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Active substance(s): SODIUM OXIDRONATE

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OSTEOCIS®
Kit for the preparation of Technetium [99mTc] Oxidronate Injection
PATIENT INFORMATION LEAFLET

1. IDENTIFICATION OF THE MEDICINAL PRODUCT
Name of the Medicinal Product
OSTEOCIS®
Kit for the preparation of Technetium [99mTc] Oxidronate Injection.
Qualitative Composition
Sodium oxidronate.
Quantitative Composition
Each vial contains 3 mg of sodium oxidronate.
Pharmaceutical Form
The product is a powder which, when mixed with a solution of the radioactive
substance sodium pertechnetate [99mTc] forms a technetium [99mTc] oxidronate.
Pharmaco-Therapeutic Group
Technetium [99mTc] oxidronate is a diagnostic radiopharmaceutical. When injected
the radiopharmaceutical temporarily collects in a particular organ of the body.
Because the substance contains a small amount of radioactivity it can be detected
from outside the body using special cameras, and a picture, known as a scan, can
be taken. This scan will show exactly the distribution of the radioactivity within the
organ and the body. This can give the physician valuable information about
structure and function of that organ.
Name and Address of the Holder of the Marketing Authorisation
CIS bio international
B.P. 32
91192 Gif-sur-Yvette Cedex
FRANCE
PL/11876/0006

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Name and Address of the Manufacturer
CIS bio international
B.P. 32
91192 Gif-sur-Yvette Cedex
FRANCE
2. WHEN IS THE PRODUCT USED ?
When injected, technetium [99mTc] oxidronate circulates in the blood and collects in
the bones. A scan will then help your physician to determine if there is any bone
abnormality.
3. WARNINGS
When should this Product not be used ?
There are no special circumstances in which this product must not be used.
IN CASE OF DOUBT IT IS ESSENTIAL TO CONSULT YOUR PHYSICIAN
Special Warnings
The use of technetium [99mTc] oxidronate does involve administration of small
amounts of radioactivity. The risk this involves is very small and your physician will
not consider carrying out the investigation unless he believes that the risk is
outweighed by the potential benefit of the study.
Precautions for Use
In order to ensure the most efficient use of the product, you are recommended to
avoid strenuous exercise after injection until satisfactory scans have been taken.
Because technetium [99mTc] oxidronate is administered as a single dose by trained
personnel there are no precautions which are your responsibility.
Your physician will inform you if you need to take any special precautions after use
of this product.
IN CASE OF DOUBT DO NOT HESITATE TO CONSULT YOUR PHYSICIAN
Interactions with other Medicinal Products and other Forms of Interaction
Some medicines may affect the quality of the scans obtained from technetium
[99mTc] oxidronate examinations.
IN ORDER TO AVOID POSSIBLE INTERACTIONS WITH OTHER MEDICINAL
PRODUCTS, ANY OTHER CURRENT MEDICATION MUST BE NOTIFIED TO
YOUR PHYSICIAN.

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Pregnancy-Lactation
It is important to tell your physician if there is any possibility that you are pregnant.
Special consideration is given to the use of radiopharmaceuticals during
pregnancy. Your physician will only use this product if he considers that the
potential benefit outweighs the risk.
Tell your physician if you are breast-feeding as he may delay the investigation until
breast-feeding is completed or ask you to stop breast-feeding for a short while until
the radioactivity is no longer in your body.
Effects on Ability to Drive or to Operate Machinery
Technetium [99mTc] oxidronate has no effect on your fitness to drive or to operate
machinery.
Sportsmen and Sportswomen
There are no particular precautions for the use of technetium [99mTc] oxidronate by
people engaged in active sport.
List of those Excipients, Knowledge of which is important for the Safe Use of
the Medicinal Product in certain Patients
This product contains no ingredients which might necessitate special consideration
being given to it's use for particular types of patients.
4. HOW IS THIS PRODUCT USED ?
Dosage
Your physician will decide on the amount of radioactive technetium [99mTc]
oxidronate to be used. This will be the minimum amount necessary to give a scan
clear enough to supply the required information. Doses may be from 40 MBq for
small children, up to a maximum of 700 MBq (Megabecquerel - the unit in which
radioactivity is measured).
Method and Route of Administration
Technetium [99mTc] oxidronate is administered by injection into a vein.
Frequency of Administration and appropriate Time of Administration
One injection is sufficient to provide your physician with the information needed.
Before the scan you will be told to urinate. This will increase the quality of the
scan.

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Duration of the treatment
Scans may be taken during a few minutes after the injection in some cases or at
2 or 3 hours after the injection.
Action to be taken in the case of an Overdose
Since technetium [99mTc] oxidronate is administered by a physician under strictly
controlled conditions there is a little chance of possible overdose.
Action to be taken when one or more doses have not been taken
Not applicable in the case of this medicinal product.
Risk of withdrawal effects
No such risks occur with this product.
5. UNDESIRABLE EFFECTS
Technetium [99mTc] oxidronate does not normally produce any side effects.
Some allergic type reaction have been notified (rash, itching and skin irritation
several hours after injection). On rare occasions, fall in blood pressure,
hypotensive symptoms, nausea, vomiting, flushing, headache, malaise, swelling of
the extremities and pain in joints have been reported.
INFORM YOUR PHYSICIAN IF YOU EXPERIENCE ANY ILL-EFFECTS
6. STORAGE
The product label includes the appropriate storage conditions and the expiry date
for the batch of product. Hospital personnel will ensure that the product is stored
correctly and not administered to you after the stated expiry date.
7. DATE OF LAST REVISION OF THE PACKAGE LEAFLET
04/2006

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OSTEOCIS®

Kit for the preparation of Technetium [99mTc] Oxidronate Injection

USER PACKAGE LEAFLET

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IDENTIFICATION OF THE MEDICINAL PRODUCT
Trade name of the medicinal product
OSTEOCIS®
Kit for the preparation of Technetium [99mTc] Oxidronate Injection
Qualitative and quantitative composition
OSTEOCIS®, kit for the preparation of Technetium [99mTc] Oxidronate
Injection, consists of 5 multidose vials, each containing the following
sterile, pyrogen-free, freeze-dried product under nitrogen :
Sodium oxidronate (I.N.N.)
Stannous chloride dihydrate
Ascorbic acid
Sodium chloride

:
:
:
:

3.0
0.45
0.75
10.0

mg
mg
mg
mg

The product contains no antimicrobial preservative.
The product is to be used after reconstitution by the addition of sterile,
pyrogen-free, isotonic sodium pertechnetate [99mTc] injection, allowing
the preparation of Technetium [99mTc] Oxidronate Injection (technetium
[99mTc] hydroxymethylene diphosphonate, i.e. technetium [99mTc] HMDP).
Nature and contents of container
15 ml, colourless, European Pharmacopoeia type I, drawn glass vials,
closed with rubber stoppers and aluminium capsules.
Pharmaceutical form
Powder for injection.
Pharmaco-therapeutic group
Radiopharmaceutical product for diagnostic use.

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Name and address of the marketing authorisation holder
CIS bio international
B.P. 32
91192 Gif-sur-Yvette Cedex
FRANCE
Tel. : +33-(0)1.69.85.70.70
Fax : +33-(0)1.69.85.70.71

Marketing authorisation n° : PL/11876/0006

Name and address of the manufacturer
CIS bio international
B.P. 32
91192 Gif-sur-Yvette Cedex
FRANCE
Tel. : +33-(0)1.69.85.70.70
Fax : +33-(0)1.69.85.70.71

PHARMACODYNAMIC PROPERTIES
At the chemical concentrations of radiopharmaceutical and excipients
used for diagnostic procedures technetium [99mTc] oxidronate does not
appear to exert any pharmacodynamic effect.

PHARMACOKINETIC PROPERTIES
Intravenously administered technetium [99mTc] oxidronate is rapidly
distributed throughout the extracellular space. Skeletal uptake begins
almost immediately and proceeds rapidly. 30 minutes post injection 10 %
of the initial dose is still present in whole blood. At 1 hour, 2 hours,
3 hours and 4 hours after injection these values are resp. 5 %, 3 %,
1.5 % and 1 %. Clearance from the body takes place via the kidneys. Of
the administered activity about 30 % is cleared within the first hour, 48 %
within two hours and 60 % within 6 hours.

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PRECLINICAL SAFETY DATA
This agent is not intended for regular or continuous administration.
Reproduction, mutagenicity studies and long-term carcinogenicity studies
have not been carried out.
Minimal liver abnormalities are seen at the level of 30 mg/kg in rats. In
subacute toxicity studies rats do not react to the administration of
10 mg/kg/day for 14 days, dogs show histological changes in the liver
(microgranuloma) after 3 and 10 mg/kg/day for 14 days. In dogs, treated
for 14 consecutive days, long-lasting indurations at the site of injection
were observed.

RADIATION DOSIMETRY
For this product the effective dose equivalent resulting from an
administered activity of 700 MBq (18.9 mCi) is typically 5.6 mSv (per
70 kg individual).
For an administered activity of 700 MBq (18.9 mCi) the typical radiation
dose to the target organ (bone) is 44.1 mGy and the typical radiation
dose to the critical organ (bladder wall) is 35 mGy.
In cases of high bone uptake and/or severely impaired kidney function,
the effective dose equivalent resulting from an administered activity of
700 MBq (18.9 mCi) of technetium [99mTc] oxidronate is 5.7 mSv. The
typical radiation dose to the target organ is 84 mGy and the typical
radiation dose to the critical organ (red marrow) is 12.6 mGy.
[99mTc] technetium disintegrates with the emission of gamma radiation
with an energy of 140 keV and a half life of 6 hours to [99Tc] technetium
which can be regarded as quasi stable.
The dosimetry data were quoted from ICRP publication 53 for
phosphonates.

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Radiation exposure (normal bone uptake)
as absorbed dose / injected activity (mGy/MBq)
Organ
Adrenals
Bladder wall
Bone surface
Breast
Stomach wall
Small intestine
Upper large
intestine
Lower large
intestine
Kidneys
Liver
Lungs
Ovaries
Pancreas
Red marrow
Spleen
Testes
Thyroid
Uterus
Other tissue
Effective
dose equivalent
(mSv/MBq)

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Adult

Children (age in years)

0.0019
0.050
0.063
0.00088
0.0012
0.0023
0.0020

15
0.0027
0.062
0.082
0.00088
0.0015
0.0028
0.0025

10
0.0039
0.090
0.13
0.0014
0.0025
0.0044
0.0038

5
0.0060
0.13
0.22
0.0022
0.0037
0.0066
0.0062

1
0.011
0.24
0.53
0.0042
0.0070
0.012
0.011

0.0038

0.0047

0.0072

0.010

0.017

0.0073
0.0013
0.0013
0.0035
0.0016
0.0096
0.0014
0.0024
0.0010
0.0061
0.0019

0.0089
0.0016
0.0016
0.0046
0.0020
0.013
0.0018
0.0033
0.0016
0.0076
0.0023

0.013
0.0024
0.0024
0.0066
0.0030
0.020
0.0028
0.0055
0.0022
0.012
0.0033

0.018
0.0038
0.0036
0.0097
0.0046
0.038
0.0043
0.0084
0.0035
0.017
0.0050

0.033
0.0070
0.0069
0.016
0.0085
0.075
0.0081
0.016
0.0056
0.028
0.0089

0.0080

0.010

0.015

0.025

0.050

Radiation exposure
(high bone uptake and/or severely impaired kidney function)
as absorbed dose / injected activity (mGy/MBq)
Organ
Adrenals
Bladder wall
Bone surface
Breast
Stomach wall
Small intestine
Upper large
intestine
Lower large
intestine
Kidneys
Liver
Lungs
Ovaries
Pancreas
Red marrow
Spleen
Testes
Thyroid
Uterus
Other tissue
Effective
dose equivalent
(mSv/MBq)

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Adult

Children (age in years)

0.0035
0.0025
0.12
0.0021
0.0026
0.0031
0.0029

15
0.0050
0.0035
0.16
0.0021
0.0032
0.0038
0.0036

10
0.0072
0.0054
0.26
0.0032
0.0051
0.0057
0.0053

5
0.011
0.0074
0.43
0.0051
0.0073
0.0085
0.0086

1
0.021
0.015
1.0
0.0096
0.014
0.016
0.015

0.0034

0.0042

0.0065

0.0096

0.018

0.0030
0.0027
0.0030
0.0029
0.0032
0.018
0.0026
0.0023
0.0024
0.0029
0.0030

0.0037
0.0033
0.0037
0.0041
0.0040
0.023
0.0034
0.0027
0.0037
0.0037
0.0036

0.0056
0.0049
0.0053
0.0059
0.0059
0.037
0.0051
0.0039
0.0054
0.0054
0.0053

0.0087
0.0075
0.0081
0.0089
0.0089
0.072
0.0078
0.0060
0.0083
0.0082
0.0081

0.016
0.014
0.015
0.016
0.016
0.14
0.015
0.011
0.014
0.015
0.015

0.0082

0.011

0.017

0.028

0.061

DIAGNOSTIC INDICATIONS
After reconstitution with sodium pertechnetate [99mTc] solution the agent
may be used for bone scintigraphy, where it delineates areas of altered
osteogenesis.

NECESSARY INFORMATION BEFORE TAKING THE MEDICINAL
PRODUCT
Contra-indications
There are no specific contra-indications.

Special warnings and special precautions for use.
In infants and children particular attention should be paid to the relatively
higher radiation exposure of the epiphyses in growing bone.
Appropriate precautions should be taken concerning the activity which is
eliminated by the patients, to avoid any contamination. To reduce the
radiation exposure to the bladder wall, sufficient hydration of the patient
and frequent voiding is recommended.
To avoid accumulation of tracer in the musculature it is advised that
strenuous exercise be discouraged immediately after injection until
satisfactory bone imaging has been effected.
Inadvertent or accidental subcutaneous administration of technetium
[99mTc] oxidronate should be avoided as perivascular inflammation has
been described.
This radiopharmaceutical may be received, used and administered only
by authorised persons in hospitals. Its receipt, storage, use, transfer and
disposal are subject to the regulations and the appropriate licenses of
the local competent official organisations.

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Radiopharmaceuticals intended for administration to patients should be
prepared by the user in a manner which satisfies both radiation safety
and pharmaceutical quality requirements. Appropriate aseptic
precautions should be taken, complying with the requirements of Good
Pharmaceutical Manufacturing Practice for pharmaceuticals.

Interaction with other medicaments and other forms of interaction
The accumulation of technetium [99mTc] oxidronate in the skeleton, and
thus the quality of the scintigraphic procedure, may be decreased after
medication with chelates, with diphosphonates, after tetracycline or after
iron containing drugs.
Regular medication with aluminium containing drugs (notably antacids)
may lead to abnormal high accumulation of technetium [99mTc] in the
liver, presumably caused by formation of labelled colloids.

Pregnancy and lactation
When it is necessary to administer radioactive medicinal products to
women of childbearing potential, information should always be sought
about pregnancy. Any woman who has missed a period should be
assumed to be pregnant until proven otherwise. Where uncertainty exists
it is important that radiation exposure should be the minimum consistent
with achieving the desired clinical information. Alternative techniques
which do not involve ionising radiation should be considered.
Radionuclide procedures carried out on pregnant women also involve
radiation doses to the foetus. Only imperative investigations should be
carried out during pregnancy when likely benefit exceeds the risk
incurred by mother and foetus. Administration of 700 MBq technetium
[99mTc] oxidronate to a patient with normal bone uptake results in an
absorbed dose to the uterus of 4.27 mGy. The dose decreases to
2.03 mGy in patients with high bone uptake and/or severely impaired
kidney function. Doses above 0.5 mGy would be regarded as a potential
risk for the foetus.

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Before administering a radioactive medicinal product to a mother who is
breast feeding consideration should be given as to whether the
investigation could be reasonably delayed until the mother has ceased
breast feeding and as to whether the most appropriate choice of
radiopharmaceutical has been made, bearing in mind the secretion of
activity in breast milk. If the administration is considered necessary, one
breast feed should be banked prior to injection and the subsequent one
discarded after injection. Breast feeding can be restarted 4 hours post
injection.

Effects on ability to drive and use machines
Effects on the ability to drive or to operate machines have not been
described.

List of excipients
Stannous chloride dihydrate
Ascorbic acid
Sodium chloride

Incompatibilities
None known.

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NECESSARY AND USUAL INSTRUCTIONS FOR PROPER USE
Posology and method of administration
The average activity administered by single intravenous injection is
500 MBq i.e. 300 - 700 MBq (13.5 mCi, i.e. 8.1 - 18.9 mCi) in a 50 to
70 kg adult. Other activities may be justifiable. There is no special
dosage regimen for the elderly patient. The dose to be administered to a
child should be a fraction of the adult dose calculated from the body
weight according to the following table.
3 kg
4 kg
6 kg
8 kg
10 kg
12 kg
14 kg
16 kg
18 kg
20 kg

=
=
=
=
=
=
=
=
=
=

0.10
0.14
0.19
0.23
0.27
0.32
0.36
0.40
0.44
0.46

22 kg
24 kg
26 kg
28 kg
30 kg
32 kg
34 kg
36 kg
38 kg
40 kg

=
=
=
=
=
=
=
=
=
=

0.50
0.53
0.56
0.58
0.62
0.65
0.68
0.71
0.73
0.76

42 kg
44 kg
46 kg
48 kg
50 kg
52 - 54 kg
56 - 58 kg
60 - 62 kg
64 - 66 kg
68 kg

=
=
=
=
=
=
=
=
=
=

0.78
0.80
0.82
0.85
0.88
0.90
0.92
0.96
0.98
0.99

In very young children (up to 1 year) a minimum dose of 40 MBq
(1.1 mCi) is necessary in order to obtain images of sufficient quality.
Images obtained shortly after injection (e.g. in the so-called "3-phase
bone scan" procedure) will only partly reflect metabolic bone activity.
Late phase static scintigraphy should be performed not earlier than
2 hours after injection. The patient should void before scanning.

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Instructions for use/handling
-

Method of preparation
Usual precautions regarding sterility and radioprotection should be
respected.
Take a vial from the kit and put it in an appropriate lead shielding.
Using a hypodermic syringe, introduce through the rubber stopper
2 to 10 ml of sterile and pyrogen-free sodium pertechnetate [99mTc]
injection, radioactivity varying as a function of the volume from 0.74 to
maximum 11.1 GBq (from 20 to maximum 300 mCi). Sodium
pertechnetate [99mTc] injection should comply with European
Pharmacopoeia specifications.
Do not use a breather needle as the contents are under nitrogen :
after introduction of the volume of sodium pertechnetate [99mTc]
injection, without removing the needle, withdraw an equivalent
volume of nitrogen in order to avoid excess pressure in the vial.
Shake for about 2 minutes.
The obtained preparation is a clear and colourless solution, with a pH
ranging between 5.0 and 7.0.
Limpidity of the solution after preparation, pH, radioactivity and
gamma spectrum should be checked before use.
The vial should never be opened and must be kept inside its lead
shielding. The solution should be removed aseptically through the
stopper with a sterile lead protected syringe .

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-

Quality control
The quality of labelling (radiochemical purity) could be checked
according to the following procedure.
Method
Thin-layer chromatography
Materials and reagents
1. Adsorbent
2 ITLC-SG GELMAN strips (A and B) for thin-layer
chromatography (2.5 x 20 cm) coated with silica gel. Trace a
starting line 2.5 cm from one of the ends of each strip.
2. Nitrogen
3. Solvents
Solvent A : 0.9 % sodium chloride solution
Solvent B : methanol-acetone (1/1)
4. Containers
Appropriate containers, such as 1000 ml Erlenmeyer flasks. Keep
the containers stoppered and flush with a nitrogen stream before
use.
5. Miscellaneous
Forceps, scissors, syringes, needles, appropriate counting
assembly.
Procedure
Do not let air enter the vial to be tested and store all vials containing
radioactive solution in lead shieldings.
1. Apply a spot of the preparation to the starting line of strip A using
a syringe and needle. Apply another spot of the preparation to the
starting line of strip B. Note the time. Dry under nitrogen.
2. Using forceps, introduce each strip vertically into the
corresponding container for development (i.e. container with
solvent A for strip A and container with solvent B for strip B), with
the starting line downward. Stopper the containers.

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3. When the solvent has reached the top of the strips, use the
forceps to remove each strip and dry in the air.
4. After identifying the strips, cut strip A at Rf = 0.1 and strip B at
Rf = 0.9.
5. Separately count each section of the strips and record the
obtained values (use an appropriate detection apparatus with a
constant counting time, and known geometry and background
noise).
6. Calculations
Correct the counting data for background noise.
Calculate the percentage of hydrolysed technetium [99mTc] from
counting data for the A strip :
% hydrolysed 99mTc =

Error!

× 100

Calculate the percentage of free technetium [99mTc] from counting
data for the B strip :
% free 99mTc =

Error!

× 100

Calculate the percentage
(radiochemical purity) :

of

bound

technetium

[99mTc]

% bound 99mTc = 100 % - (% hydrolysed 99mTc + % free 99mTc)
7. The percentage of bound 99mTc (radiochemical purity) should be
more than 95 % and the percentage of total hydrolysed 99mTc and
free 99mTc should be less than 5 %.
The administration of radiopharmaceuticals creates risks for other
persons from external radiation or contamination from spills of urine,
vomiting, etc. Radiation protection precautions in accordance with
national regulations must therefore be taken.
Radioactive waste must be disposed of in conformity with the relevant
national and international regulations.

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Overdose
In the event of the administration of a radiation overdose with technetium
[99mTc] oxidronate the absorbed dose to the patient should be reduced
where possible by increasing the elimination of the radionuclide from the
body by forced diuresis and bladder voiding.

UNDESIRABLE EFFECTS
Adverse drug effects are extremely rare following administration of
technetium [99mTc] oxidronate injection. Reports suggest an incidence of
not more than one in 200 000 administrations. Symptoms of
anaphylactoid reactions are rash, nausea, hypotension and sometimes
arthralgia. Onset of symptoms may be delayed 4 to 24 hours after
administration.
For each patient, exposure to ionising radiation must be justifiable on the
basis of likely benefit. The activity administered must be such that the
resulting radiation dose is as low as reasonably achievable bearing in
mind the need to obtain the intended diagnostic result.
Exposure to ionising radiation is linked with cancer induction and a
potential for development of hereditary defects. For diagnostic nuclear
medicine investigations the current evidence suggests that these
adverse effects will occur with low frequency because of the low
radiation doses incurred.
For most diagnostic investigations using a nuclear medicine procedure
the radiation dose delivered (EDE) is less than 20 mSv. Higher doses
may be justified in some clinical circumstances.

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SHELF LIFE
The expiry date for this kit is 12 months from the day of manufacture.
The expiry date is indicated on the outer packaging and on each vial.
The expiry date for the labelled product is 8 hours after labelling.

Special precautions for storage
This kit must be stored at a temperature ranging between +2°C and
+8°C.
The labelled product must be stored at a temperature ranging between
+2°C and +8°C.

DATE OF REVISION OF THE TEXT
04/2006

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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