Lurasidone was firstapproved for medical use in the United States in 2010, for treating schizophrenia.[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 is not FDA approved for treatingmanic symptoms associated with bipolar disorder despite its FDA approval for treating bipolar depression.Generic versions wereapproved 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]
TheEuropean Medicines Agency approved lurasidone for the treatment of schizophrenia for people aged 13 years and older.[23][8] Its use in Europe for bipolar disorder is considered off-label.[24] In the United States, it is used to treat schizophrenia for people aged 13 years and older. In July 2013, lurasidone received approval for bipolar I depression.[25][26][27][28] This includes depressive episodes of bipolar disorder age 10 and over as a monotherapy, and in conjunction with lithium or valproate in adults.[29]
In June 2020, lurasidone was approved in Japan, eight years after its first approval in the United States.[30] In Japan it is approved forbipolar depression andschizophrenia.[31][32][33] Lurasidone is not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia.[34]
Few available atypical antipsychotics are known to possess antidepressant efficacy in bipolar disorder (with the notable exceptions beingcariprazine,[35]quetiapine,[36][37][38][39]olanzapine[40][41][42] and possiblyasenapine[43]) as a monotherapy. The majority of atypical antipsychotics are known to possess significantantimanic activity,[44] however lurasidone is unusual as it was never studied for acute mania.[45]
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".[46]
As with other atypical neuroleptics, lurasidone should be used with caution in theelderly because it puts them at an increased risk for astroke ortransient ischemic attack;[55][56] however, these risks are not likely to be greater than those associated with antipsychotics of other classes.[57] Similarly, lurasidone should not be used to treat dementia-related psychosis, as evidence has shown increased mortality with antipsychotic use.[58]
TheBritish National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[63] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[64] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[64] Less commonly there may be a feeling of the world spinning,numbness, or muscle pains.[64] Symptoms generally resolve after a short period of time.[64]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[65] It may also result in reoccurrence of the condition that is being treated.[66] Rarely tardive dyskinesia can occur when the medication is stopped.[64]
Blood plasma concentrations may be increased when combined withCYP3A4 inhibitors (e.g.ketoconazole,clarithromycin,ritonavir, andvoriconazole) possibly leading to more side effects. This has been clinically verified for ketoconazole, 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.[82]
ID-14283, the mainactive metabolite. The hydroxylation of thenorbornane ring is highlighted.[83] The other active metabolite, ID-14326, has the OH group inendo position.[84]The main inactivation step by oxidative N-dealkylation produces the metabolites ID-11614 and ID-20219.[84][85]
Lurasidone is taken by mouth and should be taken with a meal of at least 350 calories to ensure maximumabsorption.[86] It has an estimated absorption rate of 9 to 19%.[3] Studies have shown that when lurasidone is taken with food, absorption increases about twofold.[9]
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.
In schizophrenia, lurasidone has a recommended dose range of 40-160 mg. In bipolar depression, lurasidone has a slightly lower recommended dose range of 20-120 mg.[87]
Lurasidone is extensivelymetabolised by CYP3A4 leading to contraindication of both strong inhibitors as well as strong inducers of this enzyme,[88] 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][55]
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[84]), 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.[85]:59–61
Lurasidone was approved in theUnited States for the treatment ofschizophrenia in October 2010[94][95] and for the treatment of depressive episodes associated withbipolar I disorder in June 2013.[25][27][28] In 2015, lurasidone was studied for major depressive disorder withmixed features in arandomized trial and had a positive result, however it did not receive an FDA indication for it.[45][96] In 2017, the FDA approved lurasidone for schizophrenia in adolescents age 13-17. In 2018, lurasidone was approved for bipolar depression in children and adolescents age 10-17.[87]
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.[97]
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.[98] TheEuropean Commission has granted a marketing authorization for once-daily oral lurasidone for the treatment of schizophrenia in adults.[99] 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.[100][17][18]
In India, this drug is available under the brand names of Atlura, Lurace, Lurafic, Luramax (Sun Pharma), Lurasid, Lurastar, Latuda, Lurata[101] and additionally as Alsiva, Emsidon, Lurakem, Luratrend, Tablura, and Unisidon.[102]
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