vicky3 2009-10-30 11:24
FDA安全性變更：Symbyax、Zoladex與INOmax
作者：Yael Waknine
出處：WebMD醫學新聞
October 14, 2009 — 美國食品藥物管理局（FDA）已經核准使用抗精神分裂藥物病患發生白血球低下或中性球低下風險的安全性警語變更，包括olanzapine；使用促性腺荷爾蒙釋放激素致效劑，包括goserelin acetate造成高血糖的可能性；以及左心室功能不全患者接受吸入性一氧化氮治療惡化心臟衰竭的可能。
【使用抗精神分裂藥物可能與白血球低下/中性球低下風險有關】
FDA已經核准非典型抗精神分裂藥物的仿單變更，警告發生白血球低下/中性球低下在時序上的關聯；也曾有顆粒球低下的報告。8月31日時，Symbyax（與fluoxetine HCl合併上市；禮來藥廠）的仿單更新。
發生白血球低下/中性球低下高風險病患，包括原本就已經白血球低下（WBC）或是有藥物引起的白血球低下/中性球低下病史，在開始的頭幾個月，都應該經常監測全血球數目（CBC）。在第一個臨床顯著白血球數目下降的病徵出現時，且被認定與其他原因無關，應該停用抗精神分裂藥物。
發生臨床顯著中性球低下的病患們應該嚴密地監測是否有發燒或是其他感染病徵，如果症狀發生的話應該立即治療。嚴重中性球低下（絕對中性球數目低於1000 mm3）應該停用抗精神分裂藥物，並且監測白血球數目，直到恢復為止。
Olanzapine/fluoxetine適用於與成人雙極性異常憂鬱症狀的急性治療，以及對於兩種不同抗憂鬱藥物治療無效的重鬱症。
【促性腺激素釋放荷爾蒙致效劑與高血糖風險有關】
FDA已經核准goserelin acetate植入物仿單標示變更，警告使用促性腺激素釋放荷爾蒙致效劑發生高血糖的風險。8月31日時，Zoladex（阿斯特捷利康藥廠）的仿單標示更新。
FDA表示，高血糖可以以新發生的糖尿病，或是已罹患糖尿病病患的血糖控制變差表現。接受Goserelin治療病患建議常規地監測血糖。
Goserlin適用於併用flutamide處理局部受限攝護腺癌，以及進展性攝護腺癌病患的緩和治療。
【使用一氧化氮（INOmax）病患可能惡化左心室收縮功能】
8月26日，FDA核准吸入性一氧化氮（INOmax；INO治療有限公司）安全性標示變更，警告左心室收縮功能不佳的心臟衰竭病患，心臟衰竭惡化的可能性。
在這個狀況下使用吸入性一氧化氮，即使是短期使用，可能增加肺部微血管契壓，導致肺水腫與其他嚴重不良反應。
一氧化氮被用在低血氧呼吸衰竭的足產與近足產（懷孕週數>34週）嬰兒，且有肺高壓臨床或是心臟超音波證據。對這些新生兒使用一氧化氮已經被證實改善氧合且降低體外循環維生系統需求。
FDA Safety Changes: Symbyax, Zoladex, INOmax
By Yael Waknine
Medscape Medical News
October 14, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to warn of the risk for leukopenia/neutropenia in patients receiving antipsychotics, including olanzapine; the potential for hyperglycemia in patients receiving treatment with gonadotropin-releasing hormone agonists, including goserelin acetate; and the potential for heart failure in patients with left ventricular dysfunction receiving treatment with inhaled nitric oxide.
Antipsychotic Agents May Be Linked to Risk for Leukopenia/Neutropenia
The FDA approved class labeling revisions for the atypical antipsychotic agent olanzapine to warn of a temporal relationship with the development of leukopenia/neutropenia; agranulocytosis has also been reported. On August 31, the label for Symbyax (marketed in combination with fluoxetine HCl; Eli Lilly Co) was updated.
Patients with risk factors for leukopenia/neutropenia, such as preexisting low white blood cell count (WBC) or a history of drug-induced leukopenia/neutropenia, should have frequent monitoring of complete blood count (CBC) during the first few months of treatment. Antipsychotic therapy should be discontinued at the first sign of a clinically significant decline in WBC that cannot be attributed to other causes.
Patients with clinically significant neutropenia should be carefully monitored for fever or other signs of infection and treated promptly if symptoms occur. Antipsychotic therapy should be discontinued for severe neutropenia (absolute neutrophil counts < 1000 mm3) and WBC monitored until recovery.
Olanzapine/fluoxetine is indicated for the acute treatment of depressive episodes associated with bipolar I disorder in adults, and treatment-resistant major depressive disorder that does not respond to 2 separate trials of different antidepressants.
Gonadotropin-Releasing Hormone Agonists Linked to Risk for Hyperglycemia
The FDA approved class labeling revisions for goserelin acetate implants to warn of the potential for hyperglycemia in patients receiving treatment with gonadotropin-releasing hormone agonists. On August 31, the label for Zoladex (AstraZeneca) was updated.
Hyperglycemia can manifest as new-onset diabetes mellitus or the worsening of glycemic control in established cases, the FDA said. Regular monitoring of blood glucose levels is recommended for patients receiving goserelin therapy.
Goserelin is indicated with flutamide for the management of locally confined prostate cancer and the palliative treatment of advanced prostate cancer.
Use of Inhaled Nitric Oxide (INOmax) May Worsen Left Ventricular Dysfunction
On August 26, the FDA approved safety labeling revisions for inhaled nitric oxide (INOmax; INO Therapeutics, Inc) to warn of the potential for heart failure in patients with preexisting left ventricular dysfunction.
Use of inhaled nitric oxide in this setting, even for short durations, may increase pulmonary capillary wedge pressure, leading to pulmonary edema and other serious adverse events.
Nitric oxide is used to promote capillary and pulmonary dilatation in term and near-term (> 34 weeks' gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension. Use of nitric oxide in these neonates has been shown to improve oxygenation and reduce the need for extracorporeal membrane oxygenation.