N05BE01 - Buspirone |
Propably not porphyrinogenic |
PNP |
Rationale
Buspirone is not an inhibitor or an inducer of CYP3A4 or CYP1A2.
Risk for gastrointestinal adverse events in the form of nausea, abdominal pain, diarrhoea, obstipation and vomiting motivates vigilance against insufficient intake of food, especially of carbohydrate.
Chemical description
Buspirone is a serotonin agonist, but has also effects on dopamine receptors.
Therapeutic characteristics
Buspirone is indicated for the treatment of anxiety disorders.
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, abdominal pain, diarrhoea, obstipation and vomiting. Other common side effects are nervousness, insomnia, depression, confusion, paraesthesia, tremor, tachycardia, chest pain musculoskeletal pain and fatigue.
Metabolism and pharmakokinetics
Buspirone is metabolised via CYP3A4 (SPC). Metabolites include 5-hydroxy-buspirone which is inactive and 1-pyrimidinylpiperazine which is 1 to 20% as potent as buspirone (Gammans 1986). The elimination half-life is 2-11 hours.
Buspirone did not have any statistical significant effect on the AUC of diazepam, a CYP3A4 and CYP2C19 substrate (SPC), when they were co-administered (Gammans 1986 and SPC). When co-administered with haloperidol, a CYP1A2, CYP2D6 and CYP3A4 substrate (Cheng 2010), buspirone did not affect the pharmacokinetics of haloperidol significantly (Huang 1996). These data indicate that buspirone is not an inhibitor or an inducer of CYP3A4 or CYP1A2. It is also listed as an unlikely major perpetrator of CYP3A (Polasek 2011).
Published experience
Uneventful use of buspiron in a patient with documented acute intermittent porphyria (Holroyd 1999).
References
- Scientific articles
- Cheng JW, Frishman WH, Aronow WS. Updates on cytochrome p450-mediated cardiovascular drug interactions. Dis Mon. 2010 Mar;56(3):163-79. PMID 20189501. #1003
- Gammans RE, Mayol RF, LaBudde JA. Metabolism and disposition of buspirone. Am J Med. 1986 Mar 31;80(3B):41-51. #2678
- Holroyd S, Seward RL. Psychotropic drugs in acute intermittent porphyria. Clin Pharmacol Ther. 1999 Sep;66(3):323-5. PMID 10511069. #2679
- Huang HF, Jann MW, et al. Lack of pharmacokinetic interaction between buspirone and haloperidol in patients with schizophrenia. J Clin Pharmacol. 1996 Oct;36(10):963-9. PMID 8930784. #4676
- Polasek TM, Lin FP, et al. Perpetrators of pharmacokinetic drug-drug interactions arising from altered cytochrome P450 activity: a criteria-based assessment. Br J Clin Pharmacol. 2011 May;71(5):727-36. PMID 21223357. #4322
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Diazepam. #2681
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Buspirone. #2682
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