Information about the product

1. hyaluronic acid-based sterile solution for intravesical application

2. Hyaluronic acid-based sterile solution
for intravesical application
Colourless clear viscous gel
of hyaluronic acid of non-animal
origin /sterile, apyrogenic,
with physiological values of pH/
Viscoelastic protector
of intercellular matrix
of vesical and urethral
urothelium
50 ml80 mg
Mechanical action:
barrier/lubrication
Humidifying: high extent of water
binding
Healing properties: normalisation
of cellular migration and proliferation
Filling the spatial defects
PROPERTIES
hyaluronic acid-based sterile solution for intravesical application

3. Temporary protection and regeneration
of urinary bladder mucosa in different
procedures
/cystoscopy, radiation therapy, etc./
Chronic/recurring cystitis
Interstitial cystitis
Hyperactive urinary bladder
Cystitis-mediated urinary
retention or tumours
Radiation cystitis
INDICATIONS Empty the urinary bladder prior to admini-
stration of INSTYLAN
The procedure should be performed by a specially
trained physician in a properly equipped room and
in strict adherence to all aseptic precautions
INSTYLAN is administered intravesically once a week
The treatment course includes 4-12 instillations
The temperature of INSTYLAN solution should be not
less than 20°С
Retain INSTYLAN in the urinary bladder for at least 30 min
MODE OF
APPLICATION
hyaluronic acid-based sterile solution for intravesical application

4. SAFETY
Clinical studies have demonstrated a high incidence
of objective responses in intravesical application
of hyaluronic acid /HA/
EFFICACY
Clinical studies have demonstrated high rates of
objective response in intravesical application of /HA/
Objective response rates in clinical studies with intravesical
application of hyaluronic acid
Kallestrup Leppilahti Morales Riedl Sánchez
Macías
100
75
50
25
0
%
86%
68%
73% 71% 70%
REGENERATION OF THE MUCOUS MEMBRANE
OF THE URINARY BLADDER
Hyaluronic acid plays a key role in restoring the GAG layer and produces its effect in the submucosa,
exactly where the process of epithelial regeneration initiates
Destroyed condition Partially restored condition Restored condition

5. CLINICAL STUDIES*
Painful bladder syndrome /PBS/ interstitial cystitis /IC/
Author
Morales, et al.
Kallestrup, et al.
Leppilahti, et al.
Daha, et al.
Gupta, et al.
Sánchez macías, et al.
Ahmad, et al.
Riedl, et al.
TOTAL
The number
of patients
25
20
11
48
36
21
23
121
305
The percentage of patients
with objective responses
71
65
64
89
55
70
74
84
The number of patients with
objective responses
17
13
7
43
20
15
17
103
220
Year
1996
2005
2002
2005
2005
2005
2008
2008
Radiation cystitis /RC/
Author
Delgado et al.
Diamantopoulos et al.
Gonzalez Patiño et al.
TOTAL
The number
of patients
45
20
14
78
The percentage of patients
with objective responses
nd
80
nd
Year
2003
2004
2008
Recurrent bacterial cystitis
Author
Constantinides, et al.
Lianos, et al.
Lipovac, et al.
The number
of patients
40
20
20
The percentage of patients
with objective responses
nd
70
nd
Year
2004
2005
2007
nd=nodata
*Thebelowlistincludesthenamesofclinicalstudiesthatwerepublishedand/orpresented
atscientificcongresses/meetings

6. QUALITATIVE COMPOSITION.
Sodium hyaluronate. Excipients: water for injection,
sodium chloride, phosphate buffer.
Classification of the product. Medical device – sterilized
and pyrogen-free – Class IIa.
PACKAGE. 50 ml pre-filled disposable plastic bag which
contains 0.16% (80 mg/50 ml) of hyaluronic acid solution.
Each package contains: 1 plastic bag containing INSTYLAN
sterile solution. The medical device has been sterilized by
steam sterilization.
INDICATIONS. INSTYLAN is intended for irrigation into
bladder cavity that provides the formation of a viscous
elastic film on the surface of mucous layer to:
• protecting it from external effects during various
surgeries (ureteroscopy, cystoscopy, transurethral
resection of adenoma and radiation therapy of lesser
pelvis organs, etc),
• protect it from the harmful impact of bladder content
(urina) in case of injury or from inflammation of the
mucous layer of the bladder, like cystitis.
INSTYLAN is intended for irrigation of the bladder when
using a urological catheter. The irrigation provides
temporary protection and restoration of bladder mucous
layer during various surgeries (urethra cystoscopy,
radiation therapy, etc).
WARNINGS AND SPECIAL PRECAUTIONS FOR USE
• Do not use if the solution is not transparent and
colorless.
• Do not use if the packaging has been opened or is
damaged.
• The product must be used immediately after opening.
• The product is intended for single use. After use, the
unused product is no longer sterile. Do not use product
residuals;
• Do not reuse. Once the product has been used for the
first time, any residuals of the product are not suitable
for the repeated use as the product is no longer sterile.
• Do not resterilize. Repeated sterilization may cause
cross-contamination.
• Do not freeze.
• The product must not be administered orally.
SPECIAL WARNING
• Do not use the solution in patients with known
hypersensitivity to hyaluronic acid, or those with a
history of allergic reactions to any component of the
product.
• Irrigation into the bladder should be provided by a
trained medical specialist in specialized premise with
appropriate equipment and aseptic conditions.
• Do not inject the solution into blood vessels.
• Do not use the product with pregnant or lactating
woman, or children.
ADVERSE REACTIONS AND SIDE EFFECTS. None.
HOW TO USE
• Check package integrity before use.
• Check the expiration date indicated on the bag. Do not
use after the expiry date.
• Take one of the plastic bags containing INSTYLAN
Solution.
• Make sure that the bladder of the patient has been
previously emptied
• Remove the cap
• Irrigate the patient`s bladder using an urological
catheter.
For cystitis treatments: it is suggest that the sterile
solution INSTYLAN is used weekly for the first month and
with less frequency in the following months.
The frequency of use of sterile solution INSTYLAN must
be determined by the doctor who established the
treatment.
SHELF LIFE. 2 years in an intact package.
HOW TO STORE. Store at temperatures between 5°C
to 30°C (inclusive), away from direct light and heat, in the
adequately sealed packaging. The expiry date is applied to
the products which are correctly stored in an intact
package.
DISPOSAL. The product must be disposed of in
accordance with the applicable laws on medical waste.
1936
REFERENCES.
1. Miodosky et al. Treatment of post-hematopoietic stem
cell transplantation hemorrhagic cystitis with
intravesical sodium hyaluronate. Bone Narrow
Transplantation 2006; 38,507-11.
2. Monheit et al. Hyaluronic acid fillers. Dermatologic
Therapy 2006, Vol.19, 141-150.
3. Kallestrup et al. Treatment of Interstitial Cystitis with
Cystistat: A Hyaluronic Acid product. Scan J Ural & Neph,
2005; 39: 143-147.
4. Leppilahti et al. Effect of diagnostic hydrodistension
and four intravesical hyaluronic acid instillations on
bladder ICAM-1 intensity and association of ICAM-1
intensity with clinical response in patients with
interstitial cystitis, Urol 60:46-51, 2002.
5. Morales et al. Intravesical hyaluronic acid in the
treatment of refractory interstitial cystitis. J Urol 1996
Jul;156(1):45-8
6. Riedl et al. Hyaluronan treatment of interstitial
cystitis/painful bladder syndrome. Int. Urogynecol J
Pelvic Floor Dysfunct 2008 May; 19(5): 717-21.
7. J. Sanchez Macias et al. Bladder instillations with
Hyaluronic Acid in the treatment of Interstitial Cystitis.
Our experience. Abstract presented at the 70th National
Congress of Urology, Spain 2005
8. Daha et al. Is a Maximal Bladder Capacity of >400 cc an
Automatic Exclusion Criteria for Interstitial Cystitis?
2002 SIU.
9. Gupta et al. The potassium sensitivity test: a predictor
of treatment response in interstitial cystitis. BJU
International, Volume 96, Iss 7, November 2005,
1063-1066.
10. Ahmad et al. Sequential hydrodistension and
intravesical instillation of hyaluronic acid under general
anaesthesia for treatment of refractory interstitial
cystitis : a pilot study. Int Uroynecol J Pelvic Floor
Dysfunct 2008 Apr 19 (4) : 543-546
11. Constantinides et al. Prevention of recurrent bacterial
cystitis by intravesical administration of Hyaluronic
Acid: a pilot study BJU International 2004;93,1262-1266.
12. Lianos E. et al. Effects of intravesical sodium
hyaluronate on vesical mucosa in recurrent chronic
bacterial cystitis. Journal of Endourology, Jul 2005, Vol.
19, No. supplement 1: p1-p121
13. Lipovac et al. Prevention of recurrent bacterial urinary
treatment by intravesical instillation of hyaluronic acid.
International Journal of Gynecology and Obstetrics,
March 2007;96(3): 192-5.
14. Delgado et al. HA in the prevention of RC cystitis.
ASCO 2003.
15. Diamantopoulos et al. Use of sodium hyaluronate in
patients suffering from post-radiation cystitis. ESTRO,
October 2004.
16. Riedl et al. Hyaluronan treatment of interstitial
cystitis/painful bladder syndrome. Int. Urogynecol J
Pelvic Floor Dysfunct 2008 May; 19(5): 717-21.
DIACO Biofarmaceutici S.R.L.
Via Flavia 124, 34147 Trieste, Italy
www.diaco.it
hyaluronic acid-based sterile solution
for intravesical application