MIG JUNIOR oral susp 40mg/ml 100ml

1. NAME OF THE MEDICINAL PRODUCT

MIG Junior 40 mg/ml oral suspension MIG Junior 40 mg/ml oral suspension

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml of oral suspension contains 40 mg of ibuprofen.

Excipients with known effect: liquid maltitol 0.5 g/ml and 5.79 mg sodium per 1 ml oral suspension.

For the full list of excipients, see section 6.1.

3.PHARMACEUTICAL FORM

Oral suspension

White or almost white viscous suspension.

4.CLINICAL DATA

1. Therapeutic indications

MIG Junior is used for short-term symptomatic treatment of:

• mild to moderate pain
• high temperature

MIG Junior is indicated for children weighing over 10 kg (1 year of age), adolescents and adults.

4.2 Dosage and method of administration

Dosage

The dose is in accordance with the table below. In children and adolescents, the dose of MIG Junior is determined depending on body weight, generally from 7 to 10 mg/kg.

body weight as a single dose, up to a maximum of 30 mg/kg body weight as a total daily dose.

The interval between individual doses is in accordance with the symptoms and the maximum daily dose.

dose. Should not be less than 6 hours. The recommended maximum dose should not be exceeded.

If children and adolescents need to use this medicine for more than 3 days, or if symptoms worsen, a doctor should be consulted.

If adults need to use this product for more than 3 days in case of high fever or for more than 4 days to treat pain, or if symptoms worsen, a doctor should be consulted.

The package contains a dosing syringe for oral administration of MIG Junior.

The oral syringe is graduated in 0.25 ml increments up to a full volume of 5 ml.

5 ml of oral suspension corresponds to 200 mg of ibuprofen. The bottle should be shaken well before use.

MIG junior 40 mg/ml:

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

Special populations

Elderly population:

No specific dose adjustment is required in elderly patients. Due to the possible adverse reaction profile (see section 4.4), elderly patients should be monitored with particular care.

Kidney damage:

No dose reduction is required in patients with mild to moderate renal impairment (for patients with severe renal insufficiency see section 4.3).

Hepatic impairment (see section 5.2):

No dose reduction is required in patients with mild to moderate renal impairment.

hepatic function (for patients with severe hepatic insufficiency see section 4.3).

Paediatric population:

MIG Junior is not recommended for use in children under 1 year of age or weighing less than 10 kg.

Method of administration

For oral use and for short-term use only. The bottle should be shaken well before use.

The oral suspension can be taken regardless of food. For patients with sensitive stomachs, it is recommended that MIG Junior be taken with a meal.

4.3Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

History of bronchospasm, asthma, rhinitis, angioedema or urticaria associated with the use of acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs (NSAIDs).

Unexplained blood formation disorders.

Active or history of recurrent peptic ulcer/bleeding (two or more separate episodes of proven ulceration or bleeding).

History of gastrointestinal bleeding or perforation associated with previous NSAID treatment.

Cerebrovascular or other active hemorrhage.

Severe hepatic insufficiency, severe renal insufficiency or severe heart failure (NYHA Class IV).

Severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake). Pregnant patients in the last three months of pregnancy.

4.4 Special warnings and precautions for use

Adverse reactions can be minimised by using the lowest effective dose for the shortest duration to control symptoms (see gastrointestinal and renal risks).

cardiovascular system below). Gastrointestinal safety

Concomitant administration of MIG Junior oral suspension with NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided.

Old age:

Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal (see section 4.2).

Gastrointestinal bleeding, ulceration and perforation:

Gastrointestinal bleeding, ulceration or perforation, which can be fatal, have been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events.

The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs, in patients with a history of ulcer, especially if complicated by haemorrhage or perforation (see section 4.3), and in the elderly. These patients should start treatment with the lowest possible dose. In these patients, as well as in patients requiring

concomitant use of low-dose acetylsalicylic acid or other drugs that increase gastrointestinal risk, combination treatment with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered (see below and section 4.5).

Patients with a history of gastrointestinal toxicity, especially in the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) especially in the initial stages of treatment.

Caution is advised in patients receiving concomitant medications that may increase the risk of ulceration and bleeding, such as oral corticosteroids, anticoagulants such as

warfarin, selective serotonin reuptake inhibitors or antithrombotic agents such as acetylsalicylic acid (see section 4.5).

If gastrointestinal bleeding or ulceration occurs in patients taking MIG Junior, treatment should be discontinued.

NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section 4.8. Undesirable effects).

Cardiovascular and cerebrovascular effects

Caution (consultation with a doctor or pharmacist) is required before starting treatment in patients with a history of hypertension and/or heart failure, as fluid retention, hypertension and edema have been reported in association with NSAID treatment.

Clinical studies have shown that the use of ibuprofen, particularly at high doses (2400 mg/day), may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological studies have not

show that low doses of ibuprofen (e.g. £1200 mg/day) are associated with an increased risk of arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease

vascular disease should be treated with ibuprofen only after careful consideration and high doses (2400 mg/day) should be avoided.

Careful consideration should also be given to initiating long-term treatment in patients with risk factors for cardiovascular events (i.e. hypertension, hyperlipidemia, diabetes mellitus, smoking), especially with high doses of ibuprofen (2400 mg/day).

Severe skin reactions

Severe skin reactions, some of which are fatal, including exfoliative dermatitis,

Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients are at highest risk of developing these reactions early in the course of treatment: the onset of the reaction is in most cases within the first month of treatment. Acute generalised exanthematous pustulosis (AGEP) has been reported in association with ibuprofen-containing products. MIG Junior should be discontinued at the first appearance of

skin rash, mucosal lesions or any other sign of hypersensitivity.

Exceptionally, varicella may be the cause of serious infectious complications of the skin and soft tissues. At this time, the role of NSAIDs for

worsening of these infections. It is therefore advisable to avoid the use of MIG Junior in cases of chickenpox.

Other information:

MIG Junior should only be used after careful consideration of the benefit/risk ratio in:

• congenital disorders of porphyrin metabolism (e.g. acute intermittent porphyria),
• in systemic lupus erythematosus (SLE) and mixed connective tissue disease - increased risk of aseptic meningitis (see section 4.8).

Particularly careful monitoring by a doctor is required in the following cases:

• in case of impaired renal function (as acute deterioration of renal function may occur in patients with pre-existing renal disease);
• in case of dehydration
• in liver dysfunction;
• immediately after major surgical procedures;
• in patients who suffer from hay fever, nasal polyps, chronic swelling of the nasal mucosa or chronic obstructive respiratory diseases, as they are at increased risk of developing allergic reactions. Such reactions

may manifest in the form of asthma attacks (so-called analgesic asthma), Quincke's edema or urticaria;

• in patients who react allergically to other substances, as they are at increased risk of hypersensitivity reactions when using MIG Junior.

Severe acute hypersensitivity reactions (e.g. anaphylactic shock) have been observed very rarely. At the first signs of a hypersensitivity reaction after ingestion of MIG Junior, treatment should be discontinued. Medical measures should be taken by specialized personnel according to the symptoms.

Respiratory disorders: Caution is required when MIG Junior is taken by patients who suffer from or have a history of bronchial asthma, as NSAIDs have been reported to exacerbate bronchospasm in these patients.

Ibuprofen, the active substance of MIG Junior, may temporarily inhibit platelet function (platelet aggregation). Therefore, patients with bleeding disorders should be carefully monitored.

With prolonged use of ibuprofen (MIG Junior), regular monitoring of liver values, kidney function and blood counts is required.

Caution should be exercised in patients who are already taking other painkillers or fever-reducing medications or antibiotics.

Prolonged use of any type of painkiller for headaches can lead to their worsening. If this occurs or is suspected, consultation with a doctor is necessary.

doctor and discontinuation of treatment. The diagnosis of medication overdose headache should be considered in patients who have frequent or daily headaches despite (or because of) regular use of headache medications.

In general, regular use of painkillers, especially a combination of several

painkillers, can lead to persistent kidney damage with a risk of kidney failure (analgesic nephropathy).

When alcohol is administered concomitantly with NSAIDs, adverse reactions related to the active substance, especially with regard to the gastrointestinal tract or the central nervous system, may be intensified.

NSAIDs may mask symptoms of infection and fever. Paediatric population

There is a risk of kidney damage in dehydrated children and adolescents.

This medicinal product contains liquid maltitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.

This medicinal product contains up to 2.52 mmol (or 57.9 mg) sodium per dose. To be taken into consideration by patients on a controlled sodium diet.

4.5 Interaction with other medicinal products and other forms of interaction

Ibuprofen (like other NSAIDs) should be used with caution in combination with the following medicinal substances:

Other non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid:

The concomitant use of two or more NSAIDs may lead to an increased risk of

Gastrointestinal ulcers and bleeding due to a synergistic effect. Therefore, concomitant administration of ibuprofen with other NSAIDs should be avoided (see section 4.4).

Acetylsalicylic acid :

The simultaneous use of ibuprofen and acetylsalicylic acid is generally not recommended due to the possibility of increased adverse effects.

Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when administered concomitantly. Although there is uncertainty regarding the extrapolation of these data to

In clinical cases, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically significant effect is considered likely with occasional use of ibuprofen (see section 5.1).

Digoxin, Phenytoin, Lithium:

Concomitant administration of MIG Junior with digoxin, phenytoin or lithium may increase the serum levels of these medicinal products. With proper administration (maximum 4 days), monitoring of serum levels of lithium, digoxin and

phenytoin.

Diuretics, ACE inhibitors, beta-receptor blockers and angiotensin-II antagonists:

NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), concomitant administration of ACE inhibitors, beta-receptor blockers or angiotensin II antagonists and

agents that inhibit cyclooxygenase may lead to further damage to the

renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be used with caution, especially in the elderly. Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of combination therapy and periodically thereafter.

Concomitant use of MIG Junior and potassium-sparing diuretics may lead to hyperkalemia.

Corticosteroids:

Increased risk of gastrointestinal ulceration and bleeding (see section 4.4).

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs):

Increased risk of gastrointestinal bleeding (see section 4.4).

Anticoagulants :

NSAIDs may enhance the effects of anticoagulants such as warfarin (see section 4.4).

Methotrexate :

Administration of MIG Junior 24 hours before or after administration of methotrexate may lead to increased concentrations of methotrexate and an increase in its toxic effect.

Sulfonylureas:

Clinical studies have shown interactions between nonsteroidal anti-inflammatory drugs and antidiabetic drugs (sulfonylureas). Although no interactions have been reported to date,

Interactions between ibuprofen and sulfonylureas have been reported, and monitoring of blood sugar levels is recommended as a precautionary measure when used concomitantly.

Zidovudine :

Concomitant administration of MIG Junior oral suspension may increase the risk of joint bleeding and bruising in HIV-positive patients suffering from

hemophilia.

Cyclosporine :

The risk of nephrotoxic effects caused by ciclosporin is increased by the concomitant use of certain NSAIDs. This effect cannot be excluded also in the case of

the combination of cyclosporine with ibuprofen.

Tacrolimus :

The risk of nephrotoxicity increases with concomitant administration of this medicinal product with MIG Junior oral suspension.

Probenecid and sulfinpyrazone:

Medicinal products containing probenecid and sulfinpyrazone may delay the excretion of ibuprofen.

Quinolone antibiotics:

Animal data suggest that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of seizures.

CYP2C9 inhibitors:

Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase

exposure to ibuprofen (CYP2C9 substrate). A study with voriconazole and fluconazole (CYP2C9 inhibitors) demonstrated an increase in exposure to S(+)-ibuprofen by approximately 80 to 100%. A reduction in the ibuprofen dose should be considered when co-administered with potent CYP2C9 inhibitors, especially if high doses of ibuprofen are administered with voriconazole and fluconazole.

4.6Fertility, pregnancy and lactation

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.

Data from epidemiological studies show an increased risk of spontaneous abortions and

cardiac malformations and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformation increases from less than 1% to approximately 1.5%. The risk is thought to increase with dose and duration of therapy.

In animals, administration of prostaglandin synthesis inhibitors has resulted in increased pre- and post-implantation losses and embryo-foetal lethality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals,

who were administered prostaglandin synthesis inhibitors during the period of organogenesis.

During the first and second trimester of pregnancy, MIG Junior should not be used unless absolutely necessary. If ibuprofen (MIG Junior) is taken by women trying to conceive or during the first and second trimester of pregnancy,

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 may lead to exposure

• of the fruit of:
  • cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
  • renal dysfunction, which may progress to renal failure and oligohydramnios;
• of the mother and the newborn, at the end of pregnancy, of:
  • possible increased bleeding time, an anticoagulant effect that may occur even at very low doses;
  • suppression of uterine contractions, leading to delayed or prolonged labor.

Therefore, MIG Junior is contraindicated during the third trimester of pregnancy (see section 4.3).

Breastfeeding

Ibuprofen and its metabolites pass into breast milk in small amounts. Since no harmful effects on the breast-fed infant are known so far, in principle, short-term use of ibuprofen at recommended doses does not require discontinuation of the drug.

breastfeeding (see section 4.2).

Fertility

There is evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This is reversible upon discontinuation of treatment.

4.7 Effects on ability to drive and use machines

MIG Junior has a minor influence on the ability to drive and use machines.

When using MIG Junior, side effects such as fatigue and dizziness may occur. As a result, in some cases the ability to react may change and the ability to actively participate in road traffic and operate machinery may be impaired. This applies to a greater extent in interaction with alcohol.

4.8 Adverse drug reactions

The list of adverse reactions below covers all adverse reactions known to date for ibuprofen, including those reported after long-term use of high doses in patients with rheumatism. The frequencies given, with the exception of very rare reports, refer to short-term use of daily doses up to a maximum of 1200 mg ibuprofen (30 ml MIG Junior oral suspension,

maximum daily dose for adults and adolescents aged 12 years and over) for oral forms and a maximum of 1800 mg for suppositories.

The assessment of adverse drug reactions is based on the following frequency classification:

It should be noted that the following adverse reactions are dose-dependent and vary between patients.

The most frequently observed adverse reactions are gastrointestinal in origin. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur, especially in the elderly (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative colitis have been reported following administration.

stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4). Gastritis has been observed less frequently.

There have been reports of edema, hypertension, and heart failure in association with NSAID treatment.

Clinical studies have shown that the use of ibuprofen, especially at high doses (2400 mg/day), may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see 4.4).

Infections and infestations

Very rare: Exacerbation of infectious inflammations (e.g. development of necrotizing fasciitis) has been described in association with the systemic administration of non-steroidal anti-inflammatory drugs. This is most likely related to the mechanism of action of non-steroidal anti-inflammatory drugs.

If signs of infection appear or worsen during the use of MIG Junior, the patient is recommended to immediately consult a doctor. It should be assessed whether this is an indication for anti-infective/antibiotic therapy.

Blood and lymphatic system disorders

Very rare: Blood formation problems (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis).

The first signs may be fever, sore throat, superficial mouth sores, flu-like symptoms, severe fatigue, nosebleeds and skin bleeding. In these

In such cases, the patient should be advised to immediately stop the medication and avoid self-medication with analgesics or antipyretics and consult a doctor.

Blood counts should be monitored regularly during prolonged treatment.

Immune system disorders:

Uncommon : Hypersensitivity reactions with skin rashes and itching, as well as asthma attacks (with possible drop in blood pressure).

The patient should be instructed to notify a physician immediately and stop taking MIG Junior in this case.

Very rare: Signs of aseptic meningitis, such as headache, nausea, vomiting, fever, stiff neck or confusion. Patients with certain immune system disorders (systemic lupus erythematosus or mixed

connective tissue disease) are at higher risk.

Severe generalised hypersensitivity reactions. Signs may include: swelling of the face, tongue and lining of the larynx with narrowing of the airways, shortness of breath,

palpitations, drop in blood pressure to life-threatening shock.

If any of these symptoms appear, which may occur even with the first application, immediate medical intervention is required.

Mental disorders

Very rare: Psychotic reactions, depression.

Nervous system disorders

Uncommon: Central nervous system disorders such as headache, dizziness, insomnia, agitation, anxiety, irritability or fatigue.

Eye disorders

Uncommon : Visual disturbances. In this case the patient should be instructed to inform a doctor and discontinue ibuprofen use.

Ear and labyrinth disorders

Rare : Tinnitus.

Cardiac disorders

Very rare: Palpitations, heart failure, myocardial infarction.

Vascular disorders

Very rare: Arterial hypertension, vasculitis.

Respiratory, thoracic and mediastinal disorders

Very rare: Asthma, bronchospasm, dyspnoea and wheezing.

Gastrointestinal disorders

Common: Gastrointestinal complaints such as heartburn, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation and mild gastrointestinal bleeding, which exceptionally may lead to anemia.

Uncommon: Gastric or intestinal ulcers, sometimes with haemorrhage and perforation. Ulcerative stomatitis, exacerbation of colitis or Crohn's disease (see section 4.4), gastritis.

Very rare: Oesophagitis, pancreatitis, formation of intestinal membrane-like structures.

The administration of MIG Junior should be stopped if the patient experiences significant upper abdominal pain, vomits blood, has blood in the stool or black stools.

Hepatobiliary disorders

Very rare: Liver function disorders, liver damage, especially with prolonged treatment, liver failure, acute hepatitis.

Skin and subcutaneous tissue disorders

Uncommon: Various skin rashes

Very rare : Bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), alopecia.

Not known: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP)

Exceptionally, severe skin infections and soft tissue complications of varicella may occur (see also “Infections and Parasitoses”).

Renal and urinary disorders

Rare : Damage to kidney tissue (papillary necrosis), especially with prolonged use, increased serum uric acid concentrations in the blood.

Very rare: Decreased urine excretion and edema formation, especially in patients with

arterial hypertension or with renal failure, nephrotic syndrome, interstitial nephritis, which may be accompanied by acute renal failure.

The use of MIG Junior should be discontinued if these symptoms occur or worsen.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. This allows

to continue monitoring the benefit/risk balance of the medicinal product. From healthcare professionals

are required to report any suspected adverse reactions via the national reporting system:

Executive Agency for Medicines 8 Damyan Gruev Street

1303 Sofia

tel.: +359 28903417

website: www.bda.bg

4.9Overdose

Symptoms of overdose

Central nervous system disorders such as headache, dizziness,

dizziness, loss of consciousness (in children and myoclonic seizures), as well as abdominal pain, nausea and vomiting. In addition, gastrointestinal bleeding, impaired

renal function and impaired liver function. In addition, hypotension, respiratory depression and cyanosis may occur. In severe poisoning, metabolic acidosis may occur.

Treatment

There is no specific antidote for ibuprofen.

Therapeutic options for treating intoxication are guided by the degree, stage, and clinical symptoms according to general intensive care measures.

5.PHARMACOLOGICAL PROPERTIES

1. Pharmacodynamic properties

Pharmacotherapeutic group: Anti-inflammatory and antirheumatic products, non-steroids; propionic acid derivatives

ATC code: M01AE01

Mechanism of action:

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that

conventional animal experiments on inflammatory models, has shown efficacy by inhibiting prostaglandin synthesis. In humans, ibuprofen reduces the inflammation associated with

inflammation pain, swelling and fever. In addition, ibuprofen reversibly inhibits ADP- and collagen-induced platelet aggregation.

Clinical efficacy and safety:

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when administered concomitantly. Some pharmacodynamic studies have shown that when administered with

A single dose of 400 mg ibuprofen administered within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) reduced the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although there is uncertainty about

Extrapolating these data to clinical cases, the possibility that regular, long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid cannot be excluded. No clinically relevant effect is considered likely with infrequent use of ibuprofen (see section 4.5).

5.2Pharmacokinetic properties

Absorption:

When administered orally, ibuprofen is partially absorbed in the stomach and then completely in the small intestine. Peak plasma levels with oral administration of normal-release dosage forms are reached after 1-2 hours.

Distribution:

Plasma protein binding is about 99%. The elimination half-life in healthy individuals, as well as in those with liver and kidney diseases, is 1.8 - 3.5 hours.

Biotransformation:

Ibuprofen is metabolized in the liver (hydroxylation, carboxylation).

Elimination:

Pharmacologically inactive metabolites are eliminated entirely, primarily via the kidneys (90

%), but also through bile.

Increased levels of unbound (S)-ibuprofen, higher AUC values for unbound (S)-ibuprofen and increased AUC of the S/R enantiomers have been reported in patients with mild renal impairment compared to healthy subjects.

In patients with end-stage renal disease who are on hemodialysis, the average

The free fraction of ibuprofen is 3% compared to 1% in healthy volunteers. Severe impairment of renal function may lead to accumulation of ibuprofen metabolites. It is not

The significance of this effect is unclear. Metabolites can be eliminated by haemodialysis (see sections 4.2, 4.3 and 4.4).

In patients with cirrhosis and moderate hepatic impairment (Child Pugh's score 6-10) treated with racemic ibuprofen, an average 2-fold prolongation of the half-life was observed and the AUC ratio of the enantiomers (S/R) was significantly lower compared to healthy subjects.

controls, suggesting an impairment of the conversion of the metabolite (R)-ibuprofen to the active (S)-enantiomer (see sections 4.2, 4.3 and 4.4).

Linearity:

At doses of 200 to 400 mg, ibuprofen has been reported to exhibit linear kinetics. At higher doses, the drug exhibits nonlinear kinetics.

5.3Preclinical safety data

The subchronic and chronic toxicity of ibuprofen in animal experiments is manifested mainly in the form of lesions and ulcers in the gastrointestinal tract.

In vitro and in vivo studies do not provide clinically relevant evidence that ibuprofen has

Mutagenic effects. There is no evidence of carcinogenic effects of ibuprofen in studies in rats and mice.

Ibuprofen inhibits ovulation in rabbits and leads to impaired implantation in various animal species (rabbit, rat, mouse). Experimental studies in rats and rabbits have shown that ibuprofen crosses the placenta. After administration of doses toxic to the mother, an increased incidence of malformations (ventricular septal defects) was observed in the offspring of rats.

6.PHARMACEUTICAL DATA

1. List of excipients

Sodium benzoate (E211), Citric acid, anhydrous, Sodium citrate,

Saccharin sodium, Sodium chloride, Hypromellose,

Xanthan gum, Maltitol, liquid, Glycerol (E422), Thaumatin (E957),

Strawberry flavor (natural flavorings, corn maltodextrin, triethyl citrate (E-1505), propylene glycol (E-1520) and benzyl alcohol),

Purified water.

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years.

After first opening: 6 months

6.4 Special storage conditions

This medicinal product does not require any special storage conditions. After first opening: Store below 30°C.

6.5 Nature and contents of container

Dark polyethylene terephthalate (PET) bottles of 30 ml, 100 ml, 150 ml and 200 ml, with a child-resistant cap and a low-density polyethylene stopper.