Version July 2025
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 behaviors with antidepressant use in adults older than 24 years; there was a reduction in risk with antidepressant use in adults 65 years 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. Desvenlafaxine is not approved for use in pediatric patients.
Dosage guidance:
Dosing: Some experts suggest a lower starting dose of 25 mg once daily, particularly in patients with anxiety who are sensitive to antidepressant-associated overstimulation effects (eg, anxiety, insomnia) (Ref).
Major depressive disorder (unipolar):
Oral: Initial: 50 mg once daily. In patients who do not respond after 6 weeks (or 7 days in clinically urgent situations), may increase to 100 mg once daily. Note: Although doses >50 mg/day did not provide added benefit in clinical trials and were associated with more adverse effects, according to some experts, increasing to 100 mg/day can be useful to optimize effect if there is an insufficient response to 50 mg/day (Ref).
Vasomotor symptoms associated with menopause (alternative agent) (off-label use):
Note: Alternative for patients unable or unwilling to take estrogen (Ref).
Oral: Initial: 50 mg once daily; increase daily dose in 25 to 50 mg increments every day to target dose of 100 mg once daily. Some patients may require doses up to 150 mg/day for optimal response; however, doses >100 mg/day have greater adverse effects and limited additional benefit (Ref).
Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal and detect reemerging symptoms (Ref). For brief treatment (eg, 2 to 3 weeks) may taper over 1 to 2 weeks; <2 weeks of treatment generally does not warrant tapering (Ref). Reasons for a slower taper (eg, over 4 weeks) include prior history of antidepressant withdrawal symptoms or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).
Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches but is contraindicated when switching to or from a monoamine oxidase inhibitor (MAOI). A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between 2 serotonin-norepinephrine reuptake inhibitors), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is due to adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Switching to or from an MAOI:
Allow 14 days to elapse between discontinuing an MAOI and initiation of desvenlafaxine.
Allow 7 days to elapse between discontinuing desvenlafaxine and initiation of an MAOI according to manufacturer labeling; however, experts recommend a 14-day washout period before initiating an MAOI (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Renal function may be estimated using the Cockcroft-Gault formula.
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl 30 to 50 mL/minute: 50 mg once daily (maximum)
CrCl <30 mL/minute: 25 mg once daily or 50 mg every other day (maximum)
End-stage renal disease (ESRD) requiring hemodialysis (HD): 25 mg once daily or 50 mg every other day (maximum). Supplemental doses should not be given after HD.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate to severe impairment (Child-Pugh classes B and C): Initial: 50 mg once daily; maximum dose: 100 mg once daily
Refer to adult dosing.
Antidepressants (when used as monotherapy) may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent mania or hypomania in patients with unipolar major depressive disorder (MDD) has been reported, as many cases of bipolar disorder present in episodes of MDD (Ref).
Mechanism: Non–dose-related; idiosyncratic. Unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref).
Onset: Varied; a systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy but not thereafter (up to 4.6 years) (Ref).
Risk factors:
• Family history of bipolar disorder (Ref)
• Depressive episode with psychotic symptoms (Ref)
• Younger age at onset of depression (Ref)
• Antidepressant resistance (Ref)
• Females (Ref)
Serotonergic antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk of bleeding, particularly if used concomitantly with antiplatelets and/or anticoagulants. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications (Ref), although prospective studies have not determined if the cause of the increased risk of bleeding is due to SSRI use alone. For SNRIs, less data exists compared to SSRIs and data supporting an association with bleeding are conflicting (Ref). However, there are some observational studies that have found an increased risk for postpartum hemorrhage (exposure during late gestation), stroke, and gastrointestinal hemorrhage in patients receiving SNRIs, predominately with studies using venlafaxine (Ref). There are few data available for desvenlafaxine, aside from an isolated case report of possible acquired blood coagulation disorder in a patient receiving desvenlafaxine (Ref).
Mechanism: Possibly via inhibition of serotonin-mediated platelet activation (inhibition of the serotonin reuptake transporter) and subsequent platelet dysfunction. SNRIs may also increase gastric acidity, which can increase the risk of GI bleeding (Ref).
Onset: Varied; based on data evaluating SSRIs, it has been suggested that the onset of risk is likely delayed for several weeks until SNRI-induced platelet serotonin depletion becomes clinically significant (Ref), although the onset of bleeding may be more unpredictable if patients are taking concomitant antiplatelets, anticoagulants, or nonsteroidal anti-inflammatory drugs.
Risk factors:
Serotonergic antidepressants, in general:
• Concomitant use of antiplatelets and/or anticoagulants (Ref)
• Preexisting platelet dysfunction or coagulation disorders (eg, von Willebrand factor, left ventricular assist device patients) (Ref)
Statistically significant increases in mean blood pressure have been observed in short-term, placebo-controlled desvenlafaxine clinical trials. In general, increases in blood pressure are small and clinically insignificant; however, clinically significant blood pressure and heart rate elevation has been observed less frequently. Worsening of hypertension in a patient with previously controlled blood pressure by antihypertensives has also been described in a case report (Ref). In addition, tachycardia has been observed (Ref).
Mechanism: Believed to potentially increase blood pressure via its noradrenergic mechanism, similar to the proposed mechanism for venlafaxine, the parent compound of desvenlafaxine. However, unlike the established dose-related effect of venlafaxine on blood pressure, desvenlafaxine does not have an established dose-response (although one has been suggested). This potential difference has been attributed to the venlafaxine’s ability to exhibit differential inhibition of reuptake of noradrenaline and serotonin at different doses, which does not occur with desvenlafaxine (Ref).
Risk factors:
Based on data using venlafaxine:
• Preexisting hypertension (potential risk factor) (Ref)
• Males (potential risk factor) (Ref)
• Older adults (potential risk factor) (Ref)
Limited data from observational studies involving mostly older adults (≥50 years of age) suggest serotonin norepinephrine reuptake inhibitors (SNRIs) may be associated with an increased risk of bone fractures. Data primarily uses venlafaxine, and to lesser extent duloxetine, as the SNRI; data involving desvenlafaxine and the risk of fracture is extremely limited (Ref).
Mechanism: Time-related; mechanism not fully elucidated; postulated to be through a direct effect by serotonergic agents (selective serotonin reuptake inhibitors [SSRIs] or SNRIs) on bone metabolism via interaction with 5-HT and osteoblast, osteocyte, and/or osteoclast activity. Of note, data evaluating the effects of serotonergic agents on bone mineral density primarily involve SSRIs rather than SNRIs (Ref).
Risk factors:
Based on SSRIs and SNRIs in general:
• Long-term use (potential risk factor) (Ref)
Serotonin norepinephrine reuptake inhibitors (SNRIs) are associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or hyponatremia (including severe cases), predominantly in the elderly. Data evaluating a risk of hyponatremia with SNRIs are more limited compared to selective serotonin reuptake inhibitors (SSRIs) (with the possible exception for venlafaxine), but there are case reports involving desvenlafaxine suggesting an association (Ref).
Mechanism: May cause SIADH via release of antidiuretic hormone (ADH) via serotonin effects on 5-HT receptors and norepinephrine effects on alpha-1 adrenergic receptors (Ref) or may cause nephrogenic SIADH by increasing the sensitivity of the kidney to ADH (Ref).
Onset: Intermediate; based on data involving SSRIs, hyponatremia usually develops within the first few weeks of treatment (Ref).
Risk factors:
Based on data involving SSRIs:
• Older age (Ref)
• Females (Ref)
• Concomitant use of diuretics (Ref)
• Low body weight (Ref)
• Lower baseline serum sodium concentration (Ref)
• Volume depletion (Ref)
• History of hyponatremia (potential risk factors) (Ref)
• Symptoms of psychosis (potential risk factors) (Ref)
There is a single case report of interstitial pneumonitis associated with desvenlafaxine (Ref). In contrast, numerous reports of interstitial lung disease (eg, hypersensitivity pneumonitis, interstitial pneumonitis, acute eosinophilic pneumonia) have been documented following venlafaxine, the parent drug of desvenlafaxine (Ref).
Mechanism: Unknown; in cases associated with venlafaxine, a direct toxic effect on lung tissue and hypersensitivity reactions have been suggested as possible causes. Another proposed mechanism is the result of pulmonary hypertension leading to lung fibrosis over time (Ref). Since ~70% of venlafaxine is metabolized to desvenlafaxine, the mechanism is likely similar (Ref).
Onset: Delayed; in case reports with venlafaxine-associated interstitial pneumonitis, most patients developed symptoms months to years into use; however, several patients developed symptoms 6 to 9 months following a dose increase after months of low-dose therapy. In the single case of desvenlafaxine-associated interstitial pneumonitis, onset of symptoms occurred 6 months after a dose increase from 50 mg to 100 mg daily; previously, the patient had been maintained for 4 years on 50 mg/day (Ref).
Risk factors:
• Dose escalation (potential risk factor) (Ref)
Serotonin syndrome (or serotonin toxicity) has been reported with selective norepinephrine reuptake inhibitors (SNRIs) (particularly venlafaxine) and typically occurs with coadministration of multiple serotonergic drugs but can occur following a single serotonergic agent at high therapeutic doses or supratherapeutic doses (Ref). There is less experience with desvenlafaxine compared to venlafaxine, but serotonin toxicity has been observed with supratherapeutic doses of desvenlafaxine (Ref). The diagnosis of serotonin syndrome is made based on the Hunter Serotonin Toxicity Criteria (Ref) and may result in a spectrum of symptoms, such as anxiety, agitation, confusion, delirium, hyperreflexia, muscle rigidity, myoclonus, tachycardia, tachypnea, and tremor. Severe cases may cause hyperthermia, significant autonomic instability (ie, rapid and severe changes in blood pressure and pulse), coma, and seizures (Ref).
Mechanism: Dose-related; overstimulation of serotonin receptors, most notably 5-HT2A, by serotonergic agents (Ref). Desvenlafaxine is the major active metabolite of the serotonin-norepinephrine reuptake inhibitor, venlafaxine, and selectively inhibits serotonin and norepinephrine uptake (Ref).
Onset: Rapid; onset is typically within hours of an exposure (but delays of 24 hours or longer have been reported) (Ref).
Risk factors:
• Concomitant use of drugs that increase serotonin synthesis, block serotonin reuptake, and/or impair serotonin metabolism (eg, monoamine oxidase inhibitors [MAOIs]). Of note, concomitant use of some serotonergic agents, such as MAOIs, are contraindicated.
Serotonin norepinephrine reuptake inhibitors (SNRIs), (data primarily involves venlafaxine) have been associated with sexual disorder in both men and women. The following adverse reactions have been associated with desvenlafaxine: Anorgasmia, orgasm abnormal, erectile dysfunction, impotence, decreased libido. Desvenlafaxine is typically associated with low rates of treatment-emergent sexual dysfunction in the few clinical trials available (Ref). However, treatment-emergent sexual dysfunction is typically underreported and clinical benefit on sexual functioning is difficult to ascertain in clinical trials (Ref).
Mechanism: Based on data involving selective serotonin reuptake inhibitors (SSRIs), it has been postulated that increases in serotonin may affect other hormones and neurotransmitters involved in sexual function; in particular, testosterone's effect on sexual arousal and dopamine's role in achieving orgasm (Ref).
Risk factors:
• Depression (sexual dysfunction is commonly associated with depression; SSRI- or SNRI-associated sexual dysfunction may be difficult to differentiate in treated patients) (Ref)
Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years) in short-term studies. In adults >24 years of age, short-term studies did not show an increased risk of suicidal thinking and behavior, and in older adults ≥65 years of age, a decreased risk was observed, per the manufacturer's labeling. Although data have yielded inconsistent results regarding the association of antidepressants and risk of suicide, particularly among adults, collective evidence shows a trend of an elevated risk of suicidality in younger age groups (Ref). Of note, the risk of a suicide attempt is inherent in major depression and may persist until remission occurs.
Mechanism: Not established; one of several postulated mechanisms is that antidepressants may energize suicidal patients to act on impulses; another suggests that antidepressants may produce a worsening of depressive symptoms, leading to the emergence of suicidal thoughts and actions (Ref).
Onset: Varied; increased risk observed in short-term studies (ie, <4 months) in pediatric and young adults; it is unknown whether this risk extends to longer-term use (ie, >4 months).
Risk factors:
• Children and adolescents (Ref)
• Depression (risk of suicide is associated with major depression and may persist until remission occurs)
Withdrawal syndrome, consisting of both somatic symptoms (eg, dizziness, chills, light-headedness, vertigo, shock-like sensations, paresthesia, fatigue, headache, nausea, tremor, diarrhea, visual disturbances) and psychological/behavioral symptoms (eg, aggressive behavior, anxiety, agitation, confusion, insomnia, irritability, lethargy, mania, violent behavior), have been reported with serotonin norepinephrine reuptake inhibitors (SNRIs), including desvenlafaxine, primarily following abrupt discontinuation. Symptoms may be severe. Withdrawal symptoms may also occur following gradual tapering. In general, antidepressant discontinuation symptoms usually last a few weeks, but occasionally may persist for months or possibly even years (ie, persistent postwithdrawal disorder) (Ref).
Mechanism: Withdrawal; due to reduced availability of serotonin in the CNS with decreasing levels of the serotonergic agent. Other neurotransmission systems, including increased glutamine and dopamine, may also be affected, as well as the hypothalamic-pituitary-adrenal axis (Ref).
Onset: Rapid; withdrawal symptoms following SNRI discontinuation, symptoms typically appear within a few days of discontinuation, although late onset may also occur (Ref).
Risk factors:
• Abrupt discontinuation (rather than dose taper) or tapering the antidepressant too quickly (Ref)
• Drugs with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)
• Higher doses (Ref)
• Longer duration of treatment (eg, ≥4 weeks) (Ref)
• Prior history of antidepressant withdrawal symptoms (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Dermatologic: Hyperhidrosis (10% to 11%)
Gastrointestinal: Nausea (22% to 26%), xerostomia (11% to 17%)
Nervous system: Dizziness (10% to 13%), insomnia (9% to 12%)
1% to 10%:
Cardiovascular: Hypertension (sustained: ≤1%), syncope (<2%), tachycardia (<2%)
Dermatologic: Alopecia (<2%), skin photosensitivity (<2%), skin rash (<2%)
Endocrine & metabolic: Decreased libido (males: 4% to 5%) (table 1), hot flash (1%), hypercholesterolemia (increased by ≥50 mg/dL and ≥261 mg/dL: 3% to 4%), hyperprolactinemia (<2%), increased LDL cholesterol (increased by ≥50 mg/dL and ≥190 mg/dL: 1%), weight gain (<2%)
|
Drug (Desvenlafaxine) |
Placebo |
Population |
Dose |
Number of Patients (Desvenlafaxine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
5% |
1% |
Males |
100 mg |
157 |
239 |
|
4% |
1% |
Males |
50 mg |
108 |
239 |
Gastrointestinal: Bruxism (<2%), constipation (9%), decreased appetite (5% to 8%), vomiting (4%)
Genitourinary: Abnormal orgasm (males: 1%) (table 2), anorgasmia (males: 3%; females: 1%) (table 3), delayed ejaculation (1% to 5%), ejaculation failure (1%), ejaculatory disorder (1%), erectile dysfunction (3% to 6%) (table 4), male sexual disorder (1%), proteinuria (5% to 8%), urinary hesitancy (≤1%), urinary retention (<2%)
|
Drug (Desvenlafaxine) |
Placebo |
Population |
Dose |
Number of Patients (Desvenlafaxine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
1% |
0% |
Males |
100 mg |
157 |
239 |
|
Drug (Desvenlafaxine) |
Placebo |
Population |
Dose |
Number of Patients (Desvenlafaxine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
3% |
0% |
Males |
100 mg |
157 |
239 |
|
1% |
0% |
Females |
50 mg |
209 |
397 |
|
1% |
0% |
Females |
100 mg |
267 |
397 |
|
Drug (Desvenlafaxine) |
Placebo |
Dose |
Number of Patients (Desvenlafaxine) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
6% |
1% |
100 mg |
157 |
239 |
|
3% |
1% |
50 mg |
108 |
239 |
Hepatic: Abnormal hepatic function tests (<2%)
Hypersensitivity: Angioedema (<2%)
Nervous system: Abnormal dreams (2% to 3%), anxiety (3% to 5%), asthenia (<2%), depersonalization (<2%), disturbance in attention (1%), drowsiness (9%), fatigue (7%), jitteriness (2%), seizure (<2%), tremor (3%), vertigo (2%), yawning (1%)
Neuromuscular & skeletal: Dystonia (<2%), muscle rigidity (<2%)
Ophthalmic: Blurred vision (3% to 4%), mydriasis (2%)
Otic: Tinnitus (2%)
<1%: Nervous system: Mania
Frequency not defined:
Cardiovascular: Acute myocardial infarction, coronary occlusion, ischemic heart disease, orthostatic hypotension
Endocrine & metabolic: Increased serum triglycerides
Nervous system: Headache
Postmarketing:
Cardiovascular: Cardiomyopathy (takotsubo) (Ref), pedal edema (Ref)
Dermatologic: Stevens-Johnson syndrome
Endocrine & metabolic: Hyperglycemia (Ref), hyponatremia (SIADH) (Ref)
Gastrointestinal: Acute pancreatitis
Hematologic & oncologic: Acquired blood coagulation disorder (Ref)
Nervous system: Anosmia (including hyposmia), behavioral changes (oppositional behavior pediatric) (Ref), reversible cerebral vasoconstriction syndrome (Ref), serotonin syndrome (supratherapeutic doses) (Ref), suicidal ideation (Ref), suicidal tendencies (Ref), withdrawal syndrome (can be severe; including aggressive behavior, dyskinesia, homicidal ideation, hostility, outbursts of anger) (Ref)
Respiratory: Interstitial pneumonitis (Ref)
Hypersensitivity to desvenlafaxine, venlafaxine or any component of the formulation; use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing an MAOI); initiation of MAOIs within 7 days of discontinuing desvenlafaxine; initiation of desvenlafaxine in a patient receiving IV methylene blue.
Note: Although desvenlafaxine is contraindicated per manufacturer labeling when used in combination with linezolid, new evidence suggests that the combination is unlikely to cause serotonin syndrome (0.06% to 3% risk), and therefore these agents can be administered concomitantly when necessary. Monitor patients on this combination; average duration of serotonin toxicity is ~4 days; however, risks may be greater with longer durations of concurrent therapy. Educate patients on the signs and symptoms of serotonin syndrome (Bai 2022; Butterfield 2012; Karkow 2017; Kufel 2023; Narita 2007; Taylor 2006).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
Disease-related concerns:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen.
• Cardiovascular disease: Use caution in patients with preexisting hypertension, cardiovascular conditions, or cerebrovascular disease.
• Glaucoma: May cause mydriasis, which in susceptible individuals can lead to an episode of narrow-angle glaucoma.
• Hepatic impairment: Use caution in patients with compensated hepatic cirrhosis; clearance is decreased and average serum concentration increased; dosage adjustment is recommended in patients with moderate to severe hepatic impairment (Mauri 2014).
• Renal impairment: Use caution; clearance is decreased and plasma concentrations are increased; dosage reduction recommended.
• Seizure disorders: Use caution in patients with a previous seizure disorder.
Special populations:
• Older adult: Older adults are at increased risk for orthostatic hypotension with therapy compared to younger adults.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Generic: 50 mg, 100 mg
Tablet Extended Release 24 Hour, Oral, as succinate [strength expressed as base]:
Pristiq: 25 mg, 50 mg
Pristiq: 100 mg [contains fd&c yellow #6 (sunset yellow)]
Generic: 25 mg, 50 mg, 100 mg
Yes
Tablet, 24-hour (Desvenlafaxine ER Oral)
50 mg (per each): $5.80
100 mg (per each): $5.80
Tablet, 24-hour (Desvenlafaxine Succinate ER Oral)
25 mg (per each): $11.01 - $11.95
50 mg (per each): $11.01 - $11.95
100 mg (per each): $11.01 - $11.95
Tablet, 24-hour (Pristiq Oral)
25 mg (per each): $17.52
50 mg (per each): $17.52
100 mg (per each): $17.52
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Generic: 50 mg, 100 mg
Tablet Extended Release 24 Hour, Oral, as succinate [strength expressed as base]:
Pristiq: 50 mg, 100 mg [contains fd&c yellow #6(sunset yellow)alumin lake]
Generic: 50 mg, 100 mg
Oral:
Administer at approximately the same time each day with or without food. Swallow tablet whole; do not crush, chew, divide, or dissolve. When discontinuing therapy, gradually taper the dose (the 25 mg tablet is intended for a gradual dose reduction when discontinuing treatment).
Bariatric surgery: Desvenlafaxine is only available as an ER formulation and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery. Providers should determine if the condition being treated can be safely monitored or if a switch to an alternative is necessary (Ref).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Aptryxol: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/205583s014lbl.pdf#page=30
Desvenlafaxine extended release tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/204150s020lbl.pdf#page=33
Khedezla: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204683s007lbl.pdf#page=24
Pristiq: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021992s048lbl.pdf#page=36
Major depressive disorder: Treatment of major depressive disorder (MDD).
Vasomotor symptoms associated with menopause
Pristiq may be confused with PriLOSEC
Beers Criteria: Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) (desvenlafaxine) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).
Substrate of CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abciximab: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Abrocitinib: Agents with Antiplatelet Effects may increase antiplatelet effects of Abrocitinib. Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Alcohol (Ethyl): May increase hepatotoxic effects of Serotonin/Norepinephrine Reuptake Inhibitor. Particularly duloxetine and milnacipran. Management: Consider advising patients to avoid concomitant use of alcohol with SNRIs, particularly those using extended-release SNRI formulations, due to the risk of accelerated drug release. Heavy alcohol use has been associated with overdose and hepatotoxicity. Risk D: Consider Therapy Modification
Almotriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Alosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Alpha-/Beta-Agonists: Serotonin/Norepinephrine Reuptake Inhibitor may increase tachycardic effects of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitor may increase vasopressor effects of Alpha-/Beta-Agonists. Management: If possible, avoid coadministration of direct-acting alpha-/beta-agonists and serotonin/norepinephrine reuptake inhibitors. If coadministered, monitor for increased sympathomimetic effects (eg, increased blood pressure, chest pain, headache). Risk D: Consider Therapy Modification
Alpha2-Agonists: Serotonin/Norepinephrine Reuptake Inhibitor may decrease therapeutic effects of Alpha2-Agonists. Risk C: Monitor
Amphetamines: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor
Anagrelide: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Anticoagulants (Miscellaneous Agents): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor
Antiemetics (5HT3 Antagonists): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): Agents with Antiplatelet Effects may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Antipsychotic Agents: Serotonergic Agents (High Risk) may increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Aspirin: Serotonin/Norepinephrine Reuptake Inhibitor may increase antiplatelet effects of Aspirin. Risk C: Monitor
Brexanolone: Serotonin/Norepinephrine Reuptake Inhibitor may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Serotonin/Norepinephrine Reuptake Inhibitor. Risk X: Avoid
BusPIRone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Caplacizumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Caplacizumab. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Collagenase (Systemic): Agents with Antiplatelet Effects may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
Cyclobenzaprine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Dapoxetine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Dexmethylphenidate-Methylphenidate: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Dextromethorphan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Direct Oral Anticoagulants (DOACs): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Eletriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Epinephrine (Racemic): Serotonin/Norepinephrine Reuptake Inhibitor may increase adverse/toxic effects of Epinephrine (Racemic). Risk X: Avoid
Ergot Derivatives: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Fenfluramine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
FentaNYL: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor
Fondaparinux: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Fondaparinux. Risk C: Monitor
Gepirone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Heparin: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Heparin. Risk C: Monitor
Heparins (Low Molecular Weight): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Iobenguane Radiopharmaceutical Products: Serotonin/Norepinephrine Reuptake Inhibitor may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid
Lasmiditan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Levomethadone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Limaprost: May increase adverse/toxic effects of Agents with Antiplatelet Effects. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Linezolid: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Meperidine: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor
Metaxalone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Methadone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Methylene Blue: Serotonin/Norepinephrine Reuptake Inhibitor may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid
Metoclopramide: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Mirtazapine: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Nefazodone: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Serotonin/Norepinephrine Reuptake Inhibitor may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): Serotonin/Norepinephrine Reuptake Inhibitor may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Topical). Risk C: Monitor
Obinutuzumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and agents with antiplatelet effects, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Ondansetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opioid Agonists (metabolized by CYP3A4): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opioid Agonists: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Opipramol: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Oxitriptan: Serotonergic Agents (High Risk) may increase serotonergic effects of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
OxyCODONE: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Pentosan Polysulfate Sodium: Agents with Antiplatelet Effects may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor
Ramosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Rasagiline: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Safinamide: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Selective Serotonin Reuptake Inhibitor: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Serotonin/Norepinephrine Reuptake Inhibitor. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor
Selegiline: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Selumetinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Serotonergic Agents (High Risk, Miscellaneous): Serotonin/Norepinephrine Reuptake Inhibitor may increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonin 5-HT1D Receptor Agonists (Triptans): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonin/Norepinephrine Reuptake Inhibitor: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Serotonin/Norepinephrine Reuptake Inhibitor may increase antiplatelet effects of Serotonin/Norepinephrine Reuptake Inhibitor. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor
St John's Wort: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Syrian Rue: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Thrombolytic Agents: Agents with Antiplatelet Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Tilidine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
TraMADol: Serotonin/Norepinephrine Reuptake Inhibitor may increase adverse/toxic effects of TraMADol. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and seizures when these agents are combined. Risk C: Monitor
TraZODone: May increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Tricyclic Antidepressants: Serotonin/Norepinephrine Reuptake Inhibitor may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes when these agents are combined. Risk C: Monitor
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ziprasidone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Evaluate pregnancy status prior to initiating treatment in patients who could become pregnant. Treatment should not be withheld, but pharmacologic management may vary based on reproductive status, severity of illness, and history of antidepressant response (ACOG 2023; WFSBP [Dodd 2018]). When treating depression, serotonin-norepinephrine reuptake inhibitors are not first-line medications for use prior to conception in patients who are treatment naive or who do not have a history of effective treatment. Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (BAP [McAllister-Williams 2017]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]).
Product labeling notes sexual dysfunction has been reported with desvenlafaxine use. Depression is also associated with sexual dysfunction (Padda 2021).
Outcome data following maternal use of desvenlafaxine during pregnancy are available (Anderson 2020; Marks 2021). An increased risk of preeclampsia and spontaneous abortion may be associated with serotonin-norepinephrine reuptake inhibitor (SNRI) use; however, the quality of evidence for these outcomes is low (ACOG 2023).
Adverse effects in the newborn following SNRI exposure in the third trimester include neonatal adaptation syndrome and persistent pulmonary hypertension of the newborn. Neonatal adaptation syndrome can occur shortly after birth and typically resolves within 2 weeks. Mechanisms of neonatal adaptation syndrome are not well understood but may be due to either SNRI toxicity or withdrawal. Reducing the dose or discontinuing the SNRI prior to delivery to reduce the risk of neonatal adaptation syndrome is not recommended (ACOG 2023). Symptoms can include apnea, constant crying, cyanosis, feeding difficulty, hyperreflexia, hypo- or hypertonia, hypoglycemia, irritability, jitteriness, respiratory distress, seizures, temperature instability, tremor, and vomiting. Prolonged hospitalization, respiratory support, or tube feedings may be required.
Persistent pulmonary hypertension of the newborn is a rare complication of SNRI use during pregnancy with symptoms of respiratory distress within the first hours of life and an increased risk of neonatal mortality (ACOG 2023). Monitoring of infants exposed to SNRIs late in pregnancy is recommended (Masarwa 2019).
SNRIs may increase the risk of bleeding. Exposure late in pregnancy is associated with less than a 2-fold increase in postpartum hemorrhage. The clinical significance of this is uncertain (BAP [McAllister-Williams 2017]).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Untreated or undertreated depression is associated with preterm birth, low birth weight, preeclampsia, postpartum depression, and impaired infant attachment (associated with long-term developmental effects). Discontinuing effective medications during pregnancy increases the risk of relapse. Management should be made as part of a shared decision-making process (ACOG 2023).
Patients effectively treated for depression pre-pregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]). Treatment should not be withheld or discontinued based only on pregnancy status (ACOG 2023).
SNRIs are not first-line medications for pregnant patients who are treatment naive or who do not have a history of effective treatment with another medication (ACOG 2023; BAP [McAllister-Williams 2017]); however, desvenlafaxine may be considered as an alternative (CANMAT [MacQueen 2016]).
SNRI dosing should be initiated with half the lowest recommended dose and titrated gradually over 4 to 10 days. Dose adjustments may be required as pregnancy progresses to keep symptoms in remission (ACOG 2023).
When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Monthly monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).
Desvenlafaxine is the major active metabolite of venlafaxine; refer to the Venlafaxine monograph for additional information.
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Pregnant patients 45 years of age and younger with a history of psychiatric illness are encouraged to enroll in the National Pregnancy Registry for Antidepressants (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants).
Desvenlafaxine is present in breast milk.
Data related to the presence of desvenlafaxine in breast milk are available:
• A study was conducted in 10 mother-infant pairs following maternal use of desvenlafaxine 50 to 150 mg ER tablets once daily. Patients were 0.9 to 12.7 months postpartum (mean: 4.3 months) and duration of therapy at the time of the study was 4 to 35 days. Breast milk was sampled prior to the morning dose and at intervals over 24 hours. The 24-hour average breast milk concentrations of desvenlafaxine ranged from 275 to 1309 mcg/L. Using the highest average breast milk concentration (1309 mcg/L), authors of the study calculated the estimated daily infant dose of desvenlafaxine via breast milk to be 196 mcg/kg/day providing a relative infant dose (RID) of 10.8% compared to the weight adjusted maternal dose (1818 mcg/kg/day). Using the 24-hour mean average desvenlafaxine breast milk concentration (564 mcg/L; range: 351 to 777 mcg/L), the estimated infant dose via breast milk was calculated to be 85 mcg/kg/day (range: 53 to 117 mcg/kg/day), providing a RID 6.8% (range 5.5% to 8.1%) compared to the weight adjusted maternal dose. Maximum breast milk concentrations of desvenlafaxine occurred 2.44 to 3.79 hours after the maternal dose. Desvenlafaxine was present in infant plasma. The mean infant exposure was 5.3% of maternal plasma in 8 infants who were exclusively breastfed (Rampono 2011).
• Data are also available from a case report following maternal use of desvenlafaxine 250 mg/day for 14 weeks and breastfeeding a 5-month-old. Using the average breast milk concentration (1958 mcg/L), authors of the study calculated the estimated infant dose of desvenlafaxine via breast milk to be 294 mcg/kg/day RID of 7.8% compared to the weight adjusted maternal dose (3782 mcg/kg/day) (Ilett 2010).
• In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Anderson 2021).
Infants exposed to serotonin-norepinephrine reuptake inhibitors (SNRIs) via breast milk should be monitored for sedation and adequate weight gain (ABM [Sriraman 2015]).
Maternal use of a serotonin reuptake inhibitor (SRI) during pregnancy may delay lactogenesis (Marshall 2010); however, the underlying maternal illness and various other factors may also influence this outcome. Patients who wish to breastfeed during treatment with an SRI may need additional assistance to initiate and maintain breastfeeding (Anderson 2021).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. The presence and concentration of the drug in breast milk, efficacy of maternal treatment, and infant age should be considered when initiating a medication for the first time postpartum (ABM [Sriraman 2015]; BAP [McAllister-Williams 2017]). When first initiating an antidepressant in a patient who is treatment naive and breastfeeding, agents other than SNRIs are preferred (ABM [Sriraman 2015]; CANMAT [MacQueen 2016]); however, desvenlafaxine may be considered as an alternative (CANMAT [MacQueen 2016]). Breastfeeding may be continued in patients treated with an SNRI during pregnancy (ABM [Sriraman 2015]; ACOG 2023). Treatment should not be withheld or discontinued based only on breastfeeding status (ACOG 2023).
Desvenlafaxine is the major active metabolite of venlafaxine; refer to the Venlafaxine monograph for additional information.
May be taken with or without food.
Renal function for dosing purposes; BP should be regularly monitored, especially in patients with a high baseline BP; lipid panel (eg, total cholesterol, LDL, triglycerides); closely monitor patients for depression, clinical worsening, suicidality, psychosis, or unusual changes in behavior (eg, anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania), particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases). Intraocular pressure should be monitored in those with baseline elevations or a history of glaucoma.
Desvenlafaxine is a potent and selective serotonin and norepinephrine reuptake inhibitor.
Onset of action: Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009).
Distribution: Vd: 3.4 L/kg
Protein binding: 30%
Metabolism: Hepatic via conjugation (major pathway), and oxidation via CYP3A4 (minor pathway)
Bioavailability: ~80%
Half-life elimination: ~10 to 11 hours; prolonged in renal failure and hepatic failure
Excretion: Urine (45% as unchanged drug; ~24% as metabolites)
Altered kidney function: Elimination is correlated with creatinine clearance. The AUC increases about 42% in patients with mild renal impairment, about 56% in those with moderate renal impairment, about 108% in those with severe renal impairment, and about 116% in ESRD requiring hemodialysis. The mean terminal half-life is prolonged from 11.1 hour in control subjects to about 13.5, 15.5, 17.6, and 22.8 hours in those with mild, moderate, severe, and ESRD, respectively. Less than 5% of the drug is cleared during standard 4-hour hemodialysis.
Hepatic function impairment: Average AUC is increased by about 31% and 35% in patients with moderate and severe hepatic impairment, respectively. Clearance is decreased about 20% and 36% in patients with moderate and severe hepatic impairment, respectively. The mean half-life increased from 10 hours in healthy subjects to 13 and 14 hours in patients with moderate and severe hepatic impairment, respectively. Average AUC, clearance and mean half-life is similar in patients with mild hepatic impairment and healthy subjects.
Older adult: There is an increase in the AUC and Cmax of about 55% and 32%, respectively, in patients >75 years of age compared with patients 18 to 45 years of age. Patients 65 to 75 years of age had a 32% increase in AUC but no change in Cmax compared with patients 18 to 45 years of age.
Sex: There is an increase in the AUC and Cmax of about 10% and 25%, respectively, in women compared with men.
