Glucosamine, Ibuprofen, Chondroitin Sulfate

The composition of the drug:
active ingredients: 1 capsule contains glucosamine sulfate sodium chloride in terms of glucosamine sulfate 250 mg, chondroitin sodium sulfate 200 mg, ibuprofen 100 mg;
excipients: pregelatinized starch, crospovidone, sodium starch glycolate (type A), stearic acid, microcrystalline cellulose, magnesium stearate, povidone, anhydrous colloidal silicon dioxide; capsule shell contains: gelatin, titanium dioxide (E 171).

Dosage form. Capsules

Hard gelatin capsules in white. The contents of the capsules is a mixture containing granules and powder from white to almost white. Particle agglomerates are allowed.
It is allowed to apply the trademark of the enterprise - ST on the capsule.

Name and location of the manufacturer.
LLC "Pharmaceutical company" Health ".
Ukraine, 61013, Kharkov, st. Shevchenko, 22.

Pharmacotherapeutic group.
Combined anti-inflammatory (antirheumatic) drugs.
PBX code M01V.

Chondroitin sodium sulfate is a high molecular weight polysaccharide that takes part in the construction of cartilage, reduces the activity of enzymes that destroy articular cartilage, and stimulates the regeneration of articular cartilage. In the early stages of the inflammatory process of sodium, chondroitin sulfate inhibits its activity and, thus, slows down the degeneration of cartilage. Helps reduce pain, improves joint function and reduces the need for non-steroidal anti-inflammatory drugs for osteoarthritis of the knee and hip joints.
Glucosamine sulfate has chondroprotective properties, reduces the deficiency of glycosaminoglycans in the body and is involved in the synthesis of proteoglycans and hyaluronic acid.
Due to the ability to selectively affect cartilage, glucosamine initiates the process of sulfur fixation in the synthesis of chondroitin sulfuric acid. Glucosamine sulfate selectively acts on articular cartilage, is a specific substrate and stimulator of the synthesis of hyaluronic acid and proteoglycans, inhibits the formation of superoxide radicals and enzymes that cause damage to cartilage tissue (collagenase and phospholipase), prevents the destructive effect of glucocorticoids on chondrocytes and biosynthesis anti-inflammatory drugs.
Ibuprofen has an antipyretic, analgesic and anti-inflammatory effect. The mechanism of action is associated with non-selective blocking of cyclooxygenase (COX) of the 1st and 2nd type (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 decrease in the excitation of the thermoregulation center. Reduces morning stiffness, increases the range of motion in the joints and spine.
After oral administration of a single therapeutic dose, the maximum level in the blood plasma of sodium chondroitin sulfate is reached after 3-4 hours, in the synovial fluid - after 4-5 hours. Bioavailability is 13%. It is excreted within 24 hours, mainly by the kidneys.
After oral administration, 90% of glucosamine is absorbed in the intestines. More than 25% of the applied dose enters from the blood plasma into the cartilage and synovial membranes of the joints. In the liver, part of the drug is metabolized to urea, carbon dioxide and water. Glucosamine bioavailability is 25% due to the first passage through the liver. The highest glucosamine concentrations are determined in the liver, kidneys and articular cartilage. About 30% of the dose taken is persistent in the bone and muscle tissues for a long time. It is excreted mainly in unchanged form with urine, partially with feces. The half-life is 68 hours.
After oral administration, ibuprofen is almost completely absorbed from the gastrointestinal tract. Simultaneous eating delays absorption. Ibuprofen is metabolized in the liver (90%). The elimination half-life makes 2-3 hours. 80% of the dose is excreted in the urine, mainly in the form of metabolites.

Indications for use.
Treatment of pain in primary and secondary osteoarthritis of the joints of the limbs and intervertebral discs.

Contraindications
This medicine is contraindicated in the following cases:

• increased individual sensitivity to active substances or to other ingredients of the drug;
• the patient has a history of bronchospasm, asthma, rhinitis or skin rashes associated with the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs;
• the patient has a history of gastrointestinal bleeding or perforation after the use of non-steroidal anti-inflammatory drugs (NSAIDs);
• peptic ulcer / bleeding at present or in history (two or more distinct episodes of exacerbation of peptic ulcer and bleeding);
• diseases of the optic nerve;
• hematopoiesis disorders;
• severe renal, cardiac, or liver failure;
• phenylketonuria;
• pregnancy or lactation period.

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

Appropriate safety precautions for use.
Avoid the use of the drug Artiflex Ultra simultaneously with other non-steroidal anti-inflammatory drugs. If acetylsalicylic acid is used to inhibit platelet aggregation, consult a doctor before starting treatment with the drug.
For patients with liver or kidney disease, additional tests are recommended before starting treatment: monitoring liver and kidney function and peripheral blood tests.
Elderly people with a history of gastrointestinal diseases have an increased risk of adverse reactions when using NSAIDs, especially in the form of gastrointestinal bleeding and perforation.
Nonsteroidal anti-inflammatory drugs should be used with caution in patients who have had a history of ulcerative colitis or Crohns disease, since their condition may worsen.
There is evidence that drugs that slow cyclooxygenase / prostaglandin synthesis can cause fertility problems in women due to their effects on ovulation. This can be avoided by stopping the use of these drugs.
It is not recommended to drink alcohol during treatment with Artiflex Ultra.
Use with caution in patients with:

• systemic lupus erythematosus and systemic diseases of the connective tissue - increased risk of aseptic meningitis;
• history of arterial hypertension and / or heart failure, which were accompanied by fluid retention and edema during the use of non-steroidal anti-inflammatory drugs;
• impaired renal and / or liver function.

Special warnings.
Use during pregnancy or lactation.
There are no clinical data regarding the safety and effectiveness of the use of the drug Artiflex Ultra during pregnancy or lactation, therefore, the drug should not be prescribed during these periods.

The ability to influence the reaction rate when driving or working with other mechanisms. Unknown

Children. There is no experience with the use of the drug in children under 12 years of age.

Dosage and administration.
The drug should be used after meals with a glass of water.
Adults and children over the age of 12 years: 2 capsules 3 times a day.
Do not exceed the maximum daily dose of 12 capsules (1.2 g ibuprofen).
The total duration of treatment at the recommended dose should not exceed 20 days.

Overdose.
In case of overdose, abdominal pain, nausea, vomiting, dizziness, headache, sleep disturbance, and tinnitus may occur. In severe cases, arterial hypertension, metabolic acidosis, loss of consciousness, impaired liver and kidney function, or hepatonecrosis may occur.
Treatment: symptomatic, aimed at ensuring the vital functions of the body and normalizing the condition. Gastric lavage and oral administration of activated charcoal within 1 hour after the application of a potentially toxic dose of the drug (over 400 mg / kg) and hospitalization in the toxicology department are recommended. At the stationary stage, infusion therapy, forced diuresis, symptomatic treatment are used. There are no special antidotes.

Side effects.
Most side effects after using the drug Artiflex Ultra 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 Artiflex Ultra (600 mg) is significantly lower than its maximum daily dose (1200 mg), it is unlikely that there will be any side effects if the drug apply according to dosage recommendations. With prolonged treatment of chronic conditions, additional side effects may occur.
From the gastrointestinal tract. Abdominal pain, dyspepsia, nausea, diarrhea, flatulence, constipation and vomiting. Heartburn, ulcerative stomatitis, peptic ulcers, melena, perforation or gastrointestinal bleeding can occur, which in some cases can be fatal, especially in the elderly. In isolated cases, exacerbation of ulcerative colitis and Crohns disease was reported.
From the nervous system. Headache, depression of consciousness and disorientation, aseptic meningitis (isolated cases have been reported). Dizziness, irritability, nervousness, tinnitus, depression, drowsiness, insomnia, anxiety, psychomotor agitation, emotional instability, and convulsions may occur.
From the urinary system. There are reports of acute renal failure, papillonecrosis, especially with prolonged use, in combination with an increase in serum urea and edema. Ibuprofen can cause cystitis and hematuria, interstitial nephritis, nephrotic syndrome, oliguria, polyuria, glomerulonephritis, tubular necrosis, glomerulonephritis.
From the hepatobiliary system. Liver disorders can occur, especially with prolonged use, in the form of hepatitis, jaundice, pancreatitis, duodenitis, esophagitis, hepatorenal syndrome, hepatonecrosis, and liver failure.
On the part of the blood and lymphatic system. Hematopoietic system disorders (anemia, neutropenia, aplastic anemia, hemolytic anemia, eosinophilia, decreased hematocrit and hemoglobin level, leukopenia, thrombocytopenia, pancytopenia, agranulocytosis). The first signs are fever, sore throat, oral ulcers, flu symptoms, severe exhaustion, unexplained bleeding, and bruising. Reversible platelet aggregation, alveolitis, pulmonary eosinophilia.
On the part of the skin and subcutaneous tissue. In rare cases, severe skin reactions can occur, such as erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis. Peeling of the skin, alopecia, photosensitivity may be observed.
From the immune system.Severe reactions of hypersensitivity with the following manifestations: swelling of the face, tongue and larynx, shortness of breath, Quinckes edema, anaphylactic shock.
In patients with autoimmune disorders (systemic lupus erythematosus, systemic connective tissue diseases) during treatment with ibuprofen, isolated cases of the appearance of symptoms of aseptic meningitis were observed, namely: stiff neck, headache, nausea, vomiting, fever or disorientation.
From the cardiovascular system and cerebral circulation. Edema, arterial hypertension, and heart failure have been reported in the treatment of NSAIDs. Long-term use of ibuprofen in high doses (2400 mg / day) can lead to a slight increase in the risk of arterial thromboembolism or stroke. Cerebrovascular accidents may occur. Arterial hypotension, palpitations.
From the side of the organs of vision. Blurred vision, change in color perception, toxic amblyopia.
Other. Changes in the endocrine system and metabolism, decreased appetite, dry mucous membranes of the eyes and oral cavity, rhinitis, hearing impairment.
Reception of Artiflex Ultra should be stopped at emergence of any undesirable reaction and to see a doctor immediately.

Interaction with other drugs and other types of interactions. With simultaneous use with the drug Artiflex Ultra capsules, interaction with the following drugs may be observed:

Acetylsalicylic acid
Ibuprofen has been shown to inhibit platelet aggregation by acetylsalicylic acid. This effect can be significant with the use of enteric-coated acetylsalicylic acid preparations and / or high doses of ibuprofen. If immediate-release acetylsalicylic acid preparations (non-enteric) are used, a single dose of ibuprofen can be used 2 hours after salicylate or at least 8 hours before taking acetylsalicylic acid in order to prevent a decrease in the effects of the latter.

Cyclosporin
Concomitant use may increase the risk of nephrotoxicity.

Lithium
Plasma lithium levels increase.

Methotrexate at doses of 15 mg / week or higher
The concentration of methotrexate increases and the risk of toxic effects of methotrexate increases.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
The risk of erosive and ulcerative lesions and gastrointestinal bleeding increases (See the section "Contraindications").

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

Corticosteroids
The risk of gastrointestinal bleeding or ulceration is increased.

Antihypertensive and diuretic agents
Nonsteroidal anti-inflammatory drugs can reduce the therapeutic effect of these drugs.

Antiplatelet drugs and selective serotonin inhibitors
Increased risk of gastrointestinal bleeding.

Cardiac Glycosides
NSAIDs can exacerbate heart failure, increase blood glycosides.

Zidovudine
There is evidence of an increased risk of hemarthrosis and hematoma in HIV-infected patients using concomitant treatment with zidovudine and ibuprofen.

Mifepristone
NSAIDs are not used earlier than 8-12 days after the use of mifepristone, since they reduce its effectiveness.

Tacrolimus
Possible increased risk of nephrotoxicity with the simultaneous use of NSAIDs and tacrolimus.

Potassium-sparing diuretics
Hyperkalemia may occur.

Alcohol
Increased risk of damage to the gastrointestinal tract and prolonged bleeding.

Quinolone antibiotics
The simultaneous use of NSAIDs and quinolone antibiotics can increase the risk of seizures.

Tetracycline
The absorption of tetracycline from the gastrointestinal tract increases.

Penicillin
Penicillin absorption decreases.

Chloramphenicol
The absorption of chloramphenicol is reduced.

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Packaging.Capsules No. 60 (10x6), No. 120 (10x12) in blisters in a box.

Vacation category.Over the counter.