Medications: Wellbutrin^® – buproprion

WELLBUTRIN XL is an aminoketone antidepressant, indicated for:

• treatment of major depressive disorder (MDD) (1.1)
• prevention of seasonal affective disorder (SAD) (1.2)

DOSAGE AND ADMINISTRATION

General:

• Increase dose gradually to reduce seizure risk. (2.1, 5.3)
• Periodically reassess the dose and need for maintenance treatment. (2.2)

Major Depressive Disorder

• Starting dose: 150 mg once daily. Usual target dose: 300 mg once daily (2.2)
• After 4 days, may increase the dose to 300 mg once daily. (2.2)

Seasonal Affective Disorder

• Initiate treatment in the autumn prior to onset of seasonal depressive symptoms. (2.3)
• Starting dose: 150 mg once daily. Usual target dose: 300 mg once daily. (2.3)
• After one week, may increase the dose to 300 mg once daily. (2.3)
• Continue treatment through the winter season. (2.3)

Hepatic Impairment

• Moderate to severe hepatic impairment: 150 mg every other day (2.6)
• Mild hepatic impairment: Consider reducing the dose and/or frequency of dosing. (2.6, 8.7)

Renal Impairment

• Consider reducing the dose and/or frequency of dosing. (2.7, 8.6)

Most common adverse reactions are (incidence ≥5%; ≥2× placebo rate): dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, rash. (6.1)

• Seizure disorder. (4, 5.3)
• Current or prior diagnosis of bulimia or anorexia nervosa (4, 5.3)
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptic drugs. (4, 5.3)
• Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with WELLBUTRIN XL or within 14 days of stopping treatment with WELLBUTRIN XL. Do not use WELLBUTRIN XL within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start WELLBUTRIN XL in a patient who is being treated with linezolid or intravenous methylene blue. (4, 7.6)
• Known hypersensitivity to bupropion or other ingredients of WELLBUTRIN XL (4, 5.8)

WARNINGS AND PRECAUTIONS:

• Neuropsychiatric Adverse Events During Smoking Cessation: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events 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. Observe patients attempting to quit smoking with WELLBUTRIN XL for the occurrence of such symptoms and instruct them to discontinue WELLBUTRIN XL and contact a healthcare provider if they experience such adverse events. (5.2)
• Seizure Risk: The risk is dose-related. Can minimize risk by limiting daily dose to 450 mg and gradually increasing the dose. Discontinue if seizure occurs. (4, 5.3, 7.3)
• Hypertension: WELLBUTRIN XL can increase blood pressure. Monitor blood pressure before initiating treatment and periodically during treatment. (5.4)
• Activation of Mania/Hypomania: Screen patients for bipolar disorder and monitor for these symptoms. (5.5)
• Psychosis and Other Neuropsychiatric Reactions: Instruct patients to contact a healthcare professional if such reactions occur. (5.6)
• Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. (5.7)

• CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based on clinical exposure, but should not exceed the maximum recommended dose. (7.1)
• Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). Consider dose reduction when using with bupropion. (7.2)
• Drugs that lower seizure threshold: Dose WELLBUTRIN XL with caution. (5.3, 7.3)
• Dopaminergic Drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly with WELLBUTRIN XL. (7.4)
• MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly with WELLBUTRIN XL. (7.6)
• Drug-laboratory test interactions: WELLBUTRIN XL can cause false positive urine test results for amphetamines. (7.7)

Overdoses of up to 30 grams or more of bupropion have been reported. Seizure was reported in approximately one third of all cases. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, sinus tachycardia, and ECG changes such as conduction disturbances or arrhythmias. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses. Although most patients recovered without sequelae, deaths associated with overdoses of bupropion alone have been reported in patients ingesting large doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients. 10.2

Overdosage Management: Consult a Certified Poison Control Center for up-to-date guidance and advice. Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR). Call 1-800-222-1222 or refer to www.poison.org. There are no known antidotes for bupropion. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Consider the possibility of multiple drug overdose.