[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/second-generation-antipsychotics/) › Iloperidone

# 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.

Updated Nov 1, 2026

## Quick facts

**Group**
[Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/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.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## 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 →](https://durgical.com/en/conditions/schizophrenia/)
- Bipolar I disorder [Bipolar disorder →](https://durgical.com/en/conditions/bipolar-disorder/)

## Adverse effects

### Common

- Dizziness and orthostatic hypotension
- Fast heart rate, nasal congestion
- Sleepiness, fatigue, dry mouth
- Weight gain

### Serious (rare, important)

- Higher mortality in older people with dementia-related psychosis (boxed warning)
- QT prolongation, arrhythmia and sudden death
- Neuroleptic malignant syndrome; tardive dyskinesia
- Priapism, sometimes needing surgery
- Syncope; seizures; low white cell count; floppy iris during cataract surgery

## 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

## Memory aid

«ILOperidone = I Lower Orthostatic pressure»: alpha-1 block, so start slow and stand up slowly.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/iloperidone/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## Connections

## Related drugs 2

- [Risperidone](https://durgical.com/en/pharmacology/risperidone/)
- [Quetiapine](https://durgical.com/en/pharmacology/quetiapine/)

## Related conditions 2

- [Schizophrenia](https://durgical.com/en/conditions/schizophrenia/)
- [Bipolar disorder](https://durgical.com/en/conditions/bipolar-disorder/)

[← Back to the class: Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eeb0fcfd-e4e8-4fb1-9635-901dc9446235) (DailyMed (U.S. National Library of Medicine), 2026); [Iloperidone: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a609026.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N05AX14) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/iloperidone/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/iloperidone/