Table 4.

Antipsychotic drug interactions with DAAs

Drug (route of metabolism)	Known or potential interactions with DAAs	Comments
Aripiprazole (CYP3A4, 2D6)	Potential for ↑ aripiprazole concentrations	Use combination with caution, and monitor for aripiprazole-related toxicity (sedation, sinus tachycardia, nausea/vomiting, or dystonic reactions). Consider starting with a decreased aripiprazole dose or select an alternate agent.
Asenapine (UGT1A4, CYP1A2)	No interaction expected based on known pharmacologic characteristics	Monitor and titrate dose according to clinical response [76].
Clozapine (CYP1A2> 3A4,P-gp)	Potential for ↑ clozapine concentrations	Clozapine has a narrow therapeutic index. Use combination with caution, and monitor for clozapine-related toxicity (Bone marrow suppression, generalized seizures, severe sedation, confusion and delirium). Consider starting with a decreased clozapine dose or select an alternate agent. When available, clozapine therapeutic drug monitoring is recommended [77,78].
Olanzapine (CYP1A2, UGT,PGP>2D6)	No interaction expected based on known pharmacologic characteristics	Monitor and titrate dose according to clinical response.
Paliperidone Primarily renally excreted (59%); minor CYP dependant pathway (CYP3A4, PGP>2D6), but may not be clinically significant. Substrate and inhibitor of P-gp [79]	Potential for ↑ paliperidone concentrations	DAAs inhibit both CYP3A4 and P-gp, and clinically significant interaction, although unlikely, cannot be ruled out. Use combination with caution, and monitor for possible paliperidone-related toxicity.
Quetiapine (CYP3A4>2D6, P-gp)	Potential for ↑ quetiapine concentrations	Use combination with caution, and monitor for quetiapine-related toxicity (excessive sedation). Consider starting with a decreased quetiapine dose or select an alternate agent [80].
Risperidone (CYP2D6, P-gp>3A4)	Potential for ↑ risperidone concentrations	Unlike its active metabolite paliperidone, risperidone is primarily metabolized by CYP2D6. However, the elimination of paliperidone may be impaired. Use combination with caution, and monitor for possible risperidone-related toxicity.
Ziprasidone (CYP3A4>1A2) Minor CYP dependant pathway (33%) [78].	Potential for ↑ ziprasidone concentrations	Although clinically significant interaction unlikely, use combination with caution, and monitor for possible ziprasidone-related toxicity (QTc).