VYVANSE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VYVANSE (VYVANSE).
Lisdexamfetamine is a prodrug of dextroamphetamine, which increases synaptic concentrations of dopamine and norepinephrine by blocking their reuptake and reversing the direction of transport via the dopamine and norepinephrine transporters.
| Metabolism | Primarily metabolized by red blood cell aminopeptidases to dextroamphetamine and l-lysine. Dextroamphetamine is further metabolized via hepatic cytochrome P450 isoenzymes (CYP2D6) and by deamination and conjugation, but the parent prodrug does not undergo significant CYP-mediated metabolism. |
| Excretion | Renal: 96% (including 2.3% unchanged lisdexamfetamine, 17.2% amphetamine glucuronide, 3.8% amphetamine sulfate, 3.9% amphetamine N-acetyl, 1.9% amphetamine N-acetyl glucuronide, 0.3% other amphetamine metabolites, and 0.4% hippuric acid). Fecal: <1%. |
| Half-life | Terminal half-life of dextroamphetamine is approximately 10-12 hours in adults; clinical context: steady-state reached within 5 days. |
| Protein binding | Dextroamphetamine: ~20% bound to serum albumin; lisdexamfetamine: negligible binding. |
| Volume of Distribution | 3-4 L/kg for dextroamphetamine; clinical meaning: extensive tissue distribution. |
| Bioavailability | Oral: 96.4% (based on urinary recovery of amphetamine); conversion to dextroamphetamine is rate-limited by first-pass hydrolysis. |
| Onset of Action | Oral: 1-2 hours (clinical effect of ADHD symptoms); Tmax of dextroamphetamine is 3.7 hours after oral administration. |
| Duration of Action | Approximately 12-14 hours for ADHD symptom control; clinical note: once-daily dosing provides extended coverage due to prodrug conversion. |
| Molecular Weight | 263.34 |
Initially 30 mg orally once daily in the morning; may increase by 10 mg or 20 mg weekly up to a maximum of 70 mg/day.
| Dosage form | TABLET, CHEWABLE |
| Renal impairment | For GFR 15-30 mL/min: not recommended; for GFR <15 mL/min or dialysis: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: not studied, use with caution. |
| Pediatric use | For ages 6-17: initially 30 mg orally once daily in the morning; may increase by 10 mg or 20 mg weekly; maximum 70 mg/day. For children <6 years: not approved. |
| Geriatric use | Initiate at 30 mg once daily; titrate cautiously due to increased sensitivity and higher risk of cardiovascular events. |
| 1st trimester | Limited human data; animal studies show increased risk of fetal cardiovascular malformations and reduced fetal weight. Use only if benefit outweighs risk. |
| 2nd trimester | May cause fetal growth restriction, premature birth, and withdrawal symptoms. Avoid unless absolutely necessary. |
| 3rd trimester | Risk of neonatal withdrawal (irritability, poor feeding) and possible growth retardation. Avoid in late pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for VYVANSE (VYVANSE).
| Placental transfer | Lisdexamfetamine and its active metabolite d-amphetamine cross the placenta; fetal exposure can reach 30-50% of maternal plasma levels. |
| Breastfeeding | Excreted into breast milk in low concentrations. Potential for infant agitation, insomnia, and reduced weight gain. Use with caution and monitor infant for adverse effects. |
■ FDA Black Box Warning
Abuse and dependence: central nervous system stimulants, including Vyvanse, 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.
| Serious Effects |
History of drug abuse or dependenceConcomitant use or within 14 days of MAO inhibitorsHyperthyroidismAgitated statesKnown hypersensitivity to amphetaminesCardiovascular conditions: advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension
| Precautions | Serious cardiovascular events: sudden death, stroke, and myocardial infarction have been reported in patients with structural cardiac abnormalities or other serious heart problems., Blood pressure and heart rate increase: monitor and consider dose reduction or discontinuation if clinically significant., Psychiatric adverse events: exacerbation of pre-existing psychosis, precipitation of manic episodes in bipolar disorder, and emergence of new psychotic or manic symptoms., Seizures: may lower seizure threshold; use with caution in patients with a history of seizures., Peripheral vasculopathy: including Raynaud's phenomenon; monitor for digital changes., Long-term growth suppression: monitor growth in pediatric patients during treatment., Acute angle closure glaucoma: use with caution in patients with elevated intraocular pressure or glaucoma. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy category C. First trimester: Increased risk of congenital malformations (e.g., gastroschisis) based on amphetamine class effects; limited human data for lisdexamfetamine. Second and third trimesters: Risk of prematurity, low birth weight, and neonatal withdrawal symptoms (e.g., agitation, dysphoria, poor feeding). |
| Fetal Monitoring | Monitor maternal weight gain, blood pressure, and mental health. Fetal ultrasound for growth and anatomy. Neonatal monitoring for withdrawal symptoms during first weeks after delivery. |
| Fertility Effects | Amphetamines may impair fertility in females via altered dopamine and prolactin levels. No human data specific to lisdexamfetamine; animal studies show no major impairment. |
| Food/Dietary | Avoid high-fat meals close to administration; high-fat meals may delay absorption and reduce peak concentration, but overall exposure is unchanged. Alcohol should be avoided as it may enhance cardiovascular and CNS effects. Grapefruit juice interaction is not significant, but caution is advised. The capsule contents can be mixed with soft foods (e.g., applesauce, yogurt) for ease of administration; however, they must be consumed immediately and not stored. |
| Clinical Pearls | Vyvanse (lisdexamfetamine) is a prodrug requiring enzymatic hydrolysis to become active, which may reduce abuse potential. Monitor for cardiovascular effects: check baseline BP and HR, and reassess periodically. Avoid use with MAOIs or within 14 days. Use with caution in patients with history of substance use disorder. Prolonged use may suppress growth in children; monitor height and weight. Available in chewable tablets and capsules; both can be swallowed whole or opened and mixed with soft foods (e.g., yogurt) for immediate consumption. |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting your doctor. · Swallow capsules whole, or open and mix entire contents with soft food (e.g., yogurt, pudding) and consume immediately; do not store for later use. · Chewable tablets must be chewed thoroughly; do not swallow whole. · Avoid taking in the afternoon or evening to prevent insomnia; take in the morning. · Report any chest pain, shortness of breath, palpitations, or fainting to your doctor immediately. · Avoid alcohol and illicit stimulants while taking this medication. · Do not drive or operate heavy machinery until you know how the medication affects you; may cause dizziness or blurred vision. · This medication is habit-forming; keep in a secure place away from others, and never share it. · Regular monitoring of growth in children and vital signs is required; attend all follow-up appointments. |