Drug Interactions between bupivacaine / dexamethasone / epinephrine and quetiapine

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of quetiapine, which is primarily metabolized by the isoenzyme. In 18 psychiatric patients receiving quetiapine 300 mg twice daily, addition of the potent CYP450 3A4 inducer carbamazepine (200 mg three times daily) decreased mean quetiapine peak plasma concentration (Cmax) and systemic exposure (AUC) by 80% and 87%, respectively, and increased oral clearance (Cl/F) by 7.5-fold compared to quetiapine administered alone. The interaction has also been reported with phenytoin, another potent CYP450 3A4 inducer. In ten subjects with various affective disorders, coadministration of quetiapine (250 mg orally three times a day) with phenytoin (100 mg orally three times a day) decreased the mean steady-state Cmax, trough plasma concentration (Cmin) and AUC of quetiapine by 66%, 89% and 80%, respectively. The mean oral clearance increased by 5.5-fold. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: Pharmacologic response to quetiapine should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the quetiapine dosage adjusted as necessary. Patients should be advised to notify their physician if their symptoms worsen or their condition changes.

GENERALLY AVOID: Phenothiazines and other neuroleptics may inhibit or reverse the pressor effect of adrenaline (epinephrine), dopamine, and similar vasoconstrictors. Many of these agents, including the atypical antipsychotics, exhibit alpha-1 adrenergic blocking activity and produce hypotension as an adverse effect. Use of adrenaline or dopamine for drug-induced hypotension and circulatory collapse in patients receiving neuroleptic therapy may cause a paradoxical further lowering of blood pressure, since beta stimulation may worsen hypotension in the setting of alpha blockade.

MANAGEMENT: Adrenaline, dopamine, and similar vasoconstrictors should not be used to treat drug-induced hypotension and circulatory collapse in patients taking phenothiazines or other neuroleptic agents. Alternative vasopressor agents such as metaraminol, noradrenaline (norepinephrine), or phenylephrine should be considered, and vital signs closely monitored.