Lisdexamfetamine
Lisdexamfetamine, sold under the brand name Vyvanse among [|others], is a medication that is a derivative of amphetamine. It is mainly used to treat attention deficit hyperactivity disorder in people over the age of five as well as moderate-to-severe binge eating disorder in adults. Lisdexamfetamine is taken by mouth. In the United Kingdom it is usually less preferred than methylphenidate. Its effects generally begin within 2 hours and last for up to 12 hours.
Common side effects of lisdexamfetamine include loss of appetite, anxiety, diarrhea, trouble sleeping, irritability, and nausea. Rare but serious side effects include mania, sudden cardiac death in those with underlying heart problems, and psychosis. It has a high potential for abuse per the DEA. Serotonin syndrome may occur if used with certain other medications. Its use during pregnancy may result in harm to the baby and use during breastfeeding is not recommended by the manufacturer. Lisdexamfetamine is a central nervous system stimulant that works after being converted by the body into dextroamphetamine. Chemically, lisdexamfetamine is composed of the amino acid L-lysine, attached to dextroamphetamine.
Lisdexamfetamine was approved for medical use in the United States in 2007. A month's supply in the United Kingdom costs the British National Health Service about as of 2019 In the United States, the wholesale cost of this amount is about. In 2017, it was the 91st most commonly prescribed medication in the United States, with more than eight million prescriptions. It is a Schedule II controlled substance in the United Kingdom and a Schedule II controlled substance in the United States.
Uses
Medical
Lisdexamfetamine is used primarily as a treatment for attention deficit hyperactivity disorder and binge eating disorder; it has similar uses as those of other pharmaceutical amphetamines. Individuals over the age of 65 were not commonly tested in clinical trials of lisdexamfetamine for ADHD.Enhancing performance
Contraindications
Pharmaceutical lisdexamfetamine dimesylate is contraindicated in patients with hypersensitivity to amphetamine products or any of the formulation's inactive ingredients. It is also contraindicated in patients who have used a monoamine oxidase inhibitor within the last 14 days. Amphetamine products are contraindicated by the United States Food and Drug Administration in people with a history of drug abuse, heart disease, or severe agitation or anxiety, or in those currently experiencing arteriosclerosis, glaucoma, hyperthyroidism, or severe hypertension. The USFDA advises anyone with bipolar disorder, depression, elevated blood pressure, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome to monitor their symptoms while taking amphetamine. Amphetamine is classified in US pregnancy category C. This means that detriments to the fetus have been observed in animal studies and adequate human studies have not been conducted; amphetamine may still be prescribed to pregnant women if the potential benefits outweigh the risks. Amphetamine has also been shown to pass into breast milk, so the USFDA advises mothers to avoid breastfeeding when using it. Due to the potential for stunted growth, the USFDA advises monitoring the height and weight of children and adolescents prescribed amphetamines. Prescribing information approved by the Australian Therapeutic Goods Administration further contraindicates anorexia.Adverse effects
Products containing lisdexamfetamine have a comparable drug safety profile to those containing amphetamine.Overdose
Interactions
- Acidifying Agents: Drugs that acidify the urine, such as ascorbic acid, increase urinary excretion of dextroamphetamine, thus decreasing the half-life of dextroamphetamine in the body.
- Alkalinizing Agents: Drugs that alkalinize the urine, such as sodium bicarbonate, decrease urinary excretion of dextroamphetamine, thus increasing the half-life of dextroamphetamine in the body.
- Monoamine Oxidase Inhibitors: Concomitant use of MAOIs and central nervous system stimulants such as lisdexamfetamine can cause a hypertensive crisis.
Pharmacology
Mechanism of action
Lisdexamfetamine is an inactive prodrug that is converted in the body to dextroamphetamine, a pharmacologically active compound which is responsible for the drug's activity. After oral ingestion, lisdexamfetamine is broken down by enzymes in red blood cells to form L-lysine, a naturally occurring essential amino acid, and dextroamphetamine. The conversion of lisdexamfetamine to dextroamphetamine is not affected by gastrointestinal pH and is unlikely to be affected by alterations in normal gastrointestinal transit times.The optical isomers of amphetamine, i.e., dextroamphetamine and levoamphetamine, are TAAR1 agonists and vesicular monoamine transporter 2 inhibitors that can enter monoamine neurons; this allows them to release monoamine neurotransmitters from their storage sites in the presynaptic neuron, as well as prevent the reuptake of these neurotransmitters from the synaptic cleft.
Lisdexamfetamine 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 produce dextroamphetamine from lisdexamfetamine. As opposed to Adderall, which contains roughly equal parts of racemic amphetamine and dextroamphetamine 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%.
Pharmacokinetics
Chemistry
Lisdexamfetamine is a substituted amphetamine with an amide linkage formed by the condensation of dextroamphetamine with the carboxylate group of the essential amino acid L-lysine. The reaction occurs with retention of stereochemistry, so the product lisdexamfetamine exists as a single stereoisomer. There are many possible names for lisdexamfetamine based on IUPAC nomenclature, but it is usually named as or. The condensation reaction occurs with loss of water:Amine functional groups are vulnerable to oxidation in air and so pharmaceuticals containing them are usually formulated as salts where this moiety has been protonated. This increases stability, water solubility, and, by converting a molecular compound to an ionic compound, increases the melting point and thereby ensures a solid product. In the case of lisdexamfetamine, this is achieved by reacting with two equivalents of methanesulfonic acid to produce the dimesylate salt, a water-soluble powder with a white to off-white color.
Comparison to other formulations
Lisdexamfetamine dimesylate is one marketed formulation delivering dextroamphetamine. The following table compares the drug to other amphetamine pharmaceuticals.History, society, and culture
Lisdexamfetamine was developed by New River Pharmaceuticals, who were bought by Takeda Pharmaceuticals through its acquisition of Shire Pharmaceuticals, shortly before it began being marketed. It was developed with 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 delays its onset of action, regardless of the route of administration.On 23 April 2008, the FDA approved lisdexamfetamine for treatment of ADHD in adults. On 19 February 2009, Health Canada approved 30 mg and 50 mg capsules of lisdexamfetamine for treatment of ADHD.
In January 2015, lisdexamfetamine was approved by the U.S. Food and Drug Administration for treatment of binge eating disorder in adults.
Production quotas for 2016 in the United States were 29,750 kilograms.
Names
Lisdexamfetamine is a contraction of L-lysine-dextroamphetamine.As of July 2014 lisdexamfetamine was sold under the following brands: Elvanse, Samexid, Tyvense, Venvanse, and Vyvanse.