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| Clinical data | |
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| Trade names | Saphris, Sycrest, Secuado |
| Other names | ORG-5222 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a610015 |
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| Routes of administration | Sublingual,transdermal |
| Drug class | Atypical antipsychotic |
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| Pharmacokinetic data | |
| Bioavailability | 35% (sublingual), <2% (oral),[4][5][2][6] transdermal bioavailability is significantly higher than sublingual[7][8] |
| Protein binding | 95%[4][5][2][6] |
| Metabolism | hepatic (glucurinodation byUGT1A4 and oxidative metabolism byCYP1A2)[4][5][2][6] |
| Eliminationhalf-life | 24 hours (sublingual),[4][5][2][6] 30 hours (transdermal),[7] 33.9 hours (transdermal)[8] |
| Excretion | Kidney (50%),Fecal (40%; ~5–16% as unchanged drug in feces)[4][5][2][6] |
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| ECHA InfoCard | 100.059.828 |
| Chemical and physical data | |
| Formula | C17H16ClNO |
| Molar mass | 285.77 g·mol−1 |
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Asenapine, sold under the brand nameSaphris among others, is anatypical antipsychotic medication used to treatschizophrenia and acutemania associated with bipolar disorder as well as the medium to long-term management ofbipolar disorder.[3][9]
It was chemically derived via altering the chemical structure of the tetracyclic (atypical) antidepressant,mianserin.[10]
It was initially approved in the United States in 2009[11] and approved as ageneric medication in 2020.[12]
Asenapine has been approved by the FDA for the acute treatment of adults withschizophrenia and acute treatment of manic or mixed episodes associated withbipolar I disorder with or without psychotic features in adults.[11] In Australia asenapine's approved (and also listed on thePBS) indications include the following:[13]
In the European Union and the United Kingdom, asenapine is only licensed for use as a treatment for acute mania in bipolar I disorder.[2][6][3]
Asenapine is absorbed readily if administeredsublingually, but is poorly absorbed when swallowed.[14] Atransdermal formulation of asenapine was approved in the United States in October 2019 under the brand name Secuado.[7]
ACochranesystematic 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.[15]
For the medium-term and long-term management and control of both depressive and manic features of bipolar disorder asenapine was found to be equally effective as olanzapine, but with a substantially superior side effect profile.[9]
In acute mania, asenapine was found to be significantly superior to placebo.[9] As for its efficacy in the treatment of acute mania, a recent meta-analysis showed that it produces comparatively small improvements in manic symptoms in patients with acute mania and mixed episodes than most other antipsychotic drugs such asrisperidone andolanzapine (with the exception ofziprasidone). Drop-out rates (in clinical trials) were also unusually high with asenapine.[16] According to apost-hoc analysis of two 3-week clinical trials it may possess some antidepressant effects in patients with acute mania or mixed episodes.[17]
Adverse effect incidence[4][5][2][6]
Very common (>10% incidence) adverse effects include:
Common (1–10% incidence) adverse effects include:
Uncommon (0.1–1% incidence) adverse effects include:
Rare (0.01–0.1% incidence) adverse effects include:
Unknown incidence adverse effects
† Asenapine seems to have a relatively low weight gain liability for anatypical antipsychotic (which are notorious for their metabolic side effects) and a 2013 meta-analysis foundsignificantly less weight gain (SMD [standard mean difference in weight gained in those on placebo vs. active drug]: 0.23;95% CI: 0.07-0.39) than,paliperidone (SMD: 0.38; 95% CI: 0.27-0.48),risperidone (SMD: 0.42; 95% CI: 0.33-0.50),quetiapine (SMD: 0.43; 95% CI: 0.34-0.53),sertindole (SMD: 0.53; 95% CI: 0.38-0.68),chlorpromazine (SMD: 0.55; 95% CI: 0.34-0.76),iloperidone (SMD: 0.62; 95% CI: 0.49-0.74),clozapine (SMD: 0.65; 95% CI: 0.31-0.99),zotepine (SMD: 0.71; 95% CI: 0.47-0.96) andolanzapine (SMD: 0.74; 95% CI: 0.67-0.81) andapproximately (that is, no statistically significant difference at thep=0.05 level) as much as weight gain asaripiprazole (SMD: 0.17; 95% CI: 0.05-0.28),lurasidone (SMD: 0.10; 95% CI: –0.02-0.21),amisulpride (SMD: 0.20; 95% CI: 0.05-0.35),haloperidol (SMD: 0.09; 95% CI: 0.00-0.17) andziprasidone (SMD: 0.10; 95% CI: –0.02-0.22).[20] Its potential for elevating plasma prolactin levels seems relatively limited too according to this meta-analysis.[20] This meta-analysis also found that asenapine has approximately the same odds ratio (3.28; 95% CI: 1.37-6.69) for causing sedation [compared to placebo-treated patients] asolanzapine (3.34; 95% CI: 2.46-4.50]) andhaloperidol (2.76; 95% CI: 2.04-3.66) and a higher odds ratio (although notsignificantly) for sedation thanaripiprazole (1.84; 95% CI: 1.05-3.05),paliperidone (1.40; 95% CI: 0.85-2.19) andamisulpride (1.42; 95% CI: 0.72 to 2.51) to name a few and is hence a mild-moderately sedating antipsychotic.[20] The same meta-analysis suggested that asenapine had a relatively high risk of extrapyramidal symptoms compared to other atypical antipsychotics but a lower risk than first-generation ortypical antipsychotics.[20]
For all antipsychotics, theBritish National Formulary recommends a gradual dose reduction when discontinuing to avoid acute withdrawal syndrome or rapid relapse.[21] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[22] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[22] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[22] Symptoms generally resolve after a short period of time.[22]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis as a transient withdrawal symptom.[23] It may also result in recurrence of the condition that is being treated.[24] Rarely tardive dyskinesia can occur when the medication is stopped.[22]
| 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 highaffinity (pKi) for numerousreceptors, including theserotonin5-HT1A (8.6),5-HT1B (8.4),5-HT2A (10.2),5-HT2B (9.8),5-HT2C (10.5),5-HT5A (8.8),5-HT6 (9.5), and5-HT7 (9.9) receptors, theadrenergicα1 (8.9),α2A (8.9),α2B (9.5), andα2C (8.9) receptors, thedopamineD1 (8.9),D2 (8.9),D3 (9.4), andD4 (9.0) receptors, and thehistamineH1 (9.0) andH2 (8.2) receptors. It has much lower affinity (pKi < 5) for themuscarinic acetylcholine receptors. Asenapine behaves as a partialagonist at the 5-HT1A receptors.[26] At all other targets asenapine is anantagonist.[25]
Even relative to other atypical antipsychotics, asenapine has unusually high affinity for the5-HT2A,5-HT2C,5-HT6, and5-HT7 receptors, and very high affinity for theα2 andH1 receptors.[25]
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.
