Vyvanse Special Precautions

Abuse, Misuse and Addiction: VYVANSE has a high potential for abuse and misuse. The use of VYVANSE exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. VYVANSE can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence: Abuse as follows].
Misuse and abuse of CNS stimulants, including VYVANSE, can result in overdose and death [see Overdosage], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing VYVANSE, assess each patient's risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug. Advise patients to store VYVANSE in a safe place, preferably locked, and instruct patients to not give VYVANSE to anyone else. Throughout VYVANSE treatment, reassess each patient's risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Risks to Patients with Serious Cardiac Disease: Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage. Avoid VYVANSE use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
Increased Blood Pressure and Heart Rate: 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). Some patients may have larger increases. Monitor all VYVANSE-treated 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 manic or mixed episode. Prior to initiating VYVANSE 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 the recommended dosage, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients compared to 0% of placebo-treated patients. If such symptoms occur, consider discontinuing VYVANSE.
Long-Term Suppression of Growth in Pediatric Patients: CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. 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].
Closely monitor growth (weight and height) in VYVANSE-treated pediatric patients. 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: CNS stimulants, including VYVANSE, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports and at the therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant.
Careful observation for digital changes is necessary during VYVANSE treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for VYVANSE-treated patients who develop signs or symptoms of peripheral vasculopathy.
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.
Motor and Verbal Tics, and Worsening of Tourette's Syndrome: CNS stimulants, including amphetamine, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette's syndrome has also been reported [see Postmarketing Experience under Adverse Reactions].
Before initiating VYVANSE, assess the family history and clinically evaluate patients for tics or Tourette's syndrome. Regularly monitor VYVANSE-treated patients for the emergence or worsening of tics or Tourette's syndrome, and discontinue treatment if clinically appropriate.
Suicidal Behavior and Ideation: There have been post-marketing reports of suicide-related events in patients treated with ADHD drugs, including cases of ideation, attempts, and very rarely, completed suicide. The mechanism of this risk is not known. ADHD and its related co-morbidities may be associated with increased risk of suicidal ideation and/or behavior. Therefore, it is recommended for patients treated with ADHD drugs that caregivers and physicians monitor for signs of suicide-related behavior, including at dose initiation/optimization and drug discontinuation. Patients should be encouraged to report any distressing thoughts or feelings at any time to their healthcare professional. Patients with emergent suicidal ideation and behavior should be evaluated immediately. The physician should initiate appropriate treatment of the underlying psychiatric condition and consider a possible change in the ADHD treatment regimen.
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: VYVANSE has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see Abuse, Misuse and Addiction as previously mentioned]. VYVANSE can be diverted for non-medical use into illicit channels or distribution.
Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. 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.
Misuse and abuse of lisdexamfetamine, a prodrug of amphetamine may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including VYVANSE, can result in overdose and death [see Overdosage], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
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. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction, of a drug. Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including VYVANSE include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
Tolerance: VYVANSE may produce tolerance. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
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 Long-Term Suppression of Growth in Pediatric Patients 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.