Monograph
G02CX06 - Fezolinetant |
Propably not porphyrinogenic |
PNP |
Side effects
A common adverse reaction of fezolinetant that can be confused with an acute porphyric attack is abdominal pain.
Rationale
Fezolinetant is a substrate of CYP1A2, CYP2C9, CYP2C19 and CYP2D6, but is found not to have potential for induction or inhibition of CYP enzymes.
Chemical description
Fezolinetant is a neurokinin 3 (NK3) receptor antagonist.
Therapeutic characteristics
Fezolinetant is indicated for relieving vasomotoric symptoms in menopause. It works by blocking neurokinin B binding on the kisspeptin/neurokinin B/dynorphin neuron, which help restore neuronal activity in the thermoregulatory centre of the hypothalamus (EMA).
Fezolinetant may also cause a transient decrease in lutenizing hormone (LH) accompanied by a small decrease in sex hormone levels, but this is not considered to have clinical implications (SPC, EMA, Drugbank)
Metabolism and pharmacokinetics
Fezolinetant is metabolised by CYP1A2, CYP2C9, CYP2C19 and CYP2D6, with CYP1A2 as the primary enzyme for formation of its main metabolite, ES259564.
In vitro data has shown that fezolinetant and its metabolite ES259564 are not direct or time-dependent inhibitors of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4.
It is also shown that fezolinetant is not an inducer of CYP1A2 and that ES259564 is not an inducer of CYP1A2, CYP2B6 and CYP3A4 (EMA).
Fezolinetant is administered orally and has a half life of 9,6 hours (SPC).
References
# | Citation details | PMID |
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* | Drug reference publications | |
1. | DrugBank. Fezolinetant. (Accessed: 20.08 2024)
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* | Summary of Product Characteristics | |
2. | European Public Assessment Report, Veoza (SPC)/ (Scientific discussion). European Medicines Agency (EMA). (Published: 20.12.2023).
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3. | The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Veoza.
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