COMBISTILL 3 mg /Ml + 1 Mg/Ml Eye Drops, Suspension

Зміст інструкції

1. COMBISTILL 3 mg/ml + 1 mg/ml eye drops, suspension
   1. What is COMBISTILL and what is it used for
   2. What you need to know before using COMBISTILL
   3. How to use COMBISTILL
   4. Possible side effects
   5. How to store COMBISTILL
   6. Contents of the pack and other information

COMBISTILL 3 mg/ml + 1 mg/ml eye drops, suspension

tobramycin and dexamethasone
Generic medicine

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What COMBISTILL is and what it is used for
• 2. What you need to know before you use COMBISTILL
• 3. How to use COMBISTILL
• 4. Possible side effects
• 5. How to store COMBISTILL
• 6. Contents of the pack and other information

1. What is COMBISTILL and what is it used for

COMBISTILL contains a combination of two medicines: desamethasone, which belongs to the class
of corticosteroids and has an anti-inflammatory effect, and tobramycin, which belongs to the class of
aminoglycoside antibiotics and acts against various bacteria that can cause eye infections.
Combistill eye drops are indicated in adults and children from two years of age for the treatment of
eye inflammations when a corticosteroid is necessary and when an ocular infection
or the risk of ocular infection exists.

2. What you need to know before using COMBISTILL

Do not use COMBISTILL

• if you are allergic (hypersensitive) to tobramycin, dexamethasone or any other of the ingredients of this medicine (listed in section 6); If you suffer from:
• inflammation of the cornea (the transparent membrane covering the colored part of the eye) caused by the Herpes simplex virus (Herpes simplex keratitis)
• smallpox vaccination, chickenpox or other viral infections of the cornea and conjunctiva (the transparent membrane covering the white part of the eye and the inside of the eyelids)
• conjunctivitis with ulcerative keratitis even in the early stages (fluorescein test +).
• untreated fungal (eye mycosis) or parasitic infections of the eye
• tuberculosis of the eye
• high pressure in the eyes
• eye inflammations with pus production (acute purulent ophthalmias, purulent conjunctivitis and purulent and herpetic blepharitis), which may be masked or aggravated by corticosteroids
• stye.

Warnings and precautions
Talk to your doctor or pharmacist before using COMBISTILL.

• In some patients, sensitization (allergic reaction) to aminoglycoside antibiotics such as tobramycin, administered to the eyes, may occur. This allergic reaction can range from localized skin itching or redness to severe general allergic reactions (anaphylactic reactions) or severe skin reactions. If these symptoms occur during the use of Combistill, stop treatment and see a doctor. Also, be aware that this allergic sensitivity may also occur with other antibiotics belonging to the same class of aminoglycosides, administered both to the eyes and systemically (by injection).
• Talk to your doctor if you have or have ever had conditions such as myasthenia gravis or Parkinson's disease. These types of antibiotics can worsen muscle weakness.
• Serious toxic effects on the nervous system, ears and kidneys have occurred in patients who have been given aminoglycoside antibiotics, such as tobramycin, systemically (by injection). Be careful and see your doctor if you are using Combistill together with aminoglycoside antibiotics given systemically (by injection).
• Long-term application to the eyes of corticosteroids can cause increased pressure in the eyes (including a disease called glaucoma, with damage to the optic nerve), vision problems and cataract formation (clouding of the lens inside the eye, called the crystalline lens). If you use Combistill for a long period of time, you should have your eye pressure checked regularly and frequently. This is particularly important in children, as the risk of increased eye pressure caused by corticosteroids may be greater in children under six years of age and may appear sooner than it does in adults. Ask your doctor for advice, especially if you need to use Combistill in children. The risk of increased eye pressure induced by corticosteroids and/or cataract formation is increased in predisposed patients (e.g. in diabetic patients).
• Talk to your doctor if you experience swelling and weight gain around the trunk and face, as these are usually the first signs of a syndrome called Cushing's syndrome. Suppression of adrenal gland function may develop after discontinuation of prolonged or intensive treatment with Combistill. See your doctor before stopping treatment on your own. These risks are particularly important in children and patients treated with a medicine called ritonavir or cobicistat.
• With the use of Combistill you may become more susceptible to eye infections caused by bacteria, viruses, fungi or parasites: if your symptoms worsen or suddenly reappear, see your doctor.
• If you have a corneal ulcer that does not heal, stop therapy and see your doctor.
• Talk to your doctor before using this medicine if you have diseases that cause thinning of the eye tissues, as perforation may occur with the administration of corticosteroids to the eyes.
• Corticosteroids applied to the eyes can slow down the healing of corneal wounds. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) applied to the eyes are also known to slow down or delay healing. Concurrent application of NSAIDs and corticosteroids to the eyes may potentially increase problems with eye wound healing (see section “Other medicines and COMBISTILL”).
• Do not wear contact lenses during the treatment of eye inflammation or infection. Also read the section “Combistill contains benzalkonium chloride”.
• Use Combistill under the direct supervision of your doctor.
• Use Combistill only for application to the eyes.
• Contact your doctor if you experience blurred vision or other visual disturbances.

For athletes:the use of the drug at doses and for indications other than those
authorized, constitutes doping and may still result in a positive doping test.

Other medicines and COMBISTILL
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
Tell your doctor especially if you are taking other medicines for the eyes that contain drugs
belonging to the class of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs). The concurrent
application of NSAIDs and corticosteroids to the eyes may potentially increase problems with
healing of corneal wounds.
Talk to your doctor if you are using ritonavir or cobicistat, as they may increase the level of
dexamethasone in the blood.

Incompatibilities
The tyloxapol component contained in Combistill is incompatible with tetracycline.
Do not use Combistill together with other products for the eyes that contain tetracycline.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are
breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
Data relating to the use of tobramycin and dexamethasone in the eyes in pregnant women are not
available or are limited. Studies in animals have shown reproductive toxicity following
systemic (oral or injection) administration of dexamethasone and tobramycin.
Combistill should be used during pregnancy only if strictly necessary. See your
doctor, who will decide whether you should use Combistill during pregnancy.
Breastfeeding
It is not known whether tobramycin or dexamethasone are excreted in breast milk after
administration to the eyes. Tobramycin is excreted in breast milk after systemic administration
(by injection). No data are available on the passage of dexamethasone into human breast milk.
The risk to infants cannot be excluded. See your doctor, who will decide whether you should
stop breastfeeding or stop therapy with Combistill.
Fertility
No studies have been conducted to evaluate the effect of topical ocular administration of tobramycin
on human fertility.
Clinical data to evaluate the effect of ocular administration of dexamethasone on male or female
fertility are limited.

Driving and operating machinery
For a certain period of time after instillation of Combistill, blurred vision or other visual
disturbances may occur that may impair the ability to drive vehicles and operate machinery. If you
experience these effects, wait until your vision returns to clear
before driving vehicles and using machinery.

COMBISTILL contains benzalkonium chloride
This medicine contains 0.10 mg of benzalkonium chloride per ml, equivalent to approximately 0.0038 mg of
benzalkonium chloride per drop.
Benzalkonium chloride can be absorbed by soft contact lenses and can lead to
changes in their color. Remove contact lenses before using this medicine and wait 15
minutes before re-applying them.
Benzalkonium chloride can also cause eye irritation, especially if you have dry eyes or
corneal disorders (the most superficial transparent layer of the eye). If you experience an
abnormal sensation in your eye, burning or pain after using this medicine, talk to your doctor.

3. How to use COMBISTILL

Use this medicine following exactly the instructions of your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
COMBISTILL must be applied only to the eyes (ocular use).
This medicine, being an eye drop, must not be injected.
The recommended dose is 1 or 2 drops 4-5 times a day, following the instructions provided by your
doctor. Use the medicine for the period of time prescribed by your doctor.
The following operation is useful to limit the amount of medicine that passes into the blood after
application to the eyes:
keep the eyelid closed and at the same time apply gentle pressure with a finger on the inner corner of the
eye near the nose for at least 2 minutes.
If you are using other eye drops, allow at least 5 minutes to pass between the instillation of each medicine.

Use in children
Do not use Combistill in children under two years of age given that safety and efficacy have not been
established in this population and no data are available.
Combistill can be used in children from two years of age onwards at the same doses as for
adults.

How to apply Combistill
For correct use of the medicine, carefully read the following instructions:

• 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 gently lower the lower eyelid of the eye to form a pouch;
• invert the bottle and apply slight pressure to the body of the container;
• insert 1 or 2 drops into the eye, as prescribed by your doctor;
• keep your eye closed for 1 minute, pressing with your finger on the corner of the eye near the nose;
• repeat the operation also in the other eye if your 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.

Avoid contact between the dropper tip and 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 eye damage and which can also cause vision loss.
The dropper tip delivers a drop with a predefined volume. Therefore, do not attempt to widen the
hole in the dropper. After finishing the treatment, some medicine may remain in the
bottle. Do not attempt to remove excess COMBISTILL from the bottle.

If you use more COMBISTILL than you should
Considering that the medicine is applied to the eyes, it is difficult for cases of
overdose to occur. However, if this should happen, wash your eye thoroughly with running water.
Do not use more of the medicine until the time scheduled for the next administration.

If you forget to use COMBISTILL
If you forget to use Combistill, do not worry and apply it as soon as you remember. However, if it is almost
time for the next dose, skip the missed dose and return to the regular dosing schedule.
Do not use a double dose to make up for a missed dose.

If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
With the use of eye drops based on tobramycin 3 mg/ml and dexamethasone 1 mg/ml, the following
side effects have been reported.
Uncommon (may affect up to 1 in 100 people)

• increased pressure in the eye(s), eye pain, eye itching, eye discomfort, eye irritation. Rare ( may affect up to 1 in 1,000)
• inflammation of the surface of the eye (keratitis), eye allergy, blurred vision, dry eye, eye redness, unpleasant taste. Not known (frequency cannot be estimated from the available data)
• swelling of the eyelids, redness of the eyelids, increased pupil size, increased tear production, blurred vision, increased hair growth on the body (especially in women), muscle weakness and atrophy, purple stretch marks on the skin of the body, increased blood pressure, irregular or absent menstrual cycle, changes in protein and calcium levels in the body, delayed growth in children and adolescents, and swelling and weight gain of the body and face (called “Cushing’s syndrome”) (see section 2, “Warnings and precautions”); severe allergic reactions (hypersensitivity), dizziness, headache, nausea, abdominal discomfort, rash, severe skin reactions (erythema multiforme), facial swelling, itching.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, please tell your doctor or pharmacist. You can also report side effects directly through the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store COMBISTILL

Keep this medicine out of the sight and reach of children.
Store the medicine at a temperature below 25°C. Do not refrigerate or freeze. Do not use the
medicine more than 28 days after the first opening of the container.
Do not use this medicine after the expiry date which is stated on the outer packaging and
on the label after “Exp.”.
The expiry date refers to the last day of that month.
The expiry date refers to the product in intact packaging, correctly stored.
Store in the original packaging, protected from light.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

WhatCOMBISTILL contains

• 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 adjuster), hydroxyethylcellulose, water for injections.

Description of the appearance of COMBISTILL and contents of the pack
5 ml dropper bottle made of low density polyethylene (LDPE).

Marketing Authorisation Holder
Bruschettini S.r.l. - Via Isonzo, 6 – 16147 Genova – Italy

Manufacturer
Rafarm Hellas S.A. Pharmaceutical Company - Thesi Pousi- Xatzi Agiou Louka, 19002, Paiania –
Attiki – Greece