What is the recommended use and dosage of Lisdexamfetamine (Vyvanse) for attention deficit hyperactivity disorder (ADHD)?

Lisdexamfetamine (Vyvanse) for ADHD: Recommended Use and Dosage

Primary Recommendation

Start lisdexamfetamine at 30 mg once daily in the morning for both adults and pediatric patients 6 years and older, with weekly dose adjustments of 10-20 mg increments up to a maximum of 70 mg daily. 1

Indications and Patient Selection

• Lisdexamfetamine is FDA-approved for ADHD treatment in adults and children 6 years and older 1
• Use stimulants like lisdexamfetamine as first-line therapy for ADHD, though approval status varies by country (first-line in the United States, second-line in many European countries) 2
• If methylphenidate fails to provide adequate benefit after appropriate dosage and duration, lisdexamfetamine should be the preferred next option over non-stimulants 2
• Lisdexamfetamine may be particularly preferred in adolescents due to its lower abuse potential compared to other stimulants, as the prodrug formulation makes extraction of the stimulant component more difficult 3

Dosing Protocol

Starting Dose

• Begin with 30 mg orally once daily in the morning 1, 3
• Alternative starting dose of 20 mg may be considered in some patients 3
• Administer with or without food 1
• Avoid afternoon doses due to insomnia risk 1

Dose Titration

• Increase by 10 mg or 20 mg increments at approximately weekly intervals 1
• Maximum recommended dose is 70 mg once daily 1, 3
• Titration should be guided by symptom response and tolerability 4

Special Populations: Renal Impairment

• Severe renal impairment (GFR 15 to <30 mL/min/1.73 m²): maximum 50 mg daily 1
• End-stage renal disease (GFR <15 mL/min/1.73 m²): maximum 30 mg daily 1

Administration Methods

Lisdexamfetamine can be administered in two ways 1:

1. Swallow capsules whole, or
2. Open capsules and mix entire contents with yogurt, water, or orange juice:
   • Use a spoon to break apart any compacted powder 1
   • Mix until completely dispersed 1
   • Consume the entire mixture immediately—do not store 1
   • A film containing inactive ingredients may remain after consumption 1

• Do not divide a single dose; take at least one full capsule or chewable tablet per day 1

Mechanism and Duration of Action

• Lisdexamfetamine is a prodrug that requires enzymatic hydrolysis (predominantly by red blood cells) to convert to the active d-amphetamine 5, 4
• This rate-limiting conversion reduces abuse liability and overdose potential compared to immediate-release amphetamines 6
• Provides efficacy for a full treatment day, with demonstrated effectiveness up to 14 hours post-dose in adults 5
• In children, efficacy extends through 6 PM based on parent ratings 4

Efficacy Evidence

Pediatric Patients (6-12 years)

• Significant improvements in ADHD Rating Scale Version IV (ADHD-RS-IV) scores compared to placebo (P < 0.001) 4
• Improvements in behavioral measures including Swanson, Kotkin, Agler, M-Flynn, and Pelham deportment subscales (P < 0.001) 4
• Long-term studies (up to 12 months) showed >60% improvement from baseline in ADHD-RS-IV (P < 0.001) 4

Adult Patients

• All doses (30,50, and 70 mg) showed significant improvements in ADHD-RS scores at endpoint (P < 0.001 for all doses) 4
• Improvements observed within the first week of treatment across all active treatment arms 4

Pretreatment Screening Requirements

Before initiating lisdexamfetamine, assess 1:

1. Cardiac disease: Obtain careful personal and family history of sudden death or ventricular arrhythmia, and perform physical examination
2. Tic disorders: Evaluate family history and clinically assess for motor or verbal tics or Tourette's syndrome

Common Adverse Effects

The most frequently reported adverse events include 1, 4:

• Decreased appetite
• Insomnia
• Upper abdominal pain
• Headache
• Irritability
• Weight loss
• Nausea
• Dry mouth 7

Most adverse events are mild to moderate in intensity and consistent with the amphetamine class profile 7, 4

Critical Safety Warnings

Abuse and Misuse Potential

• Lisdexamfetamine has high potential for abuse and misuse despite its prodrug formulation 1
• Educate patients and families about proper storage and disposal of unused medication 1
• Monitor regularly for signs of abuse, misuse, and addiction throughout treatment 1
• Lisdexamfetamine is a controlled substance 2

Cardiovascular Monitoring

• Monitor blood pressure and heart rate regularly, as stimulants can cause cardiovascular effects 2
• Assess for cardiac disease before initiating treatment 1

Weight and Growth Monitoring

• Pediatric patients younger than 6 years experience more long-term weight loss than older patients 1
• Lisdexamfetamine is not indicated for weight loss; use of sympathomimetics for weight loss has been associated with serious cardiovascular adverse events 1

Drug Interactions Requiring Dose Adjustment

Agents that alter urinary pH significantly impact amphetamine blood levels 1:

• Acidifying agents (e.g., ascorbic acid) decrease blood levels—may require dose increase 1
• Alkalinizing agents (e.g., sodium bicarbonate) increase blood levels—may require dose decrease 1

Contraindicated Combinations

• Do not use with MAOIs or within 14 days of stopping MAOIs due to hypertensive crisis risk 1
• This includes linezolid and intravenous methylene blue 1

Treatment Adjustments and Individualization

• Adjustment and changes to the pharmacological regimen are the rule, not the exception 2
• Consider severity of symptoms, presence of comorbidities, periods of day requiring symptom relief, and patient preferences 2
• Changes may be needed due to symptomatology shifts, psychosocial situation changes, or normal development (e.g., weight gain) 2
• Different extended-release stimulant formulations allow for individualization when needed 2

Available Formulations

Lisdexamfetamine capsules are available in 1:

• 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg strengths
• Chewable tablets available as alternative (can substitute on mg-per-mg basis) 1