Elinzanetant

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 1 notifications to the ECHA C&L Inventory.

In preregistration clinical trials, serum ALT or AST elevations above 3 times the upper limit of normal (ULN) occurred in 0.6% of patients taking elinzanetant vs 0.4% of placebo recipients. The elevations were asymptomatic and transient, resolving promptly after stopping therapy and sometimes despite drug continuation. Nevertheless, the elevations appeared to be related to therapy and arose most frequently during the first few months of treatment. In the safety profiles of elinzanetant therapy in 713 women enrolled in 3 controlled trials, there were no instances of clinically apparent liver injury with jaundice. Nevertheless, the clinical experience with elinzanetant outside of controlled trials has been limited. Fezolinetant, the initial NK inhibitor approved for treatment of menopausal symptoms was found to cause rare instances of liver injury with jaundice within a year of its release. For these reasons the product label for elinzanetant recommends testing for routine liver tests before treatment, again at 3 months after starting the drug, and monitoring patients for symptoms of liver injury regularly throughout therapy.

Elinzanetant is a non-hormonal, selective, dual neurokinin 1 (NK-1) and 3 (NK-3) receptor antagonist indicated for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. Peptide neurotransmitters and neuropeptides, such as neurokinin A, Substance P, and neurokinin B (NKB), and kisspeptin, are involved in the regulation the neuroendocrine and reproductive function. During menopause, declining estrogen levels lead to hyperactivation of kisspeptin/NKB/dynorphin (KNDy) neurons in the brain, disrupting thermoregulation and causing VMS. Overexpression of neurokinin B and Substance P - a key endogenous ligand for NK1 receptors - in the hypothalamus of postmenopausal women was also reported. Substance P and NK1 receptor signalling has also been implicated in sleep disturbances and peripheral vasodilation in menopause. Elinzanetant blocks NK-1 and NK-3 receptor signalling on these KNDy neurons, modulating neuronal activity involved in thermoregulation. Elinzanetant exhibits high affinity for human NK-1 receptors (mean K value of 0.37 nM) and NK-3 receptors (mean K value of 3.0 nM).

Elinzanetant is primarily metabolized by CYP3A4 to yield three principal metabolites - M27, M30/34, and M18/21. These three metabolites are active and have comparable affinities for the human NK-1 and NK-3 receptors as elinzanetant. Elinzanetant covers 39% of the total exposure in human plasma, with all its metabolites expected to make up the rest.