Instructions for Teraflex Advance capsules bottle No. 60
Composition
active ingredients: glucosamine sulfate, sodium chondroitin sulfate, ibuprofen;
1 capsule contains 250 mg of glucosamine sulfate (as D-glucosamine sulfate potassium chloride), 200 mg of sodium chondroitin sulfate, 100 mg of ibuprofen;
excipients: PROSOLV SMCC® (microcrystalline cellulose, colloidal anhydrous silica), sodium starch glycolate (type A), crospovidone, povidone, silicon dioxide, pregelatinized starch, magnesium stearate, stearic acid, capsule shell (gelatin, FD&C blue No. 1, titanium dioxide (E 171).
Dosage form
Capsules.
Main physicochemical properties: size 0 hard gelatin capsules consisting of a blue cap and a white body with the inscription “THERAFLEX ADVANCE” and containing a white to almost white powder with a faint odor.
Pharmacotherapeutic group
Anti-inflammatory/antirheumatic drugs in combination.
ATX code M01B.
Pharmacological properties
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; and the activity of lysosomal enzymes.
Chondroitin and glucosamine are effective for 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 reduce 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 chondroprotective properties. 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 cyclooxygenase (COX) types 1 and 2 (the main enzyme in the metabolism of arachidonic acid), which leads to a decrease in the synthesis of prostaglandins, a decrease in their concentration in the cerebrospinal fluid and a decrease in the excitation of the thermoregulation center. Reduces morning stiffness, helps to increase the range of motion in the joints and spine.
The combined use of glucosamine and ibuprofen leads to an increase in the level of analgesic activity of the latter.
Pharmacokinetics
After a single oral dose of a therapeutic dose, peak plasma levels of chondroitin sulfate are reached in 3–4 hours. The bioavailability of the oral dose is 12%.
In the blood, 85% of chondroitin and its depolymerized derivatives bind to several plasma proteins.
At least 90% of the administered dose of chondroitin is first metabolized by lysosomal phosphatases, followed by depolymerization by hyaluronidase, β-glucuronidase, and β-N-acetylhexosaminidase in the liver, kidneys, and other organs.
Chondroitin and its depolymerized derivatives are eliminated primarily by renal excretion. The half-life is 5 to 15 hours.
After oral administration, glucosamine hydrochloride is rapidly and almost completely absorbed from the intestine. The pharmacokinetics of glucosamine are linear up to 1500 mg once daily, and higher doses do not result in a proportionally higher increase in maximum glucosamine concentrations.
More than 25% of the administered dose of glucosamine passes from blood plasma to cartilage tissue and synovial joint membrane.
According to the first-pass effect in the liver, more than 70% of glucosamine is metabolized to urea, carbon dioxide and water.
Excreted unchanged mainly by the kidneys in the urine and partly in the feces. The half-life is 68 hours.
After oral administration, ibuprofen is almost completely absorbed from the gastrointestinal tract. Simultaneous intake of food delays absorption. Ibuprofen is metabolized in the liver (90%). The half-life is 2–3 hours. 80% of the dose is excreted in the urine, mainly as metabolites.
Indication
Treatment of pain syndrome in primary and secondary osteoarthritis of the joints of the extremities and intervertebral discs.
Contraindication
This medicine is contraindicated in the following cases:
- increased individual sensitivity to the active substances or to other ingredients of the drug;
- history of allergic reactions (such as bronchospasm, asthma, rhinitis or skin rash, angioedema, urticaria associated with the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs);
- gastric ulcer/bleeding currently or in history (two or more clear episodes of exacerbation of ulcer and bleeding);
- optic nerve disease;
- violation of hematopoiesis;
- severe renal, cardiac or hepatic failure;
- phenylketonuria;
- cerebrovascular or other bleeding;
- diabetes;
- tendency to bleed;
- thrombophlebitis;
- the last trimester of pregnancy.
Concomitant use of the drug with other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, is contraindicated.
Interaction with other medicinal products and other types of interactions
Medicines that may interact with Teraflex Advance® capsules when used simultaneously:
Ibuprofen
The following combinations with ibuprofen should be avoided:
Acetylsalicylic acid
May lead to an increased risk of side effects. Due to the peculiarities of pharmacodynamics, it is assumed that ibuprofen may competitively inhibit the antiplatelet effect on platelets of low-dose acetylsalicylic acid when used simultaneously. The extrapolation of these data to clinical use has not been determined. The possibility that long-term use of ibuprofen may reduce the protective effect of low-dose acetylsalicylic acid in patients at increased risk of cardiovascular disease cannot be excluded. No clinical effect is expected with short-term use of ibuprofen.
Other NSAIDs, including selective COX-2 inhibitors
The risk of erosive-ulcerative lesions and gastrointestinal bleeding increases (see section "Contraindications").
The following combinations with ibuprofen should be used with caution:
Cyclosporine
The risk of nephrotoxic effects may increase.
Lithium
The level of lithium in the blood plasma increases.
Methotrexate
The plasma concentration of methotrexate increases and the risk of toxic effects of methotrexate increases.
Anticoagulants
NSAIDs may enhance the effects of anticoagulants such as warfarin.
Corticosteroids
The risk of gastrointestinal bleeding or ulceration increases.
Antihypertensives and diuretics
Nonsteroidal anti-inflammatory drugs may reduce the therapeutic effect of these drugs.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), concomitant use of angiotensin converting enzyme (ACE) inhibitors or angiotensin II antagonists and agents that inhibit cyclooxygenase may cause further deterioration of renal function, including possible acute renal failure, which is potentially reversible. The possibility of such an interaction should be considered in patients taking coxibs concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, this combination should be used with caution, especially in elderly patients. 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 drugs and selective serotonin reuptake inhibitors
The risk of gastrointestinal bleeding increases.
Cardiac glycosides
NSAIDs can exacerbate heart failure, reduce glomerular filtration rate, and increase the level of glycosides in the blood.
Zidovudine
The risk of hematological toxicity is increased when NSAIDs are used concomitantly with zidovudine. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-infected patients receiving concomitant 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 prolonged bleeding.
Quinolone antibiotics
Concomitant use of NSAIDs and quinolone antibiotics may increase the risk of seizures.
Sulfonylureas and phenytoin
Possible enhancement of the effects of drugs.
Chondroitin and glucosamine
Tetracycline
Increased absorption of tetracycline from the gastrointestinal tract.
Penicillin
Penicillin absorption decreases.
Chloramphenicol
The absorption of chloramphenicol decreases.
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 coagulation parameters.
Application features
This medicine is not intended for use in the treatment of gastrointestinal pain. Theraflex Advance® should be avoided in combination with other NSAIDs, including selective COX-2 inhibitors, due to the increased risk of ulceration or bleeding and other adverse reactions. Adverse reactions can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
Gastrointestinal bleeding, ulceration or perforation, which can be fatal and with or without prior symptoms, have been reported with all NSAIDs at any time during treatment, regardless of a previous history of serious gastrointestinal events.
The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing doses of NSAIDs, with a history of ulcer, particularly complicated by bleeding or perforation, and in elderly patients. 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 adverse reactions.
Patients with a history of gastrointestinal disorders, especially elderly patients, should report any unusual abdominal symptoms (including gastrointestinal bleeding), especially early in treatment. Caution should be exercised when 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 gastrointestinal bleeding or ulceration occurs in patients receiving ibuprofen, 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 inhibit platelet aggregation, a doctor should be consulted before starting treatment with Theraflex Advance®.
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 low doses of ibuprofen (≤ 1200 mg/day) are associated with an increased risk of myocardial infarction.
In patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease, long-term treatment should only be prescribed by a physician after careful consideration. In patients with significant risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes mellitus, smoking), long-term treatment with NSAIDs should only be prescribed after careful consideration.
Very rarely, severe skin reactions, some of which were fatal, have been reported with NSAIDs. These include exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The risk of these reactions appears to be highest early in treatment: the onset of these reactions has been observed in most cases within the first month of treatment. Ibuprofen should be discontinued at the first sign of skin rash, mucosal ulceration or any other sign of hypersensitivity.
Ibuprofen may cause bronchospasm and asthma attacks or other hypersensitivity reactions. Risk factors for such reactions include pre-existing bronchial 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 NSAIDs (in particular skin reactions, itching, urticaria).
It is not recommended to drink alcohol during treatment with Teraflex Advance®.
The drug should be used with caution in patients with:
- systemic lupus erythematosus and systemic connective tissue diseases, as the risk of aseptic meningitis increases;
- a history of arterial hypertension and/or heart failure, which were accompanied by fluid retention and edema during the use of NSAIDs;
Long-term use of NSAIDs can lead to a dose-dependent decrease in prostaglandin synthesis and provoke the development of renal failure. Patients taking diuretics are at high risk; patients with impaired liver, kidney and/or heart function.
When using NSAIDs, adverse reactions are more common in elderly patients, especially gastrointestinal bleeding and perforation, which can be fatal.
Ibuprofen may mask the symptoms of infection, which may delay appropriate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. If symptoms persist or worsen, consult a doctor.
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 may occur in patients with a history of bronchial asthma after initiation of treatment with glucosamine. Therefore, patients with asthma should be warned about the possible exacerbation of symptoms before using this medicinal product.
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 or breastfeeding
Pregnancy period
Ibuprofen
Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryo/foetal development. Epidemiological studies suggest an increased risk of miscarriage and of cardiac malformations and gastroschisis following the use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations has increased from less than 1% to approximately 1.5%. The risk is thought to increase with increasing dose and duration of treatment. Animal studies have shown that the use of prostaglandin synthesis inhibitors leads to an increase in pre- and post-implantation losses and embryo-fetal lethality. Animal studies have also reported an increased incidence of various developmental disorders, including cardiovascular malformations, when prostaglandin synthesis inhibitors are used during organogenesis.
Ibuprofen should not be used during the first and second trimesters of pregnancy.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may lead to the following effects on the fetus:
- cardiopulmonary toxicity (premature closure of the ductus arteriosus and pulmonary hypertension);
- impaired renal function, which may progress to renal failure with oligohydramnios.
In the mother and baby at the end of pregnancy:
- possible prolongation of bleeding time, antiplatelet effect may be observed even when using very low doses;
- suppression of uterine contractions, which leads to a delay in the onset or increase in the duration of labor.
As a result, ibuprofen is contraindicated during the third trimester of pregnancy.
Chondroitin sulfate and glucosamine sulfate: Clinical data on the efficacy and safety of glucosamine sulfate during pregnancy are lacking or limited. Therefore, Teraflex Advance® should not be used during the first and second trimesters of pregnancy. Teraflex Advance® is contraindicated during the third trimester of pregnancy.
Breastfeeding period
Ibuprofen may pass into breast milk in small amounts, but when used in therapeutic doses, the risk of exposure to the child is considered unlikely.
There is insufficient information on the excretion of chondroitin sulfate and glucosamine sulfate and their metabolites into breast milk. Therefore, this medicinal product should not be used in lactating women.
Fertility
There is evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may cause impaired fertility in women through effects on ovulation. This can be reversed by discontinuing these drugs. There are no data on the effects of chondroitin sulfate and glucosamine.
Ability to influence reaction speed when driving vehicles or other mechanisms
The patient should monitor changes in his reaction speed before driving or operating machinery. If any adverse reactions from the nervous system are detected, driving or operating machinery should be avoided.
Method of administration and doses
The drug should be taken after meals, with a glass of water.
Adults should take 2 capsules 3 times a day.
The total duration of treatment at the recommended dose should not exceed 10 days. If symptoms persist or worsen or if there is a need to extend the course of treatment, you should consult a doctor. The lowest effective dose should be used for the shortest necessary course of treatment. After the pain disappears, the patient can continue treatment with the drug Teraflex® in the dosage form of capsules.
Children
Children (under 18 years of age) should not use this medicine due to a lack of data on efficacy and safety.
Overdose
There is no data on overdose with this medicinal product or chondroitin and/or glucosamine. Administration of doses exceeding 400 mg/kg of ibuprofen in children may result in overdose. In adults, the dose-related effect is less clear. The half-life of ibuprofen in overdose is 1.5–3 hours.
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, apnea (especially in young children), rarely agitation and disorientation, loss of consciousness or coma; arterial hypertension, 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 bronchial asthma, exacerbation of the course of asthma is possible. In severe overdose, metabolic acidosis (including renal tubular acidosis) and hypokalemia may develop, and prothrombin time/international normalized ratio (INR) may be prolonged, probably due to interactions with blood clotting factors.
Treatment is symptomatic, aimed at ensuring airway patency, monitoring cardiac activity and other vital body functions until the condition normalizes. Gastric lavage and oral administration of activated charcoal are recommended within 1 hour after the use of a potentially toxic dose of the drug (more than 400 mg/kg) and hospitalization in a 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 bronchial asthma.
Adverse reactions
Most of the side effects after using the drug Teraflex 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 Teraflex Advance® (600 mg) is significantly lower than its maximum daily dose (1200 mg), it is unlikely that any side effects will be observed if the drug is used according to the dosage recommendations. The frequency of adverse reactions to ibuprofen is classified as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (<1/10000) and frequency unknown (cannot be estimated from the available data). The frequency of adverse reactions to Theraflex Advance® cannot be determined as these data are derived from post-marketing reports. Therefore, the frequency of these reactions is marked as unknown.
Gastrointestinal: Uncommon: abdominal pain, dyspepsia, nausea. Rare: diarrhoea, flatulence, constipation and vomiting. Rare: ulcerative stomatitis, peptic ulcers, melena, haematemesis, gastritis, perforation or gastrointestinal bleeding, which in some cases can be fatal, especially in elderly patients. Frequency not known: diaphragmatic intestinal strictures (especially with prolonged use), exacerbation of colitis and Crohn's disease, heartburn.
Nervous system disorders: Uncommon: headache. Rare: aseptic meningitis (isolated cases have been reported). In patients with autoimmune disorders (including systemic lupus erythematosus, systemic connective tissue diseases), isolated symptoms of aseptic meningitis have been observed during treatment with ibuprofen, including: neck stiffness, headache, nausea, vomiting, fever or disorientation.
Frequency unknown: dizziness, drowsiness, paresthesia, general weakness and fatigue. Only with prolonged use - depression, hallucinations, confusion, ringing in the ears.
Urinary system: Rare: acute renal failure, papillonecrosis, especially with prolonged use, in combination with increased serum urea and edema. Frequency unknown: ibuprofen may cause interstitial nephritis, nephrotic syndrome, nephrotoxicity.
Blood and lymphatic system disorders: Rare: haematopoietic disorders (anaemia, neutropenia, aplastic anaemia, haemolytic anaemia, eosinophilia, decreased haematocrit and haemoglobin, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first signs are 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 (exfoliative and bullous dermatoses) 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: Uncommon: urticaria, pruritus, rash. Rare: allergic reactions, including severe hypersensitivity reactions, swelling of the face, tongue and larynx, dyspnoea, angioedema, anaphylactic shock, anaphylaxis, anaphylactoid reactions. Frequency unknown: airway reactivity, including bronchial asthma, exacerbation of asthma, bronchospasm.
Cardiovascular and cerebrovascular disorders: Frequency unknown: edema, hypertension, decreased blood pressure, heart failure, tachycardia, palpitations have been reported with NSAIDs. Long-term use of ibuprofen in high doses (2400 mg/day) may lead to a slightly increased risk of arterial thrombosis (myocardial infarction or stroke). Cerebrovascular complications are possible.
On the part of the organs of vision. Frequency unknown: with prolonged use - visual impairment, optic neuritis.
Hearing disorders: Frequency unknown: tinnitus.
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 mucous membranes of the eyes and mouth, rhinitis, hearing impairment.
Publications have reported rare cases of extrasystoles with the use of 1200 mg of chondroitin sulfate.
Theraflex Advance® should be discontinued if any adverse reaction occurs and a doctor should be consulted immediately.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
60 or 120 capsules in a bottle, 1 bottle in a cardboard box.
Vacation category
Without a prescription.
Producer
Contract Pharmacal Corporation/Contract Pharmacal Corporation.
Location of the manufacturer and its business address
135 Adams Avenue, Hauppauge, New York 11788, USA/135 Adams Avenue, Hauppauge, New York 11788, USA.
