Kvine 2010-3-16 12:41
FDA核准緩釋型hydromorphine用於慢性疼痛
作者：Yael Waknine
出處：WebMD醫學新聞
March 3, 2010 — 美國食品藥物管理局（FDA）已經核准hydromorphine HCl緩釋錠（Exalgo，Combinato Rx有限公司）用於治療可耐受鴉片類藥物，需要長期使用持續的、定時的鴉片類止痛藥物病患，處理中重度疼痛。
這個一天使用一次的劑型使用專利滲透壓運送系統（Oros Push-Pull）提供持續釋放hydromorphine，因此避免了與立即釋放產品有關的波峰、波谷效應。
FDA根據一項為期12週的第三期臨床研究，收納了268位可以耐受鴉片類藥物病患，這些有慢性中重度下背疼痛患者被隨機分派接受持續釋放型hydromorphine或安慰劑。
結果顯示，相較於安慰劑，緩釋劑型hydromorphine（平均劑量每天37.8 mg；範圍從每天12-64 mg）在降低平均疼痛程度上，與試驗前有顯著差異，疼痛程度以病患日期進行11級分李克式數字評分（P<0.0001）。
研究中最常報告的不良事件與鴉片類藥物的安全性資訊相符，最常見的（>10%）包括便秘、噁心、嘔吐、嗜睡、頭痛與頭暈。
因為hydromorphine被認為與濫用及誤用有關，該緩釋劑型根據風險評估及降低策略，包括開方者、藥局與病患需要註冊的限制分配系統後核准。這項計畫強調必須要臨床醫師與藥師提供衛教，以及有關使用hydromorphine伴隨著風險諮詢。
緩釋劑型的hydromorphine建議劑量為每天8-64 mg；因為潛在致命劑量的風險，錠劑應該整顆吞服，不可以破壞、嚼碎、溶解、壓破或是用於注射。
緩釋劑型hydromorphine應該留給能夠耐受鴉片類藥物的慢性疼痛病患，定義為那些每天需要60 mg口服morphine的病患（或是其他鴉片類藥物相等劑量）持續一個星期以上。可以耐受非鴉片類藥物病患、或是使用於急性、術後或是間歇性疼痛可能造成潛在致命的呼吸抑制作用。
同時投予其他中樞神經系統抑制藥物以及hydromorphine對於呼吸抑制作用、低血壓、嚴重鎮靜作用甚至昏迷有加乘性作用。當hydromorphine與其他鴉片類藥物、鎮靜安眠藥物、安眠藥物、安神藥物、全身麻醉劑、phenothiazine類藥物、骨骼肌鬆弛藥物、酒精或是其他中樞神經抑制劑一起使用時，建議大量降低其中一種或是兩種藥物劑量。
緩釋劑型hydromorphine不應該使用於14天內使用單胺氧化酶或是患有顯著肺功能受損病患、癱瘓性腸絞痛、腸胃道狹窄/阻塞、或是已知對含有亞硫酸鹽藥物過敏的病患。
FDA Approves Extended-Release Hydromorphone for Chronic Pain
By Yael Waknine
Medscape Medical News
March 3, 2010 — The US Food and Drug Administration (FDA) has approved hydromorphone HCl extended-release tablets (Exalgo, CombinatoRx, Inc) for the management of moderate to severe pain in opioid-tolerant patients requiring continuous, around-the-clock opioid analgesia for an extended period.
The once-daily formulation uses a proprietary osmotic delivery system (Oros Push-Pull) to provide a steady release of hydromorphone, thereby avoiding the peaks and troughs associated with immediate-release products.
FDA approval was based on data from a 12-week phase 3 clinical trial in which 268 opioid-tolerant patients with chronic moderate-to-severe low back pain were randomly assigned to receive extended-release hydromorphone or placebo.
Results showed that extended-release hydromorphone (mean dose, 37.8 mg/day; range, 12 - 64 mg/day) was significantly more effective than placebo for reducing mean pain intensity from baseline, as measured using an 11-point Likert numerical rating scale obtained from patient diaries (P < .0001).
Adverse events most commonly reported in the study were consistent with the safety profile for opioids and most commonly (>10%) included constipation, nausea, vomiting, somnolence, headache, and dizziness.
Because hydromorphone is subject to abuse and misuse, the extended-release product was approved with a risk evaluation and mitigation strategy that includes a restricted distribution program requiring registration of prescribers, pharmacies, and patients. The program emphasizes the need for clinician and pharmacist education and patient counseling regarding the attendant risks of hydromorphone therapy.
The recommended dose of extended-release hydromorphone is 8 to 64 mg daily; because of the risk for a potentially fatal dose, tablets should be swallowed whole and not broken, chewed, dissolved, crushed, or injected.
Extended-release hydromorphone should be reserved for use in opioid-tolerant patients with chronic pain, defined as those requiring 60 mg oral morphine daily (or an equianalgesic dose of another opioid) for a week or longer. Use in non-opioid-tolerant patients or for acute, postoperative, or intermittent pain may cause potentially fatal respiratory depression.
Coadministration of other central nervous system depressants with hydromorphone has an additive effect on the risk for respiratory depression, hypotension, profound sedation, and coma. When hydromorphone is administered in conjunction with other opioids, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, skeletal muscle relaxants, alcohol, or other central nervous system depressants, significant dose reduction of one or both agents is advised.
Extended-release hydromorphone should not be used within 14 days of monoamine oxidase inhibitor therapy or in patients with significantly impaired pulmonary function, paralytic ileus, narrowed/obstructive gastrointestinal tract, or known hypersensitivity to sulfite-containing medications.