LISDEXAMFETAMINE

Class

• Neuroscience-based Nomenclature: dopamine and norepinephrine reuptake inhibitor and releaser (DN-RIRe)
• Stimulant

LISDEXAMFETAMINE commonly prescribed for

(Bold for FDA approved)

How LISDEXAMFETAMINE works

• Lisdexamfetamine is a prodrug of dextroamphetamine and is thus not active until after it has been absorbed by the intestinal tract and converted to dextroamphetamine (active component) and l-lysine

• Once converted to dextroamphetamine, it increases norepinephrine and especially dopamine actions by blocking their reuptake and facilitating their release

• Enhancement of dopamine and norepinephrine in certain brain regions (e.g., dorsolateral prefrontal cortex) may improve attention, concentration, executive dysfunction, wakefulness, and cortical inhibitory control of striatum

• Enhancement of dopamine actions in other brain regions (e.g., basal ganglia) may improve hyperactivity

• Enhancement of dopamine and norepinephrine in yet other brain regions (e.g., medial prefrontal cortex, hypothalamus) may improve depression, fatigue, sleepiness, and appetite regulation

How long until LISDEXAMFETAMINE works

• Some immediate effects can be seen with first dosing

• Can take several weeks to attain maximum therapeutic benefit, especially as dose is being titrated

Notable Side Effects

• Insomnia, headache, exacerbation of tics, nervousness, irritability, overstimulation, tremor, dizziness

• Anorexia, nausea, dry mouth, constipation, diarrhea, weight loss, dry mouth

• Peripheral vasculopathy, including Raynaud’s sydrome

• Can temporarily slow normal growth in children (controversial)

• Sexual dysfunction long-term (impotence, libido changes), but can also improve sexual dysfunction short-term

Life Threatening Side Effects

• Psychotic episodes

• Seizures

• Palpitations, tachycardia, hypertension

• Rare activation of hypomania, mania, or suicidal ideation (controversial)

• Cardiovascular adverse effects, sudden death in patients with preexisting cardiac structural abnormalities

weight gain

unusual

sedation

unusual

What to do about LISDEXAMFETAMINE side effects

• Wait

• Adjust dose

• Switch to another long-acting stimulant

• Switch to another agent

• For insomnia, avoid dosing in afternoon/ evening

usual dosage range

• ADHD: 30–70 mg/day

• Binge eating disorder: 50–70 mg/day

Dosage Forms

• Capsule 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg

• Chewable tablet 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg

long term use

• Can be used long-term for ADHD when ongoing monitoring documents continued efficacy

• For binge eating disorder, lisdexamfetamine has demonstrated maintenance of efficacy in a 26-week double-blind randomizedwithdrawal phase study

• Dependence and/or abuse may develop

• Tolerance to therapeutic effects may develop in some patients, in which case a dose increase should be considered

• Long-term stimulant use may be associated with growth suppression in children (controversial)

• Periodic monitoring of weight, blood pressure, heart rate, complete blood count, platelet counts, and liver function may be prudent

habit forming

• Schedule II drug

• Patients may develop tolerance, psychological dependence

• Theoretically less abuse potential than other stimulants when taken as directed because it is inactive until it reaches the gut and thus has delayed time to onset as well as long duration of action

Renal Impairment

• Severe impairment: maximum dose 50 mg/ day

• End-stage renal disease: maximum dose 30 mg/day

Hepatic Impairment

• Use with caution

Cardiac Impairment

• Use with caution, particularly in patients with recent myocardial infarction or other conditions that could be negatively affected by increased blood pressure

• Do not use in patients with structural cardiac abnormalities, cardiac myopathy, serious heart arrhythmia, or coronary artery disease

Elderly

• Some patients may tolerate lower doses better

Children and Adolescents

• Safety and efficacy not established in children under age 6

• Use in young children should be reserved for the expert

• d-amphetamine may worsen symptoms of behavioral disturbance and thought disorder in psychotic children

• d-amphetamine has acute effects on growth hormone; long-term effects are unknown but weight and height should be monitored during long-term treatment

• Usual dosing has been associated with sudden death in children with structural cardiac abnormalities

• Current recommendations from the American Heart Association are that it is reasonable but not mandatory to obtain an ECG prior to prescribing a stimulant to a child; the American Academy of Pediatrics does not recommend an ECG prior to starting a stimulant for most children

Pregnancy

• Controlled studies have not been conducted in pregnant women

• There is a greater risk of premature birth and low birth weight in infants whose mothers take d-amphetamine during pregnancy

• Infants whose mothers take d-amphetamine during pregnancy may experience withdrawal symptoms

• In mouse studies, d-amphetamine has been shown to have embryotoxic and teratogenic effects when administered in doses approximately 41 times the maximum recommended human dose

• Use in women of childbearing potential requires weighing potential benefits to the mother against potential risks to the fetus

• For ADHD patients, lisdexamfetamine should generally be discontinued before anticipated pregnancies

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or formula feed

• If infant shows signs of irritability, drug may need to be discontinued