N03AX09 - Lamotrigine |
Propably not porphyrinogenic |
PNP |
Rationale
Lamotrigine is not metabolized by CYP, and it is not an inducer or an inhibitor of CYP.
It has been used uneventfully by 6 patients with acute porphyria.
Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Lamotrigine is a phenylthiazine and is chemically unrelated to other anticonvulsants.
Therapeutic characteristics
Lamotrigine is an antiepileptic drug used in the treatment of partial seizures and primary and secondary generalised tonic-clonic seizures and seizures associated with Lennox-Gastaut syndrome.
It is also used for prevention of depressive episodes in patients with bipolar disorder who experience predominantly depressive episodes.
Lamotrigine is administered orally.
Common adverse reactions of lamotrigine that can be confused with an acute porphyric attack are nausea and vomiting. These adverse reactions may be potentially porphyrinogenic through reduction in caloric intake.
Hepatic exposure
Significant.
Metabolism and pharmakokinetics
Lamotrigine is metabolised mainly by glucuronic acid conjugation to inactive metabolites, mainly a 2-N-glucuronideconjugate, a 5-N-glucuronide and a 2-N-methyl metabolite. It is eliminated renaly.
There is no evidence that lamotrigine causes induction or inhibition of hepatic oxidative drug metabolising enzymes.
Lamotrigine has shown to induce the accumulation of porphyrins in chicken embryo liver cells (Hahn 1997).
IPNet drug reports
Uneventful use reported in 6 patients with acute porphyria.
References
- Scientific articles
- Biton, V., Pharmacokinetics, toxicology and safety of lamotrigine in epilepsy.Expert Opinion on Drug Metabolism and Toxicology 2006 2(6):1009-1018. #2579
- Hahn et al. Effects of new anticonvulsant medications on porphyrin synthesis in cultured liver cells. Neurology 1997, 49:97 #2581
- Drug reference publications
- DrugBank. Lamotrigine. #2580
- McEvoy GK, editor. Lamotrigine. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (16.12.2010). #2582
- Sweetman SC, editor. Martindale: The complete drug reference. Lamotrigine. Pharmaceutical Press 2009. #2585
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Lamictal. #2583
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Lamictal. #2584
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