|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; sold as Tyvense (IE), Elvanse (UK), Venvanse (BR), Vyvanse (CA, US)) 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. 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, regardless of the route of ingestion. The drug lisdexamfetamine dimesylate is the first prodrug of its kind. 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%. There is no increased onset or effect as occurs with IV administration of dextroamphetamine compared to oral use of the same. Intravenously administered lisdexamfetamine produced likability effects similar to placebo, therefore affirming the drug's ability to reduce abuse potential.
Lisdexamfetamine is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in children six to twelve years and in adults as an integral part of a total treatment program that may include other measures (i.e., psychological, educational, social). The safety and the efficacy of lisdexamfetamine dimesylate in patients three to five years old have not been established. Important side effects of therapeutic lisdexamfetamine include stunted growth in young people and, occasionally, a psychosis can occur at therapeutic doses during chronic therapy as a treatment emergent side effect. When abused at high doses the risk of experiencing and the severity of side effects increase.
Because lisdexamphetamine is active in the human brain as amphetamine, its mechanism of action is identical to that of dextroamphetamine.
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. Amphetamines act as releasing agents on the monoamine neurotransmitters dopamine and norepinephrine, thus causing massive extracellular levels of these two neurotransmitters. 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.
Lisdexamfetamine (LDX) is a therapeutically inactive molecule. After oral ingestion, LDX 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. LDX was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse-related liking. 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 LDX 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.
Vyvanse was developed by New River Pharmaceuticals, who were bought by Shire Pharmaceuticals shortly before lisdexamfetamine began being marketed. Vyvanse is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention-deficit hyperactivity disorder.
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.
Lisdexamfetamine has less potential for misuse than its active metabolite (dextroamphetamine) due to being initially inactive upon consumption via all methods, and the drug level of the active metabolite dextroamphetamine reaching a plateau within a therapeutic dosage range (both results of being a prodrug).
Common side effects
- Erectile dysfunction
- Mild agitation (restlessness)
- Xerostomia (dry mouth)
- Bruxism (jaw clenching/grinding)
- Insomnia (inability to sleep)
- Weight loss (resulting from decreased appetite)
- Diaphoresis (increased sweating)
- Parageusia (unpleasant taste)
- Upper abdominal pain
- Cold feet or hands
- Tachycardia (rapid heart rate)
Severe side effects include
- Severe aggression - some patients have reported sudden mood change, inability to control rage, physical abuse of others
- Abnormal muscle weakness or tiredness
- Anaphylaxis - a severe allergic reaction with effects including a rash, hives, itching, difficulty breathing, and generalized swelling.
- Changes in vision
- Dyspnea (shortness of breath)
- Severe headache
- Syncope (fainting)
- Angina pectoris (severe chest pain)
- Blurred vision
- Cardiac dysrhythmias - a group of cardiovascular conditions in which the electrical activity of the heart is abnormal with effects ranging from a fast heartbeat to cardiac arrest and sudden death.
- Tics - sudden, stereotyped, nonrhythmic and repetitive motor movements and/or vocalizations.
- Muscle tremors
- Severe irritability
- Severe psychomotor agitation
- Altered sexual ability or desire such as hypersexuality, erectile dysfunction, premature ejaculation, etc.
- Tachycardia (fast heartbeat)
- Slowed thinking
- Unstable emotions
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.
- Recreational drug use
- Lisdexamfetamine Dimesylate: A Prodrug Stimulant for the Treatment of ADHD in Children and Adults
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- Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers.
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- FDA Adult Approval of Vyvanse - FDA Label and Approval History
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- . February 8, 2012, retrieved on February 9, 2012.
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