Iloperidone is an atypical antipsychotic medication marketed under the brand name Fanapt. It is approved by the U.S. Food and Drug Administration for the treatment of schizophrenia in adults.
It's used to treat schizophrenia symptoms including hallucinations, delusions, and disorganized thinking.
Iloperidone blocks dopamine D2 and serotonin 5-HT2A receptors and also inhibits α1-adrenergic receptors. The combination dampens excess dopamine signaling and is the basis for its antipsychotic effect.
The primary gene involved in iloperidone metabolism is CYP2D6. CYP2D6 is an enzyme in the liver that helps break down many medications, including iloperidone. It converts the drug into inactive or less active compounds that can be eliminated from the body.
Variations in the CYP2D6 gene can alter how quickly or slowly iloperidone is metabolized. Poor metabolizers have reduced enzyme function leading to higher drug levels, while ultrarapid metabolizers clear the drug more quickly, potentially lowering its effectiveness.
Genetic differences in CYP2D6 activity group patients into phenotypes—ultrarapid, normal, intermediate, and poor metabolizers. These groups influence iloperidone blood levels, therapeutic efficacy, and the risk of side effects such as QT prolongation. Clinicians may adjust dosing based on phenotype to optimize treatment.
The following dosing guidelines are based on FDA pharmacogenetic associations for iloperidone and CYP2D6 metabolism.
| Phenotype | Clinical Consequence | Guideline Recommendation |
|---|---|---|
| Ultrarapid Metabolizer | No FDA guidance for this phenotype; potential subtherapeutic levels | Use standard dosing; monitor symptoms and adjust if needed |
| Normal Metabolizer | No FDA guidance for this phenotype; expected therapeutic exposure | Use standard dosing |
| Intermediate Metabolizer | No FDA guidance for this phenotype; mildly increased exposure | Use standard dosing; monitor for side effects |
| Poor Metabolizer | Higher systemic concentrations; increased QT prolongation risk | Reduce dosage by 50% |
| Indeterminate / Not available | Unknown impact | Initiate therapy with recommended starting dose; monitor clinically |
The FDA guidelines do not specify alternate drugs for CYP2D6 poor metabolizers of iloperidone. Clinicians may consider other atypical antipsychotics without strong CYP2D6 dependence, such as risperidone or quetiapine, based on individual patient needs and tolerability.
Gene2Rx uses the same CPIC and FDA guidelines as GeneSight, covers more medications, costs $5-$49 instead of several hundred, and works with the 23andMe or AncestryDNA data you may already have. See the full side-by-side comparison before ordering.
See the full list of drugs affected by each gene:
See how your genetics affect each product Iloperidone shows up in:
Interested in learning more about how your genetics may affect your response to medication? Get started with Gene2Rx today.
I'm Interested