Can we prescribe Zolfresh (zolpidem) to a female patient with heart failure?

Can Zolfresh (Zolpidem) Be Prescribed to a Female Patient with Heart Failure?

Zolpidem should be avoided in female patients with heart failure due to significantly increased risks of heart failure rehospitalization, cardiovascular death, and adverse cardiac events, with women being particularly vulnerable to higher drug concentrations and adverse effects.

Evidence Against Prescribing Zolpidem in Heart Failure

Cardiovascular Outcomes in Heart Failure Patients

• Z-drugs (including zolpidem) are associated with a 21% increased risk of the composite endpoint of HF rehospitalization and cardiovascular death (adjusted sub-distribution hazard ratio: 1.21,95% CI: 1.18-1.24) in patients with heart failure 1

• Specific risks include:

  • 21% higher risk of heart failure rehospitalization (SHR: 1.21,95% CI: 1.17-1.24) 1
  • 11% higher risk of cardiovascular death (SHR: 1.11,95% CI: 1.07-1.15) 1
  • 15% higher risk of all-cause mortality (HR: 1.15,95% CI: 1.11-1.18) 1

• A duration-dependent relationship exists, with worse outcomes in long-term use compared to short-term use 1

• Zolpidem can trigger atrial fibrillation in patients with cardiomyopathy, as demonstrated in a case report where a patient with Duchenne muscular dystrophy-related cardiomyopathy developed new-onset AF after zolpidem use 2

Sex-Specific Vulnerabilities in Women

• Women have significantly higher serum zolpidem concentrations than men after 8 hours: 28 vs. 20 ng/mL for 10mg immediate-release and 33 vs. 28 ng/mL for 12.5mg modified-release formulations 3

• Women experience more frequent and severe adverse drug reactions (ADRs) than men (approximately 1.5 times higher risk) and are more likely to discontinue treatment due to ADRs 4

• Women with heart failure have altered pharmacokinetics:

  • Decreased volume of distribution for hydrophilic drugs, reaching higher peak plasma levels 4
  • Increased activity of CYP3A4 (which metabolizes zolpidem), but overall higher drug exposure 4
  • Lower estimated glomerular filtration rate, causing drugs to be cleared more slowly 4

Additional Safety Concerns

• Central nervous system adverse effects are common (80.8% of ADRs in patients aged 50 or older), including confusion, dizziness, and daytime sleepiness 3

• Increased fall risk with an odds ratio of 4.28 (P <0.001) when prescribed short-term for insomnia 3

• Hip fracture risk is elevated with a relative risk of 1.92 (95% CI 1.65-2.24; P<0.001) 3

• Complex behaviors including sleepwalking, hallucinations, and increased suicidality (OR 2.08; 95% CI 1.83-2.63) have been documented 3, 5

Clinical Recommendation

Do not prescribe zolpidem (Zolfresh) to this female patient with heart failure. The evidence demonstrates clear harm with increased cardiovascular morbidity and mortality, compounded by sex-specific pharmacokinetic differences that place women at higher risk for adverse effects 1, 3, 4.

Alternative Approach

• Consider non-pharmacological interventions first: cognitive behavioral therapy for insomnia, which is effective without cardiovascular risk 3

• If pharmacotherapy is absolutely necessary, consult cardiology and consider alternatives with better safety profiles in heart failure, though the evidence base for safer alternatives in this specific population remains limited 6

• Women with heart failure already experience higher rates of ADRs with guideline-recommended heart failure drugs and require careful medication management 4