Brands, Medical Use, Clinical Data
- Immediate and sustained release tablets
Brands / Synonyms
Aplenzin; Bupropion Hcl; Wellbatrin; Wellbutrin; Wellbutrin SR; Wellbutrin XL; Zyban; Zyban
For the treatment of depression and as aid to smoking cessation.
Bupropion, an antidepressant of the aminoketone class and a non-nicotine aid to smoking cessation, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. Compared to classical tricyclic antidepressants, Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine. In addition, Bupropion does not inhibit monoamine oxidase. Bupropion produces dose-related central nervous system (CNS) stimulant effects in animals, as evidenced by increased locomotor activity, increased rates of responding in various schedule-controlled operant behavior tasks, and, at high doses, induction of mild stereotyped behavior.
Mechanism of Action
Bupropion selectively inhibits the neuronal reuptake of dopamine, norepinephrine, and serotonin; actions on dopaminergic systems are more significant than imipramine or amitriptyline whereas the blockade of norepinephrine and serotonin reuptake at the neuronal membrane is weaker for bupropion than for tricyclic antidepressants. The increase in norepinephrine may attenuate nicotine withdrawal symptoms and the increase in dopamine at neuronal sites may reduce nicotine cravings and the urge to smoke. Bupropion exhibits moderate anticholinergic effects.
For sustained release, peak plasma concentrations are achieved within 3 hours.
Symptoms of overdose include seizures, hallucinations, loss of consciousness, tachycardia, and cardiac arrest.
Biotrnasformation / Drug Metabolism
Reduction of the carbonyl groupand/or hydroxylation of the tert-butyl group of bupropion.
WELLBUTRIN is contraindicated in patients with a seizure disorder.
WELLBUTRIN is contraindicated in patients treated with ZYBANÒ
(bupropion hydrochloride) Sustained-Release Tablets, or any other medications that contain bupropion because the
incidence of seizure is dose dependent.
WELLBUTRIN is also contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa
because of a higher incidence of seizures noted in such patients treated with WELLBUTRIN.
WELLBUTRIN is contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including
The concurrent administration of WELLBUTRIN and a monoamine oxidase (MAO) inhibitor is contraindicated. At least
14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with WELLBUTRIN.
WELLBUTRIN is contraindicated in patients who have shown an allergic response to bupropion or the other
ingredients that make up WELLBUTRIN Tablets.
Few systemic data have been collected on the metabolism of WELLBUTRIN following concomitant administration with
other drugs or, alternatively, the effect of concomitant administration of WELLBUTRIN on the metabolism of other
Because bupropion is extensively metabolized, the coadministration of other drugs may affect its clinical
activity. In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by the CYP2B6
isoenzyme. Therefore, the potential exists for a drug interaction between WELLBUTRIN and drugs that affect the CYP2B6
isoenzyme (e.g., orphenadrine and cyclophosphamide). The threohydrobupropion metabolite of bupropion does not appear
to be produced by the cytochrome P450 isoenzymes. The effects of concomitant administration of cimetidine on the
pharmacokinetics of bupropion and its active metabolites were studied in 24 healthy young male volunteers. Following
oral administration of two 150-mg sustained-release tablets with and without 800 mg of cimetidine, the
pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the
AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.
While not systematically studied, certain drugs may induce the metabolism of bupropion (e.g., carbamazepine,
Animal data indicated that bupropion may be an inducer of drug-metabolizing enzymes in humans. In one study,
following chronic administration of bupropion, 100 mg 3 times daily to 8 healthy male volunteers for 14 days, there
was no evidence of induction of its own metabolism. Nevertheless, there may be the potential for clinically important
alterations of blood levels of coadministered drugs.
Drugs Metabolized by Cytochrome P450IID6 (CYP2D6): Many drugs, including most antidepressants
(SSRIs, many tricyclics), beta-blockers, antiarrhythmics, and antipsychotics are metabolized by the CYP2D6 isoenzyme.
Although bupropion is not metabolized by this isoenzyme, bupropion and hydroxybupropion are inhibitors of the CYP2D6
isoenzyme in vitro. In a study of 15 male subjects (ages 19 to 35 years) who were extensive metabolizers of the
CYP2D6 isoenzyme, daily doses of bupropion given as 150 mg twice daily followed by a single dose of 50 mg desipramine
increased the Cmax, AUC, and t1/2 of desipramine by an average of approximately 2-, 5- and
2-fold, respectively. The effect was present for at least 7 days after the last dose of bupropion. Concomitant use of
bupropion with other drugs metabolized by CYP2D6 has not been formally studied.
Therefore, co-administration of bupropion with drugs that are metabolized by CYP2D6 isoenzyme including certain
antidepressants (e.g., 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), should be approached with caution and should be initiated at the lower end of the dose
range of the concomitant medication. If bupropion is added to the treatment regimen of a patient already receiving a
drug metabolized by CYP2D6, the need to decrease the dose of the original medication should be considered,
particularly for those concomitant medications with a narrow therapeutic index.
MAO Inhibitors: Studies in animals demonstrate that the acute toxicity of bupropion is
enhanced by the MAO inhibitor phenelzine .
Levodopa and Amantadine: Limited clinical data suggest a higher incidence of adverse experiences in
patients receiving bupropion concurrently with either levodopa or amantadine. Administration of WELLBUTRIN Tablets to
patients receiving either levodopa or amantadine concurrently should be undertaken with caution, using small initial
doses and small gradual dose increases.
Drugs that Lower Seizure Threshold: Concurrent administration of WELLBUTRIN and agents (e.g.,
antipsychotics, other antidepressants, theophylline, systemic steroids, etc.) that lower seizure threshold should be
undertaken only with extreme caution. Low initial dosing and small gradual dose increases should be employed.
Nicotine Transdermal System: .
Alcohol: In post-marketing experience, there have been rare reports of adverse neuropsychiatric
events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with WELLBUTRIN. The
consumption of alcohol during treatment with WELLBUTRIN should be minimized or avoided (also see CONTRAINDICATIONS).