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SUMMARY OF THE PRODUCT CHARACTERISTICS
1
NAME OF THE MEDICINAL PRODUCT
Glucosine 625 mg film-coated tablets
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
1 tablet contains glucosamine sulphate - sodium chloride complex corresponding to 625 mg
glucosamine or 795 mg glucosamine sulphate.
Excipient: 1 tablet contains sodium 78 mg
For a full list of excipients, see section 6.1.
3
PHARMACEUTICAL FORM
Film-coated tablet
White to beige tablet, oblong, 8,5 x 19 mm.
4
CLINICAL PARTICULARS
4.1
Therapeutic indications
Relief of symptoms in mild to moderate osteoarthritis.
4.2
Posology and method of administration
Start dosage: 1 tablet 2 times daily, preferable at meals. Alternatively, the total daily dose may
be administered on one occasion.
Glucosine is not indicated for the treatment of acute painful symptoms.
The clinical effect is usually seen within 4 weeks after the start of treatment.
The lowest effective dose should be used.
Elderly
No dosage adjustment is required when treating elderly patients.
Impaired renal and/or liver function
Since no studies have been performed on patients with impaired renal and/or liver function,
no dose recommendations can be given.
Children and adolescents
Glucosine should not be given to children and adolescents under the age of 18 years.
4.3
Contraindications
Hypersensitivity to the active ingredient glucosamine or to any of the excipients.
Glucosine should not be given to patients who are allergic to shellfish as the active ingredient
is obtained from shellfish.
4.4
Special warnings and precautions for use
A doctor’s consultation is recommended to rule out the presence of joint diseases for which
other treatment should be considered.
Caution is recommended in treatment of patients with diabetes mellitus. Closer monitoring of
the blood glucose level may be required at the beginning of treatment.
Glucosine must not be given to children and adolescents under the age of 18 years since
efficacy and safety have not been shown.
Caution is recommended if glucosamine is combined with other medicinal products, since
interaction data are missing (see 4.5 Interaction with other medicinal products and other forms
of interaction).
In asthmatic patients the product should be used with caution as these patients could be more
susceptible to develop an allergic reaction to glucosamine with possible exacerbation of their
symptoms.
Glucosine contains 78 mg sodium per tablet and this is to be considered in patients on a
controlled sodium diet.
4.5
Interaction with other medicinal products and other forms of interaction
No specific drug interaction studies have been performed. However the physical-chemical
pharmacokinetic properties of glucosamine sulphate suggest a low potential for interactions.
In addition glucosamine sulphate was found not to inhibit or to induce any of the major
human CYP450 enzymes. In fact, the compound does not compete for absorption mechanisms
and, after absorption, does not bind to plasma proteins, while its metabolic fate as an
andogenous substance incorporated in proteoglycans or degraded independently of the
cytochrome enzyme system, is unlikely to give rise or to drug interactions.
The oral administration of glucosamine sulphate can enhance the gastrointestinal absorption
of tetracyclines but the clinical relevance of this interaction is probably limited.
Data on possible drug interactions with glucosamine is limited.
Increased effect of coumarin anticoagulants (e.g. warfarin) during concomitant treatment with
glucosamine has been reported in the post–marketing experience. Patients treated with
coumarin anticoagulants should therefore be monitored closely when initiating or ending
glucosamine therapy.
Non-steroidal anti-inflammatory drugs (NSAIDs) can be administered together with
glucosamine sulphate.
It is not known whether glucosamine has any effects on the pharmacokinetics of other drugs.
As possible interactions can not be ruled out, care should be taken when combining
glucosamine with other medicinal products.
4.6
Pregnancy and lactation
Pregnancy
Studies in animals did not show reproductive toxicity. There is no adequate data from the use of
glucosamine in pregnant women. Glucosine should therefore not be used during pregnancy.
Breastfeeding
There is no data available on the excretion of glucosamine in human milk. Glucosine should therefore
not be used during breastfeeding.
Fertility
In the rat, no adverse effects on fertility have been observed.
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.
Glucosine is not expected to have any effects on the ability to drive and use machines. If
dizziness or drowsiness is experienced, car driving and the operating of machinery are not
recommended.
4.8
Undesirable effects
The most frequently reported undesirable effects with the glucosamine therapy include
stomach ache and discomfort, dyspepsia, constipation, diarrhoea and nausea. Headache,
fatigue, pruritus and erythema have also been reported. The reported undesirable effects were
mild and usually transient.
The following adverse reactions have been reported in the post-marketing experience of
glucosamine: angioedema/urticaria, oedema/peripheral oedema, dizziness, blood glucose
control worsened in patients with diabetes mellitus, hepatic enzyme elevation, jaundice.
Adverse drug reactions are ranked by frequency, the most frequent first, using the following
convention: 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).
Within each frequency grouping, adverse reactions are ranked in order of decreasing
seriousness.
The following side effects have been reported:
System
Organ Class
Immune
system
disorders
Metabolism
and nutrition
disorders
Nervous
system
disorders
Vascular
disorders
Respiratory,
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)
Allergic reaction
(Hypersensitivity)
Diabetes
inadequate
control
Dizziness
Headache
Somnolence
Flushing
Asthma/
thoracic and
mediastinal
Gastrointestinal Diarrhoea
disorders
Constipation
Nausea
Flatulence
Abdominal
pain
Dyspepsia
Hepatobiliary
disorders
Skin and
subcutaneous
tissue disorders
General
Tiredness
disorders and
(Fatigue)
administration
site conditions
Investigations
Asthma
aggravated
Vomiting
Jaundice
Erythema
Pruritus
Rash
Angioedema
Urticaria
Oedema/
peripheral
oedema
Hepatic enzyme
elevation
International
normalized ratio
fluctuation
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 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.
One case of overdose has been reported. A 12-year old female who took orally 28g of
glucosamine hydrochloride. She developed arthralgia, vomiting and disorientation. The
patient fully recovered.
5
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Other anti-inflammatory and anti-rheumatic agents, non-steroids
ATC-code: M01AX05
Mechanism of action
Glucosamine is an endogenous substance. Exogenous administration of glucosamine to
animals may increase the proteoglucan synthesis in cartilage and thereby inhibit the
degradation of cartilage. Long-term studies indicate that glucosamine may have a positive
effect on the metabolism of cartilage.
However, the mechanism of action of glucosamine in humans is unknown. Clinical studies
have shown that pain relief is expected to occur after some weeks of treatment with
glucosamine.
I
Clinical efficacy and tolerability
Glucosamine sulphate has demonstrated a good tolerability over both short-term and longterm treatment courses.
5.2
Pharmacokinetic properties
Absorption.
After oral administration of 14C-labelled glucosamine, the radioactivity is rapidly and almost
completely (about 90%) absorbed systemically in healthy volunteers. The absolute
bioavailability of glucosamine in man after administration of oral glucosamine sulphate was
44%, due to first-pass effect of the liver. After oral administration of daily repeated doses of
1500 mg of glucosamine sulphate in healthy volunteers under fasting conditions, the
maximum plasma concentrations at steady-state (Cmax,ss) averaged 1602±426 ng/mml between
1.5-4 h (median; 3 h, tmax). At steady-state, AUC of the plasma concentrations vs time curve
was 14564±4138 ng.h/ml. It is unknown if meals significantly affect the drug oral
bioavailability. The pharmacokinetics of glucosamine are linear after once daily repeated
administrations in the dose interval 750-1500 mg with deviation from linearity at the dose of
3000 mg due to lower bioavailability. No gender differences were found in man with regard
to the absorption and to the bioavailability of glucosamine. The pharmacokinetics of
glucosamine was similar between healthy volunteers and patients with osteoarthritis of the
knee.
DistributionThe distribution volume is approximately 5 litres. Glucosamine does not bind to
plasma protein.
Metabolism.
The metabolic profile of glucosamine has not been studied because being an endogenous
substance; it is used as a building block for the biosynthesis of articular cartilage components.
Glucosamine is mainly metabolized through the hexosamine pathway and independently of
the cytochrome enzyme system.
Crystalline glucosamine sulphate does not act as an inhibitor nor as an inducer of the human
CYP450 isoenzymes including CYP 3A4, 1A2, 2E1, 2C9 and 2D6 even when tested at
concentrations of glucosamine 300-fold higher than the peak plasma concentrations observed
in man after therapeutic doses of crystalline glucosamine sulphate. No clinically relevant
metabolic inhibition and/or induction interactions are expected between crystalline
glucosamine sulphate and co-administered drugs that are substrates of the human CYP 450
isoforms.
Excretion.
In man, the terminal elimination half-life of glucosamine from plasma is estimated at 15 h.
After oral administration of 14C-labelled glucosamine to humans, the urinary excretion of
radioactivity was 10±9% of the administered dose while fecal excretion was 11.3±0.1%. The
mean urinary excretion of unchanged glucosamine after oral administration in man was about
1% of the administered dose suggesting that the kidney and the liver do not significantly
contribute to the elimination of glucosamine and/or of its metabolites and/or its degradation
products.
Patients with renal or hepatic impairment.
The pharmacokinetics of glucosamine were not investigated in patients with renal or hepatic
insufficiency(See section 4.2).
Children and adolescents.
The pharmacokinetics of glucosamine was not investigated in children and adolescents.
Elderly patients.
No specific pharmacokinetic studies were performed in elderly however in the clinical
efficacy and safety studies mainly elderly patients were include. Dose adjustment is not
required.
5.3
Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, toxicity to reproduction and development.
Carcinogenicity studies are not available.
Results from in vitro and in vivo studies in animals have shown that i.v. infusion of
glucosamine in suprapharmacological concentrations reduces insulin secretion, probably via
inhibition of glucokinase in the beta cells, and induces insulin resistance in peripheral tissues.
The relevance in humans is inconclusive.
6
PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Tablet core:
Povidone,
Citric acid anhydrous
Colloidal anhydrous silica
Magnesium stearate
Microcrystalline cellulose
Sodium starch glycolate (type A)
Film coating:
Macrogol 6000
Hypromellose
Paraffin.
6.2
Incompatibilities
Not applicable.
6.3
Shelf-life
2 years.
6.4
Special precautions for storage
Do not store above 25 ºC.
6.5
Nature and contents of container
60, 90 and 180 tablets in white plastic bottles with screw caps of HDPE (polyethylene).
Not all pack sizes may be marketed.
6.6
Special precautions for disposal
No special requirements.
7
MARKETING AUTHORISATION HOLDER
Recip AB, Box 906, 170 09 Solna, Sweden
8
MARKETING AUTHORISATION NUMBER(S)
21339
9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
2005-05-20 / 2009-12-30
10
DATE OF REVISION OF THE TEXT
11
2016-10-26