Bupropion Medical Information

BUPROPION (ZYBAN GENERIC)

Why is it so important that all your healthcare providers, including your pharmacists, are fully informed and coordinated about every aspect of your care?

There are hundreds of medications that can interact with bupropion. Most are not severe, but some can be life threatening. Even over-the-counter medications should be checked for interactions. All your providers should be kept informed of any medication that is added, dropped, or changed in your regimen.  

The Physician Desk Reference (PDR) lists the medications that can interact with bupropion, along with the contraindications to its use. The PDR is referenced because it is comprehensive and must be read in its entirety. Contraindications can be absolute, act as relative warnings about drug interactions, and inform patients and healthcare providers how certain conditions can affect the metabolism of bupropion, either increasing or decreasing the amount in the blood. Certain conditions can also make side effects more likely to occur. Some medications might make it more likely for bupropion to cause a seizure and bupropion might make medications less likely to work or more likely to cause side effects of their own.

A few relevant sections are summarized below concerning contraindications to using the medication and drug interactions that can alter how the drugs work or alter their side effect profile, but it is not a complete overview. Please, read the entire package insert, as well.

First, a few general pieces of information. Bupropion can be taken with food if it causes an upset stomach. The evening dose should not be taken at bedtime if it causes insomnia. Do not break the medication. Keep your medication between 68 and 77 degrees F. Keep it stored in a cool, dry, dark place with the lid tightly sealed and away from children. Throw it out if it is beyond the expiration date.

Another very important point is that sometimes bupropion is misidentified on urine screening tests as being an amphetamine, which it is not. If you are being screened for any reason, inform them that an alternate way of testing the urine should be done (e.g., gas chromatography/mass spectrometry).


CONTRAINDICATIONS / PRECAUTIONS

General Information

Bupropion is contraindicated in patients with a history of hypersensitivity to bupropion or any inactive ingredients in the formulations. Reactions can be severe, even delayed long after the medicine is started, so report any side effects you might experience.

Anorexia nervosa, bulimia, benzodiazepine withdrawal, alcoholism or sudden alcohol withdrawal, brain tumor, diabetes mellitus, low blood sugar, low sodium blood levels (electrolytes), head trauma, low oxygen levels, mass inside the head, obesity treatment, seizure disorders, seizures, stroke, substance abuse, are all contraindications to the use of bupropion.

Bupropion is contraindicated in patients with a pre-existing seizure disorder or any conditions that can increase the risk of seizures (e.g., severe head trauma, brain blood malformations, brain tumor or any mass in the head, infections in or around the brain, severe stroke, anorexia nervosa, bulimia). It is also contraindicated in cases of abrupt benzodiazepine withdrawal—as well as abrupt withdrawal from alcohol, barbiturates, or anti-epileptic drugs.  All of these are contraindicated because bupropion can cause seizures and those conditions can make it more likely to happen.

Other things that may increase the risk of seizures include alcoholism, substance abuse (e.g., cocaine or prescription abuse of stimulants such as amphetamines), disorders of the metabolism (e.g., low blood sugar, low sodium in the blood, severe liver impairment, low oxygen levels), diabetes mellitus treated with insulin or with oral medicine used to control sugar levels, excessive use of benzodiazepines (like Valium or Librium), sedative/hypnotics, or opiates (e.g., oxycodone), use of drugs for obesity treatment, or use of medications at the same time that lower the seizure threshold—that’s why you have to tell every doctor about all your medications.

Bupropion should be stopped and never used again in patients who experience a seizure during treatment. The incidence of seizures with bupropion is related to how much you take. In studies using bupropion hydrochloride sustained-release up to 300 mg/day, the incidence of seizures was about 0.1%. That is one out of a thousand. The risk goes up as the dose increases beyond that.

Do not exceed maximum recommended single or total daily dosages of any bupropion product. Patients who are taking bupropion for smoking cessation (e.g., Zyban) should not also take bupropion for depression (e.g., Wellbutrin, Aplenzin), and vice-versa. Tell us the name of every drug you are taking because bupropion comes in many names (e.g., Aplenzin, Buproban, Forfivo XL, Wellbutrin SR, Wellbutrin XL, Zyban, Zyban Advantage Pack, Budeprion XL).

We also need to know if you have had a history of drug abuse with amphetamines. The PDR notes, “During controlled trial evaluation of immediate-release bupropion, an increase in motor activity and agitation/excitement was demonstrated in normal volunteers, subjects with a history of multiple drug abuse, and depressed patients. Results from single-dose studies suggest that the recommended daily dose of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, because clinical trial results may not reliably predict the abuse potential of drugs, the benefits of treatment should be weighed against the potential for abuse prior to administering bupropion to patients with a history of substance abuse. It should be noted that bupropion extended-release formulations are intended for oral use only. The inhalation of crushed tablets or injection of dissolved bupropion has resulted in seizures and/or cases of death.”

Never abuse bupropion and let your doctor know if you have abused amphetamines, cocaine, etc., in the past.


Children, Suicidal Ideation (thoughts)

This medication should not be used in children for the purpose of smoking cessation. Even up to the age of 24, patients have an increased likelihood of having suicidal thoughts, especially when they start the medication.

Tics, Tourette Syndrome

According to the PDR, “Patients with Tourette Syndrome or tics should be closely monitored for emerging or worsening tics during treatment with bupropion. Like other stimulant medications, bupropion may precipitate motor or phonetic tics in those with Tourette Syndrome or a tic disorder.”

Behavioral changes, bipolar disorder, depression, mania, psychiatric event, schizophrenia

The use of antidepressants, such as bupropion, has been associated with the the development of mania or hypomania (psychiatric disorders) in people prone to it. That is why you must be open about having bipolar disorder or manic depression. It is also important to include any personal or family history of bipolar disorder, depression, and suicidal thoughts or actions.

The PDR states, “If a patient develops manic symptoms, bupropion should be held, and appropriate therapy initiated to treat the manic symptoms. Patients should be observed for a potential psychiatric event or worsening of pre-existing psychiatric illness (e.g., schizophrenia, depression, bipolar disorder) during treatment with bupropion, including smoking cessation products (e.g., Zyban), due to serious neuropsychiatric symptoms reported during post-marketing use of bupropion products for smoking cessation.”


While the symptoms often resolve with stopping therapy, this is not always the case. Many patients are not eligible for treatment with bupropion   because of a psychiatric history but they are still eligible for treatment with nicotine replacement products. There are other changes that can occur including hallucinations, aggressive behavior, mood changes, homicidal ideation, hostility and anxiety, to name a few—and they can occur in people with or without a history of mental illness. Some symptoms have been noted with the withdrawal of nicotine alone (with no medication) and some symptoms may be complicated by excess alcohol. The key is to be observant. The PDR states, “Advise patients and caregivers that the patient should stop taking bupropion and contact a healthcare provider immediately if agitation, depressed mood, suicidal ideation, suicidal behavior, or other behavioral changes that are not typical for the patient are observed.”

Fortunately, the risk is less than had been considered in the past and the PDR states, “The boxed warning in the bupropion smoking cessation product labeling regarding serious neuropsychiatric effects was removed in December 2016 following results from the Evaluating Adverse Events in a& Global Smoking Cessation Study (EAGLES), which was a large, randomized, double-blind, active- and placebo-controlled smoking cessation clinical trial assessing varenicline, bupropion, and nicotine replacement therapy in patients with (n = 4,003) and without (n = 3,912) a history of a psychiatric disorder. The results showed that the benefits of taking smoking cessation products outweigh the risks, which are less frequent and severe than previously suspected.”

MAOI therapy

Bupropion cannot be used with medications called Monoamine Oxidase Inhibitors (MAOIs)—examples include, rasagiline (Azilect), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate).
In fact, bupropion cannot be used in anyone who used an MAOI two weeks before starting bupropion or who may need it two weeks after stopping.
Bupropion cannot be used in anyone who is on linezolid (Zyvox), which is an antibiotic or intravenous methylene blue (used to treat a rare disorder called methemoglobinemia).

Neonates, Pregnancy

Bupropion is classified as FDA pregnancy risk category C. Most studies of bupropion during pregnancy “indicate no overall increased risk of congenital malformations. In addition, no increased risk of cardiovascular malformations during first trimester exposure to bupropion has been observed.” However, studies looking at certain heart defects in infants born to mothers who used bupropion in the first trimester have been “inconsistent.”

Pregnant smokers are encouraged to try everything short of using a medication or other aids before making the difficult choice between the benefits of using a medication to quit smoking versus the risk any medication might pose to their unborn child. Also, while not reported as a problem with bupropion, other antidepressants have been noted to cause withdrawal or even toxicity to newborns when taken during the third trimester.

Breastfeeding

Bupropion is excreted into human breast milk, and the PDR states, “caution should be exercised when bupropion is administered to a breastfeeding woman.” The patient must make the difficult evaluation that weighs the benefit to a child of breastfeeding and the risk posed by taking a medication that is excreted in breast milk, along with the risks of exposing the child to second hand smoke and nicotine.  

Liver disease

The dose of bupropion should be “reduced in patients with moderate to severe liver impairment.” They also should be followed carefully as liver failure increases the risk of seizures.

Kidney Disease, Kidney Failure, Kidney Impairment

Bupropion products should be used with extreme caution in patients with kidney disease or kidney failure because it will not be cleared out of the body efficiently and can accumulate in the bloodstream. This would make side effects much more likely to occur. The dose could be reduced but the patient should be followed closely to monitor for signs of toxicity related to high levels of bupropion.

Acute Myocardial Infarction (Heart Attack), Cardiac (Heart) Disease, Heart Failure, Hypertension (High Blood Pressure), Tobacco Smoking

Rarely, bupropion may cause a rapid or irregular heartbeat. Rarely, it can cause an increase in blood pressure. Even though rare, bupropion patients should have their blood pressure checked prior to bupropion initiation and periodically throughout treatment. Also, bupropion should be used only with caution in patients with a recent heart attack or who have unstable angina (chest pain), or unstable cardiac conditions from any cause, including congestive heart failure. Moreover, if a nicotine product (e.g., nicotine patch) is being used with bupropion, monitoring blood pressure is more important because elevations are more likely. Patients should stop smoking before initiating nicotine replacement.   

One other interesting aspect of the use of bupropion for smoking cessation is that other medications may need to have their dosages altered (e.g., theophylline—Elixophyllin, Norphyl; warfarin—Coumadin, Jantoven). According to the PDR, “Downward dosage adjustments of such drugs and more frequent monitoring may be required during smoking cessation.”

Geriatric (Elderly)


The elderly are more prone to metabolize drugs slowly, which means the same dose that might have been fine when they were 30 might be too high of a dose when they are 75. The elderly may need reduced doses and this is especially true with kidney or liver impairment. The PDR also warns that “Bupropion may also cause weight loss which may be significant for elderly or otherwise debilitated patients.”
The PDR also states, “Antidepressants may cause dizziness, nausea, diarrhea, anxiety, nervousness, insomnia, somnolence, weight gain, anorexia, or increased appetite. Many of these effects can increase the risk for falls.”

Driving or Operating Machinery, Ethanol Intoxication


Patients must use caution when driving or operating machinery or doing anything that requires they be mentally alert until they know how bupropion affects them. While some patients note a lower tolerance to alcohol consumption, the abrupt cessation in those who drink heavily is not advised.

Closed-angle Glaucoma, Increased Intraocular Pressure


Caution is recommended when prescribing bupropion to patients with closed-angle glaucoma. The reason is that bupropion can cause the pupils to dilate. This causes an increase in the pressure in the eye in some people who have a condition called closed-angle glaucoma. This is a very serious emergency since the pressure in the eye can rise rapidly and cause blindness.

Abrupt Discontinuation

Bupropion should be tapered when it is discontinued. It should be done as rapidly as possible but without being done so rapidly that it causes withdrawal.


SIDE EFFECTS

See the PDR for the very comprehensive list of possible side effects.

According to the PDR the common reactions include “agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, tremor, dizziness, excessive sweating, blurred vision, tachycardia (rapid heart rate), confusion, rash, hostility, cardiac arrhythmia (irregular heartbeat), and auditory disturbance.

The PDR notes the side effects that have been significant and resulted in stopping treatment. They occur much more commonly at doses higher than those used to treat smoking cessation but they are very important to note.
The PDR states, “The more common events causing discontinuation include neuropsychiatric disturbances (3.0%), primarily agitation and abnormalities in mental status; gastrointestinal disturbances (2.1%), primarily nausea and vomiting; neurological disturbances (1.7%), primarily seizures, headaches, and sleep disturbances; and dermatologic problems (1.4%), primarily rashes. It is important to note, however, that many of these events occurred at doses that exceed the recommended daily dose.”


Drug Interactions


What follows is neither a substitute for the package insert that is available online, nor is it meant to replace reading the PDR for the more complete and comprehensive explanation of each interaction. Your physician ultimately must weigh the relative benefits and risks of any treatment program with you.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine can increase the risk of seizures.
Acetaminophen; Butalbital: (Moderate) Can make bupropion less effective.
Acetaminophen; Butalbital; Caffeine: (Moderate) Caffeine can increase the risk of seizures, while butalbital can make bupropion less effective.
Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Caffeine can increase the risk of seizures, while butalbital and codeine can make bupropion less effective. Bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine can increase the risk of seizures. Also, bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Caffeine can increase the risk of seizures.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Caffeine can increase the risk of seizures.  
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Even non-prescription stimulants and weight loss medications can increase seizure risk; seizures may be more likely to occur in these patients with bupropion.
Acetaminophen; Codeine: (Moderate) Bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Even non-prescription stimulants and weight loss medications can increase seizure risk; seizures may be more likely to occur in these patients with bupropion.  
Acetaminophen; Oxycodone: (Moderate) Bupropion can increase the levels of oxycodone in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also the seizure risk is greater when these drugs are taken together.
Acetaminophen; Pentazocine: (Moderate) Bupropion can increase the levels of pentazocine in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also the seizure risk is greater when these drugs are taken together.
Acetaminophen; Propoxyphene: (Moderate) Bupropion can increase the levels of propoxyphene in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also the seizure risk is greater when these drugs are taken together.
Acetaminophen; Pseudoephedrine: (Major) Even non-prescription stimulants and weight loss medications can increase seizure risk; seizures may be more likely to occur in these patients with bupropion.
Acetaminophen; Tramadol: (Major) Bupropion can alter the levels of tramadol and the version into which it is converted in the blood. Both relieve pain so it is possible it will be less effective. Also the seizure risk is greater when these drugs are taken together.
Acetazolamide: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder but may be combined with anticonvulsant treatments with caution when an anticonvulsant is not used for seizure conditions. However, the patient may feel dizzy, drowsy, or more tired when taking these drugs together.
Acrivastine; Pseudoephedrine: (Major) Even non-prescription stimulants and weight loss medications can increase seizure risk; seizures may be more likely to occur in these patients with bupropion.
Alosetron: (Moderate) Alosetron combined with bupropion may seriously worsen constipation, leading to significant complications. Avoid combining these meds.
Amantadine: (Major) The simultaneous use of bupropion and amantadine may result in additive neurologic side effects such as restlessness, agitation, gait disturbance, vertigo, and dizziness. They can be severe.
Amitriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs) and increase the risk of seizures and other severe neurologic side effects. Bupropion can raise the levels of TCAs, as well.
Amitriptyline; Chlordiazepoxide: (Major) Bupropion may interact with tricyclic antidepressants (TCAs) and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of TCAs, as well.
Amobarbital: (Moderate) Amobarbital may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Amoxapine: (Major) Concurrent administration of amoxapine with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold.
Amphetamine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.  
Amphetamine; Dextroamphetamine Salts: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.  
Amphetamine; Dextroamphetamine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.  
Anticonvulsants: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact with other anticonvulsant drugs (i.e., carbamazepine, barbiturates, phenytoin, fosphenytoin, ethotoin).
Aripiprazole: (Major) Adding bupropion to aripiprazole, and other drugs in this class, requires dose adjustments of aripiprazole and many other similar medications. This should be discussed in detail with your physician.
Armodafinil: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.  
Asenapine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold. A low starting dose and small increases are recommended if this combination must be used.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine can increase the risk of seizures. (Moderate) Can make bupropion less effective.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Caffeine can increase the risk of seizures. (Moderate) Butalbital make bupropion less effective. (Moderate) Bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Caffeine can increase the risk of seizures. (Moderate) Bupropion slows the conversion of dihydocodeine to morphine. Patients may not have as good a response to codeine.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Aspirin, ASA; Oxycodone: (Moderate) Bupropion can increase the levels of oxycodone in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also the seizure risk is greater when these drugs are taken together.
Atazanavir; Cobicistat: (Moderate) Cobicistat levels can be elevated when combined with bupropion.
Atropine: (Moderate) The effects of atropine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) Bupropion cannot be given to patients receiving intravenous methylene blue as it can cause very high blood pressure. (Moderate) The effects of hyoscyamine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.(Moderate) The effects of atropine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Atropine; Difenoxin: (Moderate) The effects of atropine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Atropine; Diphenoxylate: (Moderate) The effects of atropine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Atropine; Edrophonium: (Moderate) The effects of atropine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) The effects of hyoscyamine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.(Moderate) The effects of atropine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected. (Moderate) The effects of scopolamine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected. (Moderate) Phenobarbital can make bupropion less effective. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.

Azelastine; Fluticasone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Barbiturates: (Moderate) Phenobarbital can make bupropion less effective. Patients on both should not drive or operate complex, hazardous machinery until they know they can function well on the combination.
Beclomethasone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Barbiturates may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) Bupropion cannot be given to patients receiving intravenous methylene blue as it can cause very high blood pressure. (Moderate) The effects of hyoscyamine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Benzphetamine: (Major) Bupropion increases the risk of seizures, and even more so when combined with nervous system stimulants and appetite suppressants, including benzphetamine. Concurrent use is not recommended.
Benztropine: (Moderate) The effects of benztropine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Betamethasone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Bethanechol: (Moderate) Bupropion acts in the opposite way of bethanechol. Since they work against each other using them at the same time should be avoided.
Brexpiprazole: (Major) Bupropion increases the blood level of brexpiprazole significantly. The dose of brexpiprazole must be lowered if bupropion is added and the patient observed carefully for side effects and reactions. Also, antipsychotics can further increase the risk of seizures in patients taking bupropion.
Brimonidine; Timolol: (Minor) Bupropion increases the blood level of timolol.
Brompheniramine; Hydrocodone; Pseudoephedrine: (Major)  Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Brompheniramine; Pseudoephedrine: (Major)  Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Budesonide: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Budesonide; Formoterol: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Butabarbital: (Moderate) Butabarbital may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Caffeine: (Moderate) Caffeine can increase the risk of seizures.
Caffeine; Ergotamine: (Moderate) Caffeine increases the risk of seizures.
Carbamazepine: (Moderate) Bupropion can increase the risk of seizures and carbamazepine is given for seizures so using them together is not recommended.
Carbetapentane; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Carbidopa; Levodopa: (Major) Bupropion and levodopa both increase dopamine levels. Together, they have caused restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used, a low starting dose and small increases of bupropion may be warranted.
Carbidopa; Levodopa; Entacapone: (Major) Bupropion and levodopa both increase dopamine levels. Together, they have caused restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used, a low starting dose and small increases of bupropion may be warranted.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Carbinoxamine; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Cariprazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold like antipsychotics. A low starting dose and small increases are recommended, if this combination must be used. Bupropion can increase the blood levels of antipsychotics. Caution must be exercised.
Carvedilol: (Minor) Carvedilol blood levels are increased with bupropion.
Cetirizine; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Cevimeline: (Moderate) Cevimeline levels are increased with bupropion.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Chlordiazepoxide; Clidinium: (Moderate) Both this medication and bupropion affect the nervous system. Together they can cause difficulties with the bladder, the eyes and other organs like the bowels. Together, they should be used cautiously.
Chlorpheniramine; Codeine: (Moderate) Bupropion interferes with the conversion of codeine to morphine. Patients not experience a good pain response to codeine.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Bupropion may interfere with the conversion of dihydrocodeine to dihydromorphine. In theory, patients may experience varying degrees of analgesia.
Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion. (Moderate) Bupropion may interfere with the conversion of dihydrocodeine to dihydromorphine. In theory, patients may experience varying degrees of analgesia.
Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Chlorpheniramine; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Chlorpromazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold. A low starting dose and small increases are recommended, if this combination must be used. Bupropion can increase the levels of chlorpromazine and other antipsychotics (haloperidol, risperidone)in the blood. Patients starting bupropion may need to lower their dose of chlorpromazine and patients going off bupropion may need an increase.
Ciclesonide: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Cimetidine: (Moderate) Cimetidine increases the breakdown chemicals of bupropion but what this means for the patient is unknown.
Citalopram: (Moderate) Bupropion increases the blood levels of citalopram.
Clomipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like clomipramine, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Clopidogrel: (Moderate) Clopidogrel and bupropion can increase reactions to bupropion, such as tremor, nausea, dry mouth, insomnia, headache, or seizures.
Clozapine: (Major) Bupropion can increase the levels of Clozapine in the blood. Patients starting bupropion may need to lower their dose of and patients going off bupropion may need an increase. (Major) Treatment with clozapine has been associated with cardiac arrest and sudden death. Elevated plasma concentrations of clozapine (made more likely with bupropion) may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. Furthermore, bupropion is increases the risk of seizures and it may be increased by antipsychotics.
Cobicistat: (Moderate) Cobicistat can increase the blood levels of bupropion.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Cobicistat can increase the blood levels of bupropion.
Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Cobicistat can increase the blood levels of bupropion.
Codeine: (Moderate)  Bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Codeine; Guaifenesin: (Moderate)  Bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Codeine; Phenylephrine; Promethazine: (Moderate) Bupropion increases the risk of seizures. Promethazine further increases that risk. Bupropion can increase the blood levels of promethazine. Patients starting bupropion may need to lower their dose of promethazine and patients going off bupropion may need an increase. A low starting dose and small increases of promethazine are recommended, if this combination must be used. (Moderate) Bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Codeine; Promethazine: (Moderate) Bupropion increases the risk of seizures. Promethazine further increases that risk. Bupropion can increase the levels of promethazine in the blood. Patients starting bupropion may need to lower their dose of promethazine and patients going off bupropion may need an increase. A low starting dose and small increases of promethazine are recommended, if this combination must be used.
(Moderate) Bupropion slows the conversion of codeine to morphine. Patients may not have as good a response to codeine.
Corticosteroids: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Corticotropin, ACTH: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Cortisone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Crizotinib: (Moderate) Crizotinib can increase the blood levels of bupropion.
Cyclobenzaprine: (Major) Cyclobenzaprine with bupropion increases the chance of serotonin syndrome, an uncommon condition that causes high temperature, agitation, dilated pupils, tremors, and sweating, among other symptoms. However, when used with bupropion, it can also cause dry mouth, urinary difficulties and severe constipation, even a paralyzed bowel.
Dabrafenib: (Major) Dabrafenib lowers the blood level of bupropion. Bupropion may even lose its effect.
Darifenacin: (Moderate) Bupropion can increase the blood levels of darifenacin. Together, they can also increase the likelihood of side effects common to both of them.
Darunavir; Cobicistat: (Moderate) Bupropion increases the blood level of cobicistat.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Ritonavir decreases the blood level of bupropion.
Deflazacort: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Desipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like desipramine, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Desloratadine; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Deutetrabenazine: (Major) Bupropion increases the blood level of deutetrabenazine possibly resulting in drowsiness and serious heart arrythmias.
Dexamethasone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Dexmethylphenidate: (Major) Dexmethylphenidate and bupropion both increase the risk of seizures. It should be used only with caution.
Dextroamphetamine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Dextromethorphan; Promethazine: (Moderate) Bupropion increases the risk of seizures. Promethazine further increases that risk. Bupropion can increase the levels of promethazine in the blood. Patients starting bupropion may need to lower their dose of promethazine and patients going off bupropion may need an increase. A low starting dose and small increases of promethazine are recommended, if this combination must be used.
Dicyclomine: (Moderate) Dicyclomine and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Diethylpropion: (Major) Diethylpropion and bupropion both increase the risk of seizures.
Digoxin: (Moderate) Digoxin blood levels can be lowered by bupropion.
Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion. (Moderate) Bupropion may interfere with the conversion of dihydrocodeine to dihydromorphine. In theory, patients may experience varying degrees of analgesia.
Dorzolamide; Timolol: (Minor) Bupropion increases the blood level of timolol.
Doxepin: (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like desipramine, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Doxercalciferol: (Moderate) Bupropion may slow the change of doxercalciferol to its active version, making it less likely to work.
Doxorubicin: (Major) Bupropion increases the blood level of doxorubicin making side effects of doxorubicin more likely (e.g., bone marrow suppression and heart toxicity).
Duloxetine: (Moderate) Bupropion use may cause increased duloxetine levels and more side effects.
Dutasteride; Tamsulosin: (Moderate) Tamsulosin blood levels are increased with bupropion.

Efavirenz: (Major) Efavirenz can lower the bupropion blood level. The dose of bupropion should be adjusted based on the effect it seems to have when the patient is also on based on efavirenz—but never exceeding the maximum dose.
Efavirenz; Emtricitabine; Tenofovir: (Major) Efavirenz can lower the bupropion blood level. The dose of bupropion should be adjusted based on the effect it seems to have when the patient is also on based on efavirenz—but never exceeding the maximum dose.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Efavirenz can lower the bupropion blood level. The dose of bupropion should be adjusted based on the effect it seems to have when the patient is also on based on efavirenz—but never exceeding the maximum dose.
Encainide: (Major) Encainide blood levels are elevated with bupropion. Since encainide can become toxic with just small increases in blood levels, severe reactions are possible when both drugs are given at the same time.
Ethanol: (Major) Bupropion increases the risk of seizures. Both alcohol abuse and stopping alcohol suddenly can cause seizures and death. Therefore the use of ethanol or the abrupt discontinuation of ethanol should be avoided in patients taking bupropion.
Ethotoin: (Moderate) Bupropion can increase the risk of seizures and ethotoin is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Felbamate: (Major) Bupropion can increase the risk of seizures and felbamate is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Fexofenadine; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Flavoxate: (Moderate) Flavoxate and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Flecainide: (Major) Flecainide blood levels are elevated with bupropion. Since flecainide can become toxic with just small increases in blood level, severe reactions are possible when both drugs are given at the same time.
Fludrocortisone: (Major)  Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Flunisolide: (Major)  Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Fluoxetine: (Moderate) Bupropion may increase the blood level of fluoxetine and probably many other drugs in its class (SSRIs).
Fluoxetine; Olanzapine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold. A low starting dose and small increases are recommended, if this combination must be used. Patients starting bupropion may need to lower their dose of fluoxetine and patients going off bupropion may need an increase. (Moderate) Bupropion may increase the blood level of fluoxetine and probably many other drugs in its class (SSRIs).
Fluphenazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold. A low starting dose and small increases are recommended, if this combination must be used. Bupropion can increase the blood levels of fluphenazine and other antipsychotics (haloperidol, risperidone). Patients starting bupropion may need to lower their dose of fluphenazine and patients going off bupropion may need an increase.
Fluticasone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Fluticasone; Salmeterol: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Fluticasone; Umeclidinium; Vilanterol: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Fluticasone; Vilanterol: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Fluvoxamine: (Moderate) Bupropion may increase fluvoxamine levels.
Formoterol; Mometasone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Fosphenytoin: (Moderate) Bupropion can increase the risk of seizures and felbamate is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Gabapentin: (Moderate) Bupropion can increase the risk of seizures and gabapentin is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Gefitinib: (Major) Gefitinib blood levels are increased with bupropion.
Glycopyrrolate: (Moderate) Glycopyrrolate and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Glycopyrrolate; Formoterol: (Moderate) Glycopyrrolate and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Guaifenesin; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Guanfacine: (Moderate) One case of a child who had a seizure while on both guanfacine and bupropion. The meaning is uncertain.
Haloperidol: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like haloperidol. A low starting dose and small increases are recommended, if this combination must be used. Bupropion can increase the blood levels of haloperidol and other antipsychotics (fluphenazine, risperidone). Patients starting bupropion may need to lower their dose of haloperidol and patients going off bupropion may need an increase.
Homatropine; Hydrocodone: (Moderate) Homatropine and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Hydantoins: (Moderate) Bupropion can increase the risk of seizures and hydantoins are given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Metoprolol blood levels are elevated significantly with bupropion and can cause reactions like a slow heart rate and low blood pressure.
Hydrochlorothiazide, HCTZ; Propranolol: (Minor) Propranolol blood levels may rise with bupropion and adverse effects are more likely to occur.
Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Hydrocodone; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Hydrocortisone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Hydromorphone: (Moderate) Opioids like hydromorphone can increase seizure risks, as does bupropion. Use of both at the same time may make seizures even more likely.
Hydroxyprogesterone: (Moderate) Hydroxyprogesterone may lower the blood levels of bupropion.
Hyoscyamine: (Moderate) Hyoscyamine and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected. Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with bupropion.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Severe) Bupropion cannot be given to patients receiving intravenous methylene blue as it can cause very high blood pressure. (Moderate) The effects of hyoscyamine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Ibuprofen; Oxycodone: (Moderate) Bupropion can increase the levels of oxycodone in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also, the seizure risk is greater when these drugs are taken together.
Ibuprofen; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Iloperidone: (Major) Iloperidone blood levels are increased with bupropion. Additionally, bupropion and iloperidone can increase the risk for seizures further when used together.
Imipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like imipramine, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Indacaterol; Glycopyrrolate: (Moderate) Glycopyrrolate and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Isavuconazonium: (Moderate) Isavuconazonium can decrease the blood levels of bupropion.
Isocarboxazid: (Severe) Monoamine oxidase inhibitors (MAOIs) are generally not used with bupropion, within 14 days of discontinuing treatment with bupropion, and bupropion is not started within 14 days of taking an MAOI. There is a risk of significant elevations in blood pressure.
Isoniazid, INH: (Moderate) In theory, the use of bupropion and isoniazid, INH, may result in the same high blood pressure reaction as when bupropion is taken with an MAOI. (e.g., linezolid, methylene blue, isocarboxazid).
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) In theory, the use of bupropion and isoniazid, INH, may result in the same high blood pressure reaction as when bupropion is taken with an MAOI. (e.g., linezolid, methylene blue, isocarboxazid). (Moderate) Rifampin decreases blood levels of bupropion.
Isoniazid, INH; Rifampin: (Moderate) In theory, the use of bupropion and isoniazid, INH, may result in the same high blood pressure reaction as when bupropion is taken with an MAOI. (e.g., linezolid, methylene blue, isocarboxazid). (Moderate) Rifampin decreases blood levels of bupropion.
Kava Kava, Piper methysticum: (Moderate) The German Commission E warns that anything that affects the brain may interact with the phytomedicinal kava kava, Piper methysticum.
Lacosamide: (Moderate) Bupropion can increase the risk of seizures lacosamide is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Lamotrigine: (Moderate) Bupropion can increase the risk of seizures and lamotrigine is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Levetiracetam: (Moderate) Bupropion can increase the risk of seizures and Levetiracetam is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Levodopa: (Major) Bupropion and levodopa both increase dopamine levels. Together, they have caused restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness. If levodopa is used, a low starting dose and small increases of bupropion may be warranted.
Linezolid: (Severe) Linezolid is an MAOI so when used with bupropion there is a risk of high blood pressure.
Lisdexamfetamine: (Major) The risk of seizures from bupropion may be increased with the addition of nervous system stimulants, including lisdexamfetamine. Concurrent use is not recommended.
Lofexidine: (Moderate) Lofexidine blood level is increased with the addition of bupropion and can cause a low blood pressure (especially when rising) and a slow heart rate.
Loperamide: (Moderate) Loperamide blood level is increased with the addition of bupropion and can cause reactions (i.e., fainting, irregular heart beats, cardiac arrest and death).
Loperamide; Simethicone: (Moderate) Loperamide blood level is increased with the addition of bupropion and can cause reactions (i.e., fainting, irregular heart beats, cardiac arrest and death).
Lopinavir; Ritonavir: (Moderate) Ritonavir decreases the blood level of bupropion.
Loratadine; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Lorcaserin: (Moderate) Lorcaserin with bupropion increases the chance of serotonin syndrome, an uncommon condition that causes high temperature, agitation, dilated pupils, tremors, and sweating, among other symptoms.
Loxapine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like loxapine. A low starting dose and small increases are recommended, if this combination must be used.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may lower the blood level of bupropion and make it less effective.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may lower the blood level of bupropion and make it less effective.
Maprotiline: (Major) Maprotiline with bupropion both increase the risk of seizures. should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. They also increase the levels of each when used together so a low starting dose and small increases of both drugs should be employed.
Mepenzolate: (Moderate) Glycopyrrolate and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Meperidine: (Moderate) Opioids and bupropion each increases the risk of seizures and together even more so.
Meperidine; Promethazine: (Moderate) Bupropion increases the risk of seizures. Promethazine further increases that risk. Bupropion can increase the levels of promethazine in the blood. Patients starting bupropion may need to lower their dose of promethazine and patients going off bupropion may need an increase. A low starting dose and small increases of promethazine are recommended, if this combination must be used. (Moderate) Opioids and bupropion each increases the risk of seizures and together even more so.
Mephobarbital: (Moderate) Mephobarbital may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Mesoridazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., mesoridazine). A low starting dose and small increases are recommended, if this combination must be used. Bupropion can increase the blood levels of haloperidol and other antipsychotics (fluphenazine, risperidone). Patients starting bupropion may need to lower their dose of haloperidol and patients going off bupropion may need an increase.
Methadone: (Moderate) Methadone blood levels may be increased with bupropion. Opioids increase seizure risk; seizures may be more likely if bupropion is taken at the same time.
Methamphetamine: (Major) Methamphetamine can make seizures more likely to occur if taken with bupropion.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Severe) Bupropion cannot be given to patients receiving intravenous methylene blue as it can cause very high blood pressure. (Moderate) The effects of hyoscyamine may be enhanced when combined with bupropion. Drowsiness can occur and the gastrointestinal tract, the eye, the bladder, and temperature regulation can be affected.
Methohexital: (Moderate) Methohexital may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Methscopolamine: (Moderate) Glycopyrrolate and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Methylene Blue: (Severe) Bupropion cannot be given to patients receiving intravenous methylene blue as it can cause very high blood pressure.
Methylphenidate: (Major) Methylphenidate can make seizures more likely to occur and should be used with great caution or avoided in patients taking bupropion.
Methylprednisolone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Metoclopramide: (Major) Metoclopramide blood levels are increased if taken with bupropion. Reactions are more likely with higher blood levels.
Metoprolol: (Moderate) Metoprolol blood levels are elevated significantly with bupropion and can cause reactions like a slow heart rate and low blood pressure.
Mexiletine: (Major) Bupropion can increase the blood level of mexiletine if used together.
Midazolam: (Moderate) Bupropion increases the risk of seizures as does both the abrupt withdrawal or excessive use of benzodiazepines.
Mifepristone: (Moderate) Mifepristone can increase blood levels of bupropion.
Modafinil: (Major) Seizures have occurred with the use of modafinil and bupropion, although the frequency is unknown.
Molindone: (Major) Molindone makes seizures more likely when taken with bupropion.
Mometasone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Monoamine oxidase inhibitors: (Severe) MAOIs should not be used within 14 days after the last dose of bupropion and bupropion should not be used within 14 days of stopping an MAOI. There is an increased risk of high blood pressure.
Morphine: (Moderate) Opioids increase seizure risk; seizures may be more likely if bupropion is taken at the same time.
Morphine; Naltrexone: (Moderate) Methadone blood levels may be increased with bupropion. Opioids increase seizure risk; seizures may be more likely if bupropion is taken at the same time.
Naproxen; Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Nebivolol: (Moderate) Nebivolol blood levels are increased if taken with bupropion.
Nebivolol; Valsartan: (Moderate) Nebivolol blood levels are increased if taken with bupropion.
Nelfinavir: (Minor) Nelfinavir ects how the body changes bupropion but if it is important is unknown.
Nicotine: (Moderate) Nicotine and bupropion may cause significant blood pressure elevations in some patients. Close monitoring of blood pressure is recommended if this combination is prescribed.
Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants.
Non-Ionic Contrast Media: (Major) Use of medications that can increase the chance of a seizure should be carefully evaluated when considering injecting contrast agents before radiological test. Bupropion should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours afterwards.
Nortriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like nortriptyline, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Olanzapine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., olanzapine). A low starting dose and small increases are recommended, if this combination must be used.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Ritonavir decreases the blood level of bupropion.
Oxcarbazepine: (Moderate) Bupropion can increase the risk of seizures and Levetiracetam is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Oxybutynin: (Moderate) Oxybutynin and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Oxycodone: (Moderate) Bupropion can increase the levels of oxycodone in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also the seizure risk is greater when these drugs are taken together.
Oxymorphone: (Moderate) Opioids increase seizure risk; seizures may be more likely if bupropion is taken at the same time.
Paliperidone: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., paliperidone). A low starting dose and small increases are recommended, if this combination must be used.
Paroxetine: (Moderate) Bupropion may increase the blood level of fluoxetine and probably many other drugs in its class (SSRIs).
Pemoline: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold. A low starting dose and small increases are recommended, if this combination must be used.
Pentazocine: (Moderate) Bupropion can increase the levels of pentazocine in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also the seizure risk is greater when these drugs are taken together.
Pentazocine; Naloxone: (Moderate) Bupropion can increase the levels of pentazocine in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also the seizure risk is greater when these drugs are taken together.
Pentobarbital: (Moderate) Pentobarbital may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Perphenazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g.,perphenazine). A low starting dose and small increases are recommended, if this combination must be used.
Perphenazine; Amitriptyline: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g.,perphenazine). A low starting dose and small increases are recommended, if this combination must be used. (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like amitriptyline, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Phendimetrazine: (Major) Bupropion increases seizure risk as does excessive use of phendimetrazine; seizures may be more likely to occur in these patients when using bupropion.
Phenelzine: (Severe) Phenelzine is a monoamine oxidase inhibitor (MAOI). MAOIs should not be used within 14 days after the last dose of bupropion and bupropion should not be used within 14 days of stopping an MAOI. There is an increased risk of high blood pressure.
Phenobarbital: (Moderate) Phenobarbital may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Phenothiazines: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., phenothiazines). A low starting dose and small increases are recommended, if this combination must be used.
Phentermine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Phentermine; Topiramate: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion. (Moderate) Bupropion can increase the risk of seizures and topiramate is given for seizures so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Phenylephrine; Promethazine: (Moderate) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold. A low starting dose and small increases are recommended, if this combination must be used.
Phenytoin: (Moderate) Bupropion can increase the risk of seizures and phenytoin is given for seizures, so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., phenytoin, fosphenytoin, and ethotoin).
Pimozide: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold. A low starting dose and small increases are recommended, if this combination must be used.
Prednisolone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Prednisone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.
Primidone: (Moderate) Primidone may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Procarbazine: (Severe) Procarbazine is a monoamine oxidase inhibitor (MAOI). MAOIs should not be used within 14 days after the last dose of bupropion and bupropion should not be used within 14 days of stopping an MAOI. There is an increased risk of high blood pressure.
Prochlorperazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g.,perphenazine). A low starting dose and small increases are recommended, if this combination must be used.
Promethazine: (Moderate) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold. A low starting dose and small increases are recommended, if this combination must be used.
Propafenone: (Major) Bupropion can increase the blood levels of propafenone. A lower dose of propafenone may be needed with bupropion.
Propantheline: (Moderate) Propantheline and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Propoxyphene: (Moderate) Bupropion can increase the levels of propoxyphene in the blood. Patients starting bupropion may need to lower their dose and patients going off bupropion may need an increase. Also the seizure risk is greater when these drugs are taken together.
Propranolol: (Minor) Propranolol blood levels are elevated with bupropion and can cause reactions like a slow heart rate and low blood pressure.
Protriptyline: (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like protriptyline, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Pseudoephedrine: (Major) Psychostimulants, including non-prescription stimulants and weight loss medications, are associated with an increased seizure risk; seizures may be more likely to occur with bupropion.
Ranolazine: (Moderate) Bupropion increases blood levels of ranolazine.
Rasagiline: (Severe) Rasagiline is a monoamine oxidase inhibitor (MAOI). MAOIs should not be used within 14 days after the last dose of bupropion and bupropion should not be used within 14 days of stopping an MAOI. There is an increased risk of high blood pressure.
Rifampin: (Moderate) Bupropion blood levels are decreased with rifampin.
Risperidone: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., risperidone). Dose adjustments of risperidone are vital if bupropion is taken at the same time.
Ritonavir: (Moderate) Ritonavir lowers the blood level of bupropion.
Scopolamine: (Moderate) Scopolamine and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Secobarbital: (Moderate) Secobarbital may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Selegiline: (Severe) Selegiline is a monoamine oxidase inhibitor (MAOI). MAOIs should not be used within 14 days after the last dose of bupropion and bupropion should not be used within 14 days of stopping an MAOI. There is an increased risk of high blood pressure.
Sertraline: (Moderate) Bupropion may increase the blood level of sertraline and probably many other drugs in its class (SSRIs).
Sodium Oxybate: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, such as sodium oxybate. A low starting dose and small increases are recommended, if this combination must be used.
Tamoxifen: (Major) Tamoxifen blood levels are decreased with bupropion.
Tamsulosin: (Moderate) Tamsulosin blood levels are increased with bupropion.
Theophylline, Aminophylline: (Major) Bupropion increases the risk of seizures as does aminophylline; when used together the risk is even greater.
(Major) If bupropion is used for smoking cessation, and patients stop smoking, blood levels of drugs like aminophylline and theophylline can rise. Dose adjustments may be needed.
Thiethylperazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., thiethylperazine). A low starting dose and small increases are recommended, if this combination must be used. Bupropion can increase the blood levels of thiethylperazine and other antipsychotics (fluphenazine, risperidone). Patients starting bupropion may need to lower their dose of thiethylperazine and patients going off bupropion may need an increase.
Thiopental: (Moderate) Thiopental may decrease bupropion levels in the blood. It may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded. Patients on both should not drive or operating complex, hazardous machinery until they know they can function well on the combination.
Thioridazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., Thioridazine). A low starting dose and small increases are recommended, if this combination must be used. Bupropion can increase the blood levels of thioridazine and other antipsychotics (fluphenazine, risperidone). Patients starting bupropion may need to lower their dose of thioridazine and patients going off bupropion may need an increase.
Thiothixene: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., thiothixene). Dose adjustments of thiothixene are vital if bupropion is taken at the same time.
Tiagabine: (Moderate) Bupropion can increase the risk of seizures and tiagabine is given for seizures, so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., carbamazepine, barbiturates, phenytoin, fosphenytoin, and ethotoin).
Ticlopidine: (Moderate) Ticlopidine increase blood levels of bupropion. Adverse reactions of bupropion, such as tremor, nausea, dry mouth, insomnia, headache, or seizures, may be more likely to occur.
Timolol: (Minor) Bupropion increases blood levels of timolol and result in more negative reactions.
Tobacco: (Moderate) Tobacco contains nicotine as one of its active components, but it is unclear if continuing to smoke 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 a date to stop tobacco smoking during the second week of taking bupropion. If the patient is prescribed a combination of bupropion with nicotine replacement therapy (like Nicotine patches) to stop smoking; then the patient should stop Tobacco smoking before starting to use the nicotine replacement therapy. Monitor blood pressure during smoking cessation treatment.
Tolterodine: (Moderate) Tolterodine and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Topiramate: (Moderate) Bupropion can increase the risk of seizures and tiagabine is given for seizures, so using them together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., carbamazepine, barbiturates, phenytoin, fosphenytoin, and ethotoin).
Tramadol: (Major) Bupropion can alter the levels of tramadol and the version into which it is converted in the blood. Both relieve pain so it is possible it will be less effective. Also the seizure risk is greater when these drugs are taken together.
Tranylcypromine: (Severe) Tranylcypromine is a monoamine oxidase inhibitor (MAOI). MAOIs should not be used within 14 days after the last dose of bupropion and bupropion should not be used within 14 days of stopping an MAOI. There is an increased risk of high blood pressure.
Triamcinolone: (Major) Bupropion increases the risk of seizures. Steroids can increase that risk. A low starting dose and small increases are recommended if this combination must be used.  
Triazolam: (Moderate) The abrupt withdrawal of benzodiazepines (triazolam) increases the risk of seizures; excessive use of a benzodiazepines (triazolam) increases seizure risk. Seizures may be more likely to occur in both cases with the use of bupropion.
Tricyclic antidepressants: (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like protriptyline, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Trifluoperazine: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., trifluoperazine). A low starting dose and small increases are recommended, if this combination must be used. Bupropion can increase the blood levels of trifluoperazine and other antipsychotics (phenothiazines, haloperidol, risperidone). Patients starting bupropion may need to lower their dose of trifluoperazine and patients going off bupropion may need an increase.
Trihexyphenidyl: (Moderate) Trihexyphenidyl and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and the bowels, the eye, the bladder, and temperature regulation can be affected.
Trimipramine: (Major) Bupropion may interact with tricyclic antidepressants (TCAs), like trimipramine, and increase the risk of seizures and other severe neurologic side effects. It can raise the levels of other TCAs, as well. A low starting dose and small increases are recommended, if this combination must be used.
Trospium: (Moderate) Trihexyphenidyl and bupropion can cause the same side effects and when used together the risk increases. Drowsiness can occur and Difficulties with the bowels, the bladder, and temperature regulation can occur. Drowsiness and eye difficulties are also possible.
Valproic Acid, Divalproex Sodium: (Moderate) Bupropion can increase the risk of seizures, so using anti-seizure medication with a medication that can increase seizures together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., carbamazepine, barbiturates, phenytoin, fosphenytoin, and ethotoin).
Vigabatrin: (Moderate) Bupropion can increase the risk of seizures, so using anti-seizure medication with a medication that can increase seizures together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., carbamazepine, barbiturates, phenytoin, fosphenytoin, and ethotoin).
Vortioxetine: (Major) Bupropion increases the blood level of vortioxetine so a lower dose of vortioxetine is needed if taken with bupropion.
Warfarin: (Moderate) When bupropion is used for smoking cessation, and a patient stops smoking, warfarin will be handled by the body differently. Smoking alters how well the body handles anything else that a patient consumes, even medicine. Patients who are using bupropion and stopping smoking should have the effects of warfarin monitored.
Ziprasidone: (Major) Bupropion is associated with seizures. Extreme caution is recommended during use of other drugs that lower the seizure threshold, like antipsychotics (e.g., thiothixene). Dose adjustments of thiothixene are vital if bupropion is taken at the same time.
Zolpidem: (Moderate) Rare cases of hallucinations have occurred when zolpidem was administered concurrently with bupropion. Dosage reductions in zolpidem may be needed if bupropion is used at the same time.
Zonisamide: (Moderate) Bupropion can increase the risk of seizures, so using anti-seizure medication with a medication that can increase seizures together is not recommended. Bupropion may interact chemically with anticonvulsant drugs (e.g., carbamazepine, barbiturates, phenytoin, fosphenytoin, and ethotoin).

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