_______________________________________________________________________________________________ HIGHLIGHTS OF PRESCRIBING INFORMATION
The highlights do not include all the information needed to u
Caldolor safely and effectively.
See full prescribing information for Caldolor.mxm
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CALDOLOR (ibuprofen) Injection, for intravenous u Initial U.S. Approval: 1974
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 increa the risk of rious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk may increa with duration of u. (5.1) • Caldolor is contraindicated for the treatment of peri-operative pai
n in the tting of coronary artery bypass graft (CABG) surgery. (4.3, 5.1) Gastrointestinal Risk • NSAIDs increa the risk of rious gastrointestinal (GI) adver 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. (5.2) -----------------------------INDICATIONS AND USAGE-------------------------- Caldolor is an NSAID indicated in adults for the: • Management of mild to moderate pain (1.1) • Management of moderate to vere pain as an adjunct to opioid analgesics (1.1) • Reduction of fever (1.2) -------------------------DOSAGE AND ADMINISTRATION--------------------- • Pain: 400 mg to 800 mg intravenously over 30 minutes every 6 hours as necessary. (2.1) • 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. (2.2) • Patients must be well hydrated before Caldolor administration. • Caldolor must be diluted before administration. (2.3) ------------------------DOSAGE FORMS AND STRENGTHS------------------- Vials: 400 mg/4 mL or 800 mg/8 mL (3) -------------------------------CONTRAINDICATIONS------------------------------ • Known hypernsitivity to ibuprofen or other NSAIDS (4.1) • Asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs (4.2) • U during the peri-operative period in the tting of coronary artery bypass graft (CABG) surgery (4.3, 5.1) -------------------------WARNINGS AND PRECAUTIONS----------------------• Serious and potentially fatal CV thrombotic events: U lowest effective do of Caldolor for shortest possible duration. (5.1)
• Serious and potentially fatal GI reactions: U lowest effective do of Caldolor for shortest possible duration. U with caution in patients with prior history of ulcer dia or GI bleeding. (5.2) • Hepatic effects: Range from transamina elevations to liver failure. Discontinue Caldolor immediately if abnormal liver tests persist or worn. (5.3, 5.15) • Hypertension: Can occur with NSAID treatment. Monitor blood pressure cloly during treatment with Caldolor. (5.4) • Congestive heart failure and edema: Fluid retention and edema can occur with NSAID treatment. U Caldolor with caution in patients with fluid retention or heart failure. (5.5) • Renal effects: Long-term administration of NSAIDs can result in renal papillary necrosis and other renal injury. U Caldolor with caution in patients at risk (e.g., the elderly, tho with renal impairment, heart failure, liver impairment, and tho taking diuretics or ACE inhibitors. (5.6) • 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. (5.7, 5.12) • 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. (5.8) -------------------------------ADVERSE REACTIONS------------------------------ The most common adver reactions are naua, fla
淘汰的英文tulence, 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
v/medwatch.
---------------------------------DRUG INTERACTIONS----------------------------
• ACE-inhibitors: NSAIDs may diminish the antihypertensive effect of
ACE-inhibitors. (7.3) • Aspirin: Concomitant administration of ibuprofen and aspirin is not
generally recommended becau of the potential for incread adver
effects. (7.1) --------------------------USE IN SPECIFIC POPULATIONS--------------------- • Pregnancy: Avoid u after 30 weeks gestation becau premature closure of the ductus arteriosus in the fetus may occur. (8.1) • Nursing Mothers: U with caution as it is not known if ibuprofen is excreted in human milk. (8.3) • Pediatric U: Safety and effectiveness not established in patients less than 17 years of age. (8.4) See 17 for PATIENT COUNSELING INFORMATION Revid: 06/2009
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: RISK OF SERIOUS CARDIOVASCULAR AND
巴西世界杯吉祥物GASTROINTESTINAL EVENTS 1 INDICATIONS AND USAGE 5.8 Serious Skin Reactions
1.1 Analgesia (Pain) 5.9 Pregnancy 1.2 Antipyretic (Fever)
5.10 Masking Inflammation and Fever 2 DOSAGE AND ADMINISTRATION
5.11 Hematological Effects 2.1 Analgesia (Pain) 5.12 Preexisting Asthma 2.2 Antipyretic (Fever) 5.13 Ophthalmological Effects 3 DOSAGE FORMS AND STRENGTHS 5.14 Aptic Meningitis 4 CONTRAINDICATIONS 5.15 Monitoring 4.1 Hypernsitivity 6 ADVERSE REACTIONS 4.2 Asthma and Allergic Reactions
6.1 Clinical Studies Experience
4.3 Coronary Artery Bypass Graft (CABG) 7 DRUG INTERACTIONS
5 WARNINGS AND PRECAUTIONS 7.1 Aspirin 5.1 Cardiovascular Thrombotic Events 7.2 Anticoagulants 5.2 Gastrointestinal Effects: Risk of Ulceration, Bleeding and
7.3 ACE Inhibitors Perforation
7.4 Diuretics 5.3 Hepatic Effects 7.5 Lithium 5.4 Hypertension 7.6 Methotrexate 5.5 Congestive Heart Failure and Edema 7.7 H-2 Antagonists 5.6 Renal Effects 8 USE IN SPECIFIC POPULATIONS 5.7 Anaphylactoid Reactions
8.1 Pregnancy
8.2 Labor and Delivery
8.3
Nursing
mothers
8.4 Pediatric u 14
12.1 Mechanism of action
12.3
Pharmacokinetics CLINICAL STUDIES
10
11
12 8.5 Geriatric u
OVERDOSAGE
DESCRIPTION
CLINICAL PHARMACOLOGY
16
17
14.1 Analgesia (Pain)
14.2
Antipyretic
(Fever)
HOW SUPPLIED/STORAGE AND HANDLING
PATIENT COUNSELING INFORMATION
*Sections or subctions omitted from the Full Prescribing Information are not listed.
FULL PRESCRIBING INFORMATION
WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS
Cardiovascular Risk
• Non-steroidal anti-inflammatory drugs (NSAIDs) may increa the
risk of rious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increa
with duration of u. Patients with cardiovascular dia or risk factors for cardiovascular dia may be at greater risk [e Warnings and Precautions (5.1)].
• Caldolor is contraindicated for the treatment of peri-operative pain
in the tting of coronary artery bypass graft (CABG) surgery [e Contraindications (4.3) and Warnings and Precautions (5.1)]. Gastrointestinal Risk
• NSAIDs increa the risk of rious gastrointestinal (GI) adver events including bleeding, ulceration, and perforation of the stomach
or intestines, which can be fatal. The events can occur at any time during u and without warning symptoms. Elderly patients are at greater risk for rious gastrointestinal events [e Warnings and Precautions (5.2)].
1 INDICATIONS AND USAGE
1.1 Analgesia (Pain)
Caldolor is indicated in adults for the management of mild to moderate pain and the management of moderate to vere pain as an adjunct to opioid analgesics.
1.2 Antipyretic (Fever)
Caldolor is indicated for the reduction of fever in adults.
2 DOSAGE AND ADMINISTRATION
U the lowest effective do for the shortest duration consistent with individual patient treatment goals [e Warnings and Precautions (5)]. After obrving the respon to initial therapy with Caldolor, the do and frequency should be adjusted to suit an individual patient's needs. Do not exceed 3200 mg total daily do.
To reduce the risk of renal adver reactions, patients must be well hydrated prior to administration of Caldolor.
2.1 Analgesia (Pain)
Administer 400 mg to 800 mg intravenously every 6 hours as necessary. Infusion time must be no less than 30 minutes.
2.2 Antipyretic (Fever)
Administer 400 mg intravenously, followed by 400 mg every 4 to 6 hours or 100-200 mg every 4 hours as necessary. Infusion time must be no less than 30 minutes.
2.3 Preparation and Administration
Caldolor must be diluted prior to intravenous infusion. Dilute to a final concentration of 4 mg/mL or less. Appropriate diluents include 0.9% Sodium Chloride Injection USP (normal saline), 5% Dextro Injection USP (D5W), or Lactated Ringers Solution.
• 800 mg do: Dilute 8 mL of Caldolor in no less than 200 mL of diluent.
• 400 mg do: Dilute 4 mL of Caldolor in no less than 100 mL of diluent.
Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. If visibly opaque particles, discoloration or other foreign particulates are obrved, the solution should not be ud.
Diluted solutions are stable for up to 24 hours at ambient temperature (approximately 20 to 25° C) and room lighting.
Infusion time must be no less than 30 minutes.
3 DOSAGE FORMS AND STRENGTHS
Caldolor is available as a 400 mg/4 mL single-do vial (100 mg/mL) and 800 mg/8 mL single-do vial (100 mg/mL).
4 CONTRAINDICATIONS
4.1 Hypernsitivity
Caldolor is contraindicated in patients with known hypernsitivity (e.g., anaphylactoid reactions and rious skin reactions) to ibuprofen. [e Warnings and Precautions (5.7, 5.8)]
4.2 Asthma and Allergic Reactions
Caldolor is contraindicated in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal anaphylactic-like reactions to NSAIDs have been reported in such patients [e Warnings and Precautions (5.7, 5.12)].
4.3 Coronary Artery Bypass Graft (CABG)
Caldolor is contraindicated for the treatment of perioperative pain in the tting of coronary artery bypass graft (CABG) surgery [e Warnings and Precautions (5.1)].
indispensable
5 WARNINGS AND PRECAUTIONS
5.1 Cardiovascular Thrombotic Events
Clinical trials of veral COX-2 lective and nonlective NSAIDs of up to three years’ duration have shown an incread risk of rious cardiovascular (CV) thrombotic events, myocardial infarction and stroke, which can be fatal. All NSAIDs, both COX-2 lective and nonlective, may have a similar risk. Patients with known CV dia or risk factors for CV dia may be at greater risk. To minimize the potential risk for an adver CV event in patients treated with an NSAID, u the lowest effective do for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the abnce of previous CV symptoms. Patients should be informed about the signs and/or symptoms of rious CV events and the steps to take if they occur.
homemadeTwo large, controlled clinical trials of a COX-2 lective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an incread incidence of myocardial infarction and stroke [e Contraindications (4.3)].
There is no consistent evidence that concurrent u of aspirin mitigates the incread risk of rious
CV thrombotic events associated with NSAID u. The concurrent u of aspirin and an NSAID does increa the risk of rious gastrointestinal (GI) events [e Warnings and Precautions (5.2)].
5.2 Gastrointestinal Effects: Risk of Ulceration, Bleeding, and Perforation
NSAIDs, including ibuprofen, can cau rious GI adver events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. The rious adver events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a rious upper GI adver event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caud by NSAIDs occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. The trends continue with longer duration of u, increasing the likelihood of developing a rious GI event at some time
during the cour of therapy. However, even short-term therapy is not without risk.
Prescribe NSAIDs, including Caldolor, with extreme caution in tho with a prior history of ulcer dia or GI bleeding. Patients with a prior history of peptic ulcer dia and/or GI bleeding who u NSAIDs have a greater than 10fold incread risk for developing a GI bleed compared to treated
patients with neither of the risk factors. Other factors that increa the risk of GI bleeding in patients treated with NSAIDs include concomitant u of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, u of alcohol, older age, and poor general health status. Most reports of spontaneous fatal GI events are in elderly or debilitated patients, and therefore special care should be taken in treating this population.
To minimize the potential risk for an adver GI event in patients treated with an NSAID, u the lowest effective do for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a rious GI event is suspected. This should include discontinuation of the NSAID until a rious GI adver event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.
5.3 Hepatic Effects
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, including ibuprofen. The laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more t
imes the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cas of vere hepatic reactions have been reported, including jaundice, fulminant hepatitis, liver necrosis and hepatic failure, some with fatal outcomes. A patient with symptoms and/or signs suggesting liver dysfunction, or with abnormal liver test values, should be evaluated for evidence of the development of a more vere hepatic reaction while on therapy with ibuprofen. If clinical signs and symptoms consistent with liver dia develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), ibuprofen should be discontinued.
5.4 Hypertension
NSAIDs, including ibuprofen, can lead to ont of new hypertension or worning of preexisting hypertension, either of which may contribute to the incread incidence of CV events. U NSAIDs, including ibuprofen, with caution in patients with hypertension. Monitor blood pressure cloly during the initiation of NSAID treatment and throughout the cour of therapy.
Patients taking ACE inhibitors, thiazides, or loop diuretics may have impaired respon to the therapies when taking NSAIDs.
5.5 Congestive Heart Failure and Edema
Fluid retention and edema have been obrved in some patients taking NSAIDs. U Caldolor with caution in patients with fluid retention or heart failure.
5.6 Renal Effects
U caution when initiating treatment with Caldolor in patients with considerable dehydration.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been en in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In the patients, administration of an NSAID may cau a do dependent reduction in prostaglandin formation and, condarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are tho with impaired renal function, heart failure, liver dysfunction, tho taking diuretics or ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the u of Caldolor in patients with advanced renal dia. If Caldolor therapy must be initiated in patients with advanced renal dia, cloly monitor the patient’s renal function.
5.7 Anaphylactoid Reactions
As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to ibuprofen. CALDOLOR is contraindicated in patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit vere, potentially fatal bronchospasm after taking aspirin or other NSAIDs [e Contraindications (4.2)].
5.8 Serious Skin Reactions
NSAIDs, including ibuprofen, can cau rious skin adver reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. The rious events may occur without warning. Inform patients about the signs and symptoms of rious skin manifestations, and to discontinue Caldolor at the first appearance of skin rash or any other sign of hypernsitivity.
5.9 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 [e U in Specific Populations (8.1)].
5.10 Masking Inflammation and Fever
The pharmacological activity of ibuprofen in reducing fever and inflammation may diminish the utility of the diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
5.11 Hematological Effects
Caldolor must be diluted prior to u. Infusion of the drug product without dilution can cau hemolysis [e Dosage and Administration (2.3)].
Anemia may occur in patients receiving NSAIDs, including ibuprofen. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect on erythropoiesis. In patients on long-term treatment with NSAIDs, including ibuprofen, check hemoglobin or hematocrit if they exhibit any signs or symptoms of anemia or blood loss.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effects on platelet function are less vere quantitatively, of shorter duration, and
reversible. Carefully monitor patients who may be adverly affected by alterations in platelet function, such as tho with coagulation disorders or patients receiving anticoagulants.
5.12 Preexisting Asthma
6 Patients with asthma may have aspirin-nsitive asthma.
The u of aspirin in patients with aspirin-nsitive asthma has been associated with vere bronchospasm, which can be fatal. Since cross-reactivity between aspirin and NSAIDs has been reported in such aspirin-nsitive patients, including bronchospasm, Caldolor is contraindicated in patients with this form of aspirin nsitivity and should be ud with caution in all patients with preexisting asthma.
谷歌英文搜索5.13 Ophthalmological Effects
Blurred or diminished vision, scotomata, and changes in color vision have been reported with oral ibuprofen. Discontinue ibuprofen if a patient develops such complaints, and refer the patient for an ophthalmologic examination that includes central visual fields and color vision testing.
5.14 Aptic Meningitis
Aptic meningitis with fever and coma has been obrved
in patients on oral ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue dias, it has been reported in patients who do not have underlying chronic dia. If signs or symptoms of meningitis develop in a patient on ibuprofen, give consideration to whether or not the signs or symptoms are related to ibuprofen therapy.
5.15 Monitoring
Becau rious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding.
Patients on long-term treatment with NSAIDs should have CBC and chemistry profiles checked periodically. If clinical signs and symptoms consistent with liver or renal dia develop, systemic manifestations occur (e.g., eosinophilia, rash), or abnormal liver tests persist or worn, discontinue Caldolor.
ADVERSE REACTIONS
The following rious adver reactions are discusd elwhere in the labeling:
• Cardiovascular thrombotic events [e Boxed Warning and Warnings and Precautions (5.1)]
• G astrointestinal effects [e Boxed Warning and Warnings and Precautions (5.2)]
• H epatic
effects
[e Warnings and Precautions (5.3)] • Hypertension [e Warnings and Precautions (5.4)]
• Congestive heart failure and edema [e Warnings and Precautions (5.5)]
• Renal effects [e Warnings and Precautions (5.6)]
• Anaphylactoid reactions [e Warnings and Precautions (5.7)]
• Serious skin reactions [e Warnings and Precautions
(5.8)]
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The most common adver reactions reported in clinical studies are naua, flatulence, vomiting, and headache.
The most common reason for discontinuation due to adver events in controlled trials of Caldolor is pruritus (<1%).
6.1 Clinical Studies Experience
Becau clinical trials are conducted under widely varying conditions, adver reaction rates obrved in the clinical trials of a drug cannot be compared directly to rates in the clinical trials of another drug and may not reflect the rates obrved in practice.
During clinical development, 560 patients were expod to Caldolor, 438 in pain and 122 with fever. In the pain studies, Caldolor was started intra-operatively and administered at a do of 400 mg or 800 mg every six hours for up to three days. In the fever studies, Caldolor was administered at dos of 100 mg, 200 mg, or 400 mg every four or six hours for up to 3 days.
The most frequent type of adver reaction occurring with oral ibuprofen is gastrointestinal.
Pain Studies
The incidence rates of adver reactions listed in the following table were derived from multicenter, controlled clinical studies in post-operative patients comparing Caldolor to placebo in patients also receiving morphine as needed for postoperative pain.
Table 1: Post-operative Patients with Adver Reactions Obrved in ≥ 3% of Patients in any Caldolor Treatment Group in Pain Studies*
Event
Caldolor
Placebo
(N=287)
400 mg
(N=134)
800 mg
(N=304)
Any Reaction 118 (88%) 260 (86%) 258 (90%)
Naua 77 (57%) 161 (53%) 179 (62%) Vomiting 30 (22%) 46 (15%) 50 (17%) Flatulence 10 (7%) 49 (16%) 44 (15%) Headache 12 (9%) 35 (12%) 31 (11%) Hemorrhage 13 (10%) 13 (4%) 16 (6%) Dizziness 8 (6%) 13 (4%) 5 (2%)
Edema peripheral 1 (<1%) 9 (3%) 4 (1%)
Urinary retention 7 (5%) 10 (3%) 10 (3%) Anemia 5 (4%) 7 (2%) 6 (2%)
Decread hemoglobin 4 (3%) 6 (2%) 3 (1%)
英翻汉在线翻译Dyspepsia 6 (4%)+ 4 (1%) 2 (<1%) Wound hemorrhage 4 (3%) 4 (1%) 4 (1%)
Abdominal discomfort 4 (3%)+ 2
(<1%) 0 Cough 4 (3%)+ 2 (<1%) 1 (<1%)
Hypokalemia 5 (4%) 3 (<1%) 8 (3%)
* All patients received concomitant morphine during the studies.
Fever Studies
Fever studies were conducted in febrile hospitalized patients with malaria and febrile hospitalized patients with varying caus of fever. In hospitalized febrile patients with malaria. The adver reactions obrved in at least two Caldolor-treated patients included abdominal pain and nasal congestion.
In hospitalized febrile patients (all caus), adver reactions obrved in more than two patients in any given treatment group are prented in the table below.
Table 2: Patients with Adver Reactions Obrved in
≥ 3% of Patients in any Caldolor Treatment Group in All-Cau Fever Study
Caldolor
Placebo
N=28 Event
100 mg
N=30
200 mg
N=30
400 mg
N=31
Any Reaction 27 (87%) 25 (83%) 23 (74%) 25 (89%)
Anemia 5 (17%) 6 (20%) 11 (36%) 4 (14%) Eosinophilia 7 (23%) 7 (23%) 8 (26%) 7 (25%)
Hypokalemia 4 (13%) 4 (13%) 6 (19%) 5 (18%)
Hypoproteinemia 3 (10%) 0 4 (13%) 2 (7%)
Neutropenia 2 (7%) 2 (7%) 4 (13%) 2 (7%)
Blood urea incread 0 0 3 (10%) 0
Hypernatremia 2 (7%) 0 3 (10%) 0如何提高语言表达能力
