Visucombidex

Package leaflet: Information for the user

Visucombidex 3 mg/ml + 1 mg/ml eye drops, solution, 3 mg/ml + 1 mg/ml eye drops, solution in single-dose container

tobramycin and dexamethasone
Please read all of this leaflet carefully before you start using this medicine because 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Visucombidex is and what it is used for

Visucombidex eye drops contain a combination of two medicines: dexamethasone, 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.
Visucombidex eye drops is indicated in adults and children from two years of age onwards for the treatment of eye inflammations when a corticosteroid is required and when there is either an existing eye infection or a risk of eye infection.

2. What you should know before using Visucombidex

Do not use Visucombidex:

• if you are allergic (hypersensitive) to tobramycin, dexamethasone, or any of the other ingredients of this medicine (listed in section 6);
• if you have:
  • inflammation of the cornea (the transparent membrane covering the colored part of the eye) caused by the Herpes simplex virus (herpes simplex keratitis);
  • eye infections caused by viruses (acute herpes simplex infections and most other viral diseases of the cornea), except when specific antiviral medications (chemotherapeutic agents) are used concomitantly for the treatment of Herpes virus; or if you have inflammation of the conjunctiva (the transparent membrane covering the white part of the eye and the inner eyelids) and cornea with lesions (ulcerative keratitis), even in the early stages;
  • viral inflammation of the cornea due to Herpes virus (viral herpetic keratitis); in such cases, Visucombidex will be prescribed only under strict ophthalmological supervision;
  • vaccinia, varicella, or other viral infections of the cornea and conjunctiva;
  • fungal (fungal keratitis) or parasitic eye infections that have not been treated;
  • eye infections caused by mycobacteria (ocular tuberculosis);
  • high intraocular pressure;
  • eye inflammations with pus formation (acute purulent ophthalmia, purulent conjunctivitis, purulent and herpetic blepharitis), which may be masked or worsened by corticosteroids;
  • an eyelid infection characterized by a pimple-like swelling or abscess (sty).

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

• Some patients may develop sensitization (allergic reaction) to aminoglycoside antibiotics such as tobramycin when administered into the eyes. This allergic reaction may range from localized itching or redness of the skin to severe generalized allergic reactions (anaphylactic reactions) or serious skin reactions. If you experience any of these symptoms while using Visucombidex eye drops, stop treatment immediately and consult your doctor. Also note that this allergic sensitivity may occur with other antibiotics belonging to the aminoglycoside class, whether administered into the eyes or systemically (by injection).
• Consult your doctor if you have or have ever had conditions such as myasthenia gravis or Parkinson’s disease. This type of antibiotic may worsen muscle weakness.
• In patients who have received systemic (by injection) aminoglycoside antibiotics such as tobramycin, serious toxic effects on the nervous system, ears, and kidneys have occurred. Be cautious and consult your doctor if you are using Visucombidex together with systemically administered aminoglycoside antibiotics (by injection).
• Long-term application of corticosteroids into the eyes may lead to increased intraocular pressure (including a condition called glaucoma, with optic nerve damage), visual problems, and cataract formation (clouding of the lens inside the eye, known as the crystalline lens). If you use Visucombidex eye drops for a prolonged period, you must have regular and frequent checks of your eye pressure. This is particularly important in children, as the risk of corticosteroid-induced increase in intraocular pressure may be higher in children under six years of age and may occur earlier than in adults. Consult your doctor, especially if Visucombidex eye drops are to be used in children. The risk of corticosteroid-induced increase in intraocular pressure and/or cataract formation is increased in predisposed patients (e.g., diabetic patients). If Visucombidex is used in a child, the doctor will carefully evaluate the frequency and duration of treatment and monitor intraocular pressure at the beginning of therapy with Visucombidex (see also “Warnings and precautions”).
• Consult your doctor if you experience swelling and weight gain around the trunk and face, as these are usually the first signs of a condition called Cushing's syndrome. Suppression of adrenal gland function may develop after discontinuation of prolonged or intensive treatment with Visucombidex. Do not stop treatment on your own without consulting your doctor. These risks are particularly important in children and in patients treated with a medicine called ritonavir or cobicistat.
• With the use of Visucombidex eye drops, you may become more susceptible to eye infections caused by bacteria, viruses, fungi, or parasites. If your symptoms worsen or suddenly reappear, consult your doctor.
• If you have a corneal ulcer that does not heal, discontinue treatment and consult your doctor.
• Consult your doctor before using this medicine if you have conditions causing thinning of the eye tissues, as ocular administration of corticosteroids may lead to perforation.
• Corticosteroids applied to the eyes may slow the healing of corneal wounds. It is known that NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) applied to the eyes may also slow or delay healing. Concomitant use of NSAIDs and corticosteroids in the eyes may potentially increase problems with wound healing (see section “Other medicines and Visucombidex”).
• Do not wear contact lenses during treatment of eye inflammation or infection.

Also read the section “Visucombidex eye drops contain benzalkonium chloride”.

• Use Visucombidex eye drops under direct medical supervision.
• Use Visucombidex eye drops only for ocular application.
• Contact your doctor if you experience blurred vision or other visual disturbances.

Visucombidex 3 mg/ml + 1 mg/ml eye drops, solution must not be injected.
For those engaged in sports: using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.
If you use Visucombidex for prolonged treatment beyond 10 days, your doctor will perform frequent checks of your eye pressure.
Prolonged use of corticosteroids, such as dexamethasone, may cause:

• a disease due to increased intraocular pressure (glaucoma);
• damage to the optic nerves;
• visual impairments (visual acuity and visual field defects);
• clouding of the eye’s crystalline lens (cataract).

Prolonged use of corticosteroids may favor the onset of eye infections.
It is recommended not to use Visucombidex for more than one consecutive month.
Prolonged use of antibiotics such as tobramycin may promote the development of resistant bacteria.
If you do not notice improvement within a reasonable time, your doctor will instruct you to discontinue use of Visucombidex and will prescribe appropriate therapy.

Other medicines and Visucombidex
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are using other eye medications containing NSAIDs (Non-Steroidal Anti-Inflammatory Drugs). Concomitant use of NSAIDs and corticosteroids in the eyes may potentially increase problems with corneal wound healing.
Consult your doctor if you are using ritonavir or cobicistat, as these may increase blood levels of dexamethasone.
Some medicines may enhance the effects of Visucombidex, and your doctor may wish to monitor you closely if you are taking such medicines (including certain HIV treatments: ritonavir, cobicistat).

Incompatibilities
The ingredient tyloxapol contained in Visucombidex eye drops is incompatible with tetracycline.
Do not use Visucombidex eye drops together with other eye products containing tetracycline.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
Data on the use of tobramycin and dexamethasone in the eyes of pregnant women are lacking or limited. Animal studies have shown reproductive toxicity following systemic (oral or injectable) administration of dexamethasone and tobramycin.
Visucombidex should be used during pregnancy only if strictly necessary. Consult your doctor, who will decide whether you should use Visucombidex during pregnancy.

Breastfeeding
It is not known whether tobramycin or dexamethasone is excreted in human milk following ocular administration. Tobramycin is excreted in human milk after systemic (injectable) administration.
No data are available on the passage of dexamethasone into human breast milk. Risk to the infant cannot be excluded. Consult your doctor, who will decide whether you should discontinue breastfeeding or discontinue treatment with Visucombidex.
If you are breastfeeding, your doctor will prescribe Visucombidex cautiously and under close supervision, as safety and efficacy in children under two years of age have not been established (see also “Use in children”).

Fertility
No studies have been conducted to evaluate the effect of topical ocular administration of tobramycin on human fertility.
Clinical data on the effect of ocular administration of dexamethasone on male or female fertility are limited.

Driving and use of machines
For a certain period after instillation of Visucombidex eye drops, blurred vision or other visual disturbances may occur, which could impair your ability to drive or operate machinery. If you experience these effects, wait until your vision returns to normal before driving or operating machinery.

Visucombidex 3 mg/ml + 1 mg/ml eye drops, solution in multidose container contains benzalkonium chloride.
The medicine contains 0.1 mg benzalkonium chloride per 1 ml, equivalent to 0.50 mg/ml, which may be absorbed by soft contact lenses and may alter their color.
Remove contact lenses before using this medicine and wait 15 minutes before reinserting them.
Benzalkonium chloride may also cause eye irritation, especially if you have dry eyes or corneal disorders (the outermost transparent layer of the eye). If you experience an abnormal sensation, burning, or pain in the eye after using this medicine, speak with your doctor.

3. How to use Visucombidex

Apply Visucombidex eye drops only into the eyes.
Always use this medicine exactly as your doctor has instructed. If in doubt, consult your doctor or pharmacist.
The recommended dose is:
1 or 2 drops 4–5 times daily, as prescribed by your doctor.
Use the medicine for the duration prescribed by your doctor.
The following procedure helps reduce the amount of medicine that passes into the bloodstream after eye application: keep the eyelid closed and, at the same time, apply gentle pressure with a finger at the inner corner of the eye near the nose for at least 2 minutes.
If you are using other eye drops, wait at least 5 minutes between instilling each medicine.

Use in children
Do not use Visucombidex eye drops, solution in children under two years of age, as safety and efficacy have not been established in this population and no data are available.
Visucombidex eye drops may be used in children from two years of age onwards at the same doses as recommended for adults.

How to apply Visucombidex eye drops

• Wash your hands.
• Hold the bottle/container upside down between thumb and middle finger.
• Tilt your head backward. Pull down the eyelid with a clean finger to form a pouch between the eyelid and the eye. The drop should be instilled into this pouch (Figure 1).
• Bring the tip of the bottle/container close to the eye.
• Do not touch the eye, eyelid, surrounding areas, or any other surfaces with the tip of the bottle/container to avoid contaminating the remaining drops.
• Gently press the base of the bottle/container to release one drop of Visucombidex at a time.
• If instilling drops into both eyes, repeat the same procedure for the other eye.
• Eye drops, solution in multidose container: Immediately replace the cap after use, screwing it on tightly.
• Eye drops, solution in single-dose containers: Discard the container and any remaining contents.
• If a drop misses the eye, try again.

If you use more Visucombidex than you should
Since this medicine is applied into the eyes, overdose is unlikely. However, if it occurs, thoroughly rinse the eye with running water. Do not use the medicine again until the next scheduled dose.

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

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects have been reported with the use of Visucombidex eye drops.

Uncommon (may affect up to 1 in 100 people)

• Increased eye pressure, eye pain, eye itching, eye discomfort, eye irritation.

Rare (may affect up to 1 in 1,000 people)

• 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)
Eyelid swelling, eyelid redness, increased pupil size, increased tear production, blurred vision, increased body hair growth (especially in women), muscle weakness and atrophy, purple stretch marks on the skin, 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, skin rash, severe skin reactions (erythema multiforme), facial swelling, itching.

If you are taking tobramycin at the same time via local and systemic routes (by mouth or by injection), your doctor will monitor you with regular checks.
Following the instructions contained in this leaflet reduces the risk of side effects.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via 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 Visucombidex

Keep this medicine out of the sight and reach of children.
Eye drops: store below 25°C. Do not freeze.
Do not use this medicine after the expiry date stated on the packaging after “Expiry”.
The expiry date refers to the last day of that month.
The expiry date refers to the product in its original unopened packaging, correctly stored.
Single-dose containers
The medicine must be used immediately after opening the single-dose container. Discard any remaining
solution. Use the medicine within 28 days of opening the aluminium pouch.
5 ml bottle
The medicine must be used within 28 days after first opening the bottle.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose
of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Visucombidex contains
Visucombidex 3 mg/ml + 1 mg/ml eye drops, solution in single-dose container

• The active substances are: tobramycin and sodium dexamethasone phosphate. Each single-dose container contains 0.75 mg of tobramycin and 0.329 mg of sodium dexamethasone phosphate, equivalent to 0.25 mg of dexamethasone.
• The other components are: tyloxapol, disodium edetate, anhydrous sodium sulfate, sodium chloride, sulfuric acid (pH regulator), water for injections.

Visucombidex 3 mg/ml + 1 mg/ml eye drops, solution in multidose bottle

• The active substances are: tobramycin and sodium dexamethasone phosphate. A 5 ml bottle contains 15 mg of tobramycin and 6.58 mg of sodium dexamethasone phosphate, equivalent to 5 mg of dexamethasone.
• The other components are: tyloxapol, benzalkonium chloride, disodium edetate, anhydrous sodium sulfate, sodium chloride, sulfuric acid (pH regulator), water for injections.

Each ml of eye drops contains 3 mg of tobramycin and 1 mg of dexamethasone.
Description of the appearance of Visucombidex and contents of the pack
Visucombidex is an eye drop solution.
Pack contents:

• Box containing 20 single-dose containers of 0.25 ml.
• Box containing 1 5 ml dropper bottle.

Marketing Authorization Holder
Visufarma S.p.A.
Via Alberto Cadlolo, 21
00136 Roma
Manufacturer
Genetic S.p.A.
Contrada Canfora
84084 Fisciano (SA)