Lisdexamfetamine
Encyclopedia
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
of the phenethylamine
Substituted phenethylamine
The substituted phenethylamines are chemical compounds with the 2-phenethylamine chemical structure modified at the phenyl ring, sidechain, and/or amino group. Some of them are psychoactive drugs, including stimulants, psychedelics, opioids, and entactogens, which exert their effects primarily...
and amphetamine
Substituted amphetamine
Substituted amphetamines are a chemical class of stimulants, entactogens, hallucinogens, and other drugs. They feature a phenethylamine core with a methyl group attached to the alpha carbon resulting in amphetamine, along with additional substitutions...
chemical classes. Its molecular structure
Molecular structure
The molecular structure of a substance is described by the combination of nuclei and electrons that comprise its constitute molecules. This includes the molecular geometry , the electronic properties of the...
consists of dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
coupled with the essential amino acid
Essential amino acid
An essential amino acid or indispensable amino acid is an amino acid that cannot be synthesized de novo by the organism , and therefore must be supplied in the diet.-Essentiality vs. conditional essentiality in humans:...
L-lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
.
Lisdexamfetamine itself is inactive and acts as a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
to dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
upon cleavage of the lysine portion of the molecule. It was developed for the intention of creating a longer-lasting and more difficult to abuse 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. 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 efficacy of lisdexamfetamine dimesylate in patients three to five years old have not been established.
As opposed to Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
, which contains roughly 75% dextroamphetamine and 25% levoamphetamine
Levoamphetamine
Levoamphetamine is a psychostimulant known to increase wakefulness and focus in association with decreased appetite and fatigue. Levoamphetamine is the levorotary stereoisomer of the amphetamine molecule...
, lisdexamfetamine is a single-enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
(dextro) amphetamine formula. This pure formulation may reduce side effects, but certain individuals exhibit a better clinical response to the mixed isomer preparation.
Vyvanse is also being investigated for possible treatment of Major Depressive Disorder, cognitive impairment associated with Schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, Excessive Daytime Sleepiness
Excessive daytime sleepiness
Excessive daytime sleepiness is characterized by persistent sleepiness, and often a general lack of energy, even after apparently adequate night time sleep...
, and Binge Eating Disorder
Binge eating disorder
Binge eating disorder is the most common eating disorder in the United States affecting 3.5% of females and 2% of males and is prevalent in up to 30% of those seeking weight loss treatment...
.
Dosage
Lisdexamfetamine is available under the brand-name Vyvanse. Vyvanse comes in several different dosages (see table below). These dosages are usually labeled to be taken once daily.| Vyvanse dosage strengths available | ||
|---|---|---|
| Strength | Appearance | Imprint (unique label) |
| 20 milligrams | Capsule with ivory Ivory (color) Ivory is an off-white color that resembles ivory, the material out of which the teeth and tusks of animals is made. It has a very slight tint of yellow.... colored body and cap |
NRP104 or S489 20 mg |
| 30 milligrams | Capsule with white colored body and orange colored cap | NRP104 or S489 30 mg |
| 40 milligrams | Capsule with white colored body and teal Teal (color) Teal is a medium blue-green color. It is named after the Common Teal, a member of the duck family, whose eyes are surrounded by the color.Teal is one of the initial group of 16 HTML/CSS web colors formulated in 1987, shown below.... colored cap |
NRP104 or S489 40 mg |
| 50 milligrams | Capsule with white colored body and blue colored cap | NRP104 or S489 50 mg |
| 60 milligrams | Capsule with aqua blue Aqua (color) Aqua is a tone of the color cyan which is identical to the color electric cyan, one of the three secondary colors of the HSV color wheel, along with magenta and yellow. It is precisely halfway between green and blue on the color wheel... colored body and cap |
NRP104 or S489 60 mg |
| 70 milligrams | Capsule with blue colored body and orange colored cap | NRP104 or S489 70 mg |
25 mg of Vyvanse is molecularly equivalent to a 10 mg Dexedrine Spansule (both are about 7.425 mg dextroamphetamine base), although a 25 mg Vyvanse capsule is not commercially available.
However, the molecular equivalence ratio does not mean that the respective doses of Vyvanse and Adderall XR (Spansule) are bioequivalent because the two formulations have slightly different pharmacokinetic profiles. For example, while the area under the curve for the aforementioned pharmaceuticals is equivalent, the peak exposure (Cmax) to the active compound dextroamphetamine is about 50% higher for Vyvanse than for Dexedrine XR. The conversion rate of lisdexamfetamine to dextroamphetamine base is 0.2948.
History
Vyvanse was developed by New River Pharmaceuticals, who were bought by Shire PharmaceuticalsShire Pharmaceuticals Group
Shire Plc is a Jersey-registered, Irish-headquartered manufacturer of pharmaceuticals. Originating in and with a large operational base in the United Kingdom, its brands and products include Adderall XR, Carbatrol, Fosrenol, and the recently released Vyvanse....
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
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
.
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, 30, 50 or 70mg/day of oral lisdexamfetamine caused a significantly greater improvement in ADHD-Rating Scale total score than placebo.
On February 19, 2009, Health Canada
Health Canada
Health Canada is the department of the government of Canada with responsibility for national public health.The current Minister of Health is Leona Aglukkaq, a Conservative Member of Parliament appointed to the position by Prime Minister Stephen Harper.-Branches, regions and agencies:Health Canada...
approved 30 mg and 50 mg capsules of lisdexamphetamine for treatment of ADHD.
Misuse potential
Lisdexamfetamine has less potential for misuse than its active metabolite (dextroamphetamineDextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
) due to being initially inactive upon consumption via all methods and taking longer to metabolise than dextro-amphetamine (both results of being a pro-drug). Misuse of lisdexamfetamine may cause the same extent of cardiovascular side-effects as dextro-amphetamine, but again this risk is likely to be reduced due to the method of administration.
Common side effects
Common side effects (side effects that have average rates of presentation; usually presenting in >5% of patients) of lisdexamfetamine use include:- DiscomfortDiscomfortDiscomfort may refer to:* Pain, an unpleasant sensation* Suffering, an experience of unpleasantness...
- Erectile DysfunctionErectile dysfunctionErectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
- DizzinessDizzinessDizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
- Mild agitationPsychomotor agitationPsychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
(restlessness) - NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
- XerostomiaXerostomiaXerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
(dry mouth) - BruxismBruxismBruxism is characterized by the grinding of the teeth and typically includes the clenching of the jaw. It is an oral parafunctional activity that occurs in most humans at some time in their lives. In most people, bruxism is mild enough not to be a health problem...
(jaw clenching/grinding) - AnxietyAnxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
- DiarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
- Emesis (vomiting)
- HeadacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
- InsomniaInsomniaInsomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
(inability to sleep) - Weight lossWeight lossWeight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
(decreased appetite) - EuphoriaEuphoriaEuphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...
- DiaphoresisDiaphoresisDiaphoresis is excessive sweating commonly associated with shock and other medical emergency conditions.Diaphoretic is the state of perspiring profusely, or something that has the power to cause increased perspiration....
(increased sweating) - IrritabilityIrritabilityIrritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
- ParageusiaParageusiaParageusia is the medical term for a bad taste in the mouth.One common form of parageusia is a metallic taste of food. This can be a side effect of several medications, such as acetazolamide, eszopiclone, zopiclone, metronidazole, or etoposide....
(unpleasant taste) - Upper abdominal painAbdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
- Cold Feet or Hands
- Rapid Heartbeat
Severe side effects
Very infrequent but possibly severe side effects requiring immediate medical attention may be caused by lisdexamfetamine; these serious reactions include:- Severe aggression - some patients have reported sudden mood changes, inability to control rage, physical abuse of others
- Abnormal muscle weaknessMuscle weaknessMuscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
or tiredness - AnaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
- a severe allergic reaction with effects including a rashRashA rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, hives, itching, difficulty breathingLabored breathingLabored respiration or labored breathing is an abnormal respiration characterized by evidence of increased effort to breathe, including the use of accessory muscles of respiration, stridor, grunting, or nasal flaring.-Classification:...
, and generalized swellingSwelling (medical)In medical parlance, swelling is the transient enlargement or protuberance in the body and may include tumors. According to cause, it may be congenital, traumatic, inflammatory, neoplastic or miscellaneous....
. - Changes in vision
- DyspneaDyspneaDyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
(shortness of breath) - FeverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
- Severe headache
- SyncopeSyncope (medicine)Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
(fainting)
- Angina pectoris (severe chest pain)
- Blurred visionBlurred vision-Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....
- Cardiac dysrhythmiaCardiac dysrhythmiaCardiac dysrhythmia is any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular.Some arrhythmias are life-threatening medical emergencies that can result in cardiac...
s - 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. - Seizures
- Tics - sudden, stereotyped, nonrhythmic and repetitive motor movements and/or vocalizationsSpeech productionSpeech production is the process by which spoken words are selected to be produced, have their phonetics formulated and then finally are articulated by the motor system in the vocal apparatus...
.
- Hallucinations
- Muscle tremors
- Severe irritability
- Severe psychomotor agitationPsychomotor agitationPsychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
- Altered sexual ability or desireSexual dysfunctionSexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
such as hypersexualityHypersexualityHypersexuality is extremely frequent or suddenly increased sexual urges or sexual activity. Hypersexuality is typically associated with lowered sexual inhibitions. Although hypersexuality can be caused by some medical conditions or medications, in most cases the cause is unknown...
, male impotenceErectile dysfunctionErectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
, premature ejaculationPremature ejaculationPremature ejaculation is a condition in which a man ejaculates earlier than he or his partner would like him to. Premature ejaculation is also known as rapid ejaculation, rapid climax, premature climax, or early ejaculation....
, etc. - TachycardiaTachycardiaTachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
(fast heartbeat) - Slowed thinking
- Unstable emotions
See also
- ADHD
- AdderallAdderallAdderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
- AmphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
- Anorectics
- Desoxyn
- DextroamphetamineDextroamphetamineDextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
- Dopaminergics
- MethamphetamineMethamphetamineMethamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
- MethylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
- MidodrineMidodrineMidodrine is a vasopressor/antihypotensive agent. Midodrine was approved in the United States by the Food and Drug Administration in 1996 for the treatment of orthostatic hypotension...
- Phenethylamines
- Pro-drug
- Recreational Drugs
- Stimulants