"The U.S. Food and Drug Administration today allowed marketing of the first medical device based on brain function to help assess attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years old. When used as part of "...
The following adverse reactions are discussed in greater detail in other sections of the labeling
- Serious Cardiovascular Reactions [see WARNINGS AND PRECAUTIONS]
- Blood Pressure and Heart Rate Increases [see WARNINGS AND PRECAUTIONS]
- Psychiatric Adverse Reactions [see WARNINGS AND PRECAUTIONS]
- Suppression of Growth [see WARNINGS AND PRECAUTIONS]
- Peripheral Vasculopathy, including Raynaud's phenomenon [see WARNINGS AND PRECAUTIONS]
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
Adverse Reactions Associated with Discontinuation of Treatment in ADHD Clinical Trials
In the controlled trial in patients ages 6 to 12 years (Study 1), 9% (20/218) of VYVANSE-treated patients discontinued due to adverse reactions compared to 1% (1/72) of placebo-treated patients. The most frequent adverse reactions leading to discontinuation (i.e. leading to discontinuation in at least 1% of VYVANSE-treated patients and at a rate at least twice that of placebo) were ECG voltage criteria for ventricular hypertrophy, tic, vomiting, psychomotor hyperactivity, insomnia, and rash [2 instances for each adverse reaction, i.e., 2/218 (1%)].
In the controlled trial in patients ages 13 to 17 years (Study 4), 4% (10/233) of VYVANSEtreated patients discontinued due to adverse reactions compared to 1% (1/77) of placebo-treated patients. The most frequent adverse reactions leading to discontinuation were irritability (3/233; 1%), decreased appetite (2/233; 1%), and insomnia (2/233; 1%).
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 frequent adverse reactions leading to discontinuation (i.e. leading to discontinuation in at least 1% of VYVANSE-treated patients and at a rate at least twice that 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%).
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)
|Abdominal Pain Upper||12%||6%|
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
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)
|Increased Blood Pressure||3%||0%|
|Increased Heart Rate||2%||0%|
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 [see WARNINGS AND PRECAUTIONS].
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 [see Clinical Studies]. 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.
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 10 and 11) 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 10 and 11)
|Increased Heart Rate2||7%||1%|
|Upper Abdominal Pain||2%||0%|
|Urinary Tract Infection||2%||0%|
|1 Includes all preferred terms containing the
2 Includes the preferred terms heart rate increased and tachycardia.
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: palpitations, cardiomyopathy, mydriasis, diplopia, difficulties with visual accommodation, blurred vision, eosinophilic hepatitis, anaphylactic reaction, hypersensitivity, dyskinesia, tics, bruxism, depression, dermatillomania, aggression, Stevens-Johnson Syndrome, angioedema, urticaria, seizures, libido changes, frequent or prolonged erections, and constipation.
Read the Vyvanse (lisdexamfetamine dimesylate) Side Effects Center for a complete guide to possible side effects
Clinically Important Interactions With VYVANSE
Table 5: Effect of Other Drugs on VYVANSE
|Concomitant Drug Name or Drug Class||Clinical Rationale||Clinical Recommendation|
|Acidifying and Alkalinizing Agents||Ascorbic acid and other agents that acidify urine increase urinary excretion and decrease the half-life of amphetamine. Sodium bicarbonate and other agents that alkalinize urine decrease urinary excretion and extend the half-life of amphetamine.||Adjust the dose accordingly [see DOSAGE AND ADMINISTRATION]|
Table 6: Effect of VYVANSE on Other Drugs
|Concomitant Drug Name or Drug Class||Clinical Rationale||Clinical Recommendation|
|Monoamine Oxidase Inhibitors (MAOIs)||Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure.||Do not administer VYVANSE concomitantly or within 14 days after discontinuing MAOI treatment [see CONTRAINDICATIONS]|
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 [see CLINICAL PHARMACOLOGY].
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 [see CLINICAL PHARMACOLOGY].
Drug Abuse And Dependence
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. 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 [see OVERDOSAGE].
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.
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.
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.
Read the Vyvanse Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 2/5/2015
This monograph has been modified to include the generic and brand name in many instances.
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