Monitoring CMP After Starting Fezolinetant
After starting fezolinetant for vasomotor symptoms, a Comprehensive Metabolic Panel (CMP) should be checked at baseline, 1-2 months after initiation, and then every 3-4 months thereafter.
Rationale for CMP Monitoring
Fezolinetant is a neurokinin 3 receptor antagonist approved for the treatment of moderate-to-severe vasomotor symptoms (hot flashes) associated with menopause. While the medication has demonstrated efficacy in reducing hot flash frequency and severity 1, 2, monitoring of liver function is important due to the potential for liver enzyme elevations.
Key monitoring considerations:
- Baseline testing: A CMP should be obtained before starting fezolinetant to establish baseline values
- Initial follow-up: Repeat CMP 1-2 months after starting therapy
- Ongoing monitoring: Continue CMP monitoring every 3-4 months during treatment
Evidence for Liver Monitoring
In clinical trials, liver enzyme elevations were observed in a small percentage of patients taking fezolinetant:
- In the SKYLIGHT 4 safety study, liver enzyme elevations >3× upper limit of normal occurred in 8 of 590 patients (1.4%) taking fezolinetant 30 mg and 12 of 589 patients (2.0%) taking fezolinetant 45 mg, compared to 6 of 583 (1.0%) in the placebo group 3
- These elevations were generally asymptomatic, transient, and resolved while on treatment or after discontinuation 1
- No cases of severe drug-induced liver injury (Hy's law cases) were reported 3
Monitoring Protocol
Based on established monitoring practices for medications with potential liver effects:
Baseline assessment:
- Complete CMP before starting fezolinetant
- Pay particular attention to liver function tests (AST, ALT, bilirubin)
Follow-up monitoring:
- First follow-up CMP: 1-2 months after initiation
- Subsequent monitoring: Every 3-4 months
Management of abnormal results:
- For AST/ALT >3× ULN: Consider temporary withholding of medication
- For AST/ALT >5× ULN: Consider permanent discontinuation
- Any elevation with symptoms: Evaluate promptly and consider discontinuation
Additional Considerations
- Patient education: Inform patients about potential signs of liver dysfunction (jaundice, right upper quadrant pain, fatigue, nausea)
- Risk factors: More frequent monitoring may be appropriate for patients with pre-existing liver disease or concomitant hepatotoxic medications
- Duration: Continue monitoring throughout treatment course
This monitoring approach aligns with standard practices for medications with potential hepatic effects, providing appropriate surveillance while minimizing unnecessary testing.