1. NAME OF THE MEDICINAL PRODUCT

MIG for Children 20 mg/ml oral suspension MIG for Children 20 mg/ml oral suspension

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml of suspension contains 20 mg of ibuprofen. Excipients with known action

1 ml of oral suspension contains 500 mg of liquid maltitol and 3.7 mg of sodium.

For the full list of excipients, see section 6.1.

3. MEDICINAL FORM

Oral suspension

white to off-white viscous suspension

4. CLINICAL DATA

1. Therapeutic indications

For short-term symptomatic treatment of

• fever
• mild to moderately severe pain

MIG for children is indicated for children weighing from 5 kg (age 6 months) to 29 kg weight (age 9 years).

4.2 Dosage and method of administration

Dosage

The dosage is in accordance with the table below. In children, MIG for children is dosed according to body weight or age, 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. It should not be less than 6 hours. Do not exceed the recommended dose.

For oral use.

For short-term use only.

If the use of this medicinal product is required for more than 3 days or if the symptoms worsen, a doctor should be consulted.

Adverse reactions can be minimized by using the lowest effective dose for the shortest time to control symptoms (see section 4.4).

Special groups of patients

Renal impairment (see sections 4.4 and 5.2):

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

Liver failure (see sections 4.4 and 5.2):

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

Pediatric population:

MIG for children is not recommended for use in infants under 6 months or under 5 kg.

Application method

MIG for children is taken during or after meals.

For patients with a sensitive stomach, it is recommended that MIG for children be taken with a meal.

Shake before use. For accurate dosing, a dosing syringe is included in the package (graduated from half a milliliter to 5 ml).

4.3 Contraindications

MIG for children is contraindicated in patients with:

- hypersensitivity to the active substance or any of the excipients listed in point 6.1;

• a history of bronchospasm, asthma, rhinitis, angioedema or urticaria associated with taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs);
• unexplained disorders in hematopoiesis;
• active or history of recurrent peptic ulcer/bleeding (two or more separate episodes of proven ulceration or bleeding);
• history of gastrointestinal bleeding or perforation related to previous NSAID treatment;
• cerebrovascular or other active hemorrhage;
• severe liver or kidney failure;
• severe heart failure (NYHA Class IV);
• severe dehydration (caused by vomiting, diarrhea or insufficient fluid intake);
• pregnancy in the last trimester (see item 4.6).

4.4 Special warnings and precautions for use

Adverse reactions can be minimized if the lowest effective dose is administered for the shortest time to control symptoms (see section 4.2 and section 4.8).

Gastrointestinal safety

Concomitant use of MIG for children with NSAIDs, including cyclooxygenase-2 selective inhibitors, should be avoided.

Old age

Elderly patients show an increased frequency of adverse reactions to

NSAIDs, especially gastrointestinal haemorrhage and perforation, which may be fatal (see section 4.2).

Gastrointestinal haemorrhage, ulcer and perforation:

Gastrointestinal hemorrhage, ulceration, or perforation, which may be fatal, have been reported with all NSAIDs at any time of treatment, with or without warnings.

symptoms or previous history of severe gastrointestinal events.

The risk of gastrointestinal bleeding, ulcer or perforation is higher with an increase in

doses of NSAIDs, in patients with a history of ulcer, especially if it is complicated by hemorrhage 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 in whom it is necessary

concomitant use of low-dose acetylsalicylic acid or other drugs that increase the gastrointestinal risk should be considered combined treatment with

protective agents (eg misoprostol or proton pump inhibitors) (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 early stages of treatment.

Caution is advised in patients receiving concomitant treatment that may increase the risk of ulceration and bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or

antithrombotic substances, such as acetylsalicylic acid (see section 4.5).

If gastrointestinal bleeding or ulceration occurs in patients receiving MIG for children, treatment should be discontinued.

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

Cardiovascular and cerebrovascular effects

Caution (consultation with a physician 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, especially in high doses (2400 mg/day) may be associated with a slightly increased risk of arterial thrombotic events (eg, myocardial infarction or stroke). In general, epidemiological studies do not

showed that low doses of ibuprofen (eg, £1200 mg/day) were 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 cerebral

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 (ie, hypertension,

hyperlipidemia, diabetes mellitus, smoking), especially with high doses of ibuprofen (2400 mg/day).

Severe skin reactions

Severe skin reactions, some fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported widely.

rarely in connection with the use of NSAIDs (see section 4.8). Patients are at the highest risk of these reactions early in the course of treatment: the onset of the reaction in most cases is within the first month of treatment. Reported acute generalized

acute generalized exanthematous pustulosis (AGEP) in relation to products containing ibuprofen. MIG for children should be discontinued at the first appearance of a skin rash, mucosal lesions or any other sign of

hypersensitivity.

Exceptionally, chicken pox may underlie serious infectious complications of the skin and soft tissues. At this point, the role of NSAIDs cannot be ruled out

worsening of these infections. Therefore, it is recommended to avoid the use of MIG for children in cases of chickenpox.

Other remarks

MIG for children should only be used after a strict benefit/risk assessment:

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

Particularly careful follow-up by a doctor is required:

• with impaired renal function (as acute deterioration of renal function may occur in patients with pre-existing renal disease);
• with dehydration (there is a risk of kidney damage in dehydrated children and adolescents);
• with liver dysfunction;
• immediately after major surgical procedures;
• in patients who suffer from hay fever, nasal polyps, chronic edema of the nasal mucosa or chronic obstructive respiratory diseases, as there is an increased risk of allergic reactions. They can manifest as asthma attacks (so-called analgesic asthma), angioedema or urticaria;
• in patients who react allergically to other substances, since they have an increased risk of hypersensitivity reactions when using MIG for children.

Severe acute hypersensitivity reactions (eg anaphylactic shock) have been observed very rarely. At the first signs of a hypersensitivity reaction after taking/application of MIG for children, the treatment should be stopped. In accordance with

symptoms should be treated medically by specialized personnel.

Respiratory disorders: caution is required when MIG for children is administered to patients who suffer from or have a history of bronchial asthma, as NSAIDs have been reported to increase

bronchospasm in these patients.

Ibuprofen, the active ingredient in MIG for children, can temporarily inhibit platelet function (platelet aggregation). Therefore, patients with impaired blood coagulation should be carefully monitored.

With long-term use of MIG for children, regular monitoring of liver values, kidney function and blood count is required.

Prolonged use of any type of pain reliever for a headache can make it worse. If this occurs or is suspected, consultation with

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

In general, the regular use of pain relievers, especially a combination of several

pain-relieving active substances, may lead to persistent kidney damage with the risk of kidney failure (analgesic nephropathy).

With the simultaneous use of alcohol with NSAIDs, the adverse reactions associated with the active substance, especially with regard to the gastrointestinal tract or the central nervous system, may increase.

NSAIDs can mask the symptoms of infection and high fever. Regarding women's fertility, see item 4.6.

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

This medicinal product contains 3.7 ml of sodium per milliliter. Consider in 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 with the following medicinal substances:

Other NSAIDs, including salicylates

The simultaneous administration of several NSAIDs may increase the risk of gastrointestinal ulcers and bleeding due to a synergistic effect. Therefore, the simultaneous administration of ibuprofen with other NSAIDs should be avoided (see section 4.4).

Digoxin, Phenytoin, Lithium

Concomitant administration of MIG for children with digoxin, phenytoin, and lithium may increase the serum levels of these medicinal products. With proper administration (maximum 3 days), monitoring of serum levels of lithium, digoxin and phenytoin is generally not necessary.

Diuretics, ACE-inhibitors, beta-receptor blockers and angiotensin II-antagonists NSAIDs can 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 result in additional damage to

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 consideration should be given to monitoring renal function after initiation of combination therapy and periodically thereafter.

The simultaneous use of MIG for children and potassium-sparing diuretics can lead to hyperkalemia.

Corticosteroids

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

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs)

Increased risk of gastrointestinal bleeding (see section 4.4).

Acetylsalicylic acid

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

Experimental data show that ibuprofen can competitively inhibit the effect of low doses of acetylsalicylic acid on platelet aggregation when administered simultaneously. Although there are uncertainties regarding the extrapolation of 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.

Accidental use of ibuprofen is considered unlikely to produce a clinically relevant effect (see section 5.1).

Methotrexate

The administration of MIG to children 24 hours before or after the administration of methotrexate can lead to increased concentrations of methotrexate and to an increase in its toxic effect.

Cyclosporine

The risk of kidney damage from cyclosporine may increase with the concomitant use of certain non-steroidal anti-inflammatory drugs. This effect cannot be excluded also with the combination of cyclosporine and ibuprofen.

Anticoagulants

NSAIDs can enhance the effect of anticoagulants, such as warfarin (see section 4.4).

Sulfonylureas

Clinical studies have shown interactions between nonsteroidal anti-inflammatory drugs and antidiabetic drugs (sulfonylureas). Although so far they haven't

reported interactions between ibuprofen and sulfonylureas, monitoring of blood sugar values is recommended as a precaution when they are used simultaneously.

Tacrolimus

The risk of nephrotoxicity increases with the simultaneous administration of the two medicinal products.

Zidovudine

There is evidence of an increased risk of hemarthroses and hematomas in HIV-positive hemophiliacs taking zidovudine and ibuprofen concurrently.

Probenecid and sulfinpyrazone

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

Quinolone antibiotics

Animal data indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may increase the risk of seizures.

CYP2C9 inhibitors

Concomitant administration of ibuprofen with CYP2C9 inhibitors may increase

exposure to ibuprofen (a CYP2C9 substrate). In a study with voriconazole and fluconazole

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

4.6 Fertility, pregnancy and breastfeeding

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 after the use of prostaglandin synthesis inhibitors in early pregnancy. The risk is thought to increase with dose and duration of therapy.

In animals, administration of prostaglandin synthesis inhibitors results in increased pre- and post-implantation losses and embryo-fetal lethality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals administered prostaglandin synthesis inhibitors during the period of organogenesis.

During the first and second trimesters of pregnancy, ibuprofen should not be used unless absolutely necessary. If ibuprofen is taken by women who are trying to conceive or during the first and second trimesters 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 inhibitors of prostaglandin synthesis:

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

Therefore, ibuprofen is contraindicated during the third trimester of pregnancy. Breastfeeding

Ibuprofen and its metabolites pass into breast milk in small amounts. As

as there are no known harmful effects in the infant so far, in general short-term use of ibuprofen in the recommended doses does not require discontinuation of

breastfeeding.

Fertility

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

4.7 Effects on the ability to drive and use machines

Since the use of high doses of MIG for children may cause adverse reactions from the central nervous system, such as fatigue and dizziness, in isolated cases

the ability to react and actively participate in street traffic and operating machinery may be impaired. This applies to a greater extent when combined with alcohol.

4.8 Adverse drug reactions

The following frequency is used as a basis for evaluating side effects:

Very common: ≥ 1/10;

Common: ≥1/100 to < 1/10;

Uncommon: ≥1/1,000 to < 1/100;

Rare: ≥1/10,000 to < 1/1,000;

Very rare: < 1/10,000;

Not known: frequency cannot be determined from the available data.

The following list of side effects covers all side effects that are known with ibuprofen treatment, including those with high doses for a long time in patients with rheumatism. The stated frequency refers to very rare reports, with short-term administration of doses up to a maximum of 1200 mg ibuprofen for oral dosage forms and a maximum of 1800 mg for suppositories.

It should be noted that the following side effects are dose-dependent and vary from patient to patient.

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

stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4). Gastritis has been observed less frequently. The risk of gastrointestinal bleeding depends on the administered dose and the duration of use.

Edema, hypertension and heart failure have been reported in association with NSAID treatment.

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

Infections and infestations

Very rare: exacerbation of infectious inflammation (e.g. development of necrotizing fasciitis) has been described with the use of non-steroidal anti-inflammatory drugs.

This is most likely related to the mechanism of action of nonsteroidal anti-inflammatory drugs.

If signs of infection appear or worsen during the administration of MIG for children, it is recommended that the patient immediately see a doctor. Whether this is an indication for anti-infective/antibiotic therapy should be considered.

Very rare: symptoms of aseptic meningitis with stiff neck, headache, nausea, vomiting, high fever and clouded consciousness have been observed with ibuprofen. Patients with autoimmune diseases (SLE, mixed connective tissue disease) seem to be predisposed.

Disorders of the blood and lymphatic system

Very rare: impaired blood formation (anemia, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis).

The first signs can be fever, sore throat, superficial sores in the mouth, flu-like complaints, severe fatigue, bleeding from the nose and skin. In these

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

Blood counts should be monitored regularly during long-term treatment. Disorders of the immune system

Uncommon: hypersensitivity reactions with skin rash and itching, as well as asthmatic

seizures (with a possible drop in blood pressure).

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

Very rare: severe generalized hypersensitivity reactions. They can manifest as swelling of the face, swelling of the tongue, swelling of the larynx with narrowing of the airways, respiratory distress, palpitations, a drop in blood pressure to

life-threatening shock.

If any of these symptoms occur, which can happen even with the first application, immediate medical attention is required.

Mental disorders

Very rare: psychotic reactions, depression.

Disorders of the nervous system

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

Eye disorders

Uncommon: visual disturbances. In this case, the patient should be instructed to immediately notify a physician and discontinue ibuprofen.

Ear and labyrinth disorders Rare: tinnitus.

Heart disorders

Very rare: palpitations, heart failure, myocardial infarction.

Vascular disorders

Very rare: arterial hypertension.

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, diarrhoea, constipation and mild gastrointestinal bleeding, which may exceptionally lead to anaemia.

Uncommon: gastrointestinal ulcers, with possible hemorrhage or perforation. Ulcerative stomatitis, exacerbation of colitis or Crohn's disease (see section 4.4), gastritis.

Very rare: esophagitis, pancreatitis, formation of intestinal diaphragm-like structures.

The patient should be instructed to stop taking the medicinal product and see a doctor immediately if relatively severe upper abdominal pain or melena or hematemesis occurs.

Hepato-biliary disorders

Very rare: disorders of liver function, liver damage, especially with long-term 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.

With an unknown frequency: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP).

Exceptionally, severe skin infections and soft-tissue complications can occur with chickenpox (see also "Infections and parasitosis").

Kidney and urinary tract disorders

Rare: damage to kidney tissue (papillary necrosis), especially with long-term use, increased serum concentrations of uric acid in the blood.

Very rare: decreased urinary 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.

Damage to kidney tissue (papillary necrosis) and increased blood uric acid concentrations may also occur in rare cases.

Therefore, kidney function should be monitored regularly. Reporting of suspected adverse reactions

Post-marketing reporting of suspected adverse reactions is important. This allows continued monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals are required to report any suspected adverse reaction through a national reporting system:

Executive Agency for Medicines, 8 Damyan Gruev Street

1303 Sofia

Phone: +359 28903417

website: www.bda.bg

4.9 Overdose

Symptoms of overdose

Central nervous system disorders such as headache, vertigo, dizziness and loss of consciousness (and myoclonic convulsions in children), as well as abdominal pain, nausea and vomiting may appear as symptoms of overdose. In addition, gastrointestinal

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

Therapeutic measures in case of overdose There is no specific antidote.

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

5. PHARMACOLOGICAL PROPERTIES

1. Pharmacodynamic properties

Pharmacotherapeutic group: anti-inflammatory and anti-rheumatic products, non-steroidal

Derivatives of propionic acid ATS code: M01AE01

Mechanism of action

Ibuprofen is a non-steroidal anti-inflammatory medicinal product that, in conventional animal experiments on inflammatory models, has proven effective by inhibiting the synthesis of prostaglandins. In humans, ibuprofen has an antipyretic effect, it decreases

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

Clinical efficacy and safety

Experimental data show that ibuprofen can competitively inhibit the effect of low doses of acetylsalicylic acid on platelet aggregation when administered simultaneously. Some pharmacodynamic studies show that when using

a single dose of 400 mg ibuprofen within 8 hours before or up to 30 minutes after administration of the immediate-release form of acetylsalicylic acid (81 mg), a reduction in the effect of acetylsalicylic acid on thromboxane formation or on platelet aggregation was observed. Although there are uncertainties about

extrapolation of 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. Accidental use of ibuprofen is considered unlikely to produce a clinically relevant effect (see section 4.5).

5.2 Pharmacokinetic properties

Absorption

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

Distribution

Plasma protein binding is about 99%

Biotransformation

Ibuprofen is metabolized in the liver (hydroxylation, carboxylation)

Elimination

Pharmacologically inactive metabolites are completely eliminated, mainly through the kidneys (90

%), but also through the bile. The elimination half-life in healthy subjects, as well as in those with liver and kidney disease, is 1.8 – 3.5 hours.

Kidney damage

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

In end-stage renal disease undergoing hemodialysis, the mean free fraction of ibuprofen is 3% compared to 1% in healthy volunteers. Severe disabilities of

renal function may lead to accumulation of ibuprofen metabolites. Is not

the significance of this effect is clear. Metabolites can be eliminated by hemodialysis (see sections 4.2, 4.3 and 4.4).

Liver disorder

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

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

Linear/non-linear kinetics

At doses of 200 to 400 mg, ibuprofen has been reported to exhibit linear kinetics. At higher doses, the drug shows non-linear kinetics.

5.3 Preclinical safety data

The subchronic and chronic toxicity of ibuprofen in animal studies 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 data that ibuprofen has

mutagenic effects. There was no evidence of carcinogenic effects of ibuprofen in studies in rats and mice.

Ibuprofen causes inhibition of ovulation in rabbits, as well as impaired implantation in various animal species (rabbit, rat, mouse). Experimental studies in rats and rabbits show that ibuprofen crosses the placenta. After administration of doses toxic to the mother, the generation of rats showed an increased frequency of

malformations (ventricular septal defects).

6. PHARMACEUTICAL DATA

1. List of excipients

Sodium benzoate

Citric acid, anhydrous Sodium citrate

Saccharin sodium Sodium chloride Hypromellose

Xanthan gum Liquid maltitol Glycerol Purified water

Strawberry flavor (contains substances identical to natural flavors, natural flavoring products, propylene glycol)

6.2 Incompatibilities

Not applicable

6.3 Expiry Date

3 years

After first opening the bottle: 6 months if stored below 25ºС.

6.4 Special storage conditions

This medicinal product does not require special storage conditions.

6.5 Packaging data

Amber colored polyethylene terephthalate (PET) bottle with a high density polyethylene (HDPE) screw cap secured with low density polyethylene (LDPE).