Active ingredients: Tobramycin, Dexamethasone
COMBISTILL 0.3% + 0.1% eye drops, suspension
Indications Why is Combistill used? What is it for?
What is COMBISTILL and what is it for
COMBISTILL is a "combination of two active substances: tobramycin and dexamethasone. Tobramycin belongs to a group of medicines, called aminoglycoside antibiotics, used to treat infections caused by a wide range of bacteria. Dexamethasone belongs to a group of medicines called corticosteroids that have many activities, including an important function in reducing the symptoms of inflammation.
This medicine is indicated for the treatment of inflammation of the eye, in adults and children from 2 years onwards, when a corticosteroid is needed and when there is an "infection or" there is a risk that an "infection will develop.
Contraindications When Combistill should not be used
Do not use COMBISTILL
- if you are allergic to tobramycin, dexamethasone or any of the other ingredients of this medicine (listed in section 6);
- if you have high blood pressure in the eye (intraocular hypertension);
- if you have developed an "eye infection" due to a virus (viral herpetic keratitis), especially if it is accompanied by lesions (acute herpes simplex, other ulcerative corneal virus diseases), unless treatment is associated with medicines for the treatment of the virus (specific chemotherapy) and unless prescribed by a doctor under strict control of the ophthalmologist;
- if you suffer from "inflammation of the conjunctiva (conjunctivitis) accompanied by" inflammation of the cornea (ulcerative keratitis), even in the initial phase; - if you have an "eye infection" caused by a bacterium or fungus (tuberculosis or mycosis of the eye);
- if you have "inflammation of the eye" with pus formation (acute purulent ophthalmias, purulent conjunctivitis and purulent and herpetic blepharitis), as this medicine may mask or worsen the symptoms;
- if you have inflammation of the glands at the base of the eyelids (sty).
Precautions for use What you need to know before taking Combistill
What you need to know before you use COMBISTILL
Talk to your doctor or pharmacist before using COMBISTILL.
COMBISTILL should be used under close medical supervision. Your doctor will carefully evaluate the frequency and duration of treatment by monitoring the pressure in the eye (intraocular pressure - IOP) from the start of therapy. If you use this medicine for more than 10 days, frequent blood pressure checks are recommended. inside the eyes (ocular tone). This test is of particular importance in children (See "Children" section).
It is recommended not to use the medicine for more than 30 consecutive days.
If you use COMBISTILL for long periods of time, severe eye damage (glaucoma, damage to the optic nerves, acuity and visual field defects, posterior sub-capsular cataract formation) may occur or further infections (secondary infections) may develop. , fungal infections of the cornea). Also, if used for prolonged periods, this medicine may lose its effectiveness (development of resistant microorganisms). Therefore, if you do not notice any improvement after a certain period of treatment, stop the therapy and inform your doctor to establish an adequate therapy.
Interactions Which drugs or foods can modify the effect of Combistill
Other medicines and COMBISTILL
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines, including those that do not require a prescription.
Do not use COMBISTILL together with tetracycline, a medicine used to treat infections caused by bacteria, as it is incompatible with one of the components of this medicine (Tyloxapol).
Warnings It is important to know that:
Children
The use of this medicine is not recommended in children under 2 years of age.
Children are at increased risk of steroid-induced increase in pressure in the eye and may occur earlier than it does in adults. Therefore, especially if the medicine is to be administered to a child under 6 years of age, frequent eye checks are recommended.
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
If you are pregnant or breast-feeding, use this medicine only when clearly needed and under the direct supervision of your doctor.
Driving and using machines
This medicine does not affect the ability to drive or use machines. However, at the time of applying the medicine, if you experience a momentary blurring of your vision, wait for your vision to return to normal before doing these activities.
COMBISTILL contains benzalkonium chloride
Benzalkonium chloride can cause eye irritation. Avoid contact with soft contact lenses. Remove contact lenses before application and wait at least 15 minutes before reapplying. Note the bleaching action of soft contact lenses.
Dose, Method and Time of Administration How to use Combistill: Posology
How to use COMBISTILL
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
COMBISTILL should only be applied in the eyes (ocular use). This medicine, being an eye drop, should not be injected.
The recommended dose is 1-2 drops to be introduced into the eye 4-5 times a day, depending on the judgment of the doctor.
For correct use of the medicine, please read the following instructions carefully:
- always wash your hands before using the eye drops;
- shake the bottle before use;
- open the bottle by unscrewing the cap;
- tilt your head back and slightly lower the lower lid of the eye to form a pocket;
- turn the bottle upside down and apply light pressure to the body of the container; - put 1 or 2 drops in the eye, according to medical prescription;
- keep the eye closed for 1 minute, pressing the corner of the eye near the nose with the finger;
- repeat the operation also in the other eye if the doctor has prescribed it;
- after use, close the bottle by screwing the cap back on until it adheres firmly to the container. Do not overtighten.
Do not allow the dropper tip to come into contact with the eye, the area around the eye or any other surface. This precaution is important to avoid contamination of the medicine with bacteria responsible for serious damage to the eye and which can also cause vision loss.
The dropper tip delivers one drop with a predefined volume. Therefore do not try to enlarge the dropper hole. After finishing the treatment, there may be some medicine left in the bottle. Do not try to remove excess COMBISTILL from the bottle.
Use in children
The use of this medicine is not recommended in children under 2 years of age. Above 2 years, COMBISTILL can be used at the same doses as for adults.
If you forget to use COMBISTILL
Do not use a double dose to make up for a forgotten dose.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist
Overdose What to do if you have taken too much Combistill
If you use more COMBISTILL than you should
There are no known cases of overdose. If you use an excessive dose of eye drops, wash your eye with running water.
If you accidentally take an overdose of COMBISTILL, contact your doctor or go to the nearest hospital.
Side Effects What are the side effects of Combistill
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:
Frequency not known (the frequency of which cannot be estimated from the available data)
- increased pressure inside the eye with possible development of eye disease (glaucoma) in predisposed patients after 15-20 days of treatment; - loss of transparency of the lens (posterior subcapsular cataract), following prolonged treatments;
- development or worsening of infections caused by bacteria, viruses (Herpes simplex) or fungi;
- delay in healing;
- thickening of the white part of the eye (sclera) following prolonged treatments;
- dilation of the pupils (mydriasis) following prolonged treatments;
- relaxation of the eyelids following prolonged treatments;
- allergic (hypersensitivity) reactions such as swelling and itching of the eyelids and irritation of the conjunctiva. These effects occur especially if, together with COMBISTILL, you use other aminoglycoside antibiotics (topical use). If tobramycin is also used by other routes of administration, the doctor should check the levels of this medicine in the blood.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at: www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer carton and on the label after "Expiry".
The expiry date refers to the last day of that month and to the product in intact packaging, correctly stored.
Do not store the medicine above 25 ° C.
Do not refrigerate or freeze. Store in the original packaging protected from light. Once the container is opened, the eye drops should be used within 28 days.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Contents of the pack and other information
What COMBISTILL
- The active ingredients are: tobramycin and dexamethasone. 1 ml of eye drops contains 3 mg of tobramycin and 1 mg of dexamethasone.
- The other ingredients are: benzalkonium chloride, disodium edetate, sodium chloride, sodium sulfate, tyloxapol, sodium hydroxide or sulfuric acid (pH regulator), hydroxyethylcellulose, water for injections.
Description of the appearance of COMBISTILL and contents of the package
5ml dropper bottle.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
COMBISTILL 0.3% + 0.1% EYE DROPS, SUSPENSION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of eye drops contains:
Active principles: tobramycin 3 mg, dexamethasone sodium phosphate 1 mg.
Excipient with known effects: benzalkonium chloride 0.10 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Eye drops, suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of eye inflammation when a corticosteroid is needed and when there is an eye infection or risk of eye infections in adults and children two years of age and older.
04.2 Posology and method of administration
Instill 1 or 2 drops 4-5 times a day according to medical prescription.
Pediatric population
COMBISTILL eye drops can be used in children from two years of age onwards at the same doses as for adults. Currently available data are described in section 5.1.
Safety and efficacy in children less than two years of age have not been established and no data are available.
Shake before using.
04.3 Contraindications
COMBISTILL is contraindicated in the following cases: a) intraocular hypertension; b) Acute Herpes Simplex and most of the other corneal virus diseases in the acute ulcerative phase, except in association with specific chemotherapeutic agents for the herpetic virus, conjunctivitis with ulcerative keratitis also in the initial phase (fluorescein + test). In viral herpetic keratitis it is not recommended to use it, which may possibly be permitted under the strict supervision of the ophthalmologist; c) tuberculosis of the eye; d) mycosis of the eye; e) acute purulent ophthalmias, purulent conjunctivitis and purulent and herpetic blepharitis which can be masked or aggravated by corticosteroids; f) sty; g) hypersensitivity to the active substances or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
On the occasion of prolonged treatments beyond 10 days, it is advisable to carry out frequent checks of the ocular tone. This is particularly important in pediatric patients treated with dexamethasone-containing products, as the risk of steroid-induced ocular hypertension may be greater in children under the age of six and may occur earlier than when the steroid response occurs in adults. The frequency and duration of treatment should be carefully evaluated, and intraocular pressure (IOP) should be monitored from the start of treatment, considering that the risk of steroid-induced increase in IOP is greater and occurs earlier in pediatric patients. .
It is also known that prolonged use of corticosteroids could cause glaucoma, damage to the optic nerves, defects in acuity and visual field, formation of posterior subcapsular cataracts, or favor the onset of secondary ocular infections.
Coinciding with prolonged steroid applications, the development of corneal fungal infections is likely; therefore this possibility should be considered in any type of corneal ulcer where a steroid has been used or is in use.
Uninterrupted application for more than a month is not recommended.
Prolonged use of antibiotics can favor the development of resistant microorganisms: if this should occur or if clinical improvement is not noted in a reasonable period of time, use of the preparation should be suspended and adequate therapy established.
To be used under direct medical supervision.
COMBISTILL eye drops should not be injected.
COMBISTILL eye drops contain benzalkonium chloride which may cause eye irritation.
Soft contact lenses should not be worn before application and at least 15 minutes after administration.
04.5 Interactions with other medicinal products and other forms of interaction
The tyloxapol component is incompatible with tetracycline.
04.6 Pregnancy and breastfeeding
The safety of intensive or prolonged topical steroid-based therapies during pregnancy has not been fully established.
Pregnancy
In pregnant women, the product should be administered in cases of real need, under the direct supervision of the doctor.
Feeding time
It is not known whether this drug is excreted with breast milk therefore, in lactating women, the product should be administered with caution and under direct medical supervision.
04.7 Effects on ability to drive and use machines
COMBISTILL does not interfere with visual activity.
04.8 Undesirable effects
The undesirable effects reported following the use of the steroid / antibiotic combination can be attributed to only one of the components or to both even if it is not known to what extent. The undesirable effects due to the steroid are: increase in intraocular pressure with possible development of glaucoma after 15-20 days of topical application in patients predisposed to glaucoma or glaucomatosis; formation of posterior subcapsular cataract following prolonged treatments; development or aggravation of bacterial, Herpes simplex or fungal infections; delayed healing; manifestation after prolonged administration , of serious side effects such as thickening of the sclera, mydriasis, sagging of the eyelids.
The most frequently encountered secondary effect after topical use of tobramycin is hypersensitivity which manifests itself with swelling, eyelid itching and conjunctival erythema: these reactions occur in less than 3% of patients and are also found after the topical use of others. Aminoglycoside antibiotics Total serum concentration should be monitored when tobramycin is administered simultaneously topically and systemically.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous 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 www .agenziafarmaco.gov.it / it / responsible.
04.9 Overdose
Taking into account the route of administration, topical ocular, cases of overdose are unlikely to occur. However, should this happen, wash the eye thoroughly with running water.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
COMBISTILL eye drops specialty ophthalmic contains two active ingredients: tobramycin as an antibiotic and dexamethasone as an anti-inflammatory. Tobramycin is a well known aminoglycoside antibiotic, effective in infections caused by a wide range of gram-positive and gram-negative ocular pathogens; in particular, it is active against Pseudomonas, Proteus, Klebsiella, E. coli and Staphylococcus. Dexamethasone is a powerful anti-inflammatory that can penetrate the anterior segment; it is able to inhibit the inflammatory response of a mechanical, chemical or immunological nature. Dexamethasone is able to inhibit edema, the opening of the blood-water barrier, neovascularization, the proliferation of fibroblasts and other phenomena that characterize the various phases of the inflammatory process.
Pediatric population
The safety and efficacy of tobramycin 0.3% and dexamethasone 0.1% eye drops in children has been established based on extensive clinical experience, but only limited data are available. In a clinical study of another product consisting of eye drops, 0.3% tobramycin suspension and 0.1% dexamethasone in the treatment of bacterial conjunctivitis, 29 pediatric patients, aged 1 to 17 years, were treated with 1 or 2 drops of eye drops, suspension every 4 or 6 hours for 5 or 7 days. In this study, no differences were observed between adults and pediatric patients in the safety profile.
05.2 Pharmacokinetic properties
COMBISTILL eye drops are administered directly into the conjunctival sac. Bioavailability studies in rabbits show that, following topical ocular administration, tobramycin is absorbed in the cornea and dexamethasone in the cornea and aqueous humor.
The efficacy and safety of the combination of tobramycin 0.3% + dexamethasone 0.1% eye drops have been demonstrated following repeated topical ocular administration in rabbits for one month and in monkeys for three months. From these studies it emerged that the combination of tobramycin 0.3% + dexamethasone 0.1% eye drops does not have irritating power in rabbits and monkeys when treated, topically, according to the regimen envisaged for humans.
05.3 Preclinical safety data
Tobramycin: Animal studies have shown that tobramycin has a qualitatively similar toxicological profile to gentamicin with less severe side effects. No severe ocular toxicity was found in rabbits and humans either after topical ocular administration or after subconjunctival injection. both in healthy eyes and in eyes with induced keratitis.
Dexamethasone: The toxicity of dexamethasone is well documented in the literature. Like all corticosteroids, when administered systemically in high doses, dexamethasone inhibits pituitary gland activity, electrolyte disturbances, hyperglycemia and glycosuria, increased risk of infection, peptic ulcer, Cushing's syndrome, posterior subcapsular cataract. of dexamethasone present in COMBISTILL (0.1%), the frequency of administration and dosage show a low incidence of systemic effects following the clinical use of the product.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Benzalkonium chloride, disodium edetate, sodium chloride, sodium sulfate, tyloxapol, sodium hydroxide or sulfuric acid (pH regulator), hydroxyethylcellulose, water for injections.
06.2 Incompatibility
The tyloxapol component is incompatible with tetracycline.
06.3 Period of validity
2 years.
Shelf life after first opening the container: 28 days.
06.4 Special precautions for storage
Do not store above 25 ° C. Do not refrigerate or freeze.
Store in the original container to protect from light.
Do not use after the expiry date indicated on the outer package and on the label.
The expiry date refers to the product in intact packaging, correctly stored.
Keep this medicine out of the reach and sight of children.
06.5 Nature of the immediate packaging and contents of the package
5 ml dropper bottle in low density polyethylene
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Bruschettini S.r.l.
Via Isonzo 6
16147 Genoa
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 041033010 - "0.3% + 0.1% Eye drops, suspension" Dropper bottle 5 ml
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
01 July 2013
10.0 DATE OF REVISION OF THE TEXT
January 2016
