amphetamine/dextroamphetamine

Amphetamine/dextroamphetamine is a combination drug used in the treatment of attention deficit hyperactivity disorder (ADHD), and narcolepsy, a chronic sleep disorder that causes daytime drowsiness. Amphetamine, the active component in the combination, is a sympathomimetic amine stimulant drug which mimics the action of natural chemicals in the brain that stimulate the sympathetic nervous system.

Amphetamine raises the levels of brain chemicals (neurotransmitters) that stimulate the central nervous system (CNS), including dopamine, norepinephrine and to a lesser extent, serotonin. Amphetamine increases these neurotransmitter levels by stimulating their release from the nerve cells (neurons) and also by blocking their reabsorption (reuptake), a natural process after completion of neurotransmission. Amphetamine also inhibits monoamine oxidase, an enzyme that breaks down these monoamine neurotransmitters.

Dopamine, norepinephrine and serotonin have multiple functions that include regulation of digestion, sleep-wake cycle, movement, attention, memory, motivation and pleasure. The exact therapeutic effect of amphetamine in ADHD is not clear, however, increase in the levels of these neurotransmitters are thought to improve concentration and reduce hyperactive and impulsive behaviors associated with ADHD. Amphetamine stimulates daytime wakefulness, which can improve nighttime quality of sleep, in patients with narcolepsy.

Amphetamine/dextroamphetamine combines four salts of amphetamine and dextroamphetamine and is available in two formulations, instant and extended release. Stimulants such as amphetamine also increase heart rate, blood pressure and blood glucose, and dilate the respiratory tract. Stimulants have a high potential for abuse, misuse, tolerance, dependence and addiction, because of their stimulating effect, and are some of the most commonly misused and abused illegal street drugs. 

• Do not use amphetamine/dextroamphetamine to treat patients with known hypersensitivity to amphetamine or any component of the formulation, or other sympathomimetic amines. There have been reports of angioedema and severe allergic reactions (anaphylaxis) associated with amphetamine products.
• Do not prescribe amphetamine/dextroamphetamine in the following conditions:
  • Symptomatic cardiovascular disease
  • Moderate to severe hypertension
  • Advanced plaque formation in the arteries (arteriosclerosis)
  • Hyperthyroidism
  • Glaucoma, a condition that damages the optic nerve
  • Agitated states
  • History of drug abuse
• Do not use amphetamine/dextroamphetamine concurrently or within 14 days after the administration of monoamine oxidase inhibitor (MAOI) antidepressants or other drugs such as linezolid and intravenous methylene blue, it can lead to a hypertensive crisis.
• CNS stimulants, including amphetamine/dextroamphetamine, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess risk of abuse before prescribing, and monitor patients for signs of abuse and dependence while on therapy. Caution the patient, family and caregivers.
• Do not use amphetamine/dextroamphetamine in patients with coronary artery disease, structural cardiac abnormalities or other heart diseases. Stroke, heart attack (myocardial infarction) and sudden death have been reported with even recommended doses.
• CNS stimulants increase blood pressure and heart rate, monitor patients for potential hypertension and tachycardia.
• Potential psychiatric adverse effects of amphetamine/dextroamphetamine include:
  • Exacerbation of symptoms of behavior disturbance in patients with pre-existing psychotic disorders.
  • Induction of mixed or manic episodes in patients with bipolar disorder. Patient’s risk factors for bipolar disorder should be assessed before initiating treatment with amphetamine/dextroamphetamine
  • Emergence of new psychotic or manic symptoms such as hallucinations, delusional thinking and mania in children and adolescents without a prior history of psychotic illness or mania.
  • Aggressive and hostile behavior in children and adolescents with ADHD.
• Chronic use of amphetamines can suppress growth in pediatric patients. Monitor growth during treatment in children, and if a child does not have the expected growth and weight gain, consider interrupting amphetamine/dextroamphetamine treatment.
• Amphetamine/dextroamphetamine can lower seizure threshold in patients with or without a history of seizures or prior EEG abnormalities. Discontinue the drug if seizure occurs.
• Treatment with amphetamine/dextroamphetamine can cause peripheral vascular diseases (vasculopathy), including Raynaud’s phenomenon. Monitor patients for signs and symptoms and consider dose adjustment or discontinuation based on severity.
• Concurrent use of amphetamine/dextroamphetamine with drugs that increase serotonin level, including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), MAOIs, tricyclic antidepressants and other drugs can lead to serotonin syndrome, a potentially life-threatening reaction. Monitor patient and stop all serotonergic drugs if signs and symptoms of serotonin syndrome develop.
• Amphetamine/dextroamphetamine therapy may cause blurry vision or difficulty focusing (accommodation disorder).
• Amphetamines may exacerbate motor and phonic tics and Tourette’s syndrome. Evaluate patients for Tourette’s syndrome before initiating treatment.
• Prescribe and dispense the least feasible amount of amphetamine/dextroamphetamine at one time to reduce risk of overdose. Do not substitute amphetamine for other amphetamine products on mg-per-mg basis. Medication errors or substitution can lead to overdose. Use with caution in patients who take other sympathomimetic drugs.

Common side effects of amphetamine/dextroamphetamine include:

• Dry mouth (xerostomia)
• Loss of appetite (anorexia)
• Reduced appetite
• Weight loss
• Nausea
• Vomiting
• Diarrhea
• Indigestion (dyspepsia)
• Abdominal pain
• Tooth infection
• Teeth clenching (bruxism)
• Headache
• Insomnia
• Mood swings (emotional lability)
• Nervousness
• Agitation
• Irritability
• Feeling jittery
• Anxiety
• Depression
• Dizziness
• Drowsiness (somnolence)
• Speech disorder
• Twitching
• Weakness (asthenia)
• High blood pressure (hypertension)
• Rapid heart rate (tachycardia)
• Fever
• Infection
• Urinary tract infection
• Painful menstruation (dysmenorrhea)
• Erectile dysfunction
• Sweating
• Light sensitivity reaction
• Accidental injury

Less common side effects of amphetamine/dextroamphetamine include:

• Unpleasant taste
• Constipation
• Palpitations
• Heart attack (myocardial infarction)
• Sudden death
• Shortness of breath (dyspnea)
• Fatigue
• Psychotic episodes at recommended doses
• Overstimulation
• Restlessness
• Euphoria
• Movement disorder (dyskinesia)
• Feeling of unease (dysphoria)
• Tremor
• Tics
• Aggression
• Anger
• Stuttering
• Excessive talkativeness (logorrhea)
• Skin picking (dermatillomania)
• Numbness, tingling and skin crawling sensations (paresthesia)
• Blurred vision
• Dilation of pupils
• Allergic skin reactions including:
  • Rash
  • Hives (urticaria)
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
• Hypersensitivity reactions including:
  • Swelling under the skin and mucous tissues (angioedema)
  • Severe allergic reaction (anaphylaxis)
• Hair loss (alopecia)
• Changes in libido
• Impotence
• Frequent or prolonged erections
• Breakdown of muscle tissue (rhabdomyolysis)
• Raynaud’s phenomenon, a condition with reduced blood flow to extremities

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Each tab/cap contains equal portions of the following: amphetamine aspartate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate

Tablet: Schedule II

• 5 mg (1.25 mg/1.25 mg/1.25 mg/1.25 mg)
• 10 mg (2.5 mg/2.5 mg/2.5 mg/2.5 mg)
• 20 mg (5 mg/5 mg/5 mg/5 mg)
• 30 mg (7.5 mg/7.5 mg/7.5 mg/7.5 mg)

Capsule, extended-release: Schedule II

• 5 mg (1.25 mg/1.25 mg/1.25 mg/1.25 mg) (Adderall XR)
• 10 mg (2.5 mg/2.5 mg/2.5 mg/2.5 mg) (Adderall XR)
• 12.5 mg (3.125 mg/3.125 mg/3.125 mg/3.125 mg) (Mydayis)
• 15 mg (3.75 mg/3.75 mg/3.75 mg/3.75 mg) (Adderall XR)
• 20 mg (5 mg/5 mg/5 mg/5 mg) (Adderall XR)
• 25 mg (6.25 mg/6.25 mg/6.25 mg/6.25 mg) (Adderall XR, Mydayis)
• 30 mg (7.5 mg/7.5 mg/7.5 mg/7.5 mg) (Adderall XR)
• 37.5 mg (9.375 mg/9.375 mg/9.375 mg/9.375 mg) (Mydayis)
• 50 mg (12.5 mg/12.5 mg/12.5 mg/12.5 mg) (Mydayis)

Adult:

Attention Deficit Hyperactivity Disorder (ADHD)

• Tablet: 5 mg orally once daily initially; may increase by 5-10 mg/day once a week; administer daily dose in 2-3 doses; not to exceed 40 mg/day

Extended-release capsule

• Adderall XR
  • 20 mg orally once every morning initially or switching from another medication
  • May increase by increments of 5-10 mg/week; not to exceed 60 mg/day
• Mydayis
  • 18-55 years: 12.5 mg once every morning initially
  • May increase by increments of 12.5 mg/week; not to exceed 50 mg/day
  • Note: 25 mg once every morning may be considered as an initial dose for some patients

Narcolepsy

Amphetamine/dextroamphetamine

• 5-60 mg orally once daily; may increase by 10 mg/day once a week
• No more than 60 mg given once daily or divided doses with intervals of 4-6 hours between doses

Dosing Modifications

Extended release

• Severe renal impairment (GFR 15 to below 30 mL/min/1.73m²): Reduce recommended dose to 15 mg orally once daily
• End stage renal disease (ESRD [GFR below 15 ml/min/1.73m²]): Not recommended

Pediatric:

Attention Deficit Hyperactivity Disorder (ADHD)

Tablet

• Children below 3 years: Safety and efficacy not established
• Age 3-6 years: 2.5 mg/day; may increase by 2.5 mg once a week; not to exceed 40 mg once daily or divided once every 8 hours; use intervals of 4-6 hours between additional doses
• Children above 6 years: 5 mg orally once daily or once every 12 hours; may increase by 5 mg once a week; not to exceed 40 mg once daily or divided once 8 hours; use intervals of 4-6 hours between additional doses

Capsule, extended-release

• (Adderall XR)
  • Children below 6 years: Safety and efficacy not established
  • Children 6 years to below 13 years: 5-10 mg orally once every morning initially; may increase by 5-10 mg/day once a week; not to exceed 30 mg/day
  • Children 13-17 years: 10 mg orally once every morning initially; may increase to 20 mg/day after 1 week if symptoms not controlled; doses up to 60 mg/day have been used, but there is no evidence that higher doses increase effectiveness
• Mydayis
  • Children below 13 years: Safety and efficacy not established; younger children experienced higher plasma exposure than those aged 13 years or older at the same dose, and experienced higher rates of adverse reactions, mainly insomnia and decreased appetite
  • Children 13-17 years: 12.5 mg once every morning initially
  • May increase by increments of 12.5 mg/week; not to exceed 50 mg/day

Narcolepsy

• Children below 6 years: Safety and efficacy not established
• Children 6-12 years: 5 mg/day orally initially in divided doses; may increase by 5 mg/day once every week; not to exceed 60 mg once daily or divided doses with intervals of 4-6 hours between doses
• Children above 12 years: 10 mg/day orally initially; may increase by 10 mg/day once every week; not to exceed 60 mg given once daily or divided doses with intervals of 4-6 hours between doses

Dosing Modifications

Severe renal impairment

• Children below 6 years: Not established
• Children 6-17 years: 5 mg once daily recommended; not to exceed 20 mg once daily for children 6 to 12 years of age
• End stage renal disease (ESRD [GFR below 15 mL/min/1.73m²]): Not recommended

Addiction/overdose

• Amphetamine, the active component of amphetamine/dextroamphetamine has a high potential for addiction, abuse and misuse that can result in overdose and death. Amphetamine/dextroamphetamine use can lead to tolerance and dependence and cause withdrawal symptoms such as fatigue, sleep disturbances, unhappy mood, agitation and depression, upon discontinuation.
• Acute amphetamine overdose symptoms include restlessness, tremor, overactive reflexes (hyperreflexia), rapid breathing, hallucination, confusion, aggression, panic, fatigue, high body temperature (hyperpyrexia) and muscle breakdown (rhabdomyolysis). Cardiovascular symptoms include irregular heart rhythms (arrhythmias), changes in blood pressure and circulatory collapse, and gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps.
• Overdose can also cause serotonin syndrome, a potentially life-threatening condition due to excessive levels of serotonin, a chemical (neurotransmitter) in the brain. Severe overdose can cause convulsions, coma and death.
• Treatment for amphetamine overdose is symptomatic and supportive care. Any undigested drug from the gastrointestinal tract may be eliminated with gastric lavage and administration of activated charcoal. Benzodiazepines may be used for sedation and to control seizures. Take into consideration the prolonged release of amphetamine.
• Individual patient response to amphetamine varies widely. Consult with a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice for treatment of overdosage.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of amphetamine/dextroamphetamine include:
  • iobenguane I 123
  • isocarboxazid
  • linezolid
  • phenelzine
  • procarbazine
  • rasagiline
  • safinamide
  • selegiline
  • selegiline transdermal
  • tranylcypromine
• Serious interactions of amphetamine/dextroamphetamine include:
  • amitriptyline
  • amoxapine
  • cabergoline
  • clomipramine
  • desflurane
  • desipramine
  • desvenlafaxine
  • dihydroergotamine
  • dihydroergotamine intranasal
  • doxapram
  • doxepin
  • ergoloid mesylates
  • ergotamine
  • ether
  • imipramine
  • iobenguane I 131
  • isocarboxazid
  • ozanimod
• Amphetamine/dextroamphetamine has moderate interactions with at least 200 different drugs.
• Amphetamine/dextroamphetamine has mild interactions with at least 56 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Available data on the use of amphetamine/dextroamphetamine in pregnant women are insufficient to identify a drug-related risk for major birth defects and miscarriage.
• Amphetamine constricts blood vessels and hence can reduce blood flow to the placenta. It can stimulate uterine contractions and lead do premature delivery and low birth weight.
• Use of amphetamine/dextroamphetamine during pregnancy should be restricted to only when clearly needed and potential benefits justify potential fetal risks.
• If amphetamine/dextroamphetamine is used during pregnancy, monitor the newborn infant for withdrawal symptoms such as agitation, irritability, excessive drowsiness, and feeding difficulties.
• Amphetamine is present in breastmilk and may also interfere with milk production, especially if lactation is not well established.
• Although there are no reports of adverse effects on the breastfed infant from maternal use of amphetamine/dextroamphetamine, long term neurodevelopmental effects are not known.
• Amphetamine/dextroamphetamine use is not recommended in nursing mothers because of the potential for serious adverse reactions in the breastfed infant, including increase in blood pressure and heart rate, and peripheral vasculopathy.

• Amphetamine/dextroamphetamine is a Schedule II controlled substance. Diversion of Schedule II products is subject to criminal penalty.
• Take amphetamine/dextroamphetamine exactly as prescribed, do not take larger or more frequent doses.
• Amphetamine/dextroamphetamine has a high risk for abuse, addiction and dependency, and can lead to fatal overdose, exercise caution.
• Report to your physician immediately if you experience:
  • Heart-related symptoms such as chest pain with exertion, unexplained fainting or other such symptoms
  • Symptoms of peripheral vasculopathy such as numbness, pain, skin color change, sensitivity to temperature, or appearance of unexplained wounds in your fingers or toes.
  • Symptoms of serotonin syndrome, which may include changes in mental state, rapid heart rate, swings in blood pressure, dizziness, excessive sweating, flushing, high temperature, tremor, muscle twitches, rigidity, coordination difficulty, seizures, nausea, vomiting and diarrhea.
• Discontinue amphetamine/dextroamphetamine and report to your physician immediately if a seizure occurs.
• If your child is receiving amphetamine/dextroamphetamine treatment, monitor their growth and if expected growth and weight gain are not present, report to the physician.
• Amphetamine can impair mental and physical ability. Avoid driving, operating heavy machinery or other potentially hazardous tasks.
• Avoid drinking alcohol while taking amphetamine/dextroamphetamine, it can potentiate the drug effects.
• Store amphetamine/dextroamphetamine safely out of reach of children and others. Dispose of remaining unused or expired medicine by a medicine take-back program.
• In case of overdose, immediately seek medical care or contact Poison Control.