Drug Interactions between R.E.C.K. and ziprasidone

MONITOR: Phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents may potentiate the blood pressure lowering capabilities of other drugs with hypotensive effects due to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the phenothiazine, TCA, or neuroleptic. The severity of this interaction may be affected by the agent's affinity for the alpha-1 adrenoceptor. One in vitro study demonstrated an affinity for the alpha-1 adrenoceptor for some of these medications that was similar to, or greater than, those of alpha blocker medications used to treat hypertension. Examples of drugs evaluated in this study with a high affinity included amitriptyline, clomipramine, chlorpromazine, clozapine, doxepin, flupenthixol, lurasidone, nortriptyline, perphenazine, paliperidone, quetiapine, risperidone, sertindole, and ziprasidone. On the other hand, examples of those with lower affinities included aripiprazole, lofepramine, protriptyline, sulpiride, and amisulpride.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines, tricyclic antidepressants (TCAs), or certain antipsychotic (neuroleptic) agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine, TCA, or neuroleptic may be appropriate, especially in the elderly. It may also be advisable to consider using a phenothiazine, TCA, or neuroleptic medication with a lower affinity for the alpha-1 adrenoceptor when possible. Patients should be counseled to avoid rising abruptly from a sitting or recumbent position and to notify their healthcare provider if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

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.