ST LOUIS (MD Consult) - On March 18, 2010, the US Food and Drug Administration (FDA) announced the approval of Carbaglu (carglumic acid) for the treatment of acute hyperammonemia caused by deficiency of the hepatic enzyme N-acetylglutamate synthase (NAGS deficiency) in pediatric and adult patients. The drug is also approved for use as maintenance therapy for chronic hyperammonemia that results from NAGS deficiency.

According to a press release by the pharmaceutical company, Recordati, NAGS deficiency is a very rare, lifelong, life-threatening clinical condition involving extreme hyperammonemia, a situation that can lead to permanent and irreversible damage of the central nervous system. Manifestations of the disease begin shortly after birth. Without appropriate treatment, the disease progresses rapidly and patients experience cerebral edema, coma, and eventually death. Rapid diagnosis and prompt, effective treatment are essential to prevent permanent neurologic damage.

The safety and efficacy of Carbaglu were studied in 23 patients with NAGS deficiency who received the treatment for durations ranging from 6 months to 21 years. Patients treated with Carbaglu showed reductions in blood-ammonia levels within 24 hours and demonstrated normalized ammonia levels within 3 days. The majority of study participants appeared to maintain normal plasma ammonia levels with long-term Carbaglu treatment.

Adverse effects experienced by patients receiving Carbaglu included vomiting, diarrhea, headache, pyrexia, tonsillitis, anemia, abdominal pain, ear infection, and nasal and throat inflammation.

Carbaglu should only be administered by a physician experienced in treating metabolic disorders. The recommended initial dose of Carbaglu is 100 to 250 mg/kg/d for treatment of acute hyperammonemia. Use of other ammonia-lowering therapies with Carbaglu during episodes of acute hyperammonemia is recommended. Dosing should be adjusted in accordance with a patient's ammonia levels and symptomology.

圣路易斯(MD Consult)——2010年3月18日，美国食品药品管理局(FDA)宣布批准Carbaglu (carglumic 酸)作为儿童和成人肝脏N-乙酰谷氨酸合成酶（NAGS）缺乏所致急性高氨血症的治疗药物。同时还批准该药物作为NAGS缺乏所致慢性高氨血症的维持治疗药物。

 

该药物生产厂家Recordati公司在一次新闻发布会上称，NAGS缺乏是一种极为罕见、持续终生并可危及生命的临床疾病，表现为血氨极度升高，并进而引发永久性、不可逆的中枢神经系统损害。这种疾病的临床表现开始于出生后不久。如未经适当治疗，疾病将迅速进展，患者发生脑水肿、昏迷，并最终导致死亡。早期诊断和及时有效的治疗对于预防永久性神经系统损害至关重要。

有研究已在病程长达6个月至21年的23例接受治疗的NAGS 缺乏患者中评估了Carbaglu的安全性和疗效。接受Carbaglu治疗的患者24h内血氨水平下降，且在3天内恢复正常。研究中多数参与者在长期接受Carbaglu治疗的情况下血氨水平似乎维持正常。

Carbaglu 治疗者发生的不良反应包括呕吐、腹泻、头痛、发热、扁桃体炎、贫血、腹痛、耳部感染以及鼻和咽喉炎症。

Carbaglu仅可由有代谢疾患治疗经验的医生处方。治疗急性高氨血症的建议初始剂量为100~250 mg/(kg•d)。建议在急性高氨血症发作期间与其他降低血氨的治疗联合应用。药物剂量调整应以患者的血氨水平及症状学为依据。