Evodia by Herbal Terra

There is insufficient reliable information available about the effectiveness of evodia.

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There is insufficient reliable information available about the safety of evodia when used orally. In animal studies, evodia has induced QT interval prolongation and Torsade de pointes (97035). It is not clear what dose, if any, is required to produce a similar effect in humans.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Active constituents in evodia have uterine stimulant activity in animal models. Evodia might also decrease litter size in animal models (15229). Theoretically, taking evodia during pregnancy might adversely affect pregnancy outcome.

LACTATION:
Insufficient reliable information available; avoid using.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking evodia with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.  Details In vitro and animal studies show that rutaecarpine, a constituent of evodia, inhibits platelet aggregation (15222,15223,15238,107912).

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, evodia might decrease the levels and clinical effects of caffeine.  Details In animal models, evodia extract decreases caffeine levels by up to 71%. Evodia extract induces hepatic cytochrome P450 1A2 (CYP1A2) enzyme, of which caffeine is a substrate (15241).

CHLORZOXAZONE (Parafon Forte, Paraflex) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, evodia might decrease the levels and clinical effects of chlorzoxazone.  Details Animal research shows that administration of rutaecarpine, a constituent of evodia, with chlorzoxazone reduces the area under the curve (AUC) of chlorzoxazone by 84% and increases its clearance by 646%. This interaction is likely due to induction of cytochrome P450 2E1 (CYP2E1) by rutaecarpine (107913).

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, drugs that inhibit CYP1A2 might increase the levels and clinical effects of evodia.  Details The evodia constituent rutaecarpine is metabolized by CYP1A2 (15253).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Evodia might reduce the levels and clinical effects of CYP1A2 substrates through induction of CYP1A2.  Details Evodia extract and the evodia constituent rutaecarpine induce hepatic CYP1A2 enzyme activity (15227,15230,15241,15253). Evodia decreases levels of theophylline and caffeine, CYP1A2 substrates, by about 70% in animal models (15227,15241).

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, evodia might reduce the levels and clinical effects of CYP2E1 substrates through induction of CYP2E1.  Details Animal research suggests that rutaecarpine, a constituent of evodia, induces CYP2E1 activity. In rats, rutaecarpine increases markers of CYP2E1 activity, and administration of rutaecarpine with chlorzoxazone, a known CYP2E1 substrate, reduces the area under the curve (AUC) of chlorzoxazone by 84% and increases its clearance by 646% (107913).

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking CYP3A4 inducers might decrease the levels and clinical effects of evodia.  Details Animal research shows that concomitant administration of dexamethasone, a known CYP3A4 inducer, with the alkaloid constituents of evodia significantly reduces the area under the curve (AUC), maximum concentration (Cmax), and half-life of these constituents (107911).

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of evodia.  Details Animal research shows that concomitant administration of ketoconazole, a known CYP3A4 inhibitor, with the alkaloid constituents of evodia significantly increases the area under the curve (AUC), maximum concentration (Cmax), and half-life of these constituents (107911).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, evodia might increase the levels and clinical effects of CYP3A4 substrates.  Details In vitro research shows that evodia extract inhibits hepatic CYP3A4 (15236). This effect has not been reported in humans.

QT INTERVAL-PROLONGING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, evodia might have an additive effect with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.  Details Evodia has demonstrated dose-dependent activity as a proarrhythmic agent in animal and in vitro studies. Evodia infusion in animals extends the action duration potential and induces prolongation of the QT interval and Torsade de pointes (97035).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, evodia might decrease the levels and clinical effects of theophylline.  Details The evodia constituent rutaecarpine decreases theophylline levels and half-life by about 70% in animal models (15227). This constituent appears to induce hepatic cytochrome P450 1A2 (CYP1A2) enzyme activity, of which theophylline is a substrate (15227,15230). Rutaecarpine is the primary active constituent of evodia; however, it is not known if the whole crude extract of evodia also causes this interaction.

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General ...There is no reliable evidence regarding the safety of evodia from clinical trials. In animal studies, evodia has induced QT prolongation and Torsade de pointes (97035).

Cardiovascular ...In animal studies, evodia acts as a proarrhythmic agent with a dose-dependent effect. Evodia infusion has resulted in QT prolongation and Torsade de pointes (97035). It is not clear what dose of evodia, if any, is required to produce a similar effect in humans.

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