Lurasidone was first approved for medical use in the United States in 2010.[2] In 2013, it was approved in Canada and by the U.S.Food and Drug Administration (FDA) to treatbipolar depression, either as monotherapy or adjunctively withlithium orvalproate.[15][16] It has no effect onmanic symptoms and is more potent for treatingmajor depressive disorder or depressive episodes associated with bipolar disorder. Generic versions were approved in the United States in 2019, and became available in 2023.[17][18] In 2021, it was the 193rd most commonly prescribed medication in the United States, with more than 2million prescriptions.[19][20]
Lurasidone is used to treatschizophrenia andbipolar disorder.[2][21] In bipolar disorder, it has been studied both as a monotherapy and adjunctive treatment to lithium or valproate.[22]
The European Medicines Agency approved lurasidone for the treatment of schizophrenia for people aged 13 years and older,[23] but not for bipolar disorder.[8] In the United States, it is used to treat schizophrenia for people aged 13 years and older, as well as depressive episodes of bipolar disorder age 10 and over as a monotherapy, and in conjunction with lithium or valproate in adults.[24]
In July 2013, lurasidone received approval for bipolar I depression.[25][26][27][28]
Few available atypical antipsychotics are known to possess antidepressant efficacy in bipolar disorder (with the notable exceptions beingcariprazine,[33]quetiapine,[34][35][36][37]olanzapine[38][39][40] and possiblyasenapine[41]) as a monotherapy, even though the majority of atypical antipsychotics are known to possess significantantimanic activity,[42] which is yet to be clearly demonstrated for lurasidone.
In the early post approval period lurasidone-treated patients with bipolar disorder were retrospectively found to have more complex clinical profiles, comorbidities, and prior treatment history compared to patients initiated with other atypical antipsychotics. The study authors suggest this may be due to "the overall clinical profile of lurasidone, the role perceived for lurasidone in the therapeutic armamentarium by practitioners, and the recent introduction of lurasidone into clinical practice during the study period."[43]
Lurasidone is not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia.[44]
Lurasidone iscontraindicated in individuals who are taking strong inhibitors of the liver enzymeCYP3A4 (ketoconazole,clarithromycin,ritonavir,levodropropizine, etc.) or inducers (carbamazepine,St. John's wort,phenytoin,rifampicin etc.).[45] The use of lurasidone in pregnant women has not been studied and is not recommended; in animal studies, no risks have been found.[46] Excretion in breast milk is also unknown; lurasidone is not recommended for breastfeeding women.[47] In the United States, it is not indicated for use in children.[citation needed] The enzyme CYP3A4 is involved in the digestion of drugs. Inhibitors such as grapefruit juice block its function resulting in too much drug in the body.[48]
As with other atypical neuroleptics, lurasidone should be used with caution in the elderly because it puts them at an increased risk for astroke ortransient ischemic attack;[53][54] however, these risks are not likely to be greater than those associated with antipsychotics of other classes.[55] Similarly, lurasidone should not be used to treat dementia-related psychosis, as evidence has shown increased mortality with antipsychotic use.[56]
TheBritish National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[61] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[62] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[62] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[62] Symptoms generally resolve after a short period of time.[62]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[63] It may also result in reoccurrence of the condition that is being treated.[64] Rarely tardive dyskinesia can occur when the medication is stopped.[62]
Blood plasma concentrations may be increased when combined withCYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, ritonavir, and voriconazole) possibly leading to more side effects. This has been clinically verified forketoconazole, which increases lurasidone exposure by a factor of 9, and is also expected for other 3A4 inhibitors such asgrapefruit juice. Co-administration of CYP3A4 inducers likerifampicin,carbamazepine orSt. John's wort can reduce plasma levels of lurasidone and itsactive metabolite, and consequently decrease the effects of the drug. For rifampicin, the reduction was sixfold in a study.[9]
The relationship between dose andD2 receptor occupancy levels were 41–43% for 10 mg, 51–55% for 20 mg, 63–67% for 40 mg, 77–84% for 60 mg, and 73–79% for 80 mg.[80]
ID-14283, the mainactive metabolite. The hydroxylation of thenorbornane ring is highlighted.[81] The other active metabolite, ID-14326, has the OH group inendo position.[82]The main inactivation step by oxidative N-dealkylation produces the metabolites ID-11614 and ID-20219.[82][83]
Lurasidone is taken by mouth and has an estimated absorption rate of 9 to 19%.[3] Studies have shown that when lurasidone is taken with food, absorption increases about twofold. Peak blood plasma concentrations are reached after one to three hours. About 99% of the circulating substance are bound toplasma proteins.[9] Efficacy data for lurasidone have been evaluated for doses of 20 mg to 120 mg daily.
Lurasidone is extensively metabolised by CYP3A4 leading to contraindication of both strong inhibitors as well as strong inducers of this enzyme,[84] but has negligible affinity to othercytochrome P450 enzymes. It is transported byP-glycoprotein andABCG2 and also inhibits these carrier proteinsin vitro. It also inhibits the solute carrier proteinSLC22A1, but no other relevant transporters.[9][53]
Main metabolism pathways are oxidative N-dealkylation between thepiperazine and cyclohexane rings,hydroxylation of thenorbornane ring, and S-oxidation.[9][83]:59 Other pathways are hydroxylation of the cyclohexane ring and reductive cleavage of theisothiazole ring followed by S-methylation.[82] The two relevant active metabolites are the norbornane hydroxylation products called ID-14283 and ID-14326, the former reaching pharmacologically relevant blood plasma concentrations. The two major inactive metabolites are the N-dealkylation products (thecarboxylic acid ID-20219 and the piperazine ID-11614[82]), and a norbornane hydroxylated derivative of ID-20219 (ID-20220). Of lurasidone and its metabolites circulating in the blood, the native drug makes up 11%, the main active metabolite 4%, and the inactive carboxylic acids 24% and 11%, respectively.[3][9] Several dozen metabolites have been identified altogether.[83]:59–61
Biological half-life is given as 18 hours or 20 to 40 hours in different sources. 80% or 67% of aradiolabelled dose was recovered from the feces, and 9% or 19% from the urine.[3][9]
Lurasidone is astructural analogue ofziprasidone. Lurasidone shows a very close pharmacological profile and has been synthesized similarly to ziprasidone.[86]
In the United States, because a number of doses have the same price per tablet, pill splitting has been used to decrease costs.[89] In 2019, generic versions were approved in the United States; however, they only became available in 2023 due to drug patents.[17][18]
In India, this drug is available under the brand names of Atlura, Lurace, Lurafic, Luramax (Sun Pharma), Lurasid, Lurastar, Latuda, Lurata[90] and additionally as Alsiva, Emsidon, Lurakem, Luratrend, Tablura, and Unisidon.[91]
Lurasidone was approved in the United States for the treatment ofschizophrenia in October 2010[92][93] and for the treatment of depressive episodes associated withbipolar I disorder in June 2013.[25][27][28] It received regulatory approval in the United Kingdom in September 2014. In October 2014,NHS Scotland advised use of lurasidone for schizophrenic adults who have not seen improvements with previous antipsychotics due to problems that arise from weight gain or changes in metabolic pathways when taking other medications.[94] TheCommittee for Medicinal Products for Human Use (CHMP) of theEuropean Medicines Agency (EMA) issued a positive opinion for it in January 2014, and it was approved for medical use by the EMA in March 2014.[8] It was launched inCanada for the treatment of schizophrenia in September 2012,Health Canada giving their Summary Basis of Decision (SBD) as favourable on 15 October 2012.[95] TheEuropean Commission has granted a marketing authorization for once-daily oral lurasidone for the treatment of schizophrenia in adults.[96] It is approved for use in the EU.[8]
Generic versions of lurasidone were approved for use in the United States in January 2019 and became available in 2023.[97]
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