Zolmitriptan is possibly a CYP1A2 substrate. It is not an inhibitor or inducer of CYP enzymes. Risk for gastrointestinal adverse events in the form of nausea and vomiting motivates vigilance against insufficient intake of food, especially of carbohydrate.

Zolmitriptan is a serotonin-receptor agonist.

Zolmitriptan is indicated for the acute relief of migraine attacks, with or without aura. 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 abdominal pain, nausea and vomiting. Other common side effects are paraesthesia, muscle weakness and myalgia. Some of the symptoms can be related to the underlying condition.

Zolmitriptan is metabolised to three major metabolites: the indole acetic acid, the N-oxide and N-desmethyl analogues. The former is active and is expected to contribute therapeutically. Over 60 % of one oral dose is excreted mainly as the indole acetic acid in the urine and about 30% is excreted mainly as unchanged drug in faeces. The half-life elimination is 4.7 hours in healthy volunteers. The half-life elimination for the active N-desmethyl metabolite is 5.7 hours (SPC). Co-administration of zolmitriptan with cimetidine, an unspecific CYP inhibitor, increased the AUC of zolmitriptan and the active metabolite by 48% and 105% respectively (Dixon 1998 and SPC). This indicates that zolmitriptan and the active metabolite is a substrate of possibly several CYP enzymes. Two clinical studies showed that co-administration of zolmitriptan with rifampicin (Dixon 1998 and SPC) and fluoxetine (Smith 1998 and Wild 1999) a CYP3A4 inducer, and CYP2D6 and CYP3A4 inhibitor respectively, had no effect on the pharmacokinetics of zolmitriptan (Dixon 1998 and Smith 1998) or its metabolites (Smith 1998). These studies indicate that zolmitriptan and its metabolites are not substrates of CYP2D6 or CYP3A4. In vitro data indicates that Zolmitriptan is metabolised by CYP1A2 (Dixon 1998, Pelkonen 2008 and Wild 1999). Other in vivo data indicates that zolmitriptan is also a substrate of monoamine oxidase A (Rolan 1997 and SPC). No drug-drug interactions with zolmitriptan as a perpetrator are observed (Interaksjoner and Interaktionsdatabasen), which indicate that zolmitriptan is not an inhibitor or inducer of CYP enzymes.

C.Andersson; patient inquiry: used without ill effects (n=1).

Uneventful use reported in 8 patients with acute porphyria.