關於雙膦酸鹽藥物 (bisphosphonates)和pioglitazone安全性的最新資訊 Latest safety updates on bisphosphonates and pioglitazone

 

  • 雙膦酸鹽藥物 (bisphosphonates)：增加食道癌的證據不充份
                在評估雙膦酸鹽藥物(包括alendronate, risedronate, ibandronate和etidronate)是否會增加食道癌風險的數個觀察性研究中, 因各研究使用不同的方法而受偏差和混雜的影響, 可能對風險的評估產生差異和矛盾的結果。目前並沒有足夠的資料證實雙膦酸鹽藥物可引起食道癌, 而食道癌也是罕見的, 特別在女性身上。美國食物及藥物管理局(USFDA)認為, 口服雙膦酸鹽藥物減少骨質疏鬆病人嚴重骨折風險的效益仍高於其潛在的風險。 目前評估工作仍在進行中, 建議醫生﹑藥劑師及其他衛生專業人士：
  1. 留意服用雙膦酸鹽藥物的病人有否出現食道炎及其他關於食道的不良反應, 特別是病人在沒有按指示服用藥物的情況下。
  2. 對於沒有症狀的病人, 沒有充份數據支持對其進行內窺鏡檢查。
  3. 對病人作諮詢時：
    1. 教導病人嚴格依照獲處方的口服雙膦酸鹽藥物的指示服用藥物, 所有口服雙膦酸鹽藥物應在早上起床後立即以一杯清水送服, 然後30分鐘至1小時內不要躺下和飲食。
    2. 目前並沒有足夠的資料證明口服雙膦酸鹽藥物會增加食道癌的發生率。
    3. 如病人出現吞嚥困難或疼痛﹑胸部疼痛﹑胃酸倒流或倒流情況惡化, 可能是食道不良反應的症狀, 應告知醫生。
    4. 如病人具有延緩食道排空的症狀﹑不能站立或直坐30分鐘至1小時或血鈣濃度過低時, 不應服用口服雙膦酸鹽藥物。

 

  • Pioglitazone: 增加膀胱癌的風險微小
                歐盟藥物管理局(EMA)回顧數個臨床前﹑臨床﹑流行病學以及自願通報的研究數據, 皆顯示服用pioglitazone的糖尿病人出現膀胱癌的風險會略為增加。除此以外, 數據顯示服用最長療程以及最高累積劑量的糖尿病人出現膀胱癌的風險較高, 然而, 也不能排除短期服用該藥的風險。事實上, 某些糖尿病人在接受其他藥物的治療方案後仍得不到理想的效果, 而需要處方pioglitazone。EMA認為需要對服用pioglitazone的病人與沒有服用該藥的糖尿病人出現膀胱癌的類型﹑演變以及嚴重性進行更多比較和分析, 目前並不清楚此不良反應是早發效應, 或是隨時間或劑量增加的累積效應, 同時也需要對風險的特點, 包括風險的期間以及隨年齡增加的危險因子作進一步研究。
            EMA在對含有pioglitazone的藥物與出現膀胱癌之間關係作回顧後認為, 這些藥物對於某些第2型糖尿病人具有確切的治療價值, 但服用這些藥物的病人會有略為增加出現膀胱癌的風險。然而, 上述風險可透過適當的選擇和排除病人的措施, 以及定期對病人作效益和安全性的個體化評估予以減少, 建議醫生﹑藥劑師及其他衛生專業人士：
  1. 對於患有膀胱癌或具有相關病史或出現不明原因的肉眼可見血尿的病人, 不要處方含有pioglitazone的藥物。
  2. 於開始使用pioglitazone 治療前, 應評估病人是否具有的膀胱癌危險因子。
  3. 由於膀胱癌的風險隨年齡增加, 因此對年長病人, 應謹慎考慮效益及風險之間的平衡。
  4. 醫生應於處方pioglitazone後的每3至6個月對病人進行覆診, 以確定病人在服用該藥後能獲得應有的療效時, 才繼續服用藥物。
  5. 建議醫生謹慎選擇病人和監測療效。

 

 

  • Bisphosphonates: Inconclusive evidence on increased esophageal cancers
                There are various observational studies to evaluate whether the bisphosphonates class, including alendronate, risedronate, ibandronate and etidronate, is associated with an increased risk of esophageal cancers.   Differences in methodologies in these observational studies are subject to bias and confounding, which may account for the discrepant findings and conflicting data on this risk. At this time, there is not enough information to make definitive conclusions about a possible association of bisphosphonates and esophageal cancers.  It is also important to note that esophageal cancer is rare, especially in women.  The United States Food and Drug Administration (USFDA) believes that the benefits of oral bisphosphonate drugs in reducing the risk of serious fractures in people with osteoporosis continue to outweigh their potential risks.  While the USFDA’s review is ongoing, the following recommendations are advised for physicians, pharmacists and other health professionals:
  1. esophagitis and other esophageal events have been reported, particularly in patients who do not follow the specific directions for use of oral bisphosphonates.
  2. there are insufficient data to recommend endoscopic screening of asymptomatic patients.
  3. notify patients of the following:
    1. instruct patients to carefully follow the directions for use of the oral bisphosphonate drug they are prescribed for and to be followed carefully. All oral bisphosphonate drugs should be taken first thing in the morning after awakening, with a full glass of plain water.  Then do not lie down or eat or drink anything for at least 30 to 60 minutes.
    2. there is conflicting information on whether oral bisphosphonate drugs can affect your chance of developing esophageal cancer.
    3. talk to their physicians if they develop swallowing difficulties, chest pain, new or worsening heartburn, or have trouble or pain when they swallow. These may be signs of problems of the esophagus.
    4. they should not take oral bisphosphonates if they have esophageal conditions that delay emptying of the esophagus, or if they cannot stand or sit upright for at least 30 to 60 minutes, or have low calcium levels in their blood.

 

  • Pioglitazone: Small increased risk of bladder cancer
               European Medicines Agency (EMA) reviewed evidences from different study sources namely preclinical, clinical, epidemiological and spontaneous reports, all of them showed a small increased risk of bladder cancer for diabetic patients treated with pioglitazone. Apart from that fact, data also noted that such increased risk of bladder cancer in diabetic patients occurred, in particular, for those who had the drug for the longest durations and with the highest cumulative doses.  However, a possible risk of bladder cancer development after short term treatment cannot be excluded.  Needless to say that, there are still patients with some diabetic types who cannot be adequately treated by other treatments but will benefit from pioglitazone treatment.  The Agency agreed that there is a need for further analysis of the types, evolution and severity of bladder cancer in patients treated with pioglitazone compared to diabetics not treated with pioglitazone. It remains unclear as to whether it is an early effect or a risk with prolonged use/high cumulative dose.  Futher details on the characterisation of the risk, in particular the risk period and risk with increasing age factors should further be investigated. 
            Upon finalizing the reviews on the pioglitazone-containing medicines and the occurrence of bladder cancer, EMA confirmed that these medicines remain a valid treatment option for certain patients with type 2 diabetes but that there is a small increased risk of bladder cancer in patients taking these medicines. However, such the small increased risk could be reduced by appropriate patient selection and exclusion, including a requirement for periodic review of the efficacy and safety of the individual patient’s treatment.It is advised for physicians, pharmacists and other health professionals:
  1. not to prescribe these medicines in patients with current or a history of bladder cancer or in patients with uninvestigated macroscopic haematuria.
  2. risk factors for bladder cancer should be assessed before initiating pioglitazone treatment.
  3. In light of age-related risks, the balance of benefits and risks should be considered carefully both before initiating and during treatment in the elderly.
  4. prescribers should review the treatment of patients on pioglitazone after three to six months (and regularly afterwards) to ensure that only patients who are deriving sufficient benefit continue to take it.
  5. prescribers are advised to carefully select patients and monitor response to treatment.
     

           參考資料/References and websites：

             https://www.fda.gov/Drugs/DrugSafety/ucm263320.htm

             https://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2011/07/news_detail_001311.jsp&murl=menus/news_and_events/news_and_events.jsp&mid=WC0b01ac058004d5c1