Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | 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.

DESOXYN (NDA-005378)

(METHAMPHETAMINE HYDROCHLORIDE)

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

Download Data

Expand all

09/24/2024 (SUPPL-32)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Pregnancy and Lactation Labeling Rule (PLLR) conversion:

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including DESOXYN, during pregnancy. Healthcare providers are encouraged to advise patients to register by contacting the National Pregnancy Registry for ADHD Medications at 1- 866-961-2388 or visiting online at www.womensmentalhealth.org/research/pregnancyregistry/adhd-medications/.

Risk Summary

Available data from epidemiologic studies and postmarketing reports on use of methamphetamine and amphetamine in pregnant women over decades of use have not identified a drug-associated risk of major birth defects or miscarriage. Neonates exposed to amphetamines in utero are at risk for withdrawal symptoms following delivery. Adverse pregnancy outcomes including premature delivery and low birth weight have been seen in infants born to mothers taking amphetamines during pregnancy (see Clinical Considerations).

In animals, administration of methamphetamine during organogenesis resulted in developmental toxicity, including neonatal death and fetal malformations, at doses equivalent to the maximum recommended human dose (MRHD) on a mg/m2 basis. Oral administration of methamphetamine to rats during pregnancy, pregnancy and lactation, or lactation resulted in developmental toxicity in the offspring, including, neonatal mortality and delayed development, at a maternal dose similar to the MRHD on a mg/m2 basis.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Amphetamines, such as DESOXYN, cause vasoconstriction and thereby decrease placental perfusion. In addition, amphetamines can stimulate uterine contractions, increasing the risk of premature delivery. Infants born to mothers taking amphetamines during pregnancy have an increased risk of premature delivery and low birth weight.

Monitor infants born to mothers taking methamphetamine for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness.

Data

Animal Data

Based on published data, methamphetamine administration during the period of organogenesis caused malformations and pup mortality in mammals at doses equivalent to the maximum recommended human dose (MRHD) on a mg/m2 basis. Oral administration of methamphetamine (0, or 3.75 mg/kg) to pregnant rats during gestation, throughout gestation and lactation, or only during lactation resulted in an increase in neonatal pup mortality. Delayed somatic development (pinna unfolding and eye opening) and impairments in neurobehavioral development (righting reflex, incline plane test, and forelimb grip strength) were observed in the pups. The dose with adverse effects was equivalent to the MRHD of 25 mg on a mg/m2 basis.

8.2 Lactation

Pregnancy and Lactation Labeling Rule (PLLR) conversion:

Risk Summary

Based on limited case reports in the published literature, methamphetamine and its active metabolite, amphetamine, are present in human milk. 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 doses 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 DESOXYN.

Other

Physician Labeling Rule (PLR) conversion; please refer to label for complete information.

10/13/2023 (SUPPL-38)

Approved Drug Label (PDF)

Boxed Warning

Additions and/or revisions underlined:

WARNING: ABUSE, MISUSE, AND ADDICTION

DESOXYN 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 DESOXYN, can result in overdose and death (see OVERDOSAGE), and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

Before prescribing DESOXYN, 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 DESOXYN 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 DRUG Abuse AND DEPENDENCE).

5 Warnings and Precautions

WARNINGS

Additions and/or revisions underlined:

Abuse, Misuse, and Addiction

DESOXYN has a high potential for abuse and misuse. The use of DESOXYN exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. DESOXYN can be diverted for non-medical use into illicit channels or distribution (see DRUG ABUSE and DEPENDENCE: Abuse). Misuse and abuse of CNS stimulants, including DESOXYN can result in overdose and death (see OVERDOSAGE), and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

Before prescribing DESOXYN, 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 amphetamine sulfate in a safe place, preferably locked, and instruct patients to not give DESOXYN to anyone else. Throughout DESOXYN treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

…

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

CNS stimulants, including amphetamine sulfate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported. Before initiating DESOXYN, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome with DESOXYN and discontinue treatment if clinically appropriate.

PRECAUTIONS

Additions and/or revisions underlined:

…

Information for Patients:

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 DESOXYN, which can lead to overdose and death, and proper disposal of any unused drug (see WARNINGS, DRUG ABUSE AND DEPENDENCE, and OVERDOSAGE). Advise patients to store DESOXYN in a safe place, preferably locked, and instruct patients to not give DESOXYN 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 DESOXYN. Instruct the patients to notify their healthcare provider if emergence or worsening of tics or Tourette’s syndrome occurs (see WARNINGS).

…

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

MEDICATION GUIDE

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

02/25/2022 (SUPPL-37)

Approved Drug Label (PDF)

6 Adverse Reactions

Additions underlined

…

Gastrointestinal: Diarrhea, constipation, dryness of mouth, unpleasant taste, intestinal ischemia, and other gastrointestinal disturbances.

…

05/19/2017 (SUPPL-34)

Approved Drug Label (PDF)

6 Adverse Reactions

(Additions and/or revisions are underlined)

Skin and Subcutaneous Tissue Disorders: Alopecia.

01/04/2017 (SUPPL-31)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions are underlined)

In patients known to be hypersensitive to amphetamine, or other components of DESOXYN. 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

WARNINGS

(Additions and/or revisions are underlined)

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 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. The potential for a pharmacokinetic interaction exists with the co-administration of CYP2D6 inhibitors which may increase the risk with increased exposure to DESOXYN. In these situations, consider an alternative nonserotonergic 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 DESOXYN with MAOI drugs is contraindicated.

Discontinue treatment with DESOXYN and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of DESOXYN with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate DESOXYN 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.

7 Drug Interactions

(Additions and/or revisions are underlined)

Acidifying Agents

Lower blood levels and efficacy of amphetamines. Increase dose based on clinical response. Examples of acidifying agents include gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid HCl, ascorbic acid) and urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts).

Alkalinizing Agents

Increase blood levels and potentiate the action of amphetamine. Co-administration of DESOXYN and gastrointestinal alkalinizing agents should be avoided. Examples of alkalinizing agents include gastrointestinal alkalinizing agents (e.g., sodium bicarbonate) and urinary alkalinizing agents (e.g., acetazolamide, some thiazides).

Tricyclic Antidepressants

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. Monitor frequently and adjust or use alternative therapy based on clinical response. Examples of tricyclic antidepressants include desipramine, Protriptyline.

CYP2D6 Inhibitors

The concomitant use of DESOXYN and CYP2D6 inhibitors may increase the exposure of DESOXYN compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during DESOXYN initiation and after a dosage increase. If serotonin syndrome occurs, discontinue DESOXYN and the CYP2D6 inhibitor. Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir.

Serotonergic Drugs

The concomitant use of DESOXYN and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during DESOXYN initiation or dosage increase. If serotonin syndrome occurs, discontinue DESOXYN and the concomitant serotonergic drug(s). Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort.

MAO Inhibitors

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. Do not administer DESOXYN concomitantly or within 14 days after discontinuing MAOI. Examples of MAOIs include selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue.

Proton Pump Inhibitors

Time to maximum concentration (Tmax) of amphetamine is decreased compared to when administered alone. Monitor patients for changes in clinical effect and adjust therapy based on clinical response. An example of a proton pump inhibitor is omeprazole.