Lisdexamphetamine does not show potential for induction or mechanism-based inhibition of Cytochrome P450 enzymes. Nausea and reduced appetite are very common side effects of lisdexamphetamine. Continuous attention to ensure a sufficient carbohydrate intake is recommended. Attention is also motivated as the drug may initiate a hypothalamic-pituitary-adrenal (HPA) response with features common to the potentially porphyrinogenic response to fasting.

Lisdexamphetamine dimesylate is a prodrug to dextro-amphetamine.

Lisdexamphetamine is used for the treatment of Attention Deficit/Hyperactivity Disorder (ADHD) in pediatric populations. The pathogenic mechanisms behind ADHD are not known, amphetamines conceivably act by increasing presynaptic release of dopamine and other biogenic brain amines, and/or blocking of reuptake. The activation of the HPA axis gives rise to a physiological reaction in parts analogous to the potentially porphyrinogenic fasting response, Weight loss is very common in children and adolescents taking lisdexamphetamine. Common adverse reactions of lisdexamphetamine that may be confused with symptoms of an acute porphyric attack are nausea, vomiting, tachycardia, diarrhoea, insomnia, psychomotor hyperactivity, agitation and anxiety.

Significant, but probably not relevant as no pharmacokinetic porphyrinogenic effects are suspected.

Lisdexamphetamine is converted to dextro-amphetamine and L-lysine, which is believed to occur by first-pass intestinal and/or hepatic metabolism not involving CYP enzymes. The formation of 4-hydroxy-amfetamine from amphetamine is mediated in part by CYP2D6. In vitro experiments with human microsomes indicate minor inhibition of CYP2D6 by amphetamine and minor inhibition of CYP1A2, 2D6, and 3A4 by one or more metabolites. The clinical significance of this interaction is expected to be minimal (Hutson 2014, SPC). Lisdexamphetamine is not a mechanism based inhibitor of CYP3A4, CYP2C9, CYP2C19, CYP2D6 or CYP1A2 (Krishnan 2007).