Drug Detail:Adderall xr (Amphetamine and dextroamphetamine [ am-fet-a-meen-and-dex-troe-am-fet-a-meen ])
Drug Class: CNS stimulants
Highlights of Prescribing Information
ADDERALL XR® (mixed salts of a single-entity amphetamine product) extended release capsules, for oral use, CII
Initial U.S. Approval: 2001
WARNING: ABUSE AND DEPENDENCE
See full prescribing information for complete boxed warning
- CNS stimulants, including ADDERALL XR, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence (5.1, 9.3)
- Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy (9.2, 9.3).
Indications and Usage for Adderall XR
ADDERALL XR, a CNS stimulant, is indicated for the treatment of attention deficit hyperactivity disorder (ADHD). (1)
- Children (ages 6-12): Efficacy was established in one 3-week outpatient, controlled trial and one analogue classroom, controlled trial in children with ADHD. (14)
- Adolescents (ages 13-17): Efficacy was established in one 4-week controlled trial in adolescents with ADHD. (14)
- Adults: Efficacy was established in one 4-week controlled trial in adults with ADHD. (14)
Adderall XR Dosage and Administration
- Pediatric patients (ages 6-17): 10 mg once daily in the morning. Maximum dose for children 6-12 years of age is 30 mg once daily. (2.2, 2.3, 2.4)
- Adults: 20 mg once daily in the morning. (2.5)
- Pediatric patients (ages 6-17) with severe renal impairment: 5 mg once daily in the morning. Maximum dose for children 6- 12 years of age with severe renal impairment is 20 mg once daily. (2.6, 8.6)
- Adults with severe renal impairment: 15 mg once daily in the morning. (2.6, 8.6)
- Patients with ESRD: not recommended. (2.6, 8.6)
Dosage Forms and Strengths
- Extended release capsules: 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg (3)
Contraindications
- Advanced arteriosclerosis (4)
- Symptomatic cardiovascular disease (4)
- Moderate to severe hypertension (4)
- Hyperthyroidism (4)
- Known hypersensitivity or idiosyncrasy to amphetamine (4)
- Glaucoma (4)
- Agitated states (4)
- History of drug abuse (4)
- During or within 14 days following the administration of monoamine oxidase inhibitors (MAOI) (4, 7.1)
Warnings and Precautions
- Serious Cardiovascular Reactions: Sudden death has been reported with usual doses of CNS stimulants in children and adolescents with structural cardiac abnormalities or other serious heart problems; sudden death, stroke, and myocardial infarction have been reported in adults taking CNS stimulants at usual doses. Stimulant drugs should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious heart problems. (5.2)
- Increase in Blood Pressure: Monitor blood pressure and pulse at appropriate intervals. Use with caution in patients for whom blood pressure increases may be problematic. (5.2)
- Psychiatric Adverse Events: Stimulants may cause treatment-emergent psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychosis. Evaluate for bipolar disorder prior to stimulant use. Monitor for aggressive behavior. (5.3)
- Long-Term Suppression of Growth: Monitor height and weight at appropriate intervals. (5.4)
- Seizures: May lower the convulsive threshold. Discontinue in the presence of seizures. (5.5)
- Peripheral Vasculopathy, including Raynaud's phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants. (5.6)
- Serotonin Syndrome: Increased risk when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. If it occurs, discontinue ADDERALL XR and initiate supportive treatment (4, 5.7, 10).
- Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment. (5.8)
- Tics: May exacerbate tics. Evaluate for tics and Tourette's syndrome prior to stimulant administration. (5.9)
Adverse Reactions/Side Effects
- Children (ages 6 to 12): Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, emotional lability, vomiting, nervousness, nausea, and fever. (6.1)
- Adolescents (ages 13 to 17): Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, weight loss, and nervousness. (6.1)
- Adults: Most common adverse reactions ≥5% and with a higher incidence than on placebo were dry mouth, loss of appetite, insomnia, headache, weight loss, nausea, anxiety, agitation, dizziness, tachycardia, diarrhea, asthenia, and urinary tract infections. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-800-828-2088 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Drug Interactions
- MAOI antidepressants are contraindicated; MAOIs potentiate the effects of amphetamine. Do not administer ADDERALL XR during or within 14 days after use of MAOI. (4, 7.1)
- Alkalinizing agents (GI antacids and urinary): These agents increase blood levels of amphetamine. (7.1)
- Acidifying agents (GI and urinary): These agents reduce blood levels of amphetamine. (7.1)
- Adrenergic blockers, antihistamines, antihypertensives, phenobarbital, phenytoin, veratrum alkaloids, and ethosuximide: Effects may be reduced by amphetamines. (7.1)
- Tricyclic antidepressants, norepinephrine, and meperidine: Effects may be potentiated by amphetamines. (7.1)
Use In Specific Populations
- Pregnancy: May cause fetal harm. (8.1)
- Lactation: Breastfeeding not recommended. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 2/2022
Full Prescribing Information
WARNING: ABUSE AND DEPENDENCE
CNS stimulants, including ADDERALL XR, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy [see Warnings and Precautions (5.1) and Drug Abuse and Dependence (9.2, 9.3)].
1. Indications and Usage for Adderall XR
1.1 Attention Deficit Hyperactivity Disorder
ADDERALL XR® is indicated for the treatment of attention deficit hyperactivity disorder (ADHD).
The efficacy of ADDERALL XR in the treatment of ADHD was established on the basis of two controlled trials in children aged 6 to 12, one controlled trial in adolescents aged 13 to 17, and one controlled trial in adults who met DSM-IV® criteria for ADHD [see Clinical Studies (14)].
A diagnosis of ADHD (DSM-IV®) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; "on the go;" excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.
2. Adderall XR Dosage and Administration
2.1 Important Information Prior to Initiating Treatment
Prior to initiating treatment with ADDERALL XR, assess for the presence of cardiac disease (e.g., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions (5.2)].
Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy. Maintain careful prescription records, educate patients about abuse, monitor for signs for abuse and overdose, and periodically re-evaluate the need for ADDERALL XR use [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9)].
2.2 Dosing Considerations for All Patients
Individualize the dosage according to the therapeutic needs and response of the patient. Administer ADDERALL XR at the lowest effective dosage.
Based on bioequivalence data, patients taking divided doses of immediate-release ADDERALL, (for example, twice daily), may be switched to ADDERALL XR at the same total daily dose taken once daily. Titrate at weekly intervals to appropriate efficacy and tolerability as indicated.
ADDERALL XR extended release capsules may be taken whole, or the capsule may be opened and the entire contents sprinkled on applesauce. If the patient is using the sprinkle administration method, the sprinkled applesauce should be consumed immediately; it should not be stored. Patients should take the applesauce with sprinkled beads in its entirety without chewing. The dose of a single capsule should not be divided. The contents of the entire capsule should be taken, and patients should not take anything less than one capsule per day.
ADDERALL XR may be taken with or without food.
ADDERALL XR should be given upon awakening. Afternoon doses should be avoided because of the potential for insomnia.
Where possible, ADDERALL XR therapy should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.
2.3 Children
In children with ADHD who are 6-12 years of age and are either starting treatment for the first time or switching from another medication, start with 10 mg once daily in the morning; daily dosage may be adjusted in increments of 5 mg or 10 mg at weekly intervals. When in the judgment of the clinician a lower initial dose is appropriate, patients may begin treatment with 5 mg once daily in the morning. The maximum recommended dose for children 6-12 years of age is 30 mg/day; doses greater than 30 mg/day have not been studied in children. ADDERALL XR has not been studied in children under 6 years of age.
2.4 Adolescents
The recommended starting dose for adolescents with ADHD who are 13-17 years of age and are either starting treatment for the first time or switching from another medication is 10 mg/day. The dose may be increased to 20 mg/day after one week if ADHD symptoms are not adequately controlled.
2.5 Adults
In adults with ADHD who are either starting treatment for the first time or switching from another medication, the recommended dose is 20 mg/day.
2.6 Dosage in Patients with Renal Impairment
In adult patients with severe renal impairment (GFR 15 to < 30 mL/min/1.73m2), the recommended dose is 15 mg once daily in the morning. In pediatric patients (6 to 17 years of age) with severe renal impairment, the recommended dose is 5 mg once daily. The maximum dose for children 6 to 12 years of age with severe renal impairment is 20 mg once daily. ADDERALL XR is not recommended in patients with end stage renal disease (ESRD) (GFR < 15 mL/min/1.73m2) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
3. Dosage Forms and Strengths
ADDERALL XR 5 mg extended release capsules: Clear/blue (imprinted ADDERALL XR 5 mg)
ADDERALL XR 10 mg extended release capsules: Blue/blue (imprinted ADDERALL XR 10 mg)
ADDERALL XR 15 mg extended release capsules: Blue/white (imprinted ADDERALL XR 15 mg)
ADDERALL XR 20 mg extended release capsules: Orange/orange (imprinted ADDERALL XR 20 mg)
ADDERALL XR 25 mg extended release capsules: Orange/white (imprinted ADDERALL XR 25 mg)
ADDERALL XR 30 mg extended release capsules: Natural/orange (imprinted ADDERALL XR 30 mg)
4. 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 (5.7) and Drug Interactions (7.1)]
5. Warnings and Precautions
5.1 Potential for Abuse and Dependence
CNS stimulants, including ADDERALL XR, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy [see Boxed Warning, Drug Abuse and Dependence (9.2, 9.3)].
5.2 Serious Cardiovascular Reactions
5.4 Long-Term Suppression of Growth
Monitor growth in children during treatment with stimulants. Patients who are not growing or gaining weight as expected may need to have their treatment interrupted.
Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development.
In a controlled trial of ADDERALL XR in adolescents, mean weight change from baseline within the initial 4 weeks of therapy was −1.1 lbs. and −2.8 lbs., respectively, for patients receiving 10 mg and 20 mg ADDERALL XR. Higher doses were associated with greater weight loss within the initial 4 weeks of treatment. Chronic use of amphetamines can be expected to cause a similar suppression of growth.
5.5 Seizures
There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in the absence of seizures, and very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, ADDERALL XR should be discontinued.
5.6 Peripheral Vasculopathy, including Raynaud's Phenomenon
Stimulants, including ADDERALL XR, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.
5.7 Serotonin Syndrome
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 MAOIs, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort [see Drug Interactions (7.1)]. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism [see Clinical Pharmacology (12.3)]. The potential for a pharmacokinetic interaction exists with the co-administration of CYP2D6 inhibitors which may increase the risk with increased exposure to ADDERALL XR. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions (7.1)]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Concomitant use of ADDERALL XR with MAOI drugs is contraindicated [see Contraindications (4)].
Discontinue treatment with ADDERALL XR and any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment. Concomitant use of ADDERALL XR with other serotonergic drugs or CYP2D6 inhibitors should be used only if the potential benefit justifies the potential risk. If clinically warranted, consider initiating ADDERALL XR with lower doses, monitoring patients for the emergence of serotonin syndrome during drug initiation or titration, and informing patients of the increased risk for serotonin syndrome.
5.8 Visual Disturbance
Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.
6. Adverse Reactions/Side Effects
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 practice.
6.1 Clinical Trials 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.
6.2 Adverse Reactions Associated with the Use of Amphetamine, ADDERALL XR, or ADDERALL
The following adverse reactions have been identified during post-approval use of amphetamine, ADDERALL XR, or ADDERALL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
7. Drug Interactions
7.1 Clinically Important Interactions with Amphetamines
| Monoamine Oxidase Inhibitors (MAOIs) | |
| Clinical Impact | Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. |
| Intervention | Do not administer ADDERALL XR concomitantly or within 14 days after discontinuing MAOI [see Contraindications (4)]. |
| Examples | selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue |
| Serotonergic Drugs | |
| Clinical Impact | The concomitant use of ADDERALL XR and serotonergic drugs increases the risk of serotonin syndrome. |
| Intervention | Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during ADDERALL XR initiation or dosage increase. If serotonin syndrome occurs, discontinue ADDERALL XR and the concomitant serotonergic drug(s) [see Warnings and Precautions (5.7)]. |
| Examples | selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort |
| CYP2D6 Inhibitors | |
| Clinical Impact | The concomitant use of ADDERALL XR and CYP2D6 inhibitors may increase the exposure of ADDERALL XR compared to the use of the drug alone and increase the risk of serotonin syndrome. |
| Intervention | Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during ADDERALL XR initiation and after a dosage increase. If serotonin syndrome occurs, discontinue ADDERALL XR and the CYP2D6 inhibitor [see Warnings and Precautions (5.7) and Overdosage (10)]. |
| Examples | paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir |
| Alkalinizing Agents | |
| Clinical Impact | Increase blood levels and potentiate the action of amphetamine. |
| Intervention | Co-administration of ADDERALL XR and gastrointestinal or urinary alkalinizing agents should be avoided. |
| Examples | Gastrointestinal alkalinizing agents (e.g., sodium bicarbonate). Urinary alkalinizing agents (e.g. acetazolamide, some thiazides). |
| Acidifying Agents | |
| Clinical Impact | Lower blood levels and efficacy of amphetamines. |
| Intervention | Increase dose based on clinical response. |
| Examples | Gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl, ascorbic acid). Urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts). |
| Tricyclic Antidepressants | |
| Clinical Impact | May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. |
| Intervention | Monitor frequently and adjust or use alternative therapy based on clinical response. |
| Examples | desipramine, protriptyline |
| Proton Pump Inhibitors | |
| Clinical Impact | Time to maximum concentration (Tmax) of amphetamine is decreased compared to when administered alone. |
| Intervention | Monitor patients for changes in clinical effect and adjust therapy based on clinical response. |
| Examples | Omeprazole |
8. Use In Specific Populations
8.4 Pediatric Use
ADDERALL XR is indicated for use in children 6 years of age and older.
The safety and efficacy of ADDERALL XR in children under 6 years of age have not been studied. Long-term effects of amphetamines in children have not been well established.
8.6 Renal Impairment
Due to reduced clearance of amphetamines in patients with severe renal impairment (GFR 15 to <30 mL/min/1.73m2), the recommended dose should be reduced. ADDERALL XR is not recommended in patients with ESRD (GFR < 15 ml/min/1.73m2) [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)].
d-Amphetamine is not dialyzable.
9. Drug Abuse and Dependence
9.2 Abuse
ADDERALL XR is a CNS stimulant that contains amphetamine, which has a high potential for abuse. Abuse is characterized by impaired control of drug use, compulsive use despite harm, and craving.
Signs and symptoms of amphetamine abuse may include increased heart rate, respiratory rate, blood pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility, aggression, suicidal or homicidal ideation have also been observed. Abusers of amphetamines may use other unapproved routes of administration which can result in overdose and death [see Overdosage (10)].
To reduce the abuse of CNS stimulants, including ADDERALL XR, assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and proper storage and disposal of CNS stimulants. Monitor for signs of abuse while on therapy and re-evaluate the need for ADDERALL XR use.
9.3 Dependence
Tolerance (a state of adaptation in which exposure to a specific dose of a drug results in a reduction of the drug's desired and/or undesired effects over time, in such a way that a higher dose of the drug is required to produce the same effect that was once obtained at a lower dose) may occur during chronic therapy of CNS stimulants including ADDERALL XR.
Physical Dependence (which is manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist) may occur in patients treated with CNS stimulants including ADDERALL XR. Withdrawal symptoms after abrupt cessation of CNS stimulants include dysphoric mood; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
10. Overdosage
Manifestations of amphetamine overdose include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Fatigue and depression usually follow the central nervous system stimulation. Serotonin syndrome has been reported with amphetamine use, including ADDERALL XR. Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.
11. Adderall XR Description
ADDERALL XR extended-release capsules contain mixed salts of a single-entity amphetamine, a CNS stimulant. ADDERALL XR contains equal amounts (by weight) of four salts: dextroamphetamine sulfate, amphetamine sulfate, dextroamphetamine saccharate and amphetamine (D,L)-aspartate monohydrate. This results in a 3.1:1 mixture of dextro- to levo- amphetamine base equivalent.
The 5 mg, 10 mg, 15 mg, 20 mg, 25 mg and 30 mg strength extended release capsules are for oral administration. Adderall XR contains two types of drug-containing beads (immediate-release and delayed release) which prolong the release of amphetamine compared to the ADDERALL (immediate-release) tablet formulation.
Each capsule contains:
| Capsule Strength | 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 (D,L)-Aspartate Monohydrate | 1.25 mg | 2.5 mg | 3.75 mg | 5.0 mg | 6.25 mg | 7.5 mg |
| Dextroamphetamine Sulfate | 1.25 mg | 2.5 mg | 3.75 mg | 5.0 mg | 6.25 mg | 7.5 mg |
| Amphetamine Sulfate | 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 |
| d-amphetamine base equivalence | 2.4 mg | 4.7 mg | 7.1 mg | 9.5 mg | 11.9 mg | 14.2 mg |
| l-amphetamine base equivalence | 0.75 mg | 1.5 mg | 2.3 mg | 3.0 mg | 3.8 mg | 4.5 mg |
12. Adderall XR - Clinical Pharmacology
12.1 Mechanism of Action
Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in ADHD is not known.
12.2 Pharmacodynamics
Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.
12.3 Pharmacokinetics
Pharmacokinetic studies of ADDERALL XR have been conducted in healthy adult and pediatric (children aged 6-12 yrs) subjects, and adolescent (13-17 yrs) and children with ADHD. Both ADDERALL (immediate-release) tablets and ADDERALL XR extended release capsules contain d-amphetamine and l-amphetamine salts in the ratio of 3:1. Following administration of ADDERALL (immediate-release), the peak plasma concentrations occurred in about 3 hours for both d-amphetamine and l-amphetamine.
The time to reach maximum plasma concentration (Tmax) for ADDERALL XR is about 7 hours, which is about 4 hours longer compared to ADDERALL (immediate-release). This is consistent with the extended-release nature of the product.
Figure 1 Mean d-amphetamine and l-amphetamine Plasma Concentrations Following Administration of ADDERALL XR 20 mg (8 am) and ADDERALL (immediate-release) 10 mg Twice Daily (8 am and 12 noon) in the Fed State.
A single dose of ADDERALL XR 20 mg extended release capsules provided comparable plasma concentration profiles of both d-amphetamine and l-amphetamine to ADDERALL (immediate-release) 10 mg twice daily administered 4 hours apart.
The mean elimination half-life for d-amphetamine is 10 hours in adults; 11 hours in adolescents aged 13-17 years and weighing less than or equal to 75 kg/165 lbs; and 9 hours in children aged 6 to 12 years. For the l-amphetamine, the mean elimination half-life in adults is 13 hours; 13 to 14 hours in adolescents; and 11 hours in children aged 6 to 12 years. On a mg/kg body weight basis, children have a higher clearance than adolescents or adults (see Special Populations below).
ADDERALL XR demonstrates linear pharmacokinetics over the dose range of 20 to 60 mg in adults and adolescents weighing greater than 75 kg/165 lbs, over the dose range of 10 to 40 mg in adolescents weighing less than or equal to 75 kg/165 lbs, and 5 to 30 mg in children aged 6 to 12 years. There is no unexpected accumulation at steady state in children.
Food does not affect the extent of absorption of d-amphetamine and l-amphetamine, but prolongs Tmax by 2.5 hours (from 5.2 hrs at fasted state to 7.7 hrs after a high-fat meal) for d-amphetamine and 2.7 hours (from 5.6 hrs at fasted state to 8.3 hrs after a high fat meal) for l-amphetamine after administration of ADDERALL XR 30 mg. Opening the capsule and sprinkling the contents on applesauce results in comparable absorption to the intact capsule taken in the fasted state. Equal doses of ADDERALL XR strengths are bioequivalent.
Special Populations
Comparison of the pharmacokinetics of d- and l-amphetamine after oral administration of ADDERALL XR in children (6-12 years) and adolescent (13-17 years) ADHD patients and healthy adult volunteers indicates that body weight is the primary determinant of apparent differences in the pharmacokinetics of d- and l-amphetamine across the age range. Systemic exposure measured by area under the curve to infinity (AUC∞) and maximum plasma concentration (Cmax) decreased with increases in body weight, while oral volume of distribution (VZ/F), oral clearance (CL/F), and elimination half-life (t1/2) increased with increases in body weight.
16. How is Adderall XR supplied
ADDERALL XR 5 mg extended release capsules: Clear/blue (imprinted ADDERALL XR 5 mg), bottles of 100, NDC 54092-381-01
ADDERALL XR 10 mg extended release capsules: Blue/blue (imprinted ADDERALL XR 10 mg), bottles of 100, NDC 54092-383-01
ADDERALL XR 15 mg extended release capsules: Blue/white (imprinted ADDERALL XR 15 mg), bottles of 100, NDC 54092-385-01
ADDERALL XR 20 mg extended release capsules: Orange/orange (imprinted ADDERALL XR 20 mg), bottles of 100, NDC 54092-387-01
ADDERALL XR 25 mg extended release capsules: Orange/white (imprinted ADDERALL XR 25 mg), bottles of 100, NDC 54092-389-01
ADDERALL XR 30 mg extended release capsules: Natural/orange (imprinted ADDERALL XR 30 mg), bottles of 100, NDC 54092-391-01
17. Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Medication Guide
Read the Medication Guide that comes with ADDERALL XR before you or your child starts taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about you or your child's treatment with ADDERALL XR.
What is the most important information I should know about ADDERALL XR?
ADDERALL XR is a stimulant medicine. The following have been reported with use of stimulant medicines.
1. Heart-related problems:
- sudden death in patients who have heart problems or heart defects
- stroke and heart attack in adults
- increased blood pressure and heart rate
Tell your doctor if you or your child have any heart problems, heart defects, high blood pressure, or a family history of these problems.
Your doctor should check you or your child carefully for heart problems before starting ADDERALL XR.
Your doctor should check you or your child's blood pressure and heart rate regularly during treatment with ADDERALL XR.
Call your doctor right away if you or your child has any signs of heart problems such as chest pain, shortness of breath, or fainting while taking ADDERALL XR.
2. Mental (Psychiatric) problems:
All Patients
- new or worse behavior and thought problems
- new or worse bipolar illness
- new or worse aggressive behavior or hostility
Children and Teenagers
- new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms
Tell your doctor about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.
Call your doctor right away if you or your child have any new or worsening mental symptoms or problems while taking ADDERALL XR, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.
3. Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon]:
- Fingers or toes may feel numb, cool, painful
- Fingers or toes may change from pale, to blue, to red
Tell your doctor if you have or your child has numbness, pain, skin color change, or sensitivity to temperature in your fingers or toes.
Call your doctor right away if you have or your child has any unexplained wounds appearing on fingers or toes while taking ADDERALL XR.
What Is ADDERALL XR?
ADDERALL XR is a once daily central nervous system stimulant prescription medicine. It is used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). ADDERALL XR may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.
ADDERALL XR should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.
ADDERALL XR is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep ADDERALL XR in a safe place to prevent misuse and abuse. Selling or giving away ADDERALL XR may harm others, and is against the law.
Tell your doctor if you or your child have (or have a family history of) ever abused or been dependent on alcohol, prescription medicines or street drugs.
Who should not take ADDERALL XR?
ADDERALL XR should not be taken if you or your child:
- have heart disease or hardening of the arteries
- have moderate to severe high blood pressure
- have hyperthyroidism
- have an eye problem called glaucoma
- are very anxious, tense, or agitated
- have a history of drug abuse
- are taking or have taken within the past 14 days an anti-depression medicine called a monoamine oxidase inhibitor or MAOI.
- is sensitive to, allergic to, or had a reaction to other stimulant medicines
ADDERALL XR has not been studied in children less than 6 years old.
ADDERALL XR may not be right for you or your child. Before starting ADDERALL XR tell you or your child's doctor about all health conditions (or a family history of) including if you or your child:
- have heart problems, heart defects, or high blood pressure
- have mental problems including psychosis, mania, bipolar illness, or depression
- have tics or Tourette's syndrome
- have liver problems
- have kidney problems
- have end stage renal disease (ESRD)
- have thyroid problems
- have seizures or have had an abnormal brain wave test (EEG)
- have circulation problems in fingers and toes
- are pregnant or plan to become pregnant. It is not known if ADDERALL XR will harm your unborn baby.
- There is a pregnancy registry for females who are exposed to ADDERALL XR during pregnancy. The purpose of the registry is to collect information about the health of females exposed to ADDERALL XR and their baby. If you or your child becomes pregnant during treatment with ADDERALL XR, talk to your healthcare provider about registering with the National Pregnancy Registry of Psychostimulants at 1-866-961-2388 or visit online at https://womensmentalhealth.org/clinical-and -research-programs/pregnancyregistry/othermedications/.
- are breastfeeding or plan to breastfeed. ADDERALL XR passes into breast milk. You or your child should not breastfeed during treatment with ADDERALL XR.
Can ADDERALL XR be taken with other medicines?
Tell your doctor about all of the medicines that you or your child takes including prescription and non-prescription medicines, vitamins, and herbal supplements. ADDERALL XR and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking ADDERALL XR.
Your doctor will decide whether ADDERALL XR can be taken with other medicines.
Especially tell your doctor if you or your child takes:
- anti-depression medicines including MAOIs
- anti-psychotic medicines
- lithium
- narcotic pain medicines
- seizure medicines
- blood thinner medicines
- blood pressure medicines
- stomach acid medicines
- cold or allergy medicines that contain decongestants
Know the medicines that you or your child takes. Keep a list of your medicines with you to show your doctor and pharmacist.
Do not start any new medicine while taking ADDERALL XR without talking to your doctor first.
How should ADDERALL XR be taken?
- Take ADDERALL XR exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child.
- Take ADDERALL XR once a day in the morning when you first wake up. ADDERALL XR is an extended release capsule. It releases medicine into your body throughout the day.
- Swallow ADDERALL XR extended release capsules whole with water or other liquids. If you or your child cannot swallow the capsule, open it and sprinkle the medicine over a spoonful of applesauce. Swallow all of the applesauce and medicine mixture without chewing immediately. Follow with a drink of water or other liquid. Never chew or crush the capsule or the medicine inside the capsule.
- ADDERALL XR can be taken with or without food.
- From time to time, your doctor may stop ADDERALL XR treatment for a while to check ADHD symptoms.
- Your doctor may do regular checks of the heart and blood pressure while taking ADDERALL XR. Children should have their height and weight checked often while taking ADDERALL XR. ADDERALL XR treatment may be stopped if a problem is found during these check-ups.
- If you or your child takes too much ADDERALL XR or overdoses, call your doctor or poison control center right away, or get emergency treatment.
What are possible side effects of ADDERALL XR?
See "What is the most important information I should know about ADDERALL XR?" for information on reported heart and mental problems.
Other serious side effects include:
- slowing of growth (height and weight) in children
- seizures, mainly in patients with a history of seizures
- eyesight changes or blurred vision
Common side effects include:
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ADDERALL XR may affect you or your child's ability to drive or do other dangerous activities.
Talk to your doctor if you or your child has side effects that are bothersome or do not go away.
This is not a complete list of possible side effects. Ask your doctor or pharmacist for more information.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store ADDERALL XR?
- Store ADDERALL XR in a safe place at room temperature, 59 to 86° F (15 to 30° C).
- Keep ADDERALL XR and all medicines out of the reach of children.
General information about ADDERALL XR
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ADDERALL XR for a condition for which it was not prescribed. Do not give ADDERALL XR to other people, even if they have the same condition. It may harm them and it is against the law.
This Medication Guide summarizes the most important information about ADDERALL XR. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about ADDERALL XR that was written for healthcare professionals. For more information, you may also contact Takeda Pharmaceuticals (the maker of ADDERALL XR) at 1-800-828-2088 or visit the website at http://www.adderallxr.com.
What are the ingredients in ADDERALL XR?
Active Ingredients: dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate
Inactive Ingredients: 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
Distributed by:
Takeda Pharmaceuticals America, Inc.
Lexington, MA 02421
ADDERALL XR® is a registered trademark of
Takeda Pharmaceuticals U.S.A., Inc.
© 2020 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved.
Rev. 2/2022
This Medication Guide has been approved by the U.S. Food and Drug Administration.
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| Labeler - Takeda Pharmaceuticals America, Inc. (039997266) |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Cambrex Charles City, Inc | 782974257 | API MANUFACTURE(54092-381, 54092-385, 54092-387, 54092-389, 54092-391, 54092-383) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Patheon Manufacturing Services LLC | 079415560 | ANALYSIS(54092-381, 54092-383, 54092-385, 54092-387, 54092-389, 54092-391) , LABEL(54092-381, 54092-383, 54092-385, 54092-387, 54092-389, 54092-391) , MANUFACTURE(54092-381, 54092-383, 54092-385, 54092-387, 54092-389, 54092-391) , PACK(54092-381, 54092-383, 54092-385, 54092-387, 54092-389, 54092-391) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Unither Manufacturing LLC | 079176615 | ANALYSIS(54092-383, 54092-385, 54092-387, 54092-389, 54092-391) , MANUFACTURE(54092-383, 54092-385, 54092-387, 54092-389, 54092-391) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Sharp Packaging Services, LLC | 143696495 | LABEL(54092-381, 54092-383, 54092-385, 54092-387, 54092-389, 54092-391) , PACK(54092-381, 54092-383, 54092-385, 54092-387, 54092-389, 54092-391) | |
