Vyvanse

Uses

Vyvanse is a central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) and moderate to severe eating disorders.

For the treatment of Attention-deficit/hyperactivity disorder (ADHD) and for moderate to severe binge eating disorder in adults , .

This drug is not indicated for weight loss. Use of other sympathomimetic drugs for weight loss is associated with serious cardiovascular effects. The safety and effectiveness of this drug for the treatment of obesity have not yet been determined .

Vyvanse is also used to associated treatment for these conditions: Attention Deficit Hyperactivity Disorder (ADHD), Binge Eating Disorder (BED)

How Vyvanse works

Vyvanse is a prodrug of dextroamphetamine. The active form of this drug blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites for the reuptake of norepinephrine and dopamine in vitro . The mechanism of therapeutic action in attention deficit hyperactivity disorder (ADHD) is not fully understood , . Amphetamines have been recently found to target the trace amine-associated receptor 1 (TAAR1), which was recently discovered. This may explain some of its effects on the extraneuronal space , ,. Ultimately, the ability of this agent to increase synaptic concentrations of the catecholamine neurotransmitters noradrenaline and dopamine in the prefrontal cortex (PFC), and in the striatum, results in several behavioral changes , .

Toxicity

Acute toxicity: Symptoms of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression generally follow the symptoms central nervous system stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension and/or circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Lethal poisoning is usually preceded by convulsions and coma . Prescribers should consider that serious cardiovascular (CV) events have been reported with this class of drugs .

Long-term effects: Acute administration of high doses of amphetamine (d- or d,l-) has been shown to produce long-term neurotoxic effects, which include irreversible nerve fiber damage, in rodents. The relevance of these findings to humans is currently unknown .

Oral LD50 (rat): 7,060 mg/kg

Oral LD50 (mouse): 3,450 mg/kg

Use in Pregnancy

This drug is categorized as a Pregnancy Category C: Animal studies have shown risk to the fetus, there are no controlled studies in women, or studies in women and animals are not available .

Food Interaction

• Avoid antacids. Urinary excretion of lisdexamfetamine is elevated when the urine is more acidic. Antacids like sodium bicarbonate alkalinize the urine; therefore, they may reduce lisdexamfetamine elimination.
• Limit foods and supplements high in vitamin C. Urinary excretion of lisdexamfetamine is elevated when the urine is more acidic. Vitamin C acidifies the urine and, therefore, may increase lisdexamfetamine elimination.
• Take with or without food.

[Moderate] GENERALLY AVOID: Alcohol may potentiate the cardiovascular effects of amphetamines.

The exact mechanism of interaction is unknown.

In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm

This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone.

Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected.

The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

The interaction was suspected in a case report of a 20-year-old male who experienced retrosternal chest pain shortly after drinking alcohol and taking a double dose of his amphetamine

The patient had no family history of cardiovascular diseases, and his past medical history was remarkable only for ADHD.

Prior to the episode, the patient had not taken his medication for weeks and had been drinking whiskey the previous three nights before going to bed.

The patient was diagnosed with myocardial infarction likely secondary to amphetamine-induced coronary vasospasm.

MANAGEMENT: Concomitant use of amphetamines and alcohol should be avoided if possible, especially in patients with a history of heart disease.

Vyvanse Hypertension interaction

[Major] The use of CNS stimulants is contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc.

Sudden death has been reported in adults and children taking CNS stimulant treatment.

Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias and other symptoms have been reported in adults under treatment.

A careful assessment of the cardiovascular status should be done in patients being considered for treatment.

This includes family history, physical exam and further cardiac evaluation (EKG and echocardiogram).

Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

[Major] CNS stimulant medications have shown to increase blood pressure, and their use might be contraindicated in patients with severe hypertension.

Caution should be used when administering to patients with preexisting high blood pressure and other cardiovascular conditions.

All patients under treatment should be regularly monitored for changes in blood pressure and heart rate.

Vyvanse Drug Interaction

Major: duloxetine, duloxetine, escitalopram, escitalopram, fluoxetine, fluoxetine, bupropion, bupropion, sertraline, sertralineModerate: atomoxetine, atomoxetineUnknown: amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Vyvanse Disease Interaction

Major: cardiovascular, glaucoma, agitation, cardiac disease, hypertension, substance abuse, ticsModerate: bipolar disorders, psychotic disorders, seizure disorders, renal dysfunction

Volume of Distribution

There is no accumulation of d-amphetamine (as measured by AUC) at steady state in healthy adults and no accumulation of lisdexamfetamine dimesylate after once-daily dosing for seven consecutive days , .

Elimination Route

After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract , .

Chewable tablet form: After a single dose of 60 mg a chewable tablet in healthy subjects under fasted conditions, the Tmax of lisdexamfetamine and dextroamphetamine was reached at about 1 hour and 4.4 hour post administration, respectively .

Capsule form: Following single-dose oral (30 mg, 50 mg, or 70 mg) in patients ages 6 to 12 years with ADHD under fasted conditions, Tmax of lisdexamfetamine and dextroamphetamine was reached at about 1 hour and 3.5 hours post administration, respectively .

Half Life

The mean plasma elimination half-life of dextroamphetamine was about 12 hours after oral administration of lisdexamfetamine dimesylate .

The plasma elimination half-life of lisdexamfetamine alone averaged less than one hour in studies of lisdexamfetamine dimesylate administered in volunteer subjects .

Clearance

In a study of 47 subjects aged 55 years of age or older, amphetamine clearance was approximately 0.7L/hr/kg for subjects 55-74 years of age and 0.55L/hr/kg for subjects ≥75 years of age. This is slightly reduced compared to younger adults (approximately 1L/hr/kg for subjects 18-45 years of age) .

Elimination Route

After the oral administration of a 70mg dose of radiolabeled lisdexamfetamine dimesylate to six healthy subjects, about 96% of the oral dose radioactivity was recovered in the urine and only 0.3% recovered in the feces , .

Innovators Monograph

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