Description

Simple

A medication used to treat mental health disorders, such as ADHD and eating disorders.

Clinical

A central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) and moderate to severe eating disorders.

Overview

Also known as _Vyvanse_, lisdexamfetamine (L-lysine-d-amphetamine) is a prodrug of the psychostimulant d-amphetamine [4]. It is paired with the essential amino acid _L-lysine_. Lisdexamfetamine dimesylate increases attention span and decreases restlessness in children and adults who are overactive/hyperactive, cannot concentrate for long periods, or are easily distracted or impulsive [2].

As a central nervous system stimulant, lisdexamfetamine is utilized as an adjunct therapy in the treatment of attention deficit hyperactivity disorder (ADHD). As a prodrug, lisdexamfetamine was specifically engineered as an abuse-resistant product [10]. The mechanism by which this occurs is through delayed release after ingestion (unlike some other psychostimulant drugs, which may be abused). After oral administration and absorption, enzyme hydrolysis after contact with red blood cells metabolize lisdexamfetamine into L- lysine, a naturally occurring essential amino acid and active _d-amphetamine_, wh... Read more

Also known as _Vyvanse_, lisdexamfetamine (L-lysine-d-amphetamine) is a prodrug of the psychostimulant d-amphetamine [4]. It is paired with the essential amino acid _L-lysine_. Lisdexamfetamine dimesylate increases attention span and decreases restlessness in children and adults who are overactive/hyperactive, cannot concentrate for long periods, or are easily distracted or impulsive [2].

As a central nervous system stimulant, lisdexamfetamine is utilized as an adjunct therapy in the treatment of attention deficit hyperactivity disorder (ADHD). As a prodrug, lisdexamfetamine was specifically engineered as an abuse-resistant product [10]. The mechanism by which this occurs is through delayed release after ingestion (unlike some other psychostimulant drugs, which may be abused). After oral administration and absorption, enzyme hydrolysis after contact with red blood cells metabolize lisdexamfetamine into L- lysine, a naturally occurring essential amino acid and active _d-amphetamine_, which is responsible for the drug’s pharmacological effects. Gastrointestinal pH does not affect this conversion, and the addition of the L-lysine slows the amount of d-amphetamine available in the circulation and central nervous system [10]. Read Less

Pharmacology

Indication

For the treatment of Attention-deficit/hyperactivity disorder (ADHD) and for moderate to severe binge eating disorder in adults [FDA label], [ Read more

For the treatment of Attention-deficit/hyperactivity disorder (ADHD) and for moderate to severe binge eating disorder in adults [FDA label], [4].

This drug is not indicated for weight loss. Use of other sympathomimetic drugs for weight loss is associated with serious cardiovascular effects. The safety and effectiveness of this drug for the treatment of obesity have not yet been determined [FDA label].
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Pharmacodynamic

Lisdexamfetamine dimesylate is a prodrug of _d-amphetamine_. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulating properties [FDA label]. This agent works primarily by inducing the release of the neurotransmitters dopamine and norepinephrine from their storage areas in pres... Read more

Lisdexamfetamine dimesylate is a prodrug of _d-amphetamine_. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulating properties [FDA label]. This agent works primarily by inducing the release of the neurotransmitters dopamine and norepinephrine from their storage areas in presynaptic nerve terminals [9]. Both of these transmitters contribute to alertness, increased concentration, in addition to effort and motivation.
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Mechanism of action

Lisdexamfetamine is a prodrug of dextroamphetamine. The active form of this drug blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites for... Read more

Lisdexamfetamine is a prodrug of dextroamphetamine. The active form of this drug blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites for the reuptake of norepinephrine and dopamine in vitro [FDA label]. The mechanism of therapeutic action in attention deficit hyperactivity disorder (ADHD) is not fully understood [8], [FDA label]. Amphetamines have been recently found to target the trace amine-associated receptor 1 (TAAR1), which was recently discovered. This may explain some of its effects on the extraneuronal space [5], [6],[7]. Ultimately, the ability of this agent to increase synaptic concentrations of the catecholamine neurotransmitters noradrenaline and dopamine in the prefrontal cortex (PFC), and in the striatum, results in several behavioral changes [9], [FDA label]. Read Less

Absorption

After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract [FDA label], [8].

**Chewable tablet form:** After a single dose of 60 mg a chewable tablet in healthy subjects u... Read more

After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract [FDA label], [8].

**Chewable tablet form:** After a single dose of 60 mg a chewable tablet in healthy subjects under fasted conditions, the Tmax of lisdexamfetamine and dextroamphetamine was reached at about 1 hour and 4.4 hour post administration, respectively [FDA label].

**Capsule form:** Following single-dose oral (30 mg, 50 mg, or 70 mg) in patients ages 6 to 12 years with ADHD under fasted conditions, Tmax of lisdexamfetamine and dextroamphetamine was reached at about 1 hour and 3.5 hours post administration, respectively [FDA label]. Read Less

Protein binding

Information currently not available.

Volume of distribution

There is no accumulation of d-amphetamine (as measured by AUC) at steady state in healthy adults and no accumulation of lisdexamfetamine dimesylate after once-daily dosing for seven consecutive days [FDA label], [8 Read more

There is no accumulation of d-amphetamine (as measured by AUC) at steady state in healthy adults and no accumulation of lisdexamfetamine dimesylate after once-daily dosing for seven consecutive days [FDA label], [8]. Read Less

Clearance

In a study of 47 subjects aged 55 years of age or older, amphetamine clearance was approximately 0.7L/hr/kg for subjects 55-74 years of age and 0.55L/hr/kg for subjects ≥75 years of age. This is slightly reduced compared to younger adults (approximately 1L/hr/kg for subjects 18-45 years of age) [ Read more

In a study of 47 subjects aged 55 years of age or older, amphetamine clearance was approximately 0.7L/hr/kg for subjects 55-74 years of age and 0.55L/hr/kg for subjects ≥75 years of age. This is slightly reduced compared to younger adults (approximately 1L/hr/kg for subjects 18-45 years of age) [8]. Read Less

Half life

The mean plasma elimination half-life of dextroamphetamine was about 12 hours after oral administration of lisdexamfetamine dimesylate [FDA label].

The plasma elimination half-life of lisdexamfetamine alone averaged less than one hour in studies of lisdexamfetamine dimesylate administered in vol... Read more

The mean plasma elimination half-life of dextroamphetamine was about 12 hours after oral administration of lisdexamfetamine dimesylate [FDA label].

The plasma elimination half-life of lisdexamfetamine alone averaged less than one hour in studies of lisdexamfetamine dimesylate administered in volunteer subjects [FDA label]. Read Less

Route of elimination

After the oral administration of a 70mg dose of radiolabeled lisdexamfetamine dimesylate to six healthy subjects, about 96% of the oral dose radioactivity was recovered in the urine and only 0.3% recovered in the feces [FDA label], [ Read more

After the oral administration of a 70mg dose of radiolabeled lisdexamfetamine dimesylate to six healthy subjects, about 96% of the oral dose radioactivity was recovered in the urine and only 0.3% recovered in the feces [FDA label], [8].
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Toxicity

**Acute toxicity**: Symptoms of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression generally follow the symptoms central nervous system st... Read more

**Acute toxicity**: Symptoms of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression generally follow the symptoms central nervous system stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension and/or circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Lethal poisoning is usually preceded by convulsions and coma [FDA label]. Prescribers should consider that serious cardiovascular (CV) events have been reported with this class of drugs [8].

**Long-term effects**: Acute administration of high doses of amphetamine (d- or d,l-) has been shown to produce long-term neurotoxic effects, which include irreversible nerve fiber damage, in rodents. The relevance of these findings to humans is currently unknown [FDA label].

**Oral LD50 (rat)**: 7,060 mg/kg [MSDS]

**Oral LD50 (mouse)**: 3,450 mg/kg [MSDS]

**Use in Pregnancy**

This drug is categorized as a Pregnancy Category C: Animal studies have shown risk to the fetus, there are no controlled studies in women, or studies in women and animals are not available [FDA label]. Read Less

Adverse Effects

Contraindications