Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

DESVENLAFAXINE (NDA-204150)

(DESVENLAFAXINE)

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

Download Data

Expand all

08/18/2023 (SUPPL-20)

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, 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, 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 and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing desvenlafaxine.

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

Respiratory, thoracic and mediastinal disorders – Anosmia, hyposmia

7 Drug Interactions

DRUG INTERACTIONS

Addition of opioids to examples section of table 8; please refer to label 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].

…

Clinical Considerations

…

Maternal adverse reactions

Exposure to Desvenlafaxine in mid to late pregnancy may increase the risk for preeclampsia, and exposure to Desvenlafaxine in the month before near delivery may be associated with an increased the risk for 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 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)].

…

All trademarks are property of their respective owners.

 

MEDICATION GUIDE

Additions and/or revisions underlined:

…

Especially tell your healthcare provider if you take:

…

• tramadol, fentanyl, meperidine, methadone, or other opioids

…

09/20/2021 (SUPPL-18)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.11 Sexual Dysfunction

(Newly added subsection)

Use of SNRIs, including desvenlafaxine, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1)]. In male patients, SNRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SNRI use may result in decreased libido and delayed or absent orgasm.

It is important for prescribers to inquire about sexual function prior to initiation of desvenlafaxine and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.

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

MEDICATION GUIDE

(Additions and/or revisions underlined)

…

• Sexual problems (dysfunction). Taking serotonin and norepinephrine reuptake inhibitors (SNRIs), including desvenlafaxine, may cause sexual problems.

  Symptoms in males may include:

• Delayed ejaculation or inability to have an ejaculation

• Decreased sex drive

• Problems getting or keeping an erection Symptoms in females may include:

• Decreased sex drive

• Delayed orgasm or inability to have an orgasm

Talk to your healthcare provider if you develop any changes in your sexual function or if you have any questions or concerns about sexual problems during treatment with desvenlafaxine. There may be treatments your healthcare provider can suggest.

…

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

…

Sexual Dysfunction

Advise patients that use of desvenlafaxine extended-release tablets may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions (5.11)].

…

10/29/2019 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Serotonin Syndrome

(additions underlined)

…

Monitor all patients taking desvenlafaxine for the emergence of serotonin syndrome. Discontinue treatment with desvenlafaxine and any concomitant serotonergic agents immediately if the above symptoms occur, and  initiate supportive symptomatic treatment. If concomitant use of desvenlafaxine 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 underlined)

… For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing desvenlafaxine.

5.5 Angle Closure Glaucoma

(additions underlined)

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

5.7 Discontinuation Syndrome

(additions underlined)

Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures.A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible

6 Adverse Reactions

(additions underlined)

…

• Abnormal Increased Risk of Bleeding

 

…

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion, please refer to label)

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 and any potential adverse effects on the breastfed child from desvenlafaxine 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 to 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 to 8.1%). No adverse reactions were seen in the infants.

8.4 Pediatric Use

(additions underlined)

The safety and effectiveness of desvenlafaxine 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.

8.5 Geriatric Use

(addition underlined)

Of the 4,158 patients in pre-marketing clinical studies with desvenlafaxine, 6% were 65 years of age or older.

…

8.6 Renal Impairment

(additions 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 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 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 with NSAIDs, aspirin, other antiplatelet drugs, warfarin, or other coagulants because the combined use of 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.

…

 

Discontinuation

Advise patients not to abruptly stop taking desvenlafaxine without talking first with their healthcare professional. Patients should be aware that discontinuation effects may occur when stopping desvenlafaxine.

…

 

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 during pregnancy.

…

12/19/2017 (SUPPL-7)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

(Additions and/or revisions are underlined)

Cardiovascular system – Takotsubo cardiomyopathy.

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

MEDICATION GUIDE DESVENLAFAXINE extended-release tablets (des VEN la FAX een)

(Additions and/or revisions are underlined)

Serotonin syndrome

Rare, but potentially life-threatening conditions called serotonin syndrome can happen when medicines such as desvenlafaxine are taken with certain other medicines. Serotonin syndrome can cause serious changes in how your brain, muscles, heart and blood vessels, and digestive system work. Especially tell your healthcare provider if you take the following:

• amphetamines

01/04/2017 (SUPPL-5)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Suicidal Thoughts and Behaviors in Children, Adolescents and Young Adults

Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

5.2 Serotonin Syndrome

(additions underlined0

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including desvenlafaxine, 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), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

…

If concomitant use of desvenlafaxine 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 underlined)

The following adverse reaction has been identified during post-approval use of desvenlafaxine. 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:

Skin and subcutaneous tissue disorders –Stevens-Johnson syndrome.

Gastrointestinal system – Acute pancreatitis.

8 Use in Specific Populations

8.1 Pregnancy

(additions underlined)

When desvenlafaxine succinate was administered orally to pregnant rats throughout gestation and lactation, there was a decrease in pup weights and an increase in pup deaths during the first four days of lactation at the highest dose of 300 mg/kg/day. The cause of these deaths is not known. The no-effect dose for rat pup mortality was 10 times a human dose of 100 mg per day (on a mg/m2 basis). Post-weaning growth and reproductive performance of the progeny were not affected by maternal treatment with desvenlafaxine succinate at a dose 30 times a human dose of 100 mg per day (on a mg/m(squared) basis).

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

17 PATIENT COUNSELING INFORMATION

(additions underlined)

Serotonin Syndrome

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

09/09/2016 (SUPPL-4)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Postmarketing Experience

Addition of:

• Gastrointestinal system: Acute pancreatitis