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| Systematic (IUPAC) name | |
|---|---|
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1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone
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| Clinical data | |
| Trade names | Fanapt, Zomaril |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a609026 |
| Licence data | US FDA:link |
| Legal status |
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| Routes of administration |
Oral, injection |
| Pharmacokinetic data | |
| Protein binding | ~95% |
| Metabolism | hepatic (CYP2D6 and CYP3A4) |
| Biological half-life | 18-33 hours |
| Excretion | urine and feces |
| Identifiers | |
| CAS Registry Number | 133454-47-4 Y |
| ATC code | N05AX14 |
| PubChem | CID: 71360 |
| IUPHAR/BPS | 87 |
| ChemSpider | 64459 Y |
| UNII | VPO7KJ050N Y |
| KEGG | D02666 Y |
| ChEBI | CHEBI:65173 N |
| ChEMBL | CHEMBL14376 Y |
| Chemical data | |
| Formula | C24H27FN2O4 |
| Molecular mass | 426.481g/mol |
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Iloperidone, also known as Fanapt, Fanapta, and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia.
Contents
- 1 Availability
- 2 Pharmacology
- 3 Laboratory studies
- 4 Clinical studies
- 5 Side effects
- 6 Dosage
- 7 Regulatory approval
- 8 References
- 9 External links
Availability
It was approved by the U.S. Food and Drug Administration (FDA) for use in the United States on May 6, 2009.
Pharmacology
Iloperidone is a monoamine directed towards 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), moderate affinity for dopamine D4 (25 nM), serotonin 5HT6 (43 nM), 5HT7 (22 nM) and noradrenaline α1 receptors (0.36 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.[1][2]
Laboratory studies
Iloperidone performed well against a prepulse inhibition (PPI) experiment, which was designed to gauge the extent of sensory gating in rats, a process disrupted in schizophrenia. Prepulse inhibition is the reduction in the amount of startle the subject gives when presented with a non-startling stimulus. Those exhibiting high levels of psychosis present a deficit in PPI. Psychosis induced using PCP, apomorphine, and cirazoline, were all prevented with the concurrent administration of iloperidone. The PPI deficit normally incurred by each psychotic drug was significantly diminished by the co administration of iloperidone.[3] The results of this experiment provided strong evidence for iloperidone’s merit as an effective treatment for psychotic disorders. Iloperidone has also been shown to reduce the effects of apomorphine induced climbing behavior in mice as well as the effects of head twitching induced by 5-HT in rats.[4]
Clinical studies
Several large (n > 570 per trial), double-blind, multinational, multicentre trials showed iloperidone generally had better efficacy than placebo when using the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) scores.[1] Clinical studies have also shown that some patients treated with iloperidone show reduced extrapyramidal symptoms and weight gain. Phase II testing has shown that effectiveness in humans is possible with as low as 8 mg per day, and is tolerable up to 4 mg per day.
Side effects
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.[5]
The Approved Dose is 12–24 mg not 5 mg. However, claims of better tolerance have been reported.
In some cases (prevalence unknown), it can greatly increase agitation and aggressivity like all antipsychotics drugs.
Dosage
Vanda Pharmaceuticals has stated that they are developing both oral and injectable formulations. The injectable formulation is being developed to be administered at four week intervals.
Regulatory approval
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.[6] 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.[7]
Iloperidone won FDA approval for use treating schizophrenia in the United States on May 6, 2009.[8]
References
- ^ a b Scott L.Iloperidone: In Schizophrenia. CNSDrugs 2009; 23(10):867-880. doi:10.2165/10489070-000000000-00000.
- ^ Brunton, LL (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. New York, NY: McGraw-Hill Medical. ISBN 9780071769396.
- ^ Barr AM, Powell SB, Markou A, Geyer MA (September 2006). "Iloperidone reduces sensorimotor gating deficits in pharmacological models, but not a developmental model, of disrupted prepulse inhibition in rats". Neuropharmacology 51 (3): 457–65. doi:10.1016/j.neuropharm.2006.04.004. PMID 16762376.
- ^ Szewczak MR, Corbett R, Rush DK, Wilmot CA, Conway PG, Strupczewski JT, Cornfeldt M (September 1995). "The pharmacological profile of iloperidone, a novel atypical antipsychotic agent". The Journal of Pharmacology and Experimental Therapeutics 274 (3): 1404–13. PMID 7562515.
- ^ Sainati SM, Hubbard JW, Chi E, Grasing K, Brecher MB (July 1995). "Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic". Journal of Clinical Pharmacology 35 (7): 713–20. doi:10.1002/j.1552-4604.1995.tb04112.x. PMID 7560252.
- ^ "Vanda Pharmaceuticals Receives FDA Acceptance of Iloperidone New Drug Application" (Press release). Vanda Pharmaceuticals. November 27, 2007. Retrieved 2007-11-27.
- ^ "FDA Issues Not Approvable Letter for Iloperidone to Vanda Pharmaceuticals" (Press release). Vanda Pharmaceuticals. July 28, 2008. Retrieved 2008-08-08.
- ^ "Vanda’s Schizophrenia Drug Wins Approval From U.S. Regulators" (Press release). Bloomberg. May 6, 2009. Retrieved 2009-05-06.
External links
- Fanapt Web Site
- Fanapt Prescribing Information
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UpToDate Contents
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- 1. 第2世代抗精神病剤：薬理学、投与、および副作用の比較 second generation antipsychotic medications pharmacology administration and comparative side effects
- 2. 統合失調症に対する薬物療法：急性期および維持期の治療 pharmacotherapy for schizophrenia acute and maintenance phase treatment
- 3. 統合失調症に対する薬物療法：副作用マネージメント pharmacotherapy for schizophrenia side effect management
- 4. 成人における単極性うつ病：第2世代抗精神病薬による治療 unipolar depression in adults treatment with second generation antipsychotics
- 5. 産後精神病の治療 treatment of postpartum psychosis
English Journal
- A systematic review of meta-analyses of the efficacy of oral atypical antipsychotics for the treatment of adult patients with schizophrenia.
- Citrome L.SourceNew York Medical College , 11 Medical Park Drive, Suite 106, Pomona, NY 10970 , USA + 1 845 362 2081 ; + 1 845 362 8745 ; nntman@gmail.com.
- Expert opinion on pharmacotherapy.Expert Opin Pharmacother.2011 Oct 17. [Epub ahead of print]
- Introduction: Meta-analyses are a convenient way for clinicians and researchers to review data regarding different interventions. Meta-analyses can overcome many of the limitations of individual studies, namely the power to detect differences, and help resolve the results of inconsistent studies. A
- PMID 21999805
- Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis.
- Maher AR, Maglione M, Bagley S, Suttorp M, Hu JH, Ewing B, Wang Z, Timmer M, Sultzer D, Shekelle PG.SourceRAND Health, Southern California Evidence-Based Practice Center, 1776 Main St, Santa Monica, CA 90401, USA. Alicia.Ruelaz@cshs.org
- JAMA : the journal of the American Medical Association.JAMA.2011 Sep 28;306(12):1359-69.
- CONTEXT: Atypical antipsychotic medications are commonly used for off-label conditions such as agitation in dementia, anxiety, and obsessive-compulsive disorder.OBJECTIVE: To perform a systematic review on the efficacy and safety of atypical antipsychotic medications for use in conditions lacking ap
- PMID 21954480
Japanese Journal
- Picogram determination of iloperidone in human plasma by solid-phase extraction and by high-performance liquid chromatography-selected-ion monitoring electrospray mass spectrometry
- MUTLIB A. E.,STRUPCZEWSKI J. T.
- Journal of chromatography. B, Biomedical applications 669(2), 237-246, 1995-07-21
- NAID 10024548344
Related Links
- Iloperidone is an antipsychotic medication. It works by changing the effects of chemicals in the brain. Iloperidone is used to treat schizophrenia. Iloperidone may also be used for purposes not listed in this medication guide.
- iloperidone Fanapt Pharmacologic class: Piperidinyl-benzisoxazole derivative Therapeutic class: Antipsychotic Pregnancy risk category C FDA Box Warning • Elderly patients with dementia-related psychosis treated with ...
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