Iloperidone
Second-generation antipsychotics
Second-generation antipsychotics
An atypical antipsychotic with strong alpha-1 blockade: slow titration to avoid orthostatic hypotension, and QT prolongation to watch.
Quick facts
- Group
- Second-generation antipsychotics
- Target
- Dopamine D2 and serotonin 5-HT2 receptors (antagonist); also alpha-1 adrenergic
- Used for
- Schizophrenia in adults · Bipolar I disorder
- Key effects
- Dizziness and orthostatic hypotension · Sleepiness
- Monitor
- Blood pressure lying and standing · ECG and potassium
- ATC
- N05AX14
No doses: the clinician sets them by the current guideline.
Mechanism of action
Iloperidone is thought to work through combined antagonism at dopamine D2 and serotonin 5-HT2 receptors; its active metabolite P88 has a similar profile. It also blocks alpha-1 adrenergic receptors, which causes orthostatic hypotension, dizziness, tachycardia and nasal congestion, and is why the amount is increased slowly at the start.
- Iloperidone blocks D2 and 5-HT2 receptors
- Less dopamine signal: less psychosis
- Alpha-1 block: dizziness, fast pulse, stuffy nose
- Slow start; watch QT prolongation
Indications
- Schizophrenia in adults Schizophrenia →
- Bipolar I disorder Bipolar disorder →
Adverse effects
Common
- Dizziness and orthostatic hypotension
- Fast heart rate, nasal congestion
- Sleepiness, fatigue, dry mouth
- Weight gain
Contraindications
- Hypersensitivity to iloperidone
Key interactions
- Strong CYP2D6 inhibitors (fluoxetine, paroxetine) or CYP3A4 inhibitors (ketoconazole, clarithromycin)
- Higher iloperidone exposure and QT effect; the amount is reduced
- Other QT-prolonging drugs
- Avoided: additive QT prolongation
- Antihypertensives
- Added orthostatic hypotension
What is monitored
- Blood pressure lying and standing, and heart rate, during titration
- ECG and potassium and magnesium when at risk
- Weight, glucose and lipids
Administration and safety
- Started low and increased slowly to limit orthostatic hypotension
- Not recommended in severe hepatic impairment
Pregnancy and breastfeeding
Newborns exposed in the third trimester may have extrapyramidal or withdrawal symptoms; breastfeeding is not advised.
Nursing care
- Measures lying and standing blood pressure and pulse during the first days and after increases
- Teaches the patient to rise slowly and to report fainting or palpitations
- Warns that an erection lasting hours is an emergency
- Tells the eye surgeon about iloperidone before cataract surgery
Pharmacokinetics
- Absorption
- Taken by mouth
- Metabolism
- Liver, by CYP2D6 and CYP3A4, to active metabolites P88 and P95
- Half-life
- About 18 hours in CYP2D6 extensive metabolisers and 33 hours in poor metabolisers
Test yourself
Think of the answer, then tap the question to see it.
Why is iloperidone increased slowly at the start?
Its alpha-1 blockade causes orthostatic hypotension, dizziness and syncope.
Which ECG effect is a warning for iloperidone?
QT prolongation.
Which enzymes metabolise iloperidone?
CYP2D6 and CYP3A4; poor CYP2D6 metabolisers have a longer half-life.
Connections
← Back to the class: Second-generation antipsychotics
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - ILOPERIDONE tablet (DailyMed (U.S. National Library of Medicine), 2026); Iloperidone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.