FANAPT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FANAPT (FANAPT).
FANAPT (iloperidone) is an atypical antipsychotic that exhibits high affinity for serotonin 5-HT2A and dopamine D2 receptors, with additional antagonism at alpha1-adrenergic, alpha2-adrenergic, and histamine H1 receptors. The therapeutic efficacy is primarily attributed to combined 5-HT2A and D2 receptor antagonism.
| Metabolism | Iloperidone is extensively metabolized primarily by CYP3A4 and CYP2D6, with minor contributions from CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2E1. The major active metabolite is P88-8991 (4-hydroxyiloperidone). |
| Excretion | Renal (approximately 80% as metabolites, <1% as parent drug) and fecal (approximately 20% as metabolites). |
| Half-life | Terminal elimination half-life is approximately 26 hours (range 22-30 hours) for the sum of parent drug and active metabolites (P95, P88, and P86); steady-state achieved within 4-5 days. |
| Protein binding | Approximately 99% bound to serum proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 20-30 L/kg, indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral bioavailability is approximately 50% (due to first-pass metabolism); administration with food increases Cmax and AUC by 20-30%. |
| Onset of Action | Oral: Clinical improvement may be observed within 1-2 weeks, but full antipsychotic effect may require 4-6 weeks. |
| Duration of Action | Once-daily dosing maintains therapeutic concentrations due to long half-life; clinical effects persist for 24 hours with regular dosing. |
| Molecular Weight | 426.5 |
12-24 mg orally once daily, titrated from 1 mg twice daily on day 1, 2 mg twice daily on day 2, 4 mg twice daily on day 3, 6 mg twice daily on day 4, 8 mg twice daily on day 5, then 10 mg twice daily on day 6 and 7, followed by 12 mg once daily on day 8. Maximum dose: 24 mg/day.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease (ESRD) due to limited data. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% (maximum 12 mg/day). Child-Pugh Class C: Use not recommended. |
| Pediatric use | Not approved for use in pediatric patients (<18 years) due to lack of safety and efficacy data. |
| Geriatric use | In elderly patients (≥65 years), initiate at 1 mg twice daily and titrate slowly; maximum dose 12 mg/day due to increased sensitivity and risk of adverse effects (e.g., orthostatic hypotension). |
| 1st trimester | Risk not ruled out. Atypical antipsychotics may have increased risk of malformations, but data insufficient. Use only if benefit outweighs risk. |
| 2nd trimester | Monitor for gestational diabetes and excessive weight gain. Continued use may be justified. |
| 3rd trimester | Risk for extrapyramidal symptoms and/or withdrawal symptoms in neonates following in utero exposure. Consider tapering before delivery. |
Clinical note
Comprehensive clinical and safety monograph for FANAPT (FANAPT).
| Placental transfer | Iloperidone crosses the placenta; mean cord blood concentration approximately 24% of maternal plasma. |
| Breastfeeding | Milk levels are low; relative infant dose estimated <2%. Monitor infant for drowsiness, irritability, poor feeding. Use with caution. |
■ FDA Black Box Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. FANAPT is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
Hypersensitivity to iloperidone or any of its components
| Precautions | Increased mortality in elderly patients with dementia-related psychosis, Cerebrovascular adverse events (including stroke) in elderly patients with dementia-related psychosis, QT interval prolongation, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Metabolic changes (hyperglycemia, dyslipidemia, weight gain), Hyperprolactinemia, Orthostatic hypotension and syncope, Leukopenia, neutropenia, and agranulocytosis, Seizures, Potential for cognitive and motor impairment, Body temperature dysregulation, Dysphagia, Suicide |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and increase iloperidone levels. No other significant food interactions. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | Iloperidone (FANAPT) is classified as Pregnancy Category C. Limited human data; animal studies show no clear teratogenicity but some embryotoxicity and maternal toxicity at high doses. First trimester exposure risk cannot be excluded; use only if benefit outweighs potential fetal risk. Second and third trimester exposure may increase risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and ECG for QTc prolongation. Assess for extrapyramidal symptoms, sedation, and metabolic parameters (glucose, lipids). Fetal monitoring: ultrasound for growth and well-being in third trimester; neonatal monitoring for extrapyramidal symptoms, respiratory distress, and feeding difficulties after delivery. |
| Fertility Effects | Iloperidone may cause hyperprolactinemia, which can inhibit hypothalamic GnRH secretion, leading to reduced libido, menstrual irregularities (including amenorrhea), and impaired fertility. In males, hyperprolactinemia may cause erectile dysfunction and gynecomastia. Effects are reversible upon discontinuation. |
| Clinical Pearls | Titrate slowly to minimize orthostatic hypotension; dose adjustments needed with strong CYP3A4 inhibitors. Monitor for QT prolongation, especially with electrolyte disturbances. Use lowest effective dose due to dose-dependent adverse effects. |
| Patient Advice | Avoid grapefruit juice during treatment. · Rise slowly from sitting or lying to prevent dizziness. · Report irregular heartbeat, fainting, or severe sedation. · Avoid alcohol and other CNS depressants. · Do not stop abruptly; taper under medical supervision. |