Sign Out
Potential for Abuse and Dependence: CNS stimulants, including VYVANSE, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Drug Abuse and Dependence: Abuse and Dependence as follows].
Serious Cardiovascular Reactions: Sudden death, stroke and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during VYVANSE treatment.
Blood Pressure and Heart Rate Increases: CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mmHg) and heart rate (mean increase about 3 to 6 bpm). Monitor all patients for potential tachycardia and hypertension.
Psychiatric Adverse Reactions: Exacerbation of Pre-existing Psychosis: CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.
Induction of a Manic Episode in Patients with Bipolar Disorder: CNS stimulants may induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, and depression).
New Psychotic or Manic Symptoms: CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing VYVANSE. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in 0.1% of CNS stimulant-treated patients compared to 0% in placebo-treated patients.
Suppression of Growth: CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including VYVANSE. In a 4-week placebo-controlled trial of VYVANSE in pediatric patients ages 6 to 12 years old with ADHD, there was a dose-related decrease in weight in the VYVANSE groups compared to weight gain in the placebo group. Additionally, in studies of another stimulant, there was slowing of the increase in height [see Clinical Trials Experience under Adverse Reactions]. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. VYVANSE is not approved for use in pediatric patients below 6 years of age [see Use in Children as follows].
Peripheral Vasculopathy, including Raynaud's Phenomenon: Stimulants, including VYVANSE, are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
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 such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort [see Drugs Having Clinically Important Interactions with Amphetamines under Interactions]. The co-administration with cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with increased exposure to the active metabolite of VYVANSE (dextroamphetamine). In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drugs Having Clinically Important Interactions with Amphetamines under Interactions].
Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Concomitant use of VYVANSE with MAOI drugs is contraindicated [see Contraindications].
Discontinue treatment with VYVANSE and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment. If concomitant use of VYVANSE with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate VYVANSE with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.
Renal Impairment: Due to reduced clearance in patients with severe renal impairment (GFR 15 to <30 mL/min/1.73 m2), the maximum dose should not exceed 50 mg/day. The maximum recommended dose in ESRD (GFR <15 mL/min/1.73 m2) patients is 30 mg/day [see Pharmacology: Pharmacokinetics under Actions].
Lisdexamfetamine and d-amphetamine are not dialyzable.
Drug Abuse and Dependence: Prescription Drug: VYVANSE contains lisdexamfetamine, a prodrug of amphetamine.
Abuse: CNS stimulants, including VYVANSE, other amphetamine-containing products, and methylphenidate, have a high potential for abuse. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Abuse is characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Both abuse and misuse may lead to addiction, and some individuals may develop addiction even when taking VYVANSE as prescribed.
Signs and symptoms of amphetamine 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-controlled, 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, and 200 mg of diethylpropion hydrochloride. 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: Physical Dependence: VYVANSE may produce physical dependence from continued therapy. Physical dependence is a state of adaptation manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist. Withdrawal symptoms after abrupt cessation following prolonged high-dosage administration of CNS stimulants include extreme fatigue and depression.
Tolerance: VYVANSE may produce tolerance from continued therapy. Tolerance is a state of adaptation in which exposure to a specific dose of a drug results in a reduction of the drug's desired and/or undesired effects over time.
Use in Children: ADHD: Safety and effectiveness of VYVANSE have been established in pediatric patients with ADHD ages 6 to 17 years [see Dosage for Treatment of ADHD under Dosage & Administration; Clinical Trials Experience under Adverse Reactions; Pharmacology: Pharmacokinetics and Pharmacology: Pharmacodynamics: Clinical Studies under Actions]. Safety and effectiveness of VYVANSE have not been established in pediatric patients below the age of 6 years.
Safety and efficacy of VYVANSE were evaluated in a double-blind, randomized, parallel-group, placebo-controlled, fixed-dose study in pediatric patients ages 4 to 5 years with ADHD, followed by a 1-year open-label extension study. In these studies, patients experienced elevated rates of adverse reactions, including weight loss, decreased BMI, decreased appetite, insomnia, infections (upper respiratory and nasopharyngitis), irritability, and affect lability.
With the same VYVANSE dose, mean steady-state exposure of dextroamphetamine was approximately 44% higher in pediatric patients ages 4 to 5 years compared to the pediatric patients ages 6 to 11 years.
Growth Suppression: Growth should be monitored during treatment with stimulants, including VYVANSE, and pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Suppression of Growth as previously mentioned; Clinical Trials Experience under Adverse Reactions].
Juvenile Animal Data: Studies conducted in juvenile rats and dogs at clinically relevant doses showed growth suppression that partially or fully reversed in dogs and female rats but not in male rats after a four-week drug-free recovery period.
A study was conducted in which juvenile rats received oral doses of 4, 10, or 40 mg/kg/day of lisdexamfetamine dimesylate from day 7 to day 63 of age. These doses are approximately 0.3, 0.7, and 3 times the maximum recommended human daily dose of 70 mg on a mg/m2 basis for a child. Dose-related decreases in food consumption, body weight gain, and crown-rump length were seen; after a four-week drug-free recovery period, body weights and crown-rump lengths had significantly recovered in females but were still substantially reduced in males. Time to vaginal opening was delayed in females at the highest dose, but there were no drug effects on fertility when the animals were mated beginning on day 85 of age.
In a study in which juvenile dogs received lisdexamfetamine dimesylate for 6 months beginning at 10 weeks of age, decreased body weight gain was seen at all doses tested (2, 5, and 12 mg/kg/day, which are approximately 0.5, 1, and 3 times the maximum recommended human daily dose on a mg/m2 basis for a child). This effect partially or fully reversed during a four-week drug-free recovery period.
Use in the Elderly: Clinical studies of VYVANSE did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience and pharmacokinetic data [see Pharmacology: Pharmacokinetics under Actions] have not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
