desvenlafaxine suc er 100 mg generic pristiq

Uses

Major Depressive Disorder

Desvenlafaxine succinate is used in the treatment of major depressive disorder in adults. The antidepressant efficacy of desvenlafaxine has been established in 4 randomized, double-blind, placebo-controlled, fixed-dose studies of 8 weeks' duration in adult outpatients who met DSM-IV criteria for major depressive disorder. In all of these studies, patients receiving desvenlafaxine (50-400 mg daily as extended-release tablets) demonstrated greater improvement in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score than did patients receiving placebo. Patients receiving desvenlafaxine also demonstrated greater overall improvement as measured by the Clinical Global Impressions Scale-Improvement (CGI-I) compared with placebo recipients in 3 out of 4 of these studies. In the 2 studies that directly compared 50 mg and 100 mg of desvenlafaxine given once daily, there was no evidence of a greater therapeutic effect at the higher 100-mg dosage. In addition, adverse effects and drug discontinuances were reported more frequently at higher dosages of the drug in these studies. No age- or gender-related differences in efficacy were noted in these studies; data were insufficient to determine whether there were race-related differences in efficacy.

The manufacturer states that the efficacy of desvenlafaxine for long-term use (i.e., exceeding 8 weeks) has not been established by controlled studies. If desvenlafaxine is used for extended periods, the need for continued therapy should be reassessed periodically.

For further information on treatment of major depressive disorder and considerations in choosing the most appropriate antidepressant for a particular patient, including considerations related to patient tolerance, patient age, and cardiovascular, sedative, and suicidal risks, .

Vasomotor Symptoms

Like some other SNRIs and SSRIs, desvenlafaxine succinate has been studied for the management of vasomotor symptoms in postmenopausal women.

For further information on treatment of vasomotor symptoms in postmenopausal women and women with breast cancer, .

Dosage and Administration

Administration

Desvenlafaxine succinate is administered orally once daily with or without food at approximately the same time each day. Extended-release tablets of the drug should be swallowed whole with fluid and should not be divided, crushed, chewed, or dissolved.

Patients receiving desvenlafaxine should be monitored for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.(See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

Discontinuance symptoms have been reported when switching patients from other antidepressants, including venlafaxine, to desvenlafaxine. When switching from another antidepressant to desvenlafaxine, it may be necessary to taper the dosage of the previous antidepressant to minimize discontinuance symptoms.(See Withdrawal of Therapy under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

The manufacturer recommends that at least 2 weeks elapse between discontinuance of a monoamine oxidase (MAO) inhibitor and initiation of desvenlafaxine and that at least 7 days elapse between discontinuance of desvenlafaxine and initiation of MAO inhibitor therapy.(See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions and see also Drug Interactions: Monoamine Oxidase Inhibitors.)

Dosage

Dosage of desvenlafaxine succinate is expressed in terms of desvenlafaxine.

Because withdrawal effects may occur, abrupt discontinuance of desvenlafaxine should be avoided whenever possible. When desvenlafaxine therapy is discontinued, dosage should be tapered gradually and the patient monitored to reduce the risk of withdrawal symptoms. If intolerable symptoms occur following dosage reduction or upon discontinuance of treatment, consider reinstituting desvenlafaxine therapy at the previously prescribed dosage until symptoms abate. Clinicians may resume dosage reductions at that time but at a more gradual rate.(See Withdrawal of Therapy under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Major Depressive Disorder

For the management of major depressive disorder, the recommended dosage of desvenlafaxine in adults is 50 mg once daily. Although efficacy has been established at dosages of 50-400 mg once daily in clinical studies, no additional benefit was observed with dosages greater than 50 mg once daily, and adverse effects and discontinuances were more frequent at higher dosages.

While the optimum duration of desvenlafaxine succinate therapy has not been established, many experts state that acute depressive episodes require several months or longer of sustained antidepressant therapy. However, the manufacturer states that long-term efficacy (i.e., exceeding 8 weeks) of desvenlafaxine at a dosage of 50 mg once daily has not been studied. If desvenlafaxine therapy is prolonged, the need for continued therapy should be reassessed periodically.

Special Populations

Although there are no specific dosage recommendations for desvenlafaxine in geriatric patients, the possibility of reduced renal clearance of the drug should be considered when determining dosage. If desvenlafaxine is poorly tolerated in such patients, administering the drug every other day can be considered.

In patients with hepatic impairment, the recommended desvenlafaxine dosage is 50 mg given once daily. Dosages exceeding 100 mg daily are not recommended.

In patients with mild renal impairment, desvenlafaxine dosage adjustment is not necessary. In patients with moderate renal impairment (creatinine clearance of 30-50 mL/minute), the recommended desvenlafaxine dosage is 50 mg given once daily. The recommended dosage in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) or end-stage renal disease is 50 mg given every other day. Desvenlafaxine dosage should not be increased in patients with moderate or severe renal impairment or end-stage renal disease. Supplemental doses should not be administered to patients after dialysis.

Treatment of Pregnant Women during the Third Trimester

Because some neonates exposed to venlafaxine and other SNRIs or SSRIs late in the third trimester of pregnancy have developed severe complications, consideration may be given to cautiously tapering desvenlafaxine therapy in the third trimester prior to delivery if the drug is administered during pregnancy.(See Pregnancy under Warnings/Precautions: Specific Populations, in Cautions.)

Cautions

Contraindications

Known hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride, or any ingredient in the desvenlafaxine succinate formulation.

Concurrent or recent (i.e., within 2 weeks) therapy with a monoamine oxidase (MAO) inhibitor. At least 7 days should elapse between discontinuance of desvenlafaxine and initiation of MAO inhibitor therapy.(See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric (see Pediatric Use under Cautions: Specific Populations) patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants. This risk may persist until clinically important remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term, placebo-controlled studies of antidepressants (i.e., selective serotonin-reuptake inhibitors and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders. An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults older than 24 years of age, and a reduced risk was observed in adults 65 years of age or older.

The US Food and Drug Administration (FDA) recommends that all patients being treated with antidepressants for any indication be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, also should be advised to monitor patients on a daily basis for the emergence of agitation, irritability, or unusual changes in behavior as well as the emergence of suicidality, and to report such symptoms immediately to a health-care provider.

Although a causal relationship between the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consequently, consideration should be given to changing the therapeutic regimen or discontinuing therapy in patients whose depression is persistently worse or in patients experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if such manifestations are severe, abrupt in onset, or were not part of the patient's presenting symptoms. FDA also recommends that the drugs be prescribed in the smallest quantity consistent with good patient management, in order to reduce the risk of overdosage.

Other Warnings and Precautions

Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions

Potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with selective serotonin-reuptake inhibitors (SSRIs) and SNRIs alone, including desvenlafaxine, but particularly with concurrent use of other serotonergic drugs (including serotonin [5-hydroxytryptamine; 5-HT] type 1 receptor agonists [''triptans'']), drugs that impair the metabolism of serotonin (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists. Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea). In its most severe form, serotonin syndrome may resemble neuroleptic malignant syndrome (NMS), which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients receiving desvenlafaxine should be monitored for the development of serotonin syndrome or NMS-like signs and symptoms.(See Contraindications and see also Drug Interactions.)

Concurrent or recent (i.e., within 2 weeks) therapy with MAO inhibitors used for treatment of depression is contraindicated.(See Contraindications and see also Drug Interactions: Monoamine Oxidase Inhibitors.)

If concurrent therapy with desvenlafaxine and a 5-HT₁ receptor agonist (triptan) is clinically warranted, the patient should be observed carefully, particularly during initiation of therapy, when dosage is increased, or when another serotonergic agent is initiated.

Concomitant use of desvenlafaxine and serotonin precursors (e.g., tryptophan) is not recommended.

If serotonin syndrome or NMS signs and symptoms occur, treatment with desvenlafaxine and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, should immediately be discontinued, and supportive and symptomatic treatment initiated.

Risk of Sustained Hypertension

Sustained increases in blood pressure have been reported. In controlled studies, sustained hypertension occurred in 0.7-2.3% of patients receiving desvenlafaxine dosages from 50-400 mg daily, with a suggestion of a higher incidence (2.3%) in those receiving 400 mg of the drug daily. In addition, some cases of elevated blood pressure requiring immediate treatment have been reported with desvenlafaxine.

Sustained blood pressure increases could have adverse consequences in patients receiving the drug. Therefore, the manufacturer recommends that preexisting hypertension be controlled before initiating desvenlafaxine therapy and that regular blood pressure monitoring be performed in patients receiving the drug. Desvenlafaxine should be used cautiously in patients with preexisting hypertension or other underlying conditions that may be compromised by increases in blood pressure. Dosage reduction or drug discontinuance should be considered in patients who experience a sustained increase in blood pressure during therapy.

Abnormal Bleeding

SSRIs and SNRIs, including desvenlafaxine, may increase the risk of bleeding events. Concurrent administration of aspirin, nonsteroidal anti-inflammatory agents, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiologic studies have demonstrated an association between the use of drugs that interfere with serotonin reuptake and the occurrence of GI bleeding. Bleeding events related to SSRI and SNRI use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. The manufacturer recommends that patients be advised of the risk of bleeding associated with the concomitant use of desvenlafaxine and aspirin or other nonsteroidal anti-inflammatory agents, warfarin, or other drugs that affect coagulation or bleeding.(See Drug Interactions: Drugs Affecting Hemostasis.)

Mydriasis

Mydriasis has been reported in association with desvenlafaxine therapy. Therefore, patients with elevated intraocular pressure or those at risk of angle-closure glaucoma should be monitored during treatment with the drug.

Activation of Mania/Hypomania

Activation of mania and hypomania reported in approximately 0.1% of desvenlafaxine-treated patients during clinical studies for major depressive disorder and vasomotor symptoms. Use with caution in patients with a personal or family history of mania or hypomania.

Patients with Cardiovascular/Cerebrovascular Disease

Increases in blood pressure and small increases in heart rate were reported in clinical studies. Desvenlafaxine has not been systematically evaluated in patients with a recent history of myocardial infarction, unstable cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease; patients with these diagnoses, except for cerebrovascular disease, were excluded from clinical studies. Therefore, the manufacturer advises using desvenlafaxine with caution in patients with cardiovascular, cerebrovascular, or lipid metabolism disorders.

Effects on Lipoproteins

Dose-dependent, possibly clinically significant increases in fasting serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides reported in controlled studies. Consider measuring serum lipid concentrations during desvenlafaxine therapy.

Withdrawal of Therapy

In clinical studies, abrupt discontinuance or dosage reduction of desvenlafaxine has been associated with the appearance of withdrawal effects, including dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, and hyperhidrosis, in patients with major depressive disorder. These symptoms generally occurred more frequently with longer duration of therapy. Withdrawal effects have also been reported upon discontinuance of other SNRIs and SSRIs, particularly when abrupt; these effects have included dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. While these events are generally self-limiting, there have been serious cases. Therefore, patients should be monitored for possible withdrawal symptoms when discontinuing desvenlafaxine therapy. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.(See Dosage and Administration: Dosage.)

Seizures

Seizures have been reported in premarketing clinical studies of desvenlafaxine. Desvenlafaxine has not been systematically evaluated in patients with seizure disorders; such patients were excluded from premarketing clinical studies. The manufacturer states that the drug should be used with caution in patients with a seizure disorder.

Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Secretion

Treatment with SSRIs and SNRIs, including desvenlafaxine, may result in hyponatremia. In many cases, hyponatremia appears to be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium concentrations lower than 110 mmol/L have been reported. Geriatric individuals and patients receiving diuretics or who are otherwise volume depleted may be at greater risk of developing hyponatremia. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls; more severe and/or acute cases have been associated with hallucinations, syncope, seizures, coma, respiratory arrest, and death. Initiate appropriate medical intervention and consider drug discontinuance in patients with symptomatic hyponatremia.

Concomitant Administration of Drugs Containing Desvenlafaxine and Venlafaxine

Desvenlafaxine is the major active metabolite of venlafaxine. The manufacturer states that products containing desvenlafaxine and products containing venlafaxine should not be used concomitantly with desvenlafaxine extended-release tablets (Pristiq).(See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Interstitial Lung Disease and Eosinophilic Pneumonia

Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (the parent drug of desvenlafaxine) have been reported rarely. The possibility of such adverse effects should be considered in patients treated with desvenlafaxine who present with progressive dyspnea, cough, or chest discomfort. Such patients should be evaluated promptly and discontinuance of desvenlafaxine should be considered.

Specific Populations

Pregnancy

Category C.

Some neonates exposed to SNRIs or SSRIs late in the third trimester of pregnancy have developed complications that have sometimes been severe and required prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in special-care nurseries. Such complications may arise immediately upon delivery and usually last several days or up to 2-4 weeks. Clinical findings reported to date in the neonates have included respiratory distress, cyanosis, apnea, seizures, temperature instability or fever, feeding difficulty, dehydration, excessive weight loss, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, reduced or lack of reaction to pain stimuli, and constant crying. These clinical features appear to be consistent with either a direct toxic effect of the SNRI or SSRI or, possibly, a drug withdrawal syndrome. It should be noted that, in some cases, the clinical picture was consistent with serotonin syndrome. When treating a pregnant woman with desvenlafaxine during the third trimester of pregnancy, the clinician should carefully consider the potential risks and benefits of such therapy. Consideration may be given to cautiously tapering desvenlafaxine therapy in the third trimester prior to delivery if the drug is administered during pregnancy.(See Treatment of Pregnant Women during the Third Trimester under Dosage and Administration: Special Populations.)

Lactation

Desvenlafaxine is excreted into human milk. Because of the potential for serious advere effects in nursing infants from desvenlafaxine, discontinue nursing or the drug, taking into account the importance of the drug to the woman. The manufacturer states that desvenlafaxine should only be administered to nursing women if the expected benefits outweigh any possible risk.

Pediatric Use

Safety and effectiveness of desvenlafaxine in pediatric patients younger than 18 years of age have not been established.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients younger than 19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

These findings should be carefully considered when assessing potential benefits and risks of desvenlafaxine in a child or adolescent for any clinical use.(See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

Geriatric Use

In clinical studies of desvenlafaxine, 5% of patients studied were 65 years of age or older. Although no overall differences in safety or efficacy were observed between geriatric and younger patients in these studies, a higher incidence of systolic orthostatic hypotension was reported in patients 65 years of age or older compared with younger patients in the short-term, placebo-controlled studies. Consider possible reduced renal clearance of the drug in geriatric patients.(See Dosage and Administration: Special Populations.) The possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.

SSRIs and SNRIs, including desvenlafaxine, have been associated with clinically important hyponatremia in geriatric patients, who may be at greater risk for this adverse effect.(See Hyponatremia/Syndrome of Inappropriate Antidiuretic Hormone Secretion under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults 65 years of age or older with antidepressant therapy compared with placebo.(See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)

Hepatic Impairment

Mean elimination half-life of desvenlafaxine is increased in patients with moderate or severe hepatic impairment compared with healthy individuals and patients with mild hepatic impairment. The recommended desvenlafaxine dosage in patients with hepatic impairment is 50 mg daily; dosages exceeding 100 mg daily are not recommended in such patients.(See Dosage and Administration: Special Populations.)

Renal Impairment

In patients with moderate or severe renal impairment or end-stage renal disease, clearance of desvenlafaxine was decreased, resulting in potentially clinically significant increases in drug exposure. Dosage adjustment is necessary in such patients.(See Dosage and Administration: Special Populations.)

Common Adverse Effects

Adverse effects reported in at least 5% of patients with major depressive disorder receiving desvenlafaxine (50 or 100 mg daily) and at an incidence of at least twice that reported with placebo in short-term clinical studies include nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and sexual function disorders in males (e.g., anorgasmia, decreased libido, abnormal orgasm, delayed ejaculation, erectile dysfunction, ejaculation disorder, ejaculation failure, and sexual dysfunction).

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Desvenlafaxine minimally inhibits the cytochrome P-450 (CYP) 2D6 isoenzyme. In a study in healthy adults, concurrent administration of desvenlafaxine (100 mg daily) and desipramine (single 50-mg dose), a CYP2D6 substrate, increased peak plasma concentrations and AUCs of desipramine by approximately 25 and 17%, respectively. The manufacturer states that concomitant use of desvenlafaxine with a drug metabolized by CYP2D6 can result in higher plasma concentrations of that drug.

Desvenlafaxine does not inhibit or induce the CYP3A4 isoenzyme in vitro. Concurrent administration of desvenlafaxine (400 mg daily; 8 times the recommended dosage) and midazolam (single 4-mg dose), a CYP3A4 substrate, decreased the AUC and peak plasma concentrations of midazolam by approximately 31 and 16%, respectively. The manufacturer states that concurrent use of desvenlafaxine with a drug metabolized by CYP3A4 can result in lower exposures to that drug.

Desvenlafaxine does not inhibit CYP isoenzymes 1A2, 2A6, 2C8, 2C9, and 2C19 in vitro and is unlikely to affect the pharmacokinetics of drugs that are metabolized by these CYP isoenzymes.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 is a minor pathway for the metabolism of desvenlafaxine. Concomitant administration of ketoconazole (200 mg twice daily), a CYP3A4 inhibitor, and a single 400-mg dose of desvenlafaxine resulted in a 43% increase in AUC and an 8% increase in peak plasma concentrations of desvenlafaxine. The manufacturer states that concurrent use of desvenlafaxine with other potent CYP3A4 inhibitors may result in higher plasma concentrations of desvenlafaxine.

Inhibitors of CYP isoenzymes 1A1, 1A2, 2A6, 2D6, 2C8, 2C9, 2C19, and 2E1: clinically important pharmacokinetic interaction is unlikely.

CNS-active Drugs

The risk of concurrent administration of desvenlafaxine and other CNS-active drugs has not been systematically evaluated to date; use with caution.

Monoamine Oxidase Inhibitors

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions). Concomitant use of monoamine oxidase (MAO) inhibitors with desvenlafaxine is contraindicated. In addition, at least 2 weeks should elapse between discontinuance of an MAO inhibitor and initiation of desvenlafaxine and at least 7 days should elapse between discontinuance of desvenlafaxine and initiation of MAO inhibitor therapy.(See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Serotonergic Drugs

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) with drugs affecting serotonergic neurotransmission, including linezolid (an anti-infective agent that is an MAO inhibitor), lithium, tramadol, and St. John's wort (Hypericum perforatum); use concomitantly with caution. If serotonin syndrome or NMS signs and symptoms occur, immediately discontinue treatment with desvenlafaxine and any concurrently administered serotonergic or antidopaminergic agents and initiate supportive and symptomatic treatment. Concurrent administration of desvenlafaxine and serotonin precursors (such as tryptophan) is not recommended.(See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Selective Serotonin-reuptake Inhibitors and Selective Serotonin- and Norepinephrine-reuptake Inhibitors

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions).(See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Desvenlafaxine is the major active metabolite of venlafaxine. The manufacturer states that products containing desvenlafaxine and products containing venlafaxine should not be used concomitantly with commercially available desvenlafaxine succinate extended-release tablets (Pristiq).

5-HT1 Receptor Agonists (''Triptans'')

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) if used concurrently with 5-HT₁ receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan). If concomitant therapy is clinically warranted, the patient should be observed carefully, particularly during treatment initiation, when dosage is increased, or when another serotonergic agent is initiated.(See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) if used concurrently with aspirin or other nonsteroidal anti-inflammatory agents, warfarin, or other drugs that affect coagulation or bleeding; use with caution.

Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs were concurrently administered with warfarin or other anticoagulants. The manufacturer recommends carefully monitoring patients receiving warfarin during initiation and discontinuance of desvenlafaxine therapy.

Antipsychotic Agents and Other Dopamine Antagonists

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) if used concurrently with antipsychotic agents or other dopamine antagonists. If serotonin syndrome or NMS signs and symptoms occur, immediately discontinue treatment with desvenlafaxine and any concurrently administered antidopaminergic or serotonergic agents and initiate supportive and symptomatic treatment.(See Serotonin Syndrome or Neuroleptic Malignant Syndrome [NMS]-like Reactions under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)

Drugs that are Substrates of or Inhibitors of P-glycoprotein Transport System

Desvenlafaxine is not a substrate or an inhibitor for the P-glycoprotein transporter in vitro. The pharmacokinetics of desvenlafaxine are unlikely to be affected by drugs that inhibit the P-glycoprotein transporter, and desvenlafaxine is not likely to affect the pharmacokinetics of drugs that are substrates of the P-glycoprotein transporter.

Alcohol

In a clinical study, desvenlafaxine did not increase impairment of mental and motor skills caused by alcohol. However, the manufacturer recommends avoiding concomitant alcohol consumption during desvenlafaxine therapy.

Electroconvulsive Therapy

The risks and/or benefits of combined use of electroconvulsive therapy and desvenlafaxine have not been evaluated.