fezolinetant

General

Pronunciation:
fez-oh-lin-e-tant

Trade Name(s)

• Veozah

Ther. Class.

menopausal agents

Pharm. Class.

neurokinin 3 receptor antagonists

Indications

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 Effect(s):

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

Pharmacokinetics

Absorption: Extent of absorption unknown.

Distribution: Extensively distributed to tissues.

Metabolism and 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)

Contraindication/Precautions

Contraindicated in:

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

Use Cautiously in:

None.

Adverse Reactions/Side Effects

Derm: hot flush

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

MS: back pain

Neuro: insomnia

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

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

Tablets: 45 mg

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.