Basic Information
ID DDInter948 and DDInter252
Interaction The use of bupropion is associated with a dose-related risk of seizures. The risk may also be increased during coadministration of bupropion with other potentially epileptogenic agents such as interferons. 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. 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.
References [1] "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome, Research Triangle Park, NC. [2] "Product Information. Betaseron (interferon beta-1b)." Berlex, Richmond, CA. [3] "Product Information. Avonex (interferon beta-1a)." Biogen, Cambridge, MA. [4] "Product Information. Rebif (interferon beta-1a)." Serono Laboratories Inc, Norwell, MA. [5] "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome, Research Triangle Park, NC. [6] Posner J, Bye A, Jeal S, Peck AW, Whiteman P "Alcohol and bupropion pharmacokinetics in healthy male volunteers." Eur J Clin Pharmacol 26 (1984): 627-30 [7] Hamilton MJ, Bush MS, Peck AW "The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man." Eur J Clin Pharmacol 27 (1984): 75-80 [8] Ramcharitar V, Levine BS, Goldberger BA, Caplan YH "Bupropion and alcohol fatal intoxication: case report." Forensic Sci Int 56 (1992): 151-6
Alternative for Interferon beta-1b L03A
Alternative for Bupropion A08A

N06A
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Potential Metabolism Interactions
Substrate-Substrate Interaction:If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction:Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction:Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.