Indicated for:

Major Depressive Disorder (MDD):

• The treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM).

The efficacy of the immediate-release formulation of bupropion was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with MDD. The efficacy of the sustained-release formulation of bupropion in the maintenance treatment of MDD was established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to bupropion in an 8-week study of acute treatment.

Seasonal Affective Disorder (SAD):

• The prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD).

The efficacy of bupropion hydrochloride extended-release tablets in the prevention of seasonal major depressive episodes was established in 3 placebo-controlled trials in adult outpatients with a history of MDD with an autumn-winter seasonal pattern as defined in the DSM.

To minimize the risk of seizure, increase the dose gradually.

The recommended starting dose for MDD is 150 mg once daily in the morning. After 4 days of dosing, the dose may be increased to the target dose of 300 mg once daily in the morning.

The recommended starting dose for SAD is 150 mg once daily. After 7 days of dosing, the dose may be
increased to the target dose of 300 mg once daily in the morning. Doses above 300 mg of bupropion hydrochloride extended-release were not assessed in the SAD trials.

For the prevention of seasonal MDD episodes associated with SAD, initiate Wellbutrin XL in the autumn, prior to the onset of depressive symptoms. Continue treatment through the winter season. Taper and discontinue Wellbutrin XL in early spring. For patients treated with 300 mg per day, decrease the dose to 150 mg once daily before discontinuing Wellbutrin XL. Individualize the timing of initiation, and duration of treatment should be individualized, based on the patient’s historical pattern of seasonal MDD episodes.

In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose is 150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing.

Consider reducing the dose and/or frequency of Wellbutrin XL in patients with renal impairment (glomerular filtration rate less than 90 mL/min).

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

Wellbutrin XL is contraindicated:

• in patients with seizure disorder
• in patients with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with Wellbutrin XL
• in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
• The use of MAOIs (intended to treat psychiatric disorders) concomitantly with Wellbutrin XL or within 14 days of discontinuing treatment with Wellbutrin XL is contraindicated. There is an increased risk of hypertensive reactions when Wellbutrin XL is used concomitantly with MAOIs. The use of Wellbutrin XL within 14 days of discontinuing treatment with an MAOI is also contraindicated. Starting Wellbutrin XL in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated

Wellbutrin XL is not approved for smoking cessation treatment; however, bupropion HCl sustained-release is approved for this use. Serious neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation. These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses.

Antidepressant treatment can precipitate a manic, mixed, or hypomanic manic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. Prior to initiating Wellbutrin XL, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression). Wellbutrin XL is not approved for the treatment of bipolar depression.

Wellbutrin XL can cause seizure. The risk of seizure is dose-related. The dose should not exceed 300 mg once daily. Increase the dose gradually. 

The risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Wellbutrin XL is contraindicated in patients with a seizure disorder or conditions that increase the risk of seizure (e.g., severe head injury, arteriovenous malformation, CNS tumor or CNS infection, severe stroke, anorexia nervosa or bulimia, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. The following conditions can also increase the risk of seizure: concomitant use of other medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids), metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia), or use of illicit drugs (e.g., cocaine) or abuse or misuse of prescription drugs such as CNS stimulants. Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or insulin, use of anorectic drugs, excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates.

Treatment with Wellbutrin XL can result in elevated blood pressure and hypertension. Assess blood pressure before initiating treatment with Wellbutrin XL, and monitor periodically during treatment. The risk of hypertension is increased if Wellbutrin XL is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity.

Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs including Wellbutrin XL may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Anaphylactoid/anaphylactic reactions have occurred during clinical trials with bupropion. Reactions have been characterized by pruritus, urticaria, angioedema, and dyspnea, requiring medical treatment. In addition, there have been rare, spontaneous postmarketing reports of erythema multiforme, Stevens Johnson syndrome, and anaphylactic shock associated with bupropion.

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).

Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of Wellbutrin XL may be necessary when co-administered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose.

Carbamazepine, Phenobarbital, Phenytoin: While not systematically studied, these drugs may induce metabolism of bupropion and may decrease bupropion exposure. 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.

Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, co-administration 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.

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.

Bupropion, levodopa, and amantadine have dopamine agonist effects. CNS toxicity has been reported when bupropion was co-administered with levodopa or amantadine. Adverse reactions have included restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness.

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.

Study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (VSD) are inconsistent and do not allow conclusions regarding a possible association. Animal studies: fetal malformations and skeletal variations.

Bupropion and its metabolites are present in human milk.

GoToSource

• Use in patients under the age of 18. GoToSource 

• Dosage greater than 300 mg per day in patients without hepatic or renal impairment. GoToSource

• Smoking cessation, bipolar disorder, attention-deficit/hyperactivity disorder and weight loss. GoToSource

• Antidepressant-induced sexual dysfunction, social phobia, post-traumatic stress disorder, neuropathic pain, cocaine addiction and eating disorders. GoToSource

• Fatigue in patients with multiple sclerosis. GoToSource

• Restless legs syndrome. GoToSource

Seizures. GoToSource

Suicidal ideation and behavior. GoToSource

Birth defects. GoToSource

Sexual dysfunction. GoToSource

Liver injury. GoToSource

Constipation. GoToSource

Pruritus (severe itching), urticaria (hives) serum-sickness like reaction (inflammatory reaction) and stevens-johnson syndrome with acute psoriatic exacerbation (severe skin reaction). GoToSource

Erythema multiforme (skin disorder). GoToSource

Psychosis. GoToSource

Angioedema (swelling in deep layers of skin) and anaphylactoid reactions (severe allergic reaction). GoToSource

Mania and hypomania. GoToSource

Hypertension (high blood pressure). GoToSource

Angle-closure glaucoma. GoToSource

Dry mouth, agitation and abuse. GoToSource

Lawsuits filed for suicides and birth defects.