`
`
`
`
`
`• Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat
`
`
`
`
`
`
` psychiatric disorders with PRISTIQ or within 7 days of stopping treatment
` with PRISTIQ. Do not use PRISTIQ within 14 days of stopping an MAOI
`
`
`
`
` intended to treat psychiatric disorders. In addition, do not start PRISTIQ in
`
` a patient who is being treated with linezolid or intravenous methylene blue
`
`(4).
`
`
` --------------------- WARNINGS AND PRECAUTIONS -----------------------
`
`
`• Serotonin Syndrome: Increased risk when co-administered with other
`
`
`
`
`
`serotonergic agents, but also when taken alone. If it occurs, discontinue
`
`
`
` PRISTIQ and serotonergic agents and initiate supportive treatment (5.2).
`
`• Elevated Blood Pressure: Control hypertension before initiating treatment.
`
`
`
`
`Monitor blood pressure regularly during treatment (5.3).
`
`• Increased Risk of Bleeding: Concomitant use of aspirin, NSAIDs, other
`
`
`
`
` antiplatelet drugs, warfarin, and other anticoagulants may increase this risk
`
` (5.4).
`• Angle Closure Glaucoma: Avoid use of antidepressants, including
`
`
` PRISTIQ, in patients with untreated anatomically narrow angles treated
`
` (5.5).
`• Activation of Mania/Hypomania: Use cautiously in patients with Bipolar
`
`
` Disorder. Caution patients about risk of activation of mania/hypomania
`
`
`(5.6).
`• Discontinuation Syndrome: Taper dose when possible and monitor for
`
`
`discontinuation symptoms (5.7).
`
`• Seizure: Can occur. Use cautiously in patients with seizure disorder (5.8).
`
`
`• Hyponatremia: Can occur in association with SIADH (5.9).
`
`
`
`• Interstitial Lung Disease and Eosinophilic Pneumonia: Can occur (5.10).
`
`
`
`• Sexual Dysfunction: PRISTIQ may cause symptoms of sexual dysfunction
`
`
`
`
` (5.11).
`
` ---------------------------- ADVERSE REACTIONS ------------------------------
`
`
`
`
`Most common adverse reactions (incidence ≥5% and twice the rate of
`
`
` placebo in the 50 or 100 mg dose groups) were: nausea, dizziness,
`insomnia, hyperhidrosis, constipation, somnolence, decreased appetite,
`
`anxiety, and specific male sexual function disorders (6.1).
`
`
`
`
`
`
` To report SUSPECTED ADVERSE REACTIONS, contact Wyeth
` Pharmaceuticals LLC, a subsidiary of Pfizer Inc., at 1-800-438-1985 or
`
`
` FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
`
`
`
` --------------------- USE IN SPECIFIC POPULATIONS -----------------------
`
`
`• Pregnancy: Third trimester use may result in neonatal discontinuation
`
`
`
`
` syndrome (8.1).
`
`
`• Geriatric Use: There is an increased incidence of orthostatic hypotension in
`
`desvenlafaxine treated patients ≥ 65 years (6.1 and 8.5).
`
`
`
`
`
`
`
`
`
` See 17 for PATIENT COUNSELING INFORMATION and Medication
`
` Guide.
`
`
`
` Revised: 8/2023
`
` HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`These highlights do not include all the information needed to use
`PRISTIQ safely and effectively. See full prescribing information for
`
` PRISTIQ.
`
` PRISTIQ® (desvenlafaxine) Extended-Release Tablets, for oral use
`
`
` Initial U.S. Approval: 2008
`
`
`
`
`
`
`
` WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
`
`
` See full prescribing information for complete boxed warning.
`
`
`
`
`
` Increased the risk of suicidal thoughts and behaviors in children,
` adolescents and young adults taking antidepressants (5.1).
`
`
` Closely monitor for clinical worsening and emergence of suicidal
`
`
` thoughts and behaviors (5.1).
`
` PRISTIQ is not approved for use in pediatric patients (8.4).
`
`
`
`
`
`•
`
`
`•
`
`
`•
`
`
`
`
`
`
`
`
`
`
`
` -------------------------RECENT MAJOR CHANGES ---------------------------
`
`
`
`
`
`
` Warnings and Precautions (5.2, 5.4) 8/2023
`
`
` ------------------------- INDICATIONS AND USAGE----------------------------
`
`
`
`
` PRISTIQ is a serotonin and norepinephrine reuptake inhibitor (SNRI)
` indicated for the treatment of adults with major depressive disorder (MDD)
`
`
`
`(1).
`
`
` ---------------------DOSAGE AND ADMINISTRATION -----------------------
`
`
`• Recommended dose: 50 mg once daily with or without food (2.1).
`
`
`
`• There was no evidence that doses greater than 50 mg per day confer any
`
`
`
`
`
` additional benefit (2.1).
`
`• The 25 mg per day dose is intended for a gradual reduction in dose when
`
`
`
`
`discontinuing treatment or dosing in severe renal and end-stage renal
`
` disease patients (2.1).
`• Discontinuation: Reduce dose gradually whenever possible (2.1).
`
`
`• Take tablets whole; do not divide, crush, chew, or dissolve (2.1).
`
`
`• Moderate renal impairment: Maximum dose 50 mg per day (2.2).
`
`
`
`
`
`
`
`
`• Severe renal impairment and end-stage renal disease: Maximum dose
`
`
` 25 mg per day or 50 mg every other day (2.2).
`
`
`
`
`• Moderate to severe hepatic impairment: Maximum dose 100 mg per day
`
`
`
`
`
`(2.3).
`
`
`
`
`
`
`
` ------------------- DOSAGE FORMS AND STRENGTHS----------------------
`
`
`• PRISTIQ extended-release tablets: 25 mg, 50 mg and 100 mg (3).
`
`
`
`
`
`
`
`
`• Each tablet contains 38 mg, 76 mg or 152 mg of desvenlafaxine succinate
`
`
`
`
`
`
` equivalent to 25 mg, 50 mg or 100 mg of desvenlafaxine, respectively (3).
`
`
`
`
`
`
`
` ---------------------------- CONTRAINDICATIONS ------------------------------
`
`
`• Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or
`
`any excipients in the PRISTIQ formulation (4).
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 5229457
`
`1
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`7 DRUG INTERACTIONS
`
`
` 7.1 Drugs Having Clinically Important Interactions with PRISTIQ
`
` 7.2 Drugs Having No Clinically Important Interactions with PRISTIQ
`
` 7.3 Alcohol
`
` 7.4 Drug-Laboratory Test Interactions
`
`8 USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`
` 8.2 Lactation
`
`8.4 Pediatric Use
`
`8.5 Geriatric Use
` 8.6 Renal Impairment
`
`
`8.7 Hepatic Impairment
`9 DRUG ABUSE AND DEPENDENCE
`
`9.1 Controlled Substance
`
`10 OVERDOSAGE
`10.1 Human Experience with Overdosage
`
`10.2 Management of Overdosage
`
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`
`12.1 Mechanism of Action
`
`12.2 Pharmacodynamics
`
`12.3 Pharmacokinetics
`
`13 NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`14 CLINICAL STUDIES
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`17 PATIENT COUNSELING INFORMATION
`
` * Sections or subsections omitted from the full prescribing information are
`
` not listed.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` FULL PRESCRIBING INFORMATION: CONTENTS*
`
` WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
`
`
`1 INDICATIONS AND USAGE
` 2 DOSAGE AND ADMINISTRATION
`
`
`
` 2.1 General Instructions for Use
` 2.2 Dosage Recommendations for Patients with Renal Impairment
`
` 2.3 Dosage Recommendations for Patients with Hepatic Impairment
`
`
` 2.4 Maintenance/Continuation/Extended Treatment
`
` 2.5 Discontinuing PRISTIQ
`
`
`
` 2.6 Switching Patients From Other Antidepressants to PRISTIQ
`
`
` 2.7 Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI)
`
`
`
` Intended to Treat Psychiatric Disorders
`
`2.8 Use of PRISTIQ with other MAOIs such as Linezolid or Methylene
`
` Blue
` 3 DOSAGE FORMS AND STRENGTHS
`
`4 CONTRAINDICATIONS
`
`5 WARNINGS AND PRECAUTIONS
` 5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult
`
` Patients
`5.2 Serotonin Syndrome
`
`5.3 Elevated Blood Pressure
`
`
` 5.4 Increased Risk of Bleeding
` 5.5 Angle Closure Glaucoma
`
` 5.6 Activation of Mania/Hypomania
`
`
`
` 5.7 Discontinuation Syndrome
`
` 5.8 Seizure
`
`
`
` 5.9 Hyponatremia
` 5.10 Interstitial Lung Disease and Eosinophilic Pneumonia
`
` 5.11 Sexual Dysfunction
`
`
`6 ADVERSE REACTIONS
`6.1 Clinical Studies Experience
`
`
` 6.2 Postmarketing Experience
`
`
`
`
`
`
`
`
`
`
`Reference ID: 5229457
`
`2
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
`
` FULL PRESCRIBING INFORMATION
`
`
`
`
`
`
`
`
` WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
`
`Antidepressants increased the risk of suicidal thoughts and behavior in children,
`adolescents, and young adults in short-term studies. These studies did not show an
`
`
`
`
` increase in the risk of suicidal thoughts and behavior with antidepressant use in patients
` over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and
`
`
`
`
`
`
` older [see Warnings and Precautions (5.1)].
`
` In patients of all ages who are started on antidepressant therapy, monitor closely for
`
`
`
` worsening, and for emergence of suicidal thoughts and behaviors. Advise families and
` caregivers of the need for close observation and communication with the prescriber [see
`
`
` Warnings and Precautions (5.1)].
`
` PRISTIQ is not approved for use in pediatric patients [see Use in Specific Populations
`
` (8.4)].
`
`
`
`
`
`
`
`INDICATIONS AND USAGE
`
`
`
`
`
`
`
`
`
`
`
`
`
` DOSAGE AND ADMINISTRATION
`
`
`
`
`1
`
` PRISTIQ is indicated for the treatment of adults with major depressive disorder (MDD) [see
`
` Clinical Studies (14)].
`
`2
`
` 2.1 General Instructions for Use
`
` The recommended dose for PRISTIQ is 50 mg once daily, with or without food. The 50 mg dose
`
`
`
` is both a starting dose and the therapeutic dose. PRISTIQ should be taken at approximately the
`same time each day. Tablets must be swallowed whole with fluid and not divided, crushed,
`
` chewed, or dissolved.
`
` In clinical studies, doses of 10 mg to 400 mg per day were studied. In clinical studies, doses of
`
`
`
`
`
`
`
`
`
` 50 mg to 400 mg per day were shown to be effective, although no additional benefit was
` demonstrated at doses greater than 50 mg per day and adverse reactions and discontinuations
`
`
`
`
` were more frequent at higher doses.
`
` The 25 mg per day dose is intended for a gradual reduction in dose when discontinuing
`
`
`
`
`
`
` treatment. When discontinuing therapy, gradual dose reduction is recommended whenever
`possible to minimize discontinuation symptoms [see Dosage and Administration (2.5) and
`
` Warnings and Precautions (5.7)].
`
`
`
`
`
`
`
`
`
`Reference ID: 5229457
`
`3
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
`
`
`
` Dosage Recommendations for Patients with Renal Impairment
`
`
`
`
`
` Dosage Recommendations for Patients with Hepatic Impairment
`
`
`
`
`
`
`
`Discontinuing PRISTIQ
`
`
`
`2.2
`
` The maximum recommended dose in patients with moderate renal impairment (24-hr creatinine
`
`
`
`
`
`
`
`
` clearance [ClCr] = 30 to 50 mL/min, Cockcroft-Gault [C-G]) is 50 mg per day. The maximum
` recommended dose in patients with severe renal impairment (ClCr 15 to 29 mL/min, C-G) or end-
`
`
`
`
`
`
`
` stage renal disease (ESRD, ClCr < 15 mL/min, C-G) is 25 mg every day or 50 mg every other
` day. Supplemental doses should not be given to patients after dialysis [see Use in Specific
`
`
` Populations (8.6) and Clinical Pharmacology (12.3)].
`
`2.3
`
` The recommended dose in patients with moderate to severe hepatic impairment (Child-Pugh
`
`
` score 7 to 15) is 50 mg per day. Dose escalation above 100 mg per day is not recommended [see
`
`
`
`
`
`
` Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
`
`
`
` 2.4 Maintenance/Continuation/Extended Treatment
`
` It is generally agreed that acute episodes of major depressive disorder require several months or
`
`
` longer of sustained pharmacologic therapy. Longer-term efficacy of PRISTIQ (50-400 mg) was
` established in two maintenance trials [see Clinical Studies (14)]. Patients should be periodically
`
`
`
` reassessed to determine the need for continued treatment.
`
` 2.5
`
` Adverse reactions may occur upon discontinuation of PRISTIQ [see Warnings and Precautions
`
`
` (5.7)]. Gradually reduce the dosage rather than stopping PRISTIQ abruptly when discontinuing
` therapy with PRISTIQ. In some patients, discontinuation may need to occur over a period of
`
`
`
`
` several months.
`
` 2.6
`
`Discontinuation symptoms have been reported when switching patients from other
`antidepressants, including venlafaxine, to PRISTIQ. Tapering of the initial antidepressant may be
`
` necessary to minimize discontinuation symptoms.
`
` Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to
` 2.7
`
`
`
` Treat Psychiatric Disorders
`
` At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric
`
`
`
` disorders and initiation of therapy with PRISTIQ. Conversely, at least 7 days should be allowed
` after stopping PRISTIQ before starting an MAOI intended to treat psychiatric disorders [see
`
`
` Contraindications (4)].
`
`
`
`
`
`
`
` Switching Patients From Other Antidepressants to PRISTIQ
`
`
`
`
`
`
`Reference ID: 5229457
`
`4
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
`
`
`
`
`
`
`
` Use of PRISTIQ with other MAOIs such as Linezolid or Methylene Blue
`
`
`
`2.8
`
` Do not start PRISTIQ in a patient who is being treated with linezolid or intravenous methylene
`
`blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent
`
`
`
` treatment of a psychiatric condition, other interventions, including hospitalization, should be
` considered [see Contraindications (4)].
`
`
`
`
` In some cases, a patient already receiving PRISTIQ therapy may require urgent treatment with
`
`
` linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous
`methylene blue treatment are not available and the potential benefits of linezolid or intravenous
`methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular
`
` patient, PRISTIQ should be stopped promptly, and linezolid or intravenous methylene blue can
` be administered. The patient should be monitored for symptoms of serotonin syndrome for
`
`
`
`
`
`
` 7 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever
` comes first. Therapy with PRISTIQ may be resumed 24 hours after the last dose of linezolid or
`
`
`
`
`
`
` intravenous methylene blue [see Warnings and Precautions (5.2)].
`
`
`
` The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by
`
`
`
`
`
` local injection) or in intravenous doses much lower than 1 mg/kg with PRISTIQ is unclear. The
`clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin
`
`
`
` syndrome with such use [see Warnings and Precautions (5.2)].
`
`
`
`3
`
`
`
`
` DOSAGE FORMS AND STRENGTHS
`
`• 25 mg Tablet: tan, square pyramid tablet debossed with “W” over “25” on the flat side
`
`
`
`
`
`• 50 mg Tablet: light pink, square pyramid tablet debossed with “W” over “50” on the
`
`
`
`
`
` flat side
`
`• 100 mg Tablet: reddish-orange, square pyramid tablet debossed with “W” over “100”
`
`
`
`
` on the flat side
`
`
`
`CONTRAINDICATIONS
`
`
`
`• Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any
`
`
` excipients in the PRISTIQ formulation. Angioedema has been reported in patients
`
` treated with PRISTIQ [see Adverse Reactions (6.1)].
`
`
`• The use of MAOIs intended to treat psychiatric disorders with PRISTIQ or within
`
`
`
` 7 days of stopping treatment with PRISTIQ is contraindicated because of an increased
`
` risk of serotonin syndrome. The use of PRISTIQ within 14 days of stopping an MAOI
`
`
`
` intended to treat psychiatric disorders is also contraindicated [see Dosage and
`
`
`
`
`
` Administration (2.7) and Warnings and Precautions (5.2)].
`
`
`
`
`
`
`
`
`4
`
`
`
`
`
`
`
`
`
`Reference ID: 5229457
`
`5
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`• Starting PRISTIQ in a patient who is being treated with MAOIs such as linezolid or
`
`
` intravenous methylene blue is also contraindicated because of an increased risk of
`
`
`
`
`
`
` serotonin syndrome [see Dosage and Administration (2.8) and Warnings and
`
` Precautions (5.2)].
`
`
`WARNINGS AND PRECAUTIONS
`
`
`
` Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients
`
`
`
`
`
`
`5
`
`5.1
`
`Patients with MDD, both adult and pediatric, may experience worsening of their depression
`
` and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in
`behavior, whether or not they are taking antidepressant medications, and this risk may persist
`
` until significant remission occurs. Suicide is a known risk of depression and certain other
`psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.
`There has been a long-standing concern, however, that antidepressants may have a role in
`inducing worsening of depression and the emergence of suicidality in certain patients during the
`
`
` early phases of treatment. Pooled analyses of short-term placebo-controlled studies of
`antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal
`
`
` thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24)
` with major depressive disorder (MDD) and other psychiatric disorders. 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.
`
`The pooled analyses of placebo-controlled studies in children and adolescents with MDD,
`
`
` obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-
` term studies of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-
`
`controlled studies in adults with MDD or other psychiatric disorders included a total of
`
`
` 295 short-term studies (median duration of 2 months) of 11 antidepressant drugs in over
` 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a
`
` tendency toward an increase in the younger patients for almost all drugs studied. There were
`
` differences in absolute risk of suicidality across the different indications, with the highest
`incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable
`
` within age strata and across indications. These risk differences (drug-placebo difference in the
` number of cases of suicidality per 1,000 patients treated) are provided in Table 1.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Table 1
`
`
`
` Drug-Placebo Difference in Number of Cases of Suicidality per 1,000
`
` Patients Treated
` Increases Compared to Placebo
` 14 additional cases
`
`
`
` 5 additional cases
` Decreases Compared to Placebo
`
` 1 fewer case
`6 fewer cases
`
`
`
`
`
`
`
`
`Age Range
`
`<18
`
`
` 18 to 24
`
` 25 to 64
`
`
`≥65
`
`
`
`
`
`
`Reference ID: 5229457
`
`6
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
` 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 drug effect on suicide.
`
` It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several
`
`months. However, there is substantial evidence from placebo-controlled maintenance studies in
`
` adults with depression that the use of antidepressants can delay the recurrence of depression.
`
` All patients being treated with antidepressants for any indication should be monitored
`
`appropriately and observed closely for clinical worsening, suicidality, and unusual changes in
`behavior, especially during the initial few months of a course of drug therapy, or at times of dose
`
` changes, either increases or decreases.
`
`The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility,
`aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have
`been reported in adult and pediatric patients being treated with antidepressants for major
`depressive disorder as well as for other indications, both psychiatric and nonpsychiatric.
`
`
` Although a causal link between the emergence of such symptoms and either the worsening of
` depression and/or the emergence of suicidal impulses has not been established, there is concern
`
`
`that such symptoms may represent precursors to emerging suicidality.
`
`Consideration should be given to changing the therapeutic regimen, including possibly
`
` discontinuing the medication, in patients whose depression is persistently worse, or who are
` experiencing emergent suicidality or symptoms that might be precursors to worsening depression
`
`
`
` or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the
`patient’s presenting symptoms.
`
`
`If the decision has been made to discontinue treatment, medication should be tapered, as rapidly
`as is feasible, but with recognition that abrupt discontinuation can be associated with certain
`
`
` symptoms [see Dosage and Administration (2.4), Warnings and Precautions (5.7)].
`
`
` Families and caregivers of patients being treated with antidepressants for major depressive
`
`
` disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the
` need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior,
`
`
` and the other symptoms described above, as well as the emergence of suicidality, and to report
`such symptoms immediately to healthcare providers. Such monitoring should include daily
`
` observation by families and caregivers.
`
` Prescriptions for PRISTIQ should be written for the smallest quantity of tablets consistent with
`
`
`good patient management, in order to reduce the risk of overdose.
`
` Screening Patients for Bipolar Disorder
`
`A major depressive episode may be the initial presentation of bipolar disorder. It is generally
`
` believed (though not established in controlled studies) that treating such an episode with an
` antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in
`
`
`
` patients at risk for bipolar disorder. Whether any of the symptoms described above represent
`
`
`Reference ID: 5229457
`
`7
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
`
`Serotonin Syndrome
`
`
`
`
`
`such a conversion is unknown. However, prior to initiating treatment with an antidepressant,
`
` patients with depressive symptoms should be adequately screened to determine if they are at risk
` for bipolar disorder; such screening should include a detailed psychiatric history, including a
`
`family history of suicide, bipolar disorder, and depression. It should be noted that PRISTIQ is
`
`not approved for use in treating bipolar depression.
`
`5.2
`
` Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective-serotonin reuptake inhibitors
`(SSRIs), including PRISTIQ, 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.
`
` Serotonin syndrome signs and 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 gastrointestinal symptoms (e.g.,
`
` nausea, vomiting, diarrhea).
`
` The concomitant use of PRISTIQ with MAOIs is contraindicated. In addition, do not initiate
`
`
`
` PRISTIQ 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 PRISTIQ, discontinue PRISTIQ before initiating
`
`
` treatment with the MAOI [see Contraindications (4), Drug Interactions (7.1)].
`
`
` Monitor all patients taking PRISTIQ for the emergence of serotonin syndrome. Discontinue
`
`
`
` treatment with PRISTIQ and any concomitant serotonergic agents immediately if the above
` symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of PRISTIQ
`
` with other serotonergic drugs is clinically warranted, inform patients of the increased risk for
`
`
` serotonin syndrome and monitor for symptoms.
`
`5.3
`
`
` Patients receiving PRISTIQ should have regular monitoring of blood pressure since increases in
`
` blood pressure were observed in clinical studies [see Adverse Reactions (6.1)]. Pre-existing
`hypertension should be controlled before initiating treatment with PRISTIQ. Caution should be
`
` exercised in treating patients with pre-existing hypertension, cardiovascular, or cerebrovascular
`conditions that might be compromised by increases in blood pressure. Cases of elevated blood
`
`pressure requiring immediate treatment have been reported with PRISTIQ.
` Sustained blood pressure increases could have adverse consequences. For patients who
`
`experience a sustained increase in blood pressure while receiving PRISTIQ, either dose
`
` reduction or discontinuation should be considered [see Adverse Reactions (6.1)].
`
`
`
`
`
`
`Elevated Blood Pressure
`
`
`
`
`Reference ID: 5229457
`
`8
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
`
`Increased Risk of Bleeding
`
`
`
`
`
`
`
` Angle Closure Glaucoma
`
`
`
`
`
`Activation of Mania/Hypomania
`
`
`
`
`5.4
`
` Drugs that interfere with serotonin reuptake inhibition, including PRISTIQ, 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
`
`PRISTIQ and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully
`
` monitor coagulation indices when initiating, titrating, or discontinuing PRISTIQ.
`
`5.5
`
` The pupillary dilation that occurs following use of many antidepressant drugs including
`
`
`
` PRISTIQ may trigger an angle closure attack in a patient with anatomically narrow angles who
` does not have a patent iridectomy. Avoid use of antidepressants, including PRISTIQ, in
`
`
`
` patients with untreated anatomically narrow angles.
`
`5.6
`
` During all MDD phase 2 and phase 3 studies, mania was reported for approximately 0.02% of
`
`
`patients treated with PRISTIQ. Activation of mania/hypomania has also been reported in a small
`
` proportion of patients with major affective disorder who were treated with other marketed
`antidepressants. As with all antidepressants, PRISTIQ should be used cautiously in patients with
`
`
` a history or family history of mania or hypomania.
`
` 5.7
`
`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
`
` [see Adverse Reactions (6.1)].
`
`
`
`
`
`
`
`
`
`
` Discontinuation Syndrome
`
`
`
` There have been postmarketing reports of serious discontinuation symptoms with PRISTIQ,
`
`
`
`
` which can be protracted and severe. Completed suicide, suicidal thoughts, and severe aggression
`(including hostility, rage, and homicidal ideation) have been observed in patients during
`
` reduction in PRISTIQ dosage, including during discontinuation. Other postmarketing reports
`describe visual changes (such as blurred vision or trouble focusing) and increased blood pressure
`
` after stopping or reducing the dose of PRISTIQ.
`
`
`
`Reference ID: 5229457
`
`9
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
`
`
`
` Seizure
`
`
`
`
`
`
`
`Patients should be monitored when discontinuing treatment with PRISTIQ. A gradual reduction
`
`
` in the dose, rather than abrupt cessation, is recommended. If intolerable symptoms occur
`following a decrease in the dose or upon discontinuation of treatment, then resuming the
`
` previously prescribed dose may be considered. Subsequently, the healthcare provider may
` continue decreasing the dose, but at a more gradual rate. In some patients, discontinuation may
`
`
` need to occur over a period of several months [see Dosage and Administration (2.5)].
`
`
`5.8
`
` Cases of seizure have been reported in pre-marketing clinical studies with PRISTIQ. PRISTIQ
`
`has not been systematically evaluated in patients with a seizure disorder. Patients with a history
`
` of seizures were excluded from pre-marketing clinical studies. PRISTIQ should be prescribed
`with caution in patients with a seizure disorder.
`
`
` 5.9 Hyponatremia
`
` Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including PRISTIQ. In
`
`
` many cases, this hyponatremia appears to be the result of the syndrome of inappropriate
` antidiuretic hormone secretion (SIADH). Cases with serum sodium lower than 110 mmol/L have
`
`
` been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs
`
`
` and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted can be at
`greater risk [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3)].
` Discontinuation of PRISTIQ should be considered in patients with symptomatic hyponatremia
`
`and appropriate medical intervention should be instituted.
`
`Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory
`impairment, confusion, weakness, and unsteadiness, which can lead to falls. Signs and symptoms
`associated with more severe and/or acute cases have included hallucination, syncope, seizure,
`
` coma, respiratory arrest, and death.
`
` 5.10
`
`Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (the parent drug
`
` of PRISTIQ) therapy have been rarely reported. The possibility of these adverse events should be
` considered in patients treated with PRISTIQ who present with progressive dyspnea, cough, or
`
`
` chest discomfort. Such patients should undergo a prompt medical evaluation, and discontinuation
`
` of PRISTIQ should be considered.
`
` 5.11 Sexual Dysfunction
`
`Use of SNRIs, including PRISTIQ, 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.
`
`
`
`
`Interstitial Lung Disease and Eosinophilic Pneumonia
`
`
`
`
`
`
`
`
`Reference ID: 5229457
`
`10
`
`This label may not be the latest approved by FDA.
`For current labeling information, please visit https://www.fda.gov/drugsatfda
`
`

`

`
`
`It is important for prescribers to inquire about sexual function prior to initiation of PRISTIQ 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 hav