Crystalline glucosamine sulfate, chondroitin sulfate.
Each sachet contains crystalline glucosamine sulfate 942 mg equivalent to glucosamine sulfate 750 mg and sodium chloride 192 mg. It also contains chondroitin sulfate sodium 600 mg.
Pharmacology: Glucosamine Sulfate: The active ingredient glucosamine sulfate is the salt of an amino-monosaccharide glucosamine which is physiologically present in the human body and used, together with sulfates, for the biosynthesis of hyaluronic acid of the synovial fluid and of glycosaminoglycans of the fundamental substance of articular cartilage.
The mechanism of action of glucosamine sulfate is therefore the stimulation of glycosaminoglycans synthesis and thus of the articular proteoglycans. Moreover, glucosamine has anti-inflammatory activities and inhibits the degradation processes of articular cartilages, thus supporting from 1 side the activity on osteoarthritis symptoms and from the other side, the possible delay of the articular structural damage evidenced in the long-term clinical studies.
Short- and medium-term clinical studies have shown that the efficacy of glucosamine sulfate on osteoarthritis symptoms is already evident after 2-3 weeks from the beginning of administration. On the other hand, the symptomatic efficacy of glucosamine sulfate treatment, versus common analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), is ideal after 6-month continuous cycles, or after 3-month cycles with an evident residual effect of 2 months after withdrawal.
Clinical studies of daily continuous treatment up to 3 years have shown a decrease on osteoarthritis symptoms and a delay, radiologically determined, of structural damage at joint level.
Chondroitin Sulfate: Chondroitin sulfate is an important component of most vertebrate tissues. It is predominantly present in the extracellular matrix surrounding cells and is most abundant in those tissues with a large extracellular matrix eg, those that form the connective tissues of the body, cartilage, skin, blood vessels and also bone, ligaments and tendons.
Chondroitin sulfate has anti-inflammatory activity and affects cartilage metabolism.
In fact, chondroitin sulfate is an inhibitor of extracellular proteases involved in the metabolism of connective tissues. The addition of chondroitin sulfate to the medium of a chondrocytes culture from human articular cartilage resulted in an increase of proteoglycans concentration of the pericellular matrix and a dose-dependent decrease in collagenolytic activity.
Oral administration of chondroitin sulfate has shown to stimulate proteoglycan production of chondrocytes; to inhibit the production of certain proteolytic enzymes.
Short and long-term clinical trials have demonstrated that chondroitin sulfate is effective in relieving symptoms of osteoarthritis.
Glucosamine and Chondroitin Sulfate Combination: Glucosamine and chondroitin sulfate synergistically act to stimulate glycosaminoglycan synthesis. Combining these substances produces, from 1 site, the upregulation of the synthetic activities in chondrocytes and, from the other site, the inhibition of degradative enzymes.
When combined in an animal osteoarthritis model, glucosamine and chondroitin sulfate were more effective than the compounds alone.
Clinical studies in animals and man have further indicated that the combination therapy is effective and allows a significant drop in NSAIDs use by osteoarthritis patients.
Analgesics and NSAIDs may be used concomitantly with Adaxil, either for rescue analgesia during possible flares of the disease, or in the initial period of treatment, when the symptomatic effects of the product may be delayed for few weeks. Physical therapy programs can be used concomitantly with Adaxil in the overall management of osteoarthritis.
Pharmacokinetics: Glucosamine: Animal and human studies, carried out with 14C-labelled glucosamine, have shown that after oral administration, glucosamine is rapidly and almost completely absorbed at systemic level (about 90% of the radioactive dose is absorbed).
The steady-state concentrations of glucosamine in plasma and in the synovial fluid after repeated once-a day doses of 1500 mg are in the range of 10 micromol and therefore in line with those which have shown a pharmacological activity in in vitro experimental models, which justify the mechanism of action and the clinical effect of the drug.
After oral absorption, glucosamine is significantly distributed in extravascular compartments (including synovial fluid) with an apparent distribution volume of 37-fold higher than the total human body water quantity. In humans, glucosamine has shown to have affinity for joint tissues.
In man, the terminal elimination half-life of glucosamine from plasma has been estimated as around 15 hrs. Experimental results show that the kidneys significantly contribute to the elimination of glucosamine and/or of its metabolites.
Chondroitin Sulfate: The bioavailability after oral administration is 15-24%. A 10% of absorbed chondroitin sulfate appears in unmetabolized form and 90% as depolymerized derivatives with lower molecular weight, as a result of first-pass effect metabolism.
Distribution volume of chondroitin sulfate is relatively low. In humans, chondroitin sulfate has shown to have affinity for joint tissues. At least 90% of chondroitin sulfate dose is 1st metabolized by lysosomal sulfateses, and after that it is depolymerized by hyaluronidases ie, β-glucuronidases and β-N-acetyl hexose amidases. Liver, kidneys and other organs are involved in the depolymerization of chondroitin sulfate.
On overage, chondroitin sulfate remains in the body 5-15 hrs. Main part of chondroitin sulfate and its depolymerized derivatives are eliminated through the kidneys.
Treatment of the symptoms of osteoarthritis ie, pain and function limitation.
Two sachets daily, preferably at meals. Adaxil must be dissolved in a glass of water before oral administration.
No cases of accidental or intentional overdose are known. The acute animal and chronic toxicological studies of Adaxil active ingredients indicate that toxic effects and symptoms of toxicity are not likely to occur, even after high overdoses.
However, if overdose occur the treatment should be symptomatic eg, hydroelectrolytic balance restoration.
Hypersensitivity to chondroitin sulfate, glucosamine sulfate or to any of the excipients of Adaxil.
Adaxil contains sorbitol 1163 mg as excipient. Therefore, patients with rare hereditary problems of fructose intolerance should not take Adaxil.
Adaxil is not indicated for the treatment of acute painful symptoms.
Since glucosamine is derived from seafood (shellfish), Adaxil should not be given to patients who are allergic to shellfish.
Adaxil contains sodium and needs to be taken into consideration by patients on a controlled sodium diet.
In patients with cardiac and/or renal insufficiency, edema and water retention was observed very rarely. This effect could be attributed to the effect of chondroitin sulfate. The administration of Adaxil to these patients should be under strict medical supervision.
No special studies were performed in patients with hepatic insufficiency. The administration of Adaxil to patients with severe hepatic insufficiency should be under strict medical supervision.
Caution is advised in treatment of patients with impaired glucose tolerance. Closer monitoring of blood sugar levels may be necessary at the beginning of treatment.
An increased effect of coumarinic anticoagulants (eg, warfarin) during concomitant treatment with glucosamine sulfate, one of the active ingredients of Adaxil may occur. Therefore, a closer monitoring of the coagulation parameters may be considered in those patients being treated with Adaxil.
Due to its chondroitin sulfate content, in case of concomitant administration of platelet anti-aggregant drugs eg, acetylsalicylic acid, dipyridamole, clopidogrel, ditazol, trifusal and ticlopidine, Adaxil should be administered under strict medical supervision.
Concurrent treatment with glucosamine sulfate may increase the gastrointestinal absorption of tetracyclines. Caution is advised in case of concomitant administration of Adaxil and tetracyclines.
The colouring agent sunset yellow (E110) may cause allergic reactions.
Effects on the Ability to Drive or Operate Machinery: No important effects on the central nervous system or motor system are known that might impair the ability to drive or use machines. However, caution is advised if somnolence or visual disturbances are experienced.
Use in pregnancy & lactation: In the absence of studies on reproductive function in humans, the use of Adaxil during pregnancy and lactation should be avoided.
In the absence of studies on reproductive function in humans, the use of Adaxil during pregnancy and lactation should be avoided.
The clinical trials have shown the good tolerability of Adaxil. Undesiderable effects have been observed in a low proportion of patients. They were transient, of minor entity and included: Cardiovascular:
Peripheral oedema, tachycardia were reported in a few patients following larger clinical trials investigating oral administration in osteoarthritis. Causal relationship has not been established.
Central Nervous System:
Drowsiness, headache, somnolence, insomnia have been observed rarely during therapy.
Nausea, vomiting, diarrhoea, dyspepsia or epigastric pain, flatulence, constipation, heartburn and anorexia have been described rarely during oral therapy with glucosamine.
Skin reactions eg, cutaneous rash, erythema, pruritus have been reported with therapeutic administration of glucosamine. Occasionally contact dermatitis, papular rash, urticaria and eczema may occur.
Isolated cases of hair loss, allergic reactions, visual disturbances and oedema were observed.
No formal drug interaction studies have been performed, however, the physicochemical and pharmacokinetic properties of glucosamine sulfate suggest a low potential for interactions.
However, interactions between the active ingredients of Adaxil and other drug substances may occur ie, between glucosamine sulfate and coumarinic anticoagulants, glucosamine sulfate and tetracyclines, chondroitin sulfate and platelet anti-aggregant drugs (see Precautions).
M01AX - Other antiinflammatory and antirheumatic agents, non-steroids ; Used in the treatment of inflammation and rheumatism.
Powd for oral soln (single-dose powd in sachet) 30's.