Download CLOSPORIL® 0.1% - Laboratorios Poen

STERILE OPHTHALMIC SOLUTION
Made in Argentina - Rx ONLY
Formula:
Each 100 ml of the ophthalmic solution contains:
Cyclosporine 0.10 g
Polyoxyl 40 stearate 7.00 g; Sodium chloride 0.36 g; Boric acid 0.33 g;
Sodium borate 0.0275 g; Disodium edetate dihydrate 0.01 g; Potassium
sorbate 0.18 g; Sodium bisulfite 0.04 g; Polyoxyl 35 castor oil 5.00 g;
Purified water q.s. 100 ml.
Therapeutic action:
Immunomodulator and anti-inflammatory of topical ophthalmic use.
CLOSPORIL ® 0.1% acts as an immunomodulator by increasing tear production in patients whose tear production is probably suppressed due to
ocular inflammation related to keratoconjunctivitis sicca.
Posology and Way of administration:
The recommended posology is the instillation of 1 drop of 0.1%
CLOSPORIL ® twice a day in both eyes every 12 hours.
CLOSPORIL ® 0.1% can be concomitantly used with artificial tears, the concurrent medications should be administered within a 15 minute time interval.
Contraindications:
CLOSPORIL ® 0.1% is contraindicated in patients with active ocular infections,
since the infection could go worse due to immunity inhibition; likewise, it is
also contraindicated in patients with known hypersensitivity to any components of the formula.
Warning:
Do not inject. Do not ingest.
The administration of CLOSPORIL ® 0.1% has not been investigated in
patients with history of herpetic keratitis.
Do not use the medication after the expiration date printed on the label.
Indications:
It is indicated for the treatment of moderate to severe keratoconjunctivitis
sicca by increasing tear secretion and maintaining ocular surface integrity.
Likewise, it provides relief of symptoms related to ocular dryness.
For the treatment of conjunctivitis vernal.
602
Pharmacological characteristics / Properties:
Pharmacological action
Cyclosporine is a potent and selective immunomodulator which acts by
inhibiting the activation of NF-kB, a nuclear factor related to the gene
regulation of cytokine immune and pro-inflammatory responses, such as
TNF, IL-1, IL-2, and IL-8.
As an anti-inflammatory agent, CLOSPORIL ® 0.1% acts on T-helper cells
identified on the ocular surface tissues and tear glands, which plays a
key role not only on the immune response but also on the inflammatory
response through the synthesis of cytokines.
The suppression of the immune response occurs on the ocular surface
because these specific pro-inflammatory cytokines are vital for the activation of T-helper cells, which cannot be synthesized or released as normally.
In Vitro cyclosporine inhibited the production of cytokines (IL-2, IL-4, IL-5,
IFN-γ) in mononuclear cells from capillary human blood (IC50: 0.0210.173 µM).
Pharmacokinetics
Cyclosporine A blood concentrations were evaluated after the topical
Precautions:
Do not touch the dropper tip with the eye or any other surface in order to
avoid the container contamination. Close the dropper container immediately
after using.
Use the product only if the container is intact.
Carcinogenesis - Mutagenesis - Fertility disorders
Systemic carcinogenesis studies were conducted in male and female mice
and rats.
In a 78 week study conducted in mice, oral doses of 1,4, and 16 mg/kg/day
were administered to the animals and evidence of significantly important
trend towards lymphocytic lymphomas in females and an increased incidence of hepatocellular carcinoma in males given moderate doses, which
significantly exceeded the control value.
In a 24 month study conducted in rats, oral doses of 0.5, 2, and 8 mg/kg/
day were administered, the incidence of cellular adenomas of pancreatic
islets significantly exceeded the control value at the low dose level. The
low doses in mice and rats are approximately 1000 and 500 times greater,
respectively, than the daily human dose of one drop of CLOSPORIL ® instilled
in both eyes of a 60 kg person (0.001 mg/kg/day) assuming that the whole
dose is absorbed.
Cyclosporine did not produced either mutagenic or genotoxic effects as it
was proved in selective tests such as: Ames Test, V79-HGPRT Test, micronucleous test in mice and Chinese hamsters, chromosome aberration test
in bone marrow of hamsters, and the DNA repair capacity test in sperm of
treated mice.
No fertility disorders were observed in studies conducted with male and
female rats, who were administered oral doses of cyclosporine up to 15 mg/
kg/day (approximately 15.000 times the daily dose of 0.001 mg/kg/day in
SURCAN S.R.L.
Alvarez Thomas 198 3°A
Buenos Aires - C1427CCO
Tel/Fax: 4553-2422
[email protected]
www.surcan.com.ar
Laboratorio/Laboratory: LABORATORIOS POEN
Producto/Product: CLOSPORIL 0,1%
Contenido/Content: SOLUCIÓN
País/Country: EXPORTACIÓN INGLÉS
Elemento/Item: PROSPECTO (FRENTE Y DORSO)
human beings).
Teratogenic effects:
No evidence of teratogenic effects during organogenesis was observed in
rats and rabbits administered oral doses of cyclosporine up to 300 mg/kg/
day. These doses administered to rats and rabbits are approximately 300,000
times greater than the daily human dose of one drop of CLOSPORIL ® instilled
in both eyes of a 60 kg person (0.001 mg/kg/day) assuming that the whole
dose is absorbed.
Non-teratogenic effects:
Harmful effects were evaluated in reproduction studies with rats and rabbits
using only toxic dose levels for the animals. At the toxic doses (30 mg/kg/
day in rats and 100 mg/kg/day in rabbits), the cyclosporine oral solution
was toxic for embryos and fetuses, as it was shown by an increased pre and
post-natal mortality, reduced fetal weight, and related delayed skeletal development. These doses are 30,000 and 100,000 times respectively greater
than the daily human dose. No evidence of toxicity was observed during
organogenesis in embryos and fetuses of rats and rabbits who were administered cyclosporine oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively. These doses given to rats and rabbits are approximately 17,000 and
30,000 times greater than the daily human dose, respectively. No adverse
events with oral doses up to 15 mg/kg/day (15,000 times greater than the
human dose) were observed.
Pregnancy
No suitable and well controlled studies have been conducted in pregnant
women. Reproduction studies in animals are not always useful response
predictors in human beings.
CLOSPORIL ® 0.1% should only be administered during pregnancy when the
potential benefit for the mother outdoes the risk for the fetus.
Lactation
After systemic administration, Cyclosporine is excreted into milk. However,
excretion of topical Cyclosporine into milk has not been established.
CLOSPORIL ® 0.1% should not be administered to lactating women.
Pediatric use
Safety and effectiveness of CLOSPORIL ® 0.1% in pediatric patients have not
been established.
Use in the elderly
Neither clinical nor safety and effective differences of CLOSPORIL ® 0.1%
were observed in the elders or in other adult patients.
Drug-drug interactions:
Drug-drug interactions have not been observed. If concurrently administered
with other eye drops, the drop instillation of each medication should be performed within a 15 minute time interval.
Storage conditions:
Store below 30° C.
Once the container is opened for the first time, it should be used within 4
weeks.
Keep drugs out of reach of children.
602
CYCLOSPORINE 0.1%
administration of CLOSPORIL ® 0.1% to human beings twice a day for 12
months. All sample values were lower than the limit of quantification (0.1
ng/mL). No quantifiable drug accumulations were observed throughout the
12 month treatment with CLOSPORIL ® 0.1% ophthalmic solution.
When a single ocular instillation of 0.05% 3H-cyclosporine ophthalmic solution is performed in white rabbits, the drug is significantly distributed to the
cornea and extra-ocular tissues such the conjunctiva, while the drug passes
to intra-ocular tissues such as the aqueous humor, iris, cylliary bodies, crystalline, and vitreous humor in insignificant amounts.
This drug is mainly metabolized by the cytochrome metabolic enzyme P450
3a (CYP3A). Therefore, the concurrent use of other drugs metabolized by the
same enzyme may result in higher blood concentrations of this drug.
When a single ocular instillation of 0.1% 3H-cyclosporine ophthalmic solution
is performed in rats, 3.1% of the drug was eliminated in urine and 92.1% in
feces after 96 hours of the ocular instillation.
On the other hand, when the ocular instillation of 0.1% 3H-cyclosporine ophthalmic solution is performed in billiary cannulated rats, the drug was eliminated by 11.7%, 3.3%, and 74.9% in the bile, urine, and feces, respectively
within the 72 hours after the administration.
Delicate use product. To be administered under prescription and medical
surveillance.
Manufactured by:
LABORATORIOS POEN S.A.C.I.F.I.
Bermúdez 1004 - C1407BDR Buenos Aires, Argentina
Technical Director:
Victor D. Colombari, Pharmacist.
Adverse reactions:
The most common adverse events were burning sensation in the eyes with
an incidence of 16%. Other adverse events (in about 1% to 5% of patients)
include ocular itching/irritation, tear secretion, sensation of foreign body in
the eye, itch, conjunctival hyperemia, photophobia, blurred vision, headache, palpebral edema, and ocular pain.
Overdosage:
In case of overdosage, go to the nearest hospital or toxicology centers.
Information to patients:
Patients should be properly instructed in handling the dropper tip correctly
so as to avoid contact with the eye and adjacent structures or any other
surfaces. Incorrect handling of the dropper container can result in contamination and ocular infections. The use of contaminated products can cause
severe ocular damage with subsequent decreased vision.
After each instillation, the dropper container should be immediately closed. If
the container remains sealed and unopened, it can be used until the expiration date printed on the label.
How supplied:
Bottle with dropper containing 5 ml of sterile ophthalmic solution.
Tamaño/Size:
ancho/wide: 150 mm
alto/high: 180 mm
N° Material: 4215828840
Pharmacode N°: 602
Código visual/Visual code: 2 - 20
Fecha/Date: 02/JUN/14
Version N°: 1
Guía de colores/Colours Guide
Pantone Black C
Colores/Colours: 1
4215828840
602
C.V. 2 - 20
CLOSPORIL 0.1%
®