Generic Name

prodrug

Mechanism

• Prodrug conversion – Lisdexamfetamine is inactive until it is cleaved in the bloodstream by red‑cell esterases, yielding dextroamphetamine.
• Central catecholamine release – Dextroamphetamine increases synaptic dopamine and norepinephrine by reversing transporter flux and inhibiting reuptake.
• Pharmacologic effect – Augmented catecholamine levels enhance attention, executive function, and inhibitory control; the gradual conversion also limits abuse potential.

Pharmacokinetics

• Absorption – Oral; peak concentrations (~3–6 hr) after first‑pass metabolism; bioavailability ≈ 100 % once activated.
• Metabolism – Non‑enzymatic hydrolysis of the leucine ester by monoamine‑amino‑acid oxidase and red‑cell esterases; no major CYP involvement.
• Half‑life – Active metabolite elimination half‑life 10–13 hr; steady‑state achieved after 5–7 days.
• Excretion – 90 % renal; primarily as unchanged amphetamine and its metabolites; unchanged drug in urine ≈ 3–5 % of dose.
• Food effect – No clinically relevant interaction; patients may take with or without food.

Indications

• Central nervous system
• ADHD in patients ≥ 6 yr (prescribing info: 6–12 yr for non‑short‑acting, 12–18 yr for short‑acting).
• ADHD in adults (≥ 18 yr).
• Gastroenterology
• Moderate to severe eating disorder (BED) in adults, with ≥ 4 binge episodes per week for ≥ 6 mo and BMI ≥ 25 kg/m² or ≥ 27 kg/m² with comorbid conditions.

Contraindications

• Contraindicated
• Uncontrolled hypertension, tachyarrhythmias, pre‑existing cardiac disease, pylorospasm, and pheochromocytoma.
• Current use of monoamine oxidase inhibitors (within 14 days).
• Severe liver/renal impairment (dose adjustments required).
• Warnings
• Cardiovascular – Monitor blood pressure (BP) and heart rate (HR); risk of ischemic events in predisposed individuals.
• Psychiatric – Potential for mania, panic attacks, agitation, or severe anxiety; caution in patients with a history of psychosis or substance abuse.
• Growth – Potential impact on height/wt in children; requires serial growth assessment.
• Abuse potential – Classified as Schedule II; prodrug design decreases “rush” but abuse in vulnerable populations still possible.

Dosing

• Starting dose – 30 mg once daily (for children 6‑12 yr) or 30 mg once daily (for 12‑18 yr) with gradual titration by 10–20 mg increments every 3–5 days.
• Maintenance – 30–70 mg/day; 70 mg/day maximum per label.
• Adults with ADHD – 30–70 mg/day; for BED 30–70 mg/day.
• Pediatric population – Titrate to effect or tolerability; reassess growth and weight at each visit.
• Formulation – Oral capsules with delayed release; take in the morning to reduce insomnia.

Adverse Effects

• Common
• Decreased appetite → weight loss
• Insomnia, irritability
• Dry mouth, headache, nausea, dizziness
• Palpitations, tachycardia
• Serious
• Hypertension or ischemic cardiovascular events
• Serotonergic syndrome in combination with other serotonergic agents
• Severe psychiatric reactions (manic, psychotic)
• Acute angle‑closure glaucoma (rare)
• Rarely, serious skin reactions (Stevens–Johnson syndrome)

Monitoring

• Baseline & periodic – Weight, BMI, height (children), BP, HR, fasting lipids in high‑risk patients.
• Psychiatric – Assessment of mood, anxiety, and potential emergence of psychotic features.
• Growth – Height/weight percentile measurements every 3–6 months in pediatric patients.
• Cardiac – ECG if tachycardia, arrhythmia, or uncontrolled hypertension develops.
• Drug interactions – Evaluate other central stimulants, MAOIs, sympathomimetics, or serotonergic agents.

Clinical Pearls

• Prodrug advantage – The synthetic linkage to leucine delays release, yielding a predictable, lower abuse‑risk profile while allowing steady platelet‑esterase‑mediated activation.
• Dosing nuance – Because lisdexamfetamine conversion is linear irrespective of dose, escalation beyond 70 mg offers little benefit but increases cardiovascular risk.
• Binge eating disorder – Lisdexamfetamine is one of the few FDA‑approved agents for BED; its appetite‑suppressant effect is a key therapeutic feature specific to this indication.
• Weight concerns – In pediatric patients, a therapeutic window of 30‑70 mg/titration should consider the delicate balance between symptom control and potential growth suppression; adjust weight‑based dosing if BMI falls below the 9th percentile.
• Medication sequencing – For patients transitioning from other stimulants, initiate at a lower dose (10–15 mg) and up‑titrate slowly; avoid concomitant use of other amphetamine preparations.
• Drug interaction wizard – Because lisdexamfetamine is not significantly metabolized by CYP enzymes, most drug interactions involve pharmacodynamic overlapping rather than clearance; avoid combine with serotonergic agents unless clinically justified and closely monitored for serotonin syndrome.

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• *This drug card provides a concise, up‑to‑date resource for medical students and practicing clinicians reviewing Lisdexamfetamine therapy. Always refer to the most recent prescribing information and national guidelines for definitive dosing and safety data.*