Ibuprofen dr. reddy's

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUPROFEN DR. REDDY'S (IBUPROFEN DR. REDDY'S)

Composition:

Active substance: ibuprofen;

1 sachet contains 400 mg of ibuprofen;

Excipients: arginine, aspartame (E 951), sucrose, sodium hydrogencarbonate, sodium saccharin, sodium lauryl sulfate, menthol flavor, peppermint flavor, purified water.

Pharmaceutical form. Granules for oral solution.

Main physicochemical properties: white or almost white granules with a minty odor, which when shaken with water produce a clear solution.

Pharmacotherapeutic group. Nonsteroidal anti-inflammatory and antirheumatic agents.

ATC code M01A E01.

Pharmacological Properties

Pharmacodynamics

Ibuprofen is a derivative of phenylpropionic acid that exerts anti-inflammatory, analgesic, and antipyretic effects. The anti-inflammatory and analgesic effects are due to pronounced inhibition of prostaglandin synthesis. Inhibition of platelet aggregation, as well as ulcerogenic effects, sodium and water retention, and bronchospasm reactions as possible adverse effects, are also caused by this same mechanism.

Ibuprofen arginine has the same pharmacological properties as ibuprofen but is characterized by higher water solubility.

The onset of action occurs approximately 30 minutes after administration.

Pharmacokinetics

Absorption

After oral administration of ibuprofen (as ibuprofen arginine) at doses of 200 mg and 400 mg, maximum plasma concentrations of ibuprofen—25 µg/mL and 57 µg/mL, respectively—are achieved within 17–24 minutes.

If the drug is taken after food intake, absorption is slower and maximum plasma concentrations are lower.

Distribution

The plasma half-life is 1.5–2 hours. Protein binding is approximately 99%.

Metabolism

Ibuprofen is metabolized in the liver and is rapidly eliminated, primarily via the kidneys, as inactive metabolites.

Excretion

Ibuprofen does not accumulate even during prolonged therapy. Ibuprofen and its metabolites are almost completely excreted within 24 hours after the last dose is administered.

Clinical characteristics

Indications. Symptomatic treatment of headache, migraine, toothache, menstrual pain, rheumatic pain, muscle and back pain.

Symptomatic treatment of symptoms of cold, influenza, and fever.

Contraindications

• Hypersensitivity to ibuprofen or to any component of the medicinal product.
• Hypersensitivity reactions (e.g., bronchospasm, bronchial asthma, rhinitis, angioedema, or urticaria) previously observed after taking ibuprofen, acetylsalicylic acid (aspirin), or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Active peptic ulcer disease / gastrointestinal bleeding or history of recurrent episodes (two or more distinct episodes of peptic ulcer or bleeding).
• Duodenal ulcer.
• History of gastrointestinal bleeding or perforation associated with NSAID therapy.
• Inflammatory bowel disease (such as Crohn's disease, ulcerative colitis).
• Severe hepatic impairment (cirrhosis and ascites), severe renal impairment (creatinine clearance < 30 mL/min); severe heart failure (NYHA class III–IV [New York Heart Association]).
• Third trimester of pregnancy (see section "Use in pregnancy or lactation").
• Cerebrovascular or other hemorrhages.
• Hemorrhagic diathesis.
• Coagulation disorders or blood clotting abnormalities.
• Severe dehydration.
• Phenylketonuria — the medicinal product contains aspartame.

Do not use for postoperative pain treatment following coronary artery bypass grafting (especially with use of cardiopulmonary bypass).

Interaction with other medicinal products and other forms of interaction

Other nonsteroidal anti-inflammatory drugs, including cyclooxygenase-2 (COX-2) inhibitors, glucocorticoids, and alcohol: enhance gastrointestinal adverse effects and increase the risk of gastrointestinal bleeding. Salicylic acid displaces ibuprofen from protein binding. Caution is recommended when used concomitantly, as the risk of gastrointestinal side effects increases.

Acetylsalicylic acid (low doses): experimental data suggest that ibuprofen may inhibit the effect of low-dose acetylsalicylic acid (aspirin) on platelet aggregation when administered concomitantly. However, the limited nature of these data and uncertainty regarding extrapolation of ex vivo findings to clinical situations do not allow definitive conclusions about regular ibuprofen use; clinically significant effects with occasional ibuprofen use are considered unlikely.

Oral anticoagulants: NSAIDs may potentiate the effects of anticoagulants such as warfarin.

Antihypertensive agents: reduced effectiveness of antihypertensive drugs is expected. Concomitant use of NSAIDs and angiotensin-converting enzyme (ACE) inhibitors or beta-blockers increases the risk of acute renal failure.

Histamine H2-receptor antagonists: no clinically significant interaction between ibuprofen and cimetidine or ranitidine has been established.

Digoxin: plasma digoxin concentration may increase.

Phenytoin: plasma phenytoin concentration may increase.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.

Antidiabetic medicinal products: ibuprofen potentiates the hypoglycemic effect of oral antidiabetic agents and insulin. Dosage adjustment may be necessary.

Diuretics: effectiveness of furosemide and thiazide diuretics may be reduced, likely due to sodium retention resulting from inhibition of renal prostaglandin synthesis.

Lithium: plasma lithium levels may increase.

Methotrexate: evidence suggests a potential increase in methotrexate plasma levels.

Cyclosporine: increased risk of nephrotoxicity.

Mifepristone: concomitant use may increase NSAID exposure. Reduced efficacy of mifepristone is possible—theoretically due to the anti-prostaglandin properties of NSAIDs. Studies indicate that concomitant administration of ibuprofen on the same day as prostaglandins does not reduce the clinical efficacy of mifepristone.

Tacrolimus: increased risk of nephrotoxicity when ibuprofen and tacrolimus are used concomitantly.

Zidovudine: concomitant use of zidovudine and ibuprofen increases the risk of hemarthrosis and hematoma in HIV-infected patients with hemophilia.

Probenecid and sulfinpyrazone: excretion of ibuprofen is delayed; the uricosuric effect of probenecid and sulfinpyrazone is diminished.

Baclofen: toxicity of baclofen may increase.

Quinolones: concomitant use with NSAIDs increases the risk of seizures.

Aminoglycosides: NSAIDs may reduce the elimination of aminoglycosides.

Voriconazole and fluconazole: concomitant use of voriconazole, fluconazole, and ibuprofen may lead to increased exposure and plasma concentration of ibuprofen.

Cholestyramine: ibuprofen and cholestyramine should be taken several hours apart due to delayed and reduced (by 25%) absorption of ibuprofen when administered concomitantly.

Herbal extracts: Ginkgo biloba potentiates the risk of bleeding associated with NSAID use.

Effect on diagnostic test results:

• Bleeding time: may be prolonged for up to 1 day after discontinuation of therapy;
• Serum glucose concentration: possible decrease;
• Creatinine clearance: possible decrease;
• Hematocrit or hemoglobin levels: possible decrease;
• Blood urea nitrogen, serum creatinine concentration, and serum potassium: possible increase;
• Liver function tests: increased transaminase levels.

Special precautions for use

Adverse effects associated with the use of ibuprofen and NSAIDs in general can be minimized by using the lowest effective dose for the shortest possible duration.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which can be fatal. Therefore, standard medical recommendations should be followed. In particular, the lowest dose should be used in frail elderly patients or patients with low body weight.

Respiratory effects

Bronchospasm, urticaria, and angioedema may occur in patients suffering from bronchial asthma, chronic rhinitis or allergic diseases, or with a history of these conditions.

Other NSAIDs

Concomitant use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 inhibitors, increases the risk of adverse reactions and should therefore be avoided.

Aseptic meningitis

Ibuprofen should be used with caution in patients with manifestations of systemic lupus erythematosus or mixed connective tissue disorders due to an increased risk of developing aseptic meningitis.

Effects on the cardiovascular and cerebrovascular systems

Placebo-controlled studies have demonstrated an increased risk of thrombotic cardiovascular and cerebrovascular complications with the use of certain selective COX-2 inhibitors. It is currently unknown whether this risk is directly correlated with the COX-1/COX-2 selectivity of individual NSAIDs.

Clinical trial data indicate that the use of high-dose ibuprofen (2400 mg daily) and long-term treatment slightly increases the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). Overall, epidemiological data do not suggest that low-dose ibuprofen (e.g., ≤1200 mg daily) increases the risk of arterial thrombotic events.

Treatment with ibuprofen should only be initiated after careful assessment in patients with uncontrolled hypertension, heart failure (NYHA class II), diagnosed ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. High doses (2400 mg/day) should be avoided in these patients.

A careful benefit-risk assessment should also be performed before initiating long-term treatment in patients with risk factors for cardiovascular complications (e.g., hypertension, hyperlipidemia, diabetes, smoking), especially if high-dose ibuprofen (2400 mg/day) is required.

Cases of Kounis syndrome have been reported in patients receiving ibuprofen. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with coronary artery spasm, which may lead to myocardial infarction.

Effects on the kidneys

Renal effects of NSAIDs include fluid retention with edema and/or hypertension. Therefore, ibuprofen should be used with caution in patients with impaired cardiac function or other conditions leading to fluid retention.

Patients with severe dehydration or postoperative volume changes should be rehydrated before starting ibuprofen treatment and closely monitored thereafter. There is a risk of impaired renal function, particularly in dehydrated children and adolescents.

As with other NSAIDs, prolonged use may lead to renal papillary necrosis and other kidney tissue damage. Renal toxicity has also been observed in patients in whom renal prostaglandins play a supportive role in renal perfusion. In such patients, NSAID use may lead to dose-dependent reduction in renal prostaglandin production, decreased renal perfusion, and induction of overt renal decompensation. These reactions are most commonly observed in patients with impaired renal, cardiac, or hepatic function, those receiving concomitant diuretics or ACE inhibitors, and elderly patients.

Effects on the gastrointestinal system

Gastrointestinal ulceration, bleeding, or perforation may occur at any time during NSAID or COX-2 selective therapy, with or without warning symptoms, regardless of prior history of such events.

To minimize risk, the lowest effective dose should be used for the shortest possible duration.

Patients with a history of gastrointestinal toxicity, especially elderly patients, should be informed about the need to report any unusual abdominal symptoms (particularly gastrointestinal bleeding).

If gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, treatment should be discontinued immediately.

Caution is recommended when patients are concurrently receiving medications that increase the risk of ulceration or bleeding, such as oral corticosteroids; anticoagulants like warfarin; selective serotonin reuptake inhibitors; or antiplatelet agents such as acetylsalicylic acid (see also section "Interaction with other medicinal products and other forms of interaction").

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions have been reported with ibuprofen, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis, which may be life-threatening or fatal (see section "Adverse reactions"). Most such reactions occurred within the first month of treatment.

If signs or symptoms suggestive of these reactions occur, ibuprofen should be discontinued immediately and alternative therapy considered (if needed).

Masking symptoms of underlying infections

Ibuprofen may mask symptoms of infection, leading to delayed initiation of appropriate treatment and potentially worsening disease course. Such symptom masking has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. Isolated cases of worsening infections (e.g., development of necrotizing fasciitis) have been reported in temporal association with NSAID use. When ibuprofen is used for fever or pain relief during infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Visual disturbances

Patients experiencing visual disturbances during treatment with ibuprofen should discontinue treatment and undergo ophthalmological examination.

Liver function tests

NSAIDs may cause elevations in liver function test parameters.

Excipients

This medicinal product contains aspartame (E951), a phenylalanine derivative, which may be harmful to patients with phenylketonuria.

This medicinal product contains sucrose. Patients with diagnosed sugar intolerance should consult a physician before taking this medicinal product. It may be harmful to teeth.

Use during pregnancy or breastfeeding

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and congenital heart defects and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to be directly proportional to the dose and duration of therapy.

Animal studies have shown that prostaglandin synthesis inhibitors increase pre- and post-implantation loss and embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, the incidence of various malformations, including cardiovascular defects, was increased.

During the first and second trimesters of pregnancy, ibuprofen should not be used unless clearly necessary.

If ibuprofen is used by a woman attempting to conceive or during the first or second trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors, including ibuprofen, pose risks to the fetus: cardiopulmonary toxicity characterized by premature closure of the ductus arteriosus and pulmonary hypertension; renal dysfunction, which may progress to renal toxicity with oligohydramnios. Prolonged bleeding may occur in both mother and child near term, and labor may be delayed. Therefore, ibuprofen is contraindicated during the last trimester of pregnancy.

Breastfeeding

NSAIDs pass into breast milk. As a precautionary measure, ibuprofen should not be taken by women who are breastfeeding. If treatment is essential, the infant should be switched to artificial feeding.

Fertility

Ibuprofen may affect female fertility and is therefore not recommended for women wishing to become pregnant. In women experiencing difficulties with conception or undergoing infertility investigations, discontinuation of ibuprofen should be considered.

Ability to affect reaction speed when driving or operating machinery. Ibuprofen may affect reaction speed; therefore, the ability to drive or operate machinery may be impaired (see section "Adverse reactions").

Method of Administration and Dosage

Dissolve the contents of the sachet in 100–200 ml of still water.

Take orally immediately after preparing the solution, preferably during or after a meal.

For use in adults and children aged 12 years and older with body weight of at least 40 kg. The maximum daily dose of ibuprofen is 20–30 mg per kilogram of body weight, divided into 3–4 doses administered at 6–8 hour intervals. The interval between doses should not be less than 4 hours. Do not exceed the maximum daily dose.

The single dose is 1 sachet (400 mg of ibuprofen). If needed, one sachet may be taken every 6 hours. The maximum daily dose is 1200 mg (3 sachets).

For short-term use only.

Use the lowest effective dose required to relieve symptoms for the shortest possible duration (see section "Special Warnings and Precautions for Use").

Elderly patients do not require special dose adjustment, except in cases of severe renal or hepatic impairment.

If symptoms worsen or persist for more than 3 days, consult a physician for diagnosis clarification and treatment adjustment. The duration of treatment is determined individually by the physician, depending on the course of the disease and the patient's condition.

Children. Not recommended for children under 12 years of age, as the dose of ibuprofen contained in the medicinal product does not correspond to the recommended dose for this age group.

Overdose

Symptoms. Common symptoms of overdose include nausea, vomiting, dizziness, drowsiness, and tremor; less frequently – headache, tinnitus, ataxia, tachycardia, miosis, reversible elevation of transaminase and bilirubin levels, and thrombocytopenia.

Severe symptoms are rare and may include loss of consciousness (coma), metabolic acidosis, seizures, and acute renal failure; apnea may occur in children under 2 years of age.

Severe symptoms may occur at doses of 400 mg/kg, although doses up to 60 g may be well tolerated, and doses up to 100 g may not result in a fatal outcome. Severe symptoms may occur even after lower doses in elderly patients, young children, patients with liver or kidney disease, and those with chronic alcohol abuse.

Treatment. In children under age who have ingested > 200 mg/kg, or in adults who have ingested > 20 g, administer activated charcoal: 1 g per kg of body weight as a single oral dose in aqueous suspension. In case of overdose with aqueous ibuprofen suspension, perform gastric lavage followed by administration of activated charcoal within 1 hour of ingestion. Initiate medical monitoring for ingestions ≥ 300 mg/kg and in all patients at increased risk. Monitoring duration is 4 hours; for extended-release formulations, monitor for 12 hours. Perform laboratory tests: transaminases, creatinine, bilirubin; in patients with clinical manifestations, additionally test blood gas analysis, electrolytes, and platelets.

Adverse Reactions

Adverse reactions associated with the use of ibuprofen are listed below by organ systems and frequency. Frequency is defined as follows: very common — ≥1/10; common — ≥1/100 and <1/10; uncommon — ≥1/1000 and <1/100; rare — ≥1/10000 and <1/1000; very rare: <1/10000; frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders

Rare: blood dyscrasias^1.

Frequency not known: anaemia.

Immune system disorders

Uncommon: hypersensitivity reactions accompanied by urticaria and pruritus^2.

Rare: systemic lupus erythematosus, aseptic meningitis in patients with autoimmune disorders such as lupus, autoimmune haemolytic anaemia, anaphylaxis.

Very rare: severe hypersensitivity reactions, symptoms of which may include facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension (anaphylaxis, angioneurotic oedema or severe shock)^2.

Frequency not known: anaphylactic shock.

Nervous system disorders

Common: headache, dizziness.

Uncommon: lethargy (especially when alcohol is consumed), somnolence.

Rare: paraesthesia.

Very rare: aseptic meningitis^3, confusion, meningeal signs.

Frequency not known: depression, psychiatric reactions.

Cardiac disorders

Frequency not known: heart failure, oedema^4, Coon’s syndrome.

Vascular disorders

Frequency not known: arterial hypertension^4, arterial thrombosis.

Respiratory, thoracic and mediastinal disorders

Uncommon: bronchial reactivity, including asthma, asthma exacerbation, bronchospasm or dyspnoea^2.

Rare: risk of acute pulmonary oedema in patients with heart failure.

Frequency not known: throat irritation.

Gastrointestinal disorders

Very common: abdominal discomfort, dyspepsia^5, diarrhoea.

Common: nausea, bloating, heartburn, abdominal pain, anorexia, constipation, flatulence, vomiting, erosive gastritis, rectal bleeding (leading to anaemia).

Uncommon: peptic ulcer, gastrointestinal haemorrhage, melaena, gastritis.

Rare: gastrointestinal ulcers or perforations with bleeding, haematemesis (sometimes fatal), ulcerative stomatitis, colitis exacerbation, Crohn’s disease exacerbation^6.

Hepatobiliary disorders

Rare: liver function abnormalities, hepatic failure.

Frequency not known: hepatic injury, hepatitis, jaundice.

Skin and subcutaneous tissue disorders

Uncommon: angioneurotic oedema.

Very rare: bullous reactions, severe cutaneous adverse reactions (including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity reactions, toxic epidermal necrolysis)^2.

Frequency not known: acute generalised exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), exacerbation of skin reactions.

Renal and urinary disorders

Rare: haematuria, renal papillary necrosis, interstitial nephritis, renal dysfunction with oedema.

Very rare: acute renal failure^7.

Psychiatric disorders

Uncommon — common: depression, anxiety, hallucinations, confusion.

Very rare: psychotic state.

Eye disorders

Uncommon — common: visual disturbances, usually reversible after discontinuation of treatment.

Rare: toxic amblyopia, optic neuritis.

Frequency not known: optic disc oedema.

Ear and labyrinth disorders

Uncommon — common: hearing disturbances, deafness.

Frequency not known: with prolonged treatment — tinnitus and dizziness.

Musculoskeletal and connective tissue disorders

Frequency not known: musculoskeletal stiffness.

Reproductive system and breast disorders

Frequency not known: menstrual disorders.

Infections and infestations

Frequency not known: exacerbation of skin reactions.

Metabolism and nutrition disorders

Frequency not known: increased uricemia, sodium and water retention or oedema.

General disorders

Frequency not known: oedema.

Investigations

Rare: abnormal liver function tests, elevated transaminase levels, colour vision disturbances.

Very rare: decreased haemoglobin levels.

Frequency not known: abnormal renal function test results.

^1 Includes anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis, granulocytopenia and haemolytic anaemia. Initial signs of these disorders include malaise, sore throat, oral ulceration, influenza-like symptoms, severe fatigue, bleeding and unexplained haematomas.

^2 Hypersensitivity reactions include: non-specific allergic reactions and anaphylaxis, respiratory tract reactivity (including asthma, asthma exacerbation, bronchospasm and dyspnoea), or various skin reactions such as pruritus, urticaria, purpura, exanthema, rash, angioneurotic oedema, and less frequently exfoliative and bullous dermatoses, including toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis and allergic vasculitis.

^3 The pathogenic mechanism of drug-induced aseptic meningitis is not fully understood. Available data on aseptic meningitis associated with NSAIDs suggest a hypersensitivity reaction (based on temporal association with drug intake and resolution of symptoms after discontinuation). Cases have been observed in patients with autoimmune diseases (systemic lupus erythematosus and mixed connective tissue disease), presenting symptoms such as nuchal rigidity, headache, nausea, vomiting, malaise or disorientation.

^4 Clinical and epidemiological data indicate that the use of ibuprofen (particularly at high doses ≥ 2400 mg/day and during long-term treatment) is associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

^5 Gastrointestinal adverse reactions are the most frequently observed.

^6 See section "Special precautions".

^7 Especially with long-term use of NSAIDs, associated with elevated serum urea levels and oedema. Also includes papillary necrosis, haematuria, dysuria, interstitial nephritis, renal insufficiency, acute renal failure.

Reporting suspected adverse reactions. Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 30 °C.

Keep out of reach of children.

Packaging. 10 or 40 sachets in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer

1. TOLL MANUFACTURING SERVICES, S.L.
2. LAMB SAN PROSPERO SPA.

Manufacturer’s location and address of place of business

1. C/ Aragoneses, 2, Madrid, 28108, Spain.
2. Via della Pace, 25/A, San Prospero (MO), 41030, Italy.

Marketing Authorisation Holder. LLC "Dr. Reddy’s Laboratories", Ukraine.

Address of Marketing Authorisation Holder. 121-A Kyivskyi Shliakh St., village Velyka Oleksandrivka, Boryspil District, Kyiv Oblast, 08320, Ukraine.

You can report a suspected adverse reaction or lack of efficacy of the medicinal product at the following phone number (24/7):

+380 44 207 51 97 or +380 50 414 39 39;

or by email: [email protected]