FDA批准首款羟考酮/对乙酰氨基酚复方药物缓释制剂
美国FDA批准首款由羟考酮和对乙酰氨基酚组成的复方药物缓释制剂(Xartemis XR, Mallinckrodt公司)，本品药物之前被称为MNK-795，用于急性疼痛严重到需要阿片类治疗药物的患者，及用于对替代药物无效、无耐受性或否则无法充分控制疼痛的患者。
该公司在3月12日发布的一份声明中指出，这款药物含有速释和缓释成分，可以让疼痛在一小时内得到缓解，每天用药两次。这次的批准主要基于在拇囊炎切除术后疼痛模型中实施的一项3期临床试验的结果。试验结果在2013年秋天的PAINWeek会议期间发布。新复方药物达到了试验的主要终点，与安慰剂相比，从基线值始超过48小时，显示对疼痛分数具有临床意义上的明显改善。
新制剂利用了Mallinckrodt公司的专利技术，包括设计、配方、药代动力学和释放特点以及Depomed公司先进的Acuform给药技术。除了安全性研究，Mallinckrodt公司还用这款缓释复方产品做了广泛的试验室检测和人滥用倾向研究。
该公司称，“虽然Xartemis XR获批的标签未包含防滥用语言，但Mallinckrodt会继续与FDA密切合作，以得到更多防滥用特征数据。”
羟考酮是管制药物列表II中的一款药物，可使患者和其他使用者暴露于阿片类药物成瘾、滥用和误用的风险之中，会导致过量和死亡。在开具Xartemis XR处方之前要评估每位患者的风险，定期监控所有患者的行为或症状的发展。
XARTEMIS XR CII
 
Pharmacological Class:
Opioid + analgesic.
 
Active Ingredient(s):
Oxycodone HCl, acetaminophen 7.5mg/325mg; bilayer ext-rel tabs.
 
Company
Mallinckrodt, Inc.
 
Indication(s):
 
Acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate. Limitations of use: reserve for use in patients for whom alternative treatment options (eg, non-opioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate.
 
Pharmacology:
 
Oxycodone is an opioid agonist and acts relatively selective for the mu receptor to produce analgesia. Acetaminophen is a non-opioid, non-salicylate analgesic and antipyretic. The mechanism by which acetaminophen exerts its therapeutic effect for analgesia is unknown. The antipyretic effect of acetaminophen is accomplished by inhibiting endogenous pyrogen action on the hypothalamic heat-regulating centers.
 
Clinical Trials:
 
The efficacy of Xartemis XR was eva luated in a multi-center, randomized, double-blind, placebo-controlled, parallel arm, multi-dose clinical trial in patients with acute pain following a unilateral first metatarsal bunionectomy. A total of 303 subjects with a mean age of 43 (range: 18–73) years, meeting criteria for randomization (pain intensity ≥4 on a 0–10 numerical pain rating scale) and receiving a fixed-dose of 2 tablets of Xartemis XR or placebo every 12 hours over 48 hours were randomized. There were 36 early discontinuations (9% from Xartemis XR, 13% from placebo). Patients were allowed to use ibuprofen 400mg every 4 hours as needed for rescue medication.
 
Mean baseline pain intensity scores were 6.2 in the Xartemis XR group (range: 4–10) and 6.0 in the placebo group (range: 1–10). Approximately 85% in the Xartemis XR group (n=150) and 98% in the placebo group (n=153) took rescue medication at least once for pain management during the 48 hours after the first dose. Median rescue medication use was 2 doses for Xartemis XR-treated subjects and 4 doses for placebo-treated subjects over the 48 hours; rescue medication was used by <50% of the Xartemis XR-treated patients after the first dose interval. Pain intensity was recorded at 2, 4, 8, and 12 hours after each dose, with additional recordings at 15, 30, 45, 60, and 90 minutes after the first dose. The median time to onset of pain relief was <1 hour for Xartemis XR. The primary endpoint was the summed pain intensity difference (change in pain from baseline) over 48 hours (SPID48), which demonstrated improvement in pain from baseline for the Xartemis XR group as compared to placebo.
 
Legal Classification:
 
CII
 
Adults:
 
Swallow whole, one tab at a time. ≥18yrs: individualize. Opioid-na?ve: 2 tabs every 12hrs; may give 2nd dose as early as 8hrs after initial dose if analgesia required at that time. Give subsequent doses of 2 tabs every 12hrs. Max acetaminophen dose: 4g/day. When discontinuing, use gradual downward titration dose of 50% every 2–4 days. Hepatic or renal impairment: initially 1 tab and adjust dose as needed.
 
Children:
 
<18yrs: not established.
 
Contraindication(s):
 
Significant respiratory depression. Acute or severe bronchial asthma or hypercarbia. Known or suspected paralytic ileus.
 
Warnings/Precautions:
 
Not interchangeable with other oxycodone/acetaminophen products. Abuse potential. Life-threatening respiratory depression; monitor first 24–72hrs during initiation of therapy and following dose increases. Accidental ingestion may cause fatal overdose (esp. in children). Increased risk of hepatotoxicity with underlying liver disease, concomitant alcohol, acetaminophen doses >4g/day or involving >1 acetaminophen-containing product. COPD, cor pulmonale, or decreased respiratory reserve, hypoxia, hypercapnia; consider alternative non-opioid analgesics. Head injury. Increased intracranial pressure. Shock. Volume depletion. Difficulty swallowing. Underlying GI disorders (eg, small GI lumen). Post-op patients; monitor for decreased bowel motility. Acute abdominal conditions. Biliary tract disease. Acute pancreatitis. Avoid abrupt cessation. Reeva luate periodically. Drug abusers. Acute alcoholism. Hepatic or renal impairment. Elderly. Cachectic. Debilitated. Pregnancy (Cat. C); potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.
 
Interaction(s)
 
Avoid concomitant other acetaminophen-containing drugs. Potentiation with alcohol, or other CNS depressants (eg, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids); monitor and consider reducing doses. May potentiate skeletal muscle relaxants. During or within 14 days of MAOIs: not recommended. May be potentiated by CYP3A4 inhibitors (eg, macrolides, azole antifungals, protease inhibitors); if needed, monitor and consider dose adjustments. Possibly potentiated by CYP2D6 inhibitors (eg, amiodarone, quinidine, antidepressants). May be antagonized by CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin) or mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol, buprenorphine); monitor and adjust. Paralytic ileus may occur with anticholinergics.
 
Adverse Reaction(s)
 
Nausea, dizziness, headache, vomiting, constipation, somnolence; orthostatic hypotension, respiratory or CNS depression, hepatotoxicity; rare: serious skin reactions or anaphylaxis; discontinue if occurs.
 
How Supplied:
 
ER tabs—100
 
LAST UPDATED:
 
5/9/2014