What is Vyvanse (lisdexamfetamine)?

Vyvanse (lisdexamfetamine) is a type of central nervous system (CNS) stimulant called an amphetamine used to treat attention deficit hyperactivity disorder (ADHD), and moderate-to-severe binge eating disorder.

Common side effects of Vyvanse include:

Serious side effects of Vyvanse include:

Drug interactions of Vyvanse include monoamine oxidase inhibitor (MAOI) antidepressants, which can increase the concentration of amphetamines and their effect. This can cause serious elevations in blood pressure (hypertensive crisis) with headaches, other signs of hypertensive crisis, and even fatal reactions. 

Vyvanse increases the effect of norepinephrine. Combining both drugs may lead to serious cardiovascular toxicity. 

There are no adequate studies of Vyvanse in pregnant women. Amphetamines may cause premature delivery, low birth weight, and withdrawal symptoms in infants born to mothers who are dependent on amphetamines. Vyvanse is excreted in breast milk. Mothers taking Vyvanse should not breastfeed.

What are the side effects of Vyvanse (lisdexamfetamine)?

Common side effects of Vyvanse include:

Other important side effects of Vyvanse include:

  • blurred vision,
  • growth retardation in children, and
  • seizures in patients with a history of seizures.

Increased blood pressure, sudden death in patients with heart problems, strokes, and heart attacks have been associated with Vyvanse. Patients may experience new or worsening of psychiatric symptoms (for example, manic episodes, hearing voices, hallucinations) or worsening of aggressive behavior or hostility.

Vyvanse like other amphetamines may be abused. Amphetamines have been associated with tolerance, psychological dependence, and social disability. Stopping amphetamines suddenly may cause a withdrawal syndrome that includes extreme fatigue and mental depression. Therefore, there use should be discontinued by slowly reducing the dose.

Priapism, defined as painful and nonpainful penile erection lasting more than 4 hours, has been reported in pediatric and adult patients treated with stimulants. The erection usually resolves when the drug is stopped. Prompt medical attention is required in the event of suspected priapism.

Vyvanse (lisdexamfetamine) side effects list for healthcare professionals

The following adverse reactions are discussed in greater detail in other sections of the labeling:

  • Known hypersensitivity to amphetamine products or other ingredients of Vyvanse
  • Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors
  • Drug Dependence
  • Serious Cardiovascular Reactions
  • Blood Pressure and Heart Rate Increases
  • Psychiatric Adverse Reactions
  • Suppression of Growth
  • Peripheral Vasculopathy, including Raynaud’s phenomenon
  • Serotonin Syndrome

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Attention Deficit Hyperactivity Disorder

The safety data in this section is based on data from the 4-week parallel-group controlled clinical studies of Vyvanse in pediatric and adult patients with ADHD.

Adverse Reactions Associated with Discontinuation of Treatment in ADHD Clinical Trials

In the controlled trial in patients ages 6 to 12 years (Study 1), 8% (18/218) of Vyvanse-treated patients discontinued due to adverse reactions compared to 0% (0/72) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were ECG voltage criteria for ventricular hypertrophy, tic, vomiting, psychomotor hyperactivity, insomnia, decreased appetite and rash [2 instances for each adverse reaction, i.e., 2/218 (1%)]. Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included abdominal pain upper, dry mouth, weight decreased, dizziness, somnolence, logorrhea, chest pain, anger and hypertension.

In the controlled trial in patients ages 13 to 17 years (Study 4), 3% (7/233) of Vyvanse-treated patients discontinued due to adverse reactions compared to 1% (1/77) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were decreased appetite (2/233; 1%) and insomnia (2/233; 1%). Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included irritability, dermatillomania, mood swings, and dyspnea.

In the controlled adult trial (Study 7), 6% (21/358) of Vyvanse-treated patients discontinued due to adverse reactions compared to 2% (1/62) of placebo-treated patients. The most frequently reported adverse reactions (1% or more and twice rate of placebo) were insomnia (8/358; 2%), tachycardia (3/358; 1%), irritability (2/358; 1%), hypertension (4/358; 1%), headache (2/358; 1%), anxiety (2/358; 1%), and dyspnea (3/358; 1%). Less frequently reported adverse reactions (less than 1% or less than twice rate of placebo) included palpitations, diarrhea, nausea, decreased appetite, dizziness, agitation, depression, paranoia and restlessness.

Adverse Reactions Occurring at an Incidence of ≥5% or More Among Vyvanse Treated Patients with ADHD in Clinical Trials

The most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) reported in children, adolescents, and/or adults were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting.

Adverse Reactions Occurring at an Incidence of 2% or More Among Vyvanse Treated Patients with ADHD in Clinical Trials

Adverse reactions reported in the controlled trials in pediatric patients ages 6 to 12 years (Study 1), adolescent patients ages 13 to 17 years (Study 4), and adult patients (Study 7) treated with Vyvanse or placebo are presented in Tables 1, 2, and 3 below.

Table 1: Adverse Reactions Reported by 2% or More of Children (Ages 6 to 12 Years) with ADHD Taking Vyvanse and at least Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 1)

Vyvanse
(n=218)
Placebo
(n=72)
Decreased Appetite39%4%
Insomnia22%3%
Abdominal Pain Upper12%6%
Irritability10%0%
Vomiting9%4%
Weight Decreased9%1%
Nausea6%3%
Dry Mouth5%0%
Dizziness5%0%
Affect lability3%0%
Rash3%0%
Pyrexia2%1%
Somnolence2%1%
Tic2%0%
Anorexia2%0%

Table 2: Adverse Reactions Reported by 2% or More of Adolescent (Ages 13 to 17 Years) Patients with ADHD Taking Vyvanse and at least Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 4)

Vyvanse
(n=233)
Placebo
(n=77)
Decreased Appetite34%3%
Insomnia13%4%
Weight Decreased9%0%
Dry Mouth4%1%
Palpitations2%1%
Anorexia2%0%
Tremor2%0%

Table 3: Adverse Reactions Reported by 2% or More of Adult Patients with ADHD Taking Vyvanse and at least Twice the Incidence in Patients Taking Placebo in a 4-Week Clinical Trial (Study 7)

Vyvanse
(n=358)
Placebo
(n=62)
Decreased Appetite27%2%
Insomnia27%8%
Dry Mouth26%3%
Diarrhea7%0%
Nausea7%0%
Anxiety6%0%
Anorexia5%0%
Feeling Jittery4%0%
Agitation3%0%
Increased Blood Pressure3%0%
Hyperhidrosis3%0%
Restlessness3%0%
Decreased Weight3%0%
Dyspnea2%0%
Increased Heart Rate2%0%
Tremor2%0%
Palpitations2%0%

In addition, in the adult population erectile dysfunction was observed in 2.6% of males on Vyvanse and 0% on placebo; decreased libido was observed in 1.4% of subjects on Vyvanse and 0% on placebo.

Weight Loss and Slowing Growth Rate in Pediatric Patients with ADHD

In a controlled trial of Vyvanse in children ages 6 to 12 years (Study 1), mean weight loss from baseline after 4 weeks of therapy was -0.9, -1.9, and -2.5 pounds, respectively, for patients receiving 30 mg, 50 mg, and 70 mg of Vyvanse, compared to a 1 pound weight gain for patients receiving placebo. Higher doses were associated with greater weight loss with 4 weeks of treatment.

Careful follow-up for weight in children ages 6 to 12 years who received Vyvanse over 12 months suggests that consistently medicated children (i.e. treatment for 7 days per week throughout the year) have a slowing in growth rate, measured by body weight as demonstrated by an age-and sex-normalized mean change from baseline in percentile, of -13.4 over 1 year (average percentiles at baseline and 12 months were 60.9 and 47.2, respectively). In a 4-week controlled trial of Vyvanse in adolescents ages 13 to 17 years, mean weight loss from baseline to endpoint was -2.7, -4.3, and -4.8 lbs., respectively, for patients receiving 30 mg, 50 mg, and 70 mg of Vyvanse, compared to a 2.0 pound weight gain for patients receiving placebo.

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e. treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. In a controlled trial of amphetamine (d-to l-enantiomer ratio of 3:1) in adolescents, mean weight change from baseline within the initial 4 weeks of therapy was -1.1 pounds and -2.8 pounds, respectively, for patients receiving 10 mg and 20 mg of amphetamine. Higher doses were associated with greater weight loss within the initial 4 weeks of treatment.

Weight Loss in Adults with ADHD

In the controlled adult trial (Study 7), mean weight loss after 4 weeks of therapy was 2.8 pounds, 3.1 pounds, and 4.3 pounds, for patients receiving final doses of 30 mg, 50 mg, and 70 mg of Vyvanse, respectively, compared to a mean weight gain of 0.5 pounds for patients receiving placebo.

Binge Eating Disorder

The safety data in this section is based on data from two 12 week parallel group, flexible-dose, placebo-controlled studies in adults with BED. Patients with cardiovascular risk factors other than obesity and smoking were excluded.

Adverse Reactions Associated with Discontinuation of Treatment in BED Clinical Trials

In controlled trials of patients ages 18 to 55 years, 5.1% (19/373) of Vyvanse-treated patients discontinued due to adverse reactions compared to 2.4% (9/372) of placebo-treated patients. No single adverse reaction led to discontinuation in 1% or more of Vyvanse-treated patients. Less commonly reported adverse reactions (less than 1% or less than twice rate of placebo) included increased heart rate, headache, abdominal pain upper, dyspnea, rash, insomnia, irritability, feeling jittery and anxiety.

The most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) reported in adults were dry mouth, insomnia, decreased appetite, increased heart rate, constipation, feeling jittery, and anxiety.

Adverse reactions reported in the pooled controlled trials in adult patients (Study 11 and 12) treated with Vyvanse or placebo are presented in Table 4 below.

Table 4: Adverse Reactions Reported by 2% or More of Adult Patients with BED Taking Vyvanse and at least Twice the Incidence in Patients Taking Placebo in 12-Week Clinical Trials (Study 11 and 12)

Vyvanse
(N=373)
Placebo
(N=372)
Dry Mouth36%7%
Insomnia120%8%
Decreased Appetite8%2%
Increased Heart Rate27%1%
Feeling Jittery6%1%
Constipation6%1%
Anxiety5%1%
Diarrhea4%2%
Decreased Weight4%0%
Hyperhidrosis4%0%
Vomiting2%1%
Gastroenteritis2%1%
Paresthesia2%1%
Pruritis2%1%
Upper Abdominal Pain2%0%
Energy Increased2%0%
Urinary Tract Infection2%0%
Nightmare2%0%
Restlessness2%0%
Oropharyngeal Pain2%0%
1 Includes all preferred terms containing the word “insomnia.”
2 Includes the preferred terms “heart rate increased” and “tachycardia.”

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Vyvanse. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events are as follows: cardiomyopathy, mydriasis, diplopia, difficulties with visual accommodation, blurred vision, eosinophilic hepatitis, anaphylactic reaction, hypersensitivity, dyskinesia, dysgeusia, tics, bruxism, depression, dermatillomania, alopecia, aggression, Stevens-Johnson Syndrome, chest pain, angioedema, urticaria, seizures, libido changes, frequent or prolonged erections, constipation, and rhabdomyolysis.

What drugs interact with Vyvanse (lisdexamfetamine)?

Drugs Having Clinically Important Interactions With Amphetamines

Table 5: Drugs having clinically important interactions with amphetamines.

MAO Inhibitors (MAOI)
Clinical ImpactMAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results.
InterventionDo not administer Vyvanse during or within 14 days following the administration of MAOI.
Examplesselegiline, isocarboxazid, phenelzine, tranylcypromine
Serotonergic Drugs
Clinical ImpactThe concomitant use of Vyvanse and serotonergic drugs increases the risk of serotonin syndrome.
InterventionInitiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Vyvanse initiation or dosage increase. If serotonin syndrome occurs, discontinue Vyvanse and the concomitant serotonergic drug(s).
Examplesselective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort
CYP2D6 Inhibitors
Clinical ImpactThe concomitant use of Vyvanse and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of Vyvanse compared to the use of the drug alone and increase the risk of serotonin syndrome.
InterventionInitiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during Vyvanse initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Vyvanse and the CYP2D6 inhibitor.
Examplesparoxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir
Alkalinizing Agents
Clinical ImpactUrinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine.
InterventionCo-administration of Vyvanse and urinary alkalinizing agents should be avoided.
ExamplesUrinary alkalinizing agents (e.g. acetazolamide, some thiazides).
Acidifying Agents
Clinical ImpactUrinary acidifying agents can lower blood levels and efficacy of amphetamines.
InterventionIncrease dose based on clinical response.
ExamplesUrinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts).
Tricyclic Antidepressants
Clinical ImpactMay enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated.
InterventionMonitor frequently and adjust or use alternative therapy based on clinical response.
Examplesdesipramine, protriptyline

Drugs Having No Clinically Important Interactions With Vyvanse

From a pharmacokinetic perspective, no dose adjustment of Vyvanse is necessary when Vyvanse is co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when Vyvanse is co-administered.

From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g. theophylline, duloxetine, melatonin), CYP2D6 (e.g. atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g. omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g. midazolam, pimozide, simvastatin) is necessary when Vyvanse is co-administered.

Does Vyvanse (lisdexamfetamine) cause addiction and withdrawal symptoms?

Drug Abuse And Dependence

Controlled Substance

Vyvanse contains lisdexamfetamine, a prodrug of amphetamine, a Schedule II controlled substance.

Abuse

CNS stimulants, including Vyvanse, other amphetamines, and methylphenidate-containing products have a high potential for abuse. Abuse is characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving.

Signs and symptoms of CNS stimulant abuse may include increased heart rate, respiratory rate, blood pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility, aggression, suicidal or homicidal ideation have also been seen. Abusers of CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which can result in overdose and death.

To reduce the abuse of CNS stimulants, including Vyvanse, assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and on proper storage and disposal of CNS stimulants, monitor for signs of abuse while on therapy, and re-evaluate the need for Vyvanse use.

Studies Of Vyvanse In Drug Abusers

A randomized, double-blind, placebo-control, cross-over, abuse liability study in 38 patients with a history of drug abuse was conducted with single-doses of 50, 100, or 150 mg of Vyvanse, 40 mg of immediate-release d-amphetamine sulphate (a controlled II substance), and 200 mg of diethylpropion hydrochloride (a controlled IV substance). Vyvanse 100 mg produced significantly less “Drug Liking Effects” as measured by the Drug Rating Questionnaire-Subject score, compared to d-amphetamine 40 mg; and 150 mg of Vyvanse demonstrated similar “Drug-Liking Effects” compared to 40 mg of d-amphetamine and 200 mg of diethylpropion.

Intravenous administration of 50 mg lisdexamfetamine dimesylate to individuals with a history of drug abuse produced positive subjective responses on scales measuring "Drug Liking", "Euphoria", "Amphetamine Effects", and "Benzedrine Effects" that were greater than placebo but less than those produced by an equivalent dose (20 mg) of intravenous d-amphetamine.

Dependence

Tolerance

Tolerance (a state of adaptation in which exposure to a drug results in a reduction of the drug’s desired and/or undesired effects over time) may occur during the chronic therapy of CNS stimulants including Vyvanse.

Dependence

Physical dependence (a state of adaptation manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist) may occur in patients treated with CNS stimulants including Vyvanse. Withdrawal symptoms after abrupt cessation following prolonged high-dosage administration of CNS stimulants include extreme fatigue and depression.

Summary

Vyvanse (lisdexamfetamine) is a type of central nervous system (CNS) stimulant called an amphetamine used to treat attention deficit hyperactivity disorder (ADHD), and moderate-to-severe binge eating disorder. Common side effects of Vyvanse include upper abdominal pain, nausea, dry mouth, dizziness, weight loss, trouble sleeping, irritability, decreased appetite, vomiting, blurred vision, growth retardation in children, and seizures in patients with a history of seizures. Vyvanse contains lisdexamfetamine, a prodrug of amphetamine, a Schedule II controlled substance. CNS stimulants, including Vyvanse, other amphetamines, and methylphenidate-containing products have a high potential for abuse.

Treatment & Diagnosis

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Professional side effects, drug interactions, and addiction sections courtesy of the U.S. Food and Drug Administration.