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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VYVANSE (VYVANSE).
| Breastfeeding | Excreted into breast milk; M/P ratio not established for lisdexamfetamine. Limited data suggest relative infant dose may be 2-14% of maternal weight-adjusted dose. Potential for infant adverse effects including irritability, poor feeding, and weight loss. Use caution; consider infant monitoring or alternative feeding. |
| 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). |
■ 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 |
["Hypersensitivity to lisdexamfetamine or any component of the formulation","Concurrent use or within 14 days of monoamine oxidase inhibitors (MAOIs)"]
| 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."] |
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| 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. |