What is Vyvanse (lisdexamfetamine) and what are its side effects?

What is Vyvanse (Lisdexamfetamine)?

Vyvanse (lisdexamfetamine) is a prodrug stimulant medication approved for treating ADHD in children 6 years and older and adults, which works by converting to dextroamphetamine after ingestion through enzymatic hydrolysis in the blood. 1

Mechanism of Action

• Lisdexamfetamine is therapeutically inactive until it is enzymatically hydrolyzed in the blood to release active dextroamphetamine 2, 3
• The active dextroamphetamine increases dopamine and norepinephrine activity in frontal lobe pathways, improving executive function and attention in ADHD patients 4
• It works by competitively inhibiting dopamine and noradrenaline transporters, increasing neurotransmitter concentrations in the synaptic cleft, and also promotes release of these neurotransmitters from neuronal cells 2

Clinical Use and Dosing

• The recommended starting dose is 20-30 mg once daily in the morning, with or without food 5, 1
• Titration typically involves increasing by 10 mg weekly to a maximum of 70 mg daily 5
• The medication provides approximately 12-13 hours of symptom control in children and 14 hours in adults 6
• Lisdexamfetamine may be preferred in adolescents due to lower abuse potential compared to other stimulants, as it requires enzymatic conversion and makes extraction more difficult 7, 5

Common Side Effects

The most frequently reported side effects in children and adults include:

In Children (6-17 years) with ADHD:

• Loss of appetite (anorexia) 1
• Decreased appetite 1
• Anxiety 1
• Insomnia/trouble sleeping 1
• Irritability 1
• Nausea, vomiting, stomach pain, and diarrhea 1
• Weight loss 1
• Dizziness and dry mouth 1

In Adults with ADHD:

• Decreased appetite 1
• Dry mouth 1
• Insomnia 1
• Anxiety 1
• Dizziness 1

Most adverse events are mild to moderate in severity and transient in nature 6, 8

Serious Side Effects and Warnings

Cardiovascular Risks:

• Sudden death has occurred in patients with heart defects or serious heart disease 1
• Increased blood pressure and heart rate require regular monitoring 1
• Peripheral vasculopathy (including Raynaud's phenomenon) can cause fingers or toes to feel numb, cool, painful, or change color 1

Psychiatric Effects:

• New or worsening behavior and thought problems 1
• New or worsening bipolar illness 1
• New psychotic symptoms (hearing voices, seeing or believing things that are not real) 1
• New manic symptoms 1

Growth Effects:

• Slowing of growth (height and weight) in children requires regular monitoring during treatment 1

Serotonin Syndrome:

• A potentially life-threatening condition can occur when combined with other serotonergic drugs (SSRIs, SNRIs, MAOIs, etc.) 1
• Symptoms include agitation, hallucinations, confusion, rapid heart rate, high body temperature, lack of coordination, nausea, vomiting, and diarrhea 1

Tics and Tourette's Syndrome:

• New or worsening motor and verbal tics may occur during treatment 1

Abuse and Dependence Potential

• Lisdexamfetamine is a Schedule II controlled substance with high potential for abuse, misuse, and addiction 1
• The prodrug design provides some protection against abuse, as it requires enzymatic conversion and produces less "drug liking" effects when taken inappropriately compared to immediate-release amphetamines 1, 3
• Physical dependence can develop with prolonged use, and withdrawal symptoms (dysphoric mood, depression, fatigue, vivid dreams, insomnia or hypersomnia, increased appetite) may occur after abrupt discontinuation 1

Special Populations

Pregnancy:

• Amphetamines cross the placental barrier 5
• Possible increased risk for gastroschisis and preeclampsia, though risks appear small 5
• Continued use in second half of pregnancy may increase risk of preterm birth 5
• Infants should be monitored for irritability, insomnia, and feeding difficulties if mother took amphetamines during pregnancy 5

Breastfeeding:

• Women should not breastfeed while taking lisdexamfetamine 1

Renal Impairment:

• Maximum dose should not exceed 50 mg/day in severe renal impairment (GFR 15 to <30 mL/min/1.73 m²) 1
• Maximum dose is 30 mg/day in end-stage renal disease (GFR <15 mL/min/1.73 m²) 1
• The drug is not dialyzable 1

Important Clinical Considerations

• Screen for cardiovascular disease and family history of sudden cardiac death before initiating treatment 1
• Assess for substance abuse history, particularly in adolescents, as diversion is a concern 7
• Monitor blood pressure, heart rate, growth parameters, and psychiatric symptoms regularly during treatment 1
• The capsule can be swallowed whole or opened and mixed with yogurt, water, or orange juice if swallowing is difficult; the mixture must be consumed immediately 1