How should Vyvanse (lisdexamfetamine) be dosed and monitored in patients with impaired renal function (creatinine clearance ≥30 mL/min and <30 mL/min)?

Vyvanse Dosing in Decreased Kidney Function

In patients with severe renal impairment (GFR 15 to <30 mL/min/1.73 m²), the maximum Vyvanse dose is 50 mg once daily; in end-stage renal disease (GFR <15 mL/min/1.73 m²), the maximum dose is 30 mg once daily. 1

Dosing Algorithm Based on Renal Function

Step 1: Calculate Creatinine Clearance or GFR

• Obtain creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) before initiating Vyvanse 1, 2
• Use the Cockcroft-Gault equation for drug dosing decisions, as pharmacokinetic studies historically used this method rather than eGFR equations 3
• Reassess renal function if clinical status changes (dehydration, acute illness, introduction of nephrotoxic medications) 4

Step 2: Apply Renal-Adjusted Maximum Doses

Normal to Mild Renal Impairment (GFR ≥30 mL/min/1.73 m²):

• Standard dosing applies: start at 30 mg once daily in the morning 1
• May titrate in 10-20 mg increments at weekly intervals 1
• Maximum dose: 70 mg once daily 1

Severe Renal Impairment (GFR 15 to <30 mL/min/1.73 m²):

• Start at 30 mg once daily 1
• Maximum dose: 50 mg once daily 1
• Do not exceed this ceiling regardless of clinical response 1

End-Stage Renal Disease (GFR <15 mL/min/1.73 m²):

• Start at 30 mg once daily 1
• Maximum dose: 30 mg once daily 1
• This applies whether or not the patient requires hemodialysis 1

Step 3: Monitor for Prolonged Drug Exposure

• D-amphetamine (the active metabolite of lisdexamfetamine) exposure increases as renal impairment worsens 5
• Peak concentrations (Cmax) of D-amphetamine decrease but total exposure (AUC) increases significantly with declining renal function 5
• This prolonged exposure necessitates the dose caps to prevent accumulation and toxicity 5

Pharmacokinetic Rationale

The dose restrictions are based on altered drug disposition in renal impairment:

• Lisdexamfetamine (the prodrug) shows minimal accumulation in mild-to-moderate renal impairment, but patients with ESRD have higher Cmax and AUC than those with normal function 5
• D-amphetamine (active metabolite) demonstrates progressively increased total exposure (AUC) as renal function declines, with the most pronounced effect in severe impairment and ESRD 5
• The prolonged D-amphetamine exposure creates risk for dose-dependent adverse effects including cardiovascular complications, insomnia, and psychiatric symptoms 1, 5

Hemodialysis Considerations

Neither lisdexamfetamine nor D-amphetamine is dialyzable:

• Almost no lisdexamfetamine and minimal D-amphetamine were recovered in dialyzate during hemodialysis 5
• Do not administer supplemental doses after dialysis sessions 5
• The 30 mg maximum daily dose applies to all ESRD patients regardless of dialysis status 1

Critical Pitfalls to Avoid

Do not use standard dosing in renal impairment:

• Failure to adjust doses in severe renal impairment or ESRD will result in excessive D-amphetamine accumulation and increased risk of cardiovascular events, hypertension, and psychiatric adverse effects 1, 5

Do not assume dialysis removes the drug:

• Unlike many renally eliminated medications, Vyvanse and its active metabolite are not cleared by hemodialysis 5
• The dose cap of 30 mg daily in ESRD applies even with regular dialysis 1

Do not overlook elderly patients:

• Elderly patients are at higher risk for unrecognized renal impairment 6
• Always calculate creatinine clearance rather than relying on serum creatinine alone, as elderly patients may have reduced muscle mass leading to falsely reassuring creatinine values 2

Do not forget to reassess renal function:

• Renal function can change during hospitalization or acute illness 6
• Deterioration in renal function requires dose reduction to maintain the appropriate renal-adjusted maximum 4, 6

Administration Guidance

• Administer once daily in the morning with or without food 1
• Avoid afternoon doses due to insomnia risk 1
• May open capsules and mix contents with yogurt, water, or orange juice if swallowing is difficult; consume entire mixture immediately 1
• Do not divide a single capsule—one capsule represents the minimum daily dose 1

Drug Interactions Affecting Renal Dosing

• Urinary acidifying agents (e.g., ascorbic acid) decrease amphetamine blood levels, while alkalinizing agents (e.g., sodium bicarbonate) increase levels 1
• Adjust Vyvanse dosage accordingly when these agents are used, but never exceed the renal-adjusted maximum dose 1