FDA核准olmesartan用於治療兒童高血壓
作者：Yael Waknine
出處：WebMD醫學新聞
February 12, 2010 — 美國食品藥物管理局（FDA）已經核准olmesartan medoxomil（Benicar錠劑，Daiichi Sankyo有限公司）用於治療6~16歲兒童高血壓的擴展適應症。血管張力素II受體阻斷劑過去僅限使用於成人。
大約有360萬美國兒童有高血壓的問題，且經常未被診斷出來。一項全國性的調查數據顯示，兒童高血壓的盛行率從1980年代後期逐漸上升，與兒童的體重平行增加。因為這種狀況代表成人高血壓一個獨立危險因子，且與心血管疾病初期危險因子有關，所以治療是很重要的。
Daiichi Sankyo藥廠研發部門臨床發展合作副總裁Reinilde Heyrman醫師在一項公司的新聞稿中表示，Daiichi Sankyo公司相信提供治療選擇協助醫師達到治療這些兒童病患，可以幫助人們有效地控制他們的高血壓。
這項核准案是根據一項針對兒童的隨機分派、雙盲研究（共302位；其中112位是黑人、190位是混血後裔），這些兒童主要罹患原發性高血壓。體重介於20~35公斤的病患被隨機分派接受2.5或20 mg olmesartan每天一次；那些體重超過35公斤者被隨機分派至每天5或40 mg。在3個星期後，病患被重新分派繼續使用olmesartan治療或是安慰劑。
起始劑量療效期的研究結果顯示，olmesartan以體重校正劑量反應模式，顯著地降低收縮與舒張壓。整體而言，兩種劑量的olmesartan（低與高），相較於試驗前，分別顯著地降低收縮壓達6.6 mmHg與11.9 mmHg。收縮壓的下降包括藥物組與安慰劑組。
在隨機分派脫離到安慰劑期時，繼續使用olmesartan治療的病患，相較於那些脫離至安慰劑的病患，最低平均收縮與舒張壓顯著較低（差異分別為3.2 mmHg與2.8 mmHg）。就如同於成人族群觀察到的，血壓下降程度在黑人病患比較小。
兒童病患使用olmesartan的耐受性良好；不良反應發生率與成人研究報告的相符，最常報告的是頭暈（發生率為3%）。
兒童使用olmesartan的劑量是根據體重計算。體重介於20~35公斤的病患，建議起始與維持劑量10 mg與20 mg每天一次；體重超過35公斤以上的病患，應該接受成人起始劑量的20 mg每天一次，且維持在每天20~40 mg。不能吞服藥錠的兒童可能可以使用即溶的懸浮液。
FDA Approves Olmesartan for the Treatment of Pediatric Hypertension
By Yael Waknine
Medscape Medical News
February 12, 2010 — The US Food and Drug Administration (FDA) has approved an expanded indication for olmesartan medoxomil (Benicar tablets, Daiichi Sanyo, Inc) for the treatment of hypertension in pediatric patients aged 6 to16 years. The angiotensin II receptor blocker previously was reserved for use in adults.
About 3.6 million American children have hypertension that often goes undiagnosed. An analysis of national survey data suggests that the prevalence of pediatric hypertension has been increasing since the late 1980s, in parallel with increases in children's weight. Treatment is important because the condition represents an independent risk factor for adult hypertension and is associated with early markers of cardiovascular disease.
"As hypertension is on the rise also in a younger population, Daiichi Sankyo believes it is important to help doctors meet the challenge of treating these pediatric patients by providing a treatment option to help people effectively manage their hypertension," said Reinilde Heyrman, MD, vice president clinical development–operations, Daiichi Sankyo Pharma Development, in a company news release.
The approval was based on data from a randomized, double-blind study of pediatric patients (n = 302; 112 black and 190 mixed racial heritage) with hypertension of predominantly essential origin. Patients who weighed from 20 to less than 35 kg were randomly assigned to receive 2.5 or 20 mg of olmesartan once daily; those who weighed 35 kg or more were randomly assigned to a daily dose of 5 or 40 mg. After 3 weeks, patients were reassigned to continued olmesartan therapy or placebo.
Results of the initial dose-response phase showed that olmesartan significantly reduced both systolic and diastolic blood pressure in a weight-adjusted dose-dependent manner. Overall, the 2 dose levels of olmesartan (low and high) significantly reduced systolic blood pressure by 6.6 and 11.9 mm Hg from the baseline, respectively. These reductions in systolic blood pressure included both drug and placebo effect.
During the randomized withdrawal to placebo phase, mean systolic and diastolic blood pressure at trough were significantly lower in patients continuing olmesartan therapy than in those withdrawn to placebo (Δ, 3.2 mm Hg and 2.8 mm Hg, respectively). As observed in adult populations, blood pressure reductions were smaller in black patients.
Pediatric use of olmesartan was well-tolerated; adverse events were similar to those reported in adult studies, with dizziness most commonly reported (incidence, 3%).
Pediatric dosing of olmesartan is based on body weight. The recommended starting and maintenance doses for patients weighing from 20 to less than 35 kg are 10 mg and 20 mg once daily, respectively; patients weighing 35 kg or greater should receive an adult starting dose of 20 mg once daily and be maintained at a daily dose of 20 to 40 mg. An extemporaneous suspension may be prepared for children unable to swallow tablets.
