DEXEDRINE SPANSULE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEXEDRINE SPANSULE (DEXEDRINE SPANSULE).
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.
| 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). |
| Molecular Weight | 135.21 |
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. |
| 1st trimester | Limited human data; animal studies show increased risk of cardiovascular malformations and cleft palate. Use only if benefit outweighs risk. |
| 2nd trimester | May increase risk of preeclampsia, premature birth, and low birth weight. Use with caution. |
| 3rd trimester | Risk of neonatal withdrawal symptoms (irritability, jitteriness, poor feeding) and possible neonatal hypertension. Avoid use. |
Clinical note
Comprehensive clinical and safety monograph for DEXEDRINE SPANSULE (DEXEDRINE SPANSULE).
| Placental transfer | Dexedrine crosses the placenta; fetal plasma levels may reach maternal levels. |
| Breastfeeding | Dexedrine is excreted into breast milk in low concentrations (relative infant dose ~2-13.8%). Monitor infant for agitation, poor feeding, and insomnia. Use lowest effective dose. Consider risk of decreased milk production. |
■ 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.
| Serious Effects |
Advanced arteriosclerosisSymptomatic cardiovascular diseaseModerate to severe hypertensionHyperthyroidismKnown hypersensitivity to amphetaminesGlaucomaAgitated statesHistory of drug abuseConcurrent use or within 14 days of MAO inhibitors
| 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. |
| Food/Dietary |
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| Lactation Rating | L3 - Moderately Safe |
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and weight gain. Fetal ultrasound for growth and anatomy. Neonatal monitoring for withdrawal symptoms and growth parameters after delivery. |
| Fertility Effects | May impair fertility in males (sperm count and motility) and females (anovulation) due to dopaminergic effects; generally reversible upon discontinuation. |
| High-fat meals significantly delay and reduce peak plasma concentrations; administer on an empty stomach for consistent effect. Avoid foods and beverages high in vitamin C (e.g., citrus fruits, juices) within 1 hour before or after dosing, as they can reduce absorption. Avoid alcohol and caffeine as they may exacerbate sympathomimetic adverse effects. |
| Clinical Pearls | Avoid administration with high-fat meals as they delay absorption and blunt peak plasma concentration. Use with caution in patients with structural cardiac abnormalities, hypertension, hyperthyroidism, or glaucoma. Monitor for growth suppression in children; treatment holidays may be considered. Do not combine with MAOIs; discontinue MAOIs for at least 14 days before starting. Potential for dependence and abuse; prescribe limited quantities with frequent follow-up. |
| Patient Advice | Take this medication exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Swallow the capsule whole; do not crush, chew, or open it. · Take the first dose in the morning to avoid insomnia; avoid late afternoon or evening dosing. · Report any chest pain, palpitations, shortness of breath, or fainting immediately. · Avoid alcohol and caffeine-containing products as they may worsen side effects. · Store at room temperature, away from heat, moisture, and light; keep out of reach of children. |