Asenapine ( English asenapine; saphris ) is an atypical antipsychotic developed by Schering-Plow. According to the corporation, taking the drug causes minimal anticholinergic and cardiovascular side effects and a small weight gain. By the end of summer 2009, a complete series of clinical trials was conducted, in which more than 3000 patients participated. Most FDA advisers voted in favor of the drug. On August 14, 2009, a positive decision was made by the agency, which approved the use of the drug for schizophrenia and bipolar disorder , and asenapine increased the number of antipsychotics used in psychiatry [1] .
| Asenapine | |
|---|---|
| Asenapinum | |
 | |
| Chemical compound | |
| IUPAC | (3a RS , 12b RS ) - rel -5-chloro-2,3,3a, 12b-tetrahydro 2-methyl-1 H- dibenz [2,3: 6,7] oxepino [4,5-c] pyrrole |
| Gross formula | C 17 H 16 ClNO |
| Molar mass | 285.77 g / mol |
| Cas | |
| Classification | |
| Farmakol. Group | Antipsychotic drugs |
| ATX | |
| Pharmacokinetics | |
| Bioavailable | 35% sublingual |
| The half-life. | 24 hours |
| Excretion | 50% with urine, 40% with feces |
| Dosage Forms | |
| pills | |
| Route of administration | |
| sublingually | |
| Other names | |
| Saphris, Sycrest | |
Some American clinical psychiatrists began to prescribe asenapine to war veterans as well for treating post-traumatic stress disorder accompanied by nightmares, although the use of the drug for this purpose has not yet been approved by the US Department of Veterans Affairs .
Content
Pharmacological Mechanism
Asenapine exhibits high affinity for many types of receptors , including serotonin 5-HT1A, 5-HT1B, 5-HT2A , 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6 and 5-HT7 receptors, adrenergic α1, α2A, α2B and α2C, dopamine D1 , D2 , D3 and D4 , histamine H1 and H2. [2] It exhibits a significantly lower affinity for muscarinic acetylcholine receptors . Asenapine is a partial agonist of 5-HT1A and D1 receptors; it exhibits the property of an antagonist to the rest of the mentioned receptors. [2]
Since asenapine blocks histamine receptors nevertheless weaker than some other atypical antipsychotics ( olanzapine , quetiapine ), it is assumed that weight gain and sedation are less characteristic for it. By blocking dopamine receptors weaker than haloperidol , asenapine relatively rarely causes extrapyramidal disorders and increased prolactin . Therefore, this drug can be considered as a treatment option in patients who are at risk of developing a metabolic syndrome , and also when other drugs have been discontinued due to unbearable side effects, such as akathisia . In addition, asenapine is less likely to prolong the QT interval on the electrocardiogram than ziprasidone . [3] However, all the effects mentioned are inherent to one extent or another, although relatively infrequently. [four]
Indications
Asenapine was approved by the FDA for the treatment of acute episodes of schizophrenia in adults and acute manic or mixed episodes (with or without psychotic symptoms) in type I bipolar affective disorder. [five]
The drug is not indicated for the treatment of depression , in clinical trials when it was taken, no weakening of depressive symptoms was found both in the short and long term. [3] Asenapine is not approved for the treatment of dementia associated with psychosis; in clinical trials in patients with dementia, he increased the risk of mortality. [6]
Application Features
Asenapine is taken sublingually (under the tongue). The drug requires a special intake regimen, taking into account, in particular, the time of nutrition and fluid intake. [7] It is recommended that you take asenapine twice a day, after which you should avoid eating food and liquids for at least 10 minutes. [eight]
If a tablet is swallowed, this drug is characterized by low bioavailability . [eight]
Side Effects
Very frequent side effects (≥1 / 10): anxiety, drowsiness. [four]
Common side effects (≤1 / 100 - <1/10): weight gain, increased appetite, dystonia , akathisia , dyskinesia , parkinsonism , sedation , dizziness, dysgeusia . [four]
Infrequent (≤1 / 1000 - <1/100): hyperglycemia , fainting, seizures, dysarthria , sinus bradycardia , bundle branch block , lengthening of the QT interval on the electrocardiogram, sinus tachycardia , orthostatic hypotension , hypotension , oral paresthesia , gloss swelling of the tongue, dysphagia , sexual dysfunction, amenorrhea [4] , anemia , hyponatremia [9] .
Rare (≤1 / 10,000 - <1/1 000): neutropenia, malignant antipsychotic syndrome , accommodation disturbance, pulmonary embolism , rhabdomyolysis , gynecomastia , galactorrhea . [four]
Frequency unknown: allergic reactions , restless legs syndrome , nausea, lesions of the oral mucosa , hypersecretion of saliva, withdrawal syndrome in newborns. [four]
The FDA reports a risk of severe allergic reactions with asenapine, which include anaphylactic shock , angioedema , decreased blood pressure , increased heart rate, swollen tongue, shortness of breath and rash. In some cases, these symptoms appeared after the first dose. [10] The FDA program encourages the reporting of side effects by healthcare providers and patients. [eleven]
With long-term administration of asenapine, such frequently occurring effects were noted as sedation , drowsiness, insomnia, depression , headaches, weight gain and changes in blood glucose levels, tremors , akathisia, parkinsonism, tardive dyskinesia . [3]
Precautions
Asenapine should be used with caution in the elderly, in patients with cardiovascular diseases ( myocardial infarction , coronary heart disease , heart failure or conduction disturbance), cerebrovascular diseases , as well as in the presence of factors predisposing to the development of hypotension ( dehydration , hypovolemia , hypotensive therapy). Caution should be exercised in the treatment of patients receiving other drugs at the same time, which may cause hypotension, bradycardia , respiratory depression, or central nervous system . [9] [6] In all the cases mentioned, an orthostatic test should be carried out regularly [9] , if hypotension occurs, the dose of asenapine [9] [6] should be reduced.
When taking asenapine, metabolic side effects may occur, so you need to monitor body weight, regularly measure fasting glucose and lipid levels. If the patient suffers from diabetes or has any other signs of the metabolic syndrome before starting asenapine, you should avoid prescribing this drug and consider other options (for example, not causing such side effects of aripiprazole , ziprasidone ). [3]
Drug Interactions
The simultaneous use of asenapine and other drugs with a known ability to extend the QTc interval should be avoided, including class 1A antiarrhythmics (e.g. quinidine , procainamide ) or class 3 (e.g. amiodarone , sotalol ), antipsychotic drugs (e.g. ziprasidone , chlorpromazine , thioridazine ), antibacterial agents (e.g. gatifloxacin , moxifloxacin ). Avoid the use of asenapine in patients with a history of cardiac arrhythmia and other factors that may increase the risk of torsade de pointes and / or sudden death due to the use of drugs that prolong the QTc interval ( bradycardia , hypokalemia , hypomagnesemia ), as well as the presence of congenital extended QT interval syndrome. [6]
Asenapine is a weak inhibitor of cytochrome P450 2D6, which reduces the likelihood of pharmacokinetic interactions, but nevertheless it should be used with caution in combination with those drugs that are metabolized by CYP2D6 (for example, paroxetine , most tricyclic antidepressants , amoxapine , captopril , duloxetine , duloxetine , , fluvoxamine , haloperidol ). According to a clinical study, asenapine significantly increased the concentration of paroxetine in the blood. In addition, since asenapine is metabolized by CYP1A2, caution should be exercised when used together with substances that induce the CYP1A2 enzyme (e.g. smoking, carbamazepine , rifampicin ) or inhibit this enzyme (e.g. fluvoxamine , ciprofloxacin , ketoconazole ). [3]
Contraindications
Asenapine should not be used in patients at risk of aspiration pneumonia . [6] In patients with severely impaired liver function ( Child-Pugh class C ), a 7-fold increase in the concentration of asenapine was noted, therefore, it is not recommended to prescribe this drug to such patients. [12]
Notes
- ↑ Schering wins US approval for antipsychotic - Reuters
- ↑ 1 2 Shahid M., Walker GB, Zorn SH, Wong EH. Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. (English) // J Psychopharmacol. : journal. - 2009. - Vol. 23 , no. 1 . - P. 65-73 . - DOI : 10.1177 / 0269881107082944 . - PMID 18308814 .
- ↑ 1 2 3 4 5 Gonzalez JM, Thompson PM, Moore TA. Review of the safety, efficacy, and side effect profile of asenapine in the treatment of bipolar 1 disorder // Patient Prefer Adherence. - 2011 .-- T. 5 . - S. 333—341 . - DOI : 10.2147 / PPA.S10968 . - PMID 21792304 .
- ↑ 1 2 3 4 5 6 Sycrest 5mg and 10mg sublingual tablets - Summary of Product Characteristics (SPC) . Electronic Medicines Compendium . Lundbeck Limited (April 18, 2013).
- ↑ Saphris (asenapine) prescribing information (PDF). Schering Corporation (August 1, 2009). Date of treatment September 5, 2009. Archived April 5, 2012.
- ↑ 1 2 3 4 5 Asenapine (Asenapine): instructions, use and formula . Radar Drug Reference. Date of treatment November 29, 2013.
- ↑ Shmukler A.B. Asenapine: use in clinical practice // Social and Clinical Psychiatry. - 2013. - T. 23 , No. 1 .
- ↑ 1 2 Henry JM, Fuller MA. Asenapine: a new antipsychotic option // J Pharm Pract. - 2011 Oct. - T. 24 , No. 5 . - S. 447–451 . - DOI : 10.1177 / 0897190011422875 . - PMID 22156709 .
- ↑ 1 2 3 4 SAPHRIS (asenapine maleate) tablet [Organon Pharmaceuticals USA ] . DailyMed Organon Pharmaceuticals USA (March 2013). Date of treatment October 23, 2013.
- ↑ FDA: risk of serious allergic reactions with Safris (September 16, 2011).
- ↑ FDA Alert: Saphris (asenapine maleate): Drug Safety Communication: Serious Allergic Reactions
- ↑ Safris ~ Official Instruction . MEDI.RU. Date of treatment November 29, 2013.