DEXEDRINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEXEDRINE (DEXEDRINE).
Dextroamphetamine is a central nervous system stimulant that enhances the activity of dopamine and norepinephrine in the brain by blocking their reuptake and increasing their release from presynaptic terminals.
| Metabolism | Primarily metabolized by CYP2D6 to 4-hydroxydextroamphetamine, which is further metabolized to various metabolites. Also undergoes deamination and oxidation. |
| Excretion | Renal: 30-45% unchanged, 50-60% as deaminated metabolites; fecal: minor (<5%) |
| Half-life | Terminal elimination half-life is 4-6 hours for dextroamphetamine; clinical effects last longer due to CNS accumulation |
| Protein binding | Approximately 16-20% bound; primarily to albumin |
| Volume of Distribution | 3.5-4.5 L/kg; indicates extensive tissue distribution, particularly CNS |
| Bioavailability | Oral: 75-100% (immediate-release), 70-90% (extended-release); rectal and parenteral routes are not clinically utilized |
| Onset of Action | Oral: 30-60 minutes (immediate-release), 1-2 hours (extended-release) |
| Duration of Action | Immediate-release: 4-6 hours; extended-release: 8-12 hours; tolerance may shorten effective duration |
| Molecular Weight | 337.45 |
5–60 mg/day orally in divided doses, typically 5–20 mg 1–3 times daily; use immediate-release or extended-release formulations per indication.
| Dosage form | TABLET |
| Renal impairment | GFR 15–30 mL/min: use with caution, consider dose reduction by 50%. GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: not recommended. |
| Pediatric use | Age 3–5 years: 2.5 mg orally once daily, increase by 2.5 mg weekly as needed (max 40 mg/day). Age ≥6 years: 5 mg orally once or twice daily, increase by 5 mg weekly (max 40 mg/day). |
| Geriatric use | Start at lowest dose (2.5–5 mg orally once daily), titrate slowly; monitor for cardiovascular effects, agitation, and weight loss. |
| 1st trimester | Avoid. Potential teratogenicity, especially cardiovascular defects and oral clefts with first-trimester exposure. Use only if benefit outweighs risk. |
| 2nd trimester | Caution. Use only if clearly needed. Associated with increased risk of preeclampsia, preterm delivery, and growth restriction. |
| 3rd trimester | Avoid in late pregnancy. Risk of neonatal withdrawal syndrome, including irritability, poor feeding, and growth retardation. |
Clinical note
Comprehensive clinical and safety monograph for DEXEDRINE (DEXEDRINE).
| Placental transfer | Crosses placenta readily; fetal serum levels approximate maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts (relative infant dose ~5-14% of maternal weight-adjusted dose). Monitor for irritability, poor weight gain, and insomnia in breastfed infants. Avoid breastfeeding if maternal use is high or infant is preterm. |
■ FDA Black Box Warning
WARNING: ABUSE AND DEPENDENCE. CNS stimulants, including DEXEDRINE, 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 |
Advanced arteriosclerosisSymptomatic cardiovascular diseaseModerate to severe hypertensionHyperthyroidismGlaucomaAgitated statesHistory of drug abuseConcurrent use of MAOIs or within 14 days of MAOI discontinuation
| Precautions | Serious cardiovascular events including sudden death in patients with pre-existing structural cardiac abnormalities or other serious heart problems, Blood pressure and heart rate increases, Psychiatric adverse events including exacerbation of pre-existing psychosis, manic episodes, and aggression, Seizures in patients with prior seizure history, Long-term suppression of growth in children, Peripheral vasculopathy including Raynaud's phenomenon, Serotonin syndrome risk when co-administered with serotonergic drugs |
| Food/Dietary | Avoid high-fat meals with immediate-release formulations as they may delay absorption; for extended-release, high-fat meals can increase peak concentration. Acidic foods (e.g., citrus fruits, fruit juices, carbonated drinks) can reduce absorption. Avoid excessive caffeine (coffee, tea, energy drinks) as it may exacerbate central nervous system stimulation and cardiovascular effects. Maintain adequate hydration. Grapefruit and other CYP2D6 inhibitors may increase effects. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show increased risk of cardiovascular malformations and cleft palate at high doses. Second/third trimester: Increased risk of preterm delivery, low birth weight, and neonatal withdrawal symptoms (hyperactivity, irritability, feeding difficulties). Dextroamphetamine is a sympathomimetic amine with potential for vasoconstriction reducing uteroplacental perfusion. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, weight, and psychiatric status (anxiety, agitation). Fetal: Serial growth ultrasounds to detect intrauterine growth restriction (IUGR); nonstress testing and biophysical profile in third trimester if signs of insufficiency. Neonatal: Observe for withdrawal symptoms (hyperactivity, poor feeding) for 48 hours after delivery. |
| Fertility Effects | Animal studies: High doses may impair male fertility (reduced spermatogenesis) and female fertility (disrupted estrous cycle). Human data insufficient; theoretical risk due to vasoconstrictive effects on reproductive organs. |
| Clinical Pearls | Monitor for hypertension, tachycardia, and mental status changes (psychosis, mania) especially at high doses. Avoid late-day dosing to prevent insomnia. Use with caution in patients with pre-existing cardiovascular disease or hyperthyroidism. Dextroamphetamine can suppress appetite and cause weight loss; monitor growth in children. Abuse potential is high; schedule II controlled substance. Can precipitate tics in susceptible individuals. Contraindicated within 14 days of MAOIs due to hypertensive crisis. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not crush or chew the extended-release capsules; swallow whole. · Avoid taking the medication in the evening or close to bedtime to prevent trouble sleeping. · Report any chest pain, shortness of breath, fainting, or rapid heart rate to your doctor immediately. · Contact your doctor if you experience new or worsening mental health symptoms such as agitation, aggression, hallucinations, or mania. · You may experience decreased appetite and weight loss; maintain a healthy diet and inform your doctor if weight loss is significant. · Do not stop taking abruptly; taper dose under medical supervision to avoid withdrawal symptoms. · This medication has potential for abuse and dependence; keep in a safe place and do not share with others. · Avoid alcohol and caffeine as they may increase side effects like jitteriness and heart palpitations. · Tell all healthcare providers you are taking this medication, especially before surgery or dental procedures. |