3. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for quetiapine are summarized in Table 5. Only those drug-drug interactions classified as clinical significance severe or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
|---|---|---|---|---|
| Atypical antipsychotics (AAs) | Antihypertensive agents | Potential for enhanced antihypertensive effects due to AA-associated alpha1-adrenergic receptor antagonism | Use cautiously together; monitor for amplified hypotensive effects | moderate (CP) |
| AAs | CNS depressants | Potential for additive CNS effects | Use cautiously together; observe patients for enhanced CNS adverse effects | moderate (CP) |
| AAs (except pimavanserin) | Drugs affecting seizure threshold (e.g., tramadol) | Increased seizure risk as AAs have been associated with seizures (incidence varies) | Avoid drug combination if possible; if combination necessary, closely monitor patients for seizure activity and discontinue therapy as indicated | major (CP) |
| AAs | Metoclopramide | Adjunctive therapy enhances potential for increased extrapyramidal symptoms (EPS) and neuroleptic malignant syndrome (NMS) as both agents block dopamine receptors | Combination contraindicated by metoclopramide manufacturer; if combination necessary, monitor for signs/symptoms of EPS or NMS-discontinue metoclopramide if symptoms develop | severe (CP) |
| Select AAs (aripiprazole, brexpiprazole, cariprazine, clozapine, iloperidone, pimavanserin, quetiapine, ziprasidone) | CYP3A4 inhibitors (e.g., ketoconazole, ritonavir*) | Potential for decreased AA clearance, increased AA serum concentrations, and enhanced pharmacologic/ adverse effects as select AAs metabolized by CYP3A4 | Monitor for enhanced AA pharmacologic/ adverse effects and adjust doses as necessary (50% dose reduction recommended for aripiprazole, brexpiprazole, iloperidone) | major, moderate (CP) |
| Select AAs (aripiprazole, brexpiprazole, clozapine, olanzapine, pimavanserin, quetiapine, risperidone, ziprasidone) | CYP3A4 inducers (e.g., carbamazepine**, phenytoin) | Potential for significant reductions in AA plasma concentrations (by as much as 50%) due to enhanced AA hepatic microsomal metabolism | Monitor AA efficacy in patients; adjust doses as necessary when CYP3A4 inducer added, deleted, or changed to therapeutic regimen (brexpiprazole dose should be doubled over 1-2 weeks when prescribed with CYP3A4 inducer) | major, moderate (CP) |
| Select AAs (aripiprazole, asenapine, clozapine, iloperidone, olanzapine, paliperidone, pimavanserin, quetiapine, risperidone, ziprasidone) | QTc interval-prolonging medications | Potential for increased cardiotoxicity (e.g., torsades de pointes, cardiac arrest) due to additive QT interval prolongation | Avoid concurrent use; if combination necessary, closely monitor cardiac function; discontinue therapy in patients with QTc measurements greater than 500 msec | severe, major (CP) |