A Comprehensive Monograph on Dextroamphetamine (DB01576)

Section 1: Introduction and Executive Summary

1.1 Overview

Dextroamphetamine is a potent small molecule drug, identified as the dextrorotatory, or (S)-enantiomer, of amphetamine. It is classified pharmacologically as a central nervous system (CNS) stimulant and a non-catecholamine sympathomimetic amine.[1] As a cornerstone therapy in the management of specific neurobehavioral disorders, its clinical utility is well-established, though it is invariably accompanied by a complex and significant risk profile that necessitates careful clinical management.

1.2 Therapeutic Indications

The United States Food and Drug Administration (FDA) has approved dextroamphetamine for two primary indications: Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy.[1] In the treatment of ADHD, dextroamphetamine functions to increase attention and decrease restlessness and impulsivity in children and adults who are overactive, easily distracted, or cannot concentrate for extended periods. It is critical to recognize that pharmacotherapy with dextroamphetamine is not a standalone treatment but is indicated as an integral component of a comprehensive therapeutic program that includes psychological, educational, and social interventions.[5] For narcolepsy, it is used to manage the primary symptom of uncontrollable daytime sleepiness.[2]

1.3 Pharmacological Synopsis

The therapeutic and psychoactive effects of dextroamphetamine are mediated primarily through its potent activity on catecholaminergic neurotransmitter systems. Its fundamental mechanism of action involves increasing the synaptic concentrations of dopamine and norepinephrine in the brain, particularly within the striatum and prefrontal cortex.[3] This is achieved through a multifaceted process involving the inhibition and reversal of transporter proteins, disruption of vesicular storage, and inhibition of enzymatic degradation.

1.4 Risk Profile and Regulatory Status

The significant potential for misuse, abuse, and dependence is a defining characteristic of dextroamphetamine. This high risk profile has led to its stringent regulation globally. In the United States, the Drug Enforcement Administration (DEA) classifies dextroamphetamine as a Schedule II controlled substance, a designation reserved for drugs with a high potential for abuse that may lead to severe psychological or physical dependence, despite having accepted medical uses.[3] It is also listed under Schedule II of the World Health Organization's 1971 Convention on Psychotropic Substances.[12] Reflecting these serious risks, the FDA has mandated a black box warning on its labeling, the most stringent warning issued by the agency. This warning explicitly highlights the high potential for abuse and the risk of serious cardiovascular adverse events and sudden death, particularly with misuse.[7]

Section 2: Historical Context and Regulatory Evolution

2.1 Synthesis and Early Discovery

The history of dextroamphetamine is intrinsically linked to its parent compound, amphetamine. Amphetamine was first synthesized in 1887 by German chemist Lazar Edeleanu, though its pharmacological properties remained unexplored for decades.[17] In the late 1920s, American chemist Gordon Alles independently re-synthesized the compound while searching for a synthetic alternative to ephedrine.[17] Subsequent investigations revealed its potent CNS stimulant effects, and a pivotal discovery was made: of the two stereoisomers, the dextrorotatory enantiomer—dextroamphetamine—was significantly more potent in its central activity than the levorotatory enantiomer.[19]

2.2 Commercialization and Expansion of Use

The commercial journey of amphetamine began in 1934 when the pharmaceutical firm Smith, Kline & French (SKF) marketed it as the Benzedrine inhaler, an over-the-counter remedy for nasal congestion.[17] By 1937, the American Medical Association had approved amphetamine sulfate tablets for treating narcolepsy and post-encephalitic Parkinsonism.[17] Recognizing the superior potency of the dextro isomer, SKF began marketing dextroamphetamine sulfate under the brand name Dexedrine in 1937.[19] Following the expiration of the original patent in 1949, fierce competition among pharmaceutical companies fueled a dramatic expansion in its prescribed uses, most notably for weight control and the management of depressive symptoms and fatigue.[17]

2.3 Military Adoption and Societal Impact

During World War II, amphetamines were widely distributed to military personnel by Allied and Axis forces alike to combat fatigue, increase alertness, and sustain performance during prolonged combat operations.[17] This widespread military use had a profound societal effect, normalizing the drug's stimulant properties and contributing to its perception as a benign tool for enhancing performance and wakefulness in the post-war civilian population.

2.4 Emergence of Abuse and Regulatory Scrutiny

The broad availability and perceived safety of amphetamines inevitably led to widespread non-medical use and abuse. Individuals discovered that the contents of the Benzedrine inhalers could be extracted for a powerful stimulant effect, and the diversion of prescription tablets became rampant.[17] From the 1940s through the 1960s, the FDA dedicated significant enforcement resources to combating the illicit distribution of amphetamines, which had become a major public health concern.[20]

2.5 The Controlled Substances Act and Modern Regulation

The escalating crisis of amphetamine abuse culminated in decisive regulatory action. With the passage of the U.S. Controlled Substances Act in 1970, amphetamines were initially placed in Schedule III. However, recognizing their exceptionally high potential for abuse, they were quickly reclassified to the more restrictive Schedule II in 1971.[18] This landmark legislation fundamentally changed the landscape of amphetamine prescribing. Dexedrine was formally approved by the FDA in 1976 for the treatment of ADHD and narcolepsy, and a standalone dextroamphetamine product received FDA approval in 2001.[1] In the modern era, regulatory oversight continues to evolve, with tools such as state-level Prescription Monitoring Programs (PMPs) being mandated to help clinicians identify potential misuse and diversion.[10]

The historical trajectory of dextroamphetamine—from an over-the-counter panacea and a tool of war to a tightly regulated Schedule II substance—is not merely an academic footnote; it is the essential context that dictates modern clinical practice. The initial period of unregulated, widespread use for a vast array of conditions directly fostered a societal perception of the drug that was disconnected from its inherent risks. The subsequent normalization through military use further embedded it into the public consciousness. This environment, combined with aggressive pharmaceutical marketing, created the conditions for a public health crisis of abuse and dependence. The stringent regulatory framework established by the Controlled Substances Act was a direct and necessary response to this crisis. Consequently, a clinician prescribing dextroamphetamine today is managing the legacy of this history. Every prescription carries the weight of this potential for misuse, which is why a history of drug abuse is an absolute contraindication and why the FDA mandates a black box warning regarding its abuse potential.[7] The past directly and profoundly shapes the present standard of care.

Section 3: Chemical Identity and Physicochemical Properties

3.1 Nomenclature and Identifiers

For the purpose of unambiguous scientific and clinical communication, dextroamphetamine is identified by a standardized set of chemical names and registry numbers.

• Chemical Name: (S)-amphetamine; (2S)-1-phenylpropan-2-amine [1]
• DrugBank ID: DB01576 [User Query]
• CAS Number: 51-64-9 [User Query]
• IUPAC Name: (2S)-1-phenylpropan-2-amine [1]
• InChI: InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3/t8-/m0/s1 [1]
• InChIKey: KWTSXDURSIMDCE-QMMMGPOBSA-N [1]
• SMILES: C[C@@H](CC1=CC=CC=C1)N [1]

3.2 Molecular and Physical Characteristics

The physicochemical properties of dextroamphetamine are critical determinants of its pharmaceutical formulation, stability, and pharmacokinetic behavior. The properties of the free base differ from its more commonly used salt forms.

The fundamental data for dextroamphetamine are consolidated in Table 1. The molecule's moderate lipophilicity, indicated by a LogP of 1.76, facilitates its passage across the blood-brain barrier, which is essential for its central nervous system activity. Its character as a weak base, quantified by a pKa of 9.9, is of paramount clinical importance, as it directly governs the pH-dependent nature of its renal excretion, a key factor in its pharmacokinetic profile and potential for drug interactions. Apparent discrepancies in its physical description are resolved by noting that the free base form is an oil or liquid at room temperature, whereas the pharmaceutically utilized salt forms, such as dextroamphetamine sulfate, are stable crystalline solids.[1]

Table 1: Key Chemical and Physical Properties of Dextroamphetamine

Property	Value	Source(s)
IUPAC Name	(2S)-1-phenylpropan-2-amine	1
CAS Number	51-64-9	[User Query]
Molecular Formula (Base)	C9​H13​N	12
Molecular Weight (Base)	135.21 g/mol	12
Physical Description	Free Base: Colorless liquid, Oil; Salts: Solid	1
Boiling Point	203.5 °C	1
Melting Point (Base)	< 25 °C	1
Water Solubility	1.74 g/L (Slightly soluble)	1
LogP	1.76	1
pKa	9.9	3

Section 4: Clinical Pharmacology

4.1 Mechanism of Action (Pharmacodynamics)

Dextroamphetamine is a non-catecholamine, sympathomimetic amine that exerts potent CNS stimulant activity.[1] Its primary pharmacodynamic effect is the substantial elevation of extracellular concentrations of the monoamine neurotransmitters dopamine and norepinephrine, particularly within the synaptic clefts of the striatum and prefrontal cortex.[3] This is not achieved through direct receptor agonism but via a complex, multi-pronged modulation of presynaptic neuronal function:

1. Competitive Inhibition and Reverse Transport: Dextroamphetamine acts as a substrate for the dopamine transporter (DAT) and the norepinephrine transporter (NET). It competitively inhibits the reuptake of dopamine and norepinephrine from the synapse back into the presynaptic neuron. More significantly, it acts as a releasing agent by reversing the normal direction of these transporters, causing them to actively efflux dopamine and norepinephrine from the cytoplasm of the neuron into the synaptic cleft.[2]
2. Vesicular Release: The drug disrupts the function of the vesicular monoamine transporter 2 (VMAT2), the protein responsible for sequestering cytoplasmic monoamines into synaptic vesicles for storage. By interfering with VMAT2, dextroamphetamine causes the leakage of vesicular dopamine and norepinephrine into the neuronal cytoplasm, thereby increasing the cytoplasmic pool available for reverse transport by DAT and NET.[9]
3. Monoamine Oxidase (MAO) Inhibition: Dextroamphetamine also exhibits weak inhibitory activity against monoamine oxidase, an enzyme that catabolizes monoamines within the presynaptic terminal. This action further increases the cytoplasmic concentration of dopamine and norepinephrine, augmenting their availability for release into the synapse.[2]

In addition to its central effects, dextroamphetamine exerts peripheral sympathomimetic actions, leading to elevations in both systolic and diastolic blood pressure, a positive chronotropic effect on the heart (tachycardia), and weak bronchodilator activity.[3] These peripheral effects are responsible for many of the drug's common and potentially serious cardiovascular adverse effects.

4.2 Pharmacokinetics (ADME)

The absorption, distribution, metabolism, and excretion (ADME) profile of dextroamphetamine is characterized by rapid absorption, wide distribution, extensive metabolism, and a clinically significant pH-dependent excretion pattern.

• Absorption: Dextroamphetamine is rapidly absorbed from the gastrointestinal tract following oral administration.[25] For immediate-release (IR) formulations, the time to reach peak plasma concentration ( Tmax​) is approximately 3 hours. For extended-release (ER) formulations, the Tmax​ is prolonged to approximately 7 hours.[3] The presence of food does not significantly affect the overall extent of absorption (bioavailability), but a high-fat meal can delay the Tmax​ of ER formulations by approximately 2 to 2.5 hours.[26] The duration of clinical effect is typically 4 to 6 hours for IR products and 8 to 12 hours for ER products.[3]
• Distribution: The drug is widely distributed throughout the body, consistent with its lipophilic nature. The volume of distribution (Vd​) is large, approximately 4 L/kg, and has been shown to increase with body weight.[3] Plasma protein binding is low, generally less than 20%, meaning a large fraction of the drug is free and pharmacologically active.[3]
• Metabolism: Dextroamphetamine undergoes extensive hepatic metabolism through several pathways, including aromatic hydroxylation to form 4-hydroxyamphetamine, and side-chain oxidation to form alpha-hydroxy-amphetamine and norephedrine. These metabolites are themselves pharmacologically active and are subject to further metabolism.[3] A key enzyme in the formation of 4-hydroxyamphetamine is cytochrome P450 2D6 (CYP2D6).[3] The gene encoding CYP2D6 is highly polymorphic in the human population, leading to distinct phenotypes of drug metabolism (e.g., poor, intermediate, extensive, and ultra-rapid metabolizers). This genetic variability can lead to significant inter-individual differences in amphetamine clearance, plasma concentrations, and, consequently, clinical response and toxicity. A patient who is a "poor metabolizer" may accumulate the drug to toxic levels on a standard dose, while an "ultra-rapid metabolizer" may clear it so quickly that they experience a diminished or absent therapeutic effect. This suggests that some cases of treatment failure or unusual sensitivity may have a pharmacogenomic basis, and for patients with anomalous responses, CYP2D6 genotyping could be a valuable tool to guide dosing.
• Excretion: Dextroamphetamine and its metabolites are primarily eliminated by the kidneys. Under normal urinary pH, approximately 30-40% of an administered dose is excreted as unchanged amphetamine.[3] The renal excretion of dextroamphetamine is highly dependent on urinary pH. This is a direct consequence of its chemical nature as a weak base with a pKa of 9.9.[3] In an acidic urine (low pH), the drug becomes more ionized, which prevents its reabsorption from the renal tubules back into the bloodstream, thereby increasing its renal clearance and shortening its duration of effect. Conversely, in an alkaline urine (high pH), the drug remains largely non-ionized, facilitating its tubular reabsorption and significantly decreasing its renal clearance, which prolongs its half-life and increases the risk of accumulation and toxicity. The urinary recovery of unchanged amphetamine can vary dramatically from as low as 1% in highly alkaline urine to as high as 75% in highly acidic urine.[26] This chemical property is the direct, mechanistic explanation for a major class of drug and food interactions. For instance, co-administration of urinary acidifying agents like ascorbic acid (Vitamin C) or consumption of large quantities of acidic fruit juices can reduce the drug's efficacy, while co-administration of urinary alkalinizing agents like sodium bicarbonate or acetazolamide can potentiate its effects and increase the risk of toxicity.[4]
• Half-Life: The mean elimination half-life (t1/2​) of dextroamphetamine varies with age. In adults, it is approximately 10 hours. In adolescents (13-17 years), it is slightly longer at around 11 hours, and in children (6-12 years), it is shorter, at approximately 9 hours.[26] On a milligram-per-kilogram basis, children exhibit higher clearance rates than adults, which accounts for the shorter half-life in this population.[26]

Section 5: Therapeutic Applications and Clinical Efficacy

5.1 Approved Indications

Dextroamphetamine is a well-established therapy for ADHD and narcolepsy, with its use guided by specific diagnostic criteria and the principle of comprehensive care.

• Attention Deficit Hyperactivity Disorder (ADHD): In patients with ADHD, dextroamphetamine is indicated to improve the core symptoms of inattention, hyperactivity, and impulsivity.[1] An adequate diagnosis is not based solely on a symptom checklist but requires a complete medical, psychological, educational, and social evaluation. The symptoms must be shown to cause clinically significant impairment in functioning across two or more settings, such as at school (or work) and at home.[8] It is imperative that drug treatment is considered one component of a total treatment program that may include psychosocial interventions and appropriate educational placement.[5]
• Narcolepsy: Dextroamphetamine is indicated for the symptomatic management of narcolepsy, a chronic neurological condition characterized by excessive daytime sleepiness and sudden, uncontrollable episodes of sleep.[2]

5.2 Formulations, Dosage, and Administration

Dextroamphetamine is available in several formulations to allow for individualized dosing strategies based on patient age, indication, and required duration of effect. A summary of available products is provided in Table 2, and recommended dosing regimens are detailed in Table 3.

Administration Guidelines:

To minimize the risk of insomnia, the last daily dose of immediate-release formulations should be administered at least 4 to 6 hours before bedtime. Extended-release formulations should be taken once daily in the morning upon awakening.3 ER capsules may be swallowed whole or, for patients with difficulty swallowing, the capsule may be opened and the entire contents sprinkled onto a spoonful of applesauce and consumed immediately without chewing. The dose from a single ER capsule should never be divided.3

Table 2: Commercially Available Dextroamphetamine Formulations in the United States

Brand Name(s)	Formulation Type	Available Strengths (mg)
Zenzedi	Immediate-Release (IR) Tablet	2.5, 5, 7.5, 10, 15, 20, 30
Dexedrine Spansule	Extended-Release (ER) Capsule	5, 10, 15
ProCentra	Oral Solution	5 mg/5 mL

Source(s): [8]

Dosing for dextroamphetamine must be highly individualized, beginning at a low dose and titrating gradually to achieve an optimal therapeutic response while minimizing adverse effects. This "start low, go slow" approach is a cornerstone of safe stimulant prescribing.

Table 3: Recommended Dosing Regimens for ADHD and Narcolepsy

Indication	Patient Population (Age)	Formulation	Initial Dose	Titration Schedule	Maximum Recommended Dose
ADHD	3–5 years	IR Tablet / Solution	2.5 mg once daily	Increase by 2.5 mg/day at weekly intervals	40 mg/day (rarely needed)
ADHD	≥6 years	IR / ER	IR: 5 mg once or twice daily; ER: 5-10 mg once daily	Increase by 5 mg/day at weekly intervals	40 mg/day (rarely needed)
Narcolepsy	6–12 years	IR / ER	5 mg once daily	Increase by 5 mg/day at weekly intervals	60 mg/day
Narcolepsy	≥12 years / Adults	IR / ER	10 mg once daily	Increase by 10 mg/day at weekly intervals	60 mg/day

Source(s): [5]

5.3 Clinical Trial Synopsis

Dextroamphetamine has been the subject of numerous clinical investigations to refine its use and explore its efficacy in various contexts. Completed clinical trials have evaluated novel formulations, such as a delayed and extended-release preparation (HLD100) specifically in children with ADHD (NCT02884544).[31] Other studies have explored the potential benefits of adjunctive therapies, including Vitamin D (NCT03103750) and Omega-3 fatty acids (NCT01399827), when used with stimulant medications for ADHD.[31] Furthermore, dextroamphetamine is included in large-scale, post-marketing observational studies designed to compare the long-term safety profiles of different ADHD medications, with a focus on rare but serious outcomes such as suicidality and psychosis (NCT04132557).[33]

Section 6: Safety Profile and Risk Management

The clinical use of dextroamphetamine requires a comprehensive understanding of its significant safety concerns, which are prominently highlighted in regulatory warnings and contraindications.

6.1 FDA Black Box Warnings

The FDA has mandated the following black box warnings for dextroamphetamine, reflecting the most serious risks associated with its use:

• High Potential for Abuse and Dependence: The labeling states that amphetamines have a high potential for abuse. Administration for prolonged periods of time may lead to drug dependence and must be avoided. This warning underscores the risk of the drug being diverted for non-therapeutic use or illicit distribution.[7]
• Serious Cardiovascular Risks: The warning explicitly states that misuse of amphetamines may cause sudden death and serious cardiovascular adverse events, including stroke and myocardial infarction.[8]

6.2 Contraindications

The use of dextroamphetamine is absolutely contraindicated in patients with certain pre-existing conditions due to an unacceptably high risk of serious adverse events. These include:

• Cardiovascular Conditions: Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, known structural cardiac abnormalities, cardiomyopathy, and serious heart rhythm abnormalities.[7]
• Psychiatric Conditions: Agitated states or a history of drug abuse.[7]
• Other Medical Conditions: Hyperthyroidism, glaucoma, or known hypersensitivity or idiosyncrasy to sympathomimetic amines.[7]
• Concurrent Medication Use: Use is contraindicated during or within 14 days following the administration of Monoamine Oxidase Inhibitors (MAOIs) due to the risk of a life-threatening hypertensive crisis.[5]

6.3 Adverse Drug Reactions

Adverse reactions to dextroamphetamine are common and can affect multiple organ systems.

• Very Common (≥10% incidence): Dry mouth (up to 35%), insomnia (up to 27%), headache (up to 26%), loss of appetite, abdominal pain, and nervousness.[38]
• Common (1% to 10% incidence): Tachycardia, palpitations, emotional lability, agitation, anxiety, dizziness, nausea, vomiting, diarrhea, and weight loss.[6]
• Cardiovascular: Clinically significant increases in systolic and diastolic blood pressure and heart rate are expected effects. Peripheral vasculopathy, including Raynaud's phenomenon (intermittent and painful reduction of blood flow to the digits), can occur.[5]
• Psychiatric: Dextroamphetamine can exacerbate pre-existing thought disorders or bipolar illness. It may induce new-onset psychotic or manic symptoms, such as hallucinations and delusional thinking, even at standard therapeutic doses in individuals without a prior history of psychosis. Increased aggression, hostility, and irritability are also reported.[5]
• Neurological: Stimulants may lower the convulsive threshold, and dextroamphetamine should be used with caution in patients with a history of seizures. It can also exacerbate motor and phonic tics and Tourette's syndrome.[13]
• Endocrine/Growth: Long-term use in children has been associated with a temporary slowing of growth (both height and weight). Regular monitoring of growth parameters is essential in pediatric patients.[14]
• Rare but Serious Reactions: These include serotonin syndrome (particularly when combined with other serotonergic drugs), which can be life-threatening; rhabdomyolysis (muscle breakdown); severe allergic reactions including anaphylaxis; and, in rare cases of severe vasculopathy, digital ulcerations.[5]

6.4 Drug and Food Interactions

Dextroamphetamine is subject to numerous clinically significant interactions that can alter its efficacy and safety. These interactions are predictable based on its pharmacodynamic and pharmacokinetic properties and are summarized in Table 4.

Table 4: Clinically Significant Drug-Drug and Drug-Food Interactions

Interacting Agent/Class	Mechanism of Interaction	Clinical Effect	Management Recommendation
Monoamine Oxidase Inhibitors (MAOIs)	Pharmacodynamic: Blockade of norepinephrine metabolism	Potentially fatal hypertensive crisis	Contraindicated. Do not use within 14 days of MAOI therapy.
Serotonergic Drugs (SSRIs, SNRIs, TCAs, Triptans)	Pharmacodynamic: Additive serotonergic effects	Increased risk of life-threatening serotonin syndrome	Monitor closely for symptoms (agitation, confusion, hyperthermia). Consider lower doses.
Antihypertensives (e.g., ACE inhibitors, beta-blockers)	Pharmacodynamic: Opposing effects on blood pressure	Decreased efficacy of the antihypertensive agent	Monitor blood pressure closely. Dose adjustments may be necessary.
Urinary Alkalinizers (e.g., Sodium Bicarbonate, Acetazolamide)	Pharmacokinetic: Decreased renal excretion of dextroamphetamine	Increased serum levels, prolonged effect, risk of toxicity	Avoid co-administration if possible. Monitor for signs of toxicity.
Urinary Acidifiers (e.g., Ascorbic Acid, Ammonium Chloride)	Pharmacokinetic: Increased renal excretion of dextroamphetamine	Decreased serum levels, reduced therapeutic effect	Avoid high doses of acidifying agents near the time of medication administration.
Alcohol	Pharmacodynamic/Pharmacokinetic	Potentiates cardiovascular effects (tachycardia, hypertension). May cause "dose dumping" from some ER formulations.	Avoid concomitant use.
Caffeine	Pharmacodynamic: Additive CNS stimulant effects	Increased nervousness, insomnia, palpitations, anxiety	Limit or avoid caffeine intake.
Acidic Juices (e.g., orange, grapefruit)	Pharmacokinetic: May decrease GI absorption and increase renal excretion	Reduced therapeutic efficacy	Avoid consumption one hour before and after taking the medication.

Source(s): [4]

6.5 Overdose and Dependence

• Acute Overdose: Manifestations of acute overdose are extensions of the drug's pharmacological effects and can include restlessness, tremor, hyperreflexia, rapid respiration, confusion, aggression, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.[5]
• Dependence and Withdrawal: Chronic use of dextroamphetamine can lead to the development of marked tolerance and severe psychological dependence.[5] Abrupt cessation of the drug following prolonged high-dosage administration can result in a withdrawal syndrome characterized by extreme fatigue and severe mental depression.[36]

Section 7: Concluding Analysis and Recommendations

7.1 Synthesis of Benefit-Risk Profile

Dextroamphetamine is a highly effective pharmacotherapy for its approved indications of ADHD and narcolepsy, capable of producing significant improvements in symptoms and functioning. However, its therapeutic benefits are inextricably linked to a substantial and multifaceted risk profile. The central challenge in its clinical use is the judicious balancing of its efficacy against the serious risks of cardiovascular events, adverse psychiatric effects, and, most notably, its high potential for abuse, misuse, and diversion. Its Schedule II classification and FDA black box warnings are not mere formalities but are foundational to its clinical identity, demanding a heightened level of diligence from prescribers and vigilance from patients and caregivers.

7.2 Recommendations for Clinical Practice

To mitigate the inherent risks and optimize the therapeutic outcomes of dextroamphetamine treatment, the following clinical practices are recommended:

• Pre-treatment Screening: A rigorous and comprehensive patient assessment is mandatory prior to initiating therapy. This must include a detailed personal and family history to screen for cardiac disease (including history of sudden death or ventricular arrhythmia), psychiatric disorders (psychosis, bipolar disorder, tic disorders, or Tourette's syndrome), and a history of substance use disorders.[7] A thorough physical examination, including baseline measurement of heart rate and blood pressure, is essential.[38]
• Ongoing Monitoring: Regular and systematic monitoring throughout treatment is critical. This should include periodic assessment of cardiovascular status (heart rate and blood pressure at each visit), psychiatric status (monitoring for the emergence of aggression, hostility, psychosis, or mania), and, in pediatric patients, regular monitoring of growth parameters (height and weight).[5]
• Patient and Family Education: Clinicians must engage in comprehensive counseling with patients and their families. This education should cover the signs and symptoms of abuse, misuse, and diversion; the importance of secure medication storage (preferably locked) and proper disposal of any unused drug; and the legal and health consequences of sharing the medication.[13] Patients should be thoroughly informed about the potential for serious cardiovascular and psychiatric side effects and instructed to report any concerning symptoms immediately. Furthermore, they must be cautioned about the potential for impairment in activities requiring alertness, such as operating machinery or vehicles, and be educated on key food and drug interactions that could alter the medication's safety and efficacy.[13]

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