THE PREPARATION DESCRIPTION IS NOT INTENDED FOR
MEDICATION WITHOUT PARTICIPATION OF THE DOCTOR!

Therapeutic actions: Bupropion is a dopamine and norepinephrine reuptake inhibitor. It is about twice as potent an inhibitor of dopamine uptake than norepinephrine uptake.

Contraindications and cautions: Caution should be exercised when treating patients with

• Liver damage (e.g. cirrhosis) as the drug levels may be higher than in other patients
• Severe kidney disease as in such patients the levels of hydroxybupropion and threo-hydrobupropion are 2-3 times higher than in normal subjects
• Severe hypertension as bupropion is known to cause hypertension
• Pediatric patients, adolescents and young adults (see below)

Adverse effects: Bupropion common side effects with are dry mouth, nausea, insomnia, tremor, excessive sweating and tinnitus. The two side effects which most often resulted in interruption of the treatment in the same trial were rash and nausea. (The development of mild to moderate skin rashes is associated with sensitivity to dye components within the pill coating. This can often be alleviated by simply prescribing a different color pill.)

Seizure is the most controversial side effect of bupropion, which caused its temporary withdrawal. The risk of seizure is highly dose-dependent: 0.1% at 100-300 mg of bupropion, 0.4% at 300-450 mg, and 2% at 600 mg. For comparison, the incidence of first unprovoked seizure in general population is 0.07-0.09%; the risk of seizure for other antidepressants is as follows: imipramine 0.1-0.6% depending on dosage, amitriptiline 0-0.06% depending on dosage, clomipramine 0.5%, maprotiline 0.4%, fluoxetine and fluvoxamine 0.2%. Experiments on mice indicate that increased susceptibility to seizure is a general side effect of antidepressants inhibiting norepinephrine transporter, such as imipramine, desipramine and reboxetine, given chronically. On the other hand, depression was reported to increase occurrence of seizures 2-7 fold as compared to the general population, so that low to moderate doses of antidepressants, including bupropion, may actually have an anti-convulsive action. Nevertheless, patients using Bupropion should still be screened for pre-disposing factors that could contribute to and/or indicate a low seizure threshold. A prescriber may also review all other medications/substances the patient might be using and make dosing decisions based on the results.

Interactions: Quite a great number of drugs show clinically significant interactions with bupropion. This may be due to interactions with drugs that are metabolized by CYP2D6 as bupropion inhibits CYP2D6 activity. However, bupropion is not metabolized by CYP2D6. Theoretically, drug interactions could occur between bupropion and substrates or inhibitors of CYP2B6 (e.g. orphenadrine, thiotepa, or cyclophosphamide).

Bupropion is known to lower the seizure threshold. Bupropion, in combination with other medications, has been suspected to induce seizures in some patients with no prior record of seizure activity.[50] While this is not a common side-effect, a growing number of cases world wide validate the need for consideration. It is not uncommon for patients to receive treatment with other antidepressant and/or atypical antipsychotic medications in combination with bupropion. For this reason, care should be taken when prescribing bupropion with other medications prone to lower the seizure threshold. Bupropion has also been known to produce seizures in combination with non-prescription (recreational) drugs such as cocaine and alcohol.

Combination with nicotine replacement therapies can elevate blood pressure, so it is recommended that the patient's blood pressure is monitored.