What are the appropriate indications, dosing regimens for children (≥6 years) and adults, contraindications, and monitoring parameters for Vyvanse (lisdexamfetamine dimesylate)?

Vyvanse (Lisdexamfetamine Dimesylate): Clinical Guide

Indications

Vyvanse is FDA-approved for ADHD in patients ≥6 years and for Binge Eating Disorder (BED) in adults. 1

ADHD

• Children ≥6 years, adolescents, and adults meeting DSM criteria for ADHD
• Either combined or hyperactive-impulsive subtypes 1

Binge Eating Disorder

• Adults with moderate to severe BED (≥3 binge days/week) 1

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Dosing Regimens

ADHD (Children ≥6 years, Adolescents, and Adults)

Start at 30 mg once daily in the morning and titrate weekly by 10-20 mg increments to a target of 30-70 mg/day. 1

Specific Protocol:

• Starting dose: 30 mg PO every morning
• Titration: Increase by 10-20 mg weekly based on response and tolerability
• Target dose range: 30-70 mg/day
• Maximum dose: 70 mg/day 1
• Administration: Take in the morning; can be swallowed whole or capsule opened and dissolved in water 1

Renal Impairment Adjustments:

• Severe renal impairment (GFR 15-29 mL/min): Maximum 50 mg/day
• End-stage renal disease (ESRD): Maximum 30 mg/day 1

Duration of Effect:

• Children: Up to 13 hours post-dose 2
• Adults: Up to 14 hours post-dose 2
• Efficacy demonstrated through 6 PM in pediatric studies 1, 3

Binge Eating Disorder (Adults Only)

Start at 30 mg once daily and titrate weekly by 20 mg to a target of 50-70 mg/day. 1

• Starting dose: 30 mg PO every morning
• Titration: Increase by 20 mg weekly
• Target dose range: 50-70 mg/day
• Maximum dose: 70 mg/day 1

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Contraindications

Absolute Contraindications

Do not prescribe Vyvanse in patients with active psychosis, concurrent MAO inhibitor use, or known hypersensitivity to amphetamine products. 4

1. Concomitant MAO inhibitor use (or within 14 days of discontinuation) - risk of hypertensive crisis and cerebrovascular accident 4

2. Active psychotic disorder - stimulants are psychotomimetic in schizophrenia, psychosis NOS, or manic episodes with psychosis 4

3. Known hypersensitivity to lisdexamfetamine or amphetamine products 4

Strong Relative Contraindications (Use with Extreme Caution):

• Symptomatic cardiovascular disease - assess cardiac status before initiating 4
• Glaucoma - sympathomimetics may increase intraocular pressure 4
• Hyperthyroidism 4
• Uncontrolled hypertension 4
• Recent stimulant abuse/dependence - requires controlled setting with close supervision 4

Conditions NOT Contraindicated (Despite Package Insert Warnings):

• Motor tics/Tourette's syndrome - controlled studies show methylphenidate does not worsen tics; amphetamines may have slightly greater effect but not absolute contraindication 4
• Controlled seizure disorder - can be used once seizures controlled with anticonvulsants 4
• Marked anxiety - not supported by recent evidence as absolute contraindication 4

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Pre-Treatment Assessment

Before initiating Vyvanse, obtain baseline vital signs (blood pressure, pulse, height, weight), perform cardiovascular screening, and assess for substance abuse history. 4

Required Baseline Evaluations:

1. Cardiovascular assessment:

   • Blood pressure and pulse
   • Screen for symptomatic cardiovascular disease
   • Consider ECG if cardiac risk factors present 4

2. Growth parameters:

   • Height and weight (establish baseline for monitoring) 4

3. Psychiatric screening:

   • Active psychosis (absolute contraindication)
   • Substance abuse history (especially in adolescents) 5
   • Mood instability 4

4. Medical history:

   • Glaucoma, hyperthyroidism, hypertension
   • Seizure disorder status
   • Renal function (adjust dose if impaired) 4, 1

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Monitoring Parameters

During Titration Phase (Weeks 1-4):

Monitor weekly via phone or office visit for symptom response using ADHD rating scales and systematic side effect assessment. 4

• Weekly contact (phone or visit) during dose adjustments 4
• ADHD Rating Scale from parents and teachers (or self-report for adults) 4
• Side effects: Systematically ask about appetite, insomnia, headaches, irritability, abdominal pain, tics 4
• Weight: At each visit to objectively assess appetite suppression 4

Maintenance Phase:

Once stabilized, monitor monthly initially, then quarterly for adults, with annual comprehensive assessments for children. 4

Children and Adolescents:

• Monthly visits until symptoms stabilized 4
• Vital signs annually during routine physical examination 4
• Height and weight at each visit 4
• ADHD symptom ratings from parents and teachers regularly 4

Adults:

• Blood pressure and pulse quarterly (by treating or primary care physician) 4
• ADHD symptom ratings from patient and significant other 4
• Monitor for tolerance if higher doses required 4

Specific Monitoring for Adolescents:

• Screen for diversion/misuse - monitor prescription refill requests 5
• Driving coverage - ensure medication covers afternoon/evening hours 5

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Common Adverse Effects

The most frequent side effects are decreased appetite (39%), insomnia (19%), upper abdominal pain (12%), and headache (12%), most occurring in the first week and being mild to moderate. 3

Incidence >10% (vs. Placebo):

• Decreased appetite: 39% vs. 4% 3
• Insomnia: 19% vs. 3% 3
• Upper abdominal pain: 12% vs. 6% 3
• Headache: 12% vs. 10% 3

Incidence 5-10%:

• Irritability: 10% vs. 0% 3
• Vomiting: 9% vs. 4% 3
• Weight decrease: 9% vs. 1% 3
• Nausea: 6% vs. 3% 3
• Diarrhea: Significant increase (RR = 4.06) 6

Management Strategies:

• Most adverse effects are mild to moderate and transient, occurring primarily in week 1 3
• Appetite suppression: Monitor weight at each visit; consider dose reduction if significant weight loss 4
• Insomnia: Ensure morning dosing; avoid late-day doses 4
• Cardiovascular effects: Mean changes minimal (-1.1 mmHg systolic, +1.5 mmHg diastolic) 7

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Clinical Efficacy Data

ADHD:

• Children (6-12 years): ADHD-RS-IV score reductions of 15.6 to 20.5 points vs. placebo (all doses p<0.001) 1
• Adolescents (13-17 years): ADHD-RS-IV score reductions of 5.5 to 8.3 points vs. placebo 1
• Adults: ADHD-RS-IV score reductions of 8.0 to 10.4 points vs. placebo 1
• Response rate: ~70% respond to first stimulant; ~90% respond if both amphetamine and methylphenidate classes tried 4

Duration of Action:

• Efficacy maintained throughout school day up to 6 PM based on parent ratings 1, 3
• Improvements observed within first week of treatment 1

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Special Populations

Preschool Children (4-5 years):

• Off-label use - limited data but Phase 2 study shows tolerability 7
• Starting dose: 5 mg (lower than standard 30 mg) 7
• Titration: More gradual, up to 30 mg maximum 7
• Package insert warns against use <6 years, though evidence emerging 4

Adolescents:

• Screen for substance abuse before initiating 5
• Monitor for diversion - consider formulations with lower abuse potential 5
• Ensure driving coverage - use longer-acting or afternoon short-acting supplementation 5

Adults:

• Same dosing as children/adolescents (30-70 mg/day) 1
• May require higher total daily doses to cover longer workday, up to 65 mg MPH equivalent or 40 mg amphetamine equivalent 4
• Quarterly blood pressure/pulse monitoring required 4

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Prodrug Pharmacology

Lisdexamfetamine is a therapeutically inactive prodrug that is enzymatically hydrolyzed in the blood to active d-amphetamine, providing consistent plasma levels and potentially reduced abuse liability. 8, 2

• Conversion: Rate-limited hydrolysis primarily in blood (not GI tract) 8, 2
• Tmax: 4.0-4.2 hours 7
• Half-life: 7.2-8.5 hours 7
• Abuse potential: Lower drug-liking scores vs. immediate-release d-amphetamine at equivalent doses 8
• Tampering resistance: Cannot be activated by crushing, snorting, or injection 5

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Key Clinical Pearls

• Lisdexamfetamine provides 13-14 hours of symptom control with once-daily dosing, eliminating need for school-day administration 2
• Start all patients at 30 mg regardless of age (except preschoolers and renal impairment) 1
• Efficacy appears within first week; if no response by week 4 at maximum dose, consider alternative stimulant 1
• Approximately 90% of ADHD patients respond if both methylphenidate and amphetamine classes are tried 4
• Cardiovascular effects are minimal in clinical trials but require baseline and ongoing monitoring 4
• Weight loss is common (9% incidence) - monitor at every visit 3