Effexor Xr

— THERAPEUTIC CATEGORIES —
  • Anxiety/OCD
  • Mood disorders
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Effexor Xr Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Venlafaxine (as HCl) 37.5mg, 75mg, 150mg; ext-rel caps.

    Pharmacological Class

    SNRI.

    See Also

      How Supplied

      XR caps—15, 30, 90

      How Supplied

      Effexor XR is supplied in 15-, 30-, and 90-count bottles, and a carton of 10 Redipak blister strips of 10 capsules each. Effexor XR is available in the following strengths:

      • 37.5 mg – grey cap/peach body with “W” and “Effexor XR” on the cap and “37.5” on the body

      • 75 mg –  peach cap and body with “W” and “Effexor XR” on the cap and “75” on the body

      • 150 mg –  dark orange cap and body with “W” and “Effexor XR” on the cap and “150” on the body

      Storage

      Store at controlled room temperature, 20° to 25°C (68° to 77°F). 

      Manufacturer

      Pfizer Inc.

      Generic Availability

      YES

      Mechanism of Action

      Preclinical studies have shown that venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake.

      Effexor Xr Indications

      Indications

      Generalized anxiety disorder (GAD). Social anxiety disorder (SAD). Panic disorder (PD).

      Effexor Xr Dosage and Administration

      Prior to Treatment Evaluations

      Screen for personal or family history of bipolar disorder, mania, or hypomania.

      Adult

      Take with food. Swallow whole or sprinkle contents on spoonful of applesauce; do not chew. GAD: Initially 75mg once daily; may start at 37.5mg once daily for 4–7 days before increasing to 75mg/day; may increase by increments of up to 75mg/day at intervals of at least 4 days. SAD: 75mg once daily. PD: Initially 37.5mg once daily for 7 days, then may increase to 75mg/day; then may increase in increments of up to 75mg/day at intervals of at least 7 days. For GAD or PD: usual max 225mg/day. Hepatic impairment: reduce by at least 50%. Renal impairment (mild or moderate): reduce by 25–50%; (severe or undergoing hemodialysis): reduce dose by at least 50%. Withdraw gradually (reduce by 75mg/day at 1-week intervals).

      Children

      Not established.

      Renal impairment

      Mild (CrCl 60-89 mL/min) or moderate (CrCl 30-59 mL/min) renal impairment: reduce the Effexor XR total daily dose by 25% to 50%.

      Severe renal impairment (CrCl <30 mL/min) or patients undergoing hemodialysis: reduce the Effexor XR total daily dose by 50% or more.

      Hepatic Impairment

      Mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment: reduce the Effexor XR total daily dose by 50%.

      Severe hepatic impairment (Child-Pugh Class C) or hepatic cirrhosis: reduce the Effexor XR total daily dose by 50% or more.

      Administration

      Swallow whole or sprinkle contents on spoonful of applesauce; do not chew.

      Nursing Considerations

      Alert patients and caregivers to monitor for the emergence of unusual behaviors, worsening depression, or suicidal ideation.

      Effexor Xr Contraindications

      Contraindications

      During or within 14 days of MAOIs (see Interactions). Concomitant linezolid or IV methylene blue.

      Effexor Xr Boxed Warnings

      Boxed Warning

      Suicidal thoughts and behaviors.

      Boxed Warning

      Suicidal Thoughts and Behaviors 

      • Increased risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies.

      • Monitor closely for clinical worsening, and emergence of suicidal thoughts and behaviors.

      • Not approved for use in pediatric patients.

      Effexor Xr Warnings/Precautions

      Warnings/Precautions

      Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; monitor closely for clinical worsening or unusual changes. Screen for bipolar disorder, mania or hypomania prior to initiation. Monitor for serotonin syndrome; discontinue immediately if occurs. Pre-existing hypertension, cardio- or cerebrovascular disease. Monitor BP before and during treatment; consider dose reduction or discontinuation if elevated BP persists. Heart disease (eg, recent MI, heart failure). Risk for bleeding events. Angle-closure glaucoma. Avoid in those with untreated anatomically narrow angles. History of mania/hypomania. Seizure disorders. Volume-depleted. Hyponatremia (esp. in elderly). Sexual dysfunction. Renal or hepatic dysfunction. Avoid abrupt disruption; monitor. Reevaluate periodically. Write ℞ for smallest practical amount. Elderly. Labor & delivery. Pregnancy; see full labeling for effects on mother and neonates. Nursing mothers.

      Warnings/Precautions

      Suicidal Thoughts and Behaviors in Adolescents and Young Adults

      • The risk of suicidal thoughts and behaviors in children, adolescents, and young adults is unknown with long-term use (eg, beyond 4 months).

      • Monitor all patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months and at times of dosage changes.

      • Counsel caregivers or family members to monitor for changes in behavior and to alert the healthcare provider.

      • If depression is persistently worse or who are experiencing emergent suicidal thoughts or behaviors, consider changing the therapeutic regimen, including discontinuing treatment.

      Serotonin Syndrome

      • See Interactions.

      • Risk of life-threatening serotonin syndrome: increased risk when Effexor XR is used concomitantly with other serotonergic drugs (including triptans, TCAs, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and drugs that impair metabolism of serotonin (eg, MAOIs).

      • Do not initiate in patients who are being treated with MAOIs (eg, linezolid or IV methylene blue). If concomitant use is necessary with an MAOI, discontinue Effexor XR before initiation of MAOI.

      • Monitor for emergence of serotonin syndrome.

      • Discontinue immediately if serotonin syndrome occurs and initiate supportive symptomatic treatment.

      Elevated Blood Pressure

      • Monitor blood pressure prior to initiation and regularly during treatment. Control pre-existing hypertension prior to initiation.

      • Use caution in patients with pre-existing hypertension or cardiovascular or cerebrovascular conditions.

      • Consider reducing dose or discontinuing treatment if sustained increase in blood pressure occurs.

      Increased Risk of Bleeding  

      • See Interactions.

      • Concomitant use with aspirin, NSAIDs, warfarin, other anticoagulants or other drugs known to affect platelet function may increase the risk of bleeding.

      • Advise patients about the increased risk of bleeding when Effexor XR is coadministered with NSAIDs, aspirin, or other drugs. 

      • If Effexor XR is used with warfarin, monitor coagulation indices when initiating, titrating, or discontinuing Effexor XR.

      Angle-Closure Glaucoma 

      • Effexor XR may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

      • Avoid use in patients with untreated anatomically narrow angles.

      Activation of Mania or Hypomania

      • Treatment with Effexor XR may precipitate a mixed/manic episode.

      • Screen for any personal or family history of bipolar disorders, mania, or hypomania prior to initiating treatment with Effexor XR.

      Discontinuation Syndrome

      • Monitor for discontinuation symptoms when discontinuing treatment with Effexor XR.

      • A gradual dosage reduction is recommended. Do not abruptly discontinue Effexor XR.

      Seizures

      • Use caution in patients with a seizure disorder.

      Hyponatremia

      • Greater risk of developing hyponatrema with SNRIs in elderly patients, patients taking diuretics, or those who are otherwise volume-depleted.

      • Consider discontinuing treatment with Effexor XR in patients with symptomatic hyponatremia, and institute appropriate medical intervention.

      Weight and Height Changes in Pediatric Patients  

      • Effexor XR is not approved for use in pediatric patients.

      Interstitial Lung Disease and Eosinophilic Pneumonia 

      • Rare reports of interstitial lung disease and eosinophilic pneumonia.

      • If this occurs, patients should undergo a prompt medical evaluation and consider discontinuing Effexor XR.

      Sexual Dysfunction

      • SNRIs, including Effexor XR, may cause symptoms of sexual dysfunction.

      • Prescribers should inquire about sexual function prior to initiation and about changes in sexual function during treatment.

      Pregnancy Considerations

      Pregnancy Exposure Registry 

      Risk Summary 

      • Available data from published epidemiologic studies on use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse fetal outcomes.

      • Available data from observational studies with venlafaxine have identified a potential increased risk for preeclampsia when used during mid to late pregnancy; exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage.

      Clinical Considerations

      • Disease-Associated Maternal and/or Embryo/Fetal Risk: Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.

      • Maternal Adverse Reactions: Use in mid to late pregnancy may increase the risk for preeclampsia, and exposure to SNRIs near delivery may increase the risk of postpartum hemorrhage.

      • Fetal/Neonatal Adverse Reactions: Neonates exposed to SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Monitor neonates exposed to Effexor XR in the third trimester of pregnancy for drug discontinuation syndrome.

      Nursing Mother Considerations

      Risk Summary

      • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Effexor XR and any potential adverse effects on the breastfed child or from the underlying maternal condition.

      Pediatric Considerations

      Safety and efficacy have not been established.

      Geriatric Considerations

      No overall differences in efficacy or safety were observed between elderly patients and younger patients.

      Greater sensitivity of some older individuals cannot be ruled out.

      Cases of clinically significant hyponatremia have been associated with elderly patients who may be at greater risk for this adverse event.

      Renal Impairment Considerations

      Dosage adjustment is recommended in patients with mild (CrCl = 60–89 mL/min), moderate (CrCl = 30–59 mL/min), or severe (CrCl <30 mL/min) renal impairment, and in patients undergoing hemodialysis.

      Hepatic Impairment Considerations

      Dosage adjustment is recommended in patients with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe (Child-Pugh Class C) hepatic impairment or hepatic cirrhosis.

      Effexor Xr Pharmacokinetics

      Absorption

      Venlafaxine is well absorbed. At least 92% of a single oral dose of venlafaxine is absorbed.

      Absolute bioavailability is ~45%.

      Distribution

      Venlafaxine is 27% and O-desmethylvenlafaxine (ODV) is 30% bound to plasma proteins. Apparent volume of distribution at steady-state is 7.5 ± 3.7 L/kg for venlafaxine and 5.7 ± 1.8 L/kg for ODV.

      Metabolism

      Following absorption, venlafaxine undergoes extensive presystemic metabolism in the liver, primarily to O-desmethylvenlafaxine (ODV), but also to N-desmethylvenlafaxine, N,O-didesmethylvenlafaxine, and other minor metabolites. 

      Elimination

      Renal (87%). Half-life: 5±2 hours (for venlafaxine); and 11±2 hours (for O-desmethylvenlafaxine). Mean ± SD plasma apparent clearance at steady-state: 1.3±0.6 L/h/kg (for venlafaxine); and 0.4±0.2 L/h/kg (for O-desmethylvenlafaxine). 

       

      Effexor Xr Interactions

      Interactions

      See Contraindications. Allow at least 14 days after MAOI discontinuance before starting venlafaxine; allow at least 7 days after venlafaxine discontinuance before starting an MAOI. Increased risk of serotonin syndrome with concomitant other serotonergic drugs (eg, other SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, methadone, meperidine, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs such as linezolid, IV methylene blue). Avoid alcohol. Potentiated by CYP3A inhibitors; consider reducing dose of venlafaxine. Potentiates CYP2D6 substrates; consider reducing dose of substrate. Concomitant weight loss agents (eg, phentermine), serotonin precursors (tryptophan supplements): not recommended. Caution with other CNS drugs, cimetidine, haloperidol, diuretics, metoprolol, drugs that inhibit CYP2D6, CYP3A4. Increased risk of bleeding with aspirin, NSAIDs, warfarin, or other drugs that affect coagulation; monitor closely. False (+) urine immunoassay screening tests for PCP and amphetamine.

      Effexor Xr Adverse Reactions

      Adverse Reactions

      Nausea, somnolence, dry mouth, sweating, abnormal ejaculation, anorexia, constipation, erectile dysfunction, decreased libido, weight changes, dizziness, insomnia, headache, nervousness, asthenia, vasodilation, abnormal dreams or vision, tremor, yawn, ecchymosis; rare: interstitial lung disease, eosinophilic pneumonia.

      Effexor Xr Clinical Trials

      Clinical Trials

      Generalized Anxiety Disorder (GAD)

      Study 1 and 2

      • The efficacy of Effexor XR was based on two 8-week, placebo-controlled, fixed-dose studies (75 to 225 mg per day) in adult outpatients meeting DSM-IV criteria for GAD.

      • Study 1 showed that treatment with Effexor XR achieved superiority over placebo for the 75, 150, and 225 mg per day doses, as measured by the HAM-A total score, both the HAM-A anxiety and tension items, and the CGI scale. The 75 and 150 mg doses were not as consistently effective as the highest dose.

      • Study 2 showed that treatment with Effexor XR 75 and 150 mg per day were more effective compared to placebo. The 75 mg/day dose was more consistently effective vs the 150 mg/day dose.

      Study 3 and 4

      • Two 6-month studies evaluated Effexor XR doses of 37.5, 75, and 150 mg per day (Study 3) and the other evaluated Effexor XR doses of 75 to 225 mg per day (Study 4). 

      • Treatment with daily doses of Effexor XR 75 mg or higher were more effective vs placebo on the HAM-A total, both the HAM-A anxiety and tension items, and the CGI scale during 6 months of treatment.

       

      Social Anxiety Disorder (also known as Social Phobia)

      • The efficacy of Effexor XR was evaluated in 4 double-blind, parallel-group, 12-week, multicenter, placebo-controlled, flexible-dose studies (studies 1–4) and one  double-blind, parallel-group, 6-month, placebo-controlled, fixed/flexible-dose study, which included doses in a range of 75 to 225 mg per day in adult outpatients meeting DSM-IV criteria for SAD (study 5).

      • In all 5 studies, treatment with Effexor XR was statistically significantly more effective vs placebo on the Liebowitz Social Anxiety Scale (LSAS) total score. 

      • There was no evidence for any greater effectiveness of the 150 to 225 mg per day group vs 75 mg per day group in the 6-month study.

       

      Panic Disorder (PD)

      Study 1 and 2

      • The efficacy of Effexor XR was evaluated in 2 double-blind, 12-week, multicenter, placebo-controlled studies (study 1 and 2) in adult outpatients meeting DSM-IV criteria for PD with or without agoraphobia. Patients received fixed doses of 75 or 150 mg per day in Study 1, and 75 or 225 mg per day in Study 2.

      • Both studies showed that treatment with Effexor XR was statistically significantly more effective for each fixed dose vs placebo on PAAS, PDSS total score, and CGI Improvement scale.

      Study 3

      • The efficacy of Effexor XR was evaluated in a longer-term study (Study 3) in adult outpatients meeting DSM-IV criteria for PD who responded during a 12-week open phase with Effexor XR (75 to 225 mg per day). Patients were randomly assigned to continue the same Effexor XR dose (75, 150, or 225 mg) or switch to placebo for observation for relapse under double-blind conditions.

      • Response during the open phase was defined as ≤ 1 full-symptom panic attack per week during the last 2 weeks of the open phase and a CGI Improvement score of 1 (very much improved) or 2 (much improved).

      • Relapse during the double-blind phase was defined as having 2 or more full-symptom panic attacks per week for 2 consecutive weeks or having discontinued due to loss of effectiveness as determined by the investigators during the study.

      • Treatment with Effexor XR achieved a statistically significantly longer time to relapse vs placebo.

      Effexor Xr Note

      Not Applicable

      Effexor Xr Patient Counseling

      Patient Counseling

      Suicidal Thoughts and Behaviors

      • Advise to look for the emergence of suicidal ideation and behavior, especially early during treatment and dose adjustments. Report symptoms to healthcare provider.

      Concomitant Medication

      • Do not take Effexor with MAOI or within 14 days of stopping an MAOI.

      Serotonin Syndrome

      • Caution about the risk of serotonin syndrome. Report to emergency room if signs or symptoms of serotonin syndrome occur.

      Elevated Blood Pressure

      • Monitor blood pressure regularly while taking Effexor XR.

      Increased Risk of Bleeding

      • Use of Effexor XR with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may increase risk of bleeding.

      • Inform your healthcare provider of any prescription or OTC medications you are currently taking or plan to take.

      Activation of Mania/Hypomania

      • Look for signs of activation.

      Cardiovascular/Cerebrovascular Disease

      • Use caution in patients with cardiovascular, cerebrovascular, or lipid metabolism disorders.

      Serum Cholesterol and Triglyceride Elevation

      • Elevations in total cholesterol, LDL and triglycerides may occur and consider measuring serum lipids.

      Discontinuation Syndrome

      • Do not abruptly stop taking Effexor XR. Monitor for discontinuation symptoms.

      Sexual Dysfunction

      • May cause sexual dysfunction in male and female patients. Discuss any changes and potential management strategies with your healthcare provider.

      Interference with Cognitive and Motor Performance 

      • Use caution when operating hazardous machinery, including automobiles.

      Alcohol

      • Avoid alcohol during treatment.

      Allergic Reactions

      • Notify healthcare provider if allergic phenomena such as rash, hives, swelling, or difficulty breathing, develops.

      Pregnancy

      • Advise pregnant women that Effexor XR use during mid to late pregnancy may lead to an increased risk for preeclampsia. Use in late pregnancy may lead to an increased risk for postpartum hemorhage and may increase the risk for neonatal complications. 

      Residual Spheroids  

      • Effexor XR contains spheroids, which release the drug slowly into the digestive tract. 

      • Patients may notice spheroids passing in the stool or via colostomy. Patients should be informed that the active medication has already been absorbed by the time the patient sees the spheroids. 

      Cost Savings Program

      Effexor XR Savings Card

      Effexor Xr Generic Name & Formulations

      Legal Class

      Rx

      General Description

      Venlafaxine (as HCl) 37.5mg, 75mg, 150mg; ext-rel caps.

      Pharmacological Class

      SNRI.

      See Also

      How Supplied

      XR caps—15, 30, 90; Tabs—Contact supplier

      How Supplied

      Effexor XR is supplied in 15-, 30-, and 90-count bottles, and a carton of 10 Redipak blister strips of 10 capsules each. Effexor XR is available in the following strengths:

      • 37.5 mg – grey cap/peach body with “W” and “Effexor XR” on the cap and “37.5” on the body

      • 75 mg –  peach cap and body with “W” and “Effexor XR” on the cap and “75” on the body

      • 150 mg –  dark orange cap and body with “W” and “Effexor XR” on the cap and “150” on the body

       

      Storage

      Store at controlled room temperature, 20° to 25°C (68° to 77°F). 

      Manufacturer

      Pfizer Inc.

      Generic Availability

      YES

      Mechanism of Action

      Preclinical studies have shown that venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake.

      Effexor Xr Indications

      Indications

      Major depressive disorder (MDD).

      Effexor Xr Dosage and Administration

      Prior to Treatment Evaluations

      Screen for personal or family history of bipolar disorder, mania, or hypomania.

      Adult

      Take with food. Swallow whole or sprinkle contents on spoonful of applesauce; do not chew. Transferring from immediate-release: give total daily dose on once-daily basis. Initially 75mg once daily; may start at 37.5mg once daily for 4–7 days before increasing to 75mg/day; may increase by increments of up to 75mg/day at intervals of at least 4 days; usual max 225mg/day. Hepatic impairment: reduce by at least 50%. Renal impairment (mild or moderate): reduce by 25–50%; (severe or undergoing hemodialysis): reduce dose by at least 50%. Withdraw gradually (reduce by 75mg/day at 1-week intervals).

      Children

      Not established.

      Renal impairment

      Mild (CrCl 60-89 mL/min) or moderate (CrCl 30-59 mL/min) renal impairment: reduce the Effexor XR total daily dose by 25% to 50%.

      Severe renal impairment (CrCl <30 mL/min) or patients undergoing hemodialysis: reduce the Effexor XR total daily dose by 50% or more.

      Hepatic Impairment

      Mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment: reduce the Effexor XR total daily dose by 50%.

      Severe hepatic impairment (Child-Pugh Class C) or hepatic cirrhosis: reduce the Effexor XR total daily dose by 50% or more.

      Administration

      Swallow whole or sprinkle contents on spoonful of applesauce; do not chew.

      Nursing Considerations

      Alert patients and caregivers to monitor for the emergence of unusual behaviors, worsening depression, or suicidal ideation.

      Effexor Xr Contraindications

      Contraindications

      During or within 14 days of MAOIs (see Interactions). Concomitant linezolid or IV methylene blue.

      Effexor Xr Boxed Warnings

      Boxed Warning

      Suicidal thoughts and behaviors.

      Boxed Warning

      Suicidal Thoughts and Behaviors 

      • Increased risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies.

      • Monitor closely for clinical worsening, and emergence of suicidal thoughts and behaviors.

      • Not approved for use in pediatric patients.

      Effexor Xr Warnings/Precautions

      Warnings/Precautions

      Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; monitor closely for clinical worsening or unusual changes. Screen for bipolar disorder, mania or hypomania prior to initiation. Monitor for serotonin syndrome; discontinue immediately if occurs. Pre-existing hypertension, cardio- or cerebrovascular disease. Monitor BP before and during treatment; consider dose reduction or discontinuation if elevated BP persists. Heart disease (eg, recent MI, heart failure). Risk for bleeding events. Angle-closure glaucoma. Avoid in those with untreated anatomically narrow angles. History of mania/hypomania. Seizure disorders. Volume-depleted. Hyponatremia (esp. in elderly). Sexual dysfunction. Renal or hepatic dysfunction. Avoid abrupt disruption; monitor. Reevaluate periodically. Write ℞ for smallest practical amount. Elderly. Labor & delivery. Pregnancy; see full labeling for effects on mother and neonates. Nursing mothers.

      Warnings/Precautions

      Suicidal Thoughts and Behaviors in Adolescents and Young Adults

      • The risk of suicidal thoughts and behaviors in children, adolescents, and young adults is unknown with long-term use (eg, beyond 4 months).

      • Monitor all patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months and at times of dosage changes.

      • Counsel caregivers or family members to monitor for changes in behavior and to alert the healthcare provider.

      • If depression is persistently worse or who are experiencing emergent suicidal thoughts or behaviors, consider changing the therapeutic regimen, including discontinuing treatment.

      Serotonin Syndrome

      • See Interactions.

      • Risk of life-threatening serotonin syndrome: increased risk when Effexor XR is used concomitantly with other serotonergic drugs (including triptans, TCAs, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and drugs that impair metabolism of serotonin (eg, MAOIs).

      • Do not initiate in patients who are being treated with MAOIs (eg, linezolid or IV methylene blue). If concomitant use is necessary with an MAOI, discontinue Effexor XR before initiation of MAOI.

      • Monitor for emergence of serotonin syndrome.

      • Discontinue immediately if serotonin syndrome occurs and initiate supportive symptomatic treatment.

      Elevated Blood Pressure

      • Monitor blood pressure prior to initiation and regularly during treatment. Control pre-existing hypertension prior to initiation.

      • Use caution in patients with pre-existing hypertension or cardiovascular or cerebrovascular conditions.

      • Consider reducing dose or discontinuing treatment if sustained increase in blood pressure occurs.

      Increased Risk of Bleeding  

      • See Interactions.

      • Concomitant use with aspirin, NSAIDs, warfarin, other anticoagulants or other drugs known to affect platelet function may increase the risk of bleeding.

      • Advise patients about the increased risk of bleeding when Effexor XR is coadministered with NSAIDs, aspirin, or other drugs. 

      • If Effexor XR is used with warfarin, monitor coagulation indices when initiating, titrating, or discontinuing Effexor XR.

      Angle-Closure Glaucoma 

      • Effexor XR may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

      • Avoid use in patients with untreated anatomically narrow angles.

      Activation of Mania or Hypomania

      • Treatment with Effexor XR may precipitate a mixed/manic episode.

      • Screen for any personal or family history of bipolar disorders, mania, or hypomania prior to initiating treatment with Effexor XR.

      Discontinuation Syndrome

      • Monitor for discontinuation symptoms when discontinuing treatment with Effexor XR.

      • A gradual dosage reduction is recommended. Do not abruptly discontinue Effexor XR.

      Seizures

      • Use caution in patients with a seizure disorder.

      Hyponatremia

      • Greater risk of developing hyponatrema with SNRIs in elderly patients, patients taking diuretics, or those who are otherwise volume-depleted.

      • Consider discontinuing treatment with Effexor XR in patients with symptomatic hyponatremia, and institute appropriate medical intervention.

      Weight and Height Changes in Pediatric Patients  

      • Effexor XR is not approved for use in pediatric patients.

      Interstitial Lung Disease and Eosinophilic Pneumonia 

      • Rare reports of interstitial lung disease and eosinophilic pneumonia.

      • If this occurs, patients should undergo a prompt medical evaluation and consider discontinuing Effexor XR.

      Sexual Dysfunction

      • SNRIs, including Effexor XR, may cause symptoms of sexual dysfunction.

      • Prescribers should inquire about sexual function prior to initiation and about changes in sexual function during treatment.

      Pregnancy Considerations

      Pregnancy Exposure Registry 

      Risk Summary 

      • Available data from published epidemiologic studies on use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse fetal outcomes.

      • Available data from observational studies with venlafaxine have identified a potential increased risk for preeclampsia when used during mid to late pregnancy; exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage.

      Clinical Considerations

      • Disease-Associated Maternal and/or Embryo/Fetal Risk: Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.

      • Maternal Adverse Reactions: Use in mid to late pregnancy may increase the risk for preeclampsia, and exposure to SNRIs near delivery may increase the risk of postpartum hemorrhage.

      • Fetal/Neonatal Adverse Reactions: Neonates exposed to SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Monitor neonates exposed to Effexor XR in the third trimester of pregnancy for drug discontinuation syndrome.

      Nursing Mother Considerations

      Risk Summary

      • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Effexor XR and any potential adverse effects on the breastfed child or from the underlying maternal condition.

      Pediatric Considerations

      Safety and efficacy have not been established.

      Geriatric Considerations

      No overall differences in efficacy or safety were observed between elderly patients and younger patients.

      Greater sensitivity of some older individuals cannot be ruled out.

      Cases of clinically significant hyponatremia have been associated with elderly patients who may be at greater risk for this adverse event.

      Renal Impairment Considerations

      Dosage adjustment is recommended in patients with mild (CrCl = 60–89 mL/min), moderate (CrCl = 30–59 mL/min), or severe (CrCl <30 mL/min) renal impairment, and in patients undergoing hemodialysis.

      Hepatic Impairment Considerations

      Dosage adjustment is recommended in patients with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe (Child-Pugh Class C) hepatic impairment or hepatic cirrhosis.

      Effexor Xr Pharmacokinetics

      Absorption

      Venlafaxine is well absorbed. At least 92% of a single oral dose of venlafaxine is absorbed.

      Absolute bioavailability is ~45%.

      Distribution

      Venlafaxine is 27% and O-desmethylvenlafaxine (ODV) is 30% bound to plasma proteins. Apparent volume of distribution at steady-state is 7.5 ± 3.7 L/kg for venlafaxine and 5.7 ± 1.8 L/kg for ODV.

      Metabolism

      Following absorption, venlafaxine undergoes extensive presystemic metabolism in the liver, primarily to O-desmethylvenlafaxine (ODV), but also to N-desmethylvenlafaxine, N,O-didesmethylvenlafaxine, and other minor metabolites. 

      Elimination

      Renal (87%). Half-life: 5±2 hours (for venlafaxine); and 11±2 hours (for O-desmethylvenlafaxine). Mean ± SD plasma apparent clearance at steady-state: 1.3±0.6 L/h/kg (for venlafaxine); and 0.4±0.2 L/h/kg (for O-desmethylvenlafaxine). 

       

      Effexor Xr Interactions

      Interactions

      See Contraindications. Allow at least 14 days after MAOI discontinuance before starting venlafaxine; allow at least 7 days after venlafaxine discontinuance before starting an MAOI. Increased risk of serotonin syndrome with concomitant other serotonergic drugs (eg, other SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, methadone, meperidine, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs such as linezolid, IV methylene blue). Avoid alcohol. Potentiated by CYP3A inhibitors; consider reducing dose of venlafaxine. Potentiates CYP2D6 substrates; consider reducing dose of substrate. Concomitant weight loss agents (eg, phentermine), serotonin precursors (tryptophan supplements): not recommended. Caution with other CNS drugs, cimetidine, haloperidol, diuretics, metoprolol, drugs that inhibit CYP2D6, CYP3A4. Increased risk of bleeding with aspirin, NSAIDs, warfarin, or other drugs that affect coagulation; monitor closely. False (+) urine immunoassay screening tests for PCP and amphetamine.

      Effexor Xr Adverse Reactions

      Adverse Reactions

      Nausea, somnolence, dry mouth, sweating, abnormal ejaculation, anorexia, constipation, erectile dysfunction, decreased libido, weight changes, dizziness, insomnia, headache, nervousness, asthenia, vasodilation, abnormal dreams or vision, tremor, yawn, ecchymosis; rare: interstitial lung disease, eosinophilic pneumonia.

      Effexor Xr Clinical Trials

      Clinical Trials

      Major Depressive Disorder (MDD)

      Study 1 and 2

      • The efficacy of Effexor XR was based on 2 placebo-controlled, short-term (8 weeks for study 1; 12 weeks for study 2), flexible-dose studies, with doses starting at 75 mg per day and ranging to 225 mg per day in adult outpatients diagnosed with MDD. 

      • Moderately depressed patients were initiated with venlafaxine 75 mg/day.

      • Both studies showed that treatment with Effexor XR achieved superiority over placebo on the primary efficacy outcome, defined as change from baseline in the HAM-D-21 total score to the endpoint visit, and on the key secondary efficacy outcome, the Clinical Global Impressions (CGI) Severity of Illness scale.

      Study 3

      • The efficacy of Effexor XR was based on a 4-week study of inpatients diagnosed with MDD with melancholia, with doses of Effexor in a range of 150 to 375 mg/day (divided 3 times daily).

      • Treatment with Effexor achieved superiority over placebo based on the HAM-D-21 total score.

      Study 4

      • In the longer-term 26-week Study 4, adult outpatients with MDD who responded to an 8-week open-label study on Effexor XR (75, 150, or 225 mg once daily) were randomly assigned to continuation of their same Effexor XR dose or placebo.

      • Response during the open-label phase was defined as CGI Severity of Illness item score of at least 3 and a HAM-D-21 total score of less than or equal to 10 at the day 56 evaluation.

      • Relapse during the double-blind phase was defined as: (1) a reappearance of MDD as defined by DSM-IV criteria and a CGI Severity of Illness item score of at least 4 (moderately ill), (2) two consecutive CGI Severity of Illness item scores of at least 4, or (3) a final CGI Severity of Illness item score of ≥4 for any patient who withdrew from the study for any reason. 

      • Treatment with Effexor XR achieved statistically significantly lower relapse rates over 26 weeks vs placebo.

      Study 5

      • In the second longer-term 52-week Study 5, adult outpatients with MDD, recurrent type, who had responded (HAM-D-21 total score ≤12 at the day 56 evaluation) and continued to be improved were randomly assigned to continue the same Effexor dose or to placebo.

      • Treatment with Effexor XR achieved statistically significantly lower relapse rates over 56 weeks vs placebo.

      Effexor Xr Note

      Not Applicable

      Effexor Xr Patient Counseling

      Patient Counseling

      Suicidal Thoughts and Behaviors

      • Advise to look for the emergence of suicidal ideation and behavior, especially early during treatment and dose adjustments. Report symptoms to healthcare provider.

      Concomitant Medication

      • Do not take Effexor with MAOI or within 14 days of stopping an MAOI.

      Serotonin Syndrome

      • Caution about the risk of serotonin syndrome. Report to emergency room if signs or symptoms of serotonin syndrome occur.

      Elevated Blood Pressure

      • Monitor blood pressure regularly while taking Effexor XR.

      Increased Risk of Bleeding

      • Use of Effexor XR with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may increase risk of bleeding.

      • Inform your healthcare provider of any prescription or OTC medications you are currently taking or plan to take.

      Activation of Mania/Hypomania

      • Look for signs of activation.

      Cardiovascular/Cerebrovascular Disease

      • Use caution in patients with cardiovascular, cerebrovascular, or lipid metabolism disorders.

      Serum Cholesterol and Triglyceride Elevation

      • Elevations in total cholesterol, LDL and triglycerides may occur and consider measuring serum lipids.

      Discontinuation Syndrome

      • Do not abruptly stop taking Effexor XR. Monitor for discontinuation symptoms.

      Sexual Dysfunction

      • May cause sexual dysfunction in male and female patients. Discuss any changes and potential management strategies with your healthcare provider.

      Interference with Cognitive and Motor Performance 

      • Use caution when operating hazardous machinery, including automobiles.

      Alcohol

      • Avoid alcohol during treatment.

      Allergic Reactions

      • Notify healthcare provider if allergic phenomena such as rash, hives, swelling, or difficulty breathing, develops.

      Pregnancy

      • Advise pregnant women that Effexor XR use during mid to late pregnancy may lead to an increased risk for preeclampsia. Use in late pregnancy may lead to an increased risk for postpartum hemorhage and may increase the risk for neonatal complications. 

      Residual Spheroids  

      • Effexor XR contains spheroids, which release the drug slowly into the digestive tract. 

      • Patients may notice spheroids passing in the stool or via colostomy. Patients should be informed that the active medication has already been absorbed by the time the patient sees the spheroids. 

      Cost Savings Program

      Effexor XR Savings Card

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