Adaxil

Powder for oral solution.
Orange powder, with characteristic orange taste and odour.
Each sachet contains: Active Ingredients: Crystalline glucosamine sulphate 942 mg equivalent to: glucosamine sulphate 750 mg, sodium chloride 192 mg, Chondroitin sulphate sodium 600 mg.
Excipients/Inactive Ingredients: Sorbitol (E 420), Citric Acid anhydrous (E 330), Orange Aroma, Acesulfame K (E 950), Sunset Yellow (E 110).

Pharmaco-therapeutic Group: Product for the treatment of osteoarthritis.
Pharmacology: ADAXIL is a medicinal product containing the active ingredients glucosamine sulphate and chondroitin sulphate.
Glucosamine sulphate: The active ingredient glucosamine sulphate is the salt of an amino-monosaccharide glucosamine which is physiologically present in the human body and used, together with sulphates, 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 sulphate 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 one 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 sulphate on osteoarthritis symptoms is evident already after 2-3 weeks from the beginning of administration. On the other hand, the symptomatic efficacy of glucosamine sulphate treatment, versus common analgesics and nonsteroidal anti-inflammatory drugs, 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 sulphate: Chondroitin sulphate 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 such as those that form the connective tissues of the body, cartilage, skin, blood vessels and also bone, ligaments and tendons.
Chondroitin sulphate has anti-inflammatory activity and affects cartilage metabolism. In fact, Chondroitin sulphate is an inhibitor of extracellular proteases involved in the metabolism of connective tissues. The addition of chondroitin sulphate 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 sulphate 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 sulphate is effective in relieving symptoms of osteoarthritis.
Glucosamine and Chondroitin sulphate combination: Glucosamine and chondroitin sulphate synergistically act to stimulate glycosaminoglycan synthesis. Combining these substances produces, from one 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 sulphate 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 μM 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 h. Experimental results show that the kidneys significantly contributes to the elimination of glucosamine and/or of its metabolites.
Chondroitin sulphate: 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 sulphate dose is first metabolized by lysosomal sulphateses, and after that it is depolymerized by hyaluronidases, i.e. β-glucuronidases and β-N-acetyl hexose amidases. Liver, kidneys and other organs are involved in the depolymerization of chondroitin sulphate.
On overage, chondroitin sulphate remains in the body 5-15 hours. Main part of chondroitin sulphate and its depolymerized derivatives are eliminated through the kidneys.

Treatment of the symptoms of osteoarthritis i.e. pain and function limitation.

The contents of two sachets daily, preferably at meals. The product must be dissolved in a glass of water before oral administration.

No cases of accidental or intentional overdose are known. The animal acute 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 e.g. hydroelectrolytic balance restoration.

Hypersensitivity to chondroitin sulphate, glucosamine sulphate or to any of the excipients.
Adaxil contains 1163 mg of sorbitol as excipient. Therefore, patients with rare hereditary problems of fructose intolerance should not take this medicine.
Since glucosamine is derived from seafood (shellfish), the product should not be given to patients who are allergic to shellfish.

Special Warnings: In the absence of studies on reproductive function in humans, the use of ADAXIL during pregnancy and lactation should be avoided.
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 adviced if somnolence or visual disturbances are experienced.
The colouring agent Sunset yellow (E110) may cause allergic reactions.
Precautions for Use: ADAXIL is not indicated for the treatment of acute painful symptoms.
Glucosamine is derived from seafood.
This medicinal product contains sodium. 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 sulphate. 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 (such as warfarin) during concomitant treatment with glucosamine sulphate, 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 sulphate content, in case of concomitant administration of platelet anti-aggregant drugs such as acetylsalicylic acid, dipyridamol, clopidogrel, ditazol, trifusal and ticlopidine, ADAXIL should be administered under strict medical supervision.
Concurrent treatment with glucosamine sulphate may increase the gastrointestinal absorption of tetracyclines. Caution is advised in case of concomitant administration of ADAXIL and tetracyclines.

The clinical trials have shown the good tolerability of the product. Undesirable 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.
Gastrointestinal: Nausea, vomiting, diarrhoea, dyspepsia or epigastric pain, flatulence, constipation, heartburn and anorexia have been described rarely during oral therapy with glucosamine.
Skin: Skin reactions such as 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.
The patient should inform his/her doctor of any undesirable effect experienced during the treatment.

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, i.e. between glucosamine sulphate and coumarinic anticoagulants, glucosamine sulphate and tetracyclines, chondroitin sulphate and platelet anti-aggregant drugs (see also Precautions for Use under Precautions).

Do not store above 30°C.

Other Drugs Acting on Musculo-Skeletal System

M01AX - Other antiinflammatory and antirheumatic agents, non-steroids ; Used in the treatment of inflammation and rheumatism.

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