From the Guidelines
Liver function tests (LFTs) should be monitored monthly in patients initiating fezolinetant (NK1 receptor antagonist) in a postmenopausal patient, as a precautionary measure to minimize the risk of liver injury, although the provided evidence does not directly relate to fezolinetant, the principle of monitoring liver function applies to medications with potential hepatotoxic effects, as seen with other drugs like bosentan and tolvaptan 1.
Key Considerations
- The evidence provided does not directly address the monitoring of liver function tests for fezolinetant, but it highlights the importance of liver function monitoring for medications that may have hepatotoxic effects, such as bosentan and tolvaptan.
- Bosentan, an endothelin-1 receptor antagonist, has been associated with dose-dependent and reversible increases in hepatic aminotransferases, leading to recommendations for monthly liver function tests 1.
- Tolvaptan, used in the treatment of autosomal dominant polycystic kidney disease (ADPKD), also carries a risk of idiosyncratic drug-induced liver injury, with guidelines suggesting frequent monitoring of LFTs, especially during the first 18 months of treatment 1.
Clinical Implications
- While fezolinetant's specific hepatotoxicity profile may not be fully elucidated in the provided evidence, the principle of cautious monitoring applies, especially in populations that may be at higher risk of liver injury.
- Baseline liver enzymes should be obtained before initiating fezolinetant to identify any pre-existing liver abnormalities.
- Patients should be educated on the symptoms of liver injury and the importance of reporting these symptoms promptly.
- In the absence of direct evidence, the approach to monitoring liver function in patients on fezolinetant should err on the side of caution, considering the potential for hepatotoxic effects observed with similar medications.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Liver Function Test Monitoring for Fezolinetant
- The frequency of liver function tests (LFTs), including liver enzymes, when initiating fezolinetant in a postmenopausal patient is not explicitly stated in the provided studies 2, 3, 4, 5, 6.
- However, the studies report on the safety and efficacy of fezolinetant, including its effects on liver enzymes 2, 5.
- In the SKYLIGHT 4 study, liver enzyme elevations more than three times the upper limit of normal occurred in 6 of 583 placebo, 8 of 590 fezolinetant 30 mg, and 12 of 589 fezolinetant 45 mg participants 2.
- The systematic review and meta-analysis found that hepatotoxicity showed a statistically insignificant, increasing trend in the fezolinetant group 5.
- Based on these findings, it is recommended to monitor liver function tests, including liver enzymes, in patients taking fezolinetant, although the exact frequency is not specified 2, 5.
Safety and Efficacy of Fezolinetant
- Fezolinetant has been shown to be effective in reducing the frequency and severity of vasomotor symptoms in postmenopausal women 3, 4, 5, 6.
- The safety profile of fezolinetant is generally favorable, with no significant differences in adverse events compared to placebo 3, 5.
- However, there is a potential risk of endometrial hyperplasia or tumors, and uterine bleeding had a lower incidence in the fezolinetant group 5.