Is there a risk for an interaction between modafinil (Modiodal) and selective serotonin reuptake in

Fråga: Is there a risk for an interaction between modafinil (Modiodal) and selective serotonin reuptake inhibitors (SSRI)?

A 30-year-old woman is treated with modafinil for narcolepsy. Co-medication with an SSRI is considered. She also takes oral contraceptives.

Sammanfattning: When modafinil is combined with sertraline, there is a risk of interaction leading to lower plasma levels of sertraline and higher levels of citalopram. This, however, can be managed by adequate therapeutic drug monitoring. Fluoxetine, fluvoxamine and paroxetine do not appear to interact pharmacokinetically. Impaired contraceptive effect upon concomitant use of modafinil is possible although the risk is probably low.

Svar: Modafinil is a central stimulant and alpha-1 adrenergic agonist prescribed as a special licence preparation in Sweden for the treatment of narcoleptic syndrome. The drug is metabolised in the liver to the major metabolite modafinil acid. Excretion is mainly through the kidneys with less than 10 per cent of the dose being eliminated unchanged (1). Since both modafinil and SSRIs have alpha-1-adrenergic effect, pharmacodynamic interactions resulting in palpitation or tachycardia may occur, although specific data are lacking.

Modafinil induces the cytochrome P450 enzyme CYP3A4 and may impair the effect of drugs such as oral contraceptives and antiepileptics when given concomitantly (2). Studies have shown that modafinil induces the isoenzymes CYP1A2 and CYP3A4 (3) in human hepatocytes. The latter metabolises sertraline (Zoloft) and the serotonergic and noradrenergic inhibitor venlafaxine (Efexor) as well as oral contraceptives. However, the changes observed in enzyme activity were modest and much less than those known for other CYP inducers. The risk of decreased effects of sertraline/venlafaxine or p-pills is probably low but cannot be excluded. Other SSRIs such as fluoxetine (Fontex), fluvoxamine (Fevarin) and paroxetine (Seroxat) are all metabolised by CYP2D6 (4). Therefore, a pharmacokinetic interaction between modafinil and these drugs is not expected. Further studies have shown that modafinil may inhibit the isoenzyme CYP2C19 (3). Co-administration of citalopram (Cipramil), partly metabolised by CYP2C19, may therefore result in elevated plasma concentrations of citalopram. However, this has not been demonstrated clinically.