lisdexamfetamine lisdexamfetamine lisdexamfetamine, sold under the brand name vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (adhd) in people over the age of five as well as moderate-to-severe binge eating disorder in adults. lisdexamfetamine is taken by mouth. its effects generally begin within two hours and last for up to 14 hours. in the united kingdom, it is usually less preferred than methylphenidate for the treatment of children. not to be confused with levoamphetamine. lisdexamfetamineclinical datatrade namesvyvanse, tyvense, elvanse, othersother namesl-lysine-d-amphetamine; (2s)-2,6-diamino-n-hexanamiden--l-lysinamideahfs/drugs.commonographmedlineplusa607047license data eu ema: by inn us dailymed: lisdexamfetamine us fda: lisdexamfetamine pregnancycategory au: b3 dependenceliabilitymoderateaddictionliabilitymoderateroutes ofadministrationby mouthatc coden06ba12 (who) legal statuslegal status au: s8 (controlled drug) br: class a3 (psychoactive drugs) ca: schedule i de: anlage iii (special prescription form required) uk: class b us: schedule ii eu: rx-only in general: ℞ (prescription only) pharmacokinetic databioavailabilityoral: 96.4%protein binding20% (as active amphetamine)metabolismhydrolysis by enzymes in red blood cells initially, subsequent metabolism followsmetabolitesdextroamphetamine (and its metabolites) and l-lysineonset of actionoral: <2 hourselimination half-lifelisdexamfetamine: <1 hourdextroamphetamine: 10–12 hduration of action10–12 hoursexcretionkidney: ~2%identifiers iupac name (2s)-2,6-diamino-n-hexanamide cas number608137-32-2 ypubchem cid11597698iuphar/bps7213drugbankdb01255 ychemspider9772458 yuniih645gul8kjkeggd08130as salt: d04747chemblchembl1201222 ycomptox dashboard (epa)dtxsid00209652 chemical and physical dataformulac15h25n3omolar mass263.385 g·mol−13d model (jsmol)interactive image smiles o=c(n(cc1ccccc1)c)(n)ccccn inchi inchi=1s/c15h25n3o/c1-12(11-13-7-3-2-4-8-13)18-15(19)14(17)9-5-6-10-16/h2-4,7-8,12,14h,5-6,9-11,16-17h2,1h3,(h,18,19)/t12-,14-/m0/s1 ykey:vobhxzcdavexey-jsgcoshpsa-n y ny (what is this?) (verify) 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 substance abuse per the drug enforcement administration (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 an inactive prodrug that works after being converted by the body into dextroamphetamine, a central nervous system (cns) stimulant. 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. in 2020, it was the 85th most commonly prescribed medication in the united states, with more than 8 million prescriptions. it is a class b controlled substance in the united kingdom and a schedule ii controlled substance in the united states. uses medical 30mg vyvanse capsules lisdexamfetamine is used primarily as a treatment for attention deficit hyperactivity disorder (adhd) and binge eating disorder; it has similar off-label uses as those of other pharmaceutical amphetamines. individuals over the age of 65 were not commonly tested in clinical trials of lisdexamfetamine for adhd. long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage, but in some cases with humans with adhd, pharmaceutical amphetamines at therapeutic dosages may improve brain development and nerve growth. reviews of magnetic resonance imaging (mri) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with adhd, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia. reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of adhd. randomized controlled trials of continuous stimulant therapy for the treatment of adhd spanning 2 years have demonstrated treatment effectiveness and safety. two reviews have indicated that long-term continuous stimulant therapy for adhd is effective for reducing the core symptoms of adhd (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function. one review highlighted a nine-month randomized controlled trial of amphetamine treatment for adhd in children that found an average increase of 4.5 iq points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling adhd symptoms and reduces the risk of developing a substance use disorder as an adult. current models of adhd suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems; these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex. psychostimulants like methylphenidate and amphetamine are effective in treating adhd because they increase neurotransmitter activity in these systems. approximately 80% of those who use these stimulants see improvements in adhd symptoms. children with adhd who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. the cochrane reviews on the treatment of adhd in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects. a cochrane review on the treatment of adhd in children with tic disorders such as tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals. cognitive performance in 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including working memory, long-term episodic memory, inhibitory control, and some aspects of attention, in normal healthy adults; these cognition-enhancing effects of amphetamine are known to be partially mediated through the indirect activation of both dopamine receptor d1 and adrenoceptor α2 in the prefrontal cortex. a systematic review from 2014 found that low doses of amphetamine also improve memory consolidation, in turn leading to improved recall of information. therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. amphetamine and other adhd stimulants also improve task saliency (motivation to perform a task) and increase arousal (wakefulness), in turn promoting goal-directed behavior. stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted adhd stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. however, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control. physical performance amphetamine is used by some athletes for its psychological and athletic performance-enhancing effects, such as increased endurance and alertness; however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies. in healthy people at oral therapeutic doses, amphetamine has been shown to increase muscle strength, acceleration, athletic performance in anaerobic conditions, and endurance (i.e., it delays the onset of fatigue), while improving reaction time. amphetamine improves endurance and reaction time primarily through reuptake inhibition and release of dopamine in the central nervous system. amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a "safety switch", allowing the core temperature limit to increase in order to access a reserve capacity that is normally off-limits. at therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature. available forms lisdexamfetamine is available as the dimesylate salt in the form of both oral capsules and chewable tablets. the capsules are available in doses of 10, 20, 30, 40, 50, 60, and 70 mg, while the chewable tablets are available in doses of 10, 20, 30, 40, 50, and 60 mg. these amounts of lisdexamfetamine dimesylate are equivalent to 5.8, 11.6, 17.3, 23.1, 28.9, 34.7, and 40.5 mg lisdexamfetamine free-base, respectively. a dose of 50 mg of lisdexamfetamine dimesylate is approximately equimolar to a 20 mg dose of dextroamphetamine sulfate or to 15 mg dextroamphetamine free-base in terms of the amount of dextroamphetamine contained. lisdexamfetamine capsules can be swallowed intact, or they can be opened and mixed into water, yogurt, or applesauce and consumed in that manner. contraindications pharmaceutical lisdexamfetamine 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 (maoi) within the last 14 days. amphetamine products are contraindicated by the united states food and drug administration (usfda) 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. however, a european consensus statement on adult adhd noted that stimulants do not worsen substance misuse in adults with adhd and comorbid substance use disorder and should not be avoided in these individuals. in any case, the statement noted that immediate-release stimulants should be avoided in those with both adhd and substance use disorder and that slower-release stimulant formulations like oros methylphenidate (concerta) and lisdexamfetamine should be preferred due to their lower misuse potential. 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. the major side effects of lisdexamfetamine in short-term clinical trials (≥5% incidence) have included decreased appetite, insomnia, dry mouth, weight loss, irritability, upper abdominal pain, nausea, vomiting, diarrhea, constipation, increased heart rate, anxiety, dizziness, and feeling jittery. rates of side effects may vary in adults, adolescents, and children. rare but serious side effects of lisdexamfetamine may include mania, sudden cardiac death in those with underlying heart problems, stimulant psychosis, and serotonin syndrome. 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. cyp2d6 inhibitors: hydroxylation via the cytochrome p450 enzyme cyp2d6 is the major pathway of metabolism of dextroamphetamine. potent cyp2d6 inhibitors, such as paroxetine, fluoxetine, bupropion, and duloxetine, among others, may inhibit the metabolism of dextroamphetamine and thereby increase exposure to it. studies characterizing this potential interaction are currently lacking. concomitant use of lisdexamfetamine with cyp2d6 inhibitors may increase the risk of serotonin syndrome due to greater drug exposure according to the fda label for lisdexamfetamine. monoamine oxidase inhibitors: concomitant use of maois and central nervous system stimulants such as lisdexamfetamine can cause a hypertensive crisis. pharmacology main section: amphetamine § pharmacodynamics mechanism of action pharmacodynamics of amphetamine in a dopamine neuron via aadc amphetamine enters the presynaptic neuron across the neuronal membrane or through dat. once inside, it binds to taar1 or enters synaptic vesicles through vmat2. when amphetamine enters synaptic vesicles through vmat2, it collapses the vesicular ph gradient, which in turn causes dopamine to be released into the cytosol (light tan-colored area) through vmat2. when amphetamine binds to taar1, it reduces the firing rate of the dopamine neuron via potassium channels and activates protein kinase a (pka) and protein kinase c (pkc), which subsequently phosphorylates dat. pka-phosphorylation causes dat to withdraw into the presynaptic neuron (internalize) and cease transport. pkc-phosphorylated dat may either operate in reverse or, like pka-phosphorylated dat, internalize and cease transport. amphetamine is also known to increase intracellular calcium, an effect which is associated with dat phosphorylation through a camkiiα-dependent pathway, in turn producing dopamine efflux. 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