N06AX11 - Mirtazapine |
Propably not porphyrinogenic |
PNP |
Rationale
Mirtazapine is not an inhibitor or an inducer of CYP2C9, CYP2C19 or CYP3A4.
Risk for gastrointestinal adverse events in the form of diarrhoea, nausea and vomiting motivates vigilance against insufficient intake of food, especially of carbohydrate.
Chemical description
Mirtazapine is a centrally active presynaptic α2-antagonist. It is a racemate and both enantiomers are pharmacologically active (Spina 2012).
Therapeutic characteristics
Mirtazapine is indicated for the treatment of depression.
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 diarrhoea, nausea and vomiting. Other common side effects are insomnia, somnolence, dizziness, tremor, arthralgia, myalgia, back pain and fatigue.
Metabolism and pharmakokinetics
Mirtazapine is metabolised by CYP2D6, CYP3A4 and CYP1A2 (Timmer 2000). The mean half-life elimination is 20-40 hours.
When co-administrated mirtazapine did not have any effect on the pharmacokinetics of carbamazepine (Sitsen 2001 and Spina 2012), a CYP3A4 substrate, which indicates that mirtazapine does not inhibit or induce CYP3A4.
Mirtazapine did not significantly affect the AUC of phenytoin, substrate of CYP2C9 and CYP2C19 (Norsk legemiddelhåndbok), when co-administrated (Spaans 2002). This indicates that mirtazapine is not an inhibitor or an inducer of CYP2C9 or CYP2C19.
IPNet drug reports
Uneventful use reported in 7 patients with acute porphyria.
References
- Scientific articles
- Pelkonen O, Turpeinen M, et al. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol. 2008 Oct;82(10):667-715. PMID 18618097. #4347
- Sitsen J, Maris F, Timmer C. Drug-drug interaction studies with mirtazapine and carbamazepine in healthy male subjects. Eur J Drug Metab Pharmacokinet. 2001 Jan-Jun;26(1-2):109-21. PMID 11554425. #2786
- Spaans E, van den Heuvel MW, et al. Concomitant use of mirtazapine and phenytoin: a drug-drug interaction study in healthy male subjects. Eur J Clin Pharmacol. 2002 Sep;58(6):423-9. PMID 12242602. #4703
- Spina E, Trifiro G, Caraci F. Clinically significant drug interactions with newer antidepressants. CNS Drugs. 2012 Jan 1;26(1):39-67. PMID 22171584. #2788
- Timmer CJ, Sitsen JM, Delbressine LP. Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet. 2000 Jun;38(6):461-74. PMID 10885584. #2789
- Drug reference publications
- Norsk legemiddelhåndbok. Fenytoin #2784
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Mirtazapine. #2785
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