Vyvanse Safety Signals & FDA Actions: What Patients and Prescribers Need to Know

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What is the main safety signal on the Vyvanse label?

The single boxed warning is abuse, misuse and addiction. The label says Vyvanse has a high potential for abuse and misuse, which can lead to a substance use disorder, including addiction; misuse and abuse of CNS stimulants can cause overdose and death, and the risk rises with higher doses or unapproved methods such as snorting or injection [1]. The label directs prescribers to assess each patient's risk before prescribing, educate patients and families about storage and disposal, and reassess risk throughout treatment [1]. Lisdexamfetamine is a Schedule II controlled substance [1].

The label describes an abuse-liability crossover study in 38 people with a history of drug abuse, comparing single doses of Vyvanse 50, 100 and 150 mg with immediate-release d-amphetamine 40 mg and diethylpropion 200 mg [1]. Vyvanse 100 mg produced significantly less drug liking than d-amphetamine 40 mg, while Vyvanse 150 mg produced drug liking similar to d-amphetamine 40 mg and diethylpropion 200 mg [1]. Intravenous lisdexamfetamine 50 mg gave positive subjective effects greater than placebo but less than intravenous d-amphetamine 20 mg [1]. Being a prodrug does not make Vyvanse non-abusable [1].

How does the label address heart and blood pressure risks?

The label warns that sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at ADHD doses [1]. It says to avoid Vyvanse in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease or other serious cardiac disease [1]. Before treatment, the label calls for a cardiac history, family history of sudden death or ventricular arrhythmia, and a physical exam [1].

CNS stimulants raise blood pressure by a mean of about 2 to 4 mm Hg and heart rate by about 3 to 6 bpm, with larger rises in some patients [1]. The label says to monitor all Vyvanse-treated patients for tachycardia and hypertension [1]. In the adult ADHD trial, increased blood pressure was reported in 3% of Vyvanse patients versus 0% on placebo, increased heart rate in 2% versus 0%, and palpitations in 2% versus 0% [1].

What psychiatric effects are listed?

The label warns that stimulants can worsen pre-existing psychosis and can induce a manic or mixed episode in patients with bipolar disorder, and it says to screen for risk factors for mania before starting [1]. In a pooled analysis of short-term placebo-controlled stimulant trials, new psychotic or manic symptoms occurred in about 0.1% of stimulant-treated patients versus 0% on placebo [1]. The label says to consider discontinuing Vyvanse if such symptoms occur [1].

What about growth, tics and circulation?

CNS stimulants are associated with weight loss and slowed growth in children [1]. In a 4-week placebo-controlled trial in children aged 6 to 12, the Vyvanse groups had dose-related decreases in weight compared with weight gain in the placebo group [1]. The label says to monitor height and weight closely and that children not growing or gaining as expected may need treatment interrupted [1]. The label also warns about motor and verbal tics and worsening Tourette's syndrome, and says to assess family history and clinically evaluate for tics before starting [1].

Peripheral vasculopathy, including Raynaud's phenomenon, is another labeled risk; signs are usually intermittent and mild, but digital ulceration and soft tissue breakdown have occurred [1]. The label says to watch for digital changes and that further evaluation such as rheumatology referral may be appropriate [1].

What interactions carry safety warnings?

MAOIs are contraindicated during Vyvanse treatment and within 14 days of stopping an MAOI, including linezolid or intravenous methylene blue, because of the risk of hypertensive crisis [1]. Serotonergic drugs, including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone and St. John's wort, increase the risk of serotonin syndrome [1]. CYP2D6 inhibitors may increase exposure to dextroamphetamine and may add to serotonin syndrome risk; the label says to start at lower doses and monitor [1].

Urinary alkalinizing agents such as sodium bicarbonate can raise amphetamine blood levels and potentiate effects, so the label says coadministration should be avoided; acidifying agents such as ascorbic acid lower amphetamine levels and efficacy, so the dose is increased based on clinical response [1]. Vyvanse can also interfere with the dopamine transporter imaging agent ioflupane I-123, and the label says to allow a washout before that test [1]. Vyvanse is contraindicated in patients with known hypersensitivity to amphetamine products or other ingredients; postmarketing reports include anaphylaxis, Stevens-Johnson syndrome, angioedema and urticaria [1].

What adverse events were most common in trials?

The label's controlled-trial tables give exact rates. In children aged 6 to 12 with ADHD, decreased appetite occurred in 39% on Vyvanse versus 4% on placebo, insomnia in 22% versus 3%, upper abdominal pain in 12% versus 6%, irritability in 10% versus 0%, vomiting in 9% versus 4%, weight decreased in 9% versus 1%, nausea in 6% versus 3%, dry mouth in 5% versus 0%, dizziness in 5% versus 0%, rash in 3% versus 0% and tic in 2% versus 0% [1].

In adults with ADHD, decreased appetite occurred in 27% versus 2%, insomnia in 27% versus 8%, dry mouth in 26% versus 3%, diarrhea in 7% versus 0%, nausea in 7% versus 0%, anxiety in 6% versus 0%, feeling jittery in 4% versus 0%, increased blood pressure in 3% versus 0%, increased heart rate in 2% versus 0% and palpitations in 2% versus 0% [1]. In adults with BED, dry mouth occurred in 36% versus 7%, insomnia in 20% versus 8%, decreased appetite in 8% versus 2%, increased heart rate in 7% versus 1%, feeling jittery in 6% versus 1%, constipation in 6% versus 1%, anxiety in 5% versus 1% and decreased weight in 4% versus 0% [1].

A 2025 meta-analysis of 93 randomized trials of methylphenidate, lisdexamfetamine and other amphetamines found a higher risk of any adverse event than placebo, with a risk ratio of 1.34 (90% CI 1.27 to 1.41) [5]. The finding held separately for lisdexamfetamine [5].

What FDA regulatory actions are documented?

The original Vyvanse capsule approval was February 23, 2007, as a new molecular entity under NDA 021977 [2]. The label now covers ADHD in adults and children 6 and older and moderate to severe BED in adults [1]. Drugs@FDA lists a priority efficacy supplement dated January 30, 2015, consistent with the BED indication added in 2015 [2]. Chewable tablets were approved January 28, 2017, under NDA 208510 [3]. A separate lisdexamfetamine oral solution, Arynta 10 mg/mL, was approved June 16, 2025, under NDA 219847 [4]. The current Vyvanse label is effective April 30, 2026 [1].

The label also states what Vyvanse is not approved for. It is not recommended in children under 6 because they had higher plasma exposure and more adverse reactions such as weight loss, and it is not indicated for weight loss; its safety and effectiveness for obesity have not been established [1]. Use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events [1].

What other monitoring and dosing limits does the label give?

Beyond the cardiac, tic, manic-risk, growth and digital-change checks described above, the label says to monitor blood pressure and pulse and to watch for signs and symptoms of abuse or misuse throughout treatment [1]. It says to take Vyvanse in the morning and avoid afternoon doses because of insomnia, and that a single dose should not be divided [1].

For renal impairment, the label sets a maximum of 50 mg per day when GFR is 15 to under 30 mL/min/1.73 m2 and 30 mg per day in end-stage renal disease [1]. The maximum recommended dose is 70 mg per day for both ADHD and BED [1].