Brand name: Pristiq
Drug class: Selective Serotonin- and Norepinephrine-reuptake Inhibitors

Medically reviewed by Drugs.com on Sep 10, 2024. Written by ASHP.

Introduction

A selective serotonin- and norepinephrine-reuptake inhibitor (SNRI); an antidepressant.

Uses for Desvenlafaxine, Desvenlafaxine Succinate

Major Depressive Disorder

Treatment of major depressive disorder in adults.

Guidelines from the American Psychiatric Association and the Department of Veterans Affairs/Department of Defense state that there is no evidence to suggest superiority of one first-line antidepressant over another. Recommended first-line agents for initial treatment of major depressive disorder include bupropion, mirtazapine, selective serotonin-reuptake inhibitors (SSRIs), SNRIs, trazodone, vilazodone, and vortioxetine. Select appropriate drug based on patient preference, response to prior therapies, and other patient- and drug-related factors.

Vasomotor Symptoms

Management of vasomotor symptoms^{† [off-label]} in postmenopausal women.

Guidelines from the North American Menopause Society recommend several treatments for vasomotor symptoms associated with menopause, including cognitive-behavioral therapy, SNRIs (including desvenlafaxine), SSRIs, fezolinetant, and gabapentin.

Related/similar drugs

Vraylar, sertraline, trazodone, Lexapro, citalopram, Zoloft, Cymbalta

Desvenlafaxine, Desvenlafaxine Succinate Dosage and Administration

General

Pretreatment Screening

• Perform a detailed psychiatric history (including family history of suicide, bipolar disorder, and depression) to assess risk of bipolar disorder prior to starting desvenlafaxine.

• Control preexisting hypertension before initiating desvenlafaxine therapy; use caution in patients with preexisting hypertension, cardiovascular, or cerebrovascular conditions that may be compromised by blood pressure increases.

• Inquire about sexual function prior to initiation of desvenlafaxine.

Patient Monitoring

• Monitor for worsening depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.

• Monitor blood pressure regularly.

• Monitor for serotonin syndrome.

• In patients receiving concomitant warfarin, monitor coagulation indices and look for signs of bleeding during initiation, titration, or discontinuance of desvenlafaxine.

• When discontinuing desvenlafaxine, monitor for discontinuance symptoms (e.g., nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances, tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, seizures).

• Inquire about changes in sexual function during treatment.

Dispensing and Administration Precautions

• To avoid medication errors, the Institute for Safe Medication Practices (ISMP) recommends that prescribers communicate both the brand and generic names for desvenlafaxine succinate (Pristiq) on the prescription order form.

Other General Considerations

• Acute episodes of major depressive disorder typically require pharmacologic treatment for several months or longer; reassess patients periodically to determine need for continued treatment.

• When discontinuing therapy, reduce dosage gradually and monitor for possible withdrawal symptoms; avoid abrupt discontinuance whenever possible. Some patients require discontinuation over a period of several months. If intolerable symptoms occur following dosage reduction or upon discontinuance of therapy, consider resuming therapy at the previously prescribed dosage and decreasing the dosage at a more gradual rate.

• If switching to desvenlafaxine from a monoamine oxidase inhibitor (MAOI) intended to treat psychiatric disorders, allow 14 days to elapse between discontinuation of the MAOI and initiation of desvenlafaxine. Conversely, if switching from desvenlafaxine to an MAOI, allow 7 days to elapse between discontinuation of desvenlafaxine and initiation of the MAOI.

• When switching from another antidepressant to desvenlafaxine, it may be necessary to taper the dosage of the previous antidepressant to minimize discontinuance symptoms.

• Do not initiate desvenlafaxine in patients receiving linezolid or IV methylene blue; if urgent treatment with linezolid or IV methylene blue is required in a patient receiving desvenlafaxine, stop desvenlafaxine and monitor for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid or IV methylene blue (whichever comes first). Resume desvenlafaxine 24 hours after the last dose of linezolid or IV methylene blue.

Administration

Oral Administration

Administer orally with or without food at approximately the same time each day.

Available in extended-release tablets as desvenlafaxine or desvenlafaxine succinate.

Swallow extended-release tablets whole with fluid; do not divide, crush, chew, or dissolve.

Dosage

Dosage of desvenlafaxine succinate expressed in terms of desvenlafaxine.

Adults

Major Depressive Disorder

Oral

50 mg once daily. Although efficacy established at dosages of 50–400 mg once daily in clinical studies, no additional benefit observed with dosages >50 mg once daily; adverse effects and discontinuances more frequent at higher dosages.

The 25-mg per day dose is intended for gradual reduction in dose when discontinuing treatment.

Vasomotor Symptoms† [off-label]

Oral

25–50 mg daily suggested initially; dosage may be titrated by that amount each day (effective dosage range, 100–150 mg daily).

Special Populations

Hepatic Impairment

Mild hepatic impairment: No specific dosage recommendations.

Moderate to severe hepatic impairment (Child-Pugh score 7–15): Initially, 50 mg once daily. Dosage increases to >100 mg daily not recommended.

Renal Impairment

Mild renal impairment (Cl_cr>50 mL/minute): No specific dosage recommendations.

Moderate renal impairment (Cl_cr 30–50 mL/minute): 50 mg once daily. Do not increase dosage.

Severe renal impairment (Cl_cr 15–29 mL/minute) or end-stage renal disease (Cl_cr <15 mL/minute) : 25 mg once daily or 50 mg every other day. Do not increase dosage and do not give supplemental doses after dialysis.

Geriatric Patients

No specific dosage recommendations at this time, but consider possibility of age-related decreases in renal function when selecting dosage.

Cautions for Desvenlafaxine, Desvenlafaxine Succinate

Contraindications

• Known hypersensitivity to desvenlafaxine, venlafaxine hydrochloride, or any ingredient in the formulation.

• Concurrent or recent (i.e., within 14 days) therapy with a monoamine oxidase inhibitor (MAOI) intended to treat psychiatric disorders. Use of an MAOI intended to treat psychiatric disorders within 7 days of desvenlafaxine discontinuance.

• Initiation of desvenlafaxine therapy in patients receiving MAOIs such as linezolid or IV methylene blue.

Warnings/Precautions

Warnings

Suicidal Thoughts and Behaviors

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults (18–24 years of age). (see Boxed Warning.) Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. Appropriately monitor and closely observe patients, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.

Appropriately monitor and closely observe patients receiving desvenlafaxine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality,.

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Bipolar disorder may initially present as a major depressive episode; take a detailed psychiatric history (including family history of suicide, bipolar disorder, and depression) prior to desvenlafaxine initiation to determine risk of bipolar disorder. Treatment of bipolar disorder with an antidepressant may precipitate development of a mixed/manic episode in patients at risk for bipolar disorder. Desvenlafaxine not indicated for use in bipolar disorder.

Other Warnings and Precautions

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported with SSRIs or SNRIs, particularly during concomitant therapy with other serotonergic drugs (e.g., 5-HT1 receptor agonists [“triptans”], tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, St. John’s Wort [Hypericum perforatum]) and drugs that impair metabolism of serotonin (e.g., MAOIs).

Monitor patients for development of serotonin syndrome. Symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or GI symptoms (e.g., nausea, vomiting, diarrhea).

Concurrent or recent (i.e., within 14 days) therapy with MAOIs used for treatment of psychiatric disorders contraindicated. Do not initiate desvenlafaxine in patients receiving MAOIs such as linezolid or IV methylene blue. If the MAOI is necessary, discontinue desvenlafaxine before initiation of the MAOI and monitor for serotonin syndrome for 7 days or until 24 hours after the last dose of the MAOI (whichever comes first).

If signs and symptoms of serotonin syndrome occur, immediately discontinue desvenlafaxine and any concurrently administered serotonergic agents; initiate supportive and symptomatic treatment.

Elevated Blood Pressure

Increases in blood pressure reported. Control preexisting hypertension before initiating desvenlafaxine therapy and regularly monitor blood pressure during therapy.

Exercise caution in patients with preexisting hypertension, cardiovascular, or cerebrovascular conditions that may be compromised by increases in blood pressure. If sustained increases in blood pressure occur, consider dosage reduction or discontinuance.

Increased Risk of Bleeding

Possible increased risk of bleeding. Concurrent administration of aspirin, NSAIAs, warfarin, and other anticoagulants may increase risk. Exposure to SNRIs associated with increased risk of postpartum hemorrhage, particularly during the month before delivery.

Advise patients of bleeding risk associated with concomitant use of antiplatelet agents or anticoagulants. Carefully monitor patients receiving warfarin therapy during initiation, titration, and discontinuation of desvenlafaxine.

Angle Closure Glaucoma

Pupillary dilation can occur, which can trigger an angle closure attack in patients with anatomically narrow angles who do not have a patent iridectomy. Avoid desvenlafaxine and other antidepressants in patients with untreated anatomically narrow angles.

Activation of Mania/Hypomania

Possible activation of mania and hypomania; use with caution in patients with personal or family history of mania or hypomania.

Discontinuation Syndrome

Adverse effects reported with abrupt discontinuance; reactions included nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Serious discontinuation symptoms reported, some protracted and severe. Completed suicide, suicidal thoughts, severe aggression, visual changes (i.e., blurred vision, trouble focusing), and increased blood pressure reported during desvenlafaxine dosage reduction and discontinuation.

Monitor for withdrawal symptoms when discontinuing desvenlafaxine. Gradual dosage reduction recommended over abrupt cessation whenever possible. If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage, then resume more gradual dosage reductions. Discontinuation period of several months may be required.

Seizures

Seizures reported in premarketing clinical studies. Desvenlafaxine not studied in patients with seizure disorders; use with caution in such patients.

Hyponatremia

Possible hyponatremia or SIADH; use with caution in patients who are volume depleted, elderly, or taking diuretics. Initiate appropriate medical intervention and consider drug discontinuance in patients with symptomatic hyponatremia.

Interstitial Lung Disease and Eosinophilic Pneumonia

Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (parent drug of desvenlafaxine) reported rarely; consider possibility in patients treated with desvenlafaxine who present with progressive dyspnea, cough, or chest discomfort. Promptly evaluate patients with these symptoms and consider discontinuance of desvenlafaxine.

Sexual Dysfunction

Sexual dysfunction reported with SNRIs (including desvenlafaxine); may include ejaculatory delay or failure, decreased libido, or erectile dysfunction in males, and decreased libido or delayed/absent orgasm in females.

Obtain detailed history of sexual function prior to initiation and during treatment with desvenlafaxine, since sexual function may not be spontaneously reported. Discuss potential management strategies with patients.

Specific Populations

Pregnancy

National Pregnancy Registry for Antidepressants monitors pregnancy outcomes in women exposed to desvenlafaxine during pregnancy. Clinicians are encouraged to register patients by calling 1-844-405-6185.

No published studies on desvenlafaxine use in pregnancy; however, available epidemiologic data with venlafaxine (parent compound) in pregnant women have not found a clear association between venlafaxine and adverse developmental outcomes.

Risks are associated with untreated depression as well as exposure to SNRIs or SSRIs during pregnancy. Possible increased risk of preeclampsia with desvenlafaxine exposure in mid to late pregnancy. Exposure to SNRIs increases risk of postpartum hemorrhage.

Complications, sometimes requiring prolonged hospitalization, respiratory support, and tube feeding, possible in neonates exposed to SNRIs or SSRIs late in the third trimester; may occur immediately upon delivery. Monitor neonates exposed to desvenlafaxine during the third trimester of pregnancy for discontinuation syndrome.

Lactation

Distributed into human milk at low levels; adverse reactions in breast-fed infants not detected. Unknown if desvenlafaxine affects milk production. Consider developmental and health benefits of breastfeeding along with mother’s clinical need for the drug and potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and effectiveness for major depressive disorder not established in pediatric patients <18 years of age. Greater risk of suicidal thinking or behavior (suicidality) associated with antidepressant treatment in children and adolescents with major depressive disorder.

Geriatric Use

No overall differences in safety or efficacy observed relative to younger adults. Consider possible reduced renal clearance in geriatric patients. Higher incidence of systolic orthostatic hypotension reported in patients ≥65 years of age.

Clinically important hyponatremia reported in geriatric patients.

Hepatic Impairment

Increased exposure in patients with moderate to severe (Child-Pugh score 7–15) hepatic impairment.

Renal Impairment

Decreased clearance and increased AUC in patients with moderate to severe (Cl_cr 15–50 mL/minute) renal impairment or end-stage renal disease (Cl_cr <15 mL/minute).

Common Adverse Effects

Nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and sexual function disorders in males.

Drug Interactions

Principally metabolized by UGT isoenzymes and to a lesser extent by CYP3A4. Does not inhibit CYP1A2, 2A6, 2C8, 2C9, 2C19, or 2D6 isoenzymes; does not inhibit or induce CYP3A4 in vitro.

Not a substrate or inhibitor of the P-glycoprotein transporter in vitro.

Drugs Metabolized by Hepatic Microsomal Enzymes

Drugs metabolized by CYP2D6 (e.g., desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine): Potential pharmacokinetic interaction (increased CYP2D6 substrate peak plasma concentrations and total exposure); possible increased risk for toxicity. When desvenlafaxine dosages ≤100 mg daily are used concomitantly with a CYP2D6 substrate, no dosage adjustment of the CYP2D6 substrate required. However, when desvenlafaxine dosages of 400 mg daily are used concurrently with a CYP2D6 substrate, reduce the dosage of the CYP2D6 substrate by up to 50%.

Drugs metabolized by CYP3A4: No dosage adjustment required.

Drugs metabolized by both CYP2D6 and CYP3A4: No dosage adjustment required.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP isoenzymes 1A1, 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, and 2E1: Clinically important pharmacokinetic interaction unlikely.

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) if used concurrently with antiplatelet or anticoagulant drugs; monitor carefully during initiation, titration, and discontinuance of desvenlafaxine.

Serotonergic Drugs

Potential pharmacologic interaction (serotonin syndrome) with serotonergic drugs. Avoid concomitant use or exercise caution and monitor. If serotonin syndrome occurs, consider discontinuing desvenlafaxine and any concurrently administered serotonergic agents.

Specific Drugs, Foods, and Laboratory Tests

Desvenlafaxine, Desvenlafaxine Succinate Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability is about 80%.

Linear and dose proportional pharmacokinetics over the single-dose range of 50–600 mg (1–12 times the recommended dosage) per day.

Following repeated oral dosing, steady-state serum concentrations attained after approximately 4–5 days.

Food

Peak plasma concentration increased about 16% when administered with a high-fat meal compared with fasting, but AUCs were similar.

Special Populations

Female patients: peak plasma concentrations approximately 26% higher compared to the reference population, with no differences in AUC.

Geriatric individuals 65–75 years of age: no change in peak plasma concentrations, but AUC was increased approximately 32% compared to the reference population.

Geriatric individuals >75 years of age: peak plasma concentrations increased approximately 32% and AUC increased 56% compared to the reference population.

No clinically significant differences in desvenlafaxine exposure based on ethnicity (White, Black, Hispanic).

Distribution

Extent

Distributed into human milk.

Plasma Protein Binding

30%; plasma protein binding is independent of plasma concentrations.

Elimination

Metabolism

Principally metabolized via conjugation by UGT isoenzymes; oxidation via CYP3A4 isoenzyme is a minor metabolic pathway.

Elimination Route

Approximately 45% of a single oral dose is eliminated unchanged in urine at 72 hours; approximately 19% of the dose is excreted as the glucuronide metabolite and <5% is excreted as the oxidative metabolite (N,O-didesmethylvenlafaxine).

Special Populations

Moderate to severe (Child-Pugh score 7–15) hepatic impairment: average AUC increased by approximately 31–35% compared to reference population.

Mild renal impairment (Cl_cr 50–80 mL/minute): AUC increased about 42%.

Moderate renal impairment (Cl_cr 30–50 mL/minute): AUC increased about 56%.

Severe renal impairment (Cl_cr 15-29 mL/minute): AUC increased about 108%.

End-stage renal disease (Cl_cr <15 mL/minute): AUC increased about 116%.

Stability

Storage

Oral

Extended-release Tablets

20–25°C (excursions permitted between 15–30°C).

Actions

• Desvenlafaxine is the principal active metabolite of venlafaxine and is an SNRI.

• Exact mechanism of antidepressant action has not been fully elucidated but appears to be associated with potentiation of serotonergic and noradrenergic activity in the CNS.

• Desvenlafaxine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake; however, inhibition of dopamine reuptake at concentrations that inhibit serotonin and norepinephrine reuptake appears unlikely in most patients.

• Desvenlafaxine does not inhibit MAO and has not demonstrated substantial affinity for muscarinic cholinergic, H₁-histaminergic, α₁-adrenergic, dopaminergic, GABA, glutamate, and opiate receptors in vitro.

Advice to Patients

• Risk of suicidality; advise patients, family, and caregivers to look for and immediately report emergence of suicidality, especially during the first few months of therapy and during periods of dosage adjustment.

• Advise patients about the importance of reading the patient information before taking desvenlafaxine and each time the prescription is refilled.

• Inform patients of potential risk of serotonin syndrome, particularly with concurrent use of 5-HT1 receptor agonists (also called triptans), tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, St. John’s Wort (Hypericum perforatum), and other serotonergic agents. Patients should immediately contact their clinician if signs and symptoms of serotonin syndrome develop.

• Advise patients not to concurrently take other products containing desvenlafaxine or venlafaxine.

• Instruct patients not to take desvenlafaxine with a MAOI or within 14 days of stopping the drug, and to allow at least 7 days after stopping desvenlafaxine before starting therapy with an MAOI.

• Risk of discontinuance symptoms when switching from other antidepressants, including venlafaxine, to desvenlafaxine. Advise patients that tapering of the previous antidepressant may be necessary to minimize the risk of such symptoms.

• Advise patients that they should have regular monitoring of blood pressure while taking desvenlafaxine.

• Advise patients, their families, and caregivers to observe desvenlafaxine-treated patients for signs of activation of mania/hypomania.

• Advise patients to notify their clinician if they develop any allergic signs or symptoms during therapy (e.g., rash, hives, swelling, difficulty breathing).

• Risk of cognitive and motor impairment; advise patients to exercise caution while operating hazardous machinery, including automobile driving, until they are reasonably certain that desvenlafaxine therapy does not adversely affect their ability to engage in such activities.

• Risk of sexual dysfunction in male and female patients; advise patients to discuss any changes in sexual function and potential management strategies with their clinician.

• Advise patients to avoid alcohol during desvenlafaxine therapy.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Advise patients about the risk of bleeding associated with concomitant use of desvenlafaxine and aspirin, nonsteroidal anti-inflammatory agents, other antiplatelet drugs, warfarin, or other anticoagulants.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to desvenlafaxine during pregnancy.

• Advise patients not to stop taking desvenlafaxine without first talking with their clinician. Advise patients that discontinuance effects may occur when stopping the drug.

• Inform patients that they may notice an inert matrix tablet passing in the stool or via colostomy, and that the active medication has already been absorbed by the time the patient sees the inert matrix tablet.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

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