英文药名：Fanapt(Iloperidone Tablets) 中文药名：伊潘立酮片 生产厂家：诺华制药 药品介绍 FDA批准Fanapt治疗精神分裂症 2003年5月6日，美国食品药品监督管理局（FDA）批准Fanapt（iloperidone，伊潘立酮）片可用于治疗成人精神分裂症（一种慢性、严重并可致残的脑部疾病）。 FDA药物评估和研究中心的精神病学产品部分主任Thomas Laughren博士说：“精神分裂症可成为一种需要终身治疗的破坏性疾病，针对该病的药物可缓解许多症状，并允许患者更好地独立生活。” 约1%的年龄≥18岁的美国成人人群受精神分裂症所困饶。其最突出的症状包括幻觉、妄想、病态思维和行为及情绪的异常表达。听见其他人未听见的说话声是最常见的幻觉类型。这些经历会使该病患者变得可怕和孤独。 Fanapt被归类为非典型抗精神病类药物。所有非典型抗精神病药都含黑框警告，即FDA级别最高的警告。警告提醒处方者，在患有痴呆相关性精神病的老年患者中非标签使用这类药物治疗行为问题可能会引起死亡危险增加。Fanapt未被批准用于痴呆相关性精神病患者。 在2项有安慰剂对照的短期临床试验中已证明了Fanapt的有效性。在这2项试验中，在减轻精神分裂症的症状方面，Fanapt均要高于安慰剂（糖丸）。 在临床试验中，通过使用Fanapt的患者报告的最常见不良反应为眩晕、口干、疲劳、鼻充血、因血压骤降而引起站立时有头部轻飘感（体位性低血压）、昏昏欲睡、心率加快（室性心动过速）和体重增加。 Fanapt由位于美国马里兰州的洛克威尔市的Vanda制药公司研发，并由位于加拿大安大略省Mississauga市的Patheon公司生产 Fanapt (iloperidone) FANAPT Rx Generic Name and Formulations: Iloperidone 1mg, 2mg, 4mg, 6mg, 8mg, 10mg, 12mg; tabs. Company: Novartis Pharmaceuticals Corp Indications for FANAPT: Acute treatment of schizophrenia. Adult: Titrate slowly. ≥18yrs: Initially 1mg twice daily, then 2mg, 4mg, 6mg, 8mg, 10mg, and 12mg twice daily on Days 2, 3, 4, 5, 6, and 7 respectively, to reach the 12mg/day to 24mg/day dose range. Reduce dose by ½ with concomitant strong CYP2D6/CYP3A4 inhibitors, or poor metabolizers of CYP2D6. Retitrate if therapy suspended >3 days. Children: <18yrs: not established. Warnings/Precautions: Increased mortality in elderly patients with dementia-related psychosis (not approved use). 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++. Moderate hepatic impairment. Severe hepatic impairment: not recommended. Diabetes or risk factors (obtain baseline fasting blood sugar). Monitor for hyperglycemia, weight changes. History of breast cancer or seizures. Orthostatic hypotension. Preexisting low WBC count or history of leukopenia/neutropenia: monitor CBC during 1st few months of therapy; discontinue if WBCs decline. If neutropenia develops, monitor for fever, signs/symptoms of infection; discontinue if severe neutropenia (absolute neutrophil count <1000/mm3) occurs. Exposure to extreme heat. Aspiration pneumonia risk. Dehydration. Suicidal tendencies. Write ℞ for the smallest practical amount. Monitor for neuroleptic malignant syndrome. Neonates: risk of extrapyramidal and/or withdrawal symptoms post delivery (due to exposure during 3rd-trimester pregnancy). Reevaluate periodically. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Avoid other drugs that cause QT prolongation (eg, quinidine, procainamide, amiodarone, sotalol, chlorpromazine, thioridazine, gatifloxacin, moxifloxacin, pentamidine, levomethadyl acetate, methadone). May potentiate antihypertensives. Caution with alcohol, CNS depressants. Potentiated by inhibitors of CYP2D6 (eg, fluoxetine, paroxetine) or CYP3A4 (eg, clarithromycin, ketoconazole). Pharmacological Class: Piperidinyl-benzisoxazole atypical. Adverse Reactions: 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, dyslipidemia, dysphagia, hyperprolactinemia, hypersensitivity reactions. Generic Availability: NO How Supplied: Tabs—60; Titration pack—8 (2 x 1mg, 2 x 2mg, 2 x 4mg, 2 x 6mg) Iloperidone (Fanapt) Indications: FDA-Approved Uses Indications and Usage FANAPT® tablets are indicated for the treatment of adults with schizophrenia. Efficacy was established in two short-term (4- and 6-week) placebo- and active-controlled studies of adult patients with schizophrenia. When deciding among the alternative treatments available for this condition, the prescriber should consider the finding that iloperidone is associated with prolongation of the QTc interval [see Warnings and Precautions ]. Prolongation of the QTc interval is associated in some other drugs with the ability to cause torsade de pointes-type arrhythmia, a potentially fatal polymorphic ventricular tachycardia which can result in sudden death. In many cases this would lead to the conclusion that other drugs should be tried first. Whether FANAPT will cause torsade de pointes or increase the rate of sudden death is not yet known. Patients must be titrated to an effective dose of FANAPT. Thus, control of symptoms may be delayed during the first 1 to 2 weeks of treatment compared to some other antipsychotic drugs that do not require a similar titration. Prescribers should be mindful of this delay when selecting an antipsychotic drug for the treatment of schizophrenia [see Dosage and Administration and Clinical Studies ]. The effectiveness of FANAPT in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use FANAPT for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient [see Dosage and Administration]. Dosage and administration Usual Dose FANAPT must be titrated slowly from a low starting dose to avoid orthostatic hypotension due to its alpha-adrenergic blocking properties. The recommended starting dose for FANAPT tablets is 1 mg twice daily. Dose increases to reach the target range of 6-12 mg twice daily (12-24 mg/day) may be made with daily dosage adjustments not to exceed 2 mg twice daily (4 mg/day). The maximum recommended dose is 12 mg twice daily (24 mg/day). FANAPT doses above 24 mg/day have not been systematically evaluated in the clinical trials. Efficacy was demonstrated with FANAPT in a dose range of 6 to 12 mg twice daily. Prescribers should be mindful of the fact that patients need to be titrated to an effective dose of FANAPT. Thus, control of symptoms may be delayed during the first 1 to 2 weeks of treatment compared to some other antipsychotic drugs that do not require similar titration. Prescribers should also be aware that some adverse effects associated with FANAPT use are dose related. FANAPT can be administered without regard to meals.  Clinical Studies The efficacy of FANAPT in the treatment of schizophrenia was supported by two placebo- and active-controlled short-term (4- and 6-week) trials. Both trials enrolled patients who met the DSM-III/IV criteria for schizophrenia. Two instruments were used for assessing psychiatric signs and symptoms in these studies. The Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) are both multi-item inventories of general psychopathology usually used to evaluate the effects of drug treatment in schizophrenia. A 6-week, placebo-controlled trial (n=706) involved two flexible dose ranges of FANAPT (12-16 mg/day or 20-24 mg/day) compared to placebo and an active control (risperidone). For the 12-16 mg/day group, the titration schedule of FANAPT was 1 mg twice daily on days 1 and 2, 2 mg twice daily on days 3 and 4, 4 mg twice daily on days 5 and 6, and 6 mg twice daily on day 7. For the 20-24 mg/day group, the titration schedule of FANAPT was 1 mg twice daily on day 1, 2 mg twice daily on day 2, 4 mg twice daily on day 3, 6 mg twice daily on days 4 and 5, 8 mg twice daily on day 6, and 10 mg twice daily on day 7. The primary endpoint was change from baseline on the BPRS total score at the end of treatment (Day 42). Both the 12-16 mg/day and the 20-24 mg/day dose ranges of FANAPT were superior to placebo on the BPRS total score. The active control antipsychotic drug appeared to be superior to FANAPT in this trial within the first 2 weeks, a finding that may in part be explained by the more rapid titration that was possible for that drug. In patients in this study who remained on treatment for at least two weeks, iloperidone appeared to have had comparable efficacy to the active control. A 4-week, placebo-controlled trial (n=604) involved one fixed dose of FANAPT (24 mg/day) compared to placebo and an active control (ziprasidone). The titration schedule for this study was similar to that for the 6-week study. This study involved titration of FANAPT starting at 1 mg twice daily on day 1 and increasing to 2, 4, 6, 8, 10 and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7. The primary endpoint was change from baseline on the PANSS total score at the end of treatment (Day 28). The 24 mg/day FANAPT dose was superior to placebo in the PANSS total score. FANAPT appeared to have similar efficacy to the active control drug which also needed a slow titration to the target dose.