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, althoughhypotension, 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.
TheBritish National Formulary recommends a gradualtaper when discontinuing antipsychotics to avoid acutewithdrawal symptoms or rapid relapse.[6] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[7] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[7] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[7] Symptoms generally resolve after a short period of time.[7]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[8] It may also result in reoccurrence of the condition that is being treated.[9] Rarely tardive dyskinesia can occur when the medication is stopped.[7]
Iloperidone exerts its effects by acting upon and antagonizing specific neurotransmitters, particularly multipledopamine andserotonin receptor subtypes. It is considered an 'atypical' antipsychotic because it displays serotonin receptor antagonism, similar to other atypical antipsychotics. The oldertypical antipsychotics are primarily dopamine antagonists.
Iloperidone has been shown to act as anantagonist at all tested receptors except for 5-HT2A. It exhibits high (nM) affinity to serotonin 5-HT2A (Ki value of 5.6 nM) where it acts as ainverse agonist. Antagonism occurs at all other receptors following dopamine D2 (6.3 nM) and D3 (7.1 nM) and α1-adrenergic receptors (0.36 nM),[10] moderate affinity for dopamine D4 (25 nM), serotonin 5-HT6 (43 nM), 5-HT7 (22 nM), and low affinity for the serotonin 5-HT1A (168 nM), dopamine D1, and histamine H1 receptors. In addition,pharmacogenomic studies identifiedsingle nucleotide polymorphisms associated with an enhanced response to iloperidone during acute treatment of schizophrenia.[4][11]
Hoechst Marion Roussel Inc. made initial inquiries into the drug; however, in May 1996, they discontinued research, and in June 1997 gave research rights toTitan Pharmaceuticals. Titan then handed over worldwide development, manufacturing and marketing rights toNovartis 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 theU.S. Food and Drug Administration (FDA) had accepted theirNew Drug Application for iloperidone, confirming the application is ready for FDA review and approval.[12] On July 28, 2008, the FDA issued anot-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.[13]
Iloperidone was approved by the FDA for the treatment of schizophrenia in the United States on May 6, 2009.[14] and for treating bipolar I disorder in April 2024.[1]
^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.PMID7560252.S2CID24518837.
^Joint Formulary Committee, BMJ, ed. (March 2009). "4.2.1".British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192.ISBN978-0-85369-845-6.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.
^Moncrieff J (July 2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse".Acta Psychiatrica Scandinavica.114 (1):3–13.doi:10.1111/j.1600-0447.2006.00787.x.PMID16774655.S2CID6267180.
^Brunton LL (2010).Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. New York, NY: McGraw-Hill Medical.ISBN9780071769396.
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