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: Due to its short half-life, withdrawal symptoms are possible after abrupt discontinuation; consider tapering to avoid withdrawal and assess for symptom recurrence (Ref). Reasons for a slower taper (eg, over 4 weeks) include 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 gradual dosage reduction) of an antidepressant treatment that has lasted for >3 weeks, particularly a drug with a half-life <24 hours (eg, paroxetine, venlafaxine, desvenlafaxine) (Ref)
• Prior history of antidepressant withdrawal symptoms (Ref)
• High dose (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%), increased LDL cholesterol (increased by ≥50 mg/dL and ≥190 mg/dL: 1%), increased serum cholesterol (increased by ≥50 mg/dL and ≥261 mg/dL: 3% to 4%), increased serum prolactin (<2%), 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: Anorgasmia (males: 3%; females: 1%) (table 2) , delayed ejaculation (1% to 5%), ejaculation failure (1%), ejaculatory disorder (1%), erectile dysfunction (3% to 6%) (table 3) , male sexual disorder (1%), orgasm abnormal (males: 1%) (table 4) , proteinuria (5% to 8%), urinary hesitancy (≤1%), urinary retention (<2%)
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 |
Drug (Desvenlafaxine) |
Placebo |
Population |
Dose |
Number of Patients (Desvenlafaxine) |
Number of Patients (Placebo) |
---|---|---|---|---|---|
1% |
0% |
Males |
100 mg |
157 |
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%), dystonia (<2%), fatigue (7%), jitteriness (2%), seizure (<2%), vertigo (2%), yawning (1%)
Neuromuscular & skeletal: Muscle rigidity (<2%), tremor (3%)
Ophthalmic: Blurred vision (3% to 4%), mydriasis (2%)
Otic: Tinnitus (2%)
<1%: Nervous system: Mania (Shaban-Rodriquez 2018)
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) (Neil 2012)
Dermatologic: Stevens-Johnson syndrome
Endocrine & metabolic: Hyperglycemia (Mekonnen 2020), hyponatremia (SIADH) (Lee 2013, Liew 2014)
Gastrointestinal: Acute pancreatitis
Hematologic & oncologic: Acquired blood coagulation disorder (Shaligram 2010)
Nervous system: Abnormal behavior (oppositional behavior pediatric) (Findling 2014), serotonin syndrome (supratherapeutic doses) (Cooper 2017), suicidal ideation (Tourain 2010), suicidal tendencies (Tourain 2010), withdrawal syndrome (can be severe; including aggressive behavior, dyskinesia, homicidal ideation, hostility, outbursts of anger (Montgomery 2009; Wu 2019)
Respiratory: Interstitial pneumonitis (Flora 2018)
Hypersensitivity to desvenlafaxine, venlafaxine or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing the MAO inhibitor); initiation of MAO inhibitor intended to treat psychiatric disorders within 7 days of discontinuing desvenlafaxine; initiation of desvenlafaxine in a patient receiving linezolid or intravenous methylene blue
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:
• 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. [DSC] = Discontinued product
Tablet Extended Release 24 Hour, Oral:
Khedezla: 50 mg [DSC]
Khedezla: 100 mg [DSC] [contains fd&c yellow #6 (sunset yellow)]
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: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Some tablets may be small enough to swallow whole by individual program standards. If deemed too large to swallow whole, consider converting to venlafaxine XR capsule since that capsule can be opened and sprinkled onto soft food of choice.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Desvenlafaxine extended release tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/204150s018lbl.pdf#page=32
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the hepatotoxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. 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 enhance the serotonergic effect 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 therapy
Alosetron: May enhance the serotonergic effect 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 therapy
Alpha-/Beta-Agonists: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect 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 Inhibitors may diminish the therapeutic effect of Alpha2-Agonists. Risk C: Monitor therapy
Amphetamines: May enhance the serotonergic effect 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 therapy
Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect 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 therapy
Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy
Aspirin: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Brexanolone: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Risk X: Avoid combination
BusPIRone: May enhance the serotonergic effect 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 therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Cyclobenzaprine: May enhance the serotonergic effect 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 therapy
Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Dapoxetine: May enhance the serotonergic effect 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 combination
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect 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 therapy
Dextromethorphan: May enhance the serotonergic effect 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 therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Eletriptan: May enhance the serotonergic effect 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 therapy
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Ergot Derivatives: May enhance the serotonergic effect 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 therapy
Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
FentaNYL: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. 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 therapy
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Iobenguane Radiopharmaceutical Products: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the therapeutic effect 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 combination
Lasmiditan: May enhance the serotonergic effect 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 therapy
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Levomethadone: May enhance the serotonergic effect 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 therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Linezolid: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect 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 therapy
Meperidine: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. 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 therapy
Metaxalone: May enhance the serotonergic effect 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 therapy
Methadone: May enhance the serotonergic effect 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 therapy
Methylene Blue: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: May enhance the serotonergic effect 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 therapy
Mirtazapine: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. 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 therapy
Monoamine Oxidase Inhibitors (Antidepressant): May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Nefazodone: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. 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 therapy
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Topical). Risk C: Monitor therapy
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ondansetron: May enhance the serotonergic effect 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 therapy
Opioid Agonists: May enhance the serotonergic effect 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 therapy
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect 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 therapy
Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect 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 therapy
Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect 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 therapy
Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ramosetron: May enhance the serotonergic effect 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 therapy
Rasagiline: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Safinamide: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Serotonin/Norepinephrine Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. 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 therapy
Selegiline: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Serotonergic Agents (High Risk, Miscellaneous): Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect 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 therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect 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 therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of other Serotonin/Norepinephrine Reuptake Inhibitors. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect of other Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. 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 therapy
St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the 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 therapy
Syrian Rue: May enhance the serotonergic effect 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 therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
TraMADol: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the adverse/toxic effect 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 therapy
TraZODone: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. 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 therapy
Tricyclic Antidepressants: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect 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 therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Serotonin/Norepinephrine Reuptake Inhibitors may enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hyper- or hypotonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. Symptoms may be due to the toxicity of the SNRIs/SSRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with treatment. The long-term effects of in utero SNRI/SSRI exposure on infant development and behavior are not known.
The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy.
Desvenlafaxine is the major active metabolite of venlafaxine; also refer to the Venlafaxine monograph.
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Healthcare providers are encouraged to enroll patients in the National Pregnancy Registry for Antidepressants (1-844-405-6185).
Desvenlafaxine is present in breast milk.
In one study, the mean relative infant dose (RID) of desvenlafaxine was 6.8% (range: 5.5% to 8.1%) when compared to a weight adjusted maternal dose of 50 to 150 mg/day.
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 (Larsen 2015).
The mean RID of desvenlafaxine was calculated by the authors of a study using a mean milk concentration of 564 mcg/L (range: 351 to 777 mcg/L), providing an estimated daily infant dose via breast milk of 85 mcg/kg/day (range: 53 to 117 mcg/kg/day). This information is from a study of 10 mother-infant pairs at 0.9 to 12.7 months postpartum (mean: 4.3 months) following maternal use of desvenlafaxine 50 or 100 mg extended-release tablets once daily with maternal doses ranging from 50 to 150 mg/day. Desvenlafaxine could also be detected in infant serum (Rampono 2011).
Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015).
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. When first initiating an antidepressant in a breastfeeding female, agents other than desvenlafaxine are preferred (Berle 2011).
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); signs/symptoms of serotonin syndrome such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, diaphoresis), neuromuscular changes (eg, tremor, rigidity, myoclonus), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures; 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.
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