Effexor XR Side Effects Center

Last updated on RxList: 9/19/2022
Effexor XR Side Effects Center

What Is Effexor XR?

Effexor XR (venlafaxine hydrochloride extended-release) is an antidepressant used to treat patients with major depressive disorders such as panic and social disorders. Effexor XR is available as a generic.

What Are Side Effects of Effexor XR?

Effexor XR may cause serious side effects including:

Get medical help right away, if you have any of the symptoms listed above.

Common side effects of Effexor XR include:

  • nausea,
  • constipation,
  • insomnia,
  • dizziness,
  • asthenia,
  • drowsiness,
  • dry mouth,
  • nervousness,
  • strange dreams,
  • blurred vision,
  • changes in appetite or weight,
  • decreased sex drive,
  • impotence,
  • difficulty having an orgasm, and
  • increased sweating.

Tell your doctor if you have unlikely but serious side effects of Effexor XR including:

  • easy bruising or bleeding,
  • decreased interest in sex,
  • changes in sexual ability,
  • muscle cramps or weakness, or
  • shaking (tremors).

Serious side effects of Effexor XR include clinical worsening of symptoms and suicide risk, especially in younger patients. Tell your doctor if you experience worsening depression or thoughts of suicide while taking Effexor XR.

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Effexor XR

Effexor XR contains venlafaxine hydrochloride in strengths of 37.5, 75, or 150 mg tablets.

What Drugs, Substances, or Supplements Interact with Effexor XR?

Effexor XR may interact with other medicines that make you sleepy (such as cold or allergy medicines, sedatives, narcotics, sleeping pills, muscle relaxers, and medicines for seizures or anxiety), nonsteroidal anti-inflammatory drugs (NSAIDs), cimetidine, ketoconazole, linezolid, lithium, haloperidol, tramadol, L-tryptophan, warfarin, almotriptan, frovatriptan, sumatriptan, naratriptan, rizatriptan, zolmitriptan, other antidepressants, or other drugs. Tell your doctor all medications and supplements you use. The dose is usually one tablet per day.

Effexor XR During Pregnancy or Breastfeeding

Effexor XR has not been adequately studied in pregnant females; risks of use must be weighed against possible benefits to the mother. Effexor has been detected in breast milk and may cause serious problems for nursing infants. Breastfeeding while using Effexor XR is not recommended. Although there are reports of use of Effexor in pediatric populations, safety and effectiveness has not been established for pediatric patients.

Additional Information

Our Effexor XR Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Learn to Spot Depression: Symptoms, Warning Signs, Medication See Slideshow
Effexor XR Consumer Information

Get emergency medical help if you have signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

  • blurred vision, eye pain or redness, seeing halos around lights;
  • cough, chest tightness, trouble breathing;
  • a seizure (convulsions);
  • unusual bleeding--nosebleeds, bleeding gums, abnormal vaginal bleeding, any bleeding that will not stop;
  • low blood sodium--headache, confusion, problems with thinking or memory, weakness, feeling unsteady; or
  • severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea

Common side effects may include:

  • headache, dizziness, drowsiness, tiredness;
  • feeling anxious, nervous, or jittery;
  • sleep problems, unusual dreams;
  • tremors;
  • fast heartbeats;
  • blurred vision;
  • nausea, vomiting, diarrhea, constipation;
  • changes in weight or appetite;
  • dry mouth, yawning;
  • increased sweating; or
  • sexual problems.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Depression is a(n) __________ . See Answer
Effexor XR Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in more detail in other sections of the labeling:

  • Hypersensitivity [see CONTRAINDICATIONS]
  • Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see WARNINGS AND PRECAUTIONS]
  • Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
  • Elevated Blood Pressure [see WARNINGS AND PRECAUTIONS]
  • Increased Risk of Bleeding [see WARNINGS AND PRECAUTIONS]
  • Angle Closure Glaucoma [see WARNINGS AND PRECAUTIONS]
  • Activation of Mania/Hypomania [see WARNINGS AND PRECAUTIONS]
  • Discontinuation Syndrome [see WARNINGS AND PRECAUTIONS]
  • Seizure [see WARNINGS AND PRECAUTIONS]
  • Hyponatremia [see WARNINGS AND PRECAUTIONS]
  • Weight and Height changes in Pediatric Patients [see WARNINGS AND PRECAUTIONS]
  • Appetite Changes in Pediatric Patients [see WARNINGS AND PRECAUTIONS]
  • Interstitial Lung Disease and Eosinophilic Pneumonia [see WARNINGS AND PRECAUTIONS]
  • Sexual Dysfunction [see WARNINGS AND PRECAUTIONS]

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

Most Common Adverse Reactions

The most commonly observed adverse reactions in the clinical study database in Effexor XR treated patients in MDD, GAD, SAD, and PD (incidence ≥5% and at least twice the rate of placebo) were: nausea (30.0%), somnolence (15.3%), dry mouth (14.8%), sweating (11.4%), abnormal ejaculation (9.9%), anorexia (9.8%), constipation (9.3%), impotence (5.3%), and decreased libido (5.1%).

Adverse Reactions Reported As Reasons For Discontinuation Of Treatment

Combined across short-term, placebo-controlled premarketing studies for all indications, 12% of the 3,558 patients who received Effexor XR (37.5-225 mg) discontinued treatment due to an adverse experience, compared with 4% of the 2,197 placebo-treated patients in those studies.

The most common adverse reactions leading to discontinuation in ≥1% of the Effexor XR treated patients in the short-term studies (up to 12 weeks) across indications are shown in Table 7.

Table 7: Incidence (%) of Patients Reporting Adverse Reactions Leading to Discontinuation in Placebo-controlled Clinical Studies (up to 12 Weeks Duration)

Body System
Adverse Reaction
Effexor XR
n = 3,558
Placebo
n = 2,197
Body as a whole
Asthenia 1.7 0.5
Headache 1.5 0.8
Digestive system
Nausea 4.3 0.4
Nervous system
Dizziness 2.2 0.8
Insomnia 2.1 0.6
Somnolence 1.7 0.3
Skin and appendages 1.5 0.6
Sweating 1.0 0.2

Common Adverse Reactions In Placebo-controlled Studies

The number of patients receiving multiple doses of Effexor XR during the premarketing assessment for each approved indication is shown in Table 8. The conditions and duration of exposure to venlafaxine in all development programs varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient (Effexor only) and outpatient studies, fixed-dose, and titration studies.

Table 8: Patients Receiving Effexor XR in Premarketing Clinical Studies

Indication Effexor XR
MDD 705a
GAD 1,381
SAD 819
PD 1,314
a In addition, in the premarketing assessment of Effexor, multiple doses were administered to 2,897 patients in studies for MDD.

The incidences of common adverse reactions (those that occurred in ≥2% of Effexor XR treated patients [357 MDD patients, 1,381 GAD patients, 819 SAD patients, and 1,001 PD patients] and more frequently than placebo) in Effexor XR treated patients in short-term, placebo-controlled, fixed-and flexible-dose clinical studies (doses 37.5 to 225 mg per day) are shown in Table 9.

The adverse reaction profile did not differ substantially between the different patient populations.

Table 9: Common Adverse Reactions: Percentage of Patients Reporting Adverse Reactions (≥2% and > placebo) in Placebo-controlled Studies (up to 12 Weeks Duration) across All Indications

Body System
Adverse Reaction
Effexor XR
n = 3,558
Placebo
n = 2,197
Body as a whole
Asthenia 12.6 7.8
Cardiovascular system
Hypertension 3.4 2.6
Palpitation 2.2 2.0
Vasodilatation 3.7 1.9
Digestive system
Anorexia 9.8 2.6
Constipation 9.3 3.4
Diarrhea 7.7 7.2
Dry mouth 14.8 5.3
Nausea 30.0 11.8
Vomiting 4.3 2.7
Nervous system
Abnormal dreams 2.9 1.4
Dizziness 15.8 9.5
Insomnia 17.8 9.5
Libido decreased 5.1 1.6
Nervousness 7.1 5.0
Paresthesia 2.4 1.4
Somnolence 15.3 7.5
Tremor 4.7 1.6
Respiratory system
Yawn 3.7 0.2
Skin and appendages
Sweating (including night sweats) 11.4 2.9
Special senses
Abnormal vision 4.2 1.6
Urogenital system
Abnormal ejaculation/orgasm (men)a 9.9 0.5
Anorgasmia (men)a 3.6 0.1
Anorgasmia (women)b 2.0 0.2
Impotence (men)a 5.3 1.0
a Percentages based on the number of men (Effexor XR, n = 1,440; placebo, n = 923)
b Percentages based on the number of women (Effexor XR, n = 2,118; placebo, n = 1,274)

Other Adverse Reactions Observed In Clinical Studies

Body as a whole - Photosensitivity reaction, chills

Cardiovascular system - Postural hypotension, syncope, hypotension, tachycardia

Digestive system - Gastrointestinal hemorrhage [see WARNINGS AND PRECAUTIONS], bruxism

Hemic/Lymphatic system - Ecchymosis [see WARNINGS AND PRECAUTIONS]

Metabolic/Nutritional - Hypercholesterolemia, weight gain [see WARNINGS AND PRECAUTIONS], weight loss [see WARNINGS AND PRECAUTIONS]

Nervous system - Seizures [see WARNINGS AND PRECAUTIONS], manic reaction [see WARNINGS AND PRECAUTIONS], agitation, confusion, akathisia, hallucinations, hypertonia, myoclonus, depersonalization, apathy

Skin and appendages - Urticaria, pruritus, rash, alopecia

Special senses - Mydriasis, abnormality of accommodation, tinnitus, taste perversion

Urogenital system - Urinary retention, urination impaired, urinary incontinence, urinary frequency increased, menstrual disorders associated with increased bleeding or increased irregular bleeding (e.g., menorrhagia, metrorrhagia)

Vital Sign Changes

In placebo-controlled premarketing studies, there were increases in mean blood pressure (see Table 10). Across most indications, a dose-related increase in mean supine systolic and diastolic blood pressure was evident in patients treated with Effexor XRs. Across all clinical studies in MDD, GAD, SAD and PD, 1.4% of patients in the Effexor XR groups experienced an increase in SDBP of ≥15 mm Hg along with a blood pressure ≥105 mm Hg, compared to 0.9% of patients in the placebo groups. Similarly, 1% of patients in the Effexor XR groups experienced an increase in SSBP of ≥20 mm Hg with a blood pressure ≥180 mm Hg, compared to 0.3% of patients in the placebo groups.

Table 10: Final On-therapy Mean Changes From Baseline in Supine Systolic (SSBP) and Diastolic (SDBP) Blood Pressure (mm Hg) in Placebo-controlled Studies

Indication (Duration) Effexor XR Placebo
≤75 mg per day >75 mg per day
SSBP SDBP SSBP SDBP SSBP SDBP
MDD
(8-12 weeks) -0.28 0.37 2.93 3.56 -1.08 -0.10
GAD
(8 weeks) -0.28 0.02 2.40 1.68 -1.26 -0.92
(6 months) 1.27 -0.69 2.06 1.28 -1.29 -0.74
SAD
(12 weeks) -0.29 -1.26 1.18 1.34 -1.96 -1.22
(6 months) -0.98 -0.49 2.51 1.96 -1.84 -0.65
PD
(10-12 weeks) -1.15 0.97 -0.36 0.16 -1.29 -0.99

Effexor XR treatment was associated with sustained hypertension (defined as Supine Diastolic Blood Pressure [SDBP] ≥90 mm Hg and ≥10 mm Hg above baseline for three consecutive on-therapy visits (see Table 11). An insufficient number of patients received mean doses of Effexor XR over 300 mg per day in clinical studies to fully evaluate the incidence of sustained increases in blood pressure at these higher doses.

Table 11: Sustained Elevations in SDBP in Effexor XR Premarketing Studies

Indication Dose Range (mg per day) Incidence (%)
MDD 75-375a 19/705 (3)
GAD 37.5-225 5/1011 (0.5)
SAD 75-225 5/771 (0.6)
PD 75-225 9/973 (0.9)
a Maximum recommended dosage for Effexor XR is 225 mg once daily.

Effexor XR was associated with mean increases in pulse rate compared with placebo in premarketing placebo-controlled studies (see Table 12) [see WARNINGS AND PRECAUTIONS].

Table 12: Approximate Mean Final On-therapy Increase in Pulse Rate (beats/min) in Effexor XR Premarketing Placebo-controlled Studies (up to 12 Weeks Duration)

Indication (Duration) Effexor XR Placebo
MDD
(12 weeks) 2 1
GAD
(8 weeks) 2 < 1
SAD
(12 weeks) 3 1
PD
(12 weeks) 1 < 1

Laboratory Changes

Serum Cholesterol

Effexor XR was associated with mean final increases in serum cholesterol concentrations compared with mean final decreases for placebo in premarketing MDD, GAD, SAD and PD clinical studies (Table 13).

Table 13: Mean Final On-therapy Changes in Cholesterol Concentrations (mg/dL) in Effexor XR Premarketing Studies

Indication (Duration) Effexor XR Placebo
MDD
(12 weeks) +1.5 -7.4
GAD
(8 weeks) +1.0 -4.9
(6 months) +2.3 -7.7
SAD
(12 weeks) +7.9 -2.9
(6 months) +5.6 -4.2
PD
(12 weeks) 5.8 -3.7

Effexor XR (venlafaxine hydrochloride) extended-release capsules treatment for up to 12 weeks in premarketing placebo-controlled trials for major depressive disorder was associated with a mean final on-therapy increase in serum cholesterol concentration of approximately 1.5 mg/dL compared with a mean final decrease of 7.4 mg/dL for placebo. Effexor XR treatment for up to 8 weeks and up to 6 months in premarketing placebo-controlled GAD trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 1.0 mg/dL and 2.3 mg/dL, respectively while placebo subjects experienced mean final decreases of 4.9 mg/dL and 7.7 mg/dL, respectively. Effexor XR treatment for up to 12 weeks and up to 6 months in premarketing placebo-controlled Social Anxiety Disorder trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 7.9 mg/dL and 5.6 mg/dL, respectively, compared with mean final decreases of 2.9 and 4.2 mg/dL, respectively, for placebo. Effexor XR treatment for up to 12 weeks in premarketing placebo-controlled panic disorder trials was associated with mean final on-therapy increases in serum cholesterol concentration of approximately 5.8 mg/dL compared with a mean final decrease of 3.7 mg/dL for placebo.

Patients treated with Effexor (immediate release) for at least 3 months in placebo-controlled 12-month extension trials had a mean final on-therapy increase in total cholesterol of 9.1 mg/dL compared with a decrease of 7.1 mg/dL among placebo-treated patients. This increase was duration dependent over the study period and tended to be greater with higher doses. Clinically relevant increases in serum cholesterol, defined as 1) a final on-therapy increase in serum cholesterol ≥50 mg/dL from baseline and to a value ≥261 mg/dL, or 2) an average on-therapy increase in serum cholesterol ≥50 mg/dL from baseline and to a value ≥261 mg/dL, were recorded in 5.3% of venlafaxine-treated patients and 0.0% of placebo-treated patients.

Serum Triglycerides

Effexor XR was associated with mean final on-therapy increases in fasting serum triglycerides compared with placebo in premarketing clinical studies of SAD and PD up to 12 weeks (pooled data) and 6 months duration (Table 14).

Table 14: Mean Final On-therapy Increases in Triglyceride Concentrations (mg/dL) in Effexor XR Premarketing Studies

Indication (Duration) Effexor XR Placebo
SAD
(12 weeks) 8.2 0.4
SAD
(6 months) 11.8 1.8
PD
(12 weeks) 5.9 0.9
PD
(6 months) 9.3 0.3

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Effexor XR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a whole - Anaphylaxis, angioedema

Cardiovascular system - QT prolongation, ventricular fibrillation, ventricular tachycardia (including torsade de pointes), takotsubo cardiomyopathy

Digestive system - Pancreatitis

Hemic/Lymphatic system - Mucous membrane bleeding [see WARNINGS AND PRECAUTIONS], blood dyscrasias (including agranulocytosis, aplastic anemia, neutropenia and pancytopenia), prolonged bleeding time, thrombocytopenia

Metabolic/Nutritional - Hyponatremia [see WARNINGS AND PRECAUTIONS], Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion [see WARNINGS AND PRECAUTIONS], abnormal liver function tests, hepatitis, prolactin increased

Musculoskeletal - Rhabdomyolysis

Nervous system - Neuroleptic Malignant Syndrome (NMS) [see WARNINGS AND PRECAUTIONS], serotonergic syndrome [see WARNINGS AND PRECAUTIONS], delirium, extrapyramidal reactions (including dystonia and dyskinesia), impaired coordination and balance, tardive dyskinesia

Respiratory system - Dyspnea, interstitial lung disease, pulmonary eosinophilia [see WARNINGS AND PRECAUTIONS]

Skin and appendages - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme

Special senses - Angle closure glaucoma [see WARNINGS AND PRECAUTIONS]

DRUG INTERACTIONS

Drugs Having Clinically Important Interactions With Effexor XR

Table 15: Clinically Important Drug Interactions with Effexor XR

Monoamine Oxidase Inhibitors (MAOI)
Clinical Impact The concomitant use of SNRIs, including Effexor XR, with MAOIs increases the risk of serotonin syndrome.
Intervention Concomitant use of Effexor XR is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]
Other Serotonergic Drugs
Clinical Impact Concomitant use of Effexor XR with other serotonergic drugs increases the risk of serotonin syndrome.
Intervention Monitor for symptoms of serotonin syndrome when Effexor XR is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinuation of Effexor XR and/or concomitant serotonergic drugs [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
Drugs that Interfere with Hemostasis
Clinical Impact Concomitant use of Effexor XR with an antiplatelet or anticoagulant drug may potentiate the risk of bleeding. This may be due to the effect of Effexor XR on the release of serotonin by platelets.
Intervention Closely monitor for bleeding for patients receiving an antiplatelet or anticoagulant drug when Effexor XR is initiated or discontinued [see WARNINGS AND PRECAUTIONS].
Effect of CYP3A Inhibitors
Clinical Impact Concomitant use of a CYP3A inhibitor increases the Cmax and AUC of venlafaxine and O-desmethylvenlafaxine (ODV) [see CLINICAL PHARMACOLOGY], which may increase the risk of toxicity of Effexor XR
Intervention Consider reducing the dose of Effexor XR.
CYP2D6 Substrates
Clinical Impact Concomitant use of Effexor XR increases Cmax and AUC of a CYP2D6 substrate, which may increase the risk of toxicity of the CYP2D6 substrate [see CLINICAL PHARMACOLOGY].
Intervention Consider reduction in dose of concomitant CYP2D6 substrates.

Other Drug Interactions With Effexor XR

Central Nervous System (CNS)-Active Drugs

The risk of using venlafaxine concomitantly with other CNS-active drugs (including alcohol) has not been systematically evaluated. Consequently, caution is advised when Effexor XR is taken concomitantly in combination with other CNS-active drugs.

Weight Loss Agents

Concomitant use of Effexor XR and weight loss agents is not recommended. The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Effexor XR is not indicated for weight loss alone or in combination with other products.

Laboratory Test Interference

False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking venlafaxine due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of venlafaxine therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish venlafaxine from PCP and amphetamine.

Drug Abuse And Dependence

Controlled Substance

Effexor XR contains venlafaxine which is not a controlled substance.

Abuse

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.

While venlafaxine has not been systematically studied in clinical studies for its potential for abuse, there was no indication of drug-seeking behavior in the clinical studies. However, it is not possible to predict on the basis of premarketing experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, providers should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of venlafaxine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

Dependence

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

In vitro studies revealed that venlafaxine has virtually no affinity for opiate, benzodiazepine, phencyclidine (PCP), or N-methyl-D-aspartic acid (NMDA) receptors.

Venlafaxine was not found to have any significant CNS stimulant activity in rodents. In primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability.

Discontinuation effects have been reported in patients receiving venlafaxine [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Effexor XR (Venlafaxine Hydrochloride Extended-Release)

© Effexor XR Patient Information is supplied by Cerner Multum, Inc. and Effexor XR Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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