DEXTROAMPHETAMINE SULFATE

Clinical safety rating: avoid

Positive evidence of fetus risks but benefits may outweigh risks in some cases

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

MAOIs can cause hypertensive crisis Alkalinizing agents increase urinary excretion and acidifying agents decrease it High potential for abuse and dependence.

Breastfeeding

Excreted into breast milk; relative infant dose approximately 5-10% of maternal weight-adjusted dose. M/P ratio not established. Reports of irritability, poor feeding, and growth suppression in nursing infants. Contraindicated in breastfeeding due to potential adverse effects; if used, monitor infant for agitation and insomnia.

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.

Warnings & precautions

■ FDA Black Box Warning

Misuse may cause serious cardiovascular events and sudden death; high potential for abuse and dependence.

Side Effect Profile

Common Effects	narcolepsy
Serious Effects

Absolute Contraindications

Hypersensitivity to sympathomimetic amines; concurrent MAOI use or within 14 days; glaucoma; hyperthyroidism; severe hypertension; symptomatic cardiovascular disease; agitated states; history of drug abuse.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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