Brufen Retard 800 mg prolonged-release tablets - summary of product characteristics (SPC) (2023)

Active ingredient: Ibuprofen BP (800mg)

For the complete list of excipients, see section 6.1.

Brufen Retard is indicated for its analgesic and anti-inflammatory effects in the treatment of rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's disease), ankylosing spondylitis, osteoarthritis and other non-rheumatoid (seronegative) arthropathies.

In the treatment of non-articular rheumatic conditions, Brufen Retard is indicated for periarticular conditions such as frozen shoulder (capsulitis), bursitis, tendinitis, tenosynovitis and low back pain; Brufen Retard can also be used for soft tissue injuries such as sprains and strains.

Brufen Retard is also indicated for its analgesic effect in the relief of mild to moderate pain, such as dysmenorrhea, dental and postoperative pain, and in the symptomatic relief of headache, including migraine.

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

Adults and children over 12 years of age: two tablets taken as a single daily dose, preferably in the afternoon, just before bedtime. Tablets should be swallowed whole with plenty of liquid and should not be chewed, broken, crushed or sucked to avoid oral discomfort and throat irritation. In severe or acute conditions, the total daily dose may be increased to three tablets in two divided doses.

Children: Not recommended for children under 12 years old.

The lowest effective dose should be used for the shortest period necessary to relieve symptoms (see section 4.4).

Elderly: The elderly are at greater risk of serious consequences of adverse reactions. If an NSAID is deemed necessary, use the lowest effective dose and for the shortest possible time. The patient should be regularly monitored for gastrointestinal bleeding during treatment with NSAIDs. If renal or hepatic function is compromised, the dose must be assessed individually.

Renal insufficiency:

Patients with mild to moderate renal impairment (see section 4.4 - Special warnings and precautions for use) and patients with severe renal impairment (see section 4.3 - Contraindications).

liver failure:

For patients with mild to moderate hepatic impairment (see section 4.4 Special warnings and precautions for use) and patients with severe hepatic impairment (see section 4.3- Contraindications).

For oral administration. Patients with a sensitive stomach are recommended to take Brufen with food. If taken shortly after meals, the onset of action of Brufen may be delayed. Take preferably with or after meals.

Brufen is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

Brufen should not be used in patients who have already experienced hypersensitivity reactions (eg asthma, urticaria, angioedema or rhinitis) after taking ibuprofen, acetylsalicylic acid or other NSAIDs.

Brufen is also contraindicated in patients with a history of gastrointestinal bleeding or perforation related to prior NSAID treatment. Brufen should not be used in patients with active recurrent peptic ulcer disease or a history of gastrointestinal bleeding (two or more distinct episodes of proven ulceration or bleeding).

Brufen should not be administered to patients with conditions involving an increased tendency to bleed.

Brufen is contraindicated in patients with severe heart failure (NYHA class IV), hepatic impairment and renal impairment (see section 4.4).

Brufen is contraindicated during the last trimester of pregnancy (see section 4.6).

Adverse reactions can be minimized by using the lowest effective dose for the shortest period of time necessary to control symptoms (see section 4.2 and gastrointestinal and cardiovascular risks below). Like other NSAIDs, ibuprofen can mask signs of infection.

Concomitant use of Brufen with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to an increased risk of ulceration or bleeding (see section 4.5).

The diagnosis of medication overuse headache (CAM) should be suspected in patients who present with frequent or daily headaches despite (or because of) regular use of analgesic medication. Patients with medication overuse headache should not be treated by increasing the analgesic dose. In such cases, the use of analgesics should be discontinued.

Concomitant consumption of excessive alcohol with NSAIDs, including ibuprofen, may increase the risk of adverse effects in the gastrointestinal tract, such as gastrointestinal or central nervous system bleeding, possibly due to the additive effect.

Geezer

The elderly have a higher frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).

pediatric population

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

Gastrointestinal bleeding, ulceration and perforation

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

The risk of gastrointestinal bleeding, ulceration or perforation is greater with increasing doses of NSAIDs, in patients with a history of ulcer, especially if complicated by bleeding or perforation (see section 4.3), and in elderly patients. These patients should start treatment on the lowest available dose. Combination therapy with protective agents (eg, misoprostol or proton pump inhibitors) should be considered for these patients and also for patients who require concomitant low-dose aspirin or other medications that may increase gastrointestinal risk (see below and section 4.5).

Patients with a history of GI disease, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding), especially in the early stages of treatment.

Caution should be exercised in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as aspirin (see section 4.5).

When gastrointestinal bleeding or ulceration occurs in patients receiving Brufen, treatment should be discontinued.

NSAIDs 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 4.8).

Respiratory disorders and hypersensitivity reactions

Caution is required if Brufen is administered to patients suffering from bronchial asthma or with a history of bronchial asthma, chronic rhinitis or allergic diseases, as NSAIDs have been reported to precipitate bronchospasm, urticaria or angioedema in these patients.

Heart, kidney and liver failure

Administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and precipitate renal failure. Regular concomitant intake of several similar analgesics further increases this risk. Patients most at risk of this reaction are those with kidney failure, heart failure, liver dysfunction, those taking diuretics, and the elderly. For these patients, use the lowest effective dose for the shortest possible time and monitor renal function, especially in patients treated long term (see also section 4.3).

Brufen should be administered with caution in patients with a history of heart failure or hypertension, as edema associated with ibuprofen administration has been reported.

Cardiovascular and cerebrovascular effects

Patients with a history of hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and counseling, as fluid retention and edema have been reported in association with NSAID treatment.

Clinical studies suggest that the use of ibuprofen, particularly at high doses (2400 mg/day), may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke. In general, epidemiological studies do not suggest that low doses of ibuprofen (eg, ≤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 should only be treated with ibuprofen after careful consideration and high doses (2400 mg/kg) should be avoided . day). Special attention should also be given before initiating long-term treatment of patients with risk factors for cardiovascular events (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking), particularly if high doses of ibuprofen (2400 mg/day) are required ).

kidney effects

Caution should be exercised when initiating treatment with ibuprofen in patients with considerable dehydration. There is a risk of kidney failure, especially in dehydrated children, adolescents and elderly people.

As with other NSAIDs, prolonged administration of ibuprofen has resulted in 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, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, potentially leading to renal failure. Patients most at risk of this reaction are those with kidney failure, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID treatment is usually followed by recovery to the pre-treatment state.

SLE and mixed connective tissue disease

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases there may be an increased risk of aseptic meningitis (see below and section 4.8).

severe skin reactions

Serious skin reactions, some of them fatal, such as 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 appear to be at greatest risk of these reactions at the start of treatment, with the onset of the reaction occurring within the first month of treatment in most cases. Acute generalized exanthematous pustulosis (AGEP) has been reported in association with ibuprofen-containing products. Brufen should be discontinued at the first appearance of rash, mucosal lesions or any other sign of hypersensitivity.

In exceptional cases, chickenpox can be the source of serious infectious complications of the skin and soft tissues. So far, a contributing role of NSAIDs in aggravating these infections cannot be ruled out. Therefore, it is advisable to avoid using ibuprofen in case of chickenpox.

hematological effects

Ibuprofen, like other NSAIDs, can interfere with platelet aggregation and prolong bleeding time in normal subjects.

aseptic meningitis

Aseptic meningitis has been observed rarely in patients taking ibuprofen. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients without underlying chronic disease.

impaired female fertility

The use of Brufen can affect female fertility and is not recommended in women trying to conceive. In women who have difficulty conceiving or who are being investigated for infertility, withdrawal from Brufen should be considered.

Masking symptoms of underlying infections

Brufen retard can mask the symptoms of the infection, which can delay starting proper treatment and thus worsen the outcome of the infection. This has been seen in community-acquired bacterial pneumonia and bacterial complications of chickenpox. When Brufen retard is given to relieve fever or pain related to an infection, infection control is recommended. In non-hospital settings, the patient should consult a physician if symptoms persist or worsen.

Caution should be exercised in patients treated with any of the following drugs, as interactions have been reported in some patients.

Antihypertensives, beta-blockers and diuretics: NSAIDs may reduce the effect of antihypertensives such as ACE inhibitors, angiotensin II receptor antagonists, beta-blockers and diuretics.

Diuretics may also increase the risk of nephrotoxicity from NSAIDs.

Cardiac glycosides: NSAIDs can exacerbate heart failure, reduce GFR and increase plasma levels of cardiac glycosides.

cholestyramine; Concomitant administration of ibuprofen and cholestyramine may reduce the absorption of ibuprofen from the gastrointestinal tract. However, the clinical significance is unknown.

Lithium: Decreased elimination of lithium.

Methotrexate: NSAIDs may inhibit tubular secretion of methotrexate and reduce methotrexate elimination.

Ciclosporin: increased risk of nephrotoxicity.

Mifepristone: Theoretically, a decrease in drug efficacy could occur due to the antiprostaglandin properties of NSAIDs. Limited evidence suggests that co-administration of NSAIDs on the day of prostaglandin administration does not negatively influence the effects of mifepristone or prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical termination of pregnancy.

Other analgesics and selective cyclooxygenase-2 inhibitors: Avoid concomitant use of two or more NSAIDs, including Cox-2 inhibitors, as this may increase the risk of adverse effects (see section 4.4).

Aspirin (acetylsalicylic acid): As with other NSAID-containing products, concomitant administration of ibuprofen and aspirin is generally not recommended due to the potential for increased adverse effects.

Experimental data suggest that ibuprofen can competitively inhibit the effect of low-dose aspirin on platelet aggregation when administered concomitantly. Although there are concerns about extrapolating these data to the clinical situation, the possibility that regular and prolonged use of ibuprofen may reduce the cardioprotective effect of low-dose aspirin cannot be excluded. No clinically relevant effects are considered likely with occasional use (see section 5.1).

Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding with NSAIDs (see section 4.4).

Anticoagulants: NSAIDs may potentiate the effects of anticoagulants such as warfarin (see section 4.4).

Quinolone antibiotics: Animal data indicate that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may be at increased risk of developing seizures.

Sulfonylureas: NSAIDs can potentiate the effects of sulfonylurea drugs. There have been rare reports of hypoglycemia in patients taking sulphonylureas receiving ibuprofen.

Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding with NSAIDs (see section 4.4).

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Zidovudine: Increased risk of haematological toxicity when NSAIDs are administered with zidovudine. There is evidence of an increased risk of haemarthrosis and hematoma in HIV(+) haemophiliacs receiving concomitant treatment with zidovudine and ibuprofen.

Aminoglycosides: NSAIDs may decrease the excretion of aminoglycosides.

Herbal extracts: Ginkgo biloba may increase the risk of bleeding with NSAIDs.

CYP2C9 inhibitors: Co-administration of ibuprofen with CYP2C9 inhibitors may increase exposure to ibuprofen (CYP2C9 substrate). In a study with voriconazole and fluconazole (CYP2C9 inhibitors), an increase in S(+)-ibuprofen exposure of approximately 80 to 100% was demonstrated. Dosage reduction of ibuprofen should be considered when strong CYP2C9 inhibitors are co-administered, particularly when high doses of ibuprofen are given with voriconazole or fluconazole.

the pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis following the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and postimplantation loss and embryofoetal lethality. Furthermore, an increased incidence of various malformations, including cardiovascular malformations, has been reported in animals receiving a prostaglandin synthesis inhibitor during the organogenetic period.

During the first and second trimester of pregnancy, Brufen should not be given unless clearly necessary. If Brufen is used by a woman trying to conceive or during the first or second trimester of pregnancy, the dose should be kept as low as possible and the duration of treatment should be as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the fetus to the following:

• Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension)

• Renal dysfunction, which may progress to renal failure with oligohydramnios.

In late pregnancy, prostaglandin synthesis inhibitors may expose the mother and newborn to the following:

• Possible prolongation of bleeding time

• Inhibition of uterine contractions, which can result in delayed or prolonged labor.

Consequently, Brufen is contraindicated during the third trimester of pregnancy.

Lactation

In the limited studies available to date, NSAIDs may appear in breast milk at very low concentrations. If possible, NSAIDs should be avoided during breastfeeding.

See section 4.4 Special warnings and special precautions for use regarding female fertility.

Gastrointestinal Disorders: The most frequently observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, especially in the elderly (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, gastrointestinal bleeding and exacerbation of colitis and Crohn's disease (see section 4.4) have been reported following administration of ibuprofen. Less frequently, gastritis, duodenal ulcer, gastric ulcer and gastrointestinal perforation have been observed.

Immune System Disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity including asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) various skin disorders including rashes of various types, pruritus, urticaria , purpura, angioedema and very rarely erythema multiforme, bullous dermatoses (including Stevens-Johnson syndrome and toxic epidermal necrolysis).

Cardiac Disorders and Vascular Disorders: Edema, hypertension, and heart failure have been reported in association with NSAID treatment. Clinical studies suggest that the use of ibuprofen, particularly at high doses (2400 mg/day), may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke (see section 4.4)..

Infections and infestations: Rhinitis and aseptic meningitis (especially in patients with existing autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4) .

Exacerbation of infection-related inflammation coinciding with the use of NSAIDs has been described. If signs of infection appear or worsen while using ibuprofen, the patient is advised to consult a physician without delay.

Skin and subcutaneous tissue disorders: In rare cases, serious skin infections and soft tissue complications may occur during a chickenpox infection (see also 'Infections and infestations').

The following adverse reactions possibly related to ibuprofen and exhibited by MedDRA frequency convention and system organ class. Frequency groups are ranked according to the following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare ( ≥ 1/10,000 to <1/1,000), Very rare (<1/10,000), and Frequency not known (cannot be estimated from available data).

Notification of suspected adverse reactions

It is important to report suspected adverse drug reactions after authorization. Allows continuous monitoring of the benefit/risk ratio of the drug. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card on Google Play or the Apple App Store.

toxicity

In general, no signs and symptoms of toxicity have been observed at doses below 100 mg/kg in children or adults. However, supportive care may be needed in some cases. Children have been observed to manifest signs and symptoms of toxicity after ingestion of 400 mg/kg or more.

Symptoms

Most patients who have ingested significant amounts of ibuprofen will develop symptoms within 4 to 6 hours.

The most commonly reported overdose symptoms include nausea, vomiting, abdominal pain, lethargy, and drowsiness. Central nervous system (CNS) effects include headache, tinnitus, dizziness, seizures, and unconsciousness. Nystagmus, metabolic acidosis, hypothermia, renal effects, gastrointestinal bleeding, coma, apnoea, diarrhea, and respiratory and central nervous system depression have also been reported rarely. In severe poisoning, metabolic acidosis may occur. Disorientation, excitement, fainting, and cardiovascular toxicity, including hypotension, bradycardia, and tachycardia, have been reported. In cases of significant overdose, kidney failure and liver damage are possible. Large overdoses are generally well tolerated when other drugs are not taken.

therapeutic measures

Patients should be treated symptomatically as needed. Within one hour of ingestion of a potentially toxic amount, the use of activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a life-threatening overdose.

Good urine output must be ensured.

Kidney and liver function should be carefully monitored.

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

Frequent or prolonged seizures should be treated with intravenous diazepam. Other measures may be indicated by the clinical condition of the patient.

Pharmacotherapeutic classification: Nonsteroidal anti-inflammatory and anti-rheumatic drugs; propionic acid derivatives.

ATC Code: M01AE01

Ibuprofen is a propionic acid derivative with analgesic, anti-inflammatory and antipyretic activity. The drug's therapeutic effect as an NSAID is thought to be due to its inhibitory effect on the enzyme cyclooxygenase, which results in a marked reduction in prostaglandin synthesis.

Experimental data suggest that ibuprofen can competitively inhibit the effect of low-dose aspirin on platelet aggregation when administered concomitantly. Some pharmacodynamic studies show that when single doses of ibuprofen 400 mg were taken 8 hours before or 30 minutes after administration of immediate-release aspirin (81 mg), there was a decrease in the effect of aspirin on thromboxane formation or platelet aggregation. Although there are concerns about extrapolating these data to the clinical situation, the possibility that regular and prolonged use of ibuprofen may reduce the cardioprotective effect of low-dose aspirin cannot be excluded. No clinically relevant effects are considered likely for occasional use of ibuprofen. (see section 4.5)

The pharmacokinetic profile of Brufen Retard compared to that of the conventional-release 400 mg tablets showed that the sustained-release formulation reduced the characteristic peaks and troughs of conventional-release tablets and provided higher levels at 5, 10, 15 and 24 hours. In comparison with the conventional release tablets, the area over time curve of plasmatic concentration for the sustained release tablets was almost identical.

Both mean plasma profiles and pre-dose plasma levels did not show significant differences between young and old age groups. In several studies, Brufen Retard produced a double-peak plasma profile when administered in the fasted state. The elimination half-life of ibuprofen is approximately 2 hours. Ibuprofen is metabolised in the liver to two inactive metabolites and these, together with unchanged ibuprofen, are excreted by the kidneys as such or as conjugates. Renal excretion is rapid and complete. Ibuprofen is extensively bound to plasma proteins.

Anhydrous colloidal silica, isopropyl alcohol*, povidone, stearic acid, xanthan gum, hypromellose, talc, Opaspray White M-1-7111B**

* removed during drying process

** includes denatured industrial alcohol*, purified water*, hypromellose, titanium dioxide

None.

administrative data

Mylan Products Ltd.

20 Closing of the station

potter's bar

herts

EN6 1TL

United Kingdom