Ibuprofen-mb

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT IBUPROFEN-MB (IBUPROFEN-MB)

Composition:

Active ingredient: ibuprofen;

One film-coated tablet contains ibuprofen 200 mg or 400 mg;

Excipients: colloidal anhydrous silicon dioxide, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate (type A), talc, magnesium stearate, film coating Opadry II White 32F580005 (hypromellose (E 464), titanium dioxide (E 171), lactose monohydrate, macrogol 4000, and sodium citrate).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

200 mg: white, round, biconvex film-coated tablets, embossed with "2" on one side and a break line on the other side;

400 mg: white, round, biconvex film-coated tablets, embossed with "4" on one side and a break line on the other side.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Ibuprofen. ATC code M01AE01.

Pharmacological properties.

Pharmacodynamics.

Ibuprofen is a propionic acid derivative that exerts analgesic, anti-inflammatory, and antipyretic effects. The therapeutic effect of the drug as a non-steroidal anti-inflammatory drug (NSAID) is considered to result from its inhibitory action on the enzyme cyclooxygenase, leading to a marked reduction in the synthesis of prostaglandins.

Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when both are used concomitantly. Some pharmacodynamic studies have shown that administration of single 400 mg doses of ibuprofen taken 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) resulted in reduced effect of acetylsalicylic acid on thromboxane formation or platelet aggregation. Although there is uncertainty regarding extrapolation of these data to the clinical setting, the possibility cannot be excluded that regular long-term use of ibuprofen may diminish the cardioprotective effect of low-dose acetylsalicylic acid. With occasional use of ibuprofen, a clinically relevant interaction is not considered likely (see section "Interaction with other medicinal products and other forms of interaction").

Pharmacokinetics.

Ibuprofen is rapidly absorbed from the gastrointestinal tract (GI tract), with peak serum concentrations reached within 1–2 hours after administration. The elimination half-life is approximately 2 hours.

Ibuprofen is metabolized in the liver into two inactive metabolites, which are excreted by the kidneys along with unchanged ibuprofen, including in conjugated form. Renal excretion is rapid and complete.

Ibuprofen is highly bound to plasma proteins.

Clinical characteristics.

Indications.

• Ibuprofen-MB is indicated for pain relief and reduction of inflammation in the treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's disease), ankylosing spondylitis, osteoarthritis, and other non-rheumatoid (seronegative) arthropathies.
• Treatment of non-articular rheumatic conditions and periarticular disorders such as frozen shoulder (capsulitis), bursitis, tendinitis, tenosynovitis, and low back pain; Ibuprofen-MB may also be used for soft tissue injuries such as sprains and ligament tears.
• Relief of mild to moderate pain associated with conditions such as dysmenorrhea, dental pain, and postoperative pain, as well as symptomatic relief of headache, including migraine headache.

Contraindications.

Ibuprofen-MB is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

Ibuprofen-MB should not be used in patients who have previously experienced hypersensitivity reactions (e.g., asthma, urticaria, angioedema, or rhinitis) following administration of ibuprofen, acetylsalicylic acid, or other NSAIDs.

Ibuprofen-MB is also contraindicated in patients with a history of gastrointestinal bleeding or perforation related to previous NSAID therapy. The medicinal product should not be used in patients with active or a history of recurrent peptic ulceration or gastrointestinal bleeding (two or more distinct episodes of proven ulceration or bleeding).

Ibuprofen-MB should not be prescribed to patients with disorders associated with increased tendency to bleeding.

The medicinal product is contraindicated in patients with severe heart failure (NYHA class IV), hepatic and renal insufficiency (see section "Special precautions for use").

Ibuprofen-MB is contraindicated during the third trimester of pregnancy (see section "Special precautions for use").

Interaction with other medicinal products and other forms of interaction.

Patients taking any of the following medicinal products should exercise caution, as interactions with ibuprofen have been observed in some patients.

Antihypertensive agents, beta-blockers, and diuretics. NSAIDs may attenuate the effect of antihypertensive agents such as ACE inhibitors, angiotensin II receptor antagonists, beta-blockers, and diuretics. Diuretics may also increase the risk of NSAID-induced nephrotoxicity.

Cardiac glycosides. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides.

Cholestyramine. Concomitant administration of ibuprofen and cholestyramine may reduce gastrointestinal absorption of ibuprofen; however, the clinical significance is unknown.

Lithium. Decreased lithium elimination.

Methotrexate. NSAIDs may inhibit tubular secretion of methotrexate and reduce methotrexate clearance.

Cyclosporine. Increased risk of nephrotoxicity.

Mifepristone. A theoretical reduction in efficacy due to the anti-prostaglandin properties of NSAIDs. Limited data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not negatively affect mifepristone- or prostaglandin-induced cervical ripening or uterine contractility, nor does it reduce the clinical efficacy of medical abortion.

Other analgesics and selective cyclooxygenase-2 (COX-2) inhibitors. Concomitant use of two or more NSAIDs, including COX-2 inhibitors, should be avoided, as this may increase the risk of adverse reactions (see section "Special precautions for use").

Acetylsalicylic acid. As with other NSAID-containing products, concomitant use of ibuprofen and acetylsalicylic acid is generally not recommended due to the potential for increased adverse reactions. Experimental data indicate that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when administered simultaneously. Although there is uncertainty regarding extrapolation of these data to clinical settings, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. No clinically significant effect is considered likely with occasional use (see section "Pharmacological properties").

Corticosteroids. Increased risk of gastrointestinal ulceration or bleeding when used with NSAIDs (see section "Special precautions for use").

Anticoagulants. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special precautions for use").

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

Sulfonylurea derivatives. NSAIDs may potentiate the effects of sulfonylurea agents. Rare cases of hypoglycemia have been reported in patients receiving sulfonylureas and ibuprofen.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs). Increased risk of gastrointestinal bleeding when used with NSAIDs (see section "Special precautions for use").

Tacrolimus. Possible increased risk of nephrotoxicity when NSAIDs are used concomitantly with tacrolimus.

Zidovudine. Increased risk of hematological toxicity with concomitant use of NSAIDs and zidovudine. Data indicate an increased risk of hemarthrosis and hematoma in HIV(+) hemophilic patients receiving concomitant treatment with zidovudine and ibuprofen.

Aminoglycosides. NSAIDs may reduce the elimination of aminoglycosides.

Herbal extracts. Ginkgo biloba may increase the risk of bleeding when used with ibuprofen.

Inhibitors of CYP2C9. Concomitant use of ibuprofen with CYP2C9 inhibitors may increase the effect of ibuprofen (a CYP2C9 substrate). Studies with voriconazole and fluconazole (CYP2C9 inhibitors) have shown an approximately 80–100% increase in exposure to S(+)-ibuprofen. Dose reduction of ibuprofen should be considered when used concomitantly with potent CYP2C9 inhibitors, especially when high doses of ibuprofen are used with voriconazole or fluconazole.

Special precautions for use.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration", as well as gastrointestinal and cardiovascular risks below).

Like other NSAIDs, ibuprofen may mask signs of infection.

Concomitant use of Ibuprofen-MB with other NSAIDs, including selective COX-2 inhibitors, should be avoided due to an increased risk of ulceration or bleeding (see section "Interaction with other medicinal products and other forms of interaction").

Medication-overuse headache (MOH) should be suspected in patients who experience frequent or daily headaches despite (or because of) regular analgesic use. Patients with medication-overuse headache should not be treated by increasing the analgesic dose. In such cases, analgesic use should be discontinued.

Concomitant excessive alcohol intake with NSAIDs, including ibuprofen, may increase the risk of gastrointestinal (GI) adverse reactions (gastrointestinal bleeding) or central nervous system (CNS) effects, possibly due to an additive effect.

Elderly patients

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

Children

In dehydrated children and adolescents, there is a risk of impaired kidney function.

Gastrointestinal bleeding, ulceration, and perforation

Gastrointestinal bleeding, ulceration, or perforation, which may be fatal, have been reported with all NSAIDs at any time during therapy, with or without prior warning symptoms or history of serious gastrointestinal disorders.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. These patients should start treatment with the lowest available dose. Combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) should be considered for these patients, as well as for patients requiring concomitant low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk (see below and section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal disorders, especially elderly patients, should report any unusual abdominal symptoms (particularly gastrointestinal bleeding), especially during the initial stages of treatment.

Caution is advised in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), SSRIs, or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").

If gastrointestinal bleeding or ulceration occurs in patients receiving Ibuprofen-MB, treatment should be discontinued.

Ibuprofen should be used with caution in patients with a history of ulcerative colitis or Crohn's disease, as these conditions may be exacerbated (see section "Adverse reactions").

Respiratory disorders and hypersensitivity reactions

Ibuprofen-MB should be used with caution in patients with bronchial asthma, chronic rhinitis, or allergic disorders, or with a history of these conditions, as NSAIDs have been reported to cause bronchospasm, urticaria, or angioedema in such patients.

Cardiac, renal, and hepatic impairment

NSAID use may lead to dose-dependent reduction in prostaglandin formation and may provoke renal impairment. Concurrent habitual use of multiple similar analgesic drugs further increases this risk. Patients at greatest risk of this reaction include those with impaired renal, cardiac, or hepatic function, those taking diuretics, and elderly patients. These patients should use the lowest effective dose for the shortest possible duration, and renal function should be monitored, especially in those undergoing long-term treatment (see section "Contraindications").

Ibuprofen-MB should be used with caution in patients with a history of heart failure or arterial hypertension, as edema associated with ibuprofen use has been reported.

Cardiovascular and cerebrovascular effects

Patients with hypertension and/or mild to moderate congestive heart failure should be monitored appropriately and consulted, as fluid retention and edema have been reported with NSAID therapy.

Clinical studies indicate that ibuprofen use, particularly at high doses (2400 mg daily), may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke. Overall, epidemiological studies do not indicate that low-dose ibuprofen (e.g., ≤1200 mg daily) is associated with an increased risk of arterial thrombotic events.

Ibuprofen should be prescribed only after careful assessment of the clinical condition in patients with uncontrolled hypertension, congestive heart failure (NYHA class II–III), established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, and high doses (2400 mg daily) should be avoided. A careful clinical evaluation 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 daily) is required.

Cases of Kounis syndrome have been reported in patients taking ibuprofen. Kounis syndrome is defined as cardiovascular symptoms secondary to an allergic or hypersensitivity reaction involving coronary artery spasm, potentially leading to myocardial infarction.

Renal effects

Initiation of ibuprofen therapy should be done with caution in patients with significant dehydration. There is a risk of impaired renal function, particularly in dehydrated children, adolescents, and elderly patients.

As with other NSAIDs, prolonged use of ibuprofen has led to renal papillary necrosis and other renal pathological changes. Renal toxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion. In these patients, NSAID use may cause dose-dependent reduction in prostaglandin formation and, consequently, renal blood flow, potentially leading to renal failure. Patients at highest risk of this reaction include those with impaired renal, cardiac, or hepatic function, those taking diuretics or ACE inhibitors, and elderly patients. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.

Renal tubular acidosis and hypokalemia may occur after acute overdose and in patients taking ibuprofen for prolonged periods at high doses (usually over 4 weeks), including doses exceeding the recommended daily dose.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease

Patients with SLE and mixed connective tissue diseases may have an increased risk of aseptic meningitis (see below and section "Adverse reactions").

Serious skin adverse reactions (SCAR)

Serious skin adverse reactions (SCAR) have been reported with ibuprofen use, including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal (see section "Special precautions for use"). Most of these reactions occurred within the first month. If signs or symptoms suggestive of these reactions appear, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).

In rare cases, varicella may lead to serious skin and soft tissue infections. At present, the influence of NSAIDs on the exacerbation of these infections cannot be excluded. Therefore, ibuprofen use should be avoided during varicella.

Masking symptoms of underlying infection

Ibuprofen-MB may mask symptoms of infection, potentially delaying appropriate treatment and worsening infection outcomes. This has been observed in bacterial pneumonia and bacterial complications of varicella. When using Ibuprofen-MB tablets for fever or pain associated with infection, infection should be monitored. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Hematological effects

Ibuprofen, like other NSAIDs, may interfere with platelet aggregation and prolong bleeding time in healthy individuals.

Aseptic meningitis

Aseptic meningitis has been observed rarely in patients taking ibuprofen. Although this is more likely to occur in patients with SLE and related connective tissue disorders, it has also been observed in patients without underlying chronic disease.

Female fertility

Use of Ibuprofen-MB may impair female fertility and is therefore not recommended for women attempting to conceive. In women experiencing conception difficulties or undergoing infertility evaluation, discontinuation of the drug should be considered.

Excipients

Ibuprofen-MB tablets contain lactose monohydrate and therefore should not be administered to patients with rare hereditary conditions of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.

This product contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage, cardiac defects, and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The risk is considered to increase with higher doses and longer duration of therapy. Animal studies have shown that prostaglandin synthesis inhibitors cause increased pre- and post-implantation loss and embryonic/fetal mortality. Furthermore, in animals treated with a prostaglandin synthesis inhibitor during the organogenetic period, increased incidences of various developmental abnormalities, including cardiovascular malformations, have been observed. From the 20th week of pregnancy, use of Ibuprofen-MB may cause oligohydramnios due to impaired fetal renal function. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction after treatment in the second trimester, most of which resolved after treatment cessation. Therefore, Ibuprofen-MB should not be prescribed during the first and second trimesters of pregnancy except in cases of extreme necessity. If the drug is used in women 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.

Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after ibuprofen exposure for several days starting from the 20th week of pregnancy. If oligohydramnios or arterial duct constriction is detected, Ibuprofen-MB should be discontinued.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus as follows:

• Cardio-pulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension).
• Impaired renal function, which may progress to renal failure with oligohydramnios (see above).

Near the end of pregnancy, prostaglandin synthesis inhibitors may affect the mother and newborn as follows:

• Possible prolongation of bleeding time.
• Inhibition of uterine contractions, which may lead to delayed or prolonged labor.

Therefore, Ibuprofen-MB is contraindicated during the third trimester of pregnancy.

Lactation

In limited available studies, NSAIDs may appear in breast milk in very low concentrations. Ibuprofen use should be avoided during breastfeeding if possible.

See section "Special precautions for use" regarding female fertility.

Ability to affect reaction speed when driving or operating machinery.

NSAIDs may cause adverse reactions such as dizziness, somnolence, fatigue, and visual disturbances. If such adverse reactions occur, patients should not drive or operate machinery.

Method of Administration and Dosage

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Precautions").

Adults and children aged 12 years and older

The recommended dose of the medicinal product Ibuprofen-MB is 1200–1800 mg per day, divided into several doses. Some patients may be maintained on a dose of 600–1200 mg daily. In cases of severe or acute conditions, dose escalation may be beneficial until the acute phase is under control, provided the total daily dose does not exceed 2400 mg in divided doses.

For younger children, more suitable dosage forms are available.

In juvenile rheumatoid arthritis, doses up to 40 mg/kg body weight per day in divided doses may be used.

Elderly patients

Elderly patients have an increased risk of serious adverse effects. If ibuprofen use is considered necessary, the lowest effective dose should be used for as short a duration as possible. Patients should be monitored regularly for gastrointestinal bleeding during NSAID therapy. In cases of renal or hepatic impairment, the dose should be individually adjusted.

Renal impairment

Patients with mild to moderate renal impairment (see section "Special Precautions") and patients with severe renal insufficiency (see section "Contraindications").

Hepatic impairment

Special considerations for patients with mild to moderate hepatic impairment (see section "Special Precautions") and patients with severe hepatic dysfunction (see section "Contraindications").

For oral use. Patients with a sensitive stomach are advised to take the medicinal product Ibuprofen-MB with food. If Ibuprofen-MB is taken shortly after a meal, the onset of action of ibuprofen may be delayed. It is preferable to take the medication during or after food intake, with sufficient fluid. Ibuprofen-MB tablets should be swallowed whole and not chewed, broken, crushed, or sucked to avoid oral discomfort and throat irritation.

It is recommended to use the lowest effective dose for the shortest duration necessary to relieve symptoms (see section "Special Precautions").

Children

The medicinal product Ibuprofen-MB should not be administered to children under 12 years of age.

Overdose

Toxicity

Signs and symptoms of toxicity are generally not observed at doses below 100 mg/kg in children or adults. However, supportive treatment may be required in some cases. Signs and symptoms of toxicity have been observed in children after ingestion of 400 mg/kg or more.

Symptoms

In most patients who have ingested a significant amount of ibuprofen, symptoms appear within 4–6 hours.

The most commonly reported symptoms of overdose include nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) effects include headache, tinnitus, dizziness, seizures, and loss of consciousness. Rarely reported effects include nystagmus, metabolic acidosis, hypothermia, renal impairment, gastrointestinal bleeding, coma, apnea, diarrhea, and CNS and respiratory depression. In severe poisoning, metabolic acidosis may occur, and prothrombin time/INR may be prolonged, likely due to effects on circulating coagulation factors. Disorientation, agitation, unconsciousness, and cardiovascular toxicity, including arterial hypotension, bradycardia, and tachycardia, have also been reported. In cases of significant overdose, renal failure and hepatic injury are possible. Large overdoses are generally well tolerated if no other drugs are co-ingested.

Prolonged use at doses higher than recommended may lead to severe hypokalemia and renal tubular acidosis. Symptoms may include decreased level of consciousness and generalized weakness (see sections "Special Precautions" and "Adverse Reactions").

Therapeutic measures

Symptomatic treatment is required for patients. Activated charcoal should be considered within one hour of ingestion of a potentially toxic amount. Additionally, in adults, gastric lavage should be considered within one hour after ingestion of a potentially life-threatening overdose.

Adequate urine output must be maintained.

Renal and hepatic function should be closely monitored.

Patients should be observed for at least four hours after ingestion of a potentially toxic amount.

Frequent or prolonged seizures should be treated with intravenous diazepam. Other interventions may be indicated based on the patient's clinical condition.

Adverse Reactions

Gastrointestinal system. Adverse reactions most commonly observed are of gastrointestinal nature. Peptic ulcers, gastrointestinal perforation, or gastrointestinal bleeding, sometimes fatal, particularly in elderly patients, may occur (see section "Special warnings and precautions for use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, vomiting, ulcerative stomatitis, gastrointestinal hemorrhage, and exacerbations of colitis and Crohn's disease have been reported following ibuprofen use (see section "Special warnings and precautions for use"). Gastritis, duodenal ulcer, gastric ulcer, and gastrointestinal perforation have been observed less frequently.

Immune system. Hypersensitivity reactions have been reported during NSAID therapy. These may include: (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity including asthma, worsening of asthma, bronchospasm, or dyspnea, or (c) various skin disorders including rashes of different types, pruritus, urticaria, purpura, angioedema, and very rarely, erythema multiforme, bullous dermatoses (including Stevens-Johnson syndrome and toxic epidermal necrolysis).

Cardiac and vascular disorders. Edema, hypertension, and heart failure have been reported in association with NSAID therapy. Clinical studies indicate that the use of ibuprofen, particularly at high doses (2400 mg daily), may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke (see section "Special warnings and precautions for use").

Infections and infestations. Rhinitis and aseptic meningitis (particularly in patients with pre-existing autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of nuchal rigidity, headache, nausea, vomiting, fever, or disorientation have been reported (see section "Special warnings and precautions for use").

Exacerbations of infectious inflammation have been observed in association with NSAID use. Therefore, if signs of infection appear or worsen during ibuprofen treatment, patients are advised to seek immediate medical attention.

Skin and subcutaneous tissue. In rare cases, severe skin infections and soft tissue complications may occur during varicella (chickenpox) (see also "Infections and infestations").

The following adverse reactions are considered probably related to ibuprofen and are presented according to frequency categories and MedDRA organ system classifications. Frequency categories are defined as follows: 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), and not known (cannot be estimated from available data).

*Renal tubular acidosis and hypokalemia have been reported under post-marketing conditions, usually after prolonged use of the ibuprofen component at doses higher than recommended.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and/or lack of efficacy of the medicinal product through the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

No special storage conditions required.

Keep out of the reach of children.

Packaging.

10 or 12 tablets in a blister; 1 blister per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

STRIDES PHARMA SCIENCE LIMITED

STRIDES PHARMA SCIENCE LIMITED

Manufacturer's address and location of manufacturing site.

No. 36/7, Suragajakkanahalli, Indlavadi Cross, Anekal Taluk, Bengaluru, Karnataka 562106, India

No. 36/7, Suragajakkanahalli, Indlavadi Cross, Anekal Taluk, Bengaluru, Karnataka 562106, India

Marketing Authorization Holder.

M.BIOTECH LIMITED

M.BIOTECH LIMITED

Address of the Marketing Authorization Holder.

Gladstone House, 77-79 High Street, Egham TW20 9HY, Surrey, United Kingdom

Gladstone House, 77-79 High Street, Egham TW20 9HY, Surrey, United Kingdom