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Desvenlafaxine

Pronunciation

Pronunciation

(des ven la FAX een)

Index Terms

  • O-desmethylvenlafaxine
  • ODV

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Khedezla: 50 mg

Khedezla: 100 mg [contains fd&c yellow #6 (sunset yellow)]

Generic: 50 mg, 100 mg

Tablet Extended Release 24 Hour, Oral, as fumarate [strength expressed as base]:

Generic: 50 mg, 100 mg

Tablet Extended Release 24 Hour, Oral, as succinate [strength expressed as base]:

Pristiq: 25 mg, 50 mg, 100 mg

Brand Names: U.S.

  • Khedezla
  • Pristiq

Pharmacologic Category

  • Antidepressant, Serotonin/Norepinephrine Reuptake Inhibitor

Pharmacology

Desvenlafaxine is a potent and selective serotonin and norepinephrine reuptake inhibitor.

Distribution

Vd: 3.4 L/kg

Metabolism

Hepatic via conjugation (major pathway), and oxidation via CYP3A4 (minor pathway)

Excretion

Urine (45% as unchanged drug; ~24% as metabolites)

Half-Life Elimination

~10 to 11 hours; prolonged in renal failure and hepatic failure

Protein Binding

30%

Special Populations: Renal Function Impairment

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.

Special Populations: 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.

Special Populations: Elderly

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.

Special Populations: Gender

There is an increase in the AUC and Cmax of about 10% and 25%, respectively, in women compared with men.

Use: Labeled Indications

Major depressive disorder: Treatment of major depressive disorder (MDD)

Contraindications

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

Dosing: Adult

Major depressive disorder (MDD): Oral: 50 mg once daily; doses up to 400 mg once daily have been studied and have shown to be effective; however, the manufacturer states there is no additional benefit at doses >50 mg per day. The Canadian labeling recommends a maximum dose of 100 mg daily.

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. The 25 mg tablet is intended for a gradual reduction in dose when discontinuing treatment. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Haddad 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).

Hot flashes (off-label use): 100 mg once daily; 150 mg once daily has also been studied and has shown to be effective, but has been associated with treatment discontinuation (Berhan 2014; Sun 2013). Titration during the first 1 to 2 weeks of therapy may help manage adverse effects at therapy initiation (Gallagher 2012).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of desvenlafaxine.

Allow 7 days to elapse between discontinuing desvenlafaxine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

US labeling:

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.

Canadian labeling:

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.

CrCl <30 mL/minute: 50 mg every other day (maximum)

ESRD requiring hemodialysis (HD): 50 mg every other day (maximum). Supplemental doses should not be given after HD.

Dosing: Hepatic Impairment

US labeling:

Mild impairment: No dosage adjustment necessary.

Moderate-to-severe impairment: Initial: 50 mg once daily; maximum dose: 100 mg once daily

Canadian labeling: No dosage adjustment necessary.

Administration

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).

Dietary Considerations

May be taken with or without food.

Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Specifically, risks of psychomotor impairment may be enhanced. Alcohol (Ethyl) may enhance the hepatotoxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Particularly duloxetine and milnacipran. Management: Patients receiving serotonin/norepinephrine reuptake inhibitors (SNRIs) should be advised to avoid alcohol. Monitor for increased psychomotor impairment and hepatotoxicity in patients who consume alcohol during treatment with SNRIs. Consider therapy modification

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. Consider therapy modification

Alpha2-Agonists: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine. Monitor therapy

Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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. Monitor therapy

ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor response. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification

Aspirin: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. 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. 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. Monitor therapy

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. 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. Monitor therapy

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

HYDROcodone: CYP3A4 Inducers (Weak) may decrease the serum concentration of HYDROcodone. Monitor therapy

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Iobenguane I 123: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Linezolid: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Avoid combination

MAO Inhibitors: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methylene Blue: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Metoclopramide: May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with serotonin/norepinephrine reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Monitor therapy

NSAID (Nonselective): Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (Nonselective). 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. Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

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. Monitor therapy

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

SAXagliptin: CYP3A4 Inducers may decrease the serum concentration of SAXagliptin. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Desvenlafaxine may enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk for bleeding may be increased. Monitor therapy

Test Interactions

May interfere with urine detection of phencyclidine and amphetamine (false-positive).

Adverse Reactions

Reported for 50 to 100 mg/day.

>10%:

Central nervous system: Dizziness (10% to 13%), insomnia (9% to 12%)

Dermatologic: Hyperhidrosis (10% to 11%)

Gastrointestinal: Nausea (22% to 26%), xerostomia (11% to 17%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (elderly 8%), syncope (<2%), tachycardia (<2%), hypertension (dose related; ≤1% of patients taking 50 to 100 mg daily had sustained diastolic BP ≥90 mm Hg)

Central nervous system: Drowsiness (≤9%), fatigue (7%), anxiety (3% to 5%), delayed ejaculation (1% to 5%), abnormal dreams (2% to 3%), anorgasmia (males ≤3%; females 1%), jitteriness (2%), depersonalization (<2%), dystonia (<2%), vertigo (≤2%), yawning (1%), disturbance in attention (≤1%), male sexual disorder (≤1%)

Dermatologic: Alopecia (<2%), skin photosensitivity (<2%), skin rash (<2%)

Endocrine & metabolic: Decreased libido (males 4% to 5%), increased serum cholesterol (increased by ≥50 mg/dL and ≥261 mg/dL: 3% to 4%), increased serum prolactin (<2%), weight gain (<2%), hot flash (1%), increased LDL cholesterol (increased by ≥50 mg/dL and ≥190 mg/dL: ≤1%)

Gastrointestinal: Constipation (9%), decreased appetite (5% to 8%), vomiting (≤4%), bruxism (<2%)

Genitourinary: Proteinuria (6% to 8%), erectile dysfunction (3% to 6%), urinary retention (<2%), ejaculation failure (≤1%), urinary hesitancy (≤1%)

Hepatic: Abnormal hepatic function tests (<2%)

Hypersensitivity: Angioedema (<2%)

Neuromuscular & skeletal: Tremor (≤3%), stiffness (<2%), weakness (<2%)

Ophthalmic: Blurred vision (3% to 4%), mydriasis (2%)

Otic: Tinnitus (≤2%)

Frequency not defined: Cardiovascular: Coronary occlusion, ischemic heart disease, myocardial infarction

<1% (Limited to important or life-threatening): Acute pancreatitis, angle-closure glaucoma, seizure, Stevens-Johnson syndrome

ALERT: U.S. Boxed Warning

Suicidal thoughts and behavior:

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. Closely monitor patients of all ages who are started on antidepressant therapy for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the health care provider. Desvenlafaxine is not approved for use in pediatric patients.

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants in children and teenagers should be dispensed with each prescription. Desvenlafaxine is not FDA approved for use in pediatric patients.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Anxiety/insomnia: May cause increase in anxiety, nervousness, and insomnia.

• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin or NSAIDs due to ulcerogenic potential. Data are inconclusive regarding extent of bleeding risk of SNRIs in combination with warfarin or other anticoagulants. Bleeding related to SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.

• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.

• Dyslipidemia: May cause significant dose-related increases in total cholesterol, LDL, and triglycerides; monitor.

• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda, 2013; Rizzoli, 2012).

• Hypertension: Dose-related increases in systolic and diastolic blood pressure have been documented. Monitor blood pressure regularly, and if sustained increases noted, consider dose reduction or discontinuation.

• Ocular effects: May cause mild pupillary dilation, which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

• Pulmonary events: Interstitial lung disease and eosinophilic pneumonia have been rarely reported with venlafaxine (the parent drug of desvenlafaxine). May present as progressive dyspnea, cough, and/or chest pain. Prompt evaluation and possible discontinuation of therapy may be necessary.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

• Sexual dysfunction: May cause or exacerbate sexual dysfunction.

• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L). Age (the elderly), volume depletion and/or concurrent use of diuretics likely increases risk. Discontinue treatment in patients with symptomatic hyponatremia.

Disease-related concerns:

• Cardiovascular disease: May cause sustained increase in blood pressure or heart rate. Control preexisting hypertension prior to initiation of desvenlafaxine. Use caution in patients with preexisting hypertension, cardiovascular conditions, or cerebrovascular disease. Hypertensive effect is dose related.

• Hepatic impairment: Use caution; clearance is decreased and average AUC is increased; the US labeling recommends a dosage adjustment in patients with hepatic impairment.

• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Desvenlafaxine is not FDA approved for the treatment of bipolar depression.

• Renal impairment: Use caution; clearance is decreased and plasma concentrations are increased; dosage reduction recommended in patients with severe renal impairment or end-stage renal disease.

• Seizure disorders: Use caution in patients with a previous seizure disorder.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: The elderly are at increased risk for orthostatic hypotension with therapy compared to younger adults.

Other warnings/precautions:

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA, 2010; Fava, 2006; Haddad, 2001; Shelton, 2001; Warner, 2006).

Monitoring Parameters

Renal function for dosing purposes; blood pressure should be regularly monitored, especially in patients with a high baseline blood pressure; lipid panel (eg, total cholesterol, LDL, triglycerides); signs/symptoms of serotonin syndrome; mental status for depression, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased). Intraocular pressure should be monitored in those with baseline elevations or a history of glaucoma.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. 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.

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, nausea, vomiting, constipation, dry mouth, sexual dysfunction, insomnia, fatigue, lack of appetite, or tablet shell in stool. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), severe headache, severe dizziness, passing out, angina, cough, shortness of breath, vision changes, eye pain, eye edema, eye redness, seizures, severe loss of strength and energy, or signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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