Wellbutrin XL Side Effects Center

Last updated on RxList: 3/22/2022
Wellbutrin XL Side Effects Center

What Is Wellbutrin XL?

Wellbutrin XL (bupropion hydrochloride extended-release) is an antidepressant used to treat major depressive disorder and seasonal affective disorder. At least one brand of bupropion (Zyban) is used to help people stop smoking by reducing cravings and other withdrawal effects. Wellbutrin XL is available in generic form.

What Are Side Effects of Wellbutrin XL?

Common side effects of Wellbutrin XL include:

Tell your doctor if you experience serious side effects of Wellbutrin XL including:
  • seizure (convulsions),
  • fast heartbeats,
  • fever,
  • swollen glands,
  • rash or itching,
  • joint pain,
  • general ill feeling,
  • confusion,
  • trouble concentrating,
  • hallucinations,
  • unusual thoughts or behavior,
  • or severe skin reaction [fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling].

Dosage for Wellbutrin XL

The initial dose of Wellbutrin XL is 150 mg/day as a single dose. The target dose is 300-mg/day.

What Drugs, Substances, or Supplements Interact with Wellbutrin XL?

Wellbutrin XL may interact with cancer medicines, heart rhythm medications, heart or blood pressure medications, other antidepressants, medicine to treat psychiatric disorders, antihistamines, asthma medications or bronchodilators, birth control pills or hormone replacement estrogens, bladder or urinary medications, antibiotics, diet pills, stimulants, ADHD medication, insulin or oral diabetes medications, medication for nausea/vomiting/motion sickness, medications to treat/prevent malaria, medicines to treat Parkinson's disease/restless leg syndrome/pituitary gland tumor, medicines used to prevent organ transplant rejection, narcotics, sedatives, steroids, theophylline, or ulcer or irritable bowel medications. Tell your doctor all medications you use.

Wellbutrin XL During Pregnancy and Breastfeeding

Wellbutrin XL should be used only when prescribed during pregnancy. Infrequently, newborns whose mothers have used certain antidepressants during the last 3 months of pregnancy may develop symptoms including persistent feeding or breathing difficulties, jitteriness, seizures or constant crying. Report symptoms to the doctor. Do not stop taking this medication unless your doctor directs you to do so. This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

Additional Information

Our Wellbutrin XL (bupropion hydrochloride extended-release) 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.


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Wellbutrin XL Consumer Information

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Get emergency medical help if you have signs of an allergic reaction (hives, itching, fever, swollen glands, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, depression, 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:

  • a seizure (convulsions);
  • confusion, unusual changes in mood or behavior;
  • blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • fast or irregular heartbeats; or
  • a manic episode--racing thoughts, increased energy, reckless behavior, feeling extremely happy or irritable, talking more than usual, severe problems with sleep.

Common side effects may include:

  • dry mouth, sore throat, stuffy nose;
  • ringing in the ears;
  • blurred vision;
  • nausea, vomiting, stomach pain, loss of appetite, constipation;
  • sleep problems (insomnia);
  • tremors, sweating, feeling anxious or nervous;
  • fast heartbeats;
  • confusion, agitation, hostility;
  • rash;
  • weight loss;
  • increased urination;
  • headache, dizziness; or
  • muscle or joint pain.

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.

Read the entire detailed patient monograph for Wellbutrin XL (Bupropion Hydrochloride Extended-Release)


Depression is a(n) __________ . See Answer
Wellbutrin XL Professional Information


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

  • Suicidal thoughts and behaviors in children, adolescents, and young adults [see WARNINGS AND PRECAUTIONS]
  • Neuropsychiatric adverse events and suicide risk in smoking cessation treatment [see WARNINGS AND PRECAUTIONS]
  • Hypertension [see WARNINGS AND PRECAUTIONS]
  • Activation of mania or hypomania [see WARNINGS AND PRECAUTIONS]
  • Psychosis and other neuropsychiatric events [see WARNINGS AND PRECAUTIONS]
  • Angle-Closure Glaucoma [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials 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 trials of another drug and may not reflect the rates observed in practice.

Commonly Observed Adverse Reactions In Controlled Clinical Trials Of Sustained-Release Bupropion Hydrochloride

Adverse reactions that occurred in at least 5% of patients treated with bupropion HCl sustained-release (300 mg and 400 mg per day) and at a rate at least twice the placebo rate are listed below.

300 mg/day of bupropion HCl sustained-release: anorexia, dry mouth, rash, sweating, tinnitus, and tremor.

400 mg/day of bupropion HCl sustained-release: abdominal pain, agitation, anxiety, dizziness, dry mouth, insomnia, myalgia, nausea, palpitation, pharyngitis, sweating, tinnitus, and urinary frequency.

Wellbutrin XL has been demonstrated to have similar bioavailability both to the immediate-release and sustained-release formulations of bupropion. The information included under this subsection and under subsection 6.2 is based primarily on data from controlled clinical trials with the sustained-release and extended-release formulations of bupropion hydrochloride.

Major Depressive Disorder

Adverse Reactions Leading to Discontinuation of Treatment with Bupropion HCl Immediate-Release, Bupropion HCl Sustained-Release, and Bupropion HCl Extended-Release in Major Depressive Disorder Trials

In placebo-controlled clinical trials with bupropion HCl sustained-release, 4%, 9%, and 11% of the placebo, 300 mg/day and 400 mg/day groups, respectively, discontinued treatment because of adverse reactions. The specific adverse reactions leading to discontinuation in at least 1% of the 300 mg/day or 400 mg/day groups and at a rate at least twice the placebo rate are listed in Table 2.

Table 2: Treatment Discontinuation Due to Adverse Reactions in Placebo-Controlled Trials in MDD

Adverse Reaction Term Placebo
Bupropion HCl Sustained-Release 300 mg/day
Bupropion HCl Sustained-Release 400 mg/day
Rash 0.0% 2.4% 0.9%
Nausea 0.3% 0.8% 1.8%
Agitation 0.3% 0.3% 1.8%
Migraine 0.3% 0.0% 1.8%

In clinical trials with bupropion HCl immediate-release, 10% of patients and volunteers discontinued due to an adverse reaction. Reactions resulting in discontinuation (in addition to those listed above for the sustained-release formulation) included vomiting, seizures, and sleep disturbances.

Adverse Reactions Occurring At An Incidence Of >1% In Patients Treated With Bupropion HCl Immediate-Release Or Bupropion HCl Sustained-Release in MDD

Table 3 summarizes the adverse reactions that occurred in placebo-controlled trials in patients treated with bupropion HCl sustained-release 300 mg/day and 400 mg/day. These include reactions that occurred in either the 300 mg or 400 mg group at an incidence of 1% or more and were more frequent than in the placebo group.

Table 3: Adverse Reactions in Placebo-Controlled Trials in Patients with MDD

Body System/Adverse Reaction Placebo
Bupropion HCl Sustained-Release 300 mg/day
Bupropion HCl Sustained-Release 400 mg/day
Body (General)
Headache 23% 26% 25%
Infection 6% 8% 9%
Abdominal pain 2% 3% 9%
Asthenia 2% 2% 4%
Chest pain 1% 3% 4%
Pain 2% 2% 3%
Fever 1% 2%
Palpitation 2% 2% 6%
Flushing 1% 4%
Migraine 1% 1% 4%
Hot flashes 1% 1% 3%
Dry mouth 7% 17% 24%
Nausea 8% 13% 18%
Constipation 7% 10% 5%
Diarrhea 6% 5% 7%
Anorexia 2% 5% 3%
Vomiting 2% 4% 2%
Dysphagia 0% 0% 2%
Myalgia 3% 2% 6%
Arthralgia 1% 1% 4%
Arthritis 0% 0% 2%
Twitch 1% 2%
Nervous System
Insomnia 6% 11% 16%
Dizziness 5% 7% 11%
Agitation 2% 3% 9%
Anxiety 3% 5% 6%
Tremor 1% 6% 3%
Nervousness 3% 5% 3%
Somnolence 2% 2% 3%
Irritability 2% 3% 2%
Memory decreased 1% 3%
Paresthesia 1% 1% 2%
Central nervous system stimulation 1% 2% 1%
Pharyngitis 2% 3% 11%
Sinusitis 2% 3% 1%
Increased cough 1% 1% 2%
Sweating 2% 6% 5%
Rash 1% 5% 4%
Pruritus 2% 2% 4%
Urticaria 0% 2% 1%
Special Senses
Tinnitus 2% 6% 6%
Taste perversion 2% 4%
Blurred vision or diplopia 2% 3% 2%
Urinary frequency 2% 2% 5%
Urinary urgency 0% 2%
Vaginal hemorrhage* 0% 2%
Urinary tract infection _† 1% 0%
*Incidence based on the number of female patients.
†Hyphen denotes adverse reactions occurring in greater than 0 but less than 0.5% of patients.

The following additional adverse reactions occurred in controlled trials of bupropion HCl immediate-release (300 to 600 mg per day) at an incidence of at least 1% more frequently than in the placebo group were: cardiac arrhythmia (5% vs. 4%), hypertension (4% vs. 2%), hypotension (3% vs. 2%), menstrual complaints (5% vs. 1%), akathisia (2% vs. 1%), impaired sleep quality (4% vs. 2%), sensory disturbance (4% vs. 3%), confusion (8% vs. 5%), decreased libido (3% vs. 2%), hostility (6% vs. 4%), auditory disturbance (5% vs. 3%), and gustatory disturbance (3% vs. 1%).

Seasonal Affective Disorder

In placebo-controlled clinical trials in SAD, 9% of patients treated with Wellbutrin XL and 5% of patients treated with placebo discontinued treatment because of adverse reactions. The adverse reactions leading to discontinuation in at least 1% of patients treated with bupropion and at a rate numerically greater than the placebo rate were insomnia (2% vs. <1%) and headache (1% vs. <1%).

Table 4 summarizes the adverse reactions that occurred in patients treated with Wellbutrin XL for up to approximately 6 months in 3 placebo-controlled trials. These include reactions that occurred at an incidence of 2% or more and were more frequent than in the placebo group.

Table 4: Adverse Reactions in Placebo-Controlled Trials in Patients with SAD

System Organ Class/Preferred Term Placebo
Bupropion HCl Extended-Release
Gastrointestinal Disorder
Dry mouth 15% 26%
Nausea 8% 13%
Constipation 2% 9%
Flatulence 3% 6%
Abdominal pain <1% 2%
Nervous System Disorders
Headache 26% 34%
Dizziness 5% 6%
Tremor <1% 3%
Infections and Infestations
Nasopharyngitis 12% 13%
Upper respiratory tract infection 8% 9%
Sinusitis 4% 5%
Psychiatric Disorders
Insomnia 13% 20%
Anxiety 5% 7%
Abnormal dreams 2% 3%
Agitation <1% 2%
Musculoskeletal and Connective Tissue Disorders
Myalgia 2% 3%
Pain in extremity 2% 3%
Respiratory, Thoracic, and Mediastinal Disorders
Cough 3% 4%
General Disorders and Administration Site Conditions
Feeling jittery 2% 3%
Skin and Subcutaneous Tissue Disorders
Rash 2% 3%
Metabolism and Nutrition Disorders
Decreased appetite 1% 4%
Reproductive System and Breast Disorders
Dysmenorrhea <1% 2%
Ear and Labyrinth Disorders
Tinnitus <1% 3%
Vascular Disorders
Hypertension 0% 2%

Changes In Body Weight

Table 5 presents the incidence of body weight changes (≥5 lbs) in the short-term MDD trials using bupropion HCl sustained-release. There was a dose-related decrease in body weight.

Table 5: Incidence of Weight Gain or Weight Loss (≥5 lbs) in MDD Trials Using Bupropion HCl Sustained-Release

Weight Change Bupropion HCl Sustained-Release 300 mg/day
Bupropion HCl Sustained-Release 400 mg/day
Gained >5 lbs 3% 2% 4%
Lost >5 lbs 14% 19% 6%

Table 6 presents the incidence of body weight changes (≥5 lbs) in the 3 SAD trials using bupropion HCl extended-release. A higher proportion of subjects in the bupropion group (23%) had a weight loss ≥5 lbs, compared to the placebo group (11%). These were relatively long-term trials (up to 6 months).

Table 6: Incidence of Weight Gain or Weight Loss (≥5 lbs) in SAD Trials Using Bupropion HCl Extended-Release

Weight Change Bupropion HCl Extended-Release 150 to 300 mg/day
Gained >5 lbs 11% 21%
Lost >5 lbs 23% 11%

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Wellbutrin XL. 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 (General)

Chills, facial edema, edema, peripheral edema, musculoskeletal chest pain, photosensitivity, and malaise.


Postural hypotension, hypertension, stroke, vasodilation, syncope, complete atrioventricular block, extrasystoles, myocardial infarction, phlebitis, and pulmonary embolism.


Abnormal liver function, bruxism, gastric reflux, gingivitis, glossitis, increased salivation, jaundice, mouth ulcers, stomatitis, thirst, edema of tongue, colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, intestinal perforation, liver damage, pancreatitis, and stomach ulcer.


Hyperglycemia, hypoglycemia, and syndrome of inappropriate antidiuretic hormone secretion.

Hemic And Lymphatic

Ecchymosis, anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia. Altered PT and/or INR, associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin.

Metabolic And Nutritional



Leg cramps, fever/rhabdomyolysis, and muscle weakness.

Nervous System

Abnormal coordination, depersonalization, emotional lability, hyperkinesia, hypertonia, hypesthesia, vertigo, amnesia, ataxia, derealization, abnormal electroencephalogram (EEG), aggression, akinesia, aphasia, coma, dysarthria, dyskinesia, dystonia, euphoria, extrapyramidal syndrome, hypokinesia, increased libido, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia.


Bronchospasm and pneumonia.


Maculopapular rash, alopecia, angioedema, exfoliative dermatitis, and hirsutism, acute generalized exanthematous pustulosis.

Special Senses

Accommodation abnormality, dry eye, deafness, increased intraocular pressure, angle-closure glaucoma, and mydriasis.


Impotence, polyuria, prostate disorder, abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, salpingitis, urinary incontinence, urinary retention, and vaginitis.


Potential For Other Drugs To Affect Wellbutrin XL

Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between Wellbutrin XL and drugs that are inhibitors or inducers of CYP2B6.

Inhibitors Of CYP2B6

Ticlopidine And Clopidogrel

Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of Wellbutrin XL may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see CLINICAL PHARMACOLOGY].

Inducers Of CYP2B6

Ritonavir, Lopinavir, And Efavirenz

Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of Wellbutrin XL may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see CLINICAL PHARMACOLOGY].

Carbamazepine, Phenobarbital, Phenytoin

While not systemically studied, these drugs may induce metabolism of bupropion and may decrease bupropion exposure [see CLINICAL PHARMACOLOGY]. If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded.

Potential For Wellbutrin XL To Affect Other Drugs

Drugs Metabolized By CYP2D6

Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of Wellbutrin XL with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, and flecainide). When used concomitantly with Wellbutrin XL, it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index.

Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with Wellbutrin XL and such drugs may require increased doses of the drug [see CLINICAL PHARMACOLOGY].

Drugs That Lower Seizure Threshold

Use extreme caution when coadministering Wellbutrin XL with other drugs that lower the seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, or systemic corticosteroids). Use low initial doses of Wellbutrin XL and increase the dose gradually [see WARNINGS AND PRECAUTIONS].

Dopaminergic Drugs (Levodopa and Amantadine)

Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was coadministered with levodopa or amantadine. Adverse reactions have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. It is presumed that the toxicity results from cumulative dopamine agonist effects. Use caution when administering Wellbutrin XL concomitantly with these drugs.

Use With Alcohol

In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with Wellbutrin XL. The consumption of alcohol during treatment with Wellbutrin XL should be minimized or avoided.

MAO Inhibitors

Bupropion inhibits the reuptake of dopamine and norepinephrine. Concomitant use of MAOIs and bupropion is contraindicated because there is an increased risk of hypertensive reactions if bupropion is used concomitantly with MAOIs. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor phenelzine. At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of treatment with Wellbutrin XL. Conversely, at least 14 days should be allowed after stopping Wellbutrin XL before starting an MAOI antidepressant [see DOSAGE AND ADMINISTRATION and CONTRAINDICATIONS].

Drug-Laboratory Test Interactions

False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. This is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

Drug Abuse And Dependence

Controlled Substance

Bupropion is not a controlled substance.



Controlled clinical studies of bupropion HCl immediate-release conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed patients demonstrated an increase in motor activity and agitation/excitement.

In a population of individuals experienced with drugs of abuse, a single dose of 400 mg bupropion produced mild amphetamine-like activity as compared to placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI), and a score intermediate between placebo and amphetamine on the Liking Scale of the ARCI. These scales measure general feelings of euphoria and drug desirability.

Findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. Nonetheless, evidence from single-dose studies does suggest that the recommended daily dosage of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, higher doses (that could not be tested because of the risk of seizure) might be modestly attractive to those who abuse CNS stimulant drugs.

Bupropion hydrochloride extended-release tablets are intended for oral use only. The inhalation of crushed tablets or injection of dissolved bupropion has been reported. Seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection.


Studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. In rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavioral response, and increase rates of responding in several schedule-controlled behavior paradigms. In primate models assessing the positive reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. In rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

Read the entire FDA prescribing information for Wellbutrin XL (Bupropion Hydrochloride Extended-Release)

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

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