Reference Center for Inborn Errors of Metabolism ToTeM, CHRU de Tours, Hôpital Clocheville, 49 Bd Béranger, 37000, Tours, France.
Pharmacie à Usage Intérieur, Hôpital Clocheville, 49 Bd Béranger, 37000, Tours, France.
Orphanet J Rare Dis. 2023 Jun 8;18(1):142. doi: 10.1186/s13023-023-02770-x.
Phenylketonuria (PKU) is a rare genetic metabolic disorder in which especially high phenylalanine (Phe) concentrations cause brain dysfunction. If untreated, this brain dysfunction results in severe microcephaly, intellectual disability, and behavioral problems. Dietary restriction of Phe is the mainstay of PKU treatment, with long-term successful outcomes. Aspartame, an artificial sweetener sometimes added into medications, is metabolized in the gut into Phe. Then, patients suffering from PKU on a Phe-restricted diet should avoid consumption of aspartame. The aim of our study was to evaluate the number of drugs containing aspartame and/or Phe as an excipient, and to quantify their corresponding Phe intake.
The list of drugs marketed in France containing aspartame and/or Phe was established using a national medication database called "Theriaque". For each drug, the corresponding daily Phe intake was calculated according to age and weight and was distributed into 3 categories: high (> 40 mg/d), medium (10 to 40 mg/d) and low (< 10 mg/d) Phe intake.
The number of drugs containing Phe or its precursor aspartame remained very limited (n = 401). Among the aspartame containing drugs, Phe intakes were significant (medium or high) for only half of them whereas there were negligible for the others. Furthermore, these medications with a significant Phe intake were limited to few pharmaceutical classes (mainly antiinfectives agents, analgesics, and drugs for nervous system), and within these classes the drugs were limited to a small number of molecules, including principally amoxicillin, amoxicillin + clavulanic acid and paracetamol/ acetaminophen.
In situations requiring the use of these molecules, we propose as an alternative, the use of an aspartame-free form of these molecules or a form with a low Phe intake. If it is not possible, we propose as second-line the use of another antibiotics or analgesics. Finally, we have to remember the benefits-risk balance to use medications containing significant Phe intake in PKU patients. Indeed, it may be better to use a Phe containing medication in the absence of an aspartame-free form of this drug rather than to leave a person with PKU without treatment.
苯丙酮尿症（PKU）是一种罕见的遗传性代谢疾病，其中特别高的苯丙氨酸（Phe）浓度会导致大脑功能障碍。如果未经治疗，这种大脑功能障碍会导致严重的小头畸形、智力残疾和行为问题。饮食限制 Phe 是 PKU 治疗的主要方法，长期以来取得了成功的结果。阿斯巴甜是一种人工甜味剂，有时添加到药物中，在肠道中代谢为 Phe。因此，接受 Phe 限制饮食的 PKU 患者应避免摄入阿斯巴甜。我们研究的目的是评估含有阿斯巴甜和/或 Phe 作为赋形剂的药物数量，并量化其相应的 Phe 摄入量。
使用名为“Theriaque”的国家药物数据库，确定法国市场上含有阿斯巴甜和/或 Phe 的药物清单。对于每种药物，根据年龄和体重计算相应的每日 Phe 摄入量，并分为 3 类：高（>40mg/d）、中（10 至 40mg/d）和低（<10mg/d）Phe 摄入量。
含有 Phe 或其前体阿斯巴甜的药物数量仍然非常有限（n=401）。在含有阿斯巴甜的药物中，只有一半的药物 Phe 摄入量较高（中或高），而其他药物则可忽略不计。此外，这些具有显著 Phe 摄入量的药物仅限于少数几个药物类别（主要是抗感染药物、镇痛药和神经系统药物），并且在这些类别中，药物仅限于少数几个分子，包括主要是阿莫西林、阿莫西林+克拉维酸和对乙酰氨基酚/扑热息痛。
在需要使用这些分子的情况下，我们建议作为替代方案，使用这些分子的无阿斯巴甜形式或低 Phe 摄入量的形式。如果不可能，我们建议作为二线药物使用另一种抗生素或镇痛药。最后，我们必须记住使用含有大量 Phe 摄入量的药物的利弊平衡，在 PKU 患者中。事实上，在没有这种药物的无 Phe 形式的情况下使用含有 Phe 的药物，可能比让 PKU 患者得不到治疗要好。
Zotero 插件
