desvenlafaxine (Rx)

Brand and Other Names:Pristiq, Khedezla
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet, extended release

  • 25mg
  • 50mg
  • 100mg
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Major Depressive Disorder

50 mg PO once daily

Higher dosages, up to 400 mg/day, have been used but have not been proved more efficacious; increased side effects have been reported

Assess periodically to determine need for continued treatment

Dosing Modifications

Renal impairment

  • CrCl ≥50 mL/min: Dosage adjustment not necessary
  • CrCl 30-50 mL/min: Not to exceed 50 mg PO qDay
  • CrCl 15-29 mL/min and end stage renal disease (ESRD), requiring hemodialysis: Not to exceed 25 mg PO once daily or 50 mg PO qDay
  • Do not administer supplemental dose after hemodialysis

Hepatic impairment

  • Recommended dosage: 50 mg PO once daily; dosages >100 mg/day not recommended

Dosing Considerations

When discontinuing, reduce dosage gradually, because abrupt discontinuance may result in adverse effects; if intolerable effects still occur, resume therapy at previously prescribed dosage and then decrease even more gradually

Discontinuation symptoms have been reported when switching patients from other antidepressants, including venlafaxine, to desvenlafaxine; taper initial antidepressant to minimize discontinuation symptoms

Wait at least 14 days between discontinuance of monoamine oxidase inhibitor (MAOI) and initiation of desvenlafaxine; wait at least 7 days between discontinuance of desvenlafaxine and initiation of MAOI

Generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy

Longer-term efficacy of desvenlafaxine (50-400 mg) was established in two maintenance trials

Patients should be periodically reassessed to determine the need for continued treatment

Using desvenlafaxine with other MAOIs such as linezolid or methylene blue

  • Do not start desvenlafaxine in a patient who is being treated with linezolid or IV methylene blue because there is increased risk of serotonin syndrome; patients who require more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered
  • If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or IV methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, promptly discontinue desvenlafaxine, and linezolid or IV methylene blue can be administered
  • See Contraindications

Safety and efficacy not established

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Interactions

Interaction Checker

and desvenlafaxine

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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            Adverse drug reactions (ADRs) shown occur with 50 mg/day dosage at rate higher than seen with placebo

            >10%

            Nausea (22-41%)

            Headache (20-29%)

            Dry mouth (11-25%)

            Hyperhidrosis (10-21%)

            Dizziness (13-16%)

            Insomnia (9-15%)

            Constipation (9-14%)

            Fatigue (7-11%)

            Diarrhea (5-11%)

            1-10%

            Decreased appetite (5-10%)

            Anxiety (0-10%)

            Elevated cholesterol and triglycerides (0-10%)

            Insomnia (0-10%)

            Tremor (2-9%)

            Proteinuria (5-8%)

            Mydriasis (2-6%)

            Male sexual dysfunction (0-6%)

            Anxiety (3-5%)

            Vertigo (1-5%)

            Blurred vision (3-4%)

            Abnormal dreams (2-4%)

            Urinary hesitation (2-4%)

            Yawning (1-4%)

            Feeling jittery (1-3%)

            Female sexual dysfunction (0-3%)

            Irritability (2%)

            Other (eg, abnormal liver function tests, increased blood prolactin, convulsion, syncope, extrapyramidal disorders, musculoskeletal stiffness, depersonalization, hypomania, bruxism, epistaxis, orthostatic hypotension) (<2%)

            Asthenia (1-2%)

            Nervousness (1-2%)

            Hot flush (1-2%)

            Rash (1-2%)

            Frequency Not Defined

            Ischemic cardiac events in patients with multiple underlying cardiac risk factors

            Gastrointestinal (GI) bleeding, hallucinations, photosensitivity reactions and severe cutaneous reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have occurred with other serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs)

            Suicidal thoughts and behaviors in adolescents and young adults

            Hyponatremia

            Interstitial lung disease and eosinophilic pneumonia

            Serotonin syndrome

            Elevated blood pressure

            Abnormal bleeding

            Narrow-angle glaucoma

            Activation of mania or hypomania

            Discontinuance syndrome

            Seizure

            Postmarketing Reports

            Cardiac disorders: Tachycardia

            General disorders and administration site conditions: Asthenia

            Investigations: Weight increased, liver function test abnormal, blood prolactin increased

            Musculoskeletal and connective tissue disorders: Musculoskeletal stiffness

            Nervous system disorders: Syncope, convulsion, dystonia

            Psychiatric disorders – Depersonalization, bruxism

            Renal and urinary disorders – Urinary retention

            Skin and subcutaneous tissue disorders – Rash, alopecia, photosensitivity reaction, angioedema.

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            Warnings

            Black Box Warnings

            Antidepressants increase risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years) in short-term studies

            Increased risk not observed in patients >24 years; slight decrease observed in patients >65 years

            In children and young adults, initiate only if benefits greatly outweigh risks

            Monitor closely for changes in behavior, clinical worsening, and suicidal tendencies during initial 1-2 months of therapy and dosage adjustments

            Patient’s family should communicate any abrupt behavioral changes to healthcare provider

            Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy

            Not approved for use in pediatric patients

            Contraindications

            Hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine formulation

            Coadministration with serotonergic drugs

            • Coadministration with MAOIs increases risk of serotonin syndrome
            • Use of MAOIs concomitantly within 14 days before initiating desvenlafaxine or within 7 days after discontinuing desvenlafaxine
            • Symptoms include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome (NMS), seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma
            • Starting desvenlafaxine in patient being treated with linezolid or IV methylene blue is contraindicated because of increased risk of serotonin syndrome
            • If linezolid or IV methylene blue must be administered, discontinue desvenlafaxine immediately and monitor for central nervous system (CNS) toxicity; therapy may be resumed 24 hours after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first

            Cautions

            Suicidality; monitor for clinical worsening and suicide risk (especially in children, adolescents, and young adults aged 18-24 years), during early phases of treatment and alterations in dosages

            Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding

            Control hypertension before initiating treatment; monitor blood pressure regularly during treatment; if sustained hypertension is observed, consider dosage reduction or discontinuance

            Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

            Use caution in patients with history of seizure disorders

            Screen patients for bipolar disorder; risk of mixed or manic episodes is increased in patients treated with antidepressants

            May precipitate shift to mania or hypomania in patients with bipolar disorder; avoid monotherapy in patients with bipolar disorder; screen for bipolar disorder patients presenting with depressive symptoms

            Cardiovascular, cerebrovascular or lipid metabolism disorders; monitor patients who have history of or are at risk for these disorders

            Monitor serum lipids periodically; risk of elevations in fasting serum total cholesterol, low-density lipoprotein (LDL) and triglycerides is increased

            Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium ≤110 mmol/L have been reported; monitor patients who are taking diuretics or at risk for volume depletion

            Rare reports of interstitial lung disease and eosinophilic pneumonia; monitor patients for progressive dyspnea, cough, or chest discomfort

            Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

            May impair congnitive abilities; use caution operating heavy machinery

            Taper dose when possible and monitor for discontinuation symptoms; adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (eg, paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures

            Serotonin syndrome

            • Consider risk of serotonin syndrome if administered concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort
            • Serotonin syndrome or NMS-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics, or serotonin precursors
            • Serotonin syndrome signs and symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (eg, nausea, vomiting, diarrhea)
            • Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding
            • Monitor for the emergence of serotonin syndrome
            • Discontinue treatment with desvenlafaxine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment
            • If concomitant use of desvenlafaxine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms See Contraindications

            Drug interactions overview

            • Concomitant use of desvenlafaxine increases peak plasma concentration and AUC of a drug primarily metabolized by CYP2D6 which may increase the risk of toxicity of the CYP2D6 substrate drugs
            • SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk
            • False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking desvenlafaxine
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            Pregnancy & Lactation

            Pregnancy

            Pregnancy exposure registry 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

            No published studies on desvenlafaxine in pregnant women; however published epidemiologic studies of pregnant women exposed to venlafaxine, the parent compound, have not reported a clear association with adverse developmental outcomes

            Exposure to SNRIs in mid to late pregnancy may increase the risk for preeclampsia, and exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage

            Exposure to SNRIs or SSRIs in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding; monitor neonates who were exposed to desvenlafaxine in the third trimester of pregnancy for drug discontinuation syndrome

            Lactation

            Available limited data from published literature show low levels of desvenlafaxine in human milk, and have not shown adverse reactions in breastfed infants

            There are no data on the effects of desvenlafaxine on milk production

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

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Potent SNRI; major active metabolite of venlafaxine

            Absorption

            Bioavailability: 80%

            Peak plasma time: 7.5 hr

            Ingestion of a high-fat meal (800-1000 calories) increased desvenlafaxine peak plasma concentration about 16% and had no effect on AUC

            Distribution

            Protein bound: 30%

            Vd: 3.4 L/kg

            Metabolism

            Primary: Conjugation (UDP-glucuronosyltransferase isoform mediated)

            Minor: CYP3A4 oxidative metabolism (N-demethylation)

            Enzymes inhibited: CYP2D6 (minimally)

            Elimination

            Half-life: 11 hr (prolonged in renal or hepatic dysfunction)

            Dialyzable: No

            Excretion, unchanged drug: Urine (45%)

            Excretion, metabolite: 19% (glucuronide); <5% (oxidative metabolite [N,O-didesmethylvenlafaxine])

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            Administration

            Oral Administration

            Take 1 tablet at about the same time each day

            Take either with or without food

            Swallow tablets whole, with fluid

            Do not divide, crush, chew, or dissolve tablets

            Avoid drinking alcohol while taking dose

            Storage

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

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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