|Trade names||Fanapt, Zomaril|
|Drug class||Atypical antipsychotic|
|Side effects||Sleepiness, dizziness, dry mouth, low blood pressure with standing, weight gain, QT prolongation|
|Onset of action||2 to 3 wks|
|Bioavailability||96% (by mouth; Tmax = 2–4 hours)|
|Metabolism||Liver (CYP2D6-mediated hydroxylation and CYP3A4-mediated O-demethylation)|
|Elimination half-life||18–33 hours|
|Excretion||urine (45.1–58.2%) and feces (19.9–22.1%)|
|Chemical and physical data|
|Molar mass||426.488 g·mol−1|
|3D model (JSmol)|
Common side effects include sleepiness, dizziness, dry mouth, low blood pressure with standing, and weight gain. Other side effects may include increased risk of death in older people with dementia, priapism, QT prolongation, neuroleptic malignant syndrome, tardive dyskinesia, milk production, and diabetes. It is believed to work by affecting dopamine and 5-hydroxytryptamine.
Iloperidone was approved for medical use in the United States in 2009. Approval was refused in Europe in 2017 due to modest benefit and concerns of side effects. In the United States, at a dose of 6 mg twice per day, a month of treatment costs about 2,100 USD as of 2021.
Iloperidone is indicated for the treatment of schizophrenia. In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, iloperidone demonstrated mild effectiveness. As effective as lurasidone, and 13 to 15% less effective than ziprasidone, chlorpromazine, and asenapine.
It generally appears to work better than placebo.
It is started at a dose of 1 mg twice per day and may be increased up to 12 mg twice per day.
Examination of the safety and tolerability of iloperidone have shown that at a 5 mg/day dose in healthy male volunteers, the drug was fairly well tolerated, although hypotension, dizziness, and somnolence were very common side effects ranging from mild to moderate in severity. A second study showed that co administration of food decreased the severity of these effects. This study also indicated that repeat administration of iloperidone could decrease the effects of hypotension.
The approved dose is 12–24 mg not 5 mg. However, claims of better tolerance have been reported.
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.
There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.
Iloperidone exerts its effects by acting upon and antagonizing specific neurotransmitters, particularly multiple dopamine and serotonin receptor subtypes. It is considered an ‘atypical’ antipsychotic because it displays serotonin receptor antagonism, similar to other atypical antipsychotics. The older typical antipsychotics are primarily dopamine antagonists.
Iloperidone has been shown to act as an antagonist at all tested receptors. It exhibits high (nM) affinity to serotonin 5HT2A (Ki value of 5.6 nM), dopamine D2 (6.3 nM) and D3 (7.1 nM) and noradrenaline α1 receptors (0.36 nM), moderate affinity for dopamine D4 (25 nM), serotonin 5HT6 (43 nM), 5HT7 (22 nM), and low affinity for the serotonin 5HT1A (168 nM), dopamine D1 and histamine H1 receptors. In addition, pharmacogenomic studies identified single nucleotide polymorphisms associated with an enhanced response to iloperidone during acute treatment of schizophrenia.
Society and culture
Hoechst Marion Roussel Inc. made initial inquiries into the drug; however, in May 1996, they discontinued research, and in June 1997 gave research rights to Titan Pharmaceuticals. Titan then handed over worldwide development, manufacturing and marketing rights to Novartis in August 1998. On June 9, 2004, Titan Pharmaceuticals announced that the Phase III development rights have been acquired by Vanda Pharmaceuticals. The original launch date was scheduled for 2002. On November 27, 2007, Vanda Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) had accepted their New Drug Application for iloperidone, confirming the application is ready for FDA review and approval. On July 28, 2008, the FDA issued a not-approvable letter to Vanda Pharmaceuticals concerning the drug, stating that further trials are required before a decision can be made concerning marketed usage of iloperidone.
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Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
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