Drug-Drug Interactions

PRISTIQ has a low potential for CYP2D6-mediated drug-drug interactions11

PRISTIQ does not have a clinically relevant effect on tamoxifen and aripiprazole, compounds that are metabolized by a combination of both CYP2D6 and CYP3A4 enzymes.

Card CTA

** This is an optional area where footnotes can live.

PRISTIQ is primarily metabolized by conjugation–independent of the CYP2D6 pathway.
You may want to consider a drug's metabolic pathway when choosing an antidepressant for patients on multiple medications.

Potential drug-drug interactions, which include contraindications and warnings and precautions, with PRISTIQ, including:

    • Monoamine oxidase inhibitors (MAOIs)*
    • Serotonergic drugs
    • Drugs that interfere with hemostasis (NSAIDs, aspirin, warfarin, anticoagulants)
    • Other interactions at PRISTIQ 400 mg dose
    • Other drugs containing desvenlafaxine or venlafaxine
    • Ethanol


          †Warnings and precautions.

      Pharmacokinetic Profile

      Drug is readily available to the systemic circulation—80% oral bioavailability

      Predictable pharmacokinetic profile, regardless of CYP2D6 metabolizer status

      Free (unbound) drug availability to cross the blood-brain barrier—30% protein binding

      Neither a substrate nor an inhibitor of P-glycoprotein transporter

      CYP2D6 Metabolizer Status

      PRISTIQ 50 mg—Demonstrated consistent pharmacokinetics, regardless of CYP2D6 metabolizer status

      Effects of metabolizer status on desvenlafaxine levels12

      Card CTA

      ** This is an optional area where footnotes can live.

      • In addition, a clinical study shows the pharmacokinetics of PRISTIQ 100 mg was similar in subjects with CYP2D6 poor and extensive metabolizer phenotypes

      Study description​​​​​​​

      Data from two open-label, 2-period, parallel-group, crossover studies, one evaluating PRISTIQ 50 mg (N=14) and one evaluating PRISTIQ 100 mg (N=14) in healthy subjects who are extensive or poor CYP2D6 substrate metabolizers. The primary objective was to determine the difference in the pharmacokinetics of PRISTIQ when influenced by CYP2D6 polymorphism.12

      1. Thase ME, Kornstein SG, Germain JM, Jiang Q, Guico-Pabia C, Ninan PT. An integrated analysis of the efficacy of desvenlafaxine compared with placebo in patients with major depressive disorder. CNS Spectr. 2009;14(3):144-154.
      2. Rosenthal JZ, Boyer P, Vialet C, Hwang E, Tourian KA. Efficacy and safety of desvenlafaxine 50 mg/d for prevention of relapse in major depressive disorder: a randomized controlled trial. J Clin Psychiatry. 2013;74(2):158-166.
      3. Soares CN, Kornstein SG, Thase ME, Jiang Q, Guico-Pabia CJ. Assessing the efficacy of desvenlafaxine for improving functioning and well-being outcome measures in patients with major depressive disorder: a pooled analysis of 9 double-blind, placebo-controlled, 8-week clinical trials. J Clin Psychiatry. 2009;70(10):1365-1371.
      4. Leon AC, Olfson M, Portera L, Farber L, Sheehan DV. Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med. 1997;27(2):93-105.
      5. Data on file. Pfizer Inc., New York, NY.
      6. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62.
      7. Clayton AH, Kornstein SG, Rosas G, Guico-Pabia C, Tourian KA. An integrated analysis of the safety and tolerability of desvenlafaxine compared with placebo in the treatment of major depressive disorder. CNS Spectr. 2009;14(4):183-195.
      8. Clayton A, Reddy S, Focht K, Musgnung J, Fayyad R. An evaluation of sexual functioning in employed outpatients with major depressive disorder treated with desvenlafaxine 50 mg or placebo. J Sex Med. 2013;10(3):768-776.
      9. Dunlop BW, Reddy S, Yang L. Symptomatic and functional improvement in employed depressed patients: a double‐blind clinical trial of desvenlafaxine versus placebo. J Clin Psychopharmacol. 2011;31:569-576.
      10. McGahuey CA, Gelenberg AJ, Laukes CA, et al. The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Ther. 2000;26(1):25-40.
      11. Preskorn SH, Nichols AI, Paul J, Patroneva AL, Helzner EC, Guico-Pabia CJ. Effect of desvenlafaxine on the cytochrome P450 2D6 enzyme system. J Psychiatr Pract. 2008;14(6):368-378.
      12. Nichols AI, Focht K, Jiang Q, Preskorn SH, Kane CP. Pharmacokinetics of venlafaxine extended release 75 mg and desvenlafaxine 50 mg in healthy CYP2D6 extensive and poor metabolizers: a randomized, open-label, two-period, parallel-group, crossover study. Clin Drug lnvestig. 2011;31(3):155-167.


      • Dosing and Administration
      • Pharmacology
      View Support & Services

      PRISTIQ 50 mg

      The starting dose is the proven effective dose

      PRISTIQ dosing

      ** This is an optional area where footnotes can live.

      PRISTIQ for MDD

      Proven efficacy with a low discontinuation rate* due to adverse events and a reduced risk of relapse in PRISTIQ responders1,2

      Tolerability data

      *In a pooled analysis of 8-week studies, discontinuation rates were 4.1% with PRISTIQ 50 mg vs 3.8% with placebo.


      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.

      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.

      PRISTIQ is not approved for use in pediatric patients.​​​​​​​

      • ​​​​​​PRISTIQ is contraindicated in patients with a known hypersensitivity to PRISTIQ or venlafaxine. Angioedema has been reported in patients treated with PRISTIQ. ​​​​​​​
      • ​​​​​​​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 an MAOI such as linezolid or intravenous methylene blue.
      Warnings and Precautions
      • All patients treated with antidepressants should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of treatment and when changing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, or suicidality that are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants should be alerted about the need to monitor patients.
      • The development of a potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs, including with PRISTIQ, both when taken alone, but especially when co-administered with other serotonergic agents (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 such events occur, immediately discontinue PRISTIQ and any concomitant serotonergic agents, and initiate supportive treatment. If concomitant use of PRISTIQ with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increase.
      • Patients receiving PRISTIQ should have regular monitoring of blood pressure, since increases in blood pressure were observed in clinical studies. Pre-existing hypertension should be controlled before starting 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. For patients who experience a sustained increase in blood pressure, either dose reduction or discontinuation should be considered.
      • SSRIs and SNRIs, including PRISTIQ, may increase the risk of bleeding events. Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may add to this risk.
      • 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 (Angle Closure Glaucoma) who does not have a patent iridectomy. Avoid use of antidepressants, including PRISTIQ, in patients with untreated anatomically narrow angles.
      • PRISTIQ is not approved for use in bipolar depression. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine the risk of bipolar disorder.
      • PRISTIQ should be used cautiously in patients with a history or family history of mania or hypomania or with a history of seizure disorder.
      • Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances, tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Patients should be monitored for symptoms when discontinuing treatment. A gradual reduction in dose rather than abrupt cessation is recommended whenever possible.
      • Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including PRISTIQ. Discontinuation of PRISTIQ should be considered in patients with symptomatic hyponatremia.
      • Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (the parent drug of PRISTIQ) therapy have been rarely reported.
      • Third trimester use may result in neonatal discontinuation syndrome.
      Adverse Reactions​​​​​
      • ​​​​​​​The most commonly observed adverse reactions in patients taking PRISTIQ vs placebo for MDD in short-term fixed-dose premarketing studies (incidence ≥5% and at least twice the rate of placebo in the 50-mg dose group) were nausea (22% vs 10%), dizziness (13% vs 5%), hyperhidrosis (10% vs 4%), constipation (9% vs 4%), and decreased appetite (5% vs 2%).

      PRISTIQ extended-release tablets are indicated for the treatment of major depressive disorder in adults.

      ​​​​​Please see Full Prescribing Information, including BOXED WARNING, and Medication Guide.


      PRISTIQ extended-release tablets are indicated for the treatment of major depressive disorder in adults.

      Please see Full Prescribing Information, including BOXED WARNING and Medication Guide.