Drug interactions between bupropion and Rebif

MONITOR CLOSELY: The use of bupropion is associated with a dose-related risk of seizures. The estimated incidence of seizures is approximately 0.1% at dosages up to 300 mg/day and 0.4% at dosages between 300 to 450 mg/day, but increases almost tenfold between 450 mg and 600 mg/day. The risk may also be increased during coadministration of bupropion with other potentially epileptogenic agents such as interferons.

MONITOR CLOSELY: Coadministration of beta interferons with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Use of beta interferons has been associated with rare cases of liver injury, including autoimmune hepatitis and severe liver damage leading to hepatic failure, some of which required transplantation. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. Symptoms of liver dysfunction typically began from 1 to 6 months following the initiation of therapy. Asymptomatic elevation of hepatic transaminases (particularly SGPT) have also been reported but is common with interferon therapy.

MANAGEMENT: Caution is advised if bupropion is administered with beta interferons, particularly in the elderly and in patients with a history of seizures or other risk factors for seizures (e.g., head trauma; brain tumor; severe hepatic cirrhosis; metabolic disorders; CNS infections; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; diabetes treated with oral hypoglycemic agents or insulin). The manufacturer recommends a lower initial dosage of bupropion and gradual dosage increments in patients receiving concurrent treatment with other potentially epileptogenic drugs. The total dose of bupropion should generally not exceed 450 mg/day (or 150 mg every other day in patients with severe hepatic cirrhosis). Bupropion should be discontinued and not restarted in patients who experience a seizure during treatment.

The risk of hepatic injury should also be considered with this combination. Liver function tests should be monitored at regular intervals and the interferon dosage reduced if SGPT rises above 5 times the upper limit of normal. The dosage may be gradually re-escalated when enzyme levels return to normal. Patients should be advised to notify their physician if they experience signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. If liver injury is suspected, interferon therapy should be promptly discontinued due to the potential for rapid progression to liver failure.