Dexedrine Spansule

(dextroamphetamine sulfate)

Dexedrine Spansule (dextroamphetamine sulfate); CII

Summary

Dexedrine Spansule is a sustained-release dextroamphetamine capsule approved for narcolepsy and for ADHD in patients aged 6 to 16. It is single-isomer dextroamphetamine, so it carries no levoamphetamine and less peripheral noradrenergic load than Adderall XR at an equivalent dose. Its role is once-daily dextroamphetamine where the immediate-release tablet would need two or three doses; the label is candid that the pellet is only more convenient, not more effective. Schedule II; brand and generic.

Forms & Strengths

• Sustained-release capsules (Spansule): 5 mg, 10 mg, 15 mg

Dosing

• Age:
  • ADHD: 6-16 y/o, the label's own upper bound. Not recommended below 6 years
  • Narcolepsy: no age bound stated; the label gives a dose ladder from age 6
• Onset: 30-60 min, from the promptly released initial fraction
• Duration: 6 to 8 hours
• Release Profile: Sustained-release pellets; an initial dose released promptly, the remainder gradually. Tmax about 8 hours against about 3 hours for the tablet
• Initial Dose:
  • ADHD, 6-16 y/o: 5 mg once or twice daily
  • Narcolepsy, 6-11 y/o: 5 mg daily
  • Narcolepsy, ≥ 12 y/o: 10 mg daily
• Titration:
  • ADHD, 6-16 y/o: 5 mg at weekly intervals
  • Narcolepsy, 6-11 y/o: 5 mg at weekly intervals
  • Narcolepsy, ≥ 12 y/o: 10 mg at weekly intervals
• Max Dose:
  • ADHD: 40 mg/day; only in rare cases will it be necessary to exceed this
  • Narcolepsy: usual range 5-60 mg/day in divided doses
• Considerations: Use once daily where appropriate; the same total dose of immediate release in divided doses is equally effective by this label. Avoid late evening doses.

Pharmacology

• Mechanism: Blocks reuptake at DAT and NET and promotes presynaptic catecholamine release via VMAT2 and TAAR1; the release component is what distinguishes amphetamines from methylphenidate
• Delivery / Release: Lower peak than the tablet (Cmax 23.5 vs 36.6 ng/mL at 15 mg), same bioavailability
• Formulation: Single-isomer dextroamphetamine sulfate; no levoamphetamine, the difference from the 3:1 mixed-salt products
• Metabolism: CYP2D6 to 4-hydroxyamphetamine, with minor CYP2D6 inhibition. Half-life about 12 hours. Renal excretion is pH dependent
• Pharmacogenomics: No genotype-directed dosing in the label; the actionable consequence is the CYP2D6-inhibitor interaction
• Class Positioning: Buys once-daily dosing and a lower peak over Zenzedi, and gives up the 3 to 5 year band. Single-isomer and later-peaking than Adderall XR

Indications

• Narcolepsy (ICD-10: G47.419): no age bound stated; dosing from age 6
• ADHD (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 6 to 16 y/o, within a total treatment program

Off-Label Uses

• ADHD at 17 and older (ICD-10: F90.x): this label stops at 16. Supported by the broader amphetamine literature; switch to a product with an adult indication.
• ADHD under 6 years (ICD-10: F90.x): insufficient. Zenzedi, the same moiety, is approved from age 3, so the floor is formulation-specific. AAP: behavioral intervention first-line (AAP 2019).
• Binge eating disorder (ICD-10: F50.81): lisdexamfetamine holds it, adults only; insufficient here.
• Where the evidence does not support use: depression augmentation; no pediatric evidence for sustained-release dextroamphetamine (AHRQ 2024).
• Cognitive enhancement without ADHD: not an indication; not supported.

Contraindications & Warnings

• Boxed Warning: Abuse, misuse, and addiction; risk of overdose and death, rising with higher doses and non-oral routes. Assess abuse risk and monitor throughout.
• Contraindicated:
  • Known hypersensitivity to amphetamine or any component
  • MAOI use, current or within 14 days
• Use with caution (label Warnings, not contraindications):
  • Structural cardiac abnormality, cardiomyopathy or serious arrhythmia; the label says avoid
  • Pre-existing hypertension; expect mean rises of 2-4 mmHg and 3-6 bpm
  • Psychosis or bipolar disorder; in psychotic children, worsened behaviour disturbance and thought disorder
  • Prior seizure or EEG abnormality
  • Peripheral vasculopathy including Raynaud phenomenon
  • Tics or Tourette syndrome, personal or family
  • Substance use disorder, patient or household
  • Symptoms secondary to environmental factors or another psychiatric disorder
• Screen before starting:
  • Cardiac and family history of sudden death or ventricular arrhythmia; ECG only if positive
  • Tics and Tourette syndrome, in child and family; this label makes that a precondition
  • Mania risk factors, including family history of suicide or bipolar disorder
  • Abuse and diversion risk
  • Baseline height, weight, blood pressure and heart rate

Drug Interactions

• MAOIs (selegiline, tranylcypromine, phenelzine, linezolid, methylene blue): hypertensive crisis; do not give within 14 days.
• Serotonergic agents (SSRIs, SNRIs, TCAs, triptans, fentanyl, lithium, tramadol, buspirone): serotonin syndrome; counsel on symptoms and stop both if it occurs.
• CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine, ritonavir): raise exposure; start lower.
• Alkalinizing agents (sodium bicarbonate, acetazolamide): raise levels; the label says avoid.
• Acidifying agents (ascorbic acid, methenamine salts): lower levels; adjust on response.
• Tricyclics (desipramine, protriptyline): sustained rise in brain d-amphetamine; monitor and adjust.
• Antiepileptics (phenytoin, phenobarbital, ethosuximide): delayed absorption; separate dosing and check levels after any stimulant change.
• Antihypertensives: hypotensive effect antagonised; recheck blood pressure after starting the stimulant.
• Antihistamines: sedative effect counteracted; do not rely on one for sleep.

Administration

• Give the first dose on waking; may be used once daily wherever appropriate.
• For narcolepsy the label's usual dose is divided; the Spansule may replace those divisions.
• Avoid late evening doses.
• Swallow whole. This label carries no instruction to open, sprinkle, crush or chew, and no data for doing so, unlike its mixed-salt siblings.
• If the child cannot swallow a capsule, switch to an IR tablet or ProCentra oral solution.
• Food does not matter; absorption is similar fed and fasted.
• The label directs prescribing the least quantity feasible at one time.
• If a dose is missed, skip it; do not double up.
• Store securely, preferably locked.

Side Effects

• Common: loss of appetite, weight loss, insomnia, overstimulation, restlessness, dry mouth, headache, dizziness, tremor, dysphoria, diarrhoea, constipation, palpitations, raised blood pressure
• Serious:
  • Sudden death with structural cardiac disease. Investigate exertional chest pain or syncope immediately.
  • Psychotic episodes at recommended doses (rare), mania and new aggression. Consider discontinuing.
  • Serotonin syndrome. Stop both drugs and treat supportively.
  • Seizures. Discontinue.
  • Peripheral vasculopathy with digital ulceration. Reduce or stop; refer if persistent.
  • Growth suppression. Interrupt if height or weight gain falls behind.
  • New or worsening motor and verbal tics. Discontinue if clinically appropriate.
  • Cardiomyopathy with chronic use, rhabdomyolysis, intestinal ischaemia.
  • Prolonged erections; painful erection beyond a few hours is a surgical emergency.

Monitoring & Labs

• Cardiovascular: heart rate and blood pressure at baseline, each dose change, and every 6 months.
• Growth: height, weight and BMI charted at baseline and every 6 months; interrupt if two major percentile lines are crossed.
• Appetite and Sleep: at every visit and dose change; ask what time the child eats and falls asleep.
• Psychiatric and tics: psychosis, mania, aggression, dysphoria and new tics at every visit.
• Peripheral vasculopathy: inspect fingers and toes at every visit.
• Abuse and Diversion: adherence, pill counts and PDMP check at every refill; set quantity limits per this label's least-quantity instruction.
• Age boundary: review the indication at the 17th birthday.
• Laboratory: none routinely.

Discontinuation & Taper

• May be stopped abruptly at therapeutic doses; no taper is required.
• Withdrawal after abrupt stop following prolonged use: dysphoria, fatigue, vivid dreams, increased appetite.
• Rebound irritability and hunger arrive later than with the IR tablet; families describe a difficult evening.
• Interrupt treatment where growth or weight gain falls behind.
• Drug holidays are reasonable where appetite or growth suppression is limiting; unlike Zenzedi, this label does not itself recommend periodic interruption.

Pregnancy & Lactation

• Pregnancy: No adequate controlled studies; animal teratogenicity only far above human doses. Amphetamine-dependent mothers have more premature delivery and low birth weight. Use only if benefit justifies fetal risk.
• Lactation: Label advises against nursing. LactMed: infant dose about 5.7% of the maternal weight-adjusted dose, infant plasma 6 to 14% of maternal, all four infants studied growing normally. (LactMed 2025)
• Milk supply: Dose-related prolactin suppression up to 40% may impair production before lactation is established. (LactMed 2025)
• Exposure Registry: None on this label; the National Pregnancy Registry for Psychostimulants (1-866-961-2388) accepts amphetamine exposures.

Counseling Points

• Counsel the family on:

  • Swallowing the capsule whole; unlike the mixed-salt capsules there is no sprinkle instruction.
  • Telling you if the child cannot swallow it, so the product changes rather than being improvised.
  • The capsule being a convenience, not an upgrade; divided immediate release works as well.
  • The later peak, around eight hours, so the hard stretch is often evening rather than mid-afternoon.
  • Vitamin C mimicking treatment failure; bicarbonate and antacids raising levels.
  • On phenytoin, phenobarbital or ethosuximide, a level check after a stimulant change is expected.
  • Moving the largest meal to breakfast and evening, with a weight check each visit.
  • The ADHD approval running to age 16; plan before the 17th birthday.
  • Locked storage; the prescription is deliberately written in the smallest workable quantity.

• Advise them to call for:

  • Chest pain on exertion, fainting, or a racing heart that does not settle.
  • New hallucinations, or new suspicious or fearful thinking.
  • Numbness, coldness or colour change in the fingers or toes.
  • A new or markedly worse tic, or a seizure of any kind.
  • Severe muscle pain with dark urine after exertion.
  • Weight loss, or clothes fitting more loosely over a few weeks.
  • A painful erection lasting more than a few hours, which is a surgical emergency.
  • Agitation, shivering, sweating or confusion after an antidepressant change.

References

1. DailyMed. DEXEDRINE SPANSULE (dextroamphetamine sulfate) sustained-release capsules prescribing information. Amneal Pharmaceuticals LLC. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cc717b9b-22ea-4c60-a1d4-ee38a40bce78
2. LactMed. Dextroamphetamine. Drugs and Lactation Database, National Institute of Child Health and Human Development. 2025. https://www.ncbi.nlm.nih.gov/books/NBK501740/
3. openFDA. NDC Directory, generic_name "dextroamphetamine". US Food and Drug Administration. 2026. https://api.fda.gov/drug/ndc.json
4. American Academy of Pediatrics. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics 144(4):e20192528. 2019. https://publications.aap.org/pediatrics/article/144/4/e20192528/81590/Clinical-Practice-Guideline-for-the-Diagnosis
5. Agency for Healthcare Research and Quality. ADHD Diagnosis and Treatment in Children and Adolescents. Comparative Effectiveness Review No. 267. 2024. https://www.ncbi.nlm.nih.gov/books/NBK602989/