fezolinetant

Therapeutic Classification: menopausal agents

Pharmacologic Classification: temporary class

Indications ⬆ ⬇

REMS

Moderate to severe vasomotor symptoms due to menopause.

Action ⬆ ⬇

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;
Concurrent use with CYP1A2 inhibitors.

Use Cautiously in:

None.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: hot flush

GI: ↑liver enzymes, abdominal pain, diarrhea

MS: back pain

Neuro: insomnia

Interactions ⬆ ⬇

Drug-drug:

CYP1A2 inhibitors, including fluvoxamine, mexiletine, and cimetidine↑ 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.

Lab Test Considerations:

Monitor for hepatic function and injury with ALT, AST, and serum bilirubin (total and direct) before starting therapy and 3 mo, 6 mo, and 9 mo after starting therapy and when symptoms (nausea, vomiting, yellowing of the skin or eyes) occur suggesting liver injury. Do not start therapy if concentration of ALT or AST ≥ two times the upper limit of normal (ULN) or if total bilirubin is elevated (≥2× ULN) for the evaluating laboratory.

Implementation ⬆ ⬇

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

Patient/Family Teaching ⬆ ⬇

Instruct patient to take fezolinetant 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. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Advise patient to notify health care professional promptly if signs and symptoms of liver problems (nausea, vomiting, yellowing of the eyes or skin, pain in the right upper abdomen) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇