IbuvenGen (Concentrate) Instructions for Use

Marketing Authorization Holder

Pharmtekhnologii LLC (Russia)

Manufactured By

Gen İlaç Ve Sağlık Ürünleri San. Ve Tic., A.Ş. (Turkey)

ATC Code

M01AE01 (Ibuprofen)

Active Substance

Ibuprofen (Rec.INN registered by WHO)

Dosage Form

IbuvenGen

Concentrate for solution for intravenous administration: vial 4 ml or 8 ml 1 or 10 pcs.

Dosage Form, Packaging, and Composition

Concentrate for solution for intravenous administration in the form of a transparent colorless solution.

Excipients: arginine – 78 mg, water for injections – up to 1 ml.

4 ml – vials of colorless glass (1) – cardboard packs.
4 ml – vials of colorless glass (10) – cardboard packs.
8 ml – vials of colorless glass (1) – cardboard packs.
8 ml – vials of colorless glass (10) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs; non-steroidal anti-inflammatory and antirheumatic drugs; propionic acid derivatives

Pharmacological Action

NSAID for intravenous administration. It has analgesic, anti-inflammatory, and antipyretic effects. The mechanism of action of ibuprofen is due to non-selective inhibition of the enzymes COX-1 and COX-2, which leads to inhibition of the synthesis of prostaglandins – mediators of pain, inflammation, and hyperthermic reaction.

Ibuprofen provides rapid analgesic, antipyretic, and anti-inflammatory effects.

Pharmacokinetics

After IV administration over 30 minutes at a dose of 400 mg, C_max and AUC are 39.2 ml/min and 109.3 µg/h/ml respectively, T_1/2 – 2.22 h; at a dose of 800 mg – C_max and AUC are 72.6 ml/min and 192.8 µg/h/ml respectively, T_1/2 – 2.44 h. Ibuprofen reversibly binds to plasma proteins (at concentrations >20 µg/ml up to 99%). Protein binding is saturable, and at concentrations of 20 µg/ml, binding is nonlinear.

Indications

Symptomatic treatment of acute postoperative pain syndrome of moderate and severe intensity when oral therapy is not appropriate.

ICD codes

Dosage Regimen

IV drip at a dose of 400-800 mg 2 times/day.

Ibuprofen for intravenous administration should be used at the lowest effective doses for the shortest duration necessary. After achieving a therapeutic effect at the initial stage of treatment, the dose and frequency of administration should be adjusted individually for each patient. The total daily dose should not exceed 1600 mg/day. To reduce the risk of adverse renal reactions, the patient should be adequately hydrated before administration.

In patients with mild or moderate hepatic or renal impairment, Ibuprofen should be used at the lowest dose and for the shortest period of time necessary to control symptoms. Continuous monitoring should be performed to assess liver function and timely detect the development of adverse events.

Adverse Reactions

Blood and lymphatic system disorders very rarely – hematopoietic disorders (anemia, leukopenia, aplastic anemia, hemolytic anemia, thrombocytopenia, pancytopenia, agranulocytosis).

Immune system disorders uncommon – nonspecific allergic reactions and anaphylactic reactions, respiratory tract reactions (bronchial asthma, including its exacerbation, bronchospasm, dyspnea, shortness of breath), skin reactions (itching, urticaria, purpura, angioedema, exfoliative and bullous dermatoses, including toxic epidermal necrolysis (Lyell’s syndrome), Stevens-Johnson syndrome, erythema multiforme), allergic rhinitis, eosinophilia; very rarely – severe hypersensitivity reactions, including facial, tongue and laryngeal edema, dyspnea, tachycardia, arterial hypotension (anaphylaxis, angioedema or severe anaphylactic shock).

Gastrointestinal disorders uncommon – abdominal pain, nausea, dyspepsia (including heartburn, bloating); rarely – diarrhea, flatulence, constipation, vomiting; very rarely – peptic ulcer, perforation or gastrointestinal bleeding, melena, hematemesis, in some cases fatal, especially in elderly patients, ulcerative stomatitis, gastritis; frequency unknown – exacerbation of colitis and Crohn’s disease.

Hepatobiliary disorders very rarely – liver function disorders, increased activity of liver transaminases, hepatitis and jaundice.

Renal and urinary disorders very rarely: acute renal failure (compensated and decompensated) especially with long-term use, combined with an increase in plasma urea concentration and the appearance of edema, hematuria and proteinuria, nephritic syndrome, nephrotic syndrome, papillary necrosis, interstitial nephritis, cystitis.

Nervous system disorders uncommon – headache; very rarely – aseptic meningitis.

Cardiac disorders frequency unknown – heart failure, peripheral edema, with long-term use increased risk of thrombotic complications (e.g., myocardial infarction), increased blood pressure.

Respiratory, thoracic and mediastinal disorders frequency unknown – bronchial asthma, bronchospasm, dyspnea.

Investigations decreased hematocrit or hemoglobin, increased bleeding time, decreased plasma glucose concentration, decreased creatinine clearance (increased plasma creatinine concentration), increased ALT and AST activity.

Contraindications

Hypersensitivity to ibuprofen and other NSAIDs; complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses, and intolerance to acetylsalicylic acid or other NSAIDs (including history); erosive and ulcerative diseases of the gastrointestinal tract (including peptic ulcer of the stomach and duodenum) or active ulcer bleeding or history (2 or more confirmed episodes of peptic ulcer or ulcer bleeding); inflammatory bowel disease (Crohn’s disease, ulcerative colitis); history of gastrointestinal ulcer bleeding or perforation provoked by NSAIDs; severe heart failure (NYHA class IV); severe hepatic failure (10-15 points on the Child-Pugh scale) or active liver disease; severe renal failure (creatinine clearance < 50 ml/min); decompensated heart failure; period before and after coronary artery bypass surgery; cerebrovascular or other bleeding (including intracranial hemorrhage), anticoagulant therapy; hemophilia and other blood clotting disorders (including hypocoagulation), hemorrhagic diatheses; pregnancy, breastfeeding period; children and adolescents under 18 years of age.

With caution

Peptic ulcer of the stomach and duodenum, other gastrointestinal diseases in history; inflammatory bowel disease (ulcerative colitis, Crohn’s disease) not in exacerbation; chronic hepatic failure of mild and moderate severity (5-9 points on the Child-Pugh scale); history of liver disease, hepatic porphyria; chronic renal failure (creatinine clearance 30-60 ml/min); chronic heart failure (NYHA functional class I-II); arterial hypertension, significant decrease in circulating blood volume (including after surgery); coronary artery disease; cerebrovascular diseases; dyslipidemia/hyperlipidemia; peripheral arterial diseases; elderly patients over 65 years of age (including those receiving diuretics, debilitated patients and those with low body weight); bronchial asthma; simultaneous use of corticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); smoking; severe somatic diseases, systemic connective tissue diseases (SLE and mixed connective tissue disease); long-term use of NSAIDs; dehydration; diabetes mellitus; hematopoietic disorders; hereditary porphyrin metabolism disorder (including acute intermittent porphyria); alcoholism.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindication: severe hepatic failure (10-15 points on the Child-Pugh scale) or active liver disease.

Use in Renal Impairment

Contraindication: severe renal failure (creatinine clearance < 50 ml/min).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with particular caution due to an increased risk of adverse reactions from the digestive system, including gastrointestinal bleeding, ulceration or perforation. Ibuprofen should be used at the lowest effective dose for the shortest period of time necessary to control symptoms.

Special Precautions

The use of NSAIDs is associated with an increased risk of thrombosis, heart attack and stroke. In people with cardiovascular disease or people predisposed to developing cardiovascular disease, the risk of developing these conditions may be high. Ibuprofen cannot be used as an analgesic in preparation for coronary artery bypass surgery.

In diseases of the digestive system, taking NSAIDs can cause bleeding, scarring, and gastrointestinal perforations. These side effects can occur at any time with or without warning symptoms. In elderly patients with gastrointestinal diseases, the risk of developing side effects is higher.

Taking NSAIDs, including ibuprofen, can cause arterial hypertension or exacerbation of existing arterial hypertension. In both cases, it can affect the development of cardiovascular diseases. Blood pressure should be monitored at the beginning of the NSAID use period and measured regularly throughout the entire period of use.

During treatment, renal and liver function should be monitored.

The use of ibuprofen may mask and complicate the diagnosis of symptoms of inflammation and the severity of pain, which may complicate diagnosis.

Effect on ability to drive vehicles and operate machinery

Ibuprofen may cause drowsiness, fatigue and blurred vision. The patient should be warned to refrain from driving vehicles and operating machinery if such symptoms occur.

Drug Interactions

Ibuprofen should not be used simultaneously with acetylsalicylic acid, except for low doses of acetylsalicylic acid (not more than 75 mg/day) prescribed by a doctor, since concomitant use may increase the risk of side effects. With simultaneous use, Ibuprofen reduces the anti-inflammatory and antiplatelet effect of acetylsalicylic acid.

The simultaneous use of two or more drugs from the NSAID group should be avoided due to a possible increase in the risk of side effects.

NSAIDs may enhance the effect of anticoagulants, in particular, warfarin and thrombolytic drugs. These combinations should be used with caution.

NSAIDs may reduce the effectiveness of antihypertensive drugs (ACE inhibitors, angiotensin II receptor antagonists) and diuretics. Diuretics and ACE inhibitors may increase the nephrotoxicity of NSAIDs.

With simultaneous use with corticosteroids, there is an increased risk of gastrointestinal ulcerative lesions and gastrointestinal bleeding.

Antiplatelet agents and selective serotonin reuptake inhibitors – increased risk of gastrointestinal bleeding.

Concomitant use of NSAIDs and cardiac glycosides may lead to worsening of heart failure, decreased glomerular filtration rate and increased plasma concentration of cardiac glycosides.

There is evidence of a possible increase in plasma lithium concentration during NSAID use.

There is evidence of a possible increase in plasma methotrexate concentration during NSAID use.

An increased risk of nephrotoxicity is observed with the simultaneous use of NSAIDs and cyclosporine.

NSAID use should be started no earlier than 8-12 days after taking mifepristone, since NSAIDs may reduce the effectiveness of mifepristone.

With simultaneous use of NSAIDs and tacrolimus, an increased risk of nephrotoxicity is possible.

Concomitant use of NSAIDs and zidovudine may lead to increased hematotoxicity. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia receiving combined treatment with zidovudine and ibuprofen.

In patients receiving combined treatment with NSAIDs and quinolone antibiotics, an increased risk of seizures is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.