DEXEDRINE SPANSULE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEXEDRINE SPANSULE (DEXEDRINE SPANSULE).

How it works

Dextroamphetamine is a central nervous system (CNS) stimulant that increases synaptic concentrations of norepinephrine and dopamine by blocking their reuptake and promoting release from presynaptic terminals.

What the body does with it

Metabolism	Primarily metabolized by cytochrome P450 (CYP) 2D6 to various metabolites including p-hydroxyamphetamine, which is then further metabolized.
Excretion	Renal excretion of unchanged drug (approximately 30-40% unchanged) and hepatic metabolism to inactive metabolites (primarily hippuric acid, benzoic acid, and hydroxylated derivatives). About 90% of a dose is excreted in urine within 48 hours, with 10-15% as unchanged dextroamphetamine; minor biliary/fecal elimination (<5% total).
Half-life	Terminal elimination half-life is 6-8 hours in adults, 10-13 hours in children, and prolonged in alkaline urine (up to 16-20 hours) due to enhanced tubular reabsorption. In hepatic impairment, half-life may extend to 12-15 hours. Steady-state is reached within 2-3 days.
Protein binding	Approximately 20% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd: 3-5 L/kg (high tissue distribution; approximately 4 L/kg in adults). Extensive distribution into brain, lungs, and other highly perfused organs; crosses placenta and enters breast milk.
Bioavailability	Oral immediate-release: 75-100% (first-pass metabolism minimal). Spansule (extended-release): approximately 90% relative bioavailability vs immediate-release (AUC equivalent but with delayed peak).
Onset of Action	Immediate-release: 30-60 minutes (peak effect 1-3 hours). Spansule (extended-release): 1-2 hours (peak effect 4-8 hours). Intravenous: immediate (1-2 minutes).
Duration of Action	Immediate-release: 4-6 hours. Spansule (extended-release): 8-12 hours (up to 14 hours in some patients). Duration is dose-dependent and affected by urinary pH (acidic urine shortens, alkaline prolongs).

Classification & Brands

Dosing & administration

5-60 mg orally once daily in the morning, using extended-release capsules.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	eGFR 30-89 mL/min: reduce dose by 50%; eGFR <30 mL/min: avoid use.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	3-5 years: 2.5-5 mg orally once daily; 6 years and older: 5-15 mg orally once daily.
Geriatric use	Start at 2.5 mg orally once daily; increase gradually; monitor for agitation, hypertension, and weight loss.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DEXEDRINE SPANSULE (DEXEDRINE SPANSULE).

Breastfeeding	Excreted in breast milk; M/P ratio not established. Potential for infant adverse effects (irritability, insomnia, growth suppression). Contraindicated per manufacturer; avoid breastfeeding.
Teratogenic Risk	First trimester: Case reports of increased risk of congenital malformations (e.g., cardiac, oral clefts). Second and third trimesters: Risk of premature delivery, low birth weight, and neonatal withdrawal (irritability, hypertonia). Increased risk of maternal hypertension and preeclampsia.

Warnings & precautions

■ FDA Black Box Warning

WARNING: ABUSE AND DEPENDENCE. CNS stimulants, including DEXEDRINE SPANSULE, 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Advanced arteriosclerosis","Symptomatic cardiovascular disease","Moderate to severe hypertension","Hyperthyroidism","Known hypersensitivity to amphetamine or other sympathomimetic amines","Glaucoma","Agitated states","History of drug abuse","During or within 14 days following administration of monoamine oxidase inhibitors (MAOIs)"]

Clinical Precautions

Precautions

["Serious cardiovascular events including sudden death, stroke, and myocardial infarction have been reported in adults and children with pre-existing cardiac abnormalities.","Blood pressure and heart rate should be monitored regularly.","Psychiatric adverse reactions including exacerbation of pre-existing psychosis, manic episodes, and aggressive behavior.","Long-term suppression of growth in children; monitor height and weight.","Risk of peripheral vasculopathy including Raynaud's phenomenon.","May have serious interactions with MAOIs; avoid concomitant use."]

Clinical Tips & Counseling

Drug interactions

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DEXEDRINE SPANSULE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEXEDRINE SPANSULE (DEXEDRINE SPANSULE).

How it works

What the body does with it

Metabolism	Primarily metabolized by cytochrome P450 (CYP) 2D6 to various metabolites including p-hydroxyamphetamine, which is then further metabolized.
Excretion	Renal excretion of unchanged drug (approximately 30-40% unchanged) and hepatic metabolism to inactive metabolites (primarily hippuric acid, benzoic acid, and hydroxylated derivatives). About 90% of a dose is excreted in urine within 48 hours, with 10-15% as unchanged dextroamphetamine; minor biliary/fecal elimination (<5% total).
Half-life	Terminal elimination half-life is 6-8 hours in adults, 10-13 hours in children, and prolonged in alkaline urine (up to 16-20 hours) due to enhanced tubular reabsorption. In hepatic impairment, half-life may extend to 12-15 hours. Steady-state is reached within 2-3 days.
Protein binding	Approximately 20% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd: 3-5 L/kg (high tissue distribution; approximately 4 L/kg in adults). Extensive distribution into brain, lungs, and other highly perfused organs; crosses placenta and enters breast milk.
Bioavailability	Oral immediate-release: 75-100% (first-pass metabolism minimal). Spansule (extended-release): approximately 90% relative bioavailability vs immediate-release (AUC equivalent but with delayed peak).
Onset of Action	Immediate-release: 30-60 minutes (peak effect 1-3 hours). Spansule (extended-release): 1-2 hours (peak effect 4-8 hours). Intravenous: immediate (1-2 minutes).
Duration of Action	Immediate-release: 4-6 hours. Spansule (extended-release): 8-12 hours (up to 14 hours in some patients). Duration is dose-dependent and affected by urinary pH (acidic urine shortens, alkaline prolongs).

Classification & Brands

Dosing & administration

5-60 mg orally once daily in the morning, using extended-release capsules.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	eGFR 30-89 mL/min: reduce dose by 50%; eGFR <30 mL/min: avoid use.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	3-5 years: 2.5-5 mg orally once daily; 6 years and older: 5-15 mg orally once daily.
Geriatric use	Start at 2.5 mg orally once daily; increase gradually; monitor for agitation, hypertension, and weight loss.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for DEXEDRINE SPANSULE (DEXEDRINE SPANSULE).

Breastfeeding	Excreted in breast milk; M/P ratio not established. Potential for infant adverse effects (irritability, insomnia, growth suppression). Contraindicated per manufacturer; avoid breastfeeding.
Teratogenic Risk	First trimester: Case reports of increased risk of congenital malformations (e.g., cardiac, oral clefts). Second and third trimesters: Risk of premature delivery, low birth weight, and neonatal withdrawal (irritability, hypertonia). Increased risk of maternal hypertension and preeclampsia.