Lisdexamfetamine

Lisdexamfetamine is the inactive prodrug of dexamfetamine, used for attention deficit hyperactivity disorder in children aged 6 years and over and in adults, and for moderate to severe binge eating disorder in adults. The prodrug design gives a smooth onset and lower misuse potential than immediate-release amfetamine, but it is still a controlled drug with a risk of misuse and dependence. It is not a weight-loss medicine.

Classification. Central nervous system stimulant, amfetamine prodrug.

Mechanism. Converted to dexamfetamine, which releases dopamine and noradrenaline and blocks their reuptake, increasing synaptic levels.

Pharmacokinetics. Absorbed in the gut and hydrolysed to dexamfetamine in red blood cells, which does not depend on liver or gut function. Peak dexamfetamine in about 3.5 to 4 hours. Prodrug half-life under 1 hour; dexamfetamine half-life about 10 to 12 hours. Effect lasts about 13 hours. Urinary pH changes alter excretion.

All regimens are oral with no loading dose.

ADHD, children aged 6 years and over and adults.

• Start 30 mg once daily in the morning (20 mg in some labels).
• Titration: increase by 10 to 20 mg at weekly intervals based on response.
• Usual 30 to 70 mg daily. Maximum 70 mg daily.

Binge eating disorder, adults.

• Start 30 mg once daily in the morning.
• Titration: increase by 20 mg weekly to 50 to 70 mg daily.
• Maximum 70 mg daily. Review need regularly and stop if no benefit.

Dose limits. Severe kidney impairment (GFR 15 to under 30 mL/min): maximum 50 mg daily. End-stage kidney disease (GFR under 15): maximum 30 mg daily. Liver impairment: no formal adjustment. Review ADHD treatment at least yearly and consider a break.

Contraindications. Concurrent monoamine oxidase inhibitor or within 14 days of stopping one, severe hypertension, symptomatic cardiovascular disease, arrhythmia, hyperthyroidism, glaucoma, agitated states, history of drug misuse, hypersensitivity. Major warning of abuse, misuse and addiction.

Serious adverse effects. Hypertension, tachycardia and arrhythmias, sudden death with structural heart disease, psychosis or mania, seizures, peripheral vasculopathy, growth slowing in children, serotonin syndrome, dependence and misuse, weight loss, depression on stopping.

Common adverse effects. Reduced appetite, dry mouth, insomnia, headache, irritability, abdominal pain, tachycardia.

Interactions. Monoamine oxidase inhibitors are contraindicated. Serotonergic medicines add serotonin syndrome risk. Medicines that acidify urine (ascorbic acid) lower levels, and alkalinising agents (sodium bicarbonate, acetazolamide) raise levels. Khat (cathinone) and other sympathomimetics add cardiovascular and psychiatric effects. Antihypertensive effect may be reduced.

Common prescribing errors. Prescribing for weight loss; starting too high; late-day dosing; using it where there is a history of stimulant misuse; omitting height, weight and blood pressure records.

Special groups.

• Pregnancy: avoid unless the benefit clearly outweighs the risk; fetal growth effects reported with amfetamines.
• Breastfeeding: dexamfetamine passes into milk; avoid.
• Children: not for children under 6 years; monitor growth.
• Older adults: limited data.
• Kidney impairment: maximum 50 mg daily in severe impairment and 30 mg daily in end-stage disease.
• Liver impairment: use with caution.

Formulations. Capsules 20 mg, 30 mg, 40 mg, 50 mg, 60 mg and 70 mg; chewable tablets 10 mg to 60 mg in some regions. Swallow whole or open the capsule and mix the contents into water or soft food and take straight away; do not store the mixture. Give in the morning with or without food.

Baseline. Blood pressure, pulse, height and weight, cardiovascular history and family history of sudden cardiac death, psychiatric history, substance use including khat and alcohol, eating behaviour.

Monitoring. Check blood pressure, pulse and weight every 3 to 6 months, and height every 6 months in children. Review need at least yearly. Ask about appetite, sleep, mood and misuse.

Stopping. No taper is needed; stop with review because mood and attention may worsen.

Referral and escalation. Refer to a specialist for diagnosis, initiation and complications. Chest pain, syncope, psychosis or fever with agitation needs urgent assessment.