Adderall XR

Name: Adderall XR

Drug interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before treatment with this medication. Ask your doctor when to start or stop taking this medication.Check the labels on all your medicines (such as cough-and-cold products, diet aids) because they may contain ingredients that could increase your heart rate or blood pressure. Ask your pharmacist about using these products safely.Avoid drinking large amounts of beverages containing caffeine (coffee, tea, colas), eating large amounts of chocolate, or taking over-the-counter products that contain caffeine. Caffeine can increase the side effects of this medication.Dextroamphetamine is very similar to lisdexamfetamine. Do not use medications containing lisdexamfetamine while using dextroamphetamine.This medication may interfere with certain medical/laboratory tests (including blood and urine steroid levels, brain scan for Parkinson's disease), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

Commonly used brand name(s)

In the U.S.

  • Adderall
  • Adderall XR
  • Mydayis

In Canada

  • Adderall XR - 10mg
  • Adderall XR - 15mg
  • Adderall XR - 20mg
  • Adderall XR - 25mg
  • Adderall XR - 30mg
  • Adderall XR - 5mg

Available Dosage Forms:

  • Tablet
  • Capsule, Extended Release

Therapeutic Class: CNS Stimulant

Chemical Class: Amphetamine

Contraindications

Adderall XR administration is contraindicated in patients with the following conditions:

  • Advanced arteriosclerosis
  • Symptomatic cardiovascular disease
  • Moderate to severe hypertension
  • Hyperthyroidism
  • In patients known to be hypersensitive to amphetamine, or other components of Adderall XR. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [see ADVERSE REACTIONS (6.2)]
  • Glaucoma
  • Agitated states
  • History of drug abuse
  • Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis [see WARNINGS AND PRECAUTIONS (5.6) and DRUG INTERACTIONS (7.1)]

Adverse Reactions

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Clinical Studies Experience

The premarketing development program for Adderall XR included exposures in a total of 1315 participants in clinical trials (635 pediatric patients, 350 adolescent patients, 248 adult patients, and 82 healthy adult subjects). Of these, 635 patients (ages 6 to 12) were evaluated in two controlled clinical studies, one open-label clinical study, and two single-dose clinical pharmacology studies (N= 40). Safety data on all patients are included in the discussion that follows. Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs.

Adverse reactions during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a smaller number of standardized event categories. In the tables and listings that follow, COSTART terminology has been used to classify reported adverse reactions.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed.

Adverse Reactions Leading to Discontinuation of Treatment

In two placebo-controlled studies of up to 5 weeks duration among children with ADHD, 2.4% (10/425) of Adderall XR-treated patients discontinued due to adverse reactions (including 3 patients with loss of appetite, one of whom also reported insomnia) compared to 2.7% (7/259) receiving placebo.

The most frequent adverse reactions leading to discontinuation of Adderall XR in controlled and uncontrolled, multiple-dose clinical trials of children (N=595) were anorexia (loss of appetite) (2.9%), insomnia (1.5%), weight loss (1.2%), emotional lability (1%), and depression (0.7%). Over half of these patients were exposed to Adderall XR for 12 months or more.

In a separate placebo-controlled 4-week study in adolescents with ADHD, five patients (2.1%) discontinued treatment due to adverse events among Adderall XR-treated patients (N=233) compared to none who received placebo (N=54). The most frequent adverse event leading to discontinuation and considered to be drug-related (i.e. leading to discontinuation in at least 1% of Adderall XR-treated patients and at a rate at least twice that of placebo) was insomnia (1.3%, n=3).

In one placebo-controlled 4-week study among adults with ADHD with doses 20 mg to 60 mg, 23 patients (12.0%) discontinued treatment due to adverse events among Adderall XR-treated patients (N=191) compared to one patient (1.6%) who received placebo (N=64). The most frequent adverse events leading to discontinuation and considered to be drug-related (i.e. leading to discontinuation in at least 1% of Adderall XR-treated patients and at a rate at least twice that of placebo) were insomnia (5.2%, n=10), anxiety (2.1%, n=4), nervousness (1.6%, n=3), dry mouth (1.6%, n=3), anorexia (1.6%, n=3), tachycardia (1.6%, n=3), headache (1.6%, n=3), and asthenia (1.0%, n=2).

Adverse Reactions Occurring in Controlled Trials

Adverse reactions reported in a 3-week clinical trial of children and a 4-week clinical trial in adolescents and adults, respectively, treated with Adderall XR or placebo are presented in the tables below.

Table 1 Adverse Reactions Reported by 2% or More of Children (6-12 Years Old) Receiving Adderall XR with Higher Incidence Than on Placebo in a 584-Patient Clinical Study
 Body System   Preferred Term  Adderall XR
 (n=374)

 Placebo
 (n=210)

 General  Abdominal Pain (stomachache)
 Fever
 Infection
 Accidental Injury
 Asthenia (fatigue)
 14%
 5%
 4%
 3%
 2%
 10%
 2%
 2%
 2%
 0%
 Digestive System  Loss of Appetite
 Vomiting
 Nausea
 Dyspepsia
 22%
 7%
 5%
 2%
 2%
 4%
 3%
 1%
 Nervous System  Insomnia
 Emotional Lability
 Nervousness
 Dizziness
 17%
 9%
 6%
 2%

 2%
 2%
 2%
 0%

 Metabolic/Nutritional  Weight Loss  4%  0%
Table 2 Adverse Reactions Reported by 5% or More of Adolescents (13-17 Years Old) Weighing ≤ 75 kg/165 lbs Receiving Adderall XR with Higher Incidence Than Placebo in a 287 Patient Clinical Forced Weekly-Dose Titration Study*
*Included doses up to 40 mg
a Appears the same due to rounding
b Dose-related adverse reactions
Note: The following reactions did not meet the criterion for inclusion in Table 2 but were reported by 2% to 4% of adolescent patients receiving Adderall XR with a higher incidence than patients receiving placebo in this study: accidental injury, asthenia (fatigue), dry mouth, dyspepsia, emotional lability, nausea, somnolence, and vomiting.
Body System Preferred Term Adderall XR
(n=233)
Placebo
(n=54)
 General Abdominal Pain (stomachache) 11% 2%
 Digestive System Loss of Appetite b 36% 2%
 Nervous System Insomnia b
Nervousness
12%
6%
4%
6%a
 Metabolic/Nutritional Weight Loss b 9% 0%
Table 3 Adverse Reactions Reported by 5% or More of Adults Receiving Adderall XR with Higher Incidence Than on Placebo in a 255 Patient Clinical Forced Weekly-Dose Titration Study*

*Included doses up to 60 mg.
a Appears the same due to rounding
Note: The following reactions did not meet the criterion for inclusion in Table 3 but were reported by 2% to 4% of adult patients receiving Adderall XR with a higher incidence than patients receiving placebo in this study: infection, photosensitivity reaction, constipation, tooth disorder (e.g., teeth clenching, tooth infection), emotional lability, libido decreased, somnolence, speech disorder (e.g., stuttering, excessive speech), palpitation, twitching, dyspnea, sweating, dysmenorrhea, and impotence.

Body System Preferred Term Adderall XR
(n=191)
Placebo
(n=64)
 General Headache
Asthenia
26%
6%
13%
5%
 Digestive System Dry Mouth
Loss of Appetite
Nausea
Diarrhea
35%
33%
8%
6%
5%
3%
3%
0%
 Nervous System

Insomnia
Agitation
Anxiety
Dizziness
Nervousness

27%
8%
8%
7%
13%
13%
5%
5%
0%
13%a
 Cardiovascular System Tachycardia 6% 3%
 Metabolic/Nutritional Weight Loss 10% 0%
 Urogenital System Urinary Tract Infection 5% 0%

Hypertension [see WARNINGS AND PRECAUTIONS (5.1)]

In a controlled 4-week outpatient clinical study of adolescents with ADHD, isolated systolic blood pressure elevations ≥15 mmHg were observed in 7/64 (11%) placebo-treated patients and 7/100 (7%) patients receiving Adderall XR 10 or 20 mg. Isolated elevations in diastolic blood pressure ≥ 8 mmHg were observed in 16/64 (25%) placebo-treated patients and 22/100 (22%) Adderall XR-treated patients. Similar results were observed at higher doses.

In a single-dose pharmacokinetic study in 23 adolescents with ADHD, isolated increases in systolic blood pressure (above the upper 95% CI for age, gender, and stature) were observed in 2/17 (12%) and 8/23 (35%), subjects administered 10 mg and 20 mg Adderall XR, respectively. Higher single doses were associated with a greater increase in systolic blood pressure. All increases were transient, appeared maximal at 2 to 4 hours post dose and not associated with symptoms.

Adverse Reactions Associated with the Use of Amphetamine, Adderall XR, or ADDERALL

The following adverse reactions have been associated with the use of amphetamine, Adderall XR, or ADDERALL:

Cardiovascular

Palpitations. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System

Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, tics, aggression, anger, logorrhea, dermatillomania, paresthesia (including formication), and bruxism.

Eye Disorders

Vision blurred, mydriasis.

Gastrointestinal

Unpleasant taste, constipation, other gastrointestinal disturbances.

Allergic

Urticaria, rash, hypersensitivity reactions including angioedema and anaphylaxis. Serious skin rashes, including Stevens-Johnson Syndrome and toxic epidermal necrolysis have been reported.

Endocrine

Impotence, changes in libido, frequent or prolonged erections.

Skin

Alopecia.

Vascular Disorders

Raynaud's phenomenon.

Musculoskeletal and Connective Tissue Disorders

Rhabdomyolysis

Adderall XR Description

Adderall XR is a once daily extended-release, single-entity amphetamine product. Adderall XR combines the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of amphetamine saccharate and d,l-amphetamine aspartate monohydrate. The Adderall XR capsule contains two types of drug-containing beads designed to give a double-pulsed delivery of amphetamines, which prolongs the release of amphetamine from Adderall XR compared to the conventional ADDERALL (immediate-release) tablet formulation.

Each capsule contains:   5 mg   10 mg   15 mg   20 mg   25 mg   30 mg
Dextroamphetamine Saccharate   1.25 mg   2.5 mg   3.75 mg   5.0 mg   6.25 mg   7.5 mg
Amphetamine Aspartate Monohydrate   1.25 mg   2.5 mg   3.75 mg   5.0 mg   6.25 mg   7.5 mg
Dextroamphetamine Sulfate USP   1.25 mg   2.5 mg   3.75 mg   5.0 mg   6.25 mg   7.5 mg
Amphetamine Sulfate USP   1.25 mg   2.5 mg   3.75 mg   5.0 mg   6.25 mg   7.5 mg
Total amphetamine base equivalence   3.1 mg   6.3 mg   9.4 mg   12.5 mg   15.6 mg   18.8 mg

Inactive Ingredients and Colors
The inactive ingredients in Adderall XR capsules include: gelatin capsules, hydroxypropyl methylcellulose, methacrylic acid copolymer, opadry beige, sugar spheres, talc, and triethyl citrate. Gelatin capsules contain edible inks, kosher gelatin, and titanium dioxide. The 5 mg, 10 mg, and 15 mg capsules also contain FD&C Blue #2. The 20 mg, 25 mg, and 30 mg capsules also contain red iron oxide and yellow iron oxide.

How Supplied/Storage and Handling

Adderall XR 5 mg capsules: Clear/blue (imprinted Adderall XR 5 mg), bottles of 100, NDC 54092-381-01

Adderall XR 10 mg capsules: Blue/blue (imprinted Adderall XR 10 mg), bottles of 100, NDC 54092-383-01

Adderall XR 15 mg capsules: Blue/white (imprinted Adderall XR 15 mg), bottles of 100, NDC 54092-385-01

Adderall XR 20 mg capsules: Orange/orange (imprinted Adderall XR 20 mg), bottles of 100, NDC 54092-387-01

Adderall XR 25 mg capsules: Orange/white (imprinted Adderall XR 25 mg), bottles of 100, NDC 54092-389-01

Adderall XR 30 mg capsules: Natural/orange (imprinted Adderall XR 30 mg), bottles of 100, NDC 54092-391-01

Dispense in a tight, light-resistant container as defined in the USP.

Store at 25° C (77° F). Excursions permitted to 15-30° C (59-86° F) [see USP Controlled Room Temperature]

Warnings

Black Box Warnings

Amphetamines have a high potential for abuse

Administration for prolonged periods may lead to dependence and must be avoided

Assess the possibility of persons obtaining amphetamines for nontherapeutic use or distribution to others

Prescribed or dispensed sparingly

Misuse of amphetamines may cause sudden death and serious cardiovascular adverse events

Contraindications

Hypersensitivity

Hyperthryroidism

Glaucoma

Hypertension, advanced arteriosclerosis, symptomatic CVD

Symptomatic cardiovascular disease

Moderate-to-severe hypertension

Agitated states, history of drug abuse

MAO inhibitors given within 14 days (risk of severe hypertensive reaction)

Cautions

Preexisting cardiac structural abnormalities associated with risk of sudden death (if abused)

Time to maximum concentration decreased when coadministered with acid-suppressing drugs (eg, proton pump inhibitors)

Associated with peripheral vasculopathy, including Raynaud phenomenon

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment

May impair ability to engage in potentially hazardouse activities due to CNS effects

Potential exists for drug dependency

Use caution in hypertension, history of psychosis, seizure disorders, elderly, or Tourette's syndrome (may unmask tics)

Abrupt discontinuation may result in symptoms for withdrawal

Sudden deaths, stroke, and myocardial infarction reported in adults taking stimulants at usual doses

Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation

Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder because of concern for possible induction of mixed/manic episode in such patients

Aggressive behavior or hostility is often observed in children and adolescents with ADHD; monitor for the appearance of or worsening of aggressive behavior or hostility

Monitor growth of children ages 7 to 10 years during treatment with stimulants; may need to interrupt therapy in patients not growing or gaining weight as expected

Stimulants may lower convulsive threshold in patients with prior history of seizure, patients with prior EEG abnormalities in absence of seizures, and very rarely, patients without a history of seizures and no prior EEG evidence of seizures; discontinue therapy in the presence of seizures

Use with caution in patients who use other sympathomimetic drugs

Amphetamines may exacerbate motor and phonic tics and Tourette’s syndrome; perform clinical evaluation for tics and Tourette’s syndrome in children and their families prior to treating with stimulant medications

Rare instances of prolonged and sometimes painful erections (priapism), sometimes requiring surgical intervention, reported with methylphenidate products; typically not reported during initiation, but often subsequent to an increase in dose; seek immediate medical attention for abnormally sustained or frequent and painful erections

Drug interaction overview

  • Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort
  • Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism; potential for a pharmacokinetic interaction exists with coadministration of CYP2D6 inhibitors which may increase risk with increased exposure to amphetamines and derivatives; in these situations, consider alternative non-serotonergic drug or alternative drug that does not inhibit CYP2D6
  • If concomitant use with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate therapy with lower doses, monitor patients for emergence of serotonin syndrome during drug initiation or titration, and inform patients of increased risk for serotonin syndrome

How it works

Adderall is a long-acting, amphetamine-type product that consists of different amphetamine salts (dextroamphetamine saccharate and sulfate, amphetamine aspartate and sulfate). Experts aren't sure exactly how Adderall works in ADHD but think it affects the reuptake of dopamine and norepinephrine, two neurotransmitters. Adderall is a central nervous system (CNS) stimulant.

Bottom Line

Adderall XR is a long-acting, once-daily formulation that combines four different amphetamine salts into one product and is used for the treatment of ADHD. Its use is limited by its potential to be addictive and cause dependence.

Tips

  • Take in the morning. Avoid taking in the afternoon because of the potential for insomnia.
  • May be taken with or without food.
  • Adderall XR capsules may be swallowed whole, or the capsule opened and the contents mixed with applesauce and consumed immediately, without chewing. Do not attempt to divide contents of a capsule or store mixed applesauce/Adderall XR product.
  • Administer at the lowest effective dosage and take exactly as directed by your doctor; never increase dosage without their advice.
  • Avoid sudden discontinuation as this can precipitate a withdrawal reaction.
  • Seek medical advice if symptoms persist or worsen despite treatment, or if new psychotic symptoms (eg, hearing voices, signs of paranoia) develop.
  • Seek urgent medical help if chest pain, shortness of breath or fainting is experienced while taking Adderall.
  • Do not drive or operate machinery if Adderal XRl impairs your judgment or reaction skills.
  • Seek medical advice if any new numbness, pain, skin color change or sensitivity or unexplained wounds occur in fingers or toes.
  • If you notice any changes in your mental state (such as feeling agitated, hallucinations), dizziness, fast heart rate, flushing, incoordination, tremor, rigidity, nausea or vomiting, seek urgent medical advice.

How should I take Adderall XR (amphetamine and dextroamphetamine)?

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Amphetamine and dextroamphetamine may be habit-forming. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. Selling or giving away this medicine is against the law.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

You may take this medicine with or without food, first thing in the morning.

Do not crush, chew, break, or open an extended-release capsule. Swallow it whole.

To make swallowing easier, you may open the capsule and sprinkle the medicine into a spoonful of applesauce. Swallow right away without chewing. Do not save the mixture for later use.

While using this medicine, your doctor will need to check your progress at regular visits. Tell any doctor who treats you that you are using this medicine.

Amphetamine and dextroamphetamine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using this medicine.

Store at room temperature away from moisture, heat, and light.

Keep track of your medicine. Amphetamine and dextroamphetamine is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

Adderall XR (amphetamine and dextroamphetamine) side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • signs of heart problems--chest pain, trouble breathing, feeling like you might pass out;

  • signs of psychosis--hallucinations (seeing or hearing things that are not real), new behavior problems, aggression, hostility, paranoia;

  • signs of circulation problems--numbness, pain, cold feeling, unexplained wounds, or skin color changes (pale, red, or blue appearance) in your fingers or toes;

  • a seizure (convulsions);

  • muscle twitches (tics); or

  • changes in your vision.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.

Amphetamine and dextroamphetamine can affect growth in children. Tell your doctor if your child is not growing at a normal rate while using this medicine.

Common side effects may include:

  • stomach pain, loss of appetite;

  • weight loss;

  • mood changes, feeling nervous;

  • fast heart rate;

  • headache, dizziness;

  • sleep problems (insomnia); or

  • dry mouth.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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