Wellbutrin (Bupropion) Drug Inofrmation

Bupropion Description, Indications, Side Effects, Warnings, Pharmacology, and Dosage
Antidepressant Basics: Wellbutrin

Generic Name: Bupropion
Brand Names: • Wellbutrin • Wellbutrin SR • Wellbutrin XL
• Zyban • Aplenzin • Buproban • Budeprion

Class: Aminoketone, Antidepressant, Smoking Cessation Agent

Updated: July 2014

Wellbutrin

What Is It?

Wellbutrin™ (bupropion hydrochloride) is an aminoketone, an antidepressant, and a smoking cessation agent. WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, and ZYBAN are registered trademarks of the GlaxoSmithKline group of companies.

What Does It Treat?

Wellbutrin is indicated and FDA approved for the treatment of:
• major depressive disorder
• seasonal affective disorder
• smoking sessation

Off-label uses include the treatment of:
• weight loss
• attention-deficit hyperactivity disorder (ADHD)
• bipolar depression
• chronic fatigue syndrome
• pathological gambling (PG)
• methamphetamine dependence
• improvement in sexual functioning in women
• augmentation of SSRIs and venlafaxine in partial and non-responders
• antidote for SSRI-induced sexual dysfunction
• dysthymic disorder (DD)

Specifically, Bupropion (Aplenzin, Wellbutrin, Wellbutrin SR, Wellbutrin XL) is used to treat depression, Bupropion (Aplenzin, Wellbutrin XL) is also used to treat seasonal affective disorder (SAD), and Bupropion (Zyban) is used for smoking sessation. The efficacy of Wellbutrin in the treatment of a major depressive episode was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult subjects with MDD.

Some people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using WELLBUTRIN. Your family or other caregivers should also be alert to changes in your mood or symptoms.

This medication guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about.

Do not start or stop any medicine while taking Wellbutrin without talking to your healthcare provider first.

Who Should Not Take Wellbutrin?

Do not take Wellbutrin if you: 1) are allergic to buproprion or any of the ingredients in Wellbutrin. See the end of this section for a complete list of ingredients in Wellbutrin; 2) are undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs; 3) have any sort of seizure disorder; 4) have a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with Wellbutrin; 5) take a monoamine oxidase inhibitor (MAOI) or have taken an MAOI in the past 14 days. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 2 weeks of stopping Wellbutrin unless directed to do so by your physician. Do not start Wellbutrin if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician. MAOIs include Parnate (Tranylcypromine), Nardil (Phenelzine), Emsam (Selegiline transdermal), and Marplan (Isocarboxazid).

Safety and effectiveness in the pediatric population have not been established. Do not give Wellbutrin to anyone younger than 18 years old without the advice of a doctor.

Before Starting Wellbutrin

Tell your healthcare provider about: 1) any medical conditions you have, including seizure disorder, cardiac, liver, kidney, or blood disease; 2) current pregnancy or plans to become pregnant; 3) current breastfeeding or plans to breastfeed; 4) any and all medications and supplements you are taking; 5) any thoughts or feelings of suicide. 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.

Patients should be told that the concomitant use of Wellbutrin and alcohol is not advised. Patients should inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, as there is a potential for interactions. Patients should notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should notify their physician if they are breast feeding an infant. While patients may notice improvement with Wellbutrin therapy, they should be advised to continue therapy as directed.

Ingredients of WELLBUTRIN:

Active ingredient: bupropion hydrochloride. Inactive ingredients: 75-mg tablet – D&C Yellow No. 10 Lake, FD&C Yellow No. 6 Lake, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide; 100-mg tablet – FD&C Red No. 40 Lake, FD&C Yellow No. 6 Lake, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide.

Indications and Usage

Wellbutrin is indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM). Bupropion (Aplenzin, Wellbutrin, Wellbutrin SR, Wellbutrin XL) is used to treat depression. Bupropion (Aplenzin, Wellbutrin XL) is also used to treat seasonal affective disorder (SAD). Bupropion (Zyban) is used for smoking sessation. Wellbutrin may also be used for purposes not listed in this medication guide. Talk to your doctor about the possible risks of using this medication for your condition.

The physician who elects to use Wellbutrin for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Contraindications

WELLBUTRIN is contraindicated in patients with a seizure disorder.

WELLBUTRIN is contraindicated 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.

WELLBUTRIN is contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs.

The use of MAOIs (intended to treat psychiatric disorders) concomitantly with WELLBUTRIN or within 14 days of discontinuing treatment with WELLBUTRIN is contraindicated. There is an increased risk of hypertensive reactions when WELLBUTRIN is used concomitantly with MAOIs. The use of WELLBUTRIN within 14 days of discontinuing treatment with an MAOI is also contraindicated. Starting WELLBUTRIN in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated

Common Side Effects

Cardiovascular: Hypertension (2.5% to 4.3% ), Tachyarrhythmia (10.8% )
Dermatologic: Pruritus (2% to 4% ), Rash (3% to 5% ), Urticaria (1% to 2% )
Gastrointestinal: Constipation (5% to 26% ), Nausea (9% to 24% )
Musculoskeletal: Arthralgia (1% to 5% ), Myalgia (2% to 6% )
Neurologic: Confusion (8.4% ), Dizziness (6% to 22.3% ), Headache (approximately 25% ), Insomnia (11% to 40% ), Tremor (2% to 21.1% )
Otic: Tinnitus (3% )
Psychiatric: Agitation (2% to 31.9% ), Anxiety (3.1% to 8% ), Hostile behavior (6% )
Reproductive: Disorder of menstruation (5% )
Respiratory: Pharyngitis (3% to 11% )
Other: Xerostomia (10% to 27.6% )

Serious Side Effects

Cardiovascular: Cardiac dysrhythmia (5.3% ), Wide QRS complex
Dermatologic: Stevens-Johnson syndrome (rare )
Immunologic: Anaphylaxis
Neurologic: Seizure (0.1% to 0.4% )
Psychiatric: Depression, exacerbation, Mania, Psychotic disorder, Suicidal thoughts

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

Suicidality and Antidepressant Drugs

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects over age 24; there was a reduction in risk with antidepressant use in subjects aged 65 and older. 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. Patients with MDD, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.

Neuropsychiatric Reactions

Serious neuropsychiatric reactions have occurred in patientstaking bupropion for smoking cessation. The majority of these reactions occurred during bupropion treatment, but some occurred in the context of discontinuing treatment. In many cases, a causal relationship to bupropion treatment is not certain, because depressed mood may be a symptom of nicotine withdrawal. However, some of the cases occurred in patients taking bupropion who continued to smoke. Although WELLBUTRIN is not approved for smoking cessation, observe all patients for neuropsychiatric reactions. Instruct the patient to contact a healthcare provider if such reactions occur.

Seizures

WELLBUTRIN can cause seizure. The risk of seizure is dose-related. The dose should not exceed 450 mg per day. Increase the dose gradually. Discontinue WELLBUTRIN and do not restart treatment if the patient experiences a seizure. The risk of seizures is also related to patient factors, clinical situations, and concomitant medications that lower the seizure threshold. Consider these risks before initiating treatment with WELLBUTRIN. WELLBUTRIN is contraindicated in patients with a seizure disorder, current or prior diagnosis of anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. The following conditions can also increase the risk of seizure: severe head injury; arteriovenous malformation; CNS tumor or CNS infection; severe stroke; 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); 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; and excessive use of alcohol, benzodiazepines, sedative/hypnotics, or opiates. Incidence of Seizure With Bupropion Use: Bupropion is associated with seizures in approximately 0.4% (4/1,000) of patients treated at doses up to 450 mg per day. The estimated seizure incidence for WELLBUTRIN increases almost 10-fold between 450 and 600 mg per day. The risk of seizure can be reduced if the dose of WELLBUTRIN does not exceed 450 mg per day, given as 150 mg 3 times daily, and the titration rate is gradual.

Hypertension

Treatment with WELLBUTRIN can result in elevated blood pressure and hypertension. Assess blood pressure before initiating treatment with WELLBUTRIN, and monitor periodically during treatment. The risk of hypertension is increased if WELLBUTRIN is used concomitantly with MAOIs or other drugs that increase dopaminergic or noradrenergic activity. Data from a comparative trial of the sustained-release formulation of bupropion HCl, nicotine transdermal system (NTS), the combination of sustained-release bupropion plus NTS, and placebo as an aid to smoking cessation suggest a higher incidence of treatment-emergent hypertension in patients treated with the combination of sustained-release bupropion and NTS. In this trial, 6.1% of subjects treated with the combination of sustained-release bupropion and NTS had treatment‑emergent hypertension compared to 2.5%, 1.6%, and 3.1% of subjects treated with sustained-release bupropion, NTS, and placebo, respectively. The majority of these subjects had evidence of pre-existing hypertension. Three subjects (1.2%) treated with the combination of sustained-release bupropion and NTS and 1 subject (0.4%) treated with NTS had study medication discontinued due to hypertension compared with none of the subjects treated with sustained-release bupropion or placebo. Monitoring of blood pressure is recommended in patients who receive the combination of bupropion and nicotine replacement. In a clinical trial of bupropion immediate-release in MDD subjects with stable congestive heart failure (N = 36), bupropion was associated with an exacerbation of pre-existing hypertension in 2 subjects, leading to discontinuation of bupropion treatment. There are no controlled trials assessing the safety of bupropion in patients with a recent history of myocardial infarction or unstable cardiac disease.

Activation of Mania/Hypomania

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, 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 is not approved for use in treating bipolar depression.

Psychosis and Other Neuropsychiatric Reactions

Depressed patients treated with WELLBUTRIN have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. Some of these patients had a diagnosis of bipolar disorder. In some cases, these symptoms abated upon dose reduction and/or withdrawal of treatment. Instruct patients to contact a healthcare professional if such reactions occur.

Hypersensitivity Reactions

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. Instruct patients to discontinue WELLBUTRIN and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction (e.g., skin rash, pruritus, hives, chest pain, edema, and shortness of breath) during treatment. There are reports of arthralgia, myalgia, fever with rash and other serum sickness-like symptoms suggestive of delayed hypersensitivity.

Overdose

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 (including QRS prolongation) 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.

Call 911 or visit your nearest hospital for all suspected overdose cases.

Pregnancy

Pregnancy Category C
Risk Summary:
Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations overall. All pregnancies, regardless of drug exposure, have a background rate of 2% to 4% for major malformations, and 15% to 20% for pregnancy loss. No clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately equal to the maximum recommended human dose (MRHD) and greater and decreased fetal weights were seen at doses twice the MRHD and greater. WELLBUTRIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations:
Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.

Human Data:
Data from the international bupropion Pregnancy Registry (675 first-trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. No increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). Data from the United Healthcare database and a case-control study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) from the National Birth Defects Prevention Study (NBDPS) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester. Study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding a possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO (n = 10; adjusted OR = 2.6; 95% CI: 1.2, 5.7), and the Slone Epidemiology case control study did not find increased risk for LVOTO. 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. The Slone Epidemiology Study found an increased risk for VSD following first trimester maternal bupropion exposure (n = 17; adjusted OR = 2.5; 95% CI: 1.3, 5.0) but did not find increased risk for any other cardiovascular malformations studied (including LVOTO as above). The NBDPS and United Healthcare database study did not find an association between first trimester maternal bupropion exposure and VSD. For the findings of LVOTO and VSD, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies.

Detailed Summary

WELLBUTRIN (bupropion hydrochloride), an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re‑uptake inhibitor, or other known antidepressant agents. Its structure closely resembles that of diethylpropion; it is related to phenylethylamines. It is designated as (±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride. The molecular weight is 276.2. The molecular formula is C13H18ClNO•HCl. Bupropion hydrochloride powder is white, crystalline, and highly soluble in water. It has a bitter taste and produces the sensation of local anesthesia on the oral mucosa. WELLBUTRIN is supplied for oral administration as 75‑mg (yellow‑gold) and 100‑mg (red) film‑coated tablets. Each tablet contains the labeled amount of bupropion hydrochloride and the inactive ingredients: 75‑mg tablet – D&C Yellow No. 10 Lake, FD&C Yellow No. 6 Lake, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide; 100‑mg tablet – FD&C Red No. 40 Lake, FD&C Yellow No. 6 Lake, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, polyethylene glycol, talc, and titanium dioxide.

Mechanism of Action

The exact mechanism of the antidepressant action of bupropion is not known, but is presumed to be related to noradrenergic and/or dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine, and does not inhibit the reuptake of serotonin. Bupropion does not inhibit monoamine oxidase.

Pharmacokinetics

Bupropion is a racemic mixture. The pharmacological activity and pharmacokinetics of the individual enantiomers have not been studied. The mean elimination half-life (±SD) of bupropion after chronic dosing is 21 (±9) hours, and steady-state plasma concentrations of bupropion are reached within 8 days.

Absorption: The absolute bioavailability of WELLBUTRIN in humans has not been determined because an intravenous formulation for human use is not available. However, it appears likely that only a small proportion of any orally administered dose reaches the systemic circulation intact. In rat and dog studies, the bioavailability of bupropion ranged from 5% to 20%. In humans, following oral administration of WELLBUTRIN, peak plasma bupropion concentrations are usually achieved within 2 hours. Plasma bupropion concentrations are dose‑proportional following single doses of 100 to 250 mg; however, it is not known if the proportionality between dose and plasma level is maintained in chronic use.

Distribution: In vitro tests show that bupropion is 84% bound to human plasma proteins at concentrations up to 200 mcg/mL. The extent of protein binding of the hydroxybupropion metabolite is similar to that for bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half that seen with bupropion.

Metabolism: Bupropion is extensively metabolized in humans. Three metabolites are active: hydroxybupropion, which is formed via hydroxylation of the tert-butyl group of bupropion, and the amino-alcohol isomers threohydrobupropion and erythrohydrobupropion, which are formed via reduction of the carbonyl group. In vitro findings suggest that CYP2B6 is the principal isoenzyme involved in the formation of hydroxybupropion, while cytochrome P450 enzymes are not involved in the formation of threohydrobupropion. Oxidation of the bupropion side chain results in the formation of a glycine conjugate of meta-chlorobenzoic acid, which is then excreted as the major urinary metabolite. The potency and toxicity of the metabolites relative to bupropion have not been fully characterized. However, it has been demonstrated in an antidepressant screening test in mice that hydroxybupropion is one‑half as potent as bupropion, while threohydrobupropion and erythrohydrobupropion are 5-fold less potent than bupropion. This may be of clinical importance because the plasma concentrations of the metabolites are as high as or higher than those of bupropion.

Drug-Drug Interactions Including P450 Interactions

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

Inhibitors of CYP2B6: Ticlopidine and Clopidogrel (not a complete list): Concomitant treatment with these drugs can increase bupropion exposure but decrease hydroxybupropion exposure. Based on clinical response, dosage adjustment of WELLBUTRIN may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel).

Inducers of CYP2B6: Ritonavir, Lopinavir, and Efavirenz (not a complete list): Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of WELLBUTRIN may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose. Carbamazepine, Phenobarbital, Phenytoin: While not systematically studied, these drugs may induce the 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.

Dosage and Administration

Dosage Forms and Strengths

• WELLBUTRIN Tablets, 75 mg of bupropion hydrochloride, are yellow-gold, round, biconvex tablets printed with “WELLBUTRIN 75” in bottles of 100 (NDC 0173-0177-55).

• WELLBUTRIN Tablets, 100 mg of bupropion hydrochloride, are red, round, biconvex tablets printed with “WELLBUTRIN 100” in bottles of 100 (NDC 0173-0178-55).

Adults
Pamelor is administered orally in the form of capsules or liquid. Lower than usual dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients than for hospitalized patients who will be under close supervision. The physician should initiate dosage at a low level and increase it gradually, noting carefully the clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a longer period of time at the lowest dose that will maintain remission. If a patient develops minor side effects, the dosage should be reduced. The drug should be discontinued promptly if adverse effects of a serious nature or allergic manifestations occur. Usual Adult Dose – 25 mg three or four times daily; dosage should begin at a low level and be increased as required. As an alternate regimen, the total daily dosage may be given once a day. When doses above 100 mg daily are administered, plasma levels of nortriptyline should be monitored and maintained in the optimum range of 50 to 150 ng/mL. Doses above 150 mg/day are not recommended.

Nursing Mothers
Bupropion and its metabolites are present in human milk. In a lactation study of 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. The average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Exercise caution when WELLBUTRIN is administered to a nursing woman.

Pediatric Use
Safety and effectiveness in the pediatric population have not been established.

Geriatric Use
Of the approximately 6,000 subjects who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation trials), 275 were aged ≥65 years and 47 were aged ≥75 years. In addition, several hundred subjects aged ≥65 years participated in clinical trials using the immediate-release formulation of bupropion (depression trials). No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function.

Renal Impairment
Consider a reduced dose and/or dosing frequency of WELLBUTRIN in patients with renal impairment (Glomerular Filtration Rate: <90 mL/min). Bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. Monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures. Hepatic Impairment
In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose of WELLBUTRIN is 75 mg daily. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing.

This dosage information does not include all the information needed to use WELLBUTRIN safely and effectively. See full prescribing information for WELLBUTRIN. The information at DepressionHealth.net is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.
This abridged guide is not the complete medication guide, and does not act as medical advice or replace the advice of a physician.
This guide is meant to be used as an educational tool and supplement to the expert advice and judgement of a physician.
Get emergency medical help or visit your nearest hospital if you have any of the signs of an allergic reaction when taking this medication:
skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
If you overdose, seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of bupropion can be fatal.
The above information derives from the following sources: FDA Monograph Citation NDA018644, Micromedex®, MedlinePlus, DailyMed. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. Disclaimer: Every effort has been made to ensure that the information provided by Depression Health Network is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This product’s label may have been updated. For more information about WELLBUTRIN, go to www.wellbutrin.com or call 1-888-825-5249. To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.