Oral methoxsalen and 5-methoxypsoralen markedly reduce caffeine clearance but clinical significance of this is uncertain
A single 1.2-mg/kg oral dose of methoxsalen (8-methoxypsoralen), given to 5 subjects with psoriasis 1 hour before a single 200mg oral dose of caffeine, reduced clearance of caffeine by 69%. The elimination half-life of caffeine over period from 2 to 16 hrs after taking methoxsalen increased tenfold (from 5.6 to 57 hours) (See reference number 1). In a similar study,8 patients with psoriasis were given caffeine 200mg with or without 5-methoxypsoralen 1.2 mg/kg. The AUC of caffeine increased by about threefold and there was a threefold decrease in its clearance (See reference number 2).
A study in patients receiving PUVA therapy (methoxsalen either orally, in 4 patients, or topically as a bath in 7 patients, plus UVA) found that clearance of a single 150mg dose of caffeine was markedly reduced in patients given oral methoxsalen but not altered in those given top
Both methoxsalen and 5-methoxypsoralen inhibit hepatic metabolism of caffeine by cytochrome P450 isoenzyme CYP1A2, thereby markedly increasing caffeine levels (See reference number 2,3).
The practical consequences of this interaction are as yet uncertain, but it seems possible that toxic effects of caffeine will be increased. In excess,caffeine (including that from tea, coffee and cola drinks) can cause jitteriness, headache and insomnia. The interaction does not appear to occur with topical methoxsalen.
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