FDA批准新型布洛芬/法莫替丁复方制剂用于治疗关节炎症状

美国食品药品管理局(FDA)已批准复方片剂—Duexis[布洛芬/法莫替丁(800 mg/26.6 mg)]用于缓解类风湿性关节炎和骨关节炎的症状和体征、同时降低上消化道溃疡风险。据生产商称，布洛芬已被证实兼具抗炎和止痛双重特性，而法莫替丁可减少能导致胃和十二指肠溃疡的胃酸分泌。据认为，将布洛芬与法莫替丁制成复方制剂，可在不改变布洛芬止痛和抗炎性能的情况下提高其消化道安全性。该药已于2011年4月份被批准上市。

Duexis的相关研究涉及1500多例存在中重度疼痛或关节炎的患者。一项核心试验的主要终点是在6个月的治疗期内胃溃疡发病率降低。另一项核心研究的主要终点是在6个月的治疗期内上消化道溃疡的发病率降低。在第一项研究中，接受Duexis治疗者的胃溃疡发病率较布洛芬单药治疗组显著降低(8.7% vs 17.6%)；在第二项研究中，接受Duexis治疗者的上消化道溃疡发病率相对于布洛芬单药治疗组显著降低(10.5% vs 20.0%)。

在这些研究中，接受Duexis治疗的患者最常见的不良反应(发生率≥1%，且高于布洛芬单药治疗组)是恶心、腹泻、便秘、上腹痛以及头痛。总体上，两项核心研究中接受Duexis治疗或布洛芬单药治疗的患者因不良事件导致的停药率相似。

Duexis不宜用于在服用阿司匹林或其他非甾体抗炎药(NSAID)之后出现哮喘、荨麻疹或过敏反应的患者。在这类患者中已有服用NSAID导致重度、罕见、致死性过敏反应的报道。Duexis禁用于治疗冠脉旁路移植术围手术期疼痛。另外，Duexis也不宜用于对其他H2受体拮抗剂有过敏史的患者。

许多骨关节炎和类风湿性关节炎患者因为长期使用非甾体抗炎剂引起上消化道溃疡，Duexis 为他们提供了新的选择。

DUEXIS

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Duexis Approved To Relieve Symptoms of Arthritis, Reduce Risk for GI Ulcers

The FDA approved Duexis (ibuprofen and famotidine) tablets for the relief of the symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcer. 

The FDA has approved Horizon Pharma, Inc’s Duexis (ibuprofen and famotidine) for the relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal (GI) ulcer. In clinical trials, upper GI ulcer was defined as gastric and/or duodenal ulcers in patients who were already taking ibuprofen for these indications.1

An estimated 46 million Americans are affected by arthritis, and by 2030, this prevalence is expected to rise by 40%, to 67 million individuals. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are effective pain relief agents, GI side effects often limit their use and may lead to serious complications.2 The patients enrolled in the clinical trials for Duexis were primarily younger than 65 years and had no prior history of GI ulcer. Clinical trials did not last longer than 6 months.1

Pharmacology/Pharmacokinetics

As with other NSAIDs, the exact mechanism of ibuprofen is unknown. It is believed to exert its analgesic and antipyretic effects through prostaglandin synthetase inhibition. Famotidine inhibits gastric acid secretion through competitive inhibition of histamine H2 -receptors.

The elimination half-life of famotidine is closely related to creatinine clearance; patients with a creatinine clearance less than 50 mL/min should not be given Duexis. The effects of gender, age, and hepatic impairment on the pharmacokinetics of Duexis have not been studied.1

Dosing and Administration

Duexis should be given as 1 tablet (ibuprofen 800 mg/famotidine 26.6 mg) orally 3 times a day. The tablet should be swallowed whole and never cut, chewed, crushed, or divided.1

Clinical Trials

Duexis was evaluated in 2 multicenter, double-blind, active-controlled, randomized 24-week trials. Patients received either Duexis or ibuprofen 800 mg in approximately a 2:1 ratio.1 The first trial showed a statistically significant reduction in the incidence of gastric ulcers in patients using Duexis (8.7%) compared with patients using ibuprofen alone (17.6%). The second trial showed a statistically significant reduction in the incidence of upper GI ulcers in patients using Duexis (10.5%) compared with patients using ibuprofen alone (20.0%).2

Contraindications, Warnings, and Precautions

Duexis carries the following boxed warning:

• NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which may be fatal. This risk may increase with duration of treatment and in patients with cardiovascular disease or risk factors for cardiovascular disease.

• Duexis is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft surgery (CABG).

• NSAIDs cause an increased risk of serious GI adverse reactions, such as bleeding, ulceration, and perforation of the stomach or intestines. These reactions may occur at any time, without warning symptoms, and may be fatal. Elderly patients are at greater risk.

Duexis is contraindicated in patients with a history of asthma, urticaria, or allergic reaction after taking aspirin or other NSAIDs, during the perioperative period of CABG surgery, in pregnant patients at 30 or more weeks’ gestation, and in patients with a known hypersensitivity to other H2 -receptor blockers.

Duexis should be used cautiously in patients with hypertension, congestive heart failure, or edema. Discontinue Duexis if bleeding, anaphylaxis, or serious skin reactions occur. Long-term use of NSAIDs can lead to renal injury. Discontinue Duexis if abnormal liver tests persist or worsen, if clinical signs and symptoms of liver disease occur, or if systemic manifestations occur. Use caution when concomitantly administering Duexis and the following medications: warfarin, aspirin, angiotensin converting enzyme inhibitors, diuretics, lithium, methotrexate, selective serotonin inhibitors, and cholestyramine. The most common adverse reactions (≥1% and greater than ibuprofen alone) are nausea, diarrhea, constipation, upper abdominal pain, and headache.2