SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Glucosamine sulphate 1500mg powder for oral solution

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each sachet contains:

Glucosamine sulphate sodium chloride 1884 mg, equivalent to glucosamine sulphate 1500 mg or 1178 mg glucosamine.

Excipients with known effect:

Each sachet contains 2.5 mg of aspartame and 2028.5 mg of sorbitol.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Powder for oral solution

White to slightly yellowish powder in single dose sachets.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Relief of symptoms in mild to moderate osteoarthritis of the knee.

4.2    Posology and method of administration

The contents of one sachet (1500 mg glucosamine sulphate) should be taken once daily. The entire contents of one sachet should be fully dissolved in at least 250 ml of water (one glass of water) before drinking.

Glucosamine is not indicated for the treatment of acute painful symptoms. Relief of symptoms (especially pain relief) may not be experienced until after some weeks of treatment or sometimes even longer. If no relief of symptoms is experienced after 2-3 months, continued treatment with glucosamine should be re-evaluated.

Additional information on special populations

Paediatric population:

Glucosamine sulphate should not be used in children and adolescents below the age of 18 years (see section 4.4).

Elderly

No specific studies have been performed in the elderly, but according to clinical experience dosage adjustment is not required when treating otherwise healthy, elderly patients.

Use in renal and liver impairment patients:

In patients with impaired renal and/or liver function no dose recommendations can be given, since no studies have been performed .

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Glucosamine sulfate tablets must not be used in patients who are allergic to shellfish as the active ingredient is obtained from shellfish.

Glucosamine sulphate must not be given to patients who suffer from phenylketonuria, since it contains aspartame, a source of phenylalanine.

4.4 Special warnings and precautions for use

A doctor must be consulted to rule out the presence of joint diseases for which other treatment should be considered.

In patients with impaired glucose tolerance, monitoring of the blood glucose levels and, where relevant, insulin requirements is recommended before start of treatment and periodically during treatment.

A report on exacerbated asthma symptoms triggered after initiation of glucosamine therapy has been described (symptoms resolved after withdrawal of glucosamine). Asthmatic patients starting on glucosamine should therefore be aware of potential worsening of symptoms.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

One sachet contains 6,6 mmol (151 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.

Glucosamine sulphate should not be used in children and adolescents under the age of 18 years since safety and efficacy have not been established.

4.5 Interaction with other medicinal products and other forms of interaction

Data on possible drug interactions with glucosamine is limited, but increased INR with coumarin anticoagulants (warfarin and acenocoumarol) has been reported. Patients treated with coumarin anticoagulants should therefore be monitored closely when initiating or ending glucosamine therapy.

Concurrent treatment with glucosamine may increase the absorption and serum concentration of tetracyclines, but the clinical relevance of this interaction is probably limited.

Due to limited documentation on potential drug interactions with glucosamine, one should generally be aware of altered response or concentration of concurrently used medicinal products.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of glucosamine in pregnant women. From animal studies only insufficient data are available. Glucosamine sulphate should not be used during pregnancy.

Breast-feeding

There are no data available on the excretion of glucosamine into human milk. The use of glucosamine sulphate during breastfeeding is therefore not recommended as there is no data on the safety for the newborn.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. If dizziness or drowsiness is experienced car driving and the operating of machinery is not recommended.

4.8 Undesirable effects

The most common adverse reactions associated with treatment with glucosamine are nausea, abdominal pain, dyspepsia, flatulence, diarrhoea and constipation. In addition, headache, somnolence, tiredness, rash, pruritus and erythema have been reported.

System Organ Class	Common (>1/100 to <1/10)	Uncommon (>1/1,000 to <1/100	Rare >1/10,00 0 to <1/1,000	Very rare <1/10,000	Unknown *
Immune system disorders					Allergic reaction
Nervous system disorders	Headache Somnolen ce Tiredness				Dizziness
Eye disorders					Visual disturbances
Gastrointesti nal disorders	Diarrhoea Constipati on Nausea Flatulence Abdomina l pain Dyspepsia
Skin and subcutaneous tissue disorders		Erythema Pruritis Rash			Hair loss

* frequency cannot be estimated from the available data

Sporadic, spontaneous cases of hypercholesterolemia have been reported, but causality has not been established.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

No case of overdose has been reported.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic products/Other anti-inflammatory and anti-rheumatic agents, non-steroids, ATC code: M01AX05

Glucosamine is an endogenous substance, a normal constituent of the polysaccharide chains of cartilage matrix and synovial fluid glucosaminoglycans. In vitro and in vivo studies have shown glucosamine stimulates the synthesis of physiological glycosaminoglycans and proteoglycans by chondrocytes and of hyaluronic acid by synoviocytes. The mechanism of action of glucosamine in humans is unknown. The period to onset of response cannot be assessed.

5.2    Pharmacokinetic properties

Glucosamine is a relatively small molecule (molecular mass 179), which is easily dissolved in water and soluble in hydrophilic organic solvents. The available information on the pharmacokinetics of glucosamine is limited. The absolute bioavailability is unknown. The distribution volume is approximately 5 litres and the half-life after intravenous administration is approximately 2 hours. Approximately 38% of an intravenous dose is excreted in the urine as unchanged substance.

5.3    Preclinical safety data

D-glucosamine has low acute toxicity. Animal experimental data relating to toxicity during repeated administration, reproduction toxicity, mutagenicity and carcinogenicity is lacking for glucosamine.

Results from in vitro studies and in vivo studies in animals have shown that glucosamine reduces insulin secretion and induces insulin resistance, probably via glucokinase inhibition in the beta cells. The clinical relevance is unknown

6.1    List of excipients

Citric acid, anhydrous (E330)

Macrogol 4000 Aspartame (E951)

Sorbitol (E420)

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

3 years.

6.4    Special precautions for storage

This medicinal product does not require any special temperature storage conditions.

6.5    Nature and contents of container

One sachet made of a three layered material comprising white Kraft paper, aluminium and low density polyethylene.

Pack sizes of 30, 60 or 90 sachets.

Not all pack-sizes may be marketed.

6.6    Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

MARKETING AUTHORISATION HOLDER

Crescent Pharma Limited,

Units 3 & 4, Quidhampton Business Units, Polhampton Lane, Overton,

Hants RG25 3ED United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 20416/0280

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

01/03/2016

10    DATE OF REVISION OF THE TEXT

01/03/2016