Theraflex Advance capsules bottle of 60 pcs

Pharmacodynamics. This drug stimulates the regeneration of cartilage tissue. It has an anti-inflammatory effect at the cellular level, stimulates the synthesis of both endogenous proteoglycans and endogenous hyaluronic acid, reduces the catabolic activity of chondrocytes by inhibiting some enzymes that destroy cartilage, such as collagenase, estalase, proteoglycanase, phospholipase-A2, n-acetylglycosaminidase, etc., and also inhibits the formation of other substances that can damage cartilage tissue (in vitro), such as superoxide radicals; the activity of lysosomal enzymes.

Chondroitin and glucosamine are effective in patients with osteoarthritis.

Chondroitin is one of the main elements of cartilage. It reduces the activity of the inflammatory process in the early stages and, thus, slows down the degeneration of cartilage tissue. It helps to reduce the intensity of pain, improves joint function and reduces the need for non-steroidal anti-inflammatory drugs in osteoarthritis of the knee and hip joints.

Glucosamine is physiologically present in the human body and has a chondroprotective effect. In vitro and in vivo studies have shown that glucosamine hydrochloride stimulates the synthesis of physiological glycosaminoglycans and proteoglycans by chondrocytes and the synthesis of hyaluronic acid by synoviocytes.

Ibuprofen has antipyretic, analgesic and anti-inflammatory effects. The mechanism of action is associated with non-selective blocking of COX type 1 and 2 (the main enzyme of arachidonic acid metabolism), which leads to a decrease in the synthesis of prostaglandins, a decrease in their concentration in the cerebrospinal fluid and a weakening of the excitation of the thermoregulation center. Reduces morning stiffness, helps to increase the range of motion in the joints and spine.

The simultaneous use of glucosamine and ibuprofen leads to an increase in the analgesic activity of the latter.

Pharmacokinetics. After a single oral administration of a therapeutic dose, the maximum level of chondroitin sulfate in the blood plasma is reached after 3-4 hours. The bioavailability of the dose that was administered orally is 12%.

In the blood, 85% of chondroitin and its depolymerized derivatives bind to several blood plasma proteins.

At least 90% of the chondroitin dose is initially metabolized by lysosomal phosphatases, then depolymerized by hyaluronidases, β-glucuronidase, and β-N-acetylhexosaminidase in the liver, kidneys, and other organs.

Chondroitin and its depolymerized derivatives are excreted mainly by the kidneys. T½ _is 5-15 hours.

After oral administration, glucosamine hydrochloride is rapidly and almost completely absorbed from the intestine. The pharmacokinetics of glucosamine are linear at doses up to 1500 mg once daily, and higher doses will not lead to a proportional increase in C _max of glucosamine.

More than 25% of the ingested dose of glucosamine passes from blood plasma to cartilage tissue and the synovial joint membrane.

According to the first-pass effect, more than 70% of glucosamine is metabolized in the liver to urea, carbon dioxide, and water.

It is excreted unchanged mainly in the urine and partially in the feces. T _½ is 68 hours.

After oral administration, ibuprofen is almost completely absorbed from the gastrointestinal tract. Simultaneous food intake delays absorption. Ibuprofen is metabolized in the liver (90%). T _½ is 2-3 hours. 80% of the dose is excreted in the urine, mainly in the form of metabolites.

Treatment of pain syndrome in patients with primary and secondary osteoarthritis of the joints of the extremities and intervertebral discs.

The drug should be taken after meals with a glass of water. Adults should take 2 capsules 3 times a day. The maximum daily dose of 12 capsules (1.2 g of ibuprofen) should not be exceeded.

The total duration of treatment at the dose should not exceed 20 days. After the pain syndrome is eliminated, the patient can continue treatment with the drug Theraflex, capsules.

Contraindicated in the following cases:

• increased individual sensitivity to the active substances or other ingredients of the drug;
• patients with a history of allergic reactions (e.g. bronchospasm, asthma, rhinitis or skin rash, angioedema, urticaria associated with the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs);
• patients with a history of gastrointestinal bleeding or perforation after taking NSAIDs;
• peptic ulcer/bleeding present or history (two or more clear episodes of exacerbation of ulcerative colitis and bleeding);
• optic nerve disease;
• hematopoiesis disorders;
• patients with severe renal, cardiac or hepatic insufficiency;
• phenylketonuria;
• cerebrovascular or other bleeding;
• diabetes;
• tendency to bleeding;
• thrombophlebitis.

The use of the drug simultaneously with other NSAIDs, including selective COX-2 inhibitors, is contraindicated.

Most of the side effects after using the drug Theraflex Advance are caused by ibuprofen and are dose-dependent. Since the recommended single dose of ibuprofen is moderate, and the usual daily dose in the drug Theraflex Advance (600 mg) is significantly lower than its maximum daily dose (1200 mg), it is unlikely that any side effects will occur if the drug is used according to the dosage recommendations.

From the digestive system: abdominal pain, dyspepsia, nausea, diarrhea, flatulence, constipation and vomiting. Heartburn, ulcerative stomatitis, peptic ulcers, melena, hematemesis, gastritis, perforation or gastrointestinal bleeding, which in some cases can be fatal, especially in the elderly, are possible. In isolated cases, exacerbation of ulcerative colitis and Crohn’s disease has been reported.

Nervous system: headache, aseptic meningitis (isolated cases have been reported). Dizziness, drowsiness, paresthesia, general weakness and fatigue may occur. Only with prolonged use – depression, hallucinations, confusion, tinnitus.

In patients with autoimmune disorders (in particular, systemic lupus erythematosus, systemic connective tissue diseases) during treatment with ibuprofen, isolated symptoms of aseptic meningitis were observed, namely: stiffness of the occipital muscles, headache, nausea, vomiting, fever or disorientation.

From the urinary system. There are reports of acute renal failure, papillonecrosis, especially with prolonged use, in combination with increased blood urea and edema. Ibuprofen can cause interstitial nephritis, nephrotic syndrome, nephrotoxicity.

On the part of the hepatobiliary system. Liver disorders are possible, especially with prolonged use, such as hepatitis, jaundice.

Blood and lymphatic system disorders: Hematopoietic system disorders (anemia, neutropenia, aplastic anemia, hemolytic anemia, eosinophilia, decreased hematocrit and hemoglobin levels, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first signs are high fever, sore throat, mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising. Reversible platelet aggregation, alveolitis, pulmonary eosinophilia.

Skin and subcutaneous tissue disorders: In rare cases, severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis may occur. Skin peeling, alopecia, photosensitivity, hyperemia, dermatitis, eczema may occur.

Immune system disorders: Allergic reactions, including severe hypersensitivity reactions, swelling of the face, tongue and larynx, shortness of breath, angioedema, anaphylactic shock, anaphylaxis, urticaria, pruritus, rash, airway reactivity including asthma, exacerbation of asthma, bronchospasm.

Cardiovascular and cerebrovascular disorders. Edema, hypertension, heart failure, tachycardia, palpitations have been reported with NSAIDs. Long-term use of ibuprofen in high doses (2400 mg/day) may lead to a small increase in the risk of arterial thrombosis (myocardial infarction or stroke). Cerebrovascular complications are possible.

From the organ of vision. With prolonged use: visual impairment, optic neuritis.

Laboratory results: Increased ALT, increased blood creatinine, increased AST, increased blood urea, increased blood bilirubin.

Others: Changes in the endocrine system and metabolism, decreased appetite, dry eyes and mouth, rhinitis, hearing impairment.

Theraflex Advance should be discontinued if any adverse reaction occurs and a doctor should be consulted immediately.

Theraflex Advance should be avoided with other NSAIDs, including selective COX-2 inhibitors, due to the increased risk of ulceration or bleeding, as well as other adverse reactions. Adverse reactions can be minimized by taking the drug at the lowest effective dose for the shortest period necessary to control symptoms.

Gastrointestinal bleeding, ulceration or perforation, which can be fatal and may or may not be accompanied by preceding symptoms, has been reported with all NSAIDs at any time during treatment, regardless of the presence of a history of severe gastrointestinal complications.

The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing doses of NSAIDs, with a history of ulceration, particularly complicated by bleeding or perforation, and in the elderly. Such patients should start treatment with the lowest available dose. Combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered for these patients, as well as for patients who require concomitant low-dose acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal complications.

Patients with a history of gastrointestinal disorders, especially the elderly, should report any unusual abdominal symptoms (including gastrointestinal bleeding), especially early in therapy. Caution should be exercised in treating 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, and antiplatelet agents such as acetylsalicylic acid.

If patients receiving ibuprofen develop gastrointestinal bleeding or ulceration, treatment should be discontinued.

NSAIDs should be used with caution in patients with a history of ulcerative colitis or Crohn’s disease, as their condition may worsen.

If acetylsalicylic acid is used to suppress platelet aggregation, a doctor should be consulted before starting treatment with Theraflex Advance.

There is evidence that drugs that inhibit COX/prostaglandin synthesis may impair female fertility by affecting ovulation. This can be reversed by discontinuing these drugs.

Clinical trial and epidemiological data suggest that the use of ibuprofen, particularly at high doses (2400 mg/day) in long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological studies do not suggest that the use of ibuprofen at low doses (≤1200 mg/day) is associated with an increased risk of myocardial infarction.

Patients with uncontrolled hypertension, congestive heart failure diagnosed with coronary artery disease, peripheral arterial disease and/or cerebrovascular disease should be prescribed long-term treatment by a doctor only after careful analysis. Individuals with significant risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) should be prescribed long-term treatment with NSAIDs only after careful consideration.

Very rarely, severe skin reactions, some of which were fatal, have been reported with NSAIDs, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The risk of such reactions appears to be highest early in treatment: the onset of such reactions in most cases was observed within the first month of treatment. Ibuprofen treatment should be discontinued at the first sign of skin rash, mucosal ulceration or any other sign of hypersensitivity.

Ibuprofen may cause bronchospasm and attacks of bronchial asthma or other hypersensitivity reactions. Risk factors for such reactions include pre-existing asthma, hay fever, nasal polyps, sensitivity to acetylsalicylic acid or chronic respiratory diseases. This also applies to patients who have experienced allergic reactions to ibuprofen or other non-steroidal anti-inflammatory drugs (in particular skin reactions, itching, urticaria).

It is not recommended to drink alcohol during treatment with the drug Theraflex Advance.

The drug should be used with caution in patients with:

• systemic lupus erythematosus and systemic connective tissue diseases – increased risk of aseptic meningitis;
• A history of hypertension and/or heart failure, which was accompanied by fluid retention and edema when using NSAIDs;
• renal and/or hepatic impairment; hepatic dysfunction increases the risk of renal toxicity and damage, as well as severe and potentially fatal hepatic reactions. For patients with liver or kidney disease, additional examinations are recommended before starting treatment: monitoring of liver and renal function and peripheral blood tests.

Long-term use of nonsteroidal anti-inflammatory drugs can lead to a dose-dependent decrease in prostaglandin synthesis and provoke the development of renal failure. Patients taking diuretics, people with impaired liver, kidney and / or heart function, elderly patients are at high risk.

Features of the use of glucosamine sulfate and chondroitin sulfate. The drug should not be used in patients with hypersensitivity (allergy) to seafood.

Exacerbation of asthma symptoms in patients with a history of bronchial asthma may occur after starting treatment with glucosamine.

Rarely, edema and/or water retention have been observed in patients with cardiac and/or renal insufficiency. This may be due to the osmotic effect of chondroitin sulfate.

You should consult a doctor if your symptoms worsen after starting this medicine.

Use during pregnancy and breastfeeding. Although the use of ibuprofen-containing drugs is contraindicated only in the third trimester of pregnancy, there are no clinical data on the efficacy and safety of glucosamine sulfate during pregnancy and breastfeeding. Therefore, the drug should not be used during these periods.

Children: There is no experience with the use of the drug in children (under 18 years of age).

Ability to influence the reaction speed when driving or operating other mechanisms. The patient should monitor changes in the reaction speed before driving or operating other mechanisms. If any undesirable effects from the nervous system are detected, such activities should be abandoned.

Medicines that may interact with Theraflex Advance capsules when used simultaneously.

ibuprofen

These combinations with ibuprofen should be avoided:

Acetylsalicylic acid. May increase the risk of side effects. Allowed if the dose of acetylsalicylic acid is not higher than 75 mg/day and has been prescribed by a doctor.

Other NSAIDs, including selective COX-2 inhibitors: Increased risk of erosive-ulcerative lesions and gastrointestinal bleeding (see Adverse Reactions).

The following combinations with ibuprofen should be used with caution: Cyclosporine. The risk of nephrotoxic effects may be increased.

Lithium: Increased plasma lithium levels.

Methotrexate at a dose of ≥15 mg/week. Increased methotrexate concentrations and risk of methotrexate toxicity.

Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin.

Corticosteroids: Increased risk of gastrointestinal bleeding or ulceration.

Antihypertensives and diuretics. NSAIDs may reduce the therapeutic effect of these drugs.

In some patients with impaired renal function (in dehydrated patients or elderly patients with impaired renal function), the concomitant use of ACE inhibitors or angiotensin II antagonists and agents that inhibit COX may cause further deterioration of renal function, including possible renal failure, potentially reversible. The possibility of such an interaction should be considered in patients receiving coxibs concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, this combination should be used with caution, especially in the elderly. Patients should be adequately hydrated, and consideration should be given to monitoring renal function at the beginning of concomitant treatment and periodically thereafter. Diuretics may increase the risk of nephrotoxicity of NSAIDs.

Antiplatelet agents and selective serotonin reuptake inhibitors: Increased risk of gastrointestinal bleeding.

Cardiac glycosides. NSAIDs can exacerbate heart failure, reduce glomerular filtration rate, and increase the level of glycosides in the blood.

Zidovudine: Concomitant use of NSAIDs with zidovudine increases the risk of hematological toxicity. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-infected patients receiving concomitant treatment with zidovudine and ibuprofen.

Mifepristone. NSAIDs should not be used earlier than 8-12 days after mifepristone administration, as they reduce its effectiveness.

Tacrolimus: There may be an increased risk of nephrotoxicity with concomitant use of NSAIDs and tacrolimus.

Potassium-sparing diuretics: Hyperkalemia may occur.

Alcohol: Increased risk of gastrointestinal damage and increased bleeding time.

Quinolone antibiotics: Concomitant use of NSAIDs and quinolone antibiotics may increase the risk of seizures.

Sulfonylureas and phenytoin. Possible enhancement of the effects of the drugs.

Chondroitin and glucosamine

Tetracycline. Increased absorption of tetracycline in the gastrointestinal tract.

Penicillin. Penicillin absorption is reduced.

Chloramphenicol. Absorption of chloramphenicol is reduced.

Cyclosporine: May affect the concentration of cyclosporine in the blood.

The physicochemical and pharmacokinetic properties of chondroitin and glucosamine indicate a low potential for interactions, and no specific interaction studies have been conducted. Chondroitin and glucosamine are compatible with NSAIDs.

According to some reports, simultaneous use of glucosamine and warfarin may increase the effect of the latter and cause bleeding. Therefore, during simultaneous use, it is necessary to monitor blood clotting parameters.

In case of overdose, abdominal pain, nausea, vomiting, diarrhea, gastrointestinal bleeding, dizziness, headache, sleep disturbances and tinnitus may occur. In severe cases, symptoms from the nervous system may occur: drowsiness, lethargy, rarely excitement and disorientation, loss of consciousness or coma, possible arrhythmia, arterial hypotension, impaired liver and kidney function or hepatonecrosis, acute renal failure, rhabdomyolysis and hypothermia; respiratory failure and cyanosis. Occasionally, convulsions are observed in overdose. In patients with BA, exacerbation of BA is possible. In severe overdose, metabolic acidosis (including renal tubular acidosis) and hypokalemia may develop, and prothrombin time / international normalized ratio may also be prolonged, probably as a result of interaction with blood clotting factors.

Treatment is symptomatic, aimed at ensuring the vital functions of the body, including ensuring airway patency, and normalizing the condition. Gastric lavage and oral administration of activated charcoal are recommended within 1 hour after the use of a potentially toxic dose of the drug (400 mg/kg body weight) and hospitalization in the toxicology department. In the inpatient stage, infusion therapy, forced diuresis, and symptomatic treatment are used. There are no specific antidotes. Frequent or prolonged seizures should be treated with intravenous diazepam or lorazepam. Bronchodilators should be used in asthma.

In the original packaging at a temperature not exceeding 25 °C.