Dextroamphetamine Saccharate, Amphetamine Aspartate Monohydrate, Dextroamphetamine Sulfate, And Amphetamine Sulfate Extended-release

Amphetamine Aspartate is a potent central nervous system (CNS) stimulant and a key component of mixed amphetamine salt formulations. It is primarily utilized in the management of Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy by modulating neurotransmitter levels in the brain.

For the treatment of ADHD in adults, the typical starting dose of mixed amphetamine salts (containing Amphetamine Aspartate) is 5 mg once or twice daily. Your healthcare provider may increase the daily dose by 5 mg at weekly intervals until the optimal therapeutic response is achieved. The maximum recommended dose for most adults is 40 mg per day, although some clinical situations may require higher doses under strict supervision. For Narcolepsy, the usual dose range is 5 mg to 60 mg per day, divided into multiple doses depending on the patient's sleep patterns and response.

• Children (ages 3 to 5): For ADHD, the starting dose is usually 2.5 mg daily. The dose may be increased in increments of 2.5 mg weekly.
• Children (ages 6 and older): The starting dose is typically 5 mg once or twice daily. Increments of 5 mg per week are common until the desired effect is reached.
• Narcolepsy: Amphetamine is rarely used for narcolepsy in children under 6. For those 6-12, the starting dose is 5 mg daily, increasing by 5 mg weekly. For those 12 and older, the starting dose is 10 mg daily.

Renal Impairment

In patients with severe renal impairment (GFR 15 to <30 mL/min/1.73 m²), the maximum dose should not exceed 20 mg per day for extended-release formulations. In patients with end-stage renal disease (ESRD), the use of Amphetamine Aspartate is generally not recommended as the drug is not efficiently cleared by dialysis.

Hepatic Impairment

While the liver is the primary site of metabolism, there are no specific quantitative guidelines for dose adjustments in hepatic impairment. However, healthcare providers usually exercise caution and may start at the lower end of the dosing spectrum due to the potential for reduced metabolic clearance.

Elderly Patients

Clinical studies for Amphetamine Aspartate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function.

Amphetamine Aspartate should be taken exactly as prescribed. For immediate-release forms, the first dose is typically taken upon awakening, with subsequent doses spaced 4 to 6 hours apart. Extended-release capsules should be taken once daily in the morning. Taking this medication late in the day may result in significant insomnia (difficulty sleeping).

Extended-release capsules should generally be swallowed whole. However, for patients who cannot swallow capsules, some brands allow the capsule to be opened and the beads sprinkled onto a tablespoon of applesauce. The mixture must be consumed immediately without chewing the beads, as crushing or chewing destroys the extended-release mechanism and can lead to a dangerous "dose dump" of the medication.

If you miss a dose, take it as soon as you remember. However, if it is already late afternoon or evening, skip the missed dose and return to your regular schedule the next morning. Do not take a double dose to make up for a missed one, as this increases the risk of cardiovascular side effects and insomnia.

An overdose of Amphetamine Aspartate can be life-threatening. Signs of acute overdose include restlessness, tremor, rapid breathing (tachypnea), confusion, aggression, hallucinations, panic states, hyperpyrexia (extremely high fever), and rhabdomyolysis (muscle breakdown). Cardiovascular effects may include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps.

In the event of a suspected overdose, contact emergency services or a poison control center immediately. Treatment usually involves supportive care, administration of activated charcoal, and medications to manage blood pressure and seizures.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or stop the medication without medical guidance, as sudden discontinuation can lead to severe withdrawal symptoms.

Most patients taking Amphetamine Aspartate will experience some level of side effects, particularly during the initial titration phase. Common effects include:

• Anorexia (Loss of Appetite): This is one of the most frequent side effects, often leading to weight loss. It is most pronounced during the middle of the day.
• Xerostomia (Dry Mouth): A decrease in saliva production can cause discomfort and increase the risk of dental cavities over time.
• Insomnia: Difficulty falling asleep or staying asleep, especially if the medication is taken too late in the day.
• Abdominal Pain: Often described as stomach cramps or nausea, which may improve if the medication is taken with a small amount of food.
• Tachycardia (Rapid Heart Rate)

Amphetamine Aspartate is a powerful stimulant that must be used with extreme caution. It is not suitable for everyone, and a comprehensive cardiovascular and psychiatric screening is mandatory before the first dose. Patients must be monitored regularly for changes in blood pressure, heart rate, and mental status.

Abuse and Dependence: Amphetamines have a high potential for abuse. Use of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.

• Cardiovascular Risks: Stimulants cause an increase in blood pressure (average 2-4 mmHg) and heart rate (average 3-6 bpm). While these increases may be minor for many, they can be life-threatening for individuals with underlying heart defects, cardiomyopathy, or serious heart rhythm abnormalities.

• MAO Inhibitors (MAOIs): Amphetamine Aspartate must not be used during or within 14 days following the administration of monoamine oxidase inhibitors (e.g., phenelzine, selegiline). This combination can trigger a hypertensive crisis—a sudden, severe increase in blood pressure that can lead to stroke or organ damage.

• Serotonergic Drugs: Combining amphetamines with SSRIs (e.g., fluoxetine), SNRIs (e.g., venlafaxine), or triptans increases the risk of Serotonin Syndrome. This occurs because amphetamine has mild serotonergic activity which can be additive.
• CYP2D6 Inhibitors: Drugs that inhibit the CYP2D6 enzyme (e.g., paroxetine, quinidine) can slow the metabolism of amphetamine, leading to toxic levels in the blood.

Amphetamine Aspartate must NEVER be used in patients with the following conditions:

• Advanced Arteriosclerosis: Hardening of the arteries, as the stimulant effects can lead to vascular rupture or heart attack.
• Symptomatic Cardiovascular Disease: Any active heart condition where increased heart rate or blood pressure poses an immediate threat.
• Moderate to Severe Hypertension: Uncontrolled high blood pressure.
• Hyperthyroidism: Excessive thyroid hormone already overstimulates the metabolism; adding a CNS stimulant can lead to a thyroid storm.
• Glaucoma: Amphetamines can increase intraocular pressure (pressure inside the eye), worsening the condition.

Amphetamine Aspartate is classified under the former FDA Pregnancy Category C. Data on its use in pregnant women are limited. However, studies suggest that infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. There is also a risk of withdrawal symptoms (neonatal abstinence syndrome) in the newborn, characterized by agitation and extreme drowsiness. Amphetamine Aspartate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Amphetamines are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants (such as tachycardia, irritability, and poor weight gain), mothers taking Amphetamine Aspartate are advised to avoid breastfeeding. Consult with a pediatrician about safe infant feeding alternatives.

Amphetamine Aspartate is FDA-approved for the treatment of ADHD in children as young as 3 years old. However, it is not recommended for children under 3. The primary concern in pediatric use is the suppression of growth. Clinical data suggests that children on long-term stimulant therapy may experience a temporary slowing in height and weight gain. Healthcare providers must monitor growth parameters closely and may suggest "medication holidays" (stopping the drug during summer breaks) to allow for catch-up growth.

Amphetamine Aspartate is a potent inducer of monoamine release. Its primary molecular target is the Trace Amine-Associated Receptor 1 (TAAR1), a G protein-coupled receptor located in the presynaptic terminal. Upon binding, it triggers the phosphorylation of the Dopamine Transporter (DAT), causing it to function in reverse. Simultaneously, it enters the neuron via DAT and inhibits the Vesicular Monoamine Transporter 2 (VMAT2), which normally packages dopamine into vesicles. This causes a massive efflux of dopamine and norepinephrine into the synapse, enhancing signal transmission in the reward and attention centers of the brain.

The pharmacodynamic effects of Amphetamine Aspartate include increased alertness, decreased fatigue, and improved mood. There is a clear dose-response relationship, where higher doses lead to greater neurotransmitter release but also a higher risk of side effects like hypertension. Tolerance to the euphoric and appetite-suppressant effects often develops within weeks, whereas the therapeutic effects for ADHD tend to remain stable over longer periods.

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