Asenapine
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Trade names | Saphris, Sycrest, Secuado |
Other names | ORG-5222 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a610015 |
License data | |
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Routes of administration | Sublingual, transdermal |
Drug class | Atypical antipsychotic |
ATC code | |
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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.[4][10]
It was chemically derived via altering the chemical structure of the tetracyclic (atypical) antidepressant, mianserin.[11]
It was initially approved in the United States in 2009
Medical uses
Asenapine has been approved by the FDA for the acute treatment of adults with schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults.[12] In Australia asenapine's approved (and also listed on the PBS) indications include the following:[14]
- Schizophrenia
- Treatment, for up to 6 months, of an episode of acute mania or mixed episodes associated with bipolar I disorder
- Maintenance treatment, as monotherapy, of bipolar I disorder
In the European Union and the United Kingdom, asenapine is only licensed for use as a treatment for acute mania in bipolar I disorder.[3][7][4]
Asenapine is absorbed readily if administered
Schizophrenia
A Cochrane systematic review found that while Asenapine has some preliminary evidence that it improves positive, negative, and depressive symptoms, it does not have enough research to merit a certain recommendation of asenapine for the treatment of schizophrenia.[16]
Bipolar disorder
For the medium-term and long-term management and control of both depressive and manic features of bipolar disorder asenapine was found be equally effective as olanzapine, but with a substantially superior side effect profile.[10]
In acute mania, asenapine was found to be significantly superior to placebo.
Adverse effects
Adverse effect incidence[5][6][3][7]
Very common (>10% incidence) adverse effects include:
Common (1–10% incidence) adverse effects include:
- Weight gain†
- Increased appetite
- Extrapyramidal side effects (EPS; such as dystonia, akathisia, dyskinesia, muscle rigidity, parkinsonism)
- Sedation
- Dizziness
- Dysgeusia (altered taste)
- Oral hypoaesthesia (numbness), only when taken sublingually. Transdermal asenapine was shown to eliminate this side effect.[8]
- Increased alanine aminotransferase
- Dyspepsia, stomach discomfort, and/or vomiting[a]
- Fatigue
Uncommon (0.1–1% incidence) adverse effects include:
- Hyperglycaemia— elevated blood glucose (sugar)
- Syncope
- Seizure
- Dysarthria
- sinus bradycardia
- Bundle branch block
- QTc interval prolongation (has a relatively low risk for causing QTc interval prolongation.[19][20])
- sinus tachycardia
- Orthostatic hypotension
- Hypotension
- Swollen tongue
- Dysphagia (difficulty swallowing)
- Glossodynia
- Oral paraesthesia
Rare (0.01–0.1% incidence) adverse effects include:
- sweating, reduced consciousness, and sudden change in blood pressure and heart rate)
- Tardive dyskinesia
- Speech disturbance
- Rhabdomyolysis
- Angioedema
- Blood dyscrasias such as agranulocytosis, leukopenia and neutropenia
- Accommodation disorder[clarification needed]
- Pulmonary embolism
- Gynaecomastia
- Galactorrhoea
Unknown incidence adverse effects
- Allergic reaction
- Restless legs syndrome
- Oral mucosal lesions (ulcerations, blistering and inflammation)
- Salivary hypersecretion
- Hyperprolactinaemia
† Asenapine seems to have a relatively low weight gain liability for an
Discontinuation
For all antipsychotics, the British National Formulary recommends a gradual dose reduction when discontinuing to avoid acute withdrawal syndrome or rapid relapse.[22] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[23] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[23] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[23] Symptoms generally resolve after a short period of time.[23]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis as a transient withdrawal symptom.[24] It may also result in recurrence of the condition that is being treated.[25] Rarely tardive dyskinesia can occur when the medication is stopped.[23]
Pharmacology
Pharmacodynamics
Site | pKi | Ki (nM) | Action |
---|---|---|---|
5-HT1A | 8.6 | 2.5 | Partial agonist |
5-HT1B | 8.4 | 4.0 | Antagonist |
5-HT2A | 10.2 | 0.06 | Antagonist |
5-HT2B | 9.8 | 0.16 | Antagonist |
5-HT2C | 10.5 | 0.03 | Antagonist |
5-HT5A | 8.8 | 1.6 | Antagonist |
5-HT6 | 9.5 | 0.25 | Antagonist |
5-HT7 | 9.9 | 0.13 | Antagonist |
α1 | 8.9 | 1.2 | Antagonist |
α2A | 8.9 | 1.2 | Antagonist |
α2B | 9.5 | 0.32 | Antagonist |
α2C | 8.9 | 1.2 | Antagonist |
D1 |
8.9 | 1.4 | Antagonist |
D2 |
8.9 | 1.3 | Antagonist |
D3 |
9.4 | 0.42 | Antagonist |
D4 |
9.0 | 1.1 | Antagonist |
H1 |
9.0 | 1.0 | Antagonist |
H2 |
8.2 | 6.2 | Antagonist |
mACh | <5 | 8128 | Antagonist |
Asenapine shows high
Even relative to other atypical antipsychotics, asenapine has unusually high affinity for the
Notes
- ^ The Phase III trials used for FDA approval in the US used lists of "elicited side effects", asking all subjects about each side effect on the list, and "nausea" was not included. The elicited side effects list included the related symptoms of "dyspepsia", "stomach discomfort", and "vomiting", and the incidence of each was higher than placebo and in the range of 1 to 10% of asenapine-treated subjects.[6]
References
- FDA. Retrieved 22 Oct 2023.
- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
- ^ a b c d e f g h "Sycrest 5mg sublingual tablets - Summary of Product Characteristics (SmPC)". (emc). Retrieved 9 September 2020.
- ^ a b c "Sycrest EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 9 September 2020.
- ^ a b c d e f "Product Information Saphris (asenapine maleate)" (PDF). TGA eBusiness Services. Merck Sharp & Dohme (Australia) Pty Limited. 14 January 2013. Retrieved 23 October 2013.
- ^ a b c d e f g "Saphris (asenapine maleate) tablet". DailyMed. Organon Pharmaceuticals. March 2013. Retrieved 23 October 2013.
- ^ a b c d e f g "Product information Sycrest – EMEA/H/C/001177 –II/0012" (PDF). European Medicines Agency. N.V. Organon. 21 February 2013. Archived from the original (PDF) on 28 July 2017. Retrieved 23 October 2013.
- ^ PMID 32943849.
- ^ PMID 33734167.
- ^ S2CID 20871442.
- PMID 20642375.
- ^ a b c "Saphris (asenapine) prescribing information" (PDF). Schering Corporation. 2009-08-01. Archived from the original (PDF) on 2009-11-22. Retrieved 2009-09-05.
- ^ "First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). Retrieved 13 February 2021.
- ISBN 978-0-9805790-9-3.
- PMID 22494521.
- PMID 26599405.
- S2CID 25512763.
- PMID 21689438.
- ^ Washington NB, Brahm NC, Kissack J (October 2012). "Which psychotropics carry the greatest risk of QTc prolongation?". Current Psychiatry. 11 (10): 36–39. Retrieved 14 April 2017.
- ISBN 978-0-470-97948-8.
- ^ S2CID 32085212.
- ISBN 978-0-85369-845-6.
Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
- ^ ISBN 9780198527480.
- S2CID 6267180.
- ISBN 9788847026797.
- ^ S2CID 206489515.
- S2CID 140204044.
External links
- "Asenapine". Drug Information Portal. U.S. National Library of Medicine.
- "Asenapine maleate". Drug Information Portal. U.S. National Library of Medicine.