2018年12月31日,Horizon Pharma是一家专注于研究、开发和商业化创新药物用于治疗罕见病和风湿性疾病的制药公司。近日，该公司宣布，美国食品和药物管理局（FDA）已批准Ravicti（glycerol phenylbutyrate，苯丁酸甘油酯）口服液扩大适用人群，纳入2个月以下患有尿素循环障碍（UCD）的婴儿.   氮是蛋白质代谢所产生的废弃产物，尿素循环可将其从血液中清除并转化为尿素，后者通过尿液排出体外。UCD患者体内氮蓄积，并以氨的形式存留在体内。   Ravicti口服液适已获FDA批准，用于作为一种氮结合剂，用于不能单用饮食蛋白限制和/或补充剂治疗的UCD成人和儿童患者的长期管理。Ravicti必须与饮食蛋白限制一起使用，在某些情况下，还必须与膳食补充剂（例如必须氨基酸、精氨酸、瓜氨酸、无蛋白质热量补充剂）一起使用。   Ravicti一项新生儿研究的首席研究员、犹他大学医院临床遗传学家Nicola Longo表示，“FDA批准Ravicti用于2个月以下的人UCD婴儿，为这些患者提供了一种新的治疗方法，该方法易于给婴儿服用和给药。UCD是一种非常严重、可能危及生命的疾病，我们希望结合早期诊断（新生儿筛查或测量氨水平）和新型治疗方法，有效改善患者的预后。”   FDA批准Ravicti扩大适用人群，是基于在2个月UCD婴儿中开展的儿科研究（n=16）的安全性、疗效和药代动力学。该研究中，10例患者从苯丁酸钠过渡到Ravicti，3例患者从静脉注射苯甲酸钠和苯乙酸钠过渡到Ravicti，3名患者为初治患者。这些患者接受Ravicti治疗的平均时间为10.7个月。结果表明，在2个月以下的UCD婴儿中，与入组研究前相比，Ravicti治疗的患者保持了稳定的氨水平，证实了Ravicti的安全性和有效性。此外，与基线值相比，Ravicti治疗期间的平均氨水平更低。   UCD是一种罕见的遗传性疾病，在美国约有1/35000的活产婴儿受到影响。它是由尿素循环中的一种酶缺乏引起的，尿素循环是一种将过量的氨从血液中转化并最终将其从身体中清除的过程。因此，患有UCD的人会经历高氨血症，或血液中氨含量升高，然后会到达大脑，造成不可逆转的脑损伤、昏迷或死亡。UCD症状可能首先出现在任何年龄，这取决于疾病的严重程度，在生命早期出现更严重的缺陷。   完整说明书附件：https://hznp.azureedge.net/public/ravicti_1-1g-ml_vial_pi_effective_us.PDF RAVICTI(苯丁酸甘油[glycerol phenylbutyrate])为口服液 RAVICTI(glycerol phenylbutyrate)liquid  [Hyperion Therapeutics, Inc.] Indication and Usage RAVICTI is indicated for use as a nitrogen-binding agent for chronic management of adult and pediatric patients ≥2 years of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (eg, essential amino acids, arginine, citrulline, protein-free calorie supplements). LIMITATIONS OF USE: •RAVICTI is not indicated for the treatment of acute hyperammonemia in patients with UCDs because more rapidly acting interventions are essential to reduce plasma ammonia levels. •The safety and efficacy of RAVICTI for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established. •The use of RAVICTI in patients <2 months of age is contraindicated. Important Safety Information WARNINGS AND PRECAUTIONS: •Neurotoxicity: Phenylacetate (PAA), a major metabolite of RAVICTI, may be toxic at levels ≥500 μg/mL. Reduce RAVICTI dosage if symptoms of neurotoxicity, including vomiting, nausea, headache, somnolence, confusion, or sleepiness, are present in the absence of high ammonia or other intercurrent illnesses. •Reduced Phenylbutyrate Absorption in Pancreatic Insufficiency or Intestinal Malabsorption: Monitor ammonia levels closely. ADVERSE EVENTS: •The most common adverse reactions (occurring in ≥10% of adult patients) reported during short-term and long-term treatment with RAVICTI were diarrhea, flatulence, and headache; and nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, dizziness, headache and fatigue, respectively. •Adverse events occurring in ≥10% of pediatric patients during long-term treatment with RAVICTI were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, and headache. DRUG INTERACTIONS: •Corticosteroids, valproic acid, or haloperidol: May increase plasma ammonia level. Monitor ammonia levels closely. •Probenecid: May affect renal excretion of metabolites of RAVICTI, including PAGN and PAA. RAVICTI Rx Generic Name and Formulations: Glycerol phenylbutyrate 1.1g/mL (delivers 1.02g/mL of phenylbutyrate); liquid. Company: Hyperion Therapeutics RECENT UPDATES 11/07/13 Monograph added. Indications for RAVICTI: Chronic management of patients ≥2 years of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Limitations of use: not for treatment of acute hyperammonemia in patients with UCDs. Safety and efficacy for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established. Adults and Children's Dose: >2 months to <2yrs: not established. ≥2yrs: Take with food. Administer dose directly into the mouth via oral syringe or dosing cup. May give by NG or gastric tube: see full labeling. Give in 3 equally divided doses; max 17.5mL (19g) daily. Must be used with dietary protein restriction and, in some cases, dietary supplements (eg, essential amino acids, arginine, citrulline, protein-free calorie supplements). Phenylbutyrate-naïve: 4.5–11.2mL/m2/day (5–12.4g/m2/day); patients with some residual enzyme activity not adequately controlled with protein restrictions: 4.5mL/m2/day. To determine starting dose in treatment-naïve patients: consider the patient’s residual urea synthetic capacity, dietary protein requirements, and diet adherence. Switching from sodium phenylbutyrate: give dose that contains the same amount of phenylbutyric acid; convert as follows: Total daily dose of Ravicti (mL) = total daily dose of sodium phenylbutyrate (g) X 0.8. Moderate-to-severe hepatic impairment: start at the lower end of dosing range. Dose adjustment and monitoring: see full labeling. Pharmacological Class: Nitrogen-binding agent. Contraindications: Children <2 months of age. Warnings/Precautions: Monitor for signs/symptoms of neurotoxicity; reduce dose if occurs. Pancreatic insufficiency or intestinal malabsorption: closely monitor ammonia levels. Hepatic or renal impairment: monitor closely. Pregnancy (Cat. C). Nursing mothers: not recommended. Interactions: Concomitant corticosteroids, valproic acid, or haloperidol may increase plasma ammonia levels; monitor closely. May be potentiated by probenecid. Adverse Reactions: Diarrhea, flatulence, headache, nausea, vomiting, decreased appetite, hyperammonemia, dizziness, fatigue, upper abdominal pain, rash. Generic Availability: NO How Supplied: Liq (25mL)—1, 4