Lurasidone
Clinical data | |
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Pronunciation | /ljʊəˈræsɪˌdoʊn/ |
Trade names | Latuda, others |
Other names | SM-13496 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a611016 |
License data |
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Pregnancy category |
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Routes of administration | By mouth |
Drug class | Atypical antipsychotic[2] |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 9–19% (oral)[3] |
Protein binding | ~99%[9] |
Metabolism | Liver (CYP3A4-mediated)[3] |
Elimination half-life | 18–40 hours[3][9] |
Excretion | Faecal (67–80%), renal (9–19%)[3][9] |
Identifiers | |
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JSmol) | |
Specific rotation | [α]20D −59° |
Melting point | 176 to 178 °C (349 to 352 °F) |
Solubility in water | 0.224 |
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Lurasidone, sold under the brand name Latuda among others, is an
Common side effects include sleepiness,
Lurasidone was first approved for medical use in the United States in 2010.[2] In 2013, it was approved in Canada, and by the United States Food and Drug Administration, to treat bipolar depression, either as monotherapy or adjunctively with lithium or valproate.[15][16] 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 2 million prescriptions.[19][20]
Medical uses
Lurasidone is used to treat schizophrenia and bipolar 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]
In June 2020, lurasidone was approved in Japan, eight years after its first approval in the United States.
Few available atypical antipsychotics are known to possess antidepressant efficacy in bipolar disorder (with the notable exceptions being quetiapine,[33][34][35][36] olanzapine[37][38][39] and possibly asenapine[40]) as a monotherapy, even though the majority of atypical antipsychotics are known to possess significant antimanic activity,[41] 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."[42]
Lurasidone is not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia.[43]
Contraindications
Lurasidone is
Side effects
Side effects are generally similar to other antipsychotics. The drug has a relatively well tolerated side effect profile, with low propensity for QTc interval changes,[49][50] weight gain and lipid-related adverse effects.[51] In a 2013 meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs it was found to produce the second least (after haloperidol) weight gain, the least QT interval prolongation, the fourth most extrapyramidal side effects (after haloperidol, zotepine and chlorpromazine) and the sixth least sedation (after paliperidone, sertindole, amisulpride, iloperidone and aripiprazole).[52]
As with other atypical neuroleptics, lurasidone should be used with caution in the elderly because it puts them at an increased risk for a stroke or transient 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]
Weight gain is reported in up to 15 and 16 percent of users.[57][58] Other possible side effects include vomiting, akathisia, dystonia, parkinsonism, somnolence, dizziness, sedation and nausea.[59][60]
Discontinuation
The British 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]
Interactions
Pharmacology
Pharmacodynamics
Site | Ki (nM) | Action | Species | Ref |
---|---|---|---|---|
SERT | >1,000 | ND | ND | [66] |
NET | ND | ND | ND | ND |
DAT | >1,000 | ND | ND | [66] |
5-HT1A | 6.75 | Partial agonist | Rat | [66] |
5-HT2A | 2.03 | Antagonist | Rat | [66] |
5-HT2B | ND | ND | ND | ND |
5-HT2C | 415 | ND | Pig | [66] |
5-HT3 | >1,000 | ND | ND | [66] |
5-HT4 | >1,000 | ND | ND | [66] |
5-HT7 | 0.5 | Antagonist | Human | [67][66] |
α1 | 47.9 | ND | Rat | [66] |
α2A | 41 | ND | Human | [66] |
α2B | ND | ND | ND | ND |
α2C | 10.8 | Antagonist | Human | [66] |
β1 | >1,000 | ND | ND | [66] |
β2 | >1,000 | ND | ND | [66] |
D1 |
262 | ND | ND | [66] |
D2 |
1.68 | Antagonist | Rat | [66] |
D3 |
15.7 | Antagonist | ND | ND |
D4.4 |
30 | ND | ND | ND |
D5 |
ND | ND | ND | ND |
H1 |
>1,000 | ND | Guinea pig | [66] |
M1 | >1,000 | ND | Human | [66] |
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. |
Lurasidone [(3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl) piperazin-1-ylmethyl]-cyclohexylmethyl}-hexahydro-4,7-methano-2Hisoindole-1,3-dione hydrochloride] ]
It has only low and likely clinically unimportant
The relationship between dose and
Pharmacokinetics
Lurasidone is taken by mouth and has an estimated absorption rate of 9 to 19%.
Lurasidone is extensively metabolised by CYP3A4 leading to contraindication of both strong inhibitors as well as strong inducers of this enzyme,[82] but has negligible affinity to other cytochrome P450 enzymes. It is transported by P-glycoprotein and ABCG2 and also inhibits these carrier proteins in vitro. It also inhibits the solute carrier protein SLC22A1, but no other relevant transporters.[9][53]
Main metabolism pathways are oxidative N-
History
Lurasidone was first synthesised circa 2003.[83]
Lurasidone is a
Lurasidone is chemically similar to perospirone (also a chemical analogue of ziprasidone), as well as risperidone, paliperidone and iloperidone.[85]
It has approval from the US
Society and culture
Cost
In Canada, as of 2014, lurasidone is generally more expensive than risperidone and quetiapine but less expensive than aripiprazole.[86]
In the US, because a number of doses have the same price per tablet, pill splitting has been used to decrease costs.[87] In 2019, generic versions were approved in the United States; however, they only became available in 2023 due to drug patents.[17][18]
Brand names
In India, this drug is available under the brand names of Atlura, Lurace, Lurafic, Luramax (Sun Pharma), Lurasid, Lurastar, Latuda, Lurata[88] and additionally as Alsiva, Emsidon, Lurakem, Luratrend, Tablura, and Unison.[89]
Regulatory approval
Lurasidone was approved in the United States for the treatment of schizophrenia in October 2010[90][91] and for the treatment of depressive episodes associated with bipolar 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.[92] The Committee for Medicinal Products for Human Use (CHMP) of the European 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 in Canada for the treatment of schizophrenia in September 2012, Health Canada giving their Summary Basis of Decision (SBD) as favourable on 15 October 2012.[93] European Commission has granted a marketing authorization for once-daily oral lurasidone for the treatment of schizophrenia in adults.[94] 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.[95]
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