Pristiq

— THERAPEUTIC CATEGORIES —
  • Mood disorders
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Pristiq Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Desvenlafaxine (as succinate) 25mg, 50mg, 100mg; ext-rel tabs.

    Pharmacological Class

    SNRI.

    How Supplied

    Tabs 25mg—30; 50mg, 100mg—14, 30, 90

    How Supplied

    Pristiq (desvenlafaxine) extended-release tablets are available as follows:

    • 25 mg – tan, square pyramid tablet debossed with “W” (over) “25” on the flat side; bottle of 30 tablets in unit-of-use package

    • 50 mg – light pink, square pyramid tablet debossed with “W” (over) “50” on the flat side; bottles of 14-, 30-, 90-count tablets in unit-of-use package and 10 blisters of 10 (HUD)

    • 100 mg – reddish-orange, square pyramid tablet debossed with “W” (over) “100” on the flat side; bottles of 14-, 30-, 90-count tablets in unit-of-use package and 10 blisters of 10 (HUD)

    Storage

    Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

    Manufacturer

    Pfizer Inc.

    Generic Availability

    YES

    Mechanism of Action

    The exact mechanism of the antidepressant action of desvenlafaxine is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Non-clinical studies have shown that desvenlafaxine is a potent and selective SNRI.

    Pristiq Indications

    Indications

    Major depressive disorder (MDD).

    Pristiq Dosage and Administration

    Prior to Treatment Evaluations

    Screen patients with depressive symptoms prior to initiating antidepressants to determine bipolar disorder risk; Pristiq is not indicated for bipolar depression.

    Pre-existing hypertension should be controlled prior to initiating treatment with Pristiq.

    Adult

    Swallow whole. 50mg once daily. Moderate renal impairment (CrCl 30–50mL/min): max 50mg/day. Severe renal impairment (CrCl <30mL/min), ESRD: max 25mg daily or 50mg every other day. Do not give supplemental dose after dialysis. Moderate to severe hepatic impairment: max 100mg/day. Withdraw gradually.

    Children

    Not established.

    Renal impairment

    Moderate renal impairment (24-hr CrCl = 30–50 mL/min, Cockcroft-Gault [C-G]): maximum dose of 50 mg per day.

    Severe renal impairment (24-hr CrCl = 15–29 mL/min, C-G) or end-stage renal disease (ESRD, CrCl <15 mL/min): maximum dose of 25 mg every day or 50 mg every other day. Do not give supplemental doses to patients after dialysis.

    Hepatic Impairment

    Moderate to severe hepatic impairment (Child-Pugh score 7–15): 50 mg per day. Maximum daily dose is 100 mg.

    Dose escalation above 100 mg per day is not recommended.

    Other Modifications

    Maintenance/Continuation/Extended Treatment

    • Periodically reassess patients to determine the need for continued treatment.

    • Longer-term efficacy of Pristiq (50–400mg) was established in 2 maintenance trials.

    Discontinuing Pristiq

    • Gradually reduce the dose of Pristiq when stopping therapy. Do not abruptly discontinue therapy. Discontinuation may need to occur over a period of several months.

    Switching Patients From Other Antidepressants to Pristiq

    • Patients have reported discontinuation symptoms when switching from other antidepressants, including venlafaxine, to Pristiq.

    • Taper the initial antidepressant to minimize discontinuation symptoms.

    Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

    • Should elapse at least 14 days from stopping MAOI (intended to treat psychiatric disorders) before starting Pristiq.

    • Should elapse at least 7 days from stopping Pristiq before starting MAOI intended to treat psychiatric disorders. 

    Use of Pristiq with other MAOIs such as Linezolid or Methylene Blue

    • Avoid initiating Pristiq in patients who are receiving linezolid or IV methylene blue due to the risk for serotonin syndrome.

    • If a patient who is currently receiving Pristiq requires urgent treatment with linezolid or IV methylene blue and there are no acceptable alternatives and the potential benefits outweigh the risks, then discontinue Pristiq promptly and administer linezolid or IV methylene blue.

      • Monitor for serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid or IV methylene blue (whichever comes first). Resume Pristiq treatment 24 hours after the last dose of linezolid or IV methylene blue.

    Administration

    Swallow tablets whole with fluid.

    Do not divide, crush, chew, or dissolve tablets.

    Pristiq Contraindications

    Contraindications

    During or within 14 days of MAOIs; do not start an MAOI during or within 7 days of desvenlafaxine. Concomitant linezolid or IV methylene blue.

    Pristiq Boxed Warnings

    Boxed Warning

    Suicidal thoughts and behaviors.

    Boxed Warning

    Suicidal Thoughts And Behaviors 

    • Increased risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies.

    • Monitor closely for clinical worsening, and emergence of suicidal thoughts and behaviors.

    • Not approved for use in pediatric patients.

    Pristiq Warnings/Precautions

    Warnings/Precautions

    Increased risk of suicidal thinking or behavior; monitor for clinical worsening or unusual changes. Screen for bipolar disorder. Monitor for serotonin syndrome; discontinue immediately if occurs. Monitor BP; reduce dose or discontinue if elevated BP persists. Cardio- or cerebrovascular disease. Angle closure glaucoma. Avoid in untreated anatomically narrow angles. History of mania/hypomania. Seizure disorder. Volume depleted. Hyponatremia (esp. in elderly). Sexual dysfunction. Renal or hepatic impairment. Avoid abrupt cessation; monitor. Reevaluate periodically. Write ℞ for smallest practical amount. Elderly. Labor & delivery. Pregnancy (avoid in 3rd trimester); see full labeling for effects on neonate. Nursing mothers.

    Warnings/Precautions

    Suicidal Thoughts and Behaviors in Adolescents and Young Adults

    • Pooled analyses of short-term placebo-controlled trials 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 18­-24) with major depressive disorder (MDD) and other psychiatric disorders.

    • No suicides occurred in any of the pediatric studies.

    • The risk of suicidal thoughts and behaviors is unknown with long-term use.

    • Monitor all patients for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months and at times of dosage changes.

    • In patients whose depression persistently worsens, consider changing the therapeutic regimen by tapering gradually if possible.

    • Families/caregivers: Monitor patients for emergence of agitation, irritability, unusual changes in behavior and report to health care provider.

    • Prescriptions for Pristiq should be written for the smallest quantity of capsules consistent with good patient management in order to reduce overdose risk.

    • Screen patients with depressive symptoms prior to initiating antidepressants to determine bipolar disorder risk; Pristiq is not indicated for bipolar depression.

    Serotonin Syndrome

    • See Interactions.

    • Serotonin syndrome: Mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia),  neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), and GI symptoms (eg, nausea, vomiting, diarrhea).

    • Has been reported with SSRIs and SNRIs, including Pristiq, and with concomitant use of serotonergic drugs (eg, triptans, tricyclic antidepressants, fentanyl, lithium, meperidine, methadone, tramadol, tryptophan, buspirone, amphetamines, St. John’s Wort) and with drugs that impair serotonin metabolism (eg, MOAIs, linezolid, IV methylene blue).

    • Monitor patients for the emergence of serotonin syndrome.

    • Concomitant use of MAOIs and Pristiq is contraindicated; discontinue Pristiq before initiating treatment with an MAOI.

    • Patients should be made aware of the potential for serotonin syndrome if concomitant use of Pristiq and other serotonergic drugs is clinically warranted.

    Elevated Blood Pressure

    • Monitor blood pressure prior to initiation and regularly during treatment. Control pre-existing hypertension prior to initiation.

    • Use caution in patients with pre-existing hypertension or cardiovascular or cerebrovascular conditions.

    • Consider reducing dose or discontinuing treatment if sustained increase in blood pressure occurs.

    Increased Risk of Bleeding  

    • See Interactions.

    • Concomitant use with aspirin, NSAIDs, warfarin, other anticoagulants or other drugs known to affect platelet function may increase the risk of bleeding.

    • Advise patients about the increased risk of bleeding when Pristiq is coadministered with NSAIDs, aspirin, or other drugs. 

    • If Pristiq is used with warfarin, monitor coagulation indices when initiating, titrating, or discontinuing Pristiq.

    Angle-Closure Glaucoma 

    • Pristiq may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

    • Avoid use in patients with untreated anatomically narrow angles.

    Activation of Mania or Hypomania

    • Treatment with Pristiq may precipitate a mixed/manic episode. During all MDD phase 2 and phase 3 studies, mania was reported for approximately 0.02% of patients treated with Pristiq.

    • Use caution in patients with a history or family history of mania or hypomania.

    Discontinuation Syndrome

    • Monitor for discontinuation symptoms when discontinuing treatment with Pristiq.

    • A gradual dosage reduction is recommended. Do not abruptly discontinue Pristiq. Consider resuming previously prescribed dose of Pristiq if intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment.

    • Discontinuation may occur over a period of several months in some patients.

    Seizures

    • Use caution in patients with a seizure disorder.

    Hyponatremia

    • Greater risk of developing hyponatrema with SNRIs in elderly patients, patients taking diuretics, or those who are otherwise volume-depleted.

    • Consider discontinuing treatment with Pristiq in patients with symptomatic hyponatremia, and institute appropriate medical intervention.

    Interstitial Lung Disease and Eosinophilic Pneumonia 

    • Rare reports of interstitial lung disease and eosinophilic pneumonia.

    • If this occurs, patients should undergo a prompt medical evaluation and consider discontinuing Pristiq.

    Sexual Dysfunction

    • SNRIs, including Pristiq, may cause symptoms of sexual dysfunction.

    • Prescribers should inquire about sexual function prior to initiation and about changes in sexual function during treatment.

    Pregnancy Considerations

    Pregnancy Exposure Registry 

    • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185. 

    Risk Summary 

    • There are no published studies on Pristiq in pregnant women. However, published epidemiologic studies of pregnant women exposed to venlafaxine have not identified a clear association with adverse developmental outcomes.

    Clinical Considerations

    • Disease-Associated Maternal and/or Embryo/Fetal Risk: A prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, showed that women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication. 

    • Maternal Adverse Reactions: Use in mid to late pregnancy may increase the risk for preeclampsia, and exposure to SNRIs near delivery may increase the risk of postpartum hemorrhage.

    • Fetal/Neonatal Adverse Reactions: Neonates exposed to SNRIs or SSRIs late in pregnancy may lead to an increased risk of neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding. Monitor neonates exposed to Pristiq in the third trimester of pregnancy for drug discontinuation syndrome.

    Nursing Mother Considerations

    Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Pristiq and any potential adverse effects on the breastfed child or from the underlying maternal condition.

    Pediatric Considerations

    • Safety and efficacy have not been established.

    Geriatric Considerations

    No overall differences in efficacy or safety were observed between elderly patients and younger patients.

    Consider possible reduced renal clearance of Pristiq in elderly patients when determining dose.

    Cases of clinically significant hyponatremia have been associated with elderly patients who may be at greater risk for this adverse event.

    Renal Impairment Considerations

    Dosage adjustment is recommended in patients with moderate or severe renal impairment (CrCl 15–50 mL/min, C-G) or end-stage renal disease (CrCL <15 mL/min, C-G).

    Hepatic Impairment Considerations

    Dosage adjustment is recommended in patients with moderate or severe hepatic impairment (Child-Pugh score 7–15).

    Pristiq Pharmacokinetics

    Absorption

    Absolute oral bioavailability: ~80% (after administration). 

    Distribution

    Volume of distribution at steady state: 3.4 L/kg. Plasma protein bound: 30% (independent of drug concentration).

    Metabolism

    Desvenlafaxine is primarily metabolized by conjugation (mediated by UGT isoforms) and, to a minor extent, through oxidative metabolism. 

    CYP3A4 mediates the oxidative metabolism (N-demethylation) of desvenlafaxine. 

    Elimination

    Approximately 45% of desvenlafaxine is excreted unchanged in urine at 72 hours after oral administration. 

    Approximately 19% of the administered dose is excreted as the glucuronide metabolite and <5% as the oxidative metabolite (N,O-didesmethylvenlafaxine) in urine.

    Pristiq Interactions

    Interactions

    See Contraindications. Avoid alcohol, concomitant venlafaxine, other forms of desvenlafaxine. Increased risk of serotonin syndrome with other serotonergic drugs (eg, SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs such as linezolid, IV methylene blue). Increased risk of bleeding with concomitant aspirin, NSAIDs, warfarin, or other drugs that affect coagulation; monitor closely. May affect CYP2D6 substrates (eg, desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine); reduce dose by up to ½ if concomitant with desvenlafaxine 400mg dose. May cause false (+) urine immunoassay screening tests for PCP and amphetamine.

    Pristiq Adverse Reactions

    Adverse Reactions

    Nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, specific male sexual dysfunction; rare: interstitial lung disease or eosinophilic pneumonia (consider discontinuing if occurs).

    Pristiq Clinical Trials

    Clinical Trials

    Studies 1–4

    • Efficacy of Pristiq (50–400 mg per day) was evaluated in four 8-week, randomized, double-blind, placebo-controlled, fixed-dose studies in adult outpatients who met the DSM-IV criteria for major depressive disorder.

    • Study 1 – Patients received Pristiq 100 mg, 200 mg, or 400mg once daily or placebo.

    • Study 2 – Patients received either Pristiq 200 mg or 400 mg once daily or placebo.

    • Studies 3 and 4 – Patients received Pristiq 50 mg or 100 mg once daily or placebo.

    • Pristiq achieved superiority over placebo as measured by improvement in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score in four studies and overall improvement, as measured by the Clinical Global Impressions Scale - Improvement (CGI-I), in three of the 4 studies.

    • For studies comparing Pristiq 50 mg/day to 100 mg/day, there was no evidence that the higher dose had greater effect. There were more frequent adverse reactions and discontinuations at higher doses.

    Study 5

    • Study 5 was a longer-term trial which included adult outpatients who met the DSM-IV criteria for MDD, who responded to 8 weeks of open-label acute treatment with desvenlafaxine 50 mg per day and remained stable for 12 weeks. Patients were randomly assigned to remain on Pristiq or switch to placebo for up to 26 weeks of observation for relapse.

    • Relapse during the double-blind phase was defined as follows: (1) a HAM-D17 total score of at least 16 at any office visit, (2) discontinuation for unsatisfactory efficacy response, (3) hospitalized for depression, (4) suicide attempt, or (5) suicide.

    • Patients who received Pristiq achieved statistically significantly longer time to relapse compared with placebo. At 26 weeks, 14% of patients in the desvenlafaxine arm had relapsed compared with 30% of patients in the placebo arm.

    Study 6

    • Study 6 was a longer-term trial which included adult outpatients who met the DSM-IV criteria for MDD, who responded to 12 weeks of acute treatment with desvenlafaxine. Patients were randomly assigned to remain on Pristiq (200 or 400 mg/day) or switch to placebo for up to 26 weeks of observation for relapse.

    • Relapse during the double-blind phase was defined as follows: (1) a HAM-D17 total score of at least 16 at any office visit, (2) a CGI-I score of ≥ 6 (versus day 84) at any office visit, or (3) discontinuation from the trial due to unsatisfactory response.

    • Patients who received Pristiq achieved statistically significantly longer time to relapse compared with placebo. At 26 weeks, 29% of patients in the desvenlafaxine arm had relapsed compared with 49% of patients in the placebo arm.

    Postmarketing Study

    • Efficacy of Pristiq at a lower dose than 50 mg per day was evaluated in an 8-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study in adult outpatients with MDD. Patients were randomly assigned to receive Pristiq 25 mg, 50 mg, or placebo.

    • Pristiq 50 mg achieved superiority to placebo, as measured by HAMD-17. The 25 mg dose was not superior to placebo.

    Pristiq Note

    Not Applicable

    Pristiq Patient Counseling

    Patient Counseling

    Suicidal Thoughts and Behaviors

    • Advise to look for the emergence of suicidal ideation and behavior, especially early during treatment and dose adjustments. Report symptoms to healthcare provider.

    Concomitant Medication

    • Do not take Pristiq with MAOI or within 14 days of stopping an MAOI and allow 7 days after stopping Pristiq before starting an MAOI.

    Serotonin Syndrome

    • Caution about the risk of serotonin syndrome. 

    Increased Risk of Bleeding

    • Use of Pristiq with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may increase risk of bleeding.

    • Inform your healthcare provider of any prescription or OTC medications you are currently taking or plan to take.

    Activation of Mania/Hypomania

    • Look for signs of activation.

    Discontinuation Syndrome

    • Do not abruptly stop taking Pristiq. Monitor for discontinuation symptoms.

    Sexual Dysfunction

    • May cause sexual dysfunction in male and female patients. Discuss any changes and potential management strategies with your healthcare provider.

    Switching Patients from Other Antidepressants to Pristiq

    • Discontinuation symptoms have been reported when switching patients from other antidepressants, including venlafaxine, to Pristiq. May need to taper the initial antidepressant to minimize discontinuation symptoms

    Interference with Cognitive and Motor Performance 

    • Caution use about operating hazardous machinery, including automobiles.

    Alcohol

    • Avoid alcohol during treatment with Pristiq.

    Allergic Reactions

    • Notify physician if allergic phenomena develops (eg, rash, hives, swelling, or difficulty breathing).

    Pregnancy

    • Advise women to notify physician if they become pregnant or intend to become pregnant during therapy. Advise patients that there is a pregnancy exposure registry.

    Residual Inert Matrix Tablet  

    • Patients may notice an inert matrix tablet passing in the stool or via colostomy. Patients should be informed that the active medication has already been absorbed by the time the patient sees the spheroids. 

    Cost Savings Program

    Pristiq Savings Card

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