Lisdexamfetamine Dimesylate

For the treatment of ADHD in adults, the recommended starting dose of Lisdexamfetamine Dimesylate is 30 mg once daily in the morning. Healthcare providers may titrate the dose in increments of 10 mg or 20 mg at approximately weekly intervals to achieve the desired clinical response. The maximum recommended dose is 70 mg per day.

For Binge Eating Disorder (BED) in adults, the starting dose is also 30 mg per day. The dose is typically increased by 20 mg weekly until a target dose of 50 mg to 70 mg per day is reached. If the patient does not tolerate the higher doses, the provider may adjust back to a lower effective dose. Clinical trials have shown that doses below 50 mg are generally less effective for BED.

Lisdexamfetamine Dimesylate is approved for pediatric patients aged 6 to 17 years for the treatment of ADHD. The starting dose is 30 mg once daily in the morning. Just as with adults, the dose may be adjusted by 10 mg or 20 mg weekly, with a maximum daily limit of 70 mg. It is not approved for use in children under the age of 6, as safety and efficacy have not been established in this age group. For pediatric patients with Binge Eating Disorder, the drug is not currently FDA-approved.

Renal Impairment

In patients with severe renal impairment (estimated GFR 15 to <30 mL/min/1.73 m²), the maximum dose should not exceed 30 mg per day. In patients with end-stage renal disease (ESRD, GFR <15 mL/min/1.73 m²), the use of Lisdexamfetamine is generally not recommended.

Hepatic Impairment

Specific dosage adjustments for hepatic impairment are not provided in the standard labeling, as the drug is primarily metabolized in the blood and excreted by the kidneys. However, clinicians should exercise caution in patients with severe liver dysfunction.

Elderly Patients

Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently. 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.

Lisdexamfetamine Dimesylate should be taken exactly as prescribed by your healthcare provider. It is usually taken once daily in the morning to avoid insomnia (difficulty sleeping). It can be taken with or without food.

• Capsules: Should ideally be swallowed whole. However, if a patient has trouble swallowing, the capsule can be opened and the entire contents dissolved in a glass of water, orange juice, or mixed into yogurt. The mixture should be consumed immediately and not stored for later use.
• Chewable Tablets: Must be chewed thoroughly before swallowing.
• Storage: Store at room temperature, 68°F to 77°F (20°C to 25°C), in a tight, light-resistant container. Keep it in a safe place, as this medication is a Schedule II controlled substance with a high potential for misuse.

If a dose is missed, it should be taken as soon as remembered in the morning. If it is already afternoon or evening, the missed dose should be skipped to prevent late-night insomnia. Do not take a double dose to make up for a missed one. Regularity is key to the effectiveness of the medication.

Signs of an overdose of Lisdexamfetamine Dimesylate can be severe and include restlessness, tremor, rapid breathing, confusion, aggression, hallucinations, panic states, hyperpyrexia (extremely high fever), and muscle pains (rhabdomyolysis). Cardiovascular effects may include arrhythmias, hypertension, or circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, and abdominal cramps.

In the event of a suspected overdose, contact the Poison Control Center immediately or seek emergency medical attention. Treatment typically involves supportive care and managing the symptoms, as there is no specific antidote for amphetamine toxicity.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or stop taking the medication without medical guidance.

Side effects are common when initiating CNS stimulants like Lisdexamfetamine Dimesylate, though many patients find they diminish over time as the body adjusts. In clinical trials, the most frequently reported adverse reactions included:

• Decreased Appetite: This is one of the most common effects, often leading to weight loss. Patients may feel a significant lack of hunger during the day, which usually returns as the medication wears off in the evening.
• Insomnia: Difficulty falling asleep or staying asleep is common, especially if the medication is taken late in the day.
• Dry Mouth (Xerostomia): A persistent feeling of thirst or a parched mouth.
• Increased Heart Rate: Patients may notice their heart beating faster or more forcefully (palpitations).
• Anxiety and Irritability: Some individuals feel "on edge" or more easily frustrated while the medication is active.

• Dizziness and Headache: These often occur during the first week of treatment.
• Gastrointestinal Issues: Including upper abdominal pain, nausea, vomiting, and diarrhea.
• Weight Loss: Significant weight reduction can occur, which requires monitoring, especially in growing children.
• Tremor: Involuntary shaking, usually in the hands.
• Hyperhidrosis: Excessive sweating regardless of temperature or physical activity.

• Raynaud’s Phenomenon: Reduced blood flow to the extremities, causing fingers or toes to feel numb, cold, or change color (turning blue or white).
• Logorrhea: Excessive or pressured speech.
• Mydriasis: Prolonged dilation of the pupils.
• Hypersensitivity: Allergic reactions including urticaria (hives) or more severe rashes.

> Warning: Stop taking Lisdexamfetamine Dimesylate and call your doctor immediately if you experience any of these serious symptoms.

• Cardiovascular Events: Sudden death in patients with pre-existing structural heart abnormalities, stroke, and myocardial infarction (heart attack). Symptoms include chest pain, shortness of breath, or fainting.
• Psychiatric Symptoms: New or worsening psychosis (hallucinations, delusional thinking) or mania. Patients may see or hear things that are not real or believe things that are not true.
• Serotonin Syndrome: A potentially life-threatening condition if taken with other serotonergic drugs. Symptoms include agitation, hallucinations, coma, fast heartbeat, muscle rigidity, or seizures.
• Peripheral Vasculopathy: Including digital ulceration and soft tissue breakdown.
• Visual Changes: Blurred vision or difficulty focusing the eyes.

Prolonged use of stimulants may be associated with several long-term considerations:

1. 1Growth Suppression: Data suggests that consistent use of stimulants in children may lead to a temporary slowing in growth rate (height and weight). Healthcare providers typically monitor growth charts closely and may suggest "drug holidays."
2. 2Tolerance and Dependence: Over time, the body may become accustomed to the drug, requiring higher doses to achieve the same effect. This can lead to physical and psychological dependence.
3. 3Cardiovascular Strain: Chronic elevation of blood pressure and heart rate may increase the risk of long-term cardiovascular issues in susceptible individuals.

Lisdexamfetamine Dimesylate carries a FDA Boxed Warning regarding its high potential for abuse and dependence.

• Abuse: Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic use or distribution to others.
• Misuse: Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. Healthcare providers must assess the risk of abuse prior to prescribing and monitor for signs of misuse and dependence during therapy.

Report any unusual symptoms to your healthcare provider. Early detection of side effects is essential for safe long-term management.

Lisdexamfetamine Dimesylate is a powerful medication that requires careful medical supervision. It is classified as a Schedule II controlled substance because it can be a target for people who abuse prescription medicines or street drugs. Keep your medication in a safe place to prevent theft. Never give your Lisdexamfetamine Dimesylate to anyone else, because it may cause death or harm them, and it is against the law.

CNS STIMULANTS, INCLUDING LISDEXAMFETAMINE DIMESYLATE, HAVE A HIGH POTENTIAL FOR ABUSE AND DEPENDENCE.

• Risk Assessment: Before prescribing, healthcare providers should assess the risk of abuse, and after prescribing, they should monitor for signs of abuse and dependence.
• Serious Risks: Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events. This warning emphasizes the need for strict adherence to prescribed dosages and regular clinical review.

• Cardiovascular Risks: Stimulant medications cause an increase in average blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 bpm). Individuals should be screened for heart problems before starting this medication. Sudden death has been reported in association with CNS stimulant treatment at recommended doses in children and adolescents with structural heart abnormalities or other serious heart problems.
• Psychiatric Adverse Events: Stimulants may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of such symptoms. If these occur, discontinuation of treatment may be necessary.
• Suppression of Growth: Monitor height and weight in pediatric patients. Those not growing or gaining weight as expected may need to have their treatment interrupted.
• Seizures: There is some clinical evidence that stimulants may lower the convulsive threshold in patients with a prior history of seizures.
• Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

Patients taking Lisdexamfetamine Dimesylate require regular follow-up appointments. Monitoring typically includes:

1. 1Blood Pressure and Heart Rate: Should be measured at baseline and periodically during treatment.
2. 2Growth Monitoring: In children, height and weight should be plotted on a growth chart at least every 3-6 months.
3. 3Psychiatric Evaluation: Ongoing assessment for the emergence of aggressive behavior, anxiety, or psychosis.
4. 4Abuse Monitoring: Checking for signs of diversion or escalating dose usage.

Lisdexamfetamine Dimesylate may impair the ability of the patient to operate heavy machinery or drive, especially during the initial period of treatment or when the dose is being adjusted. While it can improve focus in many, it can also cause dizziness or tremors in others. Patients should observe their reaction to the medication before engaging in potentially hazardous activities.

Alcohol should be avoided while taking Lisdexamfetamine Dimesylate. Alcohol can unpredictably alter the release and effects of the medication, potentially increasing the risk of side effects like rapid heart rate, high blood pressure, or extreme anxiety. Furthermore, the stimulant effect of the drug can mask the intoxicating effects of alcohol, leading to a higher risk of alcohol poisoning.

Do not stop taking this medication abruptly without consulting your doctor. Sudden discontinuation after prolonged high-dose use can result in extreme fatigue and mental depression. A gradual tapering of the dose is often recommended to minimize withdrawal symptoms and allow the brain's neurochemistry to stabilize.

> Important: Discuss all your medical conditions, especially any history of heart problems or mental health issues, with your healthcare provider before starting Lisdexamfetamine Dimesylate.

Certain medications should never be taken with Lisdexamfetamine Dimesylate due to the risk of life-threatening interactions:

• Monoamine Oxidase Inhibitors (MAOIs): Do not take Lisdexamfetamine if you are taking an MAOI (such as selegiline, phenelzine, or tranylcypromine) or have taken one within the last 14 days. This combination can cause a hypertensive crisis—a sudden, dangerous rise in blood pressure that can lead to a stroke or heart attack.

• Serotonergic Drugs: Combining Lisdexamfetamine with SSRIs (e.g., fluoxetine, sertraline), SNRIs (e.g., venlafaxine), or triptans increases the risk of Serotonin Syndrome. This is a medical emergency characterized by high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea.
• Alkalinizing Agents: Medications that make the urine more alkaline (like sodium bicarbonate or certain antacids) can reduce the excretion of amphetamine, increasing its blood levels and the risk of toxicity.
• Acidifying Agents: Conversely, agents that acidify the urine (like ascorbic acid/Vitamin C or ammonium chloride) increase the excretion of amphetamine, which can lower its effectiveness.

• Antihypertensives: Amphetamines can decrease the effectiveness of medications used to treat high blood pressure. Close monitoring of blood pressure is required.
• Tricyclic Antidepressants (TCAs): May enhance the activity of tricyclic or sympathomimetic agents causing striking increases in the concentration of d-amphetamine in the brain; the cardiovascular effects can be potentiated.
• Chlorpromazine: This antipsychotic inhibits the central stimulant effects of amphetamines and can be used to treat amphetamine poisoning.

• High-Fat Meals: While Lisdexamfetamine can be taken with food, a very high-fat meal may delay the time it takes for the drug to reach its peak concentration by about an hour, though it does not change the total amount absorbed.
• Caffeine: Consuming large amounts of caffeine (coffee, tea, energy drinks) while on this medication can exacerbate side effects like jitters, insomnia, and increased heart rate.
• Acidic Juices: Large amounts of fruit juices (like orange or grapefruit juice) consumed at the same time as the medication may theoretically decrease absorption or increase excretion due to their acidifying effect on urine, though this is more pronounced with immediate-release amphetamines than with the prodrug Lisdexamfetamine.

• St. John’s Wort: May increase the risk of serotonin syndrome when combined with stimulants.
• Melatonin: Often used by patients to combat stimulant-induced insomnia, but should be discussed with a doctor as it may affect morning alertness.
• Vitamin C: As mentioned, high doses of Vitamin C can act as a urinary acidifying agent, potentially reducing the duration of the drug's effect.

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may also interfere with urinary steroid determinations. If you are undergoing lab tests, inform the laboratory that you are taking Lisdexamfetamine Dimesylate.

For each major interaction, the management strategy usually involves either avoiding the combination, adjusting the dose, or increasing the frequency of clinical monitoring.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking to ensure your treatment plan is safe and effective.

There are several conditions and situations where Lisdexamfetamine Dimesylate must NEVER be used because the risks far outweigh any potential benefits:

• Hypersensitivity to Sympathomimetic Amines: Patients who have had an allergic reaction to any amphetamine products (e.g., Adderall, Dexedrine) should not take this drug. Reactions can range from simple rashes to life-threatening anaphylaxis.
• MAOI Use: As noted, use within 14 days of a Monoamine Oxidase Inhibitor is strictly contraindicated due to the risk of hypertensive crisis.
• Symptomatic Cardiovascular Disease: Including advanced arteriosclerosis (hardening of the arteries), moderate to severe hypertension, and heart failure.
• Hyperthyroidism: The stimulant effects of the drug can dangerously exacerbate the symptoms of an overactive thyroid, such as rapid heart rate.
• Glaucoma: Amphetamines can increase intraocular pressure, worsening narrow-angle glaucoma.
• Agitated States: Patients who are in a state of extreme agitation or restlessness may see their symptoms worsen significantly.
• History of Drug Abuse: Because of the high potential for addiction, it is contraindicated in patients with a known history of substance use disorder involving stimulants.

These conditions require a careful risk-benefit analysis by a specialist:

• Mild Hypertension: Requires very close monitoring of blood pressure.
• Tics or Tourette’s Syndrome: Stimulants may exacerbate motor and phonic tics. A clinical evaluation of the family history of tics is recommended before starting.
• Bipolar Disorder: There is a risk of inducing a mixed or manic episode in patients with bipolar disorder. Screening for risk factors for bipolar disorder is essential.
• Renal Impairment: While not an absolute contraindication, it requires significant dose reduction.

Patients who are sensitive to other CNS stimulants, such as methylphenidate (Ritalin), may not necessarily be allergic to Lisdexamfetamine, but they may experience similar side effects. However, cross-sensitivity among different amphetamine salts is very high. If a patient has had a serious adverse reaction to any amphetamine-based product, Lisdexamfetamine should be avoided.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of heart disease or mental illness, before prescribing Lisdexamfetamine Dimesylate.

Lisdexamfetamine Dimesylate is classified under the former FDA Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Data from animal studies suggest that amphetamines may have adverse effects on fetal development.

• Risks: Use of amphetamines during pregnancy may increase the risk of premature delivery and low birth weight. Infants born to mothers dependent on amphetamines may also experience withdrawal symptoms (neonatal abstinence syndrome) such as agitation and significant lassitude.
• Clinical Decision: This medication should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women of childbearing age should discuss contraception and pregnancy planning with their doctor.

Amphetamines, including the active metabolite dextroamphetamine, are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants (such as tachycardia, irritability, and poor weight gain), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Lisdexamfetamine is FDA-approved for ADHD in children aged 6 to 17. It is not approved for children under 6 due to the lack of safety data and the high sensitivity of young children to stimulant effects.

• Growth Monitoring: Long-term use in children requires careful monitoring of height and weight. If growth slows significantly, "drug holidays" (taking breaks from the medication during weekends or school vacations) may be considered by the pediatrician.
• Behavioral Changes: Parents should monitor for signs of increased aggression or emotional lability (mood swings).

Clinical studies did not include enough subjects over 65 to determine if they respond differently than younger subjects. In general, elderly patients have a higher prevalence of cardiovascular disease and reduced renal function. Therefore, if Lisdexamfetamine is prescribed, it should be started at the lowest possible dose (10-20 mg) with frequent monitoring of heart rate and blood pressure.

The kidneys play a major role in the elimination of the active metabolite.

• Severe Impairment (GFR 15-30): The maximum dose is 30 mg/day.
• ESRD (GFR < 15): Not recommended.
• Dialysis: Lisdexamfetamine and its metabolites are not significantly removed by hemodialysis.

Since the conversion of Lisdexamfetamine to dextroamphetamine occurs in the blood and not the liver, mild to moderate hepatic impairment does not typically require a dose adjustment. However, patients with severe hepatic failure should be monitored closely for overall metabolic health.

> Important: Special populations require individualized medical assessment and frequent follow-up to ensure safety and efficacy.

Lisdexamfetamine Dimesylate is a prodrug. After oral ingestion, it is converted into L-lysine (a natural amino acid) and dextroamphetamine (the active stimulant). The dextroamphetamine acts by increasing the levels of dopamine and norepinephrine in the synaptic cleft. It achieves this through two primary mechanisms:

1. 1Reuptake Inhibition: It binds to the dopamine transporter (DAT) and norepinephrine transporter (NET), preventing the reabsorption of these neurotransmitters into the presynaptic neuron.
2. 2Promoting Release: It enters the presynaptic neuron via the transporters and interacts with the Vesicular Monoamine Transporter 2 (VMAT2), causing the release of stored neurotransmitters into the cytoplasm and eventually into the synapse.

The pharmacodynamic response is characterized by improved attention, increased alertness, and decreased impulsivity. Because the conversion of the prodrug is rate-limited by the enzymatic capacity of red blood cells, the rise in d-amphetamine levels is gradual, leading to a "smooth" onset of action and a long duration of effect (up to 14 hours). This profile helps avoid the "crash" often associated with immediate-release stimulants.

| Parameter | Value |

|---|---|

| Bioavailability | >99% (as prodrug) |

| Protein Binding | 2% to 5% |

| Half-life | <1 hour (Lisdex); 12 hours (Dex) |

| Tmax | ~1 hour (Lisdex); 3.5-4.5 hours (Dex) |

| Metabolism | Hydrolysis in Red Blood Cells |

| Excretion | Renal 96%, Fecal <1% |

• Molecular Formula: C15H25N3O · 2CH4O3S
• Molecular Weight: 455.5 g/mol
• Solubility: Highly soluble in water (792 mg/mL).
• Structure: It consists of d-amphetamine covalently bonded to the amino acid L-lysine. The dimesylate salt form ensures stability and solubility.

Lisdexamfetamine Dimesylate is classified as a CNS Stimulant and a Phenethylamine derivative. It is a Schedule II controlled substance under the Controlled Substances Act. It is related to other medications like Dextroamphetamine Sulfate and Mixed Amphetamine Salts, but its prodrug delivery system is unique within the class.