UK Cystic Fibrosis Trust, 11 London Road, Bromley, Kent BR1 1BY, UK.
Expert Opin Drug Saf. 2011 Mar;10(2):197-203. doi: 10.1517/14740338.2011.552499.
At the request of the Medicines and Healthcare Regulatory Agency and in agreement with the appropriate authorities, an observational, multi-center, non-interventional, post-authorization safety study of high-strength pancreatic enzymes was conducted.
Patients with exocrine pancreatic insufficiency due to cystic fibrosis (CF) who had previously taken high doses of pancreatic enzymes received pancreatin 40,000 capsules (Creon 40,000 Minimicrospheres, Abbott GmbH, Hanover, Germany) as part of their normal treatment for up to 2 years. Initial doses were calculated to match previous established doses in lipase units, with adjustment if required.
Safety focused on serious suspected adverse drug reactions. Maldigestion symptoms and body weight were also monitored. Patients were managed according to general guidelines common to all major CF units in the UK, although minor variations were expected. The coefficient of fat absorption was not assessed as this was a safety rather than an efficacy study.
Sixty-four patients were enrolled at nine UK centers. Two deaths occurred during the study, which were considered unrelated to therapy by investigators. There were no further serious suspected adverse drug reactions related to pancreatin 40,000 and no cases of fibrosing colonopathy. Daily lipase doses were reduced by 11% after switching to pancreatin 40,000. Maldigestion symptoms improved and mean body weight increased from baseline to last observation (mean + 6.1 kg in patients < 18 years old).
No safety concerns were identified with pancreatin 40,000 therapy for up to 2 years. Daily lipase doses were not increased when switching to pancreatin 40,000.
应药品和保健产品监管局的要求，并经有关当局同意，开展了一项高强度胰酶的上市后安全性、观察性、多中心、非干预性研究。
先前接受过高剂量胰酶治疗的囊性纤维化（CF）患者因外分泌胰腺功能不全而参与研究，他们在 2 年的时间里，将接受胰酶 40,000 胶囊（Creon 40,000 Minimicrospheres，Abbott GmbH，Hanover，Germany）作为常规治疗的一部分。起始剂量根据之前的脂肪酶单位确定，如有需要则进行调整。
安全性主要关注严重疑似药物不良反应。也监测了消化不良症状和体重。患者根据英国所有主要 CF 单位共同的一般指南进行管理，尽管预计会有一些细微的差异。未评估脂肪吸收率，因为这是一项安全性而非疗效研究。
9 个英国中心共纳入 64 名患者。研究期间发生 2 例死亡，研究者认为与治疗无关。没有其他与胰酶 40,000 相关的严重疑似药物不良反应，也没有发生纤维性结肠病的病例。切换到胰酶 40,000 后，每日脂肪酶剂量减少了 11%。消化不良症状改善，平均体重从基线到最后一次观察时增加（18 岁以下患者平均增加 6.1 公斤）。
用胰酶 40,000 治疗长达 2 年未发现安全性问题。切换到胰酶 40,000 后，每日脂肪酶剂量没有增加。
