Dosing & Uses
Dosage Forms & Strengths
tablet, extended release
Pristiq
- 25mg (contains 38 mg of desvenlafaxine succinate)
- 50mg (contains 76 mg of desvenlafaxine succinate)
- 100mg (contains 152 mg of desvenlafaxine succinate)
Khedezla
- 50mg
- 100mg
Major Depressive Disorder
50 mg PO qDay
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
Pristiq
- Moderate-to-severe (CrCl <50 mL/min), or end-stage renal disease (ESRD): Adjust maximum recommended dosage
Khedezla
- Mild (CrCl ≥50 mL/min): Dosage adjustment not necessary
- Moderate (CrCl 30-50 mL/min): Not to exceed 50 mg PO qDay
- Severe (CrCl <30 mL/min) and 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
Pristiq
- Moderate-to-severe (Child-Pugh score 7-15): Adjust maximum recommended dosage
Khedezla
- Moderate-to-severe (Child-Pugh score 7-15): 50 mg PO qD; dosages >100 mg/day not recommended
Dosing Considerations
Gradually reduce dose rather than stopping therapy abruptly whenever possible; if intolerable effects still occur, resume therapy at previously prescribed dosage and then decrease even more gradually
Switching to or from a monoamine oxidase inhibitor (MAOI) to treat psychiatric disorders
- 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
- 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 IV 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
Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
Adverse drug reactions (ADRs) shown occur with 50 mg/day dosage at rate higher than seen with placebo
>10%
Nausea (22-41%)
Dry mouth (11-25%)
Hyperhidrosis (10-21%)
Dizziness (10-16%)
Insomnia (9-15%)
Constipation (9-14%)
Somnolence (4-12%)
Fatigue (7-10%)
1-10%
Increased total cholesterol of ≥50 mg/dL and an absolute value of ≥261 mg/dL (3-10%)
Decreased appetite (5-10%)
Vomiting (3-9%)
Tremor (2-9%)
Anorgasmia (3-8%)
Ejaculation delayed (1-7%)
Libido decreased (3-6%)
Triglycerides, fasting ≥327 mg/dL (2-6%)
Mydriasis (2-6%)
Vertigo (2-5%)
Anxiety (3-5%)
Blurred vision (3-4%)
Chills (1-4%)
Yawning (1-4%)
Abnormal dreams (2-3%)
Feeling jittery (1-3%)
Orgasm abnormal (1-3%)
Nervousness (<2%)
Tachycardia (<2%)
Asthenia (<2%)
Weight increased, liver function test abnormal, blood prolactin increased (<2%)
Musculoskeletal stiffness (<2%)
Syncope, convulsion, dystonia (<2%)
Depersonalization, bruxism (<2%)
Urinary retention (<2%)
Rash, alopecia, photosensitivity reaction, angioedema (<2%)
Urinary hesitation (1-2%)
Ejaculation failure (1-2%
Sexual dysfunction (1-3%)
Tinnitus (1-2%)
Dysgeusia (1-2%)
Hot flush (1-2%)
Blood pressure increased (1-2%)
Increased LDL ≥50 mg/dL and an absolute value of ≥190 mg/dl (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.
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; avoid use of antidepressants, including desvenlafaxine, in patients with untreated anatomically narrow angles
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
A gradual reduction in dosage rather than abrupt cessation recommended; 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
- False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking desvenlafaxine
-
Risk of bleeding
- 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
- For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing therapy
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.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])
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)
Images
Patient Handout
Formulary
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