Bupropion: Interactions
• Amantadine
• Amoxapine
Anticonvulsants
Antimuscarinics
Antipsychotics
Barbiturates
Benzodiazepines
Beta-blockers
• Carbamazepine
• Cimetidine
• Cocaine
• Codeine
Corticosteroids
• Cyclophosphamide
• Doxercalciferol
• Encainide
• Ethanol
• Ethotoin
• Flecainide
• Fluoxetine
• Fosphenytoin
• Furazolidone
• Guanfacine
• Ifosfamide
• Kava Kava, Piper methysticum
• Levodopa
• Linezolid
• Maprotiline
• Methadone
• Mexiletine
Monoamine oxidase inhibitors (MAOIs)
• Morphine
• Nicotine
• Orphenadrine
• Oxycodone
• Paroxetine
• Pentazocine
Phenothiazines
• Phenytoin
• Procarbazine
• Propafenone
• Propoxyphene
Psychostimulants
Radiopaque Contrast Agents
• Rifampin
• Sertraline
• Tamoxifen
• Theophylline, Aminophylline
• tobacco
• Tramadol
• Trazodone
Tricyclic antidepressants
• Valerian, Valeriana officinalis
• Valproic Acid, Divalproex Sodium
• Warfarin
• Zolpidem
Bupropion Interactions
The use of bupropion concomitantly with monoamine oxidase inhibitors (MAOIs), including drugs with MAOI-activity (e.g., furazolidone [5343], linezolid [5330], procarbazine [5356], or selegiline [5391]), is contraindicated. Although no clinical data have shown a drug interaction between bupropion and MAOIs, studies in animals indicate that bupropion-induced adverse reactions and toxicity appear to be enhanced by phenelzine. At least 14 days should elapse between the discontinuation of a MAO-inhibiting drug and the initiation of bupropion.[4781]
Nicotine transdermal systems (NTS) have been used concurrently with bupropion for smoking cessation therapy. However, when used together, the combination may induce clinically significant blood pressure elevations in some patients.[4781] Close monitoring of blood pressure is recommended if this combination is prescribed, and patients should stop smoking prior to initiating the NTS. Tobacco also contains nicotine as one of its active components, but it is unclear if smoking concurrently with bupropion use increases the risk of blood pressure elevation. Bupropion has not been reported to interact pharmacokinetically with tobacco when used as monotherapy for smoking cessation; however, when bupropion is used as monotherapy, patients should schedule to stop tobacco smoking during the second week of taking bupropion.[4781]
The use of ethanol or the abrupt discontinuation of ethanol, should be avoided in patients taking bupropion.[4781] Either ethanol abuse or abrupt discontinuation of ETOH has been associated with seizures and fatalities, and may increase the risk of seizures and/or neuropsychiatric events with bupropion treatment.[5179] Similarly, other drugs which may lower the seizure threshold should be used with great caution or avoided in patients taking bupropion. These include: some antidepressants; antipsychotics [4781]; cocaine; psychostimulants (e.g., amphetamine, dextroamphetamine and stimulant weight-loss medications); theophylline [4781]; tramadol; and systemic corticosteroids [4781]. The abrupt withdrawal of benzodiazepines may also increase seizure risks.[4781] The manufacturer recommends low initial dosing and slow dosage titration of bupropion if these combinations must be used concurrently; the patient should be closely monitored. When bupropion is used for smoking cessation, it should be noted that cessation of smoking may result in elevated serum concentrations of some drugs that are hepatically metabolized, such as theophylline or aminophylline, due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation.
Bupropion may interact with tricyclic antidepressants (TCAs).[4781] The manufacturer of bupropion warns of using any TCAs with bupropion due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus reduces the clearance of TCAs.[4718] Bupropion-induced elevations in both imipramine and desipramine plasma concentrations may occur. TCA half-lives have increased in pharmacokinetic studies. The anticholinergic effects of bupropion may be also be additive with those of the TCAs. Prolonged seizure activity has been reported following the combined use clomipramine and bupropion.[6629] The manufacturer recommends low initial dosing and slow dosage titration if these drugs must be used concurrently; the patient should be closely monitored.
Cimetidine has resulted in increased plasma concentrations of the active metabolites, threohydrobupropion and erythrobupropion, but the clinical significance is not known. Caution is warranted if other medications that are known to significantly impair multiple CYP isoenzymes are prescribed to patients on bupropion, even though clinical documentation of such interactions is lacking.[4718] Increases in bupropion serum concentrations that might occur as a result of such interactions could be clinically significant in some patients.
It should be noted that when anticonvulsants are used for the purpose of treating epilepsy (versus use in mood disorders or neuropathic pain or other non-epilepsy conditions), that bupropion should not be used by patients with a preexisting seizure disorder; this represents a disease-drug interaction, and not a drug-drug interaction per se. Bupropion may be combined with anticonvulsant treatments with caution when an anticonvulsant is used for non-epilepsy conditions (e.g., neuropathic pain, mood disorders). Bupropion may interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as carbamazepine, barbiturates, or phenytoin [5556] (as well as fosphenytoin [5265], ethotoin [4741]).[4781] Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when carbamazepine was added.[4557] Valproic acid, in multiple-dose pharmacokinetic studies, caused an increase in the plasma concentrations of the active hydroxybupropion metabolite of bupropion; no changes in the kinetics of bupropion were noted and the clinical significance of the potential interaction between valproic acid (or divalproex) and bupropion is not known.[4557] Bupropion has been shown to have no pharmacokinetic interaction with lamotrigine.[4556] No reports of a pharmacokinetic interaction between gabapentin or bupropion have been found.
Bupropion may interact with drugs that induce hepatic microsomal isoenzyme function such as rifampin.[4718] Pharmacokinetic studies describe patients who developed subtherapeutic bupropion serum concentrations when enzyme-inducing agents were added.
Use bupropion cautiously in patients taking levodopa or combination drugs containing levodopa.[4781] Limited data suggest that adverse effects due to either drug may increase if bupropion is administered concomitantly with levodopa. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if levodopa is used concurrently; the patient should be closely monitored.[4781]
Bupropion exhibits moderate anticholinergic effects.[4781] Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with bupropion.
The German Commission E and other groups warn that any substances that act on the CNS, including psychopharmacologic agents, may interact with the phytomedicinals kava kava, Piper methysticum [5559] or valerian, Valeriana officinalis.[5184] These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action.
There is one case report that describes a grand mal seizure that occurred in a child of 10 years of age receiving guanfacine and bupropion concurrently.[5185] It is not possible, based on this limited report, to determine if guanfacine was a contributor to the event. Causality has not been established.
Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro. Co-administration of bupropion with medications that are metabolized by the CYP2D6 hepatic isoenzyme should be approached with caution.[4718] [4781] Although clinical evidence of interactions is lacking, plasma concentrations of medications metabolized by CYP2D6 may be increased if bupropion is added. These medications include beta-blockers [4781]; some anti-arrhythmic agents [4781] (e.g., encainide, flecainide, mexiletine, propafenone); most antidepressants (e.g., amoxapine [5288], maprotiline [5491], TCAs, trazodone, and some SSRIs, like fluoxetine, paroxetine and sertraline [4781]); cyclobenzaprine; darifenacin [4747], mirtazapine; ondansetron; phenothiazines and many other antipsychotics (i.e., haloperidol, risperidone); tamoxifen; and tramadol. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients. This list may not be inclusive of all agents potentially affected by CYP2D6 metabolism.
Rare cases of hallucinations have occurred when zolpidem was administered concurrently with bupropion. Dosage reductions in zolpidem may be needed if bupropion is used concurrently.[5479]
Patients receiving inhibitors of the CYP2D6 isoenzyme, like bupropion [4718], will have a reduction in the metabolic conversion of codeine to morphine and therefore may not experience an adequate analgesic response to codeine. Plasma concentrations of other opiate agents metabolized by CYP2D6 (e.g., methadone, morphine, oxycodone, pentazocine, or propoxyphene) may be increased if bupropion is added. Dosage reductions in these agents may be needed. Conversely, if bupropion therapy is discontinued, dosages of these agents may need to be adjusted upward in some patients.[2173]
Bupropion and hydroxybupropion are primarily metabolized by the hepatic CYP2B6 isoenzyme. Co-administration of bupropion with medications that are also extensively metabolized by the CYP2B6 hepatic isoenzyme or affected by this isoenzyme should be approached with caution (e.g., orphenadrine, cyclophosphamide, ifosfamide).[4781] There appear to be no adverse reports at this time arising from the concurrent use of these drugs; no confirmative data are available and the potential for interaction is largely theoretical.
Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin during clinical trials and post-marketing experience.[4781] The mechanism of this potential effect is not clear. It may be prudent to monitor the INR when bupropion is added to an existing warfarin regimen. When bupropion is used for smoking cessation, it should be noted that cessation of tobacco smoking may also result in elevated serum concentrations of warfarin due to lowered induction of hepatic oxidative microsomal enzymes (tobacco smoke induces hepatic enzymes). Downward dosage adjustments of warfarin and more frequent monitoring of the INR may be required during smoking cessation.
A possible interaction of amantadine with bupropion has been reported in a few case reports. The patients affected received bupropion concurrently with amantadine and developed neurologic side effects such as restlessness, agitation, gait disturbance and dizziness; some patients required hospitalization. Discontinuation of the drugs resulted in symptom resolution. More data are required to determine the mechanism of this potential interaction. Administer amantadine cautiously with bupropion. The manufacturer recommends low initial dosing and slow dosage titration of bupropion if amantadine is used concurrently; the patient should be closely monitored.[4772][4781]
Use of medications that lower the seizure threshold should be carefully evaluated when considering intrathecal radiopaque contrast agents.[7018] Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.[5442] [5698]
Doxercalciferol is converted in the liver to 1,25-dihydroxyergocalciferol, the major active metabolite, and 1-alpha, 24-dihydroxyvitamin D2, a minor metabolite. Although not specifically studied, cytochrome P450 enzyme inhibitors including bupropion may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if bupropion is coadministered with doxercalciferol.[6904] [7566]
[ Last revised: 8/30/2005 3:06:00 PM ]
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References
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