Dextroamphetamine - Drug Monograph

Introduction

Dextroamphetamine is a central nervous system (CNS) stimulant belonging to the amphetamine class of medications. First approved by the FDA in 1976, it is primarily used for the treatment of attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. As a Schedule II controlled substance, dextroamphetamine has high potential for abuse and dependence but remains a cornerstone therapy when used appropriately under medical supervision.

Mechanism of Action

Dextroamphetamine exerts its effects primarily through multiple mechanisms in the central nervous system. It promotes the release of monoamine neurotransmitters (norepinephrine, dopamine, and to a lesser extent, serotonin) from presynaptic neurons and inhibits their reuptake. Additionally, it acts as a weak monoamine oxidase inhibitor. The increased availability of these neurotransmitters, particularly dopamine and norepinephrine in the prefrontal cortex, improves attention, focus, and impulse control in ADHD, while its stimulant properties help combat excessive daytime sleepiness in narcolepsy.

Indications

• FDA-approved indications:

- Attention-deficit/hyperactivity disorder (ADHD) in children (age 3+) and adults - Narcolepsy

• Off-label uses (require careful risk-benefit consideration):

- Treatment-resistant depression (as adjunctive therapy) - Fatigue associated with medical conditions (e.g., multiple sclerosis, cancer-related fatigue)

Dosage and Administration

• Children (6-17 years): Start 5 mg once or twice daily; increase by 5 mg increments weekly
• Adults: Start 5 mg once or twice daily; usual effective dose 20-40 mg daily in divided doses
• Maximum dose: 40 mg daily (pediatrics); 60 mg daily (adults)

• Start 10 mg daily; increase by 10 mg increments weekly
• Usual dose: 5-60 mg daily in divided doses

• Administer first dose upon awakening; subsequent doses every 4-6 hours
• Avoid late evening doses to prevent insomnia
• May be taken with or without food

• Renal impairment: Use with caution; consider dose reduction
• Hepatic impairment: Use with caution; consider dose reduction
• Geriatric: Start with lowest possible dose
• Pediatric: Not recommended under age 3 years

Pharmacokinetics

• Absorption: Well absorbed from GI tract; bioavailability 75-100%
• Distribution: Vd: 3-4 L/kg; Protein binding: 15-20%
• Metabolism: Hepatic via multiple pathways including CYP2D6; produces active metabolites
• Elimination: Half-life: 10-12 hours (adults); 6-8 hours (children); primarily renal excretion (30-40% unchanged)
• Onset of action: 30-60 minutes
• Duration: 4-6 hours (immediate-release); 8-12 hours (extended-release formulations)

Contraindications

• Known hypersensitivity to amphetamines or product components
• Advanced arteriosclerosis
• Symptomatic cardiovascular disease
• Moderate to severe hypertension
• Hyperthyroidism
• Glaucoma
• Agitated states
• History of drug abuse
• Within 14 days of MAO inhibitor use (risk of hypertensive crisis)

Warnings and Precautions

• Black Box Warning: High potential for abuse and dependence
• Cardiovascular effects: May increase BP and HR; monitor regularly
• Psychiatric effects: May exacerbate psychosis, bipolar disorder, or aggressive behavior
• Growth suppression: Monitor height and weight in pediatric patients
• Peripheral vasculopathy: Raynaud's phenomenon reported
• Serotonin syndrome: Risk when used with other serotonergic drugs
• Pregnancy: Category C; weigh risks versus benefits
• Abrupt discontinuation: May cause extreme fatigue and depression

Drug Interactions

• MAO inhibitors: Contraindicated (hypertensive crisis risk)
• Serotonergic drugs: Increased risk of serotonin syndrome
• Acidifying agents: (Vitamin C, ammonium chloride) decrease amphetamine absorption
• Alkalinizing agents: (Sodium bicarbonate, acetazolamide) increase amphetamine absorption
• Antihypertensives: May antagonize effects
• Tricyclic antidepressants: May enhance cardiovascular effects
• CYP2D6 inhibitors: May increase dextroamphetamine levels

Adverse Effects

• Insomnia
• Decreased appetite
• Dry mouth
• Headache
• Gastrointestinal disturbances
• Weight loss
• Anxiety/nervousness

• Cardiovascular: Hypertension, tachycardia, palpitations
• Psychiatric: Psychosis, mania, aggression
• Neurologic: Seizures, cerebrovascular events
• Peripheral vasculopathy
• Priapism
• Visual disturbances

Monitoring Parameters

• Baseline and periodic:

- Blood pressure and heart rate (at least quarterly) - Height and weight in children (every 3-6 months) - Cardiovascular status in patients with risk factors - Psychiatric status - Signs of misuse, abuse, or diversion

• Therapeutic efficacy:

- ADHD rating scales - Functional improvement assessments - Sleep patterns - Appetite and nutritional status

Patient Education

• Take medication exactly as prescribed; do not increase dose without medical supervision
• Avoid late afternoon or evening doses to prevent insomnia
• Report chest pain, palpitations, shortness of breath, or fainting immediately
• Monitor weight regularly; report significant weight loss
• Be aware of potential for dizziness; use caution when driving or operating machinery
• Do not abruptly stop medication; discuss taper schedule with provider
• Store medication securely to prevent misuse by others
• Inform all healthcare providers of dextroamphetamine use
• Avoid alcohol and other CNS stimulants
• Use reliable contraception while taking this medication

References

1. FDA Prescribing Information: Dextroamphetamine Sulfate Tablets (2022) 2. Stahl SM. Stahl's Essential Psychopharmacology: Prescriber's Guide. 6th ed. Cambridge University Press; 2017 3. Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921 4. Goodman DW. Lisdexamfetamine dimesylate (vyvanse), a prodrug stimulant for attention-deficit/hyperactivity disorder. P T. 2010;35(5):273-287 5. Berman SM, Kuczenski R, McCracken JT, London ED. Potential adverse effects of amphetamine treatment on brain and behavior: a review. Mol Psychiatry. 2009;14(2):123-142 6. Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018;5(9):727-738 7. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014