N06AX12 - Bupropion |
Possibly porphyrinogenic |
PSP |
Rationale
The plasma concentration of threohydrobupropion and erythrohydrobupropion is equal or higher than bupropion. Due to the lack of data on their inhibition potential towards CYP enzymes, bupropion is classified as possibly porphyrinogenic.
Risk for gastrointestinal adverse events in the form of nausea, vomiting, abdominal pain and obstipation motivates vigilance against insufficient intake of food, especially of carbohydrate.
Chemical description
Bupropion is also known as amfebutamone.
Therapeutic characteristics
Bupropion is indicated for the treatment of depression.
Very common and common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are nausea, vomiting, abdominal pain and obstipation. Other common side effects are anorexia, anxiety, hypertension, fever, chest pain and asthenia.
Metabolism and pharmacokinetics
Bupropion is metabolised by CYP2B6 to the major active metabolite hydroxybupropion. Other active metabolites are threohydrobupropion and erythrohydrobupropion (SPC). The mean half-life elimination fo r bupropion and its major active metabolite are 20 hours.
It is an inhibitor of CYP2D6 in vivo (Isoherranen 2009 and SPC).
When co-administered, carbamazepine decreased the AUC of bupropion by 90%. It is possible that carbamazepine induced the metabolism of bupropion via CYP3A4 (Ketter 1995).
The plasma concentration of threohydrobupropion and erythrohydrobupropion is equal or higher than bupropion, but their inhibition potential towards CYP450 enzymes has not been studied (SPC).
Preclinical data
A study in primary cultures of chick embryo liver cells suggests that patients with acute porphyria may be at greater risk for developing porphyric attacks when treated with bupropion (Lambrecht 1999).
References
- Scientific articles
- Isoherranen N, Hachad H, et al. Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Chem Res Toxicol. 2009 Feb;22(2):294-8. #1005
- Ketter TA, Jenkins JB, et al. Carbamazepine but not valproate induces bupropion metabolism. J Clin Psychopharmacol. 1995 Oct;15(5):327-33. #2809
- Lambrecht RW, Gildemeister OS, et al. Effects of antidepressants and benzodiazepine-type anxiolytic agents on hepatic porphyrin accumulation in primary cultures of chick embryo liver cells. J Pharmacol Exp Ther. 1999 Dec;291(3):1150-5. PMID 10565836. #4706
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Bupropion. #2811
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