伊潘立酮片获准上市是基于伊潘立酮2项纳入3000多例患者的安慰剂对照的主动控制精神分裂症患者症状和安全性的Ⅲ期临床研究结果。伊潘立酮是混合型多巴胺D2/5-羟色胺5HT2A受体阻断剂，属非典型精神抑制药。伊潘立酮高亲和性地结合于5-羟色胺5HT2A和多巴胺D2、D3受体(Ki值分别为5.6、6.3、7.1nM)。
伊潘立酮对多巴胺D4和5-羟色胺5HT6、5HT7和去甲肾上腺素NEα1受体中度亲和性(Ki值分别为25、43、22、36nM)，对5HT1A、多巴胺D1和组胺H1受体低亲和性(Ki值分别为168、216、473nM)，对胆碱能蕈毒碱受体无可检测的亲和性(Ki>1000nM)。伊潘立酮通过对多巴胺D2、D3、5-羟色胺5HT1A和去甲肾上腺素NEα1/α2c受体阻断发挥作用。伊潘立酮代谢物P88的亲和性通常≤母体化合物，而代谢物P95仅对5HT2A、NEα1A、NEα1B、NEα1D、NEα2C受体有亲和性(Ki值分别为3.91、4.7、2.7、4.7nM)。
伊潘立酮是5-羟色胺、多巴胺D2受体的拮抗剂。在3个短期和3个长期的临床试验中，总共参与试验的患者超过2 000例，伊潘立酮比目前使用的抗精神病药物的效果要好且副作用要少。伊潘立酮治疗精神分裂症的疗效经过2项安慰剂对照短期(4周和6周)临床研究的评价。两项研究遴选的患者符合DSM-Ⅲ/Ⅳ标准，伊潘立酮每日12～24mg控制精神分裂症症状显著优于安慰剂。伊潘立酮推荐剂量范围为12～24mg/日。
与目前使用的抗精神病药物比较，短期、长期的安全试验结果显示伊潘立酮的副作用要少些，患者体重增加幅度较低，伊潘立酮不会诱导患者发生糖尿病，患者锥体外系症状也较少(无静坐不能、无高催乳素血症、嗜睡发生率下降、认知能力下降较少)。但是伊潘立酮也会使QT间期延长。
伊潘立酮片的剂量规格：1mg、2mg、4mg、6mg、8mg、10mg和12mg/片。辅料：乳糖一水物，微晶纤维素，羟丙基甲基纤维素，交联聚乙烯吡洛烷酮，硬脂酸镁和微粉硅胶。
美国FDA 批准伊潘立酮片（iloperidone，Fanapt）上市，用于治疗精神分裂症。本品剂量规格：1 mg、2 mg、4 mg、6 mg、8 mg、10 mg和12 mg/片。辅料：乳糖一水物，微晶纤维素，羟丙基甲基纤维素，交联聚乙烯吡洛烷酮，硬脂酸镁和微粉硅胶。
本品获准上市是基于伊潘立酮2项纳入3 000多例患者的安慰剂对照的主动控制精神分裂症患者症状和安全性的Ⅲ期临床研究结果。伊潘立酮是混合型多巴胺D2/5-羟色胺5HT2A受体阻断剂，属非典型精神抑制药。伊潘立酮高亲和性地结合于5-羟色胺5HT2A和多巴胺D2、D3受体（Ki值分别为5.6、6.3、7.1 nM）。伊潘立酮对多巴胺D4和5-羟色胺5HT6、5HT7和去甲肾上腺素NEα1受体 中度亲和性（Ki值分别为25、43、22、36 nM），对5HT1A、多巴胺D1和组胺H1受体低亲和性（Ki值分别为168、216、473 nM），对胆碱能蕈毒碱受体无可检测的亲和性（Ki>1 000 nM）。伊潘立酮通过对多巴胺D2、D3、5-羟色胺5HT1A 和去甲肾上腺素NEα1/α2c受体阻断发挥作用。伊潘立酮代谢物P88的亲和性通常≤母体化合物，而代谢物P95仅对5HT2A、NEα1A、NEα1B、NEα1D、NEα2C受体有亲和性（Ki值分别为3.91、4.7、2.7、4.7 nM）。
本品获准上市标志着对许多现有药物治疗仅部分有效的精神分裂症患者是一新的机会，本品可更好地控制他们的症状。
伊潘立酮治疗精神分裂症的疗效经过2项安慰剂对照短期（4周和6周）临床研究的评价。两项研究遴选的患者符合DSM-Ⅲ/Ⅳ标准，伊潘立酮每日12～24 mg控制精神分裂症症状显著优于安慰剂。伊潘立酮推荐剂量范围为12 ～24 mg/日。
Manufacturer:
Novartis Pharmaceuticals Corp
Pharmacological Class:
Antipsychotic (piperidinyl-benzisoxazole atypical)
Active Ingredient(s):
Iloperidone 1mg, 2mg, 4mg, 6mg, 8mg, 10mg, 12mg; tabs.
Indication(s):
Acute treatment of schizophrenia.
Pharmacology:
Iloperidone is an atypical antipsychotic agent whose efficacy in the treatment of schizophrenia may be due to its antagonism at dopamine types 2 and 3 (D2, D3) and serotonin type 2A (5-HT2A) receptors in the CNS.
Clinical Trials:
Two placebo- and active-controlled clinical trials were conducted to assess the efficacy of iloperidone in the treatment of schizophrenia. A 6-week trial compared two doses ranges for iloperidone (12–16mg/day and 20–24mg/day, after titration) to placebo and an active control drug. The primary endpoint was the change from baseline on the Brief Psychiatric Rating Scale (BPRS) total score at the end of treatment (day 42). Both dose ranges for iloperidone were superior to placebo. Within the first 2 weeks, the active control psychiatric drug appeared to be superior to iloperidone. This may be explained by the more rapid titration that was possible for that drug.
In a 4-week trial, iloperidone 24mg/day after titration was compared to placebo and an active control drug which also required an initial titration phase. The primary efficacy endpoint was the change in baseline on the Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment (day 28). In this study, iloperidone was superior to placebo and had similar efficacy to the active control medication.
Legal Classification:
Rx
Adults:
≥18yrs: 1mg twice daily on day 1, 2mg twice daily on day 2, 4mg twice daily on day 3, 6mg twice daily on day 4, 8mg twice daily on day 5, 10mg twice daily on day 6, 12mg twice daily on day 7; target range 6–12mg twice daily; max 24mg/day. Reduce dose by 1/2 with concomitant strong inhibitors of CYP2D6 or CYP3A4. Retitrate if therapy suspended >3 days. Reassess periodically.
Children:
<18yrs: not recommended.
Precaution(s):
Bradycardia, hypokalemia, hypomagnesemia, congenital QT prolongation, recent MI, uncompensated heart failure, arrhythmias: avoid (risk of torsades de pointes/sudden death). Cardio- or cerebrovascular disease. Monitor electrolytes esp. K+, Mg++. Hepatic impairment: not recommended. Diabetes or risk factors (obtain baseline fasting blood sugar). Monitor for hyperglycemia. History of breast cancer or seizures. Orthostatic hypotension. Pre-existing low WBC count or history of leukopenia/neutropenia: monitor CBC during 1st few months of therapy; discontinue if WBCs decline. Exposure to extreme heat. Dehydration. Suicidal tendencies. Write Rx for the smallest practical amount. Monitor for neuroleptic malignant syndrome. Elderly (not for dementia-related psychosis). Pregnancy (Cat.C). Nursing mothers: not recommended.
Interaction(s):
Avoid other drugs that cause QT prolongation (eg, quinidine, amiodarone, sotalol, procainamide, chlorpromazine, thioridazine, moxifloxacin, methadone). May potentiate antihypertensives. Caution with alcohol, CNS depressants. Potentiated by inhibitors of CYP2D6 (eg, fluoxetine, paroxetine) or CYP3A4 (eg, clarithromycin, ketoconazole).
Adverse Reaction(s):
Dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, increased weight; QT prolongation (discontinue if QTc >500msec persists), priapism, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, dysphagia.
How Supplied:
Tabs—60
Titration pack—8 (2 x 1mg, 2 x 2mg, 2 x 4mg, 2 x 6mg)
Last Updated:
2/18/2010
