SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Glucosamine 1250 mg Effervescent Tablets

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each effervescent tablet contains 1250 mg glucosamine (as glucosamine hydrochloride).

Excipients:    Sorbitol (E420)

Sodium

For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Effervescent tablet.

Round, white to almost white effervescent tablets with lemon flavour.

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

Adults

1250 mg per day corresponding to one effervescent tablet Glucosamine 625 mg twice daily or one effervescent tablet Glucosamine 1250 mg once daily.

Before intake the effervescent tablets must be dissolved in at least 100 ml water ('A glass) and can be taken independently from meals.

Glucosamine is not indicated for the treatment of acute painful symptoms. Relief of symptoms (particularly pain relief) may not be experienced until after several weeks of treatment and in some cases even longer. If pain relief is not achieved after 2-3 months, continued treatment with glucosamine should be re-evaluated.

Elderly

Dose adjustment is not necessary in treatment of elderly.

Children and Adolescents

Glucosamine is not recommended for use in children and adolescents below 18 years, due to lack of data on safety and efficacy.

Impaired renal and/or hepatic function

As no studies have been conducted in patients with impaired renal and/or hepatic function, dosage recommendations cannot be given

4.3 Contraindications

Glucosamine is contraindicated in the following cases:

•    Hypersensitivity to glucosamine or to any of the excipients.

•    Patients who are allergic to shellfish as the active substance is extracted from shellfish.

4.4 Special warnings and precautions for use

A physician should be consulted to rule out the presence of joint diseases for which other treatments 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.

In patients with a known risk factor for cardiovascular disease, monitoring of the blood is recommended, since hypercholesterolemia has been observed in a few cases in patients treated with glucosamine.

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

Glucosamine contains sorbitol. Patients with hereditary problems of fructose intolerance should not take this medicine.

Glucosamine 625 mg effervescent tablets contain 13.9 mmol sodium per effervescent tablet. Should be used with caution in patients with cardiac insufficiency.

4.5 Interaction with other medicinal products and other forms of interaction

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

It has been reported that glucosamine may affect the serum concentration of ciclosporine.

Concurrent treatment with glucosamine may increase the absorption and serum concentration of tetracyclines, but the clinical relevance of these interactions 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:

Glucosamine should not be used in pregnant women.

There are no adequate data available from treatment of pregnant women with glucosamine.

Experiences based on animal trials with regard to the effects on pregnancy and the embryonal/foetal development and the post natal development (see section 5.3) are insufficient.

Lactation:

It is not known if glucosamine is excreted in human milk.

Glucosamine should not be used during breast feeding as there are no data available on safety of the newborn during lactation.

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 light headedness, drowsiness, dizziness, nausea or vomiting occurs, car driving and operating machinery is not recommended.

4.8 Undesirable effects

The most common adverse reactions associated with treatment with glucosamine are nausea, abdominal pain, indigestion, constipation, and diarrhoea. In addition, headache, tiredness, rash, itching, and flushing have been reported. The reported adverse reactions are usually mild and transitory.

In the table below, all causality adverse events are listed by system organ class and frequency (very common >1/10; common >1/100 to <1/10; uncommon >1/1,000 to <1/100; rare >1/10,000 to <1/1,000; very rare <1/10,000; not known (cannot be estimated from the available data)).

MedDRA System Organ Class	Common (>1/100 to <1/10)	Uncommon (>1/1000 to <1/100)	Not known (cannot be estimated from the available data)
Nervous system disorders	Headache Tiredness	-	Dizziness
Respiratory, thoracic and mediastinal disorders			Asthma / Asthma aggravated

Gastrointestinal disorders	Nausea Abdominal pain Indigestion Diarrhoea Constipation		Vomiting
Skin and subcutaneous tissue disorders		Rash Itching Flushing	Angioedema Urticaria
Metabolism and nutrition disorders			Diabetes mellitus inadequate control Hypercholesterola emia
General disorders and administration site conditions			Oedema / Peripheral oedema

Cases of hypercholesterolemia, asthma, aggravated and diabetes mellitus inadequate control have been reported, but causality has not been established.

Glucosamine may cause hepatic enzyme elevation and rarely jaundice.

Patients with diabetes mellitus

Blood glucose control worsened in patients with diabetes mellitus. Frequency not known.

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, website www.mhra.gov.uk/yellowcard.

4.9 Overdose

Signs and symptoms of accidental or intentional overdose with glucosamine might include headache, dizziness, disorientation, arthralgia, nausea, vomiting, diarrhoea or constipation.

In cases of overdose, treatment with glucosamine should be discontinued and standard supportive measures should be adopted as required.

In clinical trials one of five healthy young subjects experienced headache following infusion of glucosamin up to 30 g.

One case of overdose has been reported in a 12-year old female who took orally 28 g of glucosamine hydrochloride. She developed arthralgia, vomiting and disorientation. The patient fully recovered.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other anti-inflammatory and anti-rheumatic agents, non-steroidal anti-inflammatory drugs.

ATC-code: M01AX05

Glucosamine is an endogenous substance, a common constituent of the polysaccharide chains of cartilage matrix and synovial fluid glucosaminoglycans. In vitro and in vivo studies have shown that glucosamine stimulates the synthesis of physiological glucosaminoglycans 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 established.

5.2 Pharmacokinetic properties

Glucosamine hydrochloride is a relatively small molecule (molecular mass 179), which is easily dissolved in water and in soluble in hydrophilic organic solvents.

Available data on the pharmacokinetics of glucosamine are 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. Glucosamine is absorbed by a glucose transporter and does not bind to plasma proteins following the absorption into the circulation. Glucosamine is mainly excreted via the hexosamine system independently of the cytochrome enzyme system.

5.3 Preclinical safety data

Incomplete, non-clinical trials on acute and chronic toxicity of glucosamine and genotoxicity reveal no special hazard for humans beyond those mentioned in this Summary of Product Characteristics. No investigations have been performed on carcinogenicity.

Adverse damaging effects on fertility, embryo/foetal development and post natal development have not been observed in rats. Only limited data on reproduction toxicity are available in rabbits. Therefore, a teratogenic effect cannot be excluded in this species. Results from in vitro 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. Furthermore glucosamine causes an insulin resistance in the peripheral tissue. The clinical relevance of this fact is unknown.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Citric acid, anhydrous

Sodium hydrogen carbonate Sodium carbonate, anhydrous Sorbitol (E420)

Acesulfame potassium

Leucine

Lemon flavour

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 storage conditions.

6.5 Nature and contents of container

PP-tube with PE-cap with desiccant (silica gel) Strip (paper/PE/aluminium/surlyn)

Pack sizes:

PP			tubes:
20	effervescent	tablets	(2x10)
15	effervescent	tablets	(1x15)
30	effervescent	tablets	(2x15)
90	effervescent	tablets	(6x 15)
20	effervescent	tablets	(1x20)
40	effervescent	tablets	(2x20)

60 effervescent tablets (3x20)

Strips:

30 effervescent tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

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

7 MARKETING AUTHORISATION HOLDER

Medley Pharma Limited Unit 2A,

Olympic Way Sefton Business Park Liverpool L30 1RD UK

MARKETING AUTHORISATION NUMBER(S)

PL 43870/0036

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

04/08/2011

DATE OF REVISION OF THE TEXT

20/07/2015