

Lab Test Considerations:

Monitor ALT, AST, alkaline phosphatase, and bilirubin (total and direct) before starting therapy and then monthly for the 1st 3 mo, 6 mo, and 9 mo after starting therapy. If AST/ALT >3 times upper limit of normal (ULN), monitor hepatic function frequently until resolution. If AST/ALT >5 times ULN, OR AST/ALT >3 times ULN and total bilirubin > 2 times ULN. permanently discontinue fezolinetant.

Implementation ⬆ ⬇

PO: Administer once daily with or without food, at the same time each day. DNC: Swallow tablets whole. Do not break, crush, or chew.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed. Take missed doses as soon as remembered, unless there is <12 hr before next dose is due. Return to regular schedule next day.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patient to discontinue fezolinetant immediately and seek medical attention if signs or symptoms of liver abnormalities (new onset fatigue, ↓ appetite, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, abdominal pain) occur.

Evaluation/Desired Outcomes ⬆ ⬇

Reduction in frequency and severity of vasomotor symptoms due to menopause.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

0469- Astellas Pharma US, Inc.
- 0469-2460- VEOZAH
  - 0469-2460-28- 4 CARTON in 1 TRAY (0469-2460-28) / 1 BOTTLE in 1 CARTON (0469-2460-07) / 7 TABLET, FILM COATED in 1 BOTTLE

0469- Astellas Pharma US, Inc.
- 0469-2660- VEOZAH
  - 0469-2660-30- 1 BOTTLE in 1 CARTON (0469-2660-30) / 30 TABLET, FILM COATED in 1 BOTTLE

0469- Astellas Pharma US, Inc.
- 0469-2660- VEOZAH
  - 0469-2660-90- 1 BOTTLE in 1 CARTON (0469-2660-90) / 90 TABLET, FILM COATED in 1 BOTTLE

0469- Astellas Pharma US, Inc.
- 0469-2760- VEOZAH
  - 0469-2760-28- 4 CARTON in 1 TRAY (0469-2760-28) / 1 BLISTER PACK in 1 CARTON (0469-2760-07) / 7 TABLET, FILM COATED in 1 BLISTER PACK

12838- Astellas Pharma Inc.
- 12838-3360-
  - 12838-3360-9- 93000 TABLET, COATED in 1 DRUM (12838-3360-9)

51148- Bushu Pharmaceuticals, Ltd.
- 51148-014-
  - 51148-014-01- 1 BAG in 1 CONTAINER (51148-014-01) / 93000 TABLET, FILM COATED in 1 BAG

59361- Juzen Chemical Corporation
- 59361-004-
  - 59361-004-01- 20 kg in 1 DRUM (59361-004-01)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇