What is Vyvanse (lisdexamfetamine)?

What is Vyvanse (Lisdexamfetamine)?

Vyvanse (lisdexamfetamine dimesylate) is a prodrug CNS stimulant that converts to dextroamphetamine after ingestion, FDA-approved for treating ADHD in patients 6 years and older and moderate to severe binge eating disorder in adults. 1

Mechanism of Action and Pharmacology

Lisdexamfetamine is pharmacologically inactive until enzymatically hydrolyzed in the blood to its active form, dextroamphetamine. 2, 1, 3 This unique prodrug design provides several clinical advantages:

• The active metabolite (dextroamphetamine) blocks reuptake of dopamine and norepinephrine into presynaptic neurons and increases release of these monoamines into the extraneuronal space 1, 3
• The parent drug lisdexamfetamine does not bind to dopamine or norepinephrine reuptake sites, requiring conversion to be active 1
• Rate-limited enzymatic hydrolysis provides a more gradual release of active drug, reducing abuse potential compared to immediate-release dextroamphetamine formulations 4, 5

FDA-Approved Indications

Vyvanse has two distinct approved uses 1:

• ADHD treatment in adults and pediatric patients 6 years and older, where it helps increase attention and decrease impulsiveness and hyperactivity 1
• Moderate to severe binge eating disorder (BED) in adults, where it reduces the number of binge eating days 1, 6

Important limitation: Vyvanse is NOT indicated or recommended for weight loss. Use of sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events 1

Dosing and Administration

For ADHD 1:

• Starting dose: 30 mg once daily in the morning
• Titration: Increase by 10-20 mg increments at approximately weekly intervals
• Maximum dose: 70 mg once daily

For Binge Eating Disorder 1:

• Starting dose: 30 mg once daily
• Titration: Increase by 20 mg increments at approximately weekly intervals
• Target dose: 50-70 mg once daily
• Maximum dose: 70 mg once daily

Administration options 1:

• Swallow capsules whole, OR
• Open capsules and mix entire contents with yogurt, water, or orange juice; consume immediately (do not store)
• Take in the morning with or without food; avoid afternoon doses due to insomnia risk
• Food prolongs time to peak concentration by approximately 1 hour but does not affect overall absorption 1

Pharmacokinetics

The prodrug design creates a predictable pharmacokinetic profile with low variability 1:

• Time to peak for lisdexamfetamine: approximately 1 hour post-dose 1
• Time to peak for active dextroamphetamine: approximately 3.5-4.4 hours post-dose 1
• Duration of action: approximately 12 hours 5
• Linear pharmacokinetics between 30-70 mg in pediatric patients and 50-250 mg in adults 1
• No drug accumulation at steady state 1

Abuse Potential and Controlled Substance Status

Vyvanse is a Schedule II federally controlled substance (CII) with high potential for abuse, misuse, and addiction 1:

• The prodrug formulation makes extraction of the stimulant component more difficult compared to other stimulant medications 2
• Misuse via unapproved routes (snorting, injection) still carries increased risk of overdose and death 1
• Pharmacodynamic studies show reduced likability compared to immediate-release dextroamphetamine, suggesting lower abuse potential 4
• Despite reduced abuse potential, strict distribution control and monitoring remain essential 3

Serious Warnings and Precautions

Cardiovascular Risks 1:

• Sudden death has occurred in patients with heart defects or serious heart disease
• Can cause increased blood pressure and heart rate
• Requires pre-treatment cardiac assessment (careful history, family history of sudden death or ventricular arrhythmia, physical exam)

Psychiatric Risks 1:

• Can cause new or worsening behavior and thought problems
• May precipitate new or worse bipolar illness
• Can cause new psychotic symptoms (hallucinations, delusions) or manic symptoms
• Requires assessment of psychiatric history before initiating treatment

Contraindications 1:

• Known hypersensitivity to amphetamine products (anaphylaxis, Stevens-Johnson Syndrome, angioedema, urticaria reported)
• Current MAOI use or within 14 days of stopping MAOIs (risk of hypertensive crisis)

Common Adverse Effects

The most frequently reported adverse effects include 1, 6, 7:

• Decreased appetite
• Insomnia
• Dry mouth
• Headache
• Irritability
• Dizziness
• Weight loss

Most adverse events are mild to moderate in severity and consistent with amphetamine class effects 3, 7

Special Populations

Renal Impairment 1:

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

Pregnancy 2, 1:

• Amphetamines cross the placental barrier 2
• May cause harm to the unborn baby 1
• Possible small increased risks for gastroschisis (aOR 3.0; 95% CI 1.2-7.4), preeclampsia (aRR 1.29; 95% CI 1.11-1.49), and preterm birth with second-half pregnancy use (aRR 1.30; 95% CI 1.10-1.55) 2
• Monitor infants for irritability, insomnia, and feeding difficulties if mother used amphetamines during pregnancy 2

Breastfeeding 1:

• Lisdexamfetamine passes into breast milk
• Should not breastfeed during treatment

Clinical Efficacy

Clinical trials demonstrate significant superiority over placebo in both approved indications 3, 6, 7:

• ADHD studies show reductions in ADHD rating scale scores by approximately 27 points in children and 19 points in adults 5
• BED studies show significantly greater reduction in binge eating days per week with 50-70 mg daily doses 6
• Long-term studies (up to 52 weeks) demonstrate sustained efficacy and markedly reduced risk of BED relapse compared to placebo 6