Iloperidone, sold under the brand name Fanapt among others, is an

atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neurol ...

for the treatment of

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

and

bipolar I disorder Bipolar I disorder (BD-I; pronounced "type one bipolar disorder") is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other ti ...

Medical uses

Iloperidone is indicated for the treatment of

and

mania Mania, also known as manic syndrome, is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome defined as a state of Abnormality (behavior), abnormally elevated arousal, affect (psychology), affect, and energy level. During a mani ...

or mixed episodes in

. In a 2013 study in a comparison of 15

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

drugs in effectivity in treating schizophrenic symptoms, iloperidone demonstrated mild effectiveness — as effective as

lurasidone Lurasidone, sold under the brand name Latuda among others, is an atypical antipsychotic medication used to treat schizophrenia and bipolar depression. It is taken by mouth. Common side effects include sedation, indigestion, nausea, and inso ...

, and 13 to 15% less effective than

ziprasidone Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The intramuscular form may be used for ...

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar d ...

, and

asenapine Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder. I ...

. It generally appears to work better than placebo.

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 Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

, 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.

Withdrawal

The

British National Formulary The ''British National Formulary'' (BNF) is a United Kingdom (UK) pharmaceutical reference book that contains a wide spectrum of information and advice on prescribing and pharmacology, along with specific facts and details about many medicin ...

recommends a gradual

taper Taper may refer to: * Part of an object in the shape of a cone (conical) * Taper (transmission line), a transmission line gradually increasing or decreasing in size * Fishing rod taper, a measure of the flexibility of a fishing rod * Conically ta ...

when discontinuing antipsychotics to avoid acute withdrawal symptoms 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.

Pharmacology

Iloperidone exerts its effects by acting upon and antagonizing specific neurotransmitters, particularly multiple

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

and

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

receptor subtypes. It is considered an 'atypical' antipsychotic because it displays serotonin receptor antagonism, similar to other atypical antipsychotics. The older

typical antipsychotic Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics m ...

s are primarily dopamine antagonists. Iloperidone has been shown to act as an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

. Antagonism occurs at all other receptors following dopamine D₂ (6.3 nM) and D₃ (7.1 nM) and α₁-adrenergic receptors (0.36 nM), moderate affinity for dopamine D₄ (25 nM), serotonin 5-HT₆ (43 nM), 5-HT₇ (22 nM), and low affinity for the serotonin 5-HT_1A (168 nM), dopamine D₁, and histamine H₁ receptors. In addition,

pharmacogenomic Pharmacogenomics, often abbreviated "PGx," is the study of the role of the genome in drug response. Its name ('' pharmaco-'' + ''genomics'') reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup o ...

studies identified

single nucleotide polymorphisms In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...

associated with an enhanced response to iloperidone during acute treatment of schizophrenia.

History

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 Pharmaceuticals, Inc. is a biopharmaceutical company based in San Francisco, CA, developing proprietary therapeutics primarily for treating central nervous system ("CNS") disorders. In September 2018, Titan Pharmaceuticals underwent an IPO ...

. Titan then handed over worldwide development, manufacturing and marketing rights to

Novartis Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by re ...

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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) had accepted their

New Drug Application The Food and Drug Administration's (FDA) New Drug Application (NDA) is the vehicle in the United States through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing. Some 30% or less of initial ...

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. Iloperidone was approved by the FDA for the treatment of schizophrenia in the United States on May 6, 2009. and for treating bipolar I disorder in April 2024.

References

External links

Fanapt Prescribing Information
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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...

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