Drug Safety-related Labeling Changes (SrLC)

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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.

ADZENYS XR-ODT (NDA-204326)

(AMPHETAMINE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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10/13/2023 (SUPPL-11)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: ABUSE, MISUSE, AND ADDICTION

ADZENYS XR-ODT 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 ADZENYS XR-ODT, 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 ADZENYS XR-ODT, 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 ADZENYS XR-ODT treatment, reassess each patient’s risk of above, 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 Addiction

Additions and/or revisions underlined:

ADZENYS XR-ODT has a high potential for abuse and misuse. The use of ADZENYS XR- ODT exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. ADZENYS XR-ODT 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 ADZENYS XR-ODT, 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 ADZENYS XR-ODT, 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 ADZENYS XR-ODT in a safe place, preferably locked, and instruct patients to not give ADZENYS XR-ODT to anyone else. Throughout ADZENYS XR-ODT treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

5.2 Risks to Patients with Serious Cardiac Disease

Additions and/or revisions underlined:

Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage.

Avoid ADZENYS XR-ODT use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

5.3 Increased Blood Pressure and Heart Rate

Additions and/or revisions underlined:

CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Some patients may have larger increases.

Monitor all ADZENYS XR-ODT-treated patients for potential tachycardia and hypertension.

5.5 Long-Term Suppression of Growth in Pediatric Patients

Additions and/or revisions underlined:

…

Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted.

5.8 Motor and Verbal Tics, and Worsening of Tourette’s Syndrome

New subsection added:

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 ADZENYS XR-ODT, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor ADZENYS XR-ODT-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), and Drug Abuse and Dependence (9.2, 9.3)]
Hypersensitivity to amphetamine, or other components of ADZENYS XR-ODT [see Contraindications (4)]
Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors

[see Contraindications (4) and Drug Interactions (7.1)]

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)]
Peripheral Vasculopathy, including Raynaud’s phenomenon [see Warnings and Precautions (5.6)]
Serotonin Syndrome [see Warnings and Precautions (5.7)]
Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions (5.8)]

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Central Nervous System: Restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, aggression, anger, logorrhea, paresthesia (including formication), motor and verbal tics.

…

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Abuse, Misuse, and Addiction

Educate patients and their families about the risks of abuse, misuse, and addiction of ADZENYS XR-ODT, 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 ADZENYS XR-ODT in a safe place, preferably locked, and instruct patients to not give ADZENYS XR-ODT to anyone else.

…

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 ADZENYS XR-ODT. 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 (5.8)].

…

MEDICATION GUIDE

Medication Guide has undergone extensive changes; please refer to label.

02/25/2022 (SUPPL-8)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Adverse Reactions from Clinical Trials and Spontaneous Postmarketing Reports of Other Amphetamine Products

Additions underlined

…

Gastrointestinal: Unpleasant taste, constipation, intestinal ischemia, and other gastrointestinal disturbances.

…

01/04/2017 (SUPPL-2)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined:

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

5.7 Serotonin Syndrome

Newly 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 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. The co-administration with cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with increased exposure to ADZENYS XR-ODT. 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 ADZENYS XR-ODT with MAOI drugs is contraindicated.

Discontinue treatment with ADZENYS XR-ODT and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of ADZENYS XR-ODT with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate ADZENYS XR-ODT with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

6 Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling:

Addition of the following:

Serotonin Syndrome

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Newly added information:

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome with concomitant use of ADZENYS XR- ODT 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.

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.

01/28/2016 (SUPPL-1)

Approved Drug Label (PDF)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Instructions for Use (Summary in italics-please refer to label)

An instructional card containing text and illustrations was added to emphasize and otherwise strengthen the existing instructions for opening the approved child-resistant blister packaging.