Ibuprofen Injection Instructions

Approval Date:

Date of revision:

Ibuprofen Injection Instructions

Please read the instructions carefully and use under the guidance of a physician. Use

 

 

 

 

 

 

[Drug Name]

Generic name: Ibuprofen Injection

English name:Ibuprofen Injection

Hanyu Pinyin:Buluofen Zhusheye

[Composition]

The main ingredient of this product is ibuprofen, and the excipients are arginine and water for injection.

Chemical name:α-methyl-4-(< span style="font-family:Times New Roman">2-methylpropyl)phenylacetic acid.

Chemical structure formula:

 

 

 

Molecular Formula:C₁₃H₁₈O₂

Molecular weight:206.28

[Properties] This product is a clear, colorless or almost colorless liquid.

[Indications]

For the treatment of mild to moderate pain in adults and as an adjunct to opioid analgesics for the treatment of moderate to severe pain.

For the antipyretic treatment of fever in adults.

[Specifications]

(1)4ml:0.4g; (2)8ml:0.8g

[Dosage]

Use the lowest effective dose in the shortest dosing cycle based on individualized patient treatment goals.

Dose and dosing frequency should be adjusted to individual patient needs based on the patient’s response to the initiation of therapy, with the maximum daily dose for adults not exceeding3.2g, and to reduce the risk of renal adverse reactions, patients need to be adequately hydrated prior to dosing.

Dosing Instructions:

This product must be diluted before use.

The final use concentration after dilution should not exceed4mg/mL, dilution solution should be 0.9% sodium chloride injection only, not glucose injection.

0.1gDosage: Add this product < 1mlinto not less than100ml. Roman”>100ml of the dilution solution.

0.2g Dose: Add this product2mlto not less than100ml of diluent.

0.4gDosage: Add this product4mlto not less than100ml< span style="font-family:Arial">in the dilution solution.

0.8gDose: Add this product8mlto not less than200ml of diluent.

The suspended particles and discoloration of the original and diluted solution should be observed by naked eye before use , and do not use if emulsion, opaque particles, discoloration or other exogenous particles are found.

Diluted injectable solution at room temperature (20to25℃) and indoor light conditions can be maintained =”font-family:Times New Roman”>24hours stable.

Adult analgesia:

0.4g~0.8g intravenously, as needed every6< span style="font-family:equinox">hourly repeat dosing. Infusion time should be no less than < span style="font-family:Times New Roman">30< span style="font-family:equinox">minutes. Maximum daily dose3.2g.

Adult Fever:

0.4g intravenously, as needed per “font-family:Times New Roman”>4to6as needed “font-family:equinox”>hourly repeat dosing0.4gor every4hourly repeat dosing0.1to0.2g. The infusion time should be no less than 30 minutes. Maximum daily dose3.2g.

[Adverse reactions] According to foreign literature

The most common adverse reactions include nausea, flatulence, vomiting, headache, bleeding, dizziness, the incidence of the above adverse reactions< span style="font-family:Times New Roman">>5%.

Because clinical studies are conducted under different conditions, the incidence of adverse reactions in clinical trials for one drug cannot be directly compared to the incidence of adverse reactions in clinical trials for another drug and may not reflect the actual observed incidence.

Adult patients

Foreign clinical studies that included a total of560patients (analgesia438patients, fever122cases). In the analgesia study, intraoperative ibuprofen injection was given at a dose of 0.4 g or 0.8g per6hourly for 3days. In the fever study, the doses administered were 0.1g, 0.2gor0.4g for every4 or6hourly, administered continuously3day. The most common adverse reaction to oral ibuprofen is a gastrointestinal reaction.

Analgesia studies:

The incidence of adverse reactions listed in the table below is derived from multicenter, controlled clinical studies conducted abroad. These studies evaluated the efficacy of ibuprofen injection for postoperative analgesia in patients receiving concomitant postoperative morphine analgesia on demand, with placebo as a control. Table1:Ibuprofen injection in postoperative pain patients in clinical studiesObserved unadverse reactions (incidence< span style="font-family:Times New Roman">≥3%)*

* All patients in this study were treated with morphine.

Fever study:

Fever studies were conducted in hospitalized patients with malaria and multiple other causes of fever. In febrile inpatients with malaria, adverse reactions including abdominal pain and nasal congestion were observed in at least2 patients treated with ibuprofen injection.

In patients hospitalized with fever (multiple causes), all treatment groups observed2 “font-family:equine”>adverse reactions occurring in more than one case are included in the table below.

Table2: ibuprofen injection in febrile patients in clinical studies observed =”color:black”> of adverse reactions (incidence≥3%)

< span style="font-family:equals">[contraindicated]

Patients with known hypersensitivity reactions (e.g., allergic reactions and severe skin reactions) to the active ingredient and any excipients;

Patients who have induced asthma, urticaria, or allergic-like reactions after taking aspirin or other NSAIDs including it, and severe and sometimes fatal allergic reactions to NSAIDs have been reported in this group of patients.

Contraindicated in coronary artery bypass grafting (CABG) in patients treated perioperatively.

Patients with a history of gastrointestinal bleeding or perforation following the application of NSAIDs.

with active peptic ulcers/bleeding, or patients with previous recurrent ulcers/bleeding.

Patients with severe heart failure.

[Caution]

(1) Cardiovascular thrombotic events

several use selectiveCOX-2 and nonselective NSAIDs have been shown in three-year-long clinical trials to increase serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Based on the available data, it is not clear whether all NSAIDs have a similar risk of cardiovascular thrombotic events. The increase in serious cardiovascular thrombotic events from baseline caused by NSAIDs appears to be similar regardless of whether the patient has known cardiovascular disease or risk factors for that disease. However, the absolute incidence of very serious cardiovascular events was higher in patients with known cardiovascular disease or risk factors due to the elevated baseline rate. Several observational studies have found an increased risk of serious cardiovascular thrombotic events in the first week of early treatment and are consistent with an increased risk of cardiovascular thrombotic events at high doses.

To minimize the potential risk of adverse cardiovascular events in patients treated with NSAIDs, the lowest effective dose is used for the shortest possible duration of therapy. Even in the absence of prior cardiovascular symptoms, physicians and patients should remain vigilant for such events throughout the treatment cycle. Patients should be informed of the symptoms of serious cardiovascular events and what to do if they occur. Patients should be alert for signs and symptoms such as chest pain, shortness of breath, weakness, and slurred speech, and should seek medical help as soon as any of these signs and symptoms occur.

There is no consistent evidence that concomitant aspirin use attenuates the risk of increased serious cardiovascular thrombotic events associated with NSAID use. The combination of aspirin and NSAIDs such as ibuprofen increases the risk of serious gastrointestinal events.

Coronary artery bypass grafting (CABG) after surgery

In two large, controlled clinical studies, patients underwentCABGafter surgery10to14days with selectiveCOX-2 NSAIDs for analgesia were found to increase the incidence of myocardial infarction and stroke, and NSAIDs were contraindicated inCABGperioperative period. CABG

Patients after myocardial infarction

An observational study registered in Denmark showed that patients treated with NSAIDs after myocardial infarction had an increased risk of reinfarction, cardiovascular-related death, and all-cause mortality from the first week after treatment. In the same cohort study, mortality in the first year after myocardial infarction was 20/100patient-years in patients treated with NSAIDs, whereas patients without NSAIDs had a mortality rate of only12/100patient-years. Despite the decline in absolute mortality at one year after myocardial infarction, the increased relative risk of death among patients using NSAIDs has persisted for at least 4years.

Patients with recent myocardial infarction avoid this product unless the expected benefit outweighs the risk of recurrent cardiovascular thrombotic events. If ibuprofen injection is used in patients with a recent myocardial infarction, monitor the patient for symptoms of myocardial ischemia.

(2) Gastrointestinal Bleeding, ulcers and perforations

NSAIDs (including ibuprofen) cause serious gastrointestinal adverse events, including inflammation, bleeding, ulceration, esophageal perforation, gastric perforation, and perforation of the large or small intestine, and can be fatal. These adverse events can occur at any time of treatment with NSAIDs, with or without warning signs, and regardless of whether the patient has a history of adverse gastrointestinal reactions or a history of serious gastrointestinal events. Only one-fifth of patients who experienced a serious upper gastrointestinal adverse event on NSAID therapy were symptomatic. Patients receiving NSAID therapy3to6months, the incidence of resulting upper gastrointestinal ulcers, severe bleeding, or perforation is approximately1%; patients receiving nonsteroidal anti-inflammatory therapy for 1 year. The resulting incidence of upper gastrointestinal ulceration, severe bleeding, or perforation is about 2%to4%. However, even short-term treatments are not without risk.

Risk factors for gastrointestinal bleeding, ulcers, and perforation

Prior ulcers and/or a history of GI bleeding are at a10fold higher risk of developing GI bleeding with NSAIDs than patients without these risk factors :equivocal”> times. Other factors that increase the risk of GI bleeding in patients using NSAIDs include longer-term treatment with NSAIDs, combination of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors, smoking, alcohol consumption, old age, and poor health status. Most post-marketing reports of fatal gastrointestinal events occur in elderly or frail patients. In addition, patients with advanced liver disease and/ or coagulation disorders are at increased risk for gastrointestinal bleeding.

Gastrointestinal risk minimization strategies for patients treated with NSAIDs

–the lowest effective dose in the shortest time; –

–Avoid concurrent use of more than one NSAID;

–Avoid in higher risk patients unless the expected benefit outweighs the increased risk of bleeding. This group of patients, as well as patients with active GI bleeding, should consider alternative therapies to NSAIDs;

–Signs and symptoms of gastrointestinal ulceration and bleeding during NSAID therapy remain Be alert;

–If a serious gastrointestinal adverse event is suspected, immediately initiate evaluation and treatment by Discontinue use of the product until a serious gastrointestinal adverse event is ruled out;

–In combination with low-dose aspirin for prevention of cardiac disease, closely monitor patients for with evidence of gastrointestinal bleeding.

(3) Hepatotoxicity<

In clinical studies reported in patients treated with NSAIDs, approximately1% =”font-family:equivocal”> of patients with ALT orASTvalues are elevated (above the upper limit of normal3fold or more). In addition, rare and sometimes fatal cases of severe liver injury have been reported, including fulminant hepatitis, hepatic necrosis, and liver failure. Up to15% of patients treated with NSAIDs, including ibuprofen, developALTorASTvalues are elevated (less than three times the upper limit of normal). Inform the patient of warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, drowsiness, diarrhea, pruritus, jaundice, right upper abdominal pressure, and flu-like symptoms. If clinical signs and symptoms consistent with liver disease occur, or if systemic manifestations occur (e.g., eosinophilia, rash), discontinue the product immediately and perform a clinical evaluation.

(4) Hypertension< /span>

NSAIDs, including ibuprofen injection, can cause new-onset hypertension or worsen existing hypertension, either of which may lead to an increased incidence of cardiovascular events. The use of NSAIDs in patients taking angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics, or medullary diuretics may affect these The efficacy of antihypertensive drugs.

Patients with hypertension need to have their blood pressure monitored at the beginning and throughout the treatment cycle of NSAID therapy.

(5) Heart failure and edema

A meta-analysis of randomized controlled trials showed that, compared with patients treated with placebo, patients receiving selectiveCOX-2 treated patients and non-selective NSAID-treated patients had approximately2increased heart failure hospitalizations. family:equinox”>fold. In the Heart Failure Study conducted in the Danish registry, NSAIDs increased the risk of myocardial infarction, hospitalization for heart failure, and death in patients.

In addition, fluid retention and edema have been observed in some patients treated with NSAIDs. The use of ibuprofen may attenuate the effects of multiple therapeutic agents[such as diuretics, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers ( ARBs)] for cardiovascular therapeutic effects .

Patients with severe heart failure should avoid ibuprofen injection unless the expected benefit far outweighs the risk of worsening heart failure. If it must be used, patients need to be monitored closely for signs of worsening heart failure.

(6) Nephrotoxicity and hyperkalemia

Nephrotoxicity

Long-term administration of NSAIDs can lead to renal papillary necrosis and other kidney damage.

Nephrotoxicity is also seen in patients with compensatory renal prostaglandin maintenance of renal perfusion, in which the use of NSAIDs may lead to a dose-dependent reduction in prostaglandin synthesis and also leads to a dose-dependent reduction in renal blood flow, which can significantly contribute to renal failure. Individuals at highest risk for this reaction include those with renal impairment, dehydration, hypovolemia, heart failure, hepatic insufficiency, who are taking diuretics and ACEinhibitors orARBsin patients, and in the elderly. Return to pre-treatment status is usually possible after discontinuation of NSAID therapy.

No controlled trials have been conducted with this product in patients with advanced kidney disease. The renal effects caused by ibuprofen injection may accelerate the progression of renal dysfunction in patients with nephropathy.

Correction of dehydration or hypovolemic patient volume status is required prior to the use of ibuprofen injection. Patients with renal or hepatic impairment, patients with heart failure, dehydrated or hypovolemic patients need to be monitored for renal function during the use of ibuprofen injection. Avoid use of this product in patients with advanced renal disease unless the expected benefit is substantially greater than the risk of worsening renal function. If use is necessary, patients need to be monitored closely for signs of worsening renal function.

Hyperkalemia

Elevated serum potassium concentrations have been reported in patients on non-steroidal anti-inflammatory drugs . including hyperkalemia, even in some patients without renal injury. In patients with normal renal function, the effect is attributed to a hyporenin hypoaldosteronism state.

(7) Allergic reactions

Ibuprofen can cause anaphylactic reactions in patients with or without known hypersensitivity to ibuprofen and in patients with aspirin-sensitive asthma.

Once an allergic reaction occurs, emergency treatment is required.

(8) Aspirin Worsening of sensitivity asthma

Subgroups of asthmatics who may have aspirin-sensitive asthma include chronic sinusitis with nasal polyps, severe potentially fatal bronchospasm, and/ or aspirin and other NSAID intolerance. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, ibuprofen injection is contraindicated in such aspirin-sensitive patients. When ibuprofen injection is used in patients with asthma (with no known aspirin sensitivity), patients need to be monitored closely for changes in asthma signs and symptoms.

(9) Severe skin Reaction

NSAIDs including ibuprofen can cause severe adverse skin reactions such as exfoliative dermatitis, Stevens- Johnson syndrome (SJS ) and toxic epidermal necrolysis (TEN), which can be fatal. These serious events can occur without warning. Patients should be informed of the signs and symptoms of serious skin reactions and the product should be discontinued at the first sign of skin rash or other signs of an allergic reaction. This product is contraindicated in patients who have previously had a severe skin reaction to an NSAID.

(10) fetus Premature atresia of the arterial duct

Ibuprofen can cause premature closure of the fetal ductus arteriosus in pregnancies greater than or equal to30weeks of pregnancy to avoid NSAIDs, including ibuprofen injection.

(11) Hematology Toxicity

Patients treated with NSAIDs have experienced anemia, which may be due to occult blood or significant gastrointestinal blood loss, fluid retention, or due to effects on erythropoiesis that are not fully understood. Monitor hemoglobin and erythrocyte pressure product if the patient develops any signs or symptoms of anemia with ibuprofen injection.

NSAIDs, including ibuprofen injection, may increase the risk of bleeding events. Combination of their–other and lesions (e.g., clotting disorders), or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin),5-hydroxytryptamine reuptake inhibitors (SSRI) and5-hydroxytryptamine norepinephrine reuptake inhibitors (SNRI) and other conditions may increase this risk, and these patients should be monitored for signs of bleeding.

Ibuprofen injection must be diluted before use, and infusion of undiluted drug can cause hemolytic reactions.

(12) Masking symptoms of inflammation and fever

The pharmacological activity of ibuprofen injection in reducing inflammation and fever can diminish the utility of diagnostic markers in infection detection.

(13) Laboratory Monitoring

Since severe gastrointestinal bleeding, hepatotoxicity, and renal injury may occur without warning signs or symptoms, patients on long-term NSAID therapy need to consider regular monitoring of blood (CBC) and biochemical markers.

(14) Ophthalmology Impact

Blurred or reduced vision, blind spots, and changes in color vision have been reported with oral ibuprofen. If a patient presents with these complaints, then ibuprofen injection should be discontinued immediately and the patient referred for an ophthalmologic examination, including central visual field and color discrimination testing.

(15)Aseptic Meningitis

Aseptic meningitis with fever and coma has been observed in the treatment of oral ibuprofen. Although such problems are more likely to occur in patients with SLE and related connective tissue diseases, they have been reported in those without any underlying chronic disease. If signs or symptoms of meningitis are identified in patients receiving ibuprofen therapy, consideration should be given to whether the sign or symptom is associated with ibuprofen therapy.

[Medication for Pregnant and Lactating Women]

Adequate controlled studies have not been conducted in pregnant and lactating women and are not recommended.

[Medication for Children]

The safety as well as efficacy in Chinese children has not been established and is not recommended.

[Geriatric Use]

Compared to younger patients, older patients develop NSAIDs associated with Severe cardiovascular, gastrointestinal, and/ or renal The risk of adverse reactions is higher. If the expected benefit in elderly patients outweighs these potential risks, dosing is usually started at the lowest therapeutic dose and patients are strictly monitored for adverse reactions.

Clinical studies of ibuprofen injection did not include a sufficient number of patients aged≥65 years old, and therefore cannot determine whether they respond differently from younger subjects. Decreased hepatic, renal, or cardiac function and more frequent underlying disease or treatment with other drugs in elderly patients require careful dose selection, usually starting with the lowest therapeutic dose. Older patients are at increased risk for serious gastrointestinal adverse events.

[Drug Interactions]

Table3 < span style="font-family:equivocal">Clinically Significant Drug Interactions Associated with Ibuprofen

[Drug overdose] =”font-family:Times New Roman”>

Acute NSAID overdose typical symptoms are often limited to lethargy, sleepiness, nausea, vomiting, and epigastric pain, and are usually reversible with supportive therapy. Gastrointestinal bleeding events have occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred but are rare.

Because there is no known antidote to ibuprofen, symptomatic relief and supportive therapy should be instituted in the event of an overdose. Diuresis, urinary alkalinization, hemodialysis, or hemoperfusion may not be useful due to the high protein binding of ibuprofen.

[Pharmacology and Toxicology]

Pharmacology: The mechanism of action of this product may be related to the inhibition of prostaglandin synthase, with anti-inflammatory, analgesic and antipyretic effects.

[Pharmacokinetics] According to foreign literature:

Bupropion isRandSisomeric racemic mixture. In vitro and in vivo studies have shown Sisomers to play a major clinical role. Risomers are considered to be pharmacologically inactive and are slowly and incompletely (~60%) conversion to the activeS< span style="font-family:equinox">isomer. R< span style="font-family:isoline">isomers serve as a circulating reservoir for maintaining active drug levels. The pharmacokinetic parameters of this product from clinical pharmacokinetic studies in foreign volunteers are shown in the table below.

Table4:Table of pharmacokinetic parameters for intravenous administration of ibuprofen injection

	0.4gmean*(CV%)	0.8gmean*(CV%)
Patient cases	12	12
< span style="color:black">AUC(μg.h/mL)	109.3(26.4)	< span style="color:black">192.8(18.5)
Cmax(μg/mL) >	39.2(15.5 )	72.6() 13.2)
KEL(L/h)	0.32(17.9)	0.29(12.8)
T1/2< />(h) >	2.22(20.1)	2.44(12.9)

AUC

= area under the curve at drug–; >C_max = plasma peak concentration;CV= coefficient of variation;KEL = primary elimination rate constant;T_1/2 = half-life; * = infusion time60minutes

Similar to most NSAIDs, ibuprofen has a high protein binding rate (20 μg/mLat binding rates>99%< (span style="font-family:isoline">). Protein binding can be saturated and binding is nonlinear at concentrations< span style="font-family:Times New Roman">>20 μg/mL< span style="font-family:isoline">. When administered orally, age factors and fever factors affect the apparent volume of distribution of ibuprofen.

Drug Interaction Studies

Aspirin: When NSAIDs are combined with aspirin, despite clearance of free NSAIDs was not altered, NSAID protein binding was reduced, and the clinical significance of this interaction is not known.

[Storage]Shade, not to exceed30°C for airtight storage.

[Packaging]Medium borosilicate glass ampoule, (1)4ml:0.4g,4branch/box; (2)8ml:0.8g,4branches/box.

[Expiration Date]24months.

[Execution Standard]

[Approval Number]

[Manufacturer]

Company Name: Chengdu Yuan Dong Biopharmaceutical Co: Times New Roman”>

Production Address: Xiyuan Avenue, High-tech Zone, Chengdu8No.

Postal Code:611731

Quality Complaint Phone Number:028-87827168

Consultation Phone Number:028-67585099

Fax Number:028-87826048

Net
at:http://www.eastonpharma.cn