Vyvanse

Black Box Warnings

Dextroamphetamine has a high potential for abuse; particular attention should be paid to the possibility of patients obtaining dextroamphetamine for nontherapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly

Administration of dextroamphetamine for prolonged periods of time may lead to drug dependence and must be avoided

Contraindications

Hypersensitivity

Patient taking MAOIs or within 14 days of stopping MAOIs (including linezolid or IV methylene blue) owing to increased risk of hypertensive crisis

Cautions

Use with caution in hyperthyroidism, glaucoma, mild to severe hypertension, advanced arteriosclerosis, symptomatic CVD, agitated states, history of psychosis or drug abuse

May cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychosis; evaluate for bipolar disorder prior to stimulant use

Misuse of dextroamphetamine may cause sudden death and serious cardiovascular adverse events

Monitor blood pressure and pulse; consider benefits and risks before use in patients for whom blood pressure increases may be problematic

Sudden death has been reported in association with CNS stimulant treatment at recommended doses in pediatric patients with structural cardiac abnormalities or other serious heart problems; in adults, sudden death, stroke, and myocardial infarction have been reported; avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, or coronary artery disease

Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation

Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder because of concern for possible induction of mixed/manic episode in such patients; screen for risk factors for developing a manic episode before initiating

Aggressive behavior or hostility is often observed in children and adolescents with ADHD; monitor for the appearance of or worsening of aggressive behavior or hostility

Monitor growth of children ages 7 to 10 years during treatment with stimulants; may need to interrupt therapy in patients not growing or gaining weight as expected

Stimulants may lower convulsive threshold in patients with prior history of seizure, patients with prior EEG abnormalities in absence of seizures, and very rarely, patients without a history of seizures and no prior EEG evidence of seizures; discontinue therapy in the presence of seizures

Use with caution in patients who use other sympathomimetic drugs Amphetamines may exacerbate motor and phonic tics and Tourette’s syndrome; perform clinical evaluation for tics and Tourette’s syndrome in children and their families prior to treating with stimulant medications

Interrupt drug administration occasionally to assess if recurrence of behavioral symptoms sufficient to require continued treatment

Associated with peripheral vasculopathy, including Raynaud phenomenon

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment

Use of stimulants may suppress appetite, especially in children, which may cause weight loss and slows the rate of growth

Rare instances of prolonged and sometimes painful erections (priapism), sometimes requiring surgical intervention, reported with methylphenidate products; typically not reported during initiation, but often subsequent to an increase in dose; seek immediate medical attention for abnormally sustained or frequent and painful erections

Serotonin syndrome

• Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems (eg, MAOIs, SSRIs, SNRIs, triptans, TCAs, fentanyl, lithium, tramadol, tryptophan, buspirone, St John’s Wort)
• Coadministration with MAOI drugs is contraindicated (see Contraindications)
• Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by CYP2D6 and display minor CYP2D6 inhibition
• Discontinue therapy with any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment; concomitant use with other serotonergic drugs or CYP2D6 inhibitors should be used only if potential benefit justifies the potential risk
• If clinically warranted, consider initiating therapy with lower doses, monitoring patients for emergence of serotonin syndrome during drug initiation or titration, and informing patients of increased risk for serotonin syndrome

Vyvanse is a prescription medication used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Vyvanse is also used to treat binge-eating disorder in adults.

Vyvanse belongs to a group of drugs called central nervous system stimulant medications which help increase attention, decrease impulsiveness, and decrease hyperactivity in people with ADHD, by changing amounts of certain natural substances in the brain.

This medication comes in capsule form and is taken once daily, in the morning.

Common side effects of Vyvanse include dizziness, irritability, and nausea.

Vyvanse has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from Vyvanse, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

Store Vyvanse in a safe place at room temperature, 59 to 86° F (15 to 30° C). Protect from light.
Keep Vyvanse and all medicines out of the reach of children.

Vyvanse  is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep Vyvanse in a safe place to prevent misuse and abuse. Selling or giving away Vyvanse may harm others, and is against the law.

WARNING

AMPHETAMINES HAVE A HIGH POTENTIAL FOR ABUSE. ADMINISTRATION OF AMPHETAMINES FOR PROLONGED PERIODS OF TIME MAY LEAD TO DRUG DEPENDENCE AND MUST BE AVOIDED. PARTICULAR ATTENTION SHOULD BE PAID TO THE POSSIBILITY OF SUBJECTS OBTAINING AMPHETAMINES FOR NONTHERAPEUTIC USE OR DISTRIBUTION TO OTHERS, AND THE DRUGS SHOULD BE PRESCRIBED OR DISPENSED SPARINGLY.

MISUSE OF AMPHETAMINE MAY CAUSE SUDDEN DEATH AND SERIOUS CARDIOVASCULAR ADVERSE EVENTS.

Active metabolite (dextroamphetamine) inhibits MAO.1

Lisdexamfetamine is not metabolized by CYP isoenzymes.1 In vitro studies suggest only minor inhibition of CYP isoenzymes 1A2, 2D6, and 3A4 by amphetamine and/or its metabolites.1

Specific Drugs, Tests, and Foods

Lisdexamfetamine dimesylate is used to treat attention deficit hyperactivity disorder (ADHD) in adults and children 6 years of age and older. This medicine is also used to treat moderate to severe binge eating disorder (BED). It belongs to the group of medicines called central nervous system (CNS) stimulants.

Lisdexamfetamine dimesylate increases attention and decreases restlessness in children and adults who are overactive, cannot concentrate for very long, or are easily distracted and impulsive. This medicine is used as part of a total treatment program that also includes social, educational, and psychological treatment.

This medicine is available only with your doctor's prescription.

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 [see Contraindications (4)]
• Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications (4) and Drug Interactions (7.1)]
• Drug Dependence [see Boxed Warning, Warnings and Precautions (5.1), and Drug Abuse and Dependence (9.2, 9.3)]
• Serious Cardiovascular Reactions [see Warnings and Precautions (5.2)]
• Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3)]
• Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
• Suppression of Growth [see Warnings and Precautions (5.5)]
• Peripheral Vasculopathy, including Raynaud's phenomenon [see Warnings and Precautions (5.6)]
• Serotonin Syndrome [see Warnings and Precautions (5.7)]

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 [see Clinical Studies (14.1)].

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.

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 [see Warnings and Precautions (5.5)].

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 14.2]. 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.

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.

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 [see Overdosage (10)].

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.

NDC 59417-116-01

Vyvanse®
(lisdexamfetamine
dimesylate) chewable tablets

20 mg

100 CHEWABLE
TABLETS

Chew tablets completely
before swallowing. Do
not swallow tablets whole.

CII
Rx only
Shire

NDC 59417-118-01

Vyvanse®
(lisdexamfetamine
dimesylate) chewable tablets

40 mg

100 CHEWABLE
TABLETS

Chew tablets completely
before swallowing. Do
not swallow tablets whole.

CII
Rx only
Shire

Take the missed dose as soon as you remember, but not late in the day. Skip the missed dose if it is almost evening. Do not take extra medicine to make up the missed dose.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Insomnia, decreased appetite, stomach pain, irritability, nausea and dry mouth have all been reported. Psychotic thoughts, hallucinations, and manic symptoms have also been reported.
• High potential for abuse and dependence. Tolerance to the effects of Vyvanse may develop over time (this means that the same dose no longer produces the same effects).
• Withdrawal symptoms (extreme fatigue, depression) may occur if Vyvanse is abruptly stopped; taper dosage off slowly under medical advice.
• May cause dizziness and impair judgment and affect a person's ability to drive or operate machinery. Alcohol should be avoided.
• May cause serious cardiac side effects. The risk is greater in those with preexisting cardiac abnormalities or heart problems.
• May not be suitable for people with cardiac disease. Your doctor should assess you or your child for the presence of cardiac disease before Vyvanse is prescribed, which requires taking a careful family history including noting any instances of sudden death or ventricular arrhythmia and conducting a physical exam.
• May not be suitable for people with a history of drug or alcohol abuse.
• Other adverse effects include an increase in blood pressure and heart rate, exacerbation of preexisting psychiatric disorders, allergic reactions, and peripheral tissue disorders.
• May cause growth suppression and weight loss in children. The height and weight of children taking long-term Vyvanse should be monitored.
• There is currently no generic version of Vyvanse available in the United States.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

Vyvanse is a stimulant used in the treatment of ADHD and BED. It is potentially addictive and there have been reports of serious cardiac side effects in adults and children.