|Systematic (IUPAC) name|
|Trade names||Tyvense, Elvanse, Venvanse, Vyvanse|
|Licence data||US FDA:|
|Pregnancy cat.||B3 (AU) C (US)|
|Legal status||Controlled (S8) (AU) Schedule I (CA) POM (UK) Schedule II (US)|
|Metabolism||Gastro-intestinal (initial); Hepatic (extensively CYP2D6) after conversion to dextroamphetamine|
|Half-life||< 1 hour (prodrug molecule), 10-13 hours (dextroamphetamine)|
|Mol. mass||263.378 g/mol|
|(what is this?)|
Lisdexamfetamine dimesylate (L-lysine-dextroamphetamine dimesylate) is a psychostimulant prodrug of the phenethylamine and amphetamine chemical classes. Its molecular structure consists of dextroamphetamine coupled with the essential amino acid L-lysine. Lisdexamfetamine itself is inactive and acts as a prodrug to dextroamphetamine upon cleavage of the lysine portion of the molecule.
Lisdexamfetamine is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in children six to twelve years and in adults as a part of a treatment program that may include other measures (i.e., psychological, educational, social). The safety and the efficacy of lisdexamfetamine dimesylate in people three to five years old have not been established.
Lisdexamfetamine is also being investigated for possible treatment of major depressive disorder, cognitive impairment associated with schizophrenia, excessive daytime sleepiness, and binge eating disorder.
Lisdexamfetamine is a pregnancy category C drug. No adequate studies have been performed to test the use of Vyvanse during pregnancy. It is known that amphetamine use during pregnancy can lead to adverse outcomes including preterm delivery and low birth weight. Animal studies have shown that in-utero exposure to amphetamines can lead to behavioral effects such as learning and memory deficits, altered locomotor activity, and changes in sexual function.
Amphetamines are able to pass from the bloodstream into human milk. The long term effects of amphetamine exposure from breastfeeding are unknown.
Individuals over the age of 65 were not commonly tested in clinical trials of Lisdexamfetamine. Therefore, there is insufficient data to determine how older individuals respond. People over the age of 65 should start on the low end of dosing schedules due to the prevalence of decreased hepatic function, decreased renal function, and comorbidities in this population.
Abuse of amphetamines can result in a stimulant psychosis which may present with a variety of symptoms (e.g., paranoia, hallucinations, delusions). A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine induced psychosis states that about 5-15% of users fail to recover completely. The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.
- Appetite changes
- Sexual Dysfunction
- Tachycardia (rapid heart rate)
- Upper abdominal pain
- Weight loss
- Xerostomia (dry mouth)
- Cardiovascular events including sudden death, stroke, and heart attack
- Growth suppression in the pediatric population
- Peripheral vasculopathy
Vyvanse is contraindicated in patients with hypersensitivity to amphetamine products and can cause anaphylaxis, angioedema, urticaria, and Stevens-Johnson syndrome. It is also contraindicated in in patients who have ingested medications of the monoamine oxidase inhibitors class (MAOIs)within the last 14 days.
Lisdexamfetamine is a therapeutically inactive prodrug molecule that is converted in the body to the active component dextroamphetamine, of the amphetamine class. After oral ingestion, lisdexamfetamine is broken down by enzymes to form L-lysine, a naturally occurring essential amino acid, and active dextroamphetamine, which is responsible for the drug’s activity. The conversion of LDX to dextroamphetamine is not affected by gastrointestinal pH and is unlikely to be affected by alterations in normal gastrointestinal transit times.
Amphetamines are noncatecholamine, sympathomimetic amines that cause the release of catecholamines (primarily dopamine and norepinephrine) from their storage sites in the presynaptic nerve terminals. Amphetamines are also known to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and therefore increase their availability into the extraneuronal space. Although the precise mechanism of action by which amphetamines improve the symptoms of ADHD remains unknown, it is thought that amphetamines decrease ADHD symptoms due to their effects on the central nervous system.
Lisdexamphetamine was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine available to the blood stream. Because no free dextroamphetamine is present in lisdexamfetamine capsules, dextroamphetamine does not become available through mechanical manipulation, such as crushing or simple extraction. A relatively sophisticated biochemical process is needed to obtain dextroamphetamine from LDX. As opposed to Adderall, which contains roughly equal parts of racemic amphetamine and dextroamphetamic salts, lisdexamfetamine is a single-enantiomer dextroamphetamine formula. Studies conducted show that lisdexamfetamine dimesylate may have less abuse potential than dextroamphetamine and an abuse profile similar to diethylpropion at dosages that are FDA-approved for treatment of ADHD, but still has a high abuse potential when this dosage is exceeded by over 100%.
It was developed for the intention of creating a longer-lasting and less-easily-abused version of dextroamphetamine, as the requirement of conversion into dextroamphetamine via enzymes in the red blood cells increases its duration of action, regardless of the route of ingestion. The drug lisdexamfetamine dimesylate is the first prodrug of its kind.
On April 23, 2008, Vyvanse received FDA approval for the adult population. In a randomized, double-blind, four-week phase III trial in adult patients with ADHD, dosages of 30, 50 or 70 mg/day of oral lisdexamfetamine caused a significantly greater improvement in ADHD-Rating Scale total score than placebo.
On February 8, 2012, Vyvanse received FDA approval for maintenance treatment of adult ADHD.
In February 2014, Shire announced that two late-stage clinical trials had shown that Vyvanse was not an effective treatment for depression.
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