Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Phenytoin
Phenytoin may induce the metabolism of psoralens. Failure of methoxsalen therapy may be attributed to this interaction if they are administered concomitantly.

Tolbutamide
Methoxsalen is highly bound to serum albumin but can also be displaced, particularly by tolbutamide. Concomitant use of methoxsalen and tolbutamide may lead to enhanced photosensitivity.

Cytochrome P450
Methoxsalen is metabolised via cytochrome P450 (CYP1A2). Therefore, caution is required if medicinal products that are metabolised predominantly by CYP1A2 (melatonin, xanthines such as caffeine, theophylline) are administered concomitantly. Co-administration may prolong the half-life of methoxsalen and result in prolonged photosensitivity.

Although methoxsalen has been shown to be capable of both induction and inhibition of hepatic enzymes, in humans it seems to act primarily as a potent inhibitor of microsomal oxidative metabolic processes. It is therefore to be expected that interactions will occur between methoxsalen and other medicinal products whose metabolism involves the cytochrome P450 system (particularly CYP1A2). The clearance rates of caffeine were markedly reduced after methoxsalen treatment. Both conjugated and unconjugated metabolites have been identified, but neither of them showed pharmacologically relevant activity.
Photosensitising agents
Caution is also required in patients taking cytotoxic or other photosensitising agents concomitantly:
Fluoroquinolones, furosemide, retinoids, sulfonylureas, anthralin, coal tar, griseofulvin, nalidixic acid, sulfonamides, tetracyclines, halogenated salicyl aniline derivatives, thiazides, phenothiazines, methylene blue, tolonium chloride, rose Bengal, methyl orange, oral coumarin anticoagulants.