DEXTROAMPHETAMINE SULFATE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Increases extracellular levels of norepinephrine and dopamine by blocking reuptake and promoting release from presynaptic terminals, via trace amine-associated receptor 1 (TAAR1) agonism and vesicular monoamine transporter 2 (VMAT2) inhibition.
| Metabolism | Substrate of CYP2D6; primarily metabolized via deamination, hydroxylation, and conjugation; also undergoes N-dealkylation. |
| Excretion | Primarily renal (30-50% unchanged at acidic pH, less at alkaline pH); ~50% as metabolites (mostly deaminated and hydroxylated); minimal biliary/fecal. |
| Half-life | 9-11 hours (adults); clinical context: twice-daily dosing achieves steady-state in ~2-3 days. |
| Protein binding | 20-25% bound, primarily to albumin. |
| Volume of Distribution | 3.5-4.0 L/kg (extensive tissue distribution, including CNS). |
| Bioavailability | Oral IR: ~100% (well absorbed); extended-release: ~90% (relative to IR). |
| Onset of Action | Oral immediate-release: 30-60 min; oral extended-release: 1-2 hours; intravenous: immediate (seconds to minutes). |
| Duration of Action | IR: 3-6 hours; ER: 8-12 hours; clinical notes: IR may require multiple daily doses, ER provides sustained effect. |
| Molecular Weight | 368.49 |
5-60 mg/day orally divided every 4-6 hours, starting at 5 mg once or twice daily.
| Dosage form | TABLET |
| Renal impairment | GFR 15-30 mL/min: reduce dose by 50%; GFR <15 mL/min: avoid use. |
| Liver impairment | Child-Pugh class A: no adjustment; class B: reduce dose by 50%; class C: avoid use. |
| Pediatric use | 3-5 years: 2.5 mg/day orally initially, increased by 2.5 mg weekly; 6 years and older: 5 mg once or twice daily, increase by 5 mg weekly up to 40 mg/day. |
| Geriatric use | Initiate at 2.5 mg once or twice daily; titrate cautiously due to increased sensitivity and cardiovascular risk. |
| 1st trimester | Potential for teratogenic effects; use only if benefit outweighs risk. Associated with increased risk of congenital malformations, particularly cardiovascular defects, when used during first trimester. Avoid unless no alternative. |
| 2nd trimester | Risk of fetal growth restriction, premature birth, and withdrawal symptoms. Use only if clearly needed. Monitor fetal growth. |
| 3rd trimester | Increased risk of neonatal withdrawal syndrome, including irritability, feeding difficulties, and respiratory distress. Avoid in late pregnancy unless necessary. |
Clinical note
MAOIs can cause hypertensive crisis Alkalinizing agents increase urinary excretion and acidifying agents decrease it High potential for abuse and dependence.
| Placental transfer | Dextroamphetamine crosses the placenta via passive diffusion and active transport. Evidence: detected in cord blood at approximately 2-3% maternal plasma concentration. Fetal exposure is significant with chronic use. |
| Breastfeeding |
■ FDA Black Box Warning
Misuse may cause serious cardiovascular events and sudden death; high potential for abuse and dependence.
| Common Effects | narcolepsy |
| Serious Effects |
Known hypersensitivity to amphetamines or other sympathomimetic aminesConcomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI use (hypertensive crisis risk)Advanced arteriosclerosisSymptomatic cardiovascular disease (including moderate to severe hypertension, hyperthyroidism)GlaucomaAgitated statesHistory of drug abuse or dependence (amphetamine abuse potential)Concomitant use of other CNS stimulantsPatients with a history of bipolar disorder unless euthymic and stabilized on mood stabilizers (risk of manic induction)
| Precautions | While the drug is typically well-tolerated, serious thrombocytopenia, leukopenia, neutropenia, and agranulocytosis have been reported; also, hypertensive crisis if co-administered with MAOIs or within 14 days of MAOI discontinuation; serotonin syndrome risk; exacerbation of tics; growth suppression in children; long-term abuse potential. |
Loading safety data…
| Dextroamphetamine is excreted into breast milk in small amounts. Potential for infant irritability, poor feeding, and sleep disturbances. Consider alternative agents, especially in breastfeeding of premature or jaundiced infants. Monitor for infant agitation and weight gain. |
| Lactation Rating | L3 (Moderately Safe) - Use with caution |
| Teratogenic Risk | First trimester: Increased risk of major congenital malformations (e.g., cardiac, cleft palate) based on limited human data; animal studies show dose-dependent teratogenicity (cleft palate, exencephaly) at high doses. Second and third trimesters: Risk of preterm delivery, low birth weight, and neonatal withdrawal (irritability, dysphoria). Use only if potential benefit outweighs risk; avoid in first trimester if possible. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and weight gain throughout pregnancy. Assess fetal growth via ultrasound for intrauterine growth restriction. Monitor for signs of preterm labor. Evaluate neonatal for withdrawal symptoms and cardiovascular effects post-delivery. Perform echocardiogram if cardiac anomalies suspected. |
| Fertility Effects | No definitive human studies; animal data suggest possible effects on ovarian cyclicity and sperm parameters at high doses. May impair fertility due to central nervous system effects (e.g., appetite suppression, weight loss). Advise reproductive-aged patients to use effective contraception if not planning pregnancy. |
| Food/Dietary | Absorption of dextroamphetamine is enhanced by acidic foods/juices (e.g., citrus, cola) and reduced by antacids or alkalinizing agents (e.g., sodium bicarbonate). Avoid large amounts of vitamin C-rich foods/juices within 1 hour of dosing as they may decrease absorption. Alcohol should be avoided due to increased risk of cardiovascular effects and impaired judgment. Grapefruit juice may alter metabolism via CYP2D6 inhibition but interaction is not clinically significant. |
| Clinical Pearls | Dextroamphetamine sulfate is the dextrorotatory isomer of amphetamine, more potent than racemic amphetamine. Onset of action is 30-60 minutes with peak effect at 2-3 hours for immediate-release (IR) and 8-10 hours for extended-release (XR). Contraindicated in patients with agitated states, history of drug abuse, glaucoma, hyperthyroidism, or concurrent MAOI use. Monitor growth in children (height/weight) and assess for tics, Tourette's syndrome, or psychiatric symptoms (psychosis, mania). Cardiovascular risks include sudden death in patients with structural cardiac abnormalities. Use with caution in hypertension, seizures, or bipolar disorder. |
| Patient Advice | Take dextroamphetamine exactly as prescribed. Do not increase dose or take more frequently without consulting your doctor. · This medication has a high potential for abuse and dependence. Store securely and dispose of unused medication properly. · Avoid taking this medication late in the day to prevent insomnia. Take immediate-release forms 30-60 minutes before meals. · Report any chest pain, palpitations, shortness of breath, or fainting immediately. · Inform your doctor if you experience agitation, aggression, hallucinations, or new/worsening mental health symptoms. · Do not stop this medication abruptly; it may cause severe fatigue, depression, or withdrawal symptoms. · Limit caffeine intake as it may worsen side effects like nervousness, jitteriness, and insomnia. · Maintain adequate hydration and nutrition as appetite suppression may occur; monitor weight regularly in children. |