What alternative treatments are recommended for an elderly female patient with stage 3a chronic kidney disease (CKD) and persistent hot flashes despite being on Voezah (conjugated estrogens)

Alternative Management for Persistent Hot Flashes in Stage 3a CKD

Veozah (fezolinetant) should be discontinued and replaced with low-dose SSRIs or SNRIs as first-line alternatives, specifically paroxetine CR 12.5 mg daily or venlafaxine 37.5-75 mg daily, as these have the strongest evidence for efficacy in treating vasomotor symptoms and are safer than estrogen-based therapies in patients with renal impairment. 1, 2

Critical Medication Considerations in Stage 3a CKD

• Estrogen-based therapies like DUAVEE (conjugated estrogens/bazedoxifene) carry specific warnings against use in renal impairment. The FDA label explicitly states: "Use of DUAVEE in patients with renal impairment is not recommended" due to concerns about fluid retention and altered pharmacokinetics 2

• Estradiol pharmacokinetics are significantly altered in CKD, with free and total estradiol plasma concentrations being higher in women with kidney disease, suggesting at minimum a 50% dose reduction would be needed if estrogen therapy were continued 3

• However, given the FDA contraindication and fluid retention risks in a patient with already compromised kidney function, discontinuation rather than dose adjustment is the appropriate action 2

First-Line Non-Hormonal Alternatives

SSRIs/SNRIs (Preferred Option)

Paroxetine controlled-release is the most evidence-based choice:

• Paroxetine CR 12.5-25 mg daily reduces hot flash composite scores by 62-65% compared to placebo in menopausal women, including breast cancer survivors 1
• The 12.5 mg CR dose is optimal, balancing efficacy with minimizing dose-related side effects 1
• Side effects (headache, nausea, reduced appetite) are commonly mild and short-lived, with only 10-20% discontinuation rates 1

Venlafaxine is an equally effective alternative:

• Venlafaxine 37.5-75 mg daily has been extensively tested in breast cancer survivors with comparable efficacy to paroxetine 1
• Consider starting at 37.5 mg and titrating to 75 mg based on response and tolerability 1

Other SSRI options with evidence:

• Citalopram has shown benefit and may be tried if venlafaxine fails, though long-term efficacy beyond 9 months is less established 1
• Fluoxetine decreased hot flash scores by 50% versus 36% for placebo, though with marked variability (27% had worse symptoms) 1

Important SSRI/SNRI Considerations

• These agents should be stopped gradually to prevent discontinuation symptoms, particularly with short-acting agents like paroxetine and venlafaxine 1
• The mechanism of action for hot flash reduction appears independent and more rapid than antidepressant effects 1
• Optimal treatment duration is unknown; reassess response at 4-6 weeks 1
• Some women (up to 27% in studies) may experience exacerbation of vasomotor symptoms 1

Second-Line Alternatives

Gabapentin

• Consider if SSRIs/SNRIs are ineffective or not tolerated 1
• Requires dose adjustment for stage 3a CKD (eGFR 45-59 mL/min/1.73 m²) 4
• Monitor for sedation and dizziness, which may be more pronounced with renal impairment

Clonidine

• Less effective than SSRIs but may provide modest benefit 1
• Monitor blood pressure carefully, especially given CKD-related cardiovascular risk 1, 4

Critical CKD Management Priorities to Address Concurrently

Cardiovascular risk reduction must be prioritized as cardiovascular disease is the leading cause of mortality in CKD:

• Initiate statin therapy immediately if not already prescribed: Adults ≥50 years with eGFR <60 mL/min/1.73 m² (stage 3a) should receive a statin or statin/ezetimibe combination (strong recommendation, 1A) 1

• Blood pressure control: Continue or optimize ACE inhibitor or ARB therapy unless contraindicated, as these provide nephroprotection in CKD 1

• Consider SGLT2 inhibitor: For adults with eGFR 20-45 mL/min/1.73 m² and albuminuria <200 mg/g, SGLT2 inhibitors are suggested (2B recommendation); for those with albuminuria ≥200 mg/g or heart failure, they are strongly recommended (1A) 1

Monitoring and Follow-up

• Reassess hot flash frequency and severity at 4-6 weeks after initiating SSRI/SNRI therapy 1
• Monitor kidney function (eGFR and creatinine) regularly as recommended for stage 3a CKD, typically every 6-12 months if stable 1, 4
• Screen for CKD complications: Monitor potassium, bicarbonate, phosphate, and hemoglobin as stage 3a CKD can be associated with metabolic abnormalities 1

Common Pitfalls to Avoid

• Never continue estrogen-based therapy in patients with renal impairment despite persistent symptoms; the FDA explicitly contraindicates this 2
• Do not assume all hot flash treatments are equally safe in CKD—always verify renal dosing and contraindications 1, 4
• Avoid NSAIDs completely for any concurrent pain or inflammatory conditions, as these significantly increase acute kidney injury risk in stage 3a CKD 5, 6
• Do not overlook cardiovascular risk management while focusing solely on symptom control—CKD patients require comprehensive cardiovascular protection 1, 4
• Recognize the robust placebo response (up to 70% in some studies) when counseling patients about expected treatment effects 1