4. 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 LAI atypical antipsychotics are summarized in Table 6. Only those drug-drug interactions classified as clinical significance of severe or those considered life-threatening which have not yet been classified will be reviewed 1-13.
Table 6: Select LAI Atypical Antipsychotic Drug-Drug Interactions
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level |
|---|---|---|---|---|
| Aripiprazole | Citalopram | Increased risk of QT prolongation and serotonin syndrome because aripiprazole is a partial agonist of 5-HT1A and citalopram is a selective serotonin reuptake inhibitor | Avoid use | Major (DrugReax) 2-major(CP) |
| Aripiprazole | Strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) | Increased risk of aripiprazole overexposure because aripiprazole is metabolized by CYP3A4 | Monitor patient closely and adjust aripiprazole dosages as needed | Major (DrugReax) 3-moderate (CP) |
| Long-acting injectable atypical antipsychotics (LAI AAs) | CNS depressants | Increased risk of respiratory and central nervous system depression due to additive pharmacologic effects | Use cautiously together; observe patients for enhanced CNS adverse effects | Major (DrugReax) 3-moderate (CP) |
| LAI AAs | Metoclopramide | Increased risk of extrapyramidal reactions or neuroleptic malignant syndrome | Avoid use | Contraindicated (DrugReax) 1-severe,2-major (CP) |
| LAI AAs | QT interval- prolonging medications (e.g. posaconazole) | Increased risk of QT interval prolongation | Avoid use; if combined use necessary, administer cautiously together and monitor closely | Contraindicated (DrugReax) 1-severe,2-major,3-moderate (CP) |
| Olanzapine | Agents that lower seizure threshold (e.g. clomipramine) | Increased seizure risk because psychotropic drugs may reduce the seizure threshold | Use caution when administered concomitantly | Major (DrugReax) 3-moderate (CP) |
| Atypical antipsychotics | CYP3A4 and CYP1A2 inducers (e.g. carbamazepine) | Concomitant use can lead to decreased serum concentrations of atypical antipsychotics | Monitor treat efficacy and adjust atypical antipsychotic dosages as needed | Major (DrugReax) 2-major (CP) |
| Olanzapine (CYP1A2 substrate) | CYP1A2 inhibitor (e.g. fluvoxamine) | Increased olanzapine serum concentrations | Monitor patient closely and adjust olanzapine dosages as needed | Major (DrugReax) 2-major (CP) |
| Risperidone | Serotonergic agents (e.g. linezolid) | Increased risk of serotonin syndrome | Monitor patients for serotonin syndrome | Major (DrugReax) 2-major (CP) |
| Risperidone, Olanzapine | Lithium | Increased extrapyramidal symptoms; encephalopathy and brain damage have occurred in case reports due to unknown mechanism | Monitor patients closely for symptoms and monitor lithium levels | Major (DrugReax) 3-moderate (CP) |