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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
ADDERALL XR 10 (NDA-021303)
(AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
04/23/2026 (SUPPL-40)
7 Drug Interactions
7.2 Interference with Laboratory Tests
Subsection title revised
Additions and/or revisions underlined:
Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.
Allow for an adequate washout period between administration of ADDERALL XR and radioactive diagnostic agents used for dopamine transporter (DAT) visualization. ADDERALL XR can interfere with the test results of a radioactive diagnostic agent (ioflupane I-123) that is used for DAT visualization by binding and internalization of the DAT, which may result in lower DAT in the striatum. This may lead to false-positive diagnostic results.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions and/or revisions underlined:
…
Who should not take ADDERALL XR?
Do not take ADDERALL XR if you or your child:
are taking or have stopped taking within the past 14 days, a medicine called a monoamine oxidase inhibitor (MAOI), including the antibiotic linezolid or intravenous methylene blue
are allergic to amphetamine products or any of the ingredients in ADDERALL XR. See the end of this Medication Guide for a complete list of ingredients in ADDERALL XR.
Before taking ADDERALL XR tell your healthcare provider about all of your or your child’s medical conditions, including if you or your child:
have heart problems, heart disease, heart defects, or high blood pressure, or have a family history of sudden death or heart problems
…
are pregnant or plan to become pregnant. It is not known if ADDERALL XR will harm the unborn baby. Tell your healthcare provider if you or your child become pregnant or think you may be pregnant during treatment with ADDERALL XR.
…
Your healthcare provider may tell you to stop taking ADDERALL XR for a short time before you get certain imaging tests because ADDERALL XR may impact the results of some tests.
How should ADDERALL XR be taken?
Take ADDERALL XR exactly as prescribed by your or your child’s healthcare provider.
Your healthcare provider may change the dose if needed.
Take ADDERALL XR 1 time each day in the morning when you first wake up.
Taking ADDERALL XR in the afternoon may cause trouble sleeping.
ADDERALL XR can be taken with or without food.
Swallow ADDERALL XR capsules whole. If you or your child cannot swallow the capsule whole, open it and sprinkle the medicine on applesauce.
Swallow all of the applesauce and medicine mixture right away.
Do not chew the applesauce and medicine mixture.
Do not store the applesauce sprinkled with ADDERALL XR.
Do not divide the medicine in the capsule. Take all the contents in the capsule.
…
Additions and/or revisions underlined:
…
Concomitant Medications
Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions [see Drug Interactions (7.1)]. Advise patient or caregiver of steps to take with ADDERALL XR when a laboratory imaging procedure is ordered [see Drug Interactions (7.2)].
...
09/23/2025 (SUPPL-42)
5 Warnings and Precautions
5.5 Long-Term Suppression of Growth in Pediatric PatientsAdditions and/or revisions underlined:
ADDERALL XR is not approved for use and is not recommended in pediatric patients below 6 years of age [see Use in Specific Populations (8.4)].
…
8 Use in Specific Populations
8.4 Pediatric UseAdditions and/or revisions underlined:
The safety and effectiveness of ADDERALL XR have not been established in pediatric patients with ADHDless than 6 years of age.
The safety and effectiveness of ADDERALL XR have been established in pediatric patients with ADHD 6 years of age and older.
In studies evaluating extended-release amphetamine products, patients 4 to <6 years of age had higher systemic amphetamine exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had a higher incidence of adverse reactions, including weight loss.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEAdditions and/or revisions underlined:
…
What is ADDERALL XR?
ADDERALL XR is a central nervous system (CNS) stimulant prescription medicine used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD ) in adults and children 6 years of age and older. ADDERALL XR may help increase attention and decrease impulsiveness and hyperactivity in people with ADHD.
ADDERALL XR is not recommended for use in children under 6 years of age with ADHD.
…
10/13/2023 (SUPPL-38)
Boxed Warning
Additions and/or revisions underlined:
WARNING: ABUSE, MISUSE, AND ADDICTION
ADDERALL XR has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including ADDERALL XR, can result in overdose and death [see Overdosage (10)], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing ADDERALL XR, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout ADDERALL XR treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2)].
5 Warnings and Precautions
5.1 Abuse, Misuse, and AddictionAdditions and/or revisions underlined:
ADDERALL XR has a high potential for abuse and misuse. The use of ADDERALL XR exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. ADDERALL XR can be diverted for non-medical use into illicit channels
or distribution [see Drug Abuse and Dependence (9.2)]. Misuse and abuse of CNS stimulants, including ADDERALL XR, can result in overdose and death [see Overdosage (10)], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing ADDERALL XR, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug. Advise patients to store ADDERALL XR in a safe place, preferably locked, and instruct patients to not give ADDERALL XR to anyone else. Throughout ADDERALL XR treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Additions and/or revisions underlined:
CNS stimulants, including amphetamine, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported [see Adverse Reactions (6.2)].
Before initiating ADDERALL XR, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor ADDERALL XR-treated patients for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically appropriate.
6 Adverse Reactions
Additions and/or revisions underlined:
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions (5.1), Drug Abuse and Dependence (9.2, 9.3)]
Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions (5.2)]
Increased Blood Pressure and Heart Rate [see Warnings and Precautions (5.3)]
Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.5)]
Seizures [see Warnings and Precautions (5.6)]
Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions (5.7)]
Serotonin Syndrome [see Warnings and Precautions (5.8)]
Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions (5.9)]
6.2 Adverse Reactions Associated with the Use of Amphetamine, ADDERALL XR, or Adderall
Additions and/or revisions underlined:
…
Central Nervous System: Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, motor and verbal tics, aggression, anger, logorrhea, dermatillomania, paresthesia (including formication), and bruxism.
…
7 Drug Interactions
7.2 Drug-Laboratory Test InteractionsNew subsection added:
Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
…
Abuse, Misuse, and Addiction
Educate patients and their families about the risks of abuse, misuse, and addiction of ADDERALL XR, which can lead to overdose and death, and proper disposal of any unused drug [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9 .2), Overdosage (10)]. Advise patients to store ADDERALL XR in a safe place, preferably locked, and instruct patients to not give ADDERALL XR to anyone else.
…
Increased Blood Pressure and Heart Rate
Advise patients that ADDERALL XR can cause elevations in blood pressure and heart rate [see Warnings and Precautions (5.3)].
…
Motor and Verbal Tics, and Worsening of Tourette’s Syndrome
Advise patients that motor and verbal tics and worsening of Tourette’s syndrome may occur during treatment with ADDERALL XR. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourette’s syndrome occurs [see Warnings and Precautions (5.9)].
…
MEDICATION GUIDE
Medication Guide has undergone extensive changes; please refer to label.
02/25/2022 (SUPPL-36)
6 Adverse Reactions
6.2 Adverse Reactions Associated with the Use of Amphetamine, ADDERALL XR, or ADDERALLAdditions underlined
…
Gastrointestinal
Unpleasant taste, constipation, intestinal ischemia, and other gastrointestinal disturbances.
…
07/03/2019 (SUPPL-34)
5 Warnings and Precautions
5.1 Potential for Abuse and Dependence(Newly Added Subsection)
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.
6 Adverse Reactions
6.2 Adverse Reactions Associated with the Use of Amphetamine, ADDERALL XR, or ADDERALL(Additions and/or revisions are underlined)
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.
8 Use in Specific Populations
8.1 Pregnancy(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Extensive revisions – please refer to labeling)
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)
Risk Summary
Based on limited case reports in published literature, amphetamine (d- or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. It is possible that large dosages of amphetamine might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in nursing infants, advise patients that breastfeeding is not recommended during treatment with ADDERALL XR.
(Additions and/or revisions are underlined)
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.
Long-Term Growth Suppression
Growth should be monitored during treatment with stimulants, including ADDERALL XR, and pediatric patients aged 6 to 17 years who are not growing or gaining weight as expected may need to have their treatment .
Juvenile Animal Toxicity Data
Juvenile rats treated with mixed amphetamine salts early in the postnatal period through sexual maturation demonstrated transient changes in motor activity. Learning and memory was impaired at approximately 6 times the maximum recommended human dose (MRHD) given to children on a mg/m^2 basis. No recovery was seen following a drug free period. A delay in sexual maturation was observed at a dose approximately 6 times the MRHD given to children on a mg/m^2 basis, although there was no effect on fertility.
In a juvenile developmental study, rats received daily oral doses of amphetamine (d to l enantiomer ratio of 3:1) of 2, 6, or 20 mg/kg on days 7-13 of age; from day 14 to approximately day 60 of age these doses were given b.i.d. for total daily doses of 4, 12, or 40 mg/kg. The latter doses are approximately 0.6, 2, and 6 times the MRHD of 30 mg/day, given to children on a mg/m2 basis. Post dosing hyperactivity was seen at all doses; motor activity measured prior to the daily dose was decreased during the dosing period but the decreased motor activity was largely absent after an 18 day drug-free recovery period. Performance in the Morris water maze test for learning and memory was impaired at the 40 mg/kg dose, and sporadically at the lower doses, when measured prior to the daily dose during the treatment period; no recovery was seen after a 19 day drug-free period. A delay in the developmental milestones of vaginal opening and preputial separation was seen at 40 mg/kg but there was no effect on fertility.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
Pregnancy Registry
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADDERALL XR during pregnancy.
Pregnancy
Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with ADDERALL XR. Advise patients of the potential fetal effects from the use of ADDERALL XR during pregnancy.
Lactation
Advise women not to breastfeed if they are taking ADDERALL XR.
(Extensive changes; please refer to labeling)
07/16/2018 (SUPPL-29)
8 Use in Specific Populations
8.1 Pregnancy(addition underlined)
Teratogenic Effects
Pregnancy Category C.
Amphetamine, in the enantiomer ratio present in ADDERALL XR (d- to l- ratio of approximately 3:1), had no apparent effects on embryofetal morphological development or survival when orally administered to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively.
…
(new subsection added)
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)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE(additions underlined)
…
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:
…
end stage renal disease (ESRD)
…
01/06/2017 (SUPPL-32)
4 Contraindications
Additions and/or revisions underlined:
ADDERALL XR administration is contraindicated in patients with the following conditions:
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.
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.
5 Warnings and Precautions
5.6 Serotonin SyndromeNewly added subsection:
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. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism. 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. 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.
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.
7 Drug Interactions
Information has been converted to a table format; please refer to label.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditional subsections added:
17.6 Serotonin Syndrome
Caution patients about the risk of serotonin syndrome with concomitant use of ADDERALL XR and other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others such as linezolid. Advise patients to contact their
healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome.
17.7 Concomitant Medications
Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions.