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.

DESVENLAFAXINE (NDA-205583)

(DESVENLAFAXINE FUMARATE)

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

Download Data

Expand all

08/18/2023 (SUPPL-14)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Serotonin Syndrome

Additions and/or revisions underlined:

Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective-serotonin reuptake inhibitors (SSRIs), including desvenlafaxine extended-release tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John's Wort), and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications (4), Drug Interactions (7.1)]. Serotonin syndrome can also occur when these drugs are used alone.

…

5.4 Increased Risk of Bleeding

Additions and/or revisions underlined:

Drugs that interfere with serotonin reuptake inhibition, including desvenlafaxine extended-release tablets, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1)]. Bleeding events related to SSRIs and SNRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.

Inform patients about the increased risk of bleeding associated with the concomitant use of desvenlafaxine extended-release tablets and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing desvenlafaxine extended-release tablets.

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Respiratory, thoracic and mediastinal disorders - Anosmia, hyposmia

7 Drug Interactions

7.1 Drugs Having Clinically Important Interactions with desvenlafaxine extended-release tablets

Addition of opioids to examples of the other serotonergic drugs section of table 8; please refer to table for complete information

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

…

Risk summary

Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.4) and Clinical Considerations].

…

Maternal adverse reactions

Exposure to Aptryxol in mid to late pregnancy may increase the risk for preeclampsia, and exposure to Aptryxol in the month before delivery may be associated with an increased the risk of postpartum hemorrhage [see Warnings and Precautions (5.4)].

…

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of desvenlafaxine extended-release tablets with other serotonergic agents (including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines and St. John's Wort supplements) [see Warnings and Precautions (5.2)].

…

MEDICATION GUIDE

Additions and/or revisions underlined:

What should I tell my healthcare provider before taking desvenlafaxine extended-release tablets? Ask if you are not sure:

…

tramadol, fentanyl, meperidine, methadone, or other opioids

…

12/10/2019 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2Serotonin Syndrome

(additions and/or revisions underlined)

Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective-serotonin reuptake inhibitors (SSRIs), including desvenlafaxine extended-release tablets, can precipitate serotonin syndrome, a potentially life- threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort), and with drugs that impair metabolism of serotonin, i.e., MAOIs.

…

The concomitant use of desvenlafaxine extended-release tablets with MAOIs is contraindicated. In addition, do not initiate desvenlafaxine extended-release tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking desvenlafaxine extended-release tablets, discontinue desvenlafaxine extended-release tablets before initiating treatment with the MAOI.

Monitor all patients taking desvenlafaxine extended-release tablets for the emergence of serotonin syndrome. Discontinue treatment Treatmentwith desvenlafaxine extended-release tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of desvenlafaxine extended-release tablets with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

5.4 Increased Risk of Bleeding

(additions and/or revisions underlined)

Drugs that interfere with serotonin reuptake inhibition, including desvenlafaxine extended-release tablets, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the risk of bleeding associated with the concomitant use of desvenlafaxine extended-release tablets and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing desvenlafaxine extended-release tablets.

5.5 Angle Closure Glaucoma

(additions underlined)

…Avoid use of antidepressants, including desvenlafaxine extended-release tablets, in patients with untreated anatomically narrow angles.

6 Adverse Reactions

(addition underlined)

…

Abnormal Increased Risk of Bleeding

…

7 Drug Interactions

(revisions to align with the Listed Drug, Pristiq (desvenlafaxine), labeling.; please refer to label for complete information)

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion, please refer to label for complete information)

8.2 Lactation

(PLLR conversion)

Risk Summary

Available limited data from published literature show low levels of desvenlafaxine in human milk, and have not shown adverse reactions in breastfed infants (see Data). There are no data on the effects of desvenlafaxine on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for desvenlafaxine extended-release tablets and any potential adverse effects on the breastfed child from desvenlafaxine extended-release tablets or from the underlying maternal condition.

Data

A lactation study was conducted in 10 breastfeeding women (at a mean of 4.3 months postpartum) who were being treated with a 50-150 mg daily dose of desvenlafaxine for postpartum depression. Sampling was performed at steady state (up to 8 samples) over a 24 hour dosing period, and included foremilk and hindmilk. The mean relative infant dose was calculated to be 6.8% (range of 5.5-8.1%). No adverse reactions were seen in the infants.

8.4 Pediatric Use

(additions underlined)

The safety and effectiveness of desvenlafaxine extended-release tablets have not been established in pediatric patients for the treatment of MDD.

Antidepressants, such as desvenlafaxine, increase the risk of suicidal thoughts and behaviors in pediatric patients.

Additional information describing clinical studies in which efficacy was not demonstrated in pediatric patients is approved for Wyeth Pharmaceuticals Inc. a subsidiary of Pfizer Inc.’s PRISTIQ® (desvenlafaxine) Extended- Release Tablets. However, due to Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.’s marketing exclusivity rights, this product is not labeled with that pediatric information.

Juvenile Animal Studies

In a juvenile animal study, male and female rats were treated with desvenlafaxine (75, 225 and 675 mg/kg/day) starting on postnatal day (PND) 22 through 112. Behavioral deficits (longer time immobile in a motor activity test, longer time swimming in a straight channel test, and lack of habituation in an acoustic startle test) were observed in males and females but were reversed after a recovery period. A No Adverse Effect Level (NOAEL) was not identified for these deficits. The Low Adverse Effect Level (LOAEL) was 75 mg/kg/day which was associated with plasma exposure (AUC) twice the levels measured with a pediatric dose of 100 mg/day.

In a second juvenile animal study, male and female rats were administered desvenlafaxine (75, 225 or 675 mg/kg/day) for 8 to 9 weeks starting on PND 22 and were mated with naïve counterparts. Delays in sexual maturation and decreased fertility, number of implantation sites and total live embryos were observed in treated females at all doses. The LOAEL for these findings is 75 mg/kg/day which was associated with an AUC twice the levels measured with a pediatric dose of 100 mg/day. These findings were reversed at the end of a 4-week recovery period. The relevance of these findings to humans is not known.

8.6 Renal Impairment

(additions and/or revisions underlined)

Adjust the maximum recommended dosage in patients with moderate or severe renal impairment (CLcr 15 to 50 mL/min, C-G), or end-stage renal disease (CLcr < 15 mL/min, C-G).

8.7 Hepatic Impairment

(additions and/or revisions underlined)

Adjust the maximum recommended dosage in patients with moderate to severe hepatic impairment (Child-Pugh score 7 to 15).

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

MEDICATION GUIDE

(revisions to align with the Listed Drug, Pristiq (desvenlafaxine), labeling.; please refer to label for complete information)

PATIENT COUNSELING INFORMATION

(additions and/or revisions underlined)

Suicidal Thoughts and Behaviors

Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dose is adjusted up or down, and instruct them to report such symptoms to the healthcare provider.

...

Increased Risk of Bleeding

Inform patients about the concomitant use of desvenlafaxine extended-release tablets with NSAIDs, aspirin, other antiplatelet drugs, warfarin, or other coagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the-counter medications that increase the risk of bleeding.

…

Pregnancy

Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to desvenlafaxine extended-release tablets during pregnancy.

…

12/19/2017 (SUPPL-6)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions are underlined)

Cardiovascular system - Takotsubo cardiomyopathy

01/04/2017 (SUPPL-5)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Serotonin Syndrome

(Additions and/or revisions are underlined)

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including desvenlafaxine extended-release tablets, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort)…

If concomitant use of desvenlafaxine extended-release tablets with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, amphetamines, tryptophan, and St. John's Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions are underlined)

The following adverse reaction has been identified during post-approval use of desvenlafaxine extended-release tablets…

Gastrointestinal System – Acute Pancreatitis

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

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of desvenlafaxine extended-release tablets with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines and St. John's Wort supplements).