Generic Name: ibuprofen Date of Approval: June 11, 2009 Company: Cumberland Pharmaceuticals Treatment for: Pain and Fever Caldolor FDA Approves Caldolor The U.S. Food and Drug Administration has approved Caldolor, the first injectable dosage form of the common pain medication ibuprofen, to treat pain and fever. "Injectable ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) are promising pain management options," said Bob Rappaport, M.D., director, Division of Anesthesia, Analgesia and Rheumatology Drug Products in the FDA's Center for Drug Evaluation and Research. "But until now there were only oral forms of most NSAIDs. An injectable ibuprofen product can provide patients with relief from pain and fever when they cannot take oral products." Caldolor will be available for hospital use only. It is approved to be administered in 400 mg to 800 mg doses, over 30 minutes, every 6 hours for acute pain. To treat fever, the drug is approved in a 400 mg dose administered over 30 minutes, followed by 400 mg every 4 to 6 hours, or 100-200 mg every 4 hours, as necessary. In a clinical trial of 319 women who had undergone an elective abdominal hysterectomy, patients were less likely to request morphine for pain on an as-needed basis when administered Caldolor. Caldolor should be used with caution in patients with congestive heart failure, kidney impairment, at risk of blood clots and those who have a prior history of ulcers or gastrointestinal bleeding. When used in such patients, attention to using the lowest effective dose for the shortest time period is important to reduce the risk of serious adverse events. The drug has also been associated with high blood pressure, serious skin reactions, and serious allergic reactions. The most common adverse reactions reported in the controlled clinical trials were nausea, flatulence, vomiting, and headache. Caldolor is manufactured by Cumberland Pharmaceuticals Inc. Nashville, TennSource: FDAHighlights of Caldolor Prescribing InformationThese highlights do not include all the information needed to use Caldolor safely and effectively. See full prescribing information for Caldolor. WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS See full prescribing information for complete boxed warning Cardiovascular Risk Non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk may increase with duration of use. Caldolor is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. Gastrointestinal Risk NSAIDs increase the risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. Events can occur at any time without warning symptoms. Elderly patients are at greater risk. Caldolor Indications and Usage Caldolor is an NSAID indicated in adults for the: Management of mild to moderate pain Management of moderate to severe pain as an adjunct to opioid analgesics Reduction of fever Dosage and AdministrationPain: 400 mg to 800 mg intravenously over 30 minutes every 6 hours as necessary. Fever: 400 mg intravenously over 30 minutes, followed by 400 mg every 4 to 6 hours or 100-200 mg every 4 hours as necessary. Patients must be well hydrated before Caldolor administration. Caldolor must be diluted before administration. Dosage Forms and StrengthsVials: 400 mg/4 mL or 800 mg/8 mL Contraindications Known hypersensitivity to ibuprofen or other NSAIDS Asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs Use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery Warnings and Precautions Serious and potentially fatal CV thrombotic events: Use lowest effective dose of Caldolor for shortest possible duration. Serious and potentially fatal GI reactions: Use lowest effective dose of Caldolor for shortest possible duration. Use with caution in patients with prior history of ulcer disease or GI bleeding. Hepatic effects: Range from transaminase elevations to liver failure. Discontinue Caldolor immediately if abnormal liver tests persist or worsen. Hypertension: Can occur with NSAID treatment. Monitor blood pressure closely during treatment with Caldolor. Congestive heart failure and edema: Fluid retention and edema can occur with NSAID treatment. Use Caldolor with caution in patients with fluid retention or heart failure. Renal effects: Long-term administration of NSAIDs can result in renal papillary necrosis and other renal injury. Use Caldolor with caution in patients at risk (e.g., the elderly, those with renal impairment, heart failure, liver impairment, and those taking diuretics or ACE inhibitors. Anaphylactoid reactions: May occur in patients with the aspirin triad or in patients without prior exposure to Caldolor. Discontinue Caldolor immediately if an anaphylactoid reaction occurs. Serious skin reactions: Include exfoliative dermatitis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis, which can be fatal. Discontinue Caldolor if rash or other signs of local skin reaction occur. Caldolor Adverse Reactions The most common adverse reactions are nausea, flatulence, vomiting, headache, hemorrhage and dizziness (>5%). (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Cumberland Pharmaceuticals Inc. at 1-877-484-2700 or FDA at 1-800-FDA-1088 or . Drug Interactions ACE-inhibitors: NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. Aspirin: Concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential for increased adverse effects. Use in Specific Populations Pregnancy: Avoid use after 30 weeks gestation because premature closure of the ductus arteriosus in the fetus may occur. Nursing Mothers: Use with caution as it is not known if ibuprofen is excreted in human milk. Pediatric Use: Safety and effectiveness not established in patients less than 17 years of age. Patient Counseling Information Patients should be informed of the following information before initiating therapy with an NSAID. Cardiovascular Effects Ibuprofen, like other NSAIDs, may cause serious CV events such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, advise patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, and slurring of speech, and to ask for medical advice when observing any indicative sign or symptoms. Gastrointestinal Effects Ibuprofen, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, advise patients to be alert for the signs and symptoms of ulcerations and bleeding, and to ask for medical advice when observing any indicative signs or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Hepatotoxicity Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flulike" symptoms). Instruct patients to stop therapy with Caldolor and seek immediate medical therapy if any of these occur. Adverse Skin Reactions Ibuprofen, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS and TEN, which may result in hospitalization and even death. Although serious skin reactions may occur without warning, advise patients to be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and to ask for medical advice when observing any indicative sign or symptoms. Advise patients to stop Caldolor immediately if they develop any type of rash, and to contact a physician as soon as possible. Weight Gain and Edema Advise patients to promptly report to their physicians signs or symptoms of unexplained weight gain or edema during treatment with Caldolor. Anaphylactoid Reactions Inform patients of the signs of an anaphylactoid reaction (e.g. difficulty in breathing, swelling of the face or throat). If these occur, therapy should be discontinued and medical therapy initiated. Effects During Pregnancy Starting at 30 weeks gestation, Caldolor and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur. 美国FDA近日首次批准了Caldolor（布洛芬注射剂）用于治疗疼痛与发烧，这是在美国批准的第一个布洛芬注射剂，由Cumberland公司生产。     FDA官员说道：“注射型布洛芬与其它非甾体抗炎药注射剂是一种有前景的疼痛治疗药。但是现在大多数此类药物都为口服药物。布洛芬注射剂可用于减轻那些不能使用口服产品患者的疼痛与发热症状。”     Caldolor的使用剂量为400mg或800mg，经30分钟以上输注，每隔6小时一次用于急性疼痛；用于退烧时，剂量为400mg经30分钟以上输注，如果需要，每4-6小时再给予400m g，可每4小时给予100-200mg剂量。