Drug Safety-related Labeling Changes (SrLC)
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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.
EMSAM (NDA-021336)
(SELEGILINE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
07/14/2017 (SUPPL-14)
5 Warnings and Precautions
5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults(Additions and/or revisions are underlined)
In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug- placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 2.
No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide.
Table 2: Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients (Table has been revised; please refer to label)
It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression.
Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing EMSAM, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.
(Additions and/or revisions are underlined)
In patients with bipolar disorder, treating a depressive episode with EMSAM or another antidepressant may precipitate a mixed/manic episode. During Phase III trials, a manic reaction occurred in 8 out of 2,036 (0.4%) patients treated with EMSAM. Prior to initiating treatment with EMSAM, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.
6 Adverse Reactions
(Additions and/or revisions are underlined)
The following adverse reactions are discussed in greater detail in other sections of the label.
- Suicidal Thoughts and Behaviors
- Serotonin Syndrome
- Blood Pressure Elevation
- Activation of Mania/Hypomania
- External Heat
8 Use in Specific Populations
8.1 Pregnancy(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)
Risk Summary
The available data on EMSAM use in pregnant women are
not sufficient to inform a drug- associated risk of adverse
pregnancy-related outcomes. In animal embryo-fetal development studies,
transdermal administration of selegiline to rats and rabbits at doses up to 60
and 64 times the maximum recommended human dose (MRHD) respectively, produced
slight increases in malformations in both rats and rabbits, and decreased fetal
weight, delayed ossification, and embryo-fetal post-implantation loss in rats.
Most of these effects were seen at the high dose in both rats and rabbits. These
effects were not seen at 8 times and 16 times the MRHD in rats and rabbits, respectively. In a pre-natal and post-natal development
study, transdermal administration of selegiline in rats at doses 8, 24, and 60
times MRHD produced a decrease in pup weight and survival at the medium and
high doses, an increase in the number of stillborn pups at the high dose, and
delayed neurobehavioral and sexual development in pups at all doses. A
persistent effect on reproductive performance of pups born to mothers treated
at the high dose was evident. When treating a pregnant woman with EMSAM,
the physician should carefully consider both the potential risks of taking an
MAOI, particularly the risk of hypertensive crisis during pregnancy, along
with the established benefits of treating depression with an antidepressant.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions and/or revisions are underlined)
Risk Summary
There is no information regarding the presence of selegiline in human milk, or on its effects on milk production or the breastfed infant. Selegiline and its metabolites are present in the milk of lactating rats.
Because of the potential for serious adverse reactions in breastfed infants from EMSAM, including the potential for hypertensive crisis, advise a woman that breastfeeding is not recommended during treatment with EMSAM and for 5 days after the final dose.
Data
In a prenatal and postnatal development study where rats were treated with transdermal selegiline at doses approximately 8, 24, and 60 times the MRHD on days 6 to 21 of gestation and days 1 to 21 of the lactation period, concentrations of selegiline and its metabolites in milk were approximately 15 and 5 times, respectively, the concentrations in maternal plasma.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION(Additions and/or revisions are underlined)
Pregnancy: Advise the pregnant woman about the potential risk to the fetus.
Lactation: Advise a woman that breastfeeding is not recommended during treatment with EMSAM treatment and for 5 days after the final dose.
How to Use EMSAM
- Just before you apply the transdermal system, remove it from the pouch by tearing at the notches (do not use scissors). Remove half of the release liner and throw it away…
- Press the sticky side of the transdermal system firmly against the skin site that was just washed and dried. Remove the second half of the release liner and press the remaining sticky side firmly against your skin…
(Additions and/or revisions are underlined)
What is EMSAM?
… EMSAM is a transdermal system (patch) you apply to your skin.
Before you use EMSAM, tell your healthcare provider about all of your medical conditions, including if you:
- are pregnant or plan to become pregnant. EMSAM may harm your unborn baby.
- are breastfeeding or plan to breastfeed. It is not known if EMSAM passes into your breast milk. Do not breastfeed during treatment with EMSAM and for 5 days after the final dose. Talk to your healthcare provider about the best way to feed your baby if you use EMSAM.
Some of these medicines need to be stopped for up to 5 weeks before you can start using EMSAM and for 2 weeks after you stop using EMSAM.
What should I avoid while using EMSAM?
- Do not eat foods or drink beverages that contain high amounts of tyramine while using EMSAM 9 mg or EMSAM 12 mg or for 2 weeks after you stop using EMSAM 9 mg or EMSAM 12 mg. Continue to avoid tyramine-rich foods or beverages for 2 weeks after a dose reduction to EMSAM 6 mg.
- If you start and continue EMSAM 6 mg you do not need to make any diet changes.
What are the possible side effects of EMSAM?
EMSAM may cause serious side effects, including:
- serotonin syndrome…
If you suddenly have these symptoms, stop using EMSAM immediately by removing the patch and go to the nearest hospital emergency room right away.