vicky3 2009-10-26 11:37
FDA變更Arixtra、磺醯尿素類、Tobramycin的安全標示
作者：Yael Waknine
出處：WebMD醫學新聞
October 7, 2009 — 美國食品藥物管理局(FDA)核准新版安全標示，警告使用fondaparinux sodium治療之病患的出血風險增加，使用磺醯尿素類治療之葡萄糖-六-磷酸鹽去氫酶缺乏症(蠶豆症)病患的溶血性貧血風險，進行抗生素治療之後2個月以上可能發生難治型腸梭菌(Clostridium difficile)相關腹瀉。
【某些病患使用Fondaparinux (Arixtra)後出血風險增加】
8月14日，FDA核准fondaparinux sodium皮下注射劑(商品名Arixtra，GlaxoSmithKline藥廠製造)變更安全標示，以強調增加出血風險的因素。
如同其他的抗凝血劑，使用fondaparinux與出血風險有關。若用於此風險可能增加的病患時要特別注意，例如先天或後天血液異常；活性潰瘍性與血管發育異常之胃腸道疾病；出血性中風；控制不佳的動脈性高血壓；糖尿病視網膜病變；或腦部、脊椎、眼科手術後不久。
應避免同時使用其他會增加出血風險的藥物，除非有必須加以處置的狀況(例如，靜脈血栓使用維他命K拮抗劑)。需仔細觀察併用治療之病患的出血徵兆與症狀。FDA指出，給予fondaparinux之後，不論有無同時使用其他抗凝血劑，需通報與出血事件暫時有關的活化凝血活酵素時間增加的案例。
手術後不到6小時即使用fondaparinux與增加出血風險有關；需至少6至8小時才可以開始治療。
因為體重輕的病患其出血風險增加，體重低於50公斤的病患應避免在術前使用fondaparinux作為深部靜脈血栓(DVT)的預防。使用fondaparinux於治療體重輕之病患的DVT與肺栓塞(PE)時必須謹慎。
Fondaparinux也與腎功能不佳病患的出血風險增加有關，因為清除率降低。當用於肌酸酐清除率介於30 mL/min- 50 mL/min的病患時，須注意且定期評估腎功能；嚴重腎功能不佳(肌酸酐清除率< 30 mL/min) 者應停止使用此藥治療。FDA指出，fondaparinux的抗凝血效果在腎功能正常的病患可持續到停藥之後的2到4天， 腎功能不佳病患的持續期間可能更久。
Fondaparinux是一種第10a凝血因子抑制劑(抗凝血劑)，用於預防接受髖骨骨折手術、髖關節置換術、膝關節置換術、腹部手術患者的DVT。它也可與warfarin併用，而用於治療DVT或急性PE。
【使用磺醯尿素類藥物和G6PD缺乏症病患的溶血性貧血風險有關】
FDA核准磺醯尿素類藥物，如glipizide和glipizide緩釋錠、微粉化glyburide錠、glipizide/metformin HCl錠、以及glyburide錠變更安全標示，以對葡萄糖-六-磷酸鹽去氫酶缺乏症(G6PD/蠶豆症)病患提出使用警告。8月時，Glucotrol與Glucotrol XL (Pfizer,Inc藥廠)、Glynase (Pfizer, Inc藥廠)、Metaglip (Bristol-Myers Squibb Co藥廠)和Micronase (Pfizer, Inc藥廠)等的標示已經更新。
G6PD缺乏是一種X-染色體相關隱性遺傳性情況，當身體曝露在某些藥物或感染壓力時會造成紅血球破裂。 臨床表現包括溶血性貧血、腹部和/或背痛、頭昏眼花、頭痛、呼吸困難與心悸。
因為G6PD缺乏的病患使用磺醯尿素類藥物會造成溶血性貧血，因此需考量使用其他製劑。FDA指出，有些沒有G6PD缺乏的病患也出現溶血性貧血。
磺醯尿素類藥物適應症為輔助飲食和運動以改善第2型糖尿病成人病患的血糖控制。
【Tobramycin與增加治療後的難治型腸梭菌相關腹瀉有關】
8月10日，FDA核准tobramycin sulfate注射劑(APP Pharmaceuticals, Inc藥廠)變更安全標示，以警告接受此抗生素治療之病患有關難治型腸梭菌相關腹瀉(Clostridium difficile–associated diarrhea，CDAD)的風險。
使用抗生素治療會改變腸道正常菌叢，造成難治型腸梭菌過度生長，釋放出毒素A和B，而造成CDAD。幾乎所有的抗生素都與CDAD有關，嚴重度從輕微腹瀉到致命的結腸炎都有。
因為毒素產量高的難治型腸梭菌對於抗生素有抗藥性，它們與增加發病率及死亡率有關，可能需要進行結腸切除術。FDA建議，所有在使用抗生素之後出現腹瀉的病患都應考慮是否為CDAD。因為這是遲發型疾病，需小心檢查藥歷；曾經有在使用抗生素療程之後2個月以上才出現CDAD的案例。
FDA指出，已知懷疑有COAD的病患應停止使用現有的抗生素治療初步感染。需要適當的補充液體和電解質、蛋白質，使用適當的抗生素治療難治型腸梭菌，評估是否需要手術。
Tobramycin是一種氨基苷類抗生素，適應症為治療有感受性之微生物引起的嚴重細菌感染。特殊用途包括敗血病；下呼吸道感染；中樞神經系統感染；腹內感染；皮膚、骨骼與皮膚構造感染、併發/復發尿道感染。
FDA Safety Changes: Arixtra, Sulfonylureas, Tobramycin
By Yael Waknine
Medscape Medical News
October 7, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to warn of factors that increase the risk of bleeding in patients receiving treatment with fondaparinux sodium, the risk for hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency with use of sulfonylureas, and the potential for the development of Clostridium difficile–associated diarrhea more than 2 months after completion of antimicrobial therapy.
Fondaparinux (Arixtra) Bleeding Risk Increased in Certain Settings
On August 14, the FDA approved safety labeling revisions for fondaparinux sodium subcutaneous injection (Arixtra; GlaxoSmithKline) to emphasize factors that increase the risk of bleeding.
As with other anticoagulants, use of fondaparinux is linked to a risk for hemorrhage. Extreme caution is advised when treating patients with conditions that increase this risk, such as congenital or acquired bleeding disorders; active ulcerative and angiodysplastic gastrointestinal tract disease; hemorrhagic stroke; uncontrolled arterial hypertension; diabetic retinopathy; or shortly after brain, spinal, or ophthalmologic surgery.
Coadministration of other agents that increase the risk for hemorrhage should also be avoided, unless essential for management of the underlying condition (eg, vitamin K antagonists in venous thromboembolism). Patients receiving combination therapy should be carefully observed for signs and symptoms of bleeding. Isolated cases of elevated activated partial thromboplastin time temporally associated with bleeding events have been reported after administration of fondaparinux with or without concomitant use of other anticoagulants, the FDA noted.
Use of fondaparinux earlier than 6 hours after surgery has also been linked to an increased risk of bleeding; at least 6 to 8 hours should elapse before treatment is initiated.
Because of the increased risk of bleeding in low-weight patients, presurgical use of fondaparinux for deep vein thrombosis (DVT) prophylaxis should be avoided in those weighing less than 50 kg. Use of fondaparinux for the treatment of DVT and pulmonary embolism (PE) should be approached with caution in low-weight patients.
Fondaparinux is also linked to an increased risk of bleeding in patients with impaired renal function because of decreased clearance. Caution and periodic assessment of renal function are advised when treating patients with creatinine clearance ranging from 30 mL/minute to 50 mL/minute; treatment should be discontinued for severe renal impairment (creatinine clearance < 30 mL/minute). The FDA notes that the anticoagulant effect of fondaparinux persists for 2 to 4 days after discontinuation of therapy in patients with normal renal function, a period that may be extended in those with renal impairment.
Fondaparinux is a factor Xa inhibitor (anticoagulant) indicated for the prevention of DVT in patients undergoing hip fracture surgery, hip replacement surgery, knee replacement surgery, or abdominal surgery. It also may be used for the treatment of DVT or acute PE when administered in conjunction with warfarin.
Use of Sulfonylureas Linked to Hemolytic Anemia in Patients with G6PD Deficiency
The FDA approved sulfonylurea class safety labeling revisions for glipizide and glipizide extended-release tablets, micronized glyburide tablets, glipizide/metformin HCl tablets, and glyburide tablets to warn against their use in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In August, the labels for Glucotrol and Glucotrol XL (Pfizer, Inc), Glynase (Pfizer, Inc), Metaglip (Bristol-Myers Squibb Co), and Micronase (Pfizer, Inc) were updated.
G6PD deficiency is an X-linked recessive hereditary condition in which red blood cells break down when the body is exposed to the stress of infection or certain drugs. Clinical manifestations include hemolytic anemia, abdominal and/or back pain, dizziness, headache, dyspnea, and palpitations.
Because use of sulfonylureas in patients with G6PD deficiency can lead to hemolytic anemia, alternative agents should be considered. The FDA notes that hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.
Sulfonylureas are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Tobramycin Linked to Risk for Posttherapy <Clostridium difficile–Associated Diarrhea
On August 10, the FDA approved antimicrobial class safety labeling revisions for tobramycin sulfate injection (APP Pharmaceuticals, Inc) to warn of the risk for Clostridium difficile–associated diarrhea (CDAD) in patients receiving antibiotic therapy.
Use of antimicrobial agents can alter the colon's normal flora, leading to overgrowth of C difficile and subsequent release of toxins A and B that contribute to the development of CDAD. Nearly all antibiotics have been implicated in CDAD, which may range in severity from mild diarrhea to fatal colitis.
Because hypertoxin-producing strains of C difficile can be resistant to antimicrobial therapy, they are associated with increased morbidity and mortality rates and may require colectomy. The FDA advises that CDAD be considered in all patients who present with diarrhea after antibiotic use. Careful examination of medical history is required because of the potential for late-onset disease; cases of CDAD have been reported more than 2 months after completion of an antimicrobial course of therapy.
The FDA notes that current antibiotic therapy for the primary infection may need to be discontinued in patients with known or suspected CDAD. Appropriate fluid and electrolyte management, protein supplementation, antibiotic therapy for C difficile, and surgical evaluation also may be required.
Tobramycin is an aminoglycoside antibiotic indicated for the treatment of serious bacterial infections caused by susceptible microorganisms. Specific uses include septicemia; lower respiratory tract infections; central nervous system infections; intra-abdominal infections; skin, bone, and skin structure infections, and complicated/recurrent urinary tract infections.