Interactions

Alcohol appears to at least add to the hypnotic effect of kava in mice, and was also observed to increase the lethality of kava (37). These findings may be of importance because some Australian Aboriginal populations now frequently consume kava with alcohol. Concomitant use of barbiturates, melatonin, and other psychopharmacological agents might potentiate the effects of kava as well (38). The hepatotoxic potential of kava (27) also raises concerns about concomitant alcohol use.

Although a Web site (13) promoting a kava product states that it is safe to use kava in combination with benzodiazepines, a case report (39) suggests otherwise. The combination of kava and alprazolam was believed to be responsible for hospitalizing a 54-year-old man. The patient's semicomatose (lethargic and disoriented) state improved after several hours. He had been taking an undisclosed brand of kava purchased in a health food store in combination with alprazolam for 3 days. Other medications taken included cimetidine and terazosin.

In vitro evidence suggests that kava components may inhibit the metabolism of drugs by cytochrome P450 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 (40). However, in vivo studies were not confirmatory except for the case of CYP2E1. Gurley and colleagues studied the ability of kava to inhibit in vivo metabolism by several of these enzymes and found that kava coadministration had no effect on CYP1A2, CYP2D6, or CYP3A4 activity but did significantly inhibit CYP2E1 activity (41). Because very few drugs are metabolized by CYP2E1, the clinical significance of this interaction is lessened. It appears that pharmacokinetic interactions with kava are unlikely and any drug interactions will likely be related to an additive pharmacodynamic effect (e.g., sedation).

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