Document: Comfora film-coated tablet ENG SmPC change

• Comfora film-coated tablet SmPC
• Comfora film-coated tablet ENG SmPC

---

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Comfora 595 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One film-coated tablet contains: glucosamine sulphate potassium chloride corresponding to 595 mg glucosamine.

Contains 130 mg (3.3 mmol) potassium per tablet.

Excipient with known effect:

The colorant Sunset yellow FCF (E110).

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL form

Film-coated tablet.

The tablet is yellow, oblong (length 19.6 mm, width 9.1 mm).

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

Posology

Initial dose: 1 tablet twice daily. Alternatively, the full dosage may be taken as a single dose during the day. Once symptom relief has been achieved, the dosage may be reduced to 1 tablet daily. The lowest effective dose should be aimed at.

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

Elderly patients: Dosage reduction is not required in treatment of elderly patients.

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.

Paediatric population:

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

Method of administration

Swallow the tablet with a glass of water.

4.3 Contraindications

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

Comfora should not be administered to patients who are allergic to shellfish, as the active ingredient 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 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.

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

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.

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

Comfora contains 3.3 mmol (130 mg) potassium per tablet. This should be taken into consideration for patients with impaired renal function or patients who are prescribed a potassium-low diet.

The colorant Sunset yellow FCF (E110) may cause allergic reactions.

4.5 Interaction with other medicinal products and other forms of interaction

Data on possible drug interactions with glucosamine is limited. Increased effect of coumarin anticoagulants (e.g. warfarin and acenocoumarol) during concomitant treatment with glucosamine 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 available from treatment of pregnant women with glucosamine. From animal studies only insufficient data are available (see section 5.3). Comfora should therefore not be used during pregnancy.

Breastfeeding

There is no data available on the excretion of glucosamine into human milk. The use of glucosamine during breastfeeding is not recommended as the safety for the newborn has not been established.

4.7 Effects on ability to drive and use machines

No studies have been performed. Comfora is not expected to have any effects on the ability to drive a motor vehicle or use machines. However, if drowsiness is experienced, driving and operating of machinery is not recommended.

The reported undesirable effects have been mild and usually transient.

System organ class	Common (>1/100 to <1/10)	Uncommon (>1/1 000 to <1/100)	Rare (>1/10 000 to <1/1000)	Unknown frequency (can not be estimated from available data)
Metabolism and nutrition disorders				Blood glucose control worsened in patients with diabetes mellitus
Nervous system disorders	Headache Drowsiness			Dizziness
Respiratory, thoracic and mediastinal disorders				Asthma or asthma deteriorated
Gastrointestinal disorders	Abdominal pain Dyspepsia Diarrhoea Constipation Nausea			Vomiting
Hepatobiliary disorders				Hepatic enzyme elevation, Jaundice
Skin and subcutaneous tissue disorders		Skin rash Pruritus Erythema		Angioedema Urticaria
General disorders and administration site conditions				Oedema/peripheral oedema

Sporadic, spontaneous cases of hypercholesterolaemia 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 national reporting system listed in Appendix V.

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 case 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 glucosamine up to 30 g.

In addition, 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. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Non-steroid antiinflammatory and antirheumatic agent

ATC code: M01AX05

Glucosamine is an endogenous substance. Exogenous administration of glucosamine to animals may increase the proteoglycan synthesis in cartilage and consequently inhibit the decomposition of cartilage. Long-term studies indicate that glucosamine may have a positive effect on cartilage metabolism. In published clinical studies, glucosamine has been shown to provide pain relief within four weeks as well as improve mobility of affected joints in patients with mild to moderate osteoarthritis.

5.2 Pharmacokinetic properties

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

The available information about the pharmacokinetics of glucosamine is limited. The absolute bioavailability is not known. 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 as unchanged substance in the urine.

5.3 Preclinical safety data

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 and in vivo studies on 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. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:

microcrystalline cellulose

povidone

crospovidone

magnesium stearate

Film coating:

Opadry yellow (partially hydrolysed polyvinyl alcohol, titanium dioxide (E 171), macrogol, talc, quinoline yellow aluminium lake (E 104), Sunset yellow FCF aluminium lake (E110) yellow iron oxide (E 172)).

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.

Plastic bottle (polyethene) 60, 180 and 400 tablets.

PVC/PVDC/aluminium blister 60, 90 and 180 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Nordic Drugs AB

Box 300 35

200 61 Limhamn

Sweden

8. MARKETING AUTHORISATION NUMBER(S)

21847

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

21 April 2006 / 21 April 2011

10. DATE OF REVISION OF THE TEXT

25 June 2015