Download OSAFLEX 1178 mg powder for oral solution, sachet ENG

SUMMARY OF PRODUCT CHARACTERISTICS
1
NAME OF THE MEDICINAL PRODUCT
Osaflex 1178 mg powder for oral solution, sachet.
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each sachet contains: 1884 mg mixture of glucosamine hydrochloride and anhydrous
sodium sulphate, corresponding to 1500 mg glucosamine sulphate or 1178 mg
glucosamine.
Excipients with known effect:
Each sachet contains 2.5 mg aspartame (E951), 151 mg sodium and 2,028 mg sorbitol
(E420).
For the full list of excipients, see section 6.1.
3
PHARMACEUTICAL FORM
Powder for oral solution, sachet.
White, crystalline powder.
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
One sachet daily. The powder should be dissolved in a glass of water (250ml) and
drunk.
Glucosamine 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.
Osaflex should be taken at meals.
Additional information on special populations
Children and adolescents
Osaflex is not recommended for use in children and adolescents below the age of 18,
due to lack of data on safety and efficacy.
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.
Impaired renal and/or liver function
2
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.
Osaflex must not be given to patients who are allergic to shellfish as the active
substance is obtained from shellfish.
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.
In patients with a known risk factor for cardiovascular disease, monitoring of the blood
lipid levels 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 has been described (symptoms resolved after withdrawal of glucosamine).
Asthmatic patients starting on glucosamine should therefore be aware of potential
worsening of symptoms.
Osaflex contains aspartame, a source of phenylalanine, which may be harmful for
people with phenylketonuria.
Osaflex contains sorbitol. 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.
4.5
Interaction with other medicinal products and other forms of interaction
No specific drug interaction studies have been performed. However, the physicochemical and pharmacokinetic properties of glucosamine sulfate suggest a low potential
for interactions. In addition glucosamine sulfate 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 endogenous substance incorporated in proteoglycans or degradated
independently of the cytochrome system, is unlikely to give rise to drug interactions.
Increased effect of coumarin anticoagulants (e.g. warfarin) 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.
3
Non-steroidal anti-inflammatory drugs (NSAIDs) can be administered together with
glucosamine sulfate.
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
Fertility
In the rat, no adverse effects on fertility have been observed.
Pregnancy
Studies in animals did not show reproductive toxicity. There is no adequate data from
the use of glucosamine in pregnant women. Osaflex should therefore not be used during
pregnancy.
Breast Feeding
There is no data available on the excretion of glucosamine in human milk. Osaflex
should therefore not be used during breastfeeding.
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.
Glucosamine 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 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.
System Organ
Class
Common
(≥1/100 to
<1/10)
Uncommon
(≥1/1,000 to
<1/100)
Rare
(≥1/10,000
to <1/1,000)
Not known
(cannot be
estimated from
the available
data)
Immune system
disorders
Allergic reactions
(Hypersensitivity)
Metabolism and
nutrition
disordesr
Diabetes
inadequate control
Nervous system
disorders
Respiratory,
thoracic and
Headache
Tiredness
Somnolence
Dizziness
Asthma/ Asthma
aggravated
4
mediastinal
disorders
Gastrointestinal
disorders
Nausea
Abdominal
pain
Indigestion
Diarrhoea
Constipation
Flatulence
Skin and
subcutaneous
tissue disorders
Vomiting
Erythema
Rash
Itching
Flushing
Angioedema
Urticaria
General
Disorders and
Administration
Site Conditions
Oedema,
peripheral oedema
Hepatobiliary
disorders
Hepatic enzyme
increased and
jaundice
Investigations
International
normalized ratio
fluctuation
Sporadic, spontaneous cases of hypercholesterolemia have been reported, but causality
has not been established.
Reporting of suspected adverse events
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.
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: Other anti-inflammatory and anti-rheumatic agents, nonsteroidal anti-inflammatory drugs.
ATC code: M01AX05
Mechanism of action:
5
Glucosamine is an endogenous substance. Exogenous administration of glucosamine to
animals may increase the proteoglycan synthesis in cartilage and thereby inhibit the
degradation of the cartilage. Long term studies indicate that glucosamine may have a
positive effect on the metabolism of the 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.
Clinical efficacy and tolerability:
Glucosamine sulfate has demonstrated a good tolerability over both short-term and
long-term 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
sulfate was 44%, due to first-pass effect of the liver. After oral administration of daily
repeated doses of 1500 mg of glucosamine sulfate in healthy volunteers under fasting
conditions, the maximum plasma concentrations at steady-state (Cmax,ss) averaged
1602±426 ng/ml between 1.5-4 h (median: 3 h; tmax). At steady-state, the 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.
Distribution
The distribution volume is approximately 5 litres. Glucosamine does not bind to plasma
proteins.
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 sulfate 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
sulfate. No clinically relevant metabolic inhibition and/or induction interactions are
expected between crystalline glucosamine sulfate and co-administered drugs that are
substrates of the human CYP450 isoforms.
6
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.
Special population
Patients with renal or hepatic impairment
The pharmacokinetic of glucosamine was 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 included. 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 some 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
Aspartame (E951)
Sorbitol (E420)
Citric acid anhydrous
Macrogol 4000
6.2
Incompatibilities
Not applicable.
6.3
Shelf life
3 years
7
6.4
Special precautions for storage
Do not store above 30°C.
6.5
Nature and contents of container
One sachet made of a three-layered material comprising paper, aluminium and
polyethylene.
Pack-sizes of 30 and 90 sachets. Not all pack-sizes may be marketed.
6.6
Special precautions for disposal
No special requirements.
7
MARKETING AUTHORISATION HOLDER
To be completed nationally
8
MARKETING AUTHORISATION NUMBER(S)
To be completed nationally
9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
2009-07-16
10
DATE OF REVISION OF THE TEXT
2016-10-26