sertindole
{{Short description|Antipsychotic medication}}
{{Use dmy dates|date=March 2024}}
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{{Infobox drug
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| verifiedrevid = 464389408
| image = Sertindole.svg
| width = 250
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| image2 = Sertindole ball-and-stick model.png
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| pronounce =
| tradename = Serdolect, others
| Drugs.com = {{drugs.com|international|sertindole}}
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| pregnancy_AU = C
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| routes_of_administration = By mouth
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| ATC_prefix = N05
| ATC_suffix = AE03
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| legal_AU = S4
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| legal_status = Rx-only
| metabolism = Liver (mostly via CYP2D6 and CYP3A4){{cite journal | vauthors = Juruena MF, de Sena EP, de Oliveira IR | title = Sertindole in the management of schizophrenia | journal = Journal of Central Nervous System Disease | volume = 3 | pages = 75–85 | date = May 2011 | pmid = 23861640 | pmc = 3663609 | doi = 10.4137/JCNSD.S5729 }}
| metabolites =
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| elimination_half-life = 3 days
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| excretion = Faecal (the majority), Kidney (4% metabolites; 1% unchanged)
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 106516-24-9
| PubChem = 60149
| IUPHAR_ligand = 98
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB06144
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 54229
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = GVV4Z879SP
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00561
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 9122
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 12713
| NIAID_ChemDB =
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| synonyms =
| IUPAC_name = 1-[2-[4-[5-chloro-1-(4-fluorophenyl)-indol-3-yl]-1-piperidyl]ethyl]imidazolidin-2-one
| C=24 | H=26 | Cl=1 | F=1 | N=4 | O=1
| SMILES = Fc1ccc(cc1)n3c2ccc(Cl)cc2c(c3)C5CCN(CCN4C(=O)NCC4)CC5
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C24H26ClFN4O/c25-18-1-6-23-21(15-18)22(16-30(23)20-4-2-19(26)3-5-20)17-7-10-28(11-8-17)13-14-29-12-9-27-24(29)31/h1-6,15-17H,7-14H2,(H,27,31)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GZKLJWGUPQBVJQ-UHFFFAOYSA-N
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Sertindole, sold under the brand name Serdolect among others, is an antipsychotic medication. Sertindole was developed by the Danish pharmaceutical company Lundbeck and marketed under license by Abbott Labs. Like other atypical antipsychotics, it has activity at dopamine and serotonin receptors in the brain. It is used in the treatment of schizophrenia. It is classified chemically as a phenylindole derivative.
Sertindole is not approved for use in the United States and was discontinued in Australia in January 2014.{{citation needed|date=September 2020}}
Medical Uses
Sertindole appears effective as an antipsychotic in schizophrenia.{{cite journal | vauthors = Lewis R, Bagnall AM, Leitner M | title = Sertindole for schizophrenia | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD001715 | date = July 2005 | volume = 2005 | pmid = 16034864 | doi = 10.1002/14651858.CD001715.pub2 | pmc = 7025766 }} In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, sertindole was found to be slightly less effective than haloperidol, quetiapine, and aripiprazole, as effective as ziprasidone, approximately as effective as chlorpromazine and asenapine, and slightly more effective than lurasidone and iloperidone.{{cite journal | vauthors = Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–62 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}
Adverse effects
Very common (>10% incidence) adverse effects include:{{cite web|title=PRODUCT INFORMATION SERDOLECT TABLETS|work=TGA eBusiness Services|publisher=Lundbeck Australia Pty Ltd|date=16 January 2013|access-date=27 October 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-07697-3|format=PDF}}
- Headache
- Ejaculation failure
- Insomnia
- Dizziness
Common (1–10% incidence) adverse effects include:
- Urine that tests positive for red and/or white blood cells
- Sedation (causes less sedation than most antipsychotic drugs according to a recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs. Causes only slightly [and non-significantly] more sedation than amisulpride and paliperidone){{cite book | isbn = 978-0-470-97948-8 | title = The Maudsley prescribing guidelines in psychiatry | vauthors = Taylor D, Paton C, Shitij K | year = 2012 | publisher = Wiley-Blackwell | location = West Sussex }}
- Ejaculation disorder
- Erectile dysfunction
- Orthostatic hypotension
- Weight gain (which it seems to possess a similar propensity for causing as quetiapine)
Uncommon (0.1–1% incidence) adverse effects include:
{{div col|colwidth=22em}}
- Substernal chest pain
- Face oedema
- Influenza-like illness
- Neck rigidity
- Pallor
- Peripheral vascular disorder
- syncope
- Torsades de pointes
- Vasodilation
- Suicide attempt
- Amnesia
- Anxiety
- Ataxia
- Confusion
- Incoordination
- Libido decreased
- Libido increased
- Miosis
- Nystagmus
- Personality disorder
- Psychosis
- Reflexes decreased
- Reflexes increased
- Stupor
- Suicidal tendency
- Urinary retention
- Vertigo
- Diabetes mellitus
- Abnormal stools
- Gastritis
- Gingivitis
- Glossitis
- Increased appetite
- Mouth ulceration
- Rectal disorder
- Rectal haemorrhage
- Stomatitis
- Tongue disorder
- Ulcerative stomatitis
- Anaemia
- Ecchymosis
- Hypochromic anaemia
- Leukopenia
- Hyperglycaemia
- Hyperlipemia
- Oedema
- Bone pain
- Myasthenia
- Twitching
- Bronchitis
- Hyperventilation
- Pneumonia
- Sinusitis
- Furunculosis
- Herpes simplex
- Nail disorder
- Psoriasis
- Pustular Rash
- Skin discolouration
- Skin hypertrophy
- Skin ulcer
- Abnormal vision
- Keratoconjunctivitis
- Lacrimation disorder
- Otitis externa
- Pupillary disorder
- Taste perversion
- Anorgasmia
- Penis disorder (gs)
- Urinary urgency
- Hyperprolactinaemia (which it seems to cause with a higher propensity than most other atypical antipsychotics do)
- Seizures
- Galactorrhoea
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Rare (<0.1% incidence) adverse effects include:
Unknown frequency adverse events include:
- Extrapyramidal side effects (EPSE; e.g. dystonia, akathisia, muscle rigidity, parkinsonism, etc. These adverse effects are probably uncommon/rare according to a recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs which found it had the 2nd lowest effect size for causing EPSE)
- Venous thromboembolism
- QT interval prolongation (probably common; in a recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs it was found to be the most prone to causing QT interval prolongation)
Pharmacology
Safety and status
=United States=
Abbott Labs first applied for US Food and Drug Administration (FDA) approval for sertindole in 1996,[http://www.thepharmaletter.com/file/57165/zenecas-seroquel-nears-market-approval.html Zeneca's Seroquel Nears Market Approval] - The Pharma Letter, 16 July 1997 but withdrew this application in 1998 following concerns over the increased risk of sudden death from QTc prolongation.[http://www.thepharmaletter.com/file/65187/abbott-labs-withdraws-sertindole-nda.html Abbott Labs Withdraws Sertindole NDA Sertindole] - The Pharma Letter, 12 January 1998 In a trial of 2000 patients on taking sertindole, 27 patients died unexpectedly, including 13 sudden deaths.{{cite web |url=http://apps.who.int/medicinedocs/en/d/Js2256e/1.12.html#Js2256e.1.12 |archive-url=https://web.archive.org/web/20110622124240/http://apps.who.int/medicinedocs/en/d/Js2256e/1.12.html#Js2256e.1.12 |url-status=dead |archive-date=22 June 2011 |title=WHO Pharmaceuticals Newsletter 1998, No. 03&04: Regulatory actions: Sertindole - approval application withdrawn }} Lundbeck cites the results of the Sertindole Cohort Prospective (SCoP) study of 10,000 patients to support its claim that although sertindole does increase the QTc interval, this is not associated with increased rates of cardiac arrhythmias, and that patients on sertindole had the same overall mortality rate as those on risperidone.[http://sweden.lundbeck.com/investor/releases/ReleaseDetails/Release_1304142_EN.asp FDA Advisory Committee provides opinion on Serdolect for the treatment of schizophrenia] {{webarchive|url=https://web.archive.org/web/20110714002544/http://sweden.lundbeck.com/investor/releases/ReleaseDetails/Release_1304142_EN.asp |date=14 July 2011 }} - Lundbeck press release, 8 April 2009 Nevertheless, in April 2009, an FDA advisory panel voted 13-0 that sertindole was effective in the treatment of schizophrenia but 12-1 that it had not been shown to be acceptably safe.[https://web.archive.org/web/20100203094842/http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM198218.pdf Food and Drug Administration; Minutes of the Psychphamacological Drugs Advisory Committee, 7 Apr 2009] {{As of|October 2010}}, the drug has not been approved by the FDA.{{Cite web | url=http://www.serdolect.com | title=Welcome to Lundbeck's global site}}{{failed verification|date=September 2020}}
= European Union =
In the European Union, sertindole was approved and marketed in 19 member states from 1996, but its marketing authorization was suspended by the European Medicines Agency (EMA) in 1998[http://www.nelm.nhs.uk/en/NeLM-Area/News/483119/483386/483398/ EU CHMP recommends lifting ban on atypical antipsychotic Serdolect (sertindole)] {{webarchive|url=https://web.archive.org/web/20111002084501/http://www.nelm.nhs.uk/en/NeLM-Area/News/483119/483386/483398/ |date=2 October 2011 }} - National electronic Library for Medicines, NHS and the drug was withdrawn from the market. In 2002, based on new data, the EMA's Committee for Medicinal Products for Human Use (CHMP) suggested that Sertindole could be reintroduced for restricted use in clinical trials, with strong safeguards including extensive contraindications and warnings for patients at risk of cardiac dysrhythmias, a recommended reduction in maximum dose from 24 mg to 20 mg in all but exceptional cases, and extensive ECG monitoring requirement before and during treatment.[http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Sertindole_36/WC500011855.pdf COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS OPINION FOLLOWING AN ARTICLE 36 REFERRAL: SERTINDOLE] {{Webarchive|url=https://web.archive.org/web/20160304113446/http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Sertindole_36/WC500011855.pdf |date=4 March 2016 }} - European Medicines Agency, 13 September 2002[http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON019523 Restricted re-introduction of the atypical antipsychotic sertindole (Serdolect)] {{webarchive|url=https://web.archive.org/web/20101117032420/http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON019523 |date=17 November 2010 }} - MHRA, 2002 {{As of|September 2020}}, sertindole is authorized in several member states of the European Union.{{cite report | url=https://www.ema.europa.eu/documents/psusa/sertindole-list-nationally-authorised-medicinal-products-psusa/00002695/202001_en.pdf | title=Sertindole: List of nationally authorised medicinal products - PSUSA/00002695/202001 | date=3 September 2020 | id=EMA/270645/2015 | publisher=European Medicines Agency (EMA) }}
References
{{reflist}}
{{Antipsychotics}}
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Category:4-Fluorophenyl compounds