What is the recommended dose of everolimus (RAD001) post liver transplant?

Everolimus Dosing Post Liver Transplantation

The recommended starting dose of everolimus post liver transplantation is 5 mg daily for adults, with subsequent dose adjustments based on side effects and efficacy, while maintaining trough levels between 3-8 ng/ml. 1

Dosing Recommendations

Adult Patients

• Initial dose: 5 mg daily 1
• Target trough levels: 3-8 ng/ml, with 6-8 ng/ml considered optimal for most patients 2, 3
• Maximum trough level: Should not exceed 15 ng/ml 1

Pediatric Patients

• Initial dose: 2.5 mg/m² 1
• Target trough levels: Same as adults (3-8 ng/ml)

Monitoring and Dose Adjustment

When to Check Levels

• Obtain everolimus trough levels in cases of:
  • Safety concerns
  • Suspected adherence problems
  • Observed lack of efficacy 1

Dose Adjustment Algorithm

1. Start with recommended initial dose
2. Check trough levels 5-7 days after initiation (steady state is reached within 7 days) 2
3. Adjust dose based on:
   • If levels <3 ng/ml: Increase dose by 0.5-1 mg
   • If levels >8 ng/ml: Decrease dose by 0.5-1 mg
   • If mild adverse events (grade 1-2): Adjust dose before considering discontinuation 1

Special Considerations

Combination with Calcineurin Inhibitors

• When used with tacrolimus:
  • Tacrolimus trough levels should be reduced to 4-6 ng/ml (if monotherapy) or lower if combined with everolimus 1
  • Consider tacrolimus dose reduction by 30-50% when initiating everolimus

Timing of Introduction

• Everolimus can be safely introduced as early as day 7 post-transplantation 1
• Early introduction with tacrolimus minimization may be beneficial for preserving renal function 4

Drug Interactions

• Reduce everolimus dose by approximately 50% when co-administered with azoles or erythromycin 3
• Increase dose by 100-200% when given with rifampicin 3
• Monitor for interactions with other CYP3A4 inhibitors/inducers 2

Specific Clinical Scenarios

Renal Dysfunction

• Everolimus with reduced tacrolimus is recommended for patients with post-transplant renal dysfunction 1, 4
• Consider complete conversion to CNI-free everolimus-based regimen in patients with significant renal impairment 1

Hepatic Impairment

• Reduce everolimus dose by 50% in patients with hepatic impairment 2

Cancer Risk

• Everolimus is preferred in patients with history of hepatocellular carcinoma or at high risk of malignancy 1, 5

Common Adverse Effects to Monitor

• Dyslipidemia (check lipid panel regularly)
• Wound complications (higher incidence of incisional hernia)
• Infections
• Thrombocytopenia and leukocytopenia 2, 4, 5

Pitfalls and Caveats

1. Avoid using mTOR inhibitors (including everolimus) when using the combination of ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir for HCV treatment 1
2. Individualized dosing schemes may be required, including consideration of intermittent treatment in some patients 1
3. Everolimus has variable oral bioavailability, making blood concentration monitoring essential 2
4. Patients with poor clinical condition or prolonged ICU stay post-transplant typically require lower immunosuppressive doses 1

By following these guidelines, clinicians can optimize everolimus therapy post liver transplantation while minimizing adverse effects and maintaining adequate immunosuppression.