Venlafaxine (Lexi-Drugs)

ALERT: US Boxed Warning
  Suicidality and antidepressant drugs:
Pronunciation

(ven la FAX een)

Brand Names: US

Effexor XR

Brand Names: Canada

ACT Venlafaxine XR; APO-Venlafaxine XR; Auro-Venlafaxine XR; DOM-Venlafaxine XR; Effexor XR; GD-Venlafaxine XR [DSC]; M-Venlafaxine XR; MYLAN-Venlafaxine XR [DSC]; PMS-Venlafaxine XR; RAN-Venlafaxine XR; RIVA-Venlafaxine XR; SANDOZ Venlafaxine XR; TEVA-Venlafaxine XR; Venlafaxine XR

Dosing: Adult

Episodic migraine prevention (off-label use): Oral: Extended release: Initial: 37.5 mg once daily for 3 days; increase based on response and tolerability by 75 mg increments to a target dose of 75 to 150 mg once daily (Bulut 2004; CHS [Pringsheim 2012]; EFNS [Evers 2009]).

Generalized anxiety disorder: Oral: Extended release: Initial: 37.5 to 75 mg once daily; in patients who are initiated at 37.5 mg once daily, increase to 75 mg once daily after 4 to 7 days; may then be increased by ≤75 mg/day increments at intervals of ≥4 days as tolerated; usual dosage: 75 to 225 mg once daily (maximum dose: 225 mg/day).

Major depressive disorder (unipolar): Oral:

Extended release: Initial: 37.5 to 75 mg once daily; in patients who are initiated at 37.5 mg once daily, may increase to 75 mg once daily after 4 to 7 days; thereafter, may increase dose in increments of ≤75 mg/day at intervals of ≥4 days based on response and tolerability (slower intervals of every 2 to 4 weeks are appropriate in less clinically urgent situations); usual dosage: 75 to 225 mg once daily (manufacturer’s maximum dose: 225 mg/day; guidelines support doses of up to 375 mg/day based on limited experience) (APA 2010). Some experts use more rapid titrations (every 2 to 3 days) in combination with an antipsychotic (eg, quetiapine) for patients with psychotic features (Wijkstra 2010).

Immediate release: Initial: 37.5 to 75 mg/day; daily doses >37.5 mg are administered in 2 or 3 divided doses; may increase dose in increments of ≤75 mg/day at intervals of ≥4 days based on response and tolerability (slower intervals of every 2 to 4 weeks are appropriate in less clinically urgent situations); usual dosage: 75 to 375 mg/day (APA 2010) (maximum dose: 375 mg/day).

Narcolepsy with cataplexy (off-label use): Limited data available: Oral: Immediate release and extended release: Some experts suggest doses of 37.5 to 75 mg twice daily (immediate release) or 37.5 to 150 mg once daily (extended release). Initiate at a low dose and gradually increase based on response and tolerability (Scammell 2018).

Neuropathic pain associated with diabetes mellitus (off-label use): Oral: Extended release: Initial: 37.5 mg or 75 mg once daily; increase by 75 mg each week to a maximum dosage of 225 mg once daily based on tolerance and effect. An adequate duration to determine effect and to accomplish titration has been documented to be 4 to 6 weeks (Bril 2011; Kadiroglu 2008; Rowbotham 2004).

Obsessive-compulsive disorder (alternative agent) (off-label use): Note: Alternative for patients with limited or no response to SSRI therapy (APA [Koran 2007]). Oral: Immediate release and extended release: Initial: 75 mg once daily for extended release or 75 mg/day in 3 divided doses for immediate release; increase in increments of 75 mg every 2 weeks to 225 mg/day. Increase further based on response and tolerability up to 350 mg/day (Albert 2002; APA [Koran 2007]; Denys 2003).

Panic disorder: Oral: Extended release: Initial: 37.5 mg once daily for 1 week; may increase to 75 mg once daily after 7 days, may then be increased by ≤75 mg/day increments at intervals of ≥7 days; usual dosage: 75 to 225 mg once daily (maximum dose: 225 mg/day).

Posttraumatic stress disorder (off-label use): Oral: Extended release: Initial: 37.5 mg once daily; increase based on response and tolerability by ≤75 mg/day increments at intervals of ≥4 days up to 300 mg once daily. Average doses in clinical trials were ~170 mg/day (Davidson 2006a; Davidson 2006b).

Premenstrual dysphoric disorder (alternative agent) (off-label use): Continuous daily dosing regimen: Oral: Extended release: Based on limited data, some experts suggest 37.5 mg once daily initially; over the first month, increase to a usual effective dose of 75 mg once daily; in subsequent menstrual cycles, further increases in dose (eg, in 37.5 mg increments per menstrual cycle) up to 150 mg/day may be necessary in some patients for optimal response (Casper 2019).

Social anxiety disorder: Oral: Extended release: Initial: 37.5 mg once daily; increase to 75 mg/day after 1 to 2 weeks (Stein 2018). May continue to increase in increments of 75 mg each week based on response and tolerability up to 225 mg once daily (Liebowitz 2005; Pollack 2014; Stein 2005); however, doses >75 mg/day have demonstrated greater adverse effects and without greater efficacy. Manufacturer’s labeling: Dosing in the prescribing information may not reflect current clinical practice: Initial and maximum dose: 75 mg/day.

Vasomotor symptoms associated with menopause (alternative agent) (off-label use): Note: Alternative for patients unable or unwilling to take estrogen (AACE [Goodman 2011]). Oral: Immediate release and extended release: Initial: 37.5 mg once daily; may increase dose after ≥1 week based on response and tolerability to 75 mg once daily for extended release or 75 mg/day in 2 to 3 divided doses for immediate release (AACE [Goodman 2011]; Evans 2005; Loibl 2007; Loprinzi 2000; Loprinzi 2006; NAMS 2015). Note: Doses up to 150 mg/day have been evaluated; however, compared to 75 mg/day, there was no greater efficacy and adverse effects were increased (Loprinzi 2000).

Dosing conversion: Patients treated with a therapeutic dose with venlafaxine immediate release may be switched to venlafaxine ER at the nearest equivalent dose (mg/day). Following the formulation switch, individual dosage adjustments may be necessary.

Discontinuation of therapy: When discontinuing antidepressants, gradually taper the dose (eg, over 2 to 4 weeks) to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower titration (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, high doses of antidepressants, or treatment duration >3 weeks (APA 2010; Hirsch 2018a). If intolerable withdrawal symptoms occur following a dose reduction, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, and pharmacodynamics), and the degree of symptom control desired (WFSBP [Bauer 2013]; Hirsch 2018b; Ogle 2013).

Switching to or from an MAOI:

Allow 14 days to elapse between discontinuing an MAOI and initiation of venlafaxine.

Allow 7 days to elapse between discontinuing venlafaxine and initiation of an MAOI according to manufacturer labeling; however, experts recommend a 14-day washout period before initiating an MAOI (APA 2010).

Dosing: Geriatric

Refer to adult dosing. No specific recommendations for elderly; use with caution.

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Renal Impairment: Adult

Extended release:

CrCl 30 to 89 mL/minute: Reduce total daily dose by 25% to 50%.

CrCl <30 mL/minute: Reduce total daily dose by 50% or more.

Hemodialysis: Reduce total daily dose by 50% or more.

Immediate release:

GFR 10 to 70 mL/minute: Reduce total daily dose by 25%.

GFR <10 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Hemodialysis: Reduce total daily dose by 50%.

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child-Pugh class A and B): Reduce total daily dose by 50%. There is variability in clearance for patients with cirrhosis; therefore, a reduction in total daily dose of more than 50% may be necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling; however, a reduction in total daily dose of at least 50% or more is prudent in patients with cirrhosis.

Dosing: Pediatric

Attention-deficit/hyperactivity disorder (ADHD): Limited data available: Children and Adolescents 8 to <17 years: Oral: Immediate release: Initial: 12.5 mg then titrate: Children <40 kg: Increase by 12.5 mg/week to maximum daily dose: 50 mg/day in 2 divided doses or Children ≥40 kg: Increase by 25 mg/week to maximum daily dose: 75 mg/day in 3 divided doses. Dosing based on an open-label clinical 5-week trial of 16 children and adolescents (mean age: 11.6 ± 2.3 years); mean dose: 60 mg/day (1.4 mg/kg/day) in 2 to 3 divided doses; ten patients completed the study [2 were lost to follow-up; 5 discontinued therapy due to adverse effects (4 had an increase in hyperactivity; 1 had severe nausea)]; venlafaxine decreased behavioral symptoms (but not cognitive symptoms) in 7 of 16 subjects (44%) (Olvera 1996). An initial dose of 37.5 mg given 3 times/day was used in an 11-year-old female with ADHD; the dose was slowly titrated to 100 mg given 3 times/day; after 6 weeks the patient showed moderate to marked improvement in symptoms, but developed hypertension; the dose was then decreased to 75 mg given 3 times/day with normalization of blood pressure (Pleak 1995).

Autism spectrum disorders: Limited data available: Children ≥ 3 years and Adolescents: Oral: Immediate release: One retrospective report is available; 10 patients (3 to 21 years of age; mean 10.5 ± 5.6 years) with autism spectrum disorders (autism, Asperger’s syndrome, and pervasive developmental disorders not otherwise specified) received initial doses of 12.5 mg/day administered once daily at breakfast; doses were gradually titrated based on clinical response and side effects; mean final dose: 24.4 mg/day; range: 6.25 to 50 mg/day; 6 of the 10 patients were sustained-treatment responders (Hollander 2000).

Depression: Limited data available: Children ≥7 years and Adolescents ≤17 years: Note: Due to the lack of demonstrated efficacy and concerns about an increased risk for suicidal behavior, venlafaxine should be reserved for pediatric patients with major depression who do not respond to fluoxetine or sertraline (Dopheide 2006). Oral:

Immediate release: One double-blind, placebo-controlled, 6-week study is available; 33 children and adolescents (8 to 17 years of age) with major depression completed the trial (16 received venlafaxine; for children 8 to 12 years, doses were initiated at 12.5 mg once daily for 3 days, then increased to 12.5 mg twice daily for 3 days, then increased to 12.5 mg given 3 times/day for the rest of the study; for adolescents 13 to 17 years, doses were initiated at 25 mg once daily for 3 days, then increased to 25 mg twice daily for 3 days, then increased to 25 mg given 3 times/day for the rest of the study; both venlafaxine and placebo patients improved over time; however, no significant difference in symptoms was noted between groups (ie, venlafaxine did not have a significant effect on symptoms or specific behaviors); the authors suggest this lack of efficacy may be due to the low doses used and short duration of treatment (Mandoki 1997).

Extended release: A large multicenter double-blind, placebo-controlled study of venlafaxine-ER in children and adolescents 7 to 17 years of age with major depression is ongoing; this study is using higher doses; initial: 37.5 mg/day for 1 week; with increases to 75 mg/day for weeks 2 to 8; results are not yet available (Weller 2000). One report of two 16-year-old patients used higher doses of venlafaxine (final doses: 112.5 mg/day and 150 mg/day) in combination with lithium to successfully treat major depression (Walter 1998).

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 reemerging symptoms. 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).

In clinical studies with extended-release venlafaxine, tapering was achieved by reducing the daily dose by 75 mg at 1-week intervals.

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 venlafaxine.

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

Use with other MAO inhibitors (linezolid or IV methylene blue):

Do not initiate venlafaxine in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.

If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving venlafaxine and potential benefits outweigh potential risks, discontinue venlafaxine promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume venlafaxine 24 hours after the last dose of linezolid or IV methylene blue.

Dosing: Renal Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested.

Use: Labeled Indications

Generalized anxiety disorder (extended-release capsules only): Treatment of generalized anxiety disorder (GAD)

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

Panic disorder (extended-release capsules only): Treatment of panic disorder, with or without agoraphobia

Social anxiety disorder (extended-release capsules and tablets only): Treatment of social anxiety disorder, also known as social phobia

Use: Off-Label: Adult

  Episodic migraine preventionLevel of Evidence [C, G]

Data from a limited number of small clinical trials suggest that venlafaxine may be beneficial for the prevention of migraine Ref.

The European Federation of Neurological Societies recommends venlafaxine as a second-line therapy and the American Academy of Neurology and American Headache Society classifies venlafaxine as probably effective for migraine prevention. The Canadian Headache Society guidelines give venlafaxine a weak recommendation for use in migraine prophylaxis and suggest it may be a preferable option in patients with depression or anxiety. Access Full Off-Label Monograph

  Narcolepsy with cataplexyLevel of Evidence [G]

Based on the American Academy of Sleep Medicine practice parameters for the treatment of narcolepsy and other hypersomnias of central origin, venlafaxine given for cataplexy may be effective based on clinical experience, committee consensus, and a case study of 4 patients.

  Neuropathic pain associated with diabetes mellitusLevel of Evidence [B, G]

Venlafaxine has been evaluated in the management of diabetic neuropathy in controlled trials and meta-analyses demonstrating favorable effects in pain intensity and relief Ref.

European Federation of Neurological Societies (EFNS) guidelines consider venlafaxine first-line therapy in the management of diabetic neuropathy, supported by strong evidence Ref. Guidelines from the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation state that venlafaxine is probably effective and should be considered alternative treatment for painful diabetic neuropathy Ref. Similarly, a position statement by the American Diabetes Association recommends venlafaxine as a second-line option RefAccess Full Off-Label Monograph

  Obsessive-compulsive disorderLevel of Evidence [C, G]

Data from a limited number of active comparator clinical trials suggest that venlafaxine may be beneficial for the treatment of obsessive-compulsive disorder (OCD) Ref.

Based on the American Psychiatric Association practice guidelines for the treatment of patients with OCD and the Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders, venlafaxine may be considered in patients with OCD and little or no response to SSRI monotherapy or an SSRI in combination with cognitive behavior therapy Ref.

  Posttraumatic stress disorderLevel of Evidence [B, G]

Data from two randomized, double-blind trials support the use of venlafaxine in the treatment of posttraumatic stress disorder (PTSD) for the symptoms of reexperiencing, avoidance and numbing, and hyperarousal Ref.

Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders and the American Psychiatric Association guideline watch (March 2009) on the practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder, venlafaxine given for PTSD is an effective and recommended treatment option in the management of this condition. Based on the VA/DoD guidelines for the management of PTSD and acute stress disorder, venlafaxine is effective and recommended as monotherapy in patients who cannot or choose not to engage in trauma-focused psychotherapy.

  Premenstrual dysphoric disorderLevel of Evidence [C]

Data from a limited number of patients studied suggest that venlafaxine may be beneficial for the treatment of premenstrual dysphoric disorder RefAccess Full Off-Label Monograph

  Vasomotor symptoms associated with menopauseLevel of Evidence [A, G]

Data from several randomized controlled studies support the efficacy of venlafaxine for the reduction of hot flash frequency and/or severity in women with natural or medically induced menopause Ref.

Based on the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) position statement on menopause, the Endocrine Society (ES) clinical practice guideline on the treatment of symptoms of menopause, and the North American Menopause Society (NAMS) position statement on nonhormonal management of menopause-associated vasomotor symptoms, SNRIs (including venlafaxine) are an effective and recommended alternative for the management of vasomotor symptoms associated with menopause in patients with contraindications to hormonal therapy or who prefer not to use hormonal therapy. Based on the American Cancer Society (ACS)/American Society of Clinical Oncology (ASCO) breast cancer survivorship care guideline, SNRIs may be used to help mitigate vasomotor symptoms of premature menopause in women previously treated for breast cancer. Access Full Off-Label Monograph

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Anxiety Disorders:

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Panic Disorder,” 2009

Anxiety Disorders Association of Canada, “Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders,” 2014

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in primary care,” 2012

Attention Deficit Hyperactivity Disorder (ADHD):

AHA, “Cardiovascular Monitoring of Children and Adolescents with Heart Disease Receiving Medications for Attention Deficit/Hyperactivity Disorder,” April 2008

American Academy of Child and Adolescent Psychiatry, “Attention-Deficit/Hyperactivity Disorder,” 2007

American Academy of Pediatrics, “ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents,” 2011

National Collaborating Centre for Mental Health, “Attention Deficit Hyperactivity Disorder, NICE Guidelines,” 2009

Bipolar Disorder:

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD), “Collaborative Update of CANMAT Guidelines for the Management of Patients with Bipolar Disorder – Update 2013,” February 2013

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2009 on the Treatment of Acute Mania,” 2009

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the Treatment of Acute Bipolar Depression,” 2010

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the Long-term Treatment of Bipolar Disorder,” 2013

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

Canadian Network for Mood and Anxiety Treatments (CANMAT), “2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments,” 2016

National Collaborating Centre for Mental Health (NCCMH), “Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated Edition).” 2010.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder and Treatment of Chronic Depressive Disorders and Subthreshold Depressions,” 2002.

Diabetic Neuropathy:

American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine and American Academy of Physical Medicine and Rehabilitation,“Evidence-Based Guideline: Treatment of Painful Diabetic Neuropathy,” April 2011

American Diabetes Association, “Diabetic Neuropathy: A Position Statement by the American Diabetes Association,” January 2017

European Federation of Neurological Societies, “EFNS Guidelines on the Pharmacological Treatment of Neuropathic Pain: 2010 Revision,” September 2010

Menopause:

American Association of Clinical Endocrinologists (AACE), “Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Menopause,” 2011

Endocrine Society (ES), Treatment of Symptoms of the Menopause, 2015

North American Menopause Society (NAMS), Nonhormonal management of menopause-associated vasomotor symptoms, 2015

Migraine Prophylaxis:

American Academy of Neurology and American Headache Society, “Evidence-Based Guideline Update: Pharmacologic Treatment for Episodic Migraine Prevention in Adults,” April 2012

Canadian Headache Society Prophylactic Guidelines Development Group, “Canadian Headache Society guideline for migraine prophylaxis,” 2012

European Federation of Neurological Societies, “EFNS guideline on the drug treatment of migraine-revised report of an EFNS task force,” 2009

Obsessive-Compulsive Disorder (OCD):

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Obsessive-Compulsive Disorder,” 2007

Anxiety Disorders Association of Canada, “Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders,” 2014

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in primary care,” 2012

Post Traumatic Stress Disorder (PTSD):

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” 2004

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” Guideline Watch (March 2009)

Anxiety Disorders Association of Canada, “Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders,” 2014

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in primary care,” 2012

VA/DoD, “VA/DoD clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder,” 2017

Administration: Oral

Administer with food.

Extended-release formulations: Administer either in the morning or in the evening at approximately the same time each day. Swallow capsule or tablet whole with fluid; do not divide, crush, chew, or place in water. Contents of capsule may be sprinkled on a spoonful of applesauce and swallowed immediately without chewing; followed with a glass of water to ensure complete swallowing of the pellets.

Administration: Pediatric

Oral:

Immediate-release tablet: Administer with food

Extended-release capsule: Administer with food once daily at about the same time each day; swallow whole with fluid; do not crush, chew, divide, or place in water; capsule may be opened and entire contents sprinkled on spoonful of applesauce; swallow drug/food mixture immediately. Do not store for future use; do not chew contents (ie, pellets) of capsule; follow drug/food mixture with water to ensure complete swallowing of pellets.

Storage/Stability

Immediate-release tablets and extended-release capsules: Store at 20°C to 25°C (68°F to 77°F).

Extended-release tablets: Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture and humidity.

Medication Patient Education with HCAHPS Considerations

• 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 insomnia, weight loss, anxiety, lack of appetite, loss of strength and energy, fatigue, tremors, constipation, sweating a lot, nausea, dry mouth, nightmares, or yawning. 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), passing out, vision changes, eye pain, eye irritation, eye edema, agitation, irritability, panic attacks, mood changes, behavioral changes, severe headache, severe dizziness, severe anxiety, seizures, angina, shortness of breath, sexual dysfunction, cough, bone pain, 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.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric patients: High-risk medication:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Effexor XR: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020699s107lbl.pdf#page=36

Venlafaxine extended release tablet: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022104s015lbl.pdf#page=35

Antidepressant medications: http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/ucm100211.pdf

Contraindications

Hypersensitivity to venlafaxine or any component of the formulation; use of MAOIs intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing the MAOI); initiation of MAOI intended to treat psychiatric disorders within 7 days of discontinuing venlafaxine; initiation in patients receiving linezolid or IV methylene blue.

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) in short-term studies of 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 patients of all ages for clinical worsening, suicidality, or unusual changes in behavior, particularly during the first few 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. Venlafaxine is not 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 health care 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, NSAIDs, warfarin, or other anticoagulants. Bleeding related to SSRI or 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 increases in serum total cholesterol and triglycerides; monitor during long-term treatment.

• 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. 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.

• Weight loss and anorectic effects: Dose-dependent weight loss has been observed in both pediatric and adult patients; weight loss was not limited to those experiencing reduced appetite.

Disease-related concerns:

• Cardiovascular disease: May cause sustained increase in blood pressure or tachycardia. Control pre-existing hypertension prior to initiation of venlafaxine. Use caution in patients with recent history of MI, unstable heart disease, cerebrovascular conditions, or hyperthyroidism. Hypertensive effect is dose related and increases are generally modest (12 to 15 mm Hg diastolic).

• Hepatic impairment: Use caution; clearance is decreased and plasma concentrations are increased; dosage reduction recommended.

• 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, including details regarding family history of suicide, bipolar disorder, and depression. Venlafaxine 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.

• Seizure disorders: Use caution in patients with a previous seizure disorder; discontinue in any patient who develops seizures.

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: Use with caution in the elderly; may have a higher risk of SIADH or hyponatremia.

• Pediatric: Small differences in height and weight have been observed in pediatric patients receiving venlafaxine, particularly those <12 years of age, compared to placebo.

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, lightheadedness, 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).

Geriatric Considerations

Venlafaxine’s low anticholinergic activity, minimal sedation, and hypotension properties makes this a valuable antidepressant in treating elderly with depression or anxiety disorders. No dose adjustment is necessary for age alone; adjust dose for renal function in the elderly. The elderly are more prone to SSRI/SNRI-induced hyponatremia.

A systematic review and meta-analysis of antidepressant placebo-controlled trials in persons with depression and dementia found evidence “suggestive” of efficacy but not of sufficient strength to “confirm” efficacy (Nelson 2011). Older patients with depression being treated with an antidepressant should be closely monitored for response and adverse effects.

Warnings: Additional Pediatric Considerations

May cause anxiety, nervousness, and insomnia; in children treated for ADHD, an increase in hyperactivity (behavioral activation) was reported (Olvera 1996). May cause anorexia and significant, dose related weight loss; use with caution in patients where weight loss is undesirable; may adversely affect weight and height in children; monitor closely in pediatric patients; weight loss in pediatric patients was not limited to those with venlafaxine-associated anorexia; reduction in growth rate, as assessed by height, was greater in children <12 years of age than in adolescents. A case of priapism has been reported in an adolescent patient (Samuel 2000).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Venlafaxine and its active metabolite ODV cross the human placenta. An increased risk of teratogenic effects following venlafaxine exposure during pregnancy has not been observed, based on available data. The risk of spontaneous abortion may be increased. Neonatal seizures and neonatal abstinence syndrome have been noted in case reports following maternal use of venlafaxine during pregnancy. 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 SNRI 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.

Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of venlafaxine may be altered. Women should be monitored for decreased efficacy. 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.

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.

Breast-Feeding Considerations

Venlafaxine and the active metabolite ODV are present in breast milk.

In one study, the mean relative infant dose (RID) of venlafaxine + ODV was 8.1% (range: 5% to 13%) when compared to a mean weight-adjusted maternal dose of 194 mg/day (range: 37.5 to 300 mg/day).

In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000). However some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).

The mean RID of venlafaxine + ODV was calculated by the authors of a study using mean milk concentrations of 803.9 ng/mL (venlafaxine) and 1,424.2 ng/mL (ODV), providing an estimated daily infant dose via breast milk of 0.21 mg/kg/day (range: 0.071 to 0.375 mg/kg/day). This information is from a study of 13 mother-infant pairs. All but two women were using the extended release dosage form. The amount of ODV in breast milk increased over time and was greater 12 hours after the dose than earlier in the sampling interval. Venlafaxine and ODV could also be detected in infant serum (Newport 2009).

In comparison to other agents, information related to the use of venlafaxine in breastfeeding women is limited (Berle 2011). Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015).

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. When first initiating an antidepressant in a breastfeeding woman, agents other than venlafaxine are preferred. Women successfully treated with venlafaxine during pregnancy may continue use while breastfeeding if there are no other contraindications (Berle 2011).

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Actual frequency may be dependent upon formulation and/or indication.

>10%:

Central nervous system: Insomnia (18%), dizziness (16%), drowsiness (15%)

Dermatologic: Diaphoresis (11%)

Gastrointestinal: Nausea (30%), xerostomia (15%)

Neuromuscular & skeletal: Weakness (13%)

1% to 10%:

Cardiovascular: Vasodilation (4%), hypotension (<2%), orthostatic hypotension (<2%), syncope (<2%), tachycardia (<2%), increased blood pressure (1%)

Central nervous system: Nervousness (7%), yawning (4%), anorgasmia (2% to 4%), abnormal dreams (3%), paresthesia (2%), agitation (<2%), akathisia (<2%), apathy (<2%), chills (<2%), confusion (<2%), depersonalization (<2%), hallucination (<2%), hypertonia (<2%), manic reaction (<2%), myoclonus (<2%), seizure (<2%)

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

Endocrine & metabolic: Orgasm abnormal (men: ≤10%), decreased libido (5%), hypercholesterolemia (5%), hypermenorrhea (<2%), weight gain (<2%), weight loss (<2%)

Gastrointestinal: Anorexia (10%), constipation (9%), diarrhea (8%), vomiting (4%), bruxism (<2%), dysgeusia (<2%), gastrointestinal hemorrhage (<2%)

Genitourinary: Ejaculatory disorder (≤10%), impotence (5%), abnormal uterine bleeding (<2%), urinary frequency (<2%), urinary incontinence (<2%), urinary retention (<2%), urination disorder (<2%)

Neuromuscular & skeletal: Tremor (5%)

Ophthalmic: Visual disturbance (4%), accommodation disturbance (<2%), mydriasis (<2%)

Otic: Tinnitus (<2%)

Frequency not defined:

Cardiovascular: Hypertension, increased pulse

Central nervous system: Suicidal ideation

Endocrine & metabolic: Increased serum triglycerides

Hematologic & oncologic: Hematoma, petechia

Respiratory: Epistaxis

<1%, postmarketing, and/or case reports: Abnormal hepatic function tests, agranulocytosis, anaphylaxis, angioedema, angle-closure glaucoma, aplastic anemia, ataxia, cardiomyopathy (takotsubo), delirium, dyspnea, eosinophilic pneumonitis, erythema multiforme, extrapyramidal reaction (including dystonia, dyskinesia), hepatitis, hypomania, hyponatremia, increased intraocular pressure (open-angle glaucoma) (Botha 2016), increased serum prolactin, interstitial pulmonary disease, mucous membrane bleeding, neuroleptic malignant syndrome, neutropenia, pancreatitis, pancytopenia, prolonged bleeding time, prolonged Q-T Interval on ECG, rhabdomyolysis, serotonin syndrome, SIADH, Stevens-Johnson syndrome, tardive dyskinesia, thrombocytopenia, toxic epidermal necrolysis, ventricular fibrillation, ventricular tachycardia (including torsades de pointes), withdrawal syndrome

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)

Drug Interactions 

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification

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

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: 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. Risk D: Consider therapy modification

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

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

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

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

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

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Risk X: Avoid combination

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

CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: Consider therapy modification

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

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

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

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

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

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

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Indinavir: Venlafaxine may decrease the serum concentration of Indinavir. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Iobenguane Radiopharmaceutical Products: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination

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

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Linezolid: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible, and discontinue serotonin/norepinephrine reuptake inhibitors (SNRIs) prior to administration of linezolid. Risk D: Consider therapy modification

Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Risk D: Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Risk D: Consider therapy modification

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

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

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

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Risk C: Monitor therapy

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. Risk D: Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Monoamine Oxidase 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. Risk X: Avoid combination

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

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

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

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.Risk C: Monitor therapy

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

Opioid Agonists: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

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

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

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

Propafenone: May increase the serum concentration of Venlafaxine. Management: Monitor for increased venlafaxine levels/adverse effects (e.g., hallucinations, agitation, confusion) with propafenone initiation/dose increase. Conversely, monitor for decreased venlafaxine levels with profapenone discontinuation/dose decrease. Risk C: Monitor therapy

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

QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: 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. Risk C: Monitor therapy

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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

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

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

St John’s Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

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

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

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: 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. Risk C: Monitor therapy

TraZODone: Venlafaxine may enhance the serotonergic effect of TraZODone. This could result in serotonin syndrome. Risk D: Consider therapy modification

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

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

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

Voriconazole: May enhance the adverse/toxic effect of Venlafaxine. Voriconazole may increase the serum concentration of Venlafaxine. Risk C: Monitor therapy

Test Interactions

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

Monitoring Parameters

Blood pressure should be regularly monitored, especially in patients with a high baseline blood pressure; may cause mean increase in heart rate of 4-9 beats/minute; cholesterol; mental status for depression, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; signs/symptoms of serotonin syndrome, hyponatremia, discontinuation symptoms; height and weight should be monitored in children; intraocular pressure and mydriasis (in patients with raised ocular pressure or at risk of acute narrow angle glaucoma) (APA, 2010)

Advanced Practitioners Physical Assessment/Monitoring

Monitor blood pressure and weight/height at beginning of therapy and periodically throughout. Observe for clinical worsening, suicide ideation, or unusual behavior changes, especially during the initial few months of therapy or during dosage changes. Taper dosage when discontinuing.

Nursing Physical Assessment/Monitoring

Monitor blood pressure and weight/height at beginning of therapy and periodically throughout. Observe for clinical worsening, suicide ideation, or unusual behavior changes, especially during the initial few months of therapy or during dosage changes. Taper dosage when discontinuing.

Dosage Forms: US

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

Capsule Extended Release 24 Hour, Oral:

Effexor XR: 37.5 mg, 75 mg, 150 mg

Generic: 37.5 mg, 75 mg, 150 mg

Tablet, Oral:

Generic: 25 mg, 37.5 mg, 50 mg, 75 mg, 100 mg

Tablet Extended Release 24 Hour, Oral:

Generic: 37.5 mg, 75 mg, 150 mg, 225 mg

Dosage Forms: Canada

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

Capsule Extended Release 24 Hour, Oral:

Effexor XR: 37.5 mg, 75 mg, 150 mg

Generic: 37.5 mg, 75 mg, 150 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N06AX16
Generic Available (US)

Yes

Pricing: US

Capsule ER 24 Hour Therapy Pack (Effexor XR Oral)

37.5 mg (per each): $15.83

75 mg (per each): $17.73

150 mg (per each): $19.32

Capsule ER 24 Hour Therapy Pack (Venlafaxine HCl ER Oral)

37.5 mg (per each): $0.08 – $4.16

75 mg (per each): $0.10 – $4.67

150 mg (per each): $0.20 – $5.08

Tablet, 24-hour (Venlafaxine HCl ER Oral)

37.5 mg (per each): $6.18 – $8.90

75 mg (per each): $6.92 – $9.97

150 mg (per each): $7.54 – $10.86

225 mg (per each): $15.89 – $20.83

Tablets (Venlafaxine HCl Oral)

25 mg (per each): $1.94

37.5 mg (per each): $2.00

50 mg (per each): $2.06

75 mg (per each): $2.18

100 mg (per each): $2.31 – $2.32

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV have no significant activity for muscarinic cholinergic, H1-histaminergic, or alpha2-adrenergic receptors. Venlafaxine and ODV do not possess MAO-inhibitory activity. Venlafaxine functions like an SSRI in low doses (37.5 mg/day) and as a dual mechanism agent affecting serotonin and norepinephrine at doses above 225 mg/day (Harvey 2000; Kelsey 1996).

Pharmacodynamics/Kinetics

Absorption: Oral: ≥92%; extended-release has a slightly slower rate of absorption compared to immediate-release

Distribution: Vdss: Venlafaxine 7.5 ± 3.7 L/kg, ODV 5.7 ± 1.8 L/kg

Protein binding: Venlafaxine 27% ± 2%, ODV 30% ± 12%

Metabolism: Hepatic via CYP2D6 to active metabolite, O-desmethylvenlafaxine (ODV); other metabolites include N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine

Bioavailability: Oral: ~45%

Half-life elimination: Venlafaxine: 5 ± 2 hours (immediate-release), 10.7 ± 3.2 hours (extended-release); ODV: 11 ± 2 hours (immediate-release), 12.5 ± 3 hours (extended-release); prolonged with cirrhosis (venlafaxine: ~30%, ODV: ~60%), renal impairment (venlafaxine: ~50%, ODV: ~40%), and during dialysis (venlafaxine: ~180%, ODV: ~142%)

Time to peak:

Immediate release: Venlafaxine: 2 hours, ODV: 3 hours

Extended release: Venlafaxine: 6.3 ± 2.3 hours, ODV: 11.6 ± 2.9 hours

Excretion: Urine (~87%; 5% of total dose as unchanged drug; 29% of total dose as unconjugated ODV; 26% of total dose as conjugated ODV; 27% of total dose as minor inactive metabolites)

Clearance:

Adults with cirrhosis: Venlafaxine: Clearance is decreased by ~50%; ODV: Clearance is decreased by ~30%

Adults with more severe cirrhosis: Venlafaxine: Clearance is decreased by ~90%

Adults with renal impairment (GFR: 10 to 70 mL/minute): Venlafaxine: Clearance is decreased by ~24%; ODV: Clearance unchanged versus normal subjects

Adults on dialysis: Venlafaxine: Clearance decreased by ~57%; ODV: Clearance decreased by ~56%

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Elimination half-life is prolonged and clearance is reduced.

Hepatic function impairment: Elimination half-life is prolonged and clearance decreased. In patients with Child-Pugh class A and Child-Pugh class B hepatic impairment, venlafaxine oral bioavailability was increased 2- to 3-fold.

Local Anesthetic/Vasoconstrictor Precautions

Although venlafaxine is not a tricyclic antidepressant, it does block norepinephrine reuptake within CNS synapses as part of its mechanisms. It has been suggested that vasoconstrictor be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way. This is particularly important in patients taking venlafaxine, which has been noted to produce a sustained increase in diastolic blood pressure and heart rate as a side effect.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes upon discontinuation); may contribute to oral discomfort, especially in the elderly; taste perversion. See Effects on Bleeding.

Effects on Bleeding

May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin, or other anticoagulants. Bleeding related to SSRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage. Routine interruption of therapy for most dental procedures is not warranted. In medically complicated patients or extensive oral surgery, the decision to interrupt therapy must be based on the risk to benefit in an individual patient and a medical consult is suggested. If therapy is continued without interruption, the clinician should anticipate the potential for a prolonged bleeding time.

Index Terms

Venlafaxine HCl

FDA Approval Date
December 28, 1993
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Brand Names: International

Altven (AU); Alventa (HR, RO); Ansifix SR (EC); Avenfax XR (SG); Blossom (CN); Calmdown (TW); Cofexor XL ER (KR); Delvena (EG); Deprevix (HK); Dobupal (ES); Easyfor SR (TW); Efectin (AT, CZ, HU); Efectin EP (RO); Efectin ER (BG); Efexiva (HR, SI); Efexor (AE, AR, BH, BR, CH, CO, DK, EE, FI, GB, GR, IE, IT, JO, LU, NL, PE, PK, SA, SE, TR, ZA); Efexor Depot (FI, IS, NO, SE); Efexor ER (CH, NL); Efexor XL (ID, MT); Efexor XR (AE, AR, AU, BH, BR, CL, CN, CO, CY, EC, EE, HK, IL, KR, KW, LB, LT, MX, MY, NZ, PE, PH, PT, QA, SA, SG, TH, VE); Efexor-Exel (BE); Effexor (FR); Effexor SR (JP); Effexor XR (BB); Elafax (PY, UY); Elafax XR (PY, UY); Enlafax-XR (AU); Evaxiner (CR, DO); Evaxiner XR (GT, HN, NI, PA, SV); Faxine (TW); Faxnerva (EG); Idixor (EG); Ireven (IE); Lafax (BD); Lanvexin (LV); Levensa SR (KR); Maxine (PH); Neurofax SR (LK); Nevola (BD); Rafax XR (TW); Rudomel XL (GB); Sesaren XR (CR, DO, EC, GT, HN, NI, PA, SV); Trevilor (DE); Trewilor (AT); Valosine (TW); Valosine SR (TH); Vandral Retard (ES); Vaxor (JO); Vedixal (IE); Velapax (RU); Velaxin (HK, UA); Venax (BD); Venex (IE); Venexor (HK, JO); Venexor XR (TZ); Venexor XR SR (KR); Veniz XR (LK); Veniz-XR (IN); Venla (IL); Venla RBX (AU); VenlaBlue XL (GB); Venlafact SR (KR); Venlalic XL (GB); Venlasand (BE); Venlax (BD, CL, LK); Venlax Retard (CL); Venlax XR (LB); Venlaxer (UA); Venlaxor (LV); Venlift OD 75 (TZ); Venlify OD (BH); Venlor XR (HK); Venorion (NO); Vensir (IE); Vensir XL (GB); Ventaxin OR (KR); Venxor (HK); Viepax (IL); Viepax XR (IL, SG)

Venlafaxine (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(ven la FAX een)

Brand Names: US

Effexor XR

Brand Names: Canada

Effexor XR; Venlafaxine XR

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • This drug is not approved for use in children. Talk with the doctor.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It is used to treat anxiety.
  • It is used to treat panic attacks.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to venlafaxine or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking a weight loss drug.
  • If you are taking any of these drugs: Linezolid or methylene blue.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson’s disease like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If you are breast-feeding or plan to breast-feed.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • High blood pressure has happened with this drug. Have your blood pressure checked as you have been told by your doctor.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • Some people may have a higher chance of eye problems with this drug. Your doctor may want you to have an eye exam to see if you have a higher chance of these eye problems. Call your doctor right away if you have eye pain, change in eyesight, or swelling or redness in or around the eye.
  • Low blood sodium levels may happen with this drug. In very bad cases, this can be deadly. Talk with the doctor.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Taking this drug in the third trimester of pregnancy may lead to some health problems in the newborn. Talk with the doctor.
  • Long-acting capsules:
  • You may see parts of this drug in your stool. This is normal and not a cause for concern.
  • Long-acting tablets:
  • You may see the tablet shell in your stool. This is normal and not a cause for concern.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Very nervous and excitable.
  • Seizures.
  • Chest pain or pressure.
  • Shortness of breath.
  • Cough.
  • Bone pain.
  • Sex problems like lowered interest in sex or ejaculation problems.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if you take this drug with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Not able to sleep.
  • Feeling nervous and excitable.
  • Anxiety.
  • Weight loss.
  • Not hungry.
  • Feeling tired or weak.
  • Feeling sleepy.
  • Dizziness.
  • Shakiness.
  • Headache.
  • Sweating a lot.
  • Upset stomach.
  • Constipation.
  • Gas.
  • Dry mouth.
  • Strange or odd dreams.
  • Yawning.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take this drug with food.
  • Take this drug at the same time of day.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • All long-acting products:
  • Swallow whole. Do not chew, break, or crush.
  • Take with a full glass of water.
  • Long-acting capsules:
  • You may sprinkle contents of long-acting product on spoonful of applesauce. Do not chew.
  • Swallow the mixture right away. Do not store for use at a later time.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Venlafaxine (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(ven la FAX een)

Brand Names: US

Effexor XR

Brand Names: Canada

Effexor XR; Venlafaxine XR

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • This drug is not approved for use in children. Talk with the doctor.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It is used to treat anxiety.
  • It is used to treat panic attacks.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child is taking a weight loss drug.
  • If your child has taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for certain other health problems in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If your child is taking any of these drugs: Linezolid or methylene blue.
  • If your child is breast-feeding a baby:
  • Talk with the doctor if your child is breast-feeding a baby or plans to breast-feed a baby.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of side effects. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • High blood pressure has happened with this drug. Have your child’s blood pressure checked as you have been told by the doctor.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • Some people may have a higher chance of eye problems with this drug. The doctor may want your child to have an eye exam to see if your child has a higher chance of these eye problems. Call the doctor right away if your child has eye pain, change in eyesight, or swelling or redness in or around the eye.
  • Low blood sodium levels may happen with this drug. In very bad cases, this can be deadly. Talk with the doctor.
  • This drug may affect certain lab tests. Tell all of your child’s health care providers and lab workers that your child takes this drug.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • If your child is pregnant:
  • Tell the doctor if your child is pregnant or becomes pregnant. You will need to talk about the benefits and risks of your child using this drug while pregnant.
  • Taking this drug in the third trimester of pregnancy may lead to some health problems in the newborn. Talk with the doctor.
  • Long-acting capsules:
  • Parts of this drug may be seen in your child’s stool. This is normal and not a cause for concern.
  • Long-acting tablets:
  • You may see the tablet shell in your child’s stool. This is normal and not a cause for concern.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Chest pain or pressure.
  • Very nervous and excitable.
  • Seizures.
  • Shortness of breath.
  • Cough.
  • Bone pain.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if your child takes this drug with drugs for depression, migraines, or certain other drugs. Call your child’s doctor right away if your child has agitation; change in balance; confusion; hallucinations; fever; a fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
  • If your child is or may be sexually active:
  • Sex problems like lowered interest in sex or ejaculation problems.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Anxiety.
  • Weight loss.
  • Not hungry.
  • Feeling tired or weak.
  • Feeling sleepy.
  • Dizziness.
  • Shakiness.
  • Headache.
  • Feeling nervous and excitable.
  • Upset stomach.
  • Dry mouth.
  • Constipation.
  • Gas.
  • Not able to sleep.
  • Sweating a lot.
  • Strange or odd dreams.
  • Yawning.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give this drug with food.
  • Give this drug at the same time of day.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • All long-acting products:
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • Give this drug with a full glass of water.
  • Long-acting capsules:
  • You may sprinkle contents of long-acting product on applesauce. Do not let your child chew.
  • Give the mixture right away. Do not store for use at a later time.
What do I do if my child misses a dose?
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.