XALOFREE 50 mcg/ml + 5 mg/ml Drops

Contents of the leaflet

1. Package Leaflet: Information for the Patient
2. Xalofree Combi, 50 micrograms/ml + 5 mg/ml, eye drops, solution
   1. Read the package leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Contents of the Package Leaflet
3. What Xalofree Combi is and what it is used for
4. Important information before using Xalofree Combi
   1. When not to use Xalofree Combi
   2. Warnings and precautions
   3. Children and adolescents
   4. Xalofree Combi and other medicines
   5. Pregnancy and breastfeeding
   6. Driving and using machines
   7. Xalofree Combi contains phosphates
5. How to use Xalofree Combi
   1. Dosage
   2. Using contact lenses
   3. Instructions for use
   4. Using Xalofree Combi with other eye medicines
   5. Using more Xalofree Combi than you should
   6. Forgetting to use Xalofree Combi
   7. Stopping Xalofree Combi treatment
6. Possible side effects
   1. Stop using Xalofree Combi and contact your doctor immediately or go to the casualty department at your nearest hospital if you experience any of the following:
   2. Other side effects
   3. Reporting side effects
7. How to store Xalofree Combi
8. Contents of the pack and other information
   1. What Xalofree Combi contains
   2. What Xalofree Combi looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder
   5. Manufacturer
   6. Date of last revision of the package leaflet:

Package Leaflet: Information for the Patient

Xalofree Combi, 50 micrograms/ml + 5 mg/ml, eye drops, solution

Latanoprost + Timolol

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the Package Leaflet

• 1. What Xalofree Combi is and what it is used for
• 2. Important information before using Xalofree Combi
• 3. How to use Xalofree Combi
• 4. Possible side effects
• 5. How to store Xalofree Combi
• 6. Contents of the pack and other information

1. What Xalofree Combi is and what it is used for

Xalofree Combi contains two active substances: latanoprost and timolol. Latanoprost belongs to a group of medicines called prostaglandin analogues, and timolol belongs to a group of medicines called beta-blockers. Latanoprost works by increasing the outflow of fluid from the eye into the bloodstream. Timolol works by reducing the amount of fluid produced in the eye. Xalofree Combi is used to reduce high pressure in the eye in patients with open-angle glaucoma or ocular hypertension. Both conditions are associated with high pressure in the eye, which can lead to impaired vision. Your doctor will usually prescribe Xalofree Combi if other medicines have not worked well enough. Xalofree Combi is a sterile solution that does not contain preservatives.

2. Important information before using Xalofree Combi

When not to use Xalofree Combi

• if you are allergic to latanoprost, timolol, beta-blockers, or any of the other ingredients of this medicine (listed in section 6)
• if you have or have had respiratory problems such as asthma, severe chronic obstructive pulmonary disease (a serious lung disease that can cause wheezing, shortness of breath, and/or coughing)
• if you have or have had severe heart problems such as heart failure or irregular heartbeat
• in children under 18 years of age.

Warnings and precautions

Before starting treatment with Xalofree Combi, tell your doctor if you have or have had:

• coronary heart disease (symptoms may include chest pain or tightness, shortness of breath, or difficulty breathing)
• heart failure, low blood pressure
• irregular heartbeat, such as slow heart rate
• breathing difficulties, asthma, or chronic obstructive pulmonary disease
• Raynaud's disease or Raynaud's syndrome (a condition that affects blood flow to the fingers and toes)
• diabetes, as timolol may mask the symptoms of low blood sugar
• hyperthyroidism, as timolol may mask the symptoms
• planned eye surgery (including cataract surgery), or if you have had eye surgery in the past
• eye problems (such as eye pain, irritation of the eye surface, inflammation of the eye, or blurred vision)
• dry eyes
• if you wear contact lenses. You can continue to use Xalofree Combi, but follow the instructions for wearing contact lenses in section 3
• angina pectoris (especially Prinzmetal's angina)
• severe allergic reactions requiring hospital treatment
• herpes simplex virus keratitis (inflammation of the cornea caused by the herpes simplex virus) in the past or herpes simplex virus keratitis

Before using Xalofree Combi in patients with heart disease, your doctor should make sure that the heart disease is well controlled. During treatment with Xalofree Combi, your doctor may ask you to have additional heart and blood vessel tests. In patients with mixed-color irises (e.g., blue-brown, grey-brown, green-brown, yellow-brown), the color of the iris may slowly change due to an increase in the amount of brown pigment in the iris. Changes in iris color have been observed rarely in patients with uniform blue, grey, green, or brown eyes. The change in iris color is usually slow and may not be noticeable for several months or years. If you use Xalofree Combi in one eye only, the color of the iris may differ between the two eyes. The change in iris color is harmless but is likely to be permanent. If you have mixed-color irises or have noticed a change in iris color, contact your doctor. Before surgery, tell your doctor that you are using Xalofree Combi, as latanoprost and timolol may affect the action of certain anesthetics.

Children and adolescents

Xalofree Combi should not be used in patients under 18 years of age.

Xalofree Combi and other medicines

Tell your doctor or pharmacist about all medicines you are taking, including those you have bought without a prescription, and any that you plan to take. Xalofree Combi may affect the action of other medicines, and other medicines may affect the action of Xalofree Combi. Tell your doctor if you are using or plan to use medicines that lower blood pressure, heart medicines, or medicines for diabetes. Tell your doctor if you are using or plan to use any of the following medicines:

• calcium channel blockers (e.g., nifedipine, verapamil, or diltiazem) used to treat high blood pressure, angina, irregular heartbeat, or Raynaud's disease
• other medicines used to treat irregular heartbeat, including amiodarone
• digoxin, a medicine used to treat heart failure or irregular heartbeat
• quinidine, a medicine used to treat heart disease and certain types of malaria
• clonidine, a medicine used to treat high blood pressure
• other beta-blockers (e.g., medicines used to treat high blood pressure, angina, certain irregular heartbeats, heart attack, anxiety, migraine, glaucoma, or hyperthyroidism), which belong to the same group as timolol and may increase its effect
• medicines used to treat diabetes
• medicines that help you pass urine (e.g., guanethidine) or regulate bowel movements
• adrenaline (used to treat life-threatening allergic reactions caused by insect bites or stings, foods, medicines, latex, and other substances)
• antidepressants, such as fluoxetine and paroxetine
• prostaglandins, prostaglandin analogues, and prostaglandin derivatives (used to stimulate or inhibit the contraction of smooth muscle, dilate or constrict blood vessels, control blood pressure, and modulate inflammation).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor or pharmacist for advice before using Xalofree Combi. Pregnancy Xalofree Combi should not be used during pregnancy. Breastfeeding Xalofree Combi should not be used during breastfeeding. Latanoprost and timolol may pass into breast milk. Fertility In animal studies, no effects on fertility were observed in male or female animals.

Driving and using machines

After using Xalofree Combi, you may experience temporary blurred vision. If you experience this, do not drive or operate machinery until your vision is clear.

Xalofree Combi contains phosphates

The medicine contains 6.0 mg of phosphates per milliliter of solution. In patients with severe damage to the clear, front part of the eye (cornea), phosphates may rarely cause corneal calcification during treatment due to calcium deposits.

3. How to use Xalofree Combi

Always use Xalofree Combi exactly as your doctor has told you. If you are unsure, ask your doctor or pharmacist.

Dosage

Adults (including the elderly)
The recommended dose is: 1 drop into the affected eye(s) once daily.
Do not use Xalofree Combi more than once daily, as this may reduce the effectiveness of the treatment.

Using contact lenses

• Remove contact lenses before administering the drops. Contact lenses can be reinserted 15 minutes after using Xalofree Combi.

Instructions for use

Follow these steps to help you use Xalofree Combi correctly:

• 1. Wash your hands, then sit or stand comfortably.
• 2. Remove the cap (Figure 1).
• 3. Place your thumb on the dispenser cap on top of the bottle and your other fingers on the bottom of the bottle. Hold the bottle upside down (Figure 2). Before the first use, press the bottle 10 times with the dispenser facing down to activate the pump, until the first drop appears.
• 4. Tilt your head back and gently pull the lower eyelid down to create a "pocket" between your eye and eyelid.
• 5. Bring the tip of the dispenser close to your eye, without touching it.
• 6. Press the dispenser cap and the bottom of the bottle to release one drop into your eye, then release the lower eyelid (Figure 3).
• 7. Close your eye and press the corner of your eye nearest your nose gently with your finger for 1 minute, keeping your eye closed.
• 8. If you need to use Xalofree Combi in both eyes, repeat the same steps for the other eye.
• 9. Replace the cap on the bottle immediately after use.

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Only open one bottle of Xalofree Combi at a time. Do not open the bottle until the drops are needed. You should throw away the bottle with 2.5 ml after 30 days from first opening, and the bottle with 7.5 ml after 90 days from first opening to prevent infections. After this time, you should use a new bottle. To help you remember when you opened the bottle, write the date you first opened it on the carton.

Using Xalofree Combi with other eye medicines

If you are using Xalofree Combi with other eye medicines, wait at least 5 minutes between using each medicine. Apply eye ointments last.

Using more Xalofree Combi than you should

If you use more Xalofree Combi than you should, it may cause eye irritation, eye redness, and blurred vision. These symptoms should go away, but if you are concerned, contact your doctor for advice. If you accidentally swallow Xalofree Combi, contact your doctor. If you swallow a large amount of Xalofree Combi, you may experience low blood sugar, stomach pain, feeling tired, redness of the face, and dizziness, as well as excessive sweating.

Forgetting to use Xalofree Combi

If you forget to use Xalofree Combi at the usual time, wait until it is time for your next dose. Do not use a double dose to make up for a forgotten dose.

Stopping Xalofree Combi treatment

Use Xalofree Combi as instructed by your doctor, who will decide when you should stop treatment. If you want to stop using Xalofree Combi, contact your doctor. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Xalofree Combi can cause side effects, although not everybody gets them.

Stop using Xalofree Combi and contact your doctor immediately or go to the casualty department at your nearest hospital if you experience any of the following:

• allergic reactions, including hives, face, lip, tongue, and/or throat swelling, which may cause difficulty breathing or swallowing
• severe skin reactions with blistering or peeling of the skin, as well as localized and generalized rash
• stroke (symptoms may include sudden and severe headache, which may be accompanied by vomiting, dizziness, or changes in consciousness, as well as balance problems)
• heart stoppage.

The following are known side effects of Xalofree Combi. If you experience any side effects, tell your doctor. One of the side effects is the possibility of a gradual, permanent change in eye color. Xalofree Combi may cause serious changes in heart function. Tell your doctor if you experience changes in heart rate or heart function, and inform them that you are using Xalofree Combi. Known side effects that may occur when using Xalofree Combi:

Very common(affect more than 1 in 10 people):

• gradual change in eye color due to an increase in the amount of brown pigment in the colored part of the eye (iris). In patients with mixed-color irises (e.g., blue-brown, grey-brown, green-brown, yellow-brown), these changes are more likely to occur than in patients with uniform blue, grey, green, or brown eyes. The change in eye color may develop over several years. The change in eye color may be permanent and more noticeable if Xalofree Combi is used in one eye only. The change in eye color appears to be harmless. After stopping Xalofree Combi, the change in eye color does not progress.

Common(affect less than 1 in 10 people):

• eye pain, eye irritation (including feeling of something in the eye, burning, stinging, itching, or foreign body sensation)
• corneal disorders (the cornea is the first layer of the eye through which light enters the eye), including corneal inflammation
• conjunctivitis and other conjunctival disorders, blepharitis, eye redness
• abnormal vision, increased sensitivity to light (photophobia)
• headache
• high blood sugar levels (diabetes)
• high cholesterol levels
• depression
• excessive hair growth and skin disorders.

Uncommon(affect less than 1 in 100 people):

• blurred vision, increased tearing
• skin rash and/or itching.

Other side effects

Like other eye medicines, Xalofree Combi (latanoprost with timolol) is absorbed into the bloodstream. The frequency of side effects with eye drops is lower than with medicines taken orally or intravenously. The following side effects have been reported with the individual components of Xalofree Combi (latanoprost and timolol) and may also occur with Xalofree Combi. These include side effects observed with beta-blockers (e.g., timolol) used to treat eye diseases. Very common(affect more than 1 in 10 people):

• changes in eyelashes and vellus hair in the eyelids (increased length, thickness, and pigmentation).

Common(affect less than 1 in 10 people):

• irritation or damage to the eye surface, dry eyes, eyelid swelling.

Uncommon(affect less than 1 in 100 people):

• unstable angina (chest pain caused by physical exertion or stress), worsening of angina in patients with existing heart disease
• nausea, vomiting.

Frequency not known(cannot be estimated from the available data):

• development of herpes simplex virus keratitis (inflammation of the cornea caused by the herpes simplex virus)
• swelling around the eyes, inflammation of the iris and/or uvea (the middle layer of the eye)
• swelling of the back of the eye (macular edema), including cystoid macular edema
• swelling and/or ulcers of the cornea
• misdirected eyelashes (which may cause eye irritation), development of double row of eyelashes
• formation of fluid-filled areas in the iris (iris cysts)
• changes in the eye socket and eyelids resulting in deepening of the eyelid sulcus
• skin reactions on the eyelids, scarring conjunctivitis
• darkening of the skin around the eyes
• detachment of the retina (a layer at the back of the eye) following filtration surgery, which can cause vision problems
• double vision, reduced corneal sensitivity
• drooping eyelids (causing the eyes to be half-closed)
• angina, irregular heartbeat, heart failure, irregular heartbeat, slow heart rate
• congestive heart failure (a disease characterized by shortness of breath and swelling of the feet and legs due to fluid accumulation), chest pain
• edema (fluid accumulation), low blood pressure
• poor circulation (causing numbness and paleness of fingers and toes), Raynaud's phenomenon (a condition that affects blood flow to the fingers and toes)
• asthma, worsening of asthma, shortness of breath
• bronchospasm (mainly in patients with existing lung disease), cough, stuffy nose
• pulmonary edema (fluid accumulation in the lungs), breathing difficulties (respiratory failure)
• joint pain, muscle pain not caused by exercise
• psoriasis-like rash (with silvery scales) or worsening of psoriasis symptoms
• excessive hair loss
• low blood sugar levels
• memory loss, difficulty sleeping (insomnia), nightmares
• feeling confused, hallucinations, anxiety, disorientation, agitation
• reduced blood flow to the brain, dizziness
• worsening of myasthenia gravis symptoms (muscle weakness and pain in patients with this disease)
• tingling or numbness in the limbs
• sudden fainting or feeling of fainting
• ringing in the ears (tinnitus)
• stomach pain, diarrhea, dry mouth, taste disturbances, nausea
• sexual dysfunction, decreased libido
• weakness, fatigue.

Other side effects reported with phosphate-containing eye drops: In patients with severe damage to the clear, front part of the eye (cornea), phosphates may rarely cause corneal calcification during treatment due to calcium deposits.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, please inform your doctor or pharmacist. You can also report side effects directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. You can also report side effects to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Xalofree Combi

Keep out of the sight and reach of children. Before opening the bottle for the first time:

• Xalofree Combi should be stored in the refrigerator (at a temperature of 2°C to 8°C). Do not freeze.
• Keep the bottle in the outer carton to protect it from light.

After opening the bottle:

• you do not need to store Xalofree Combi in the refrigerator. Do not store above 25°C. Keep the bottle in the outer carton to protect it from light.
• Bottle of 2.5 ml: shelf-life after first opening: 30 days. Bottle of 7.5 ml: shelf-life after first opening: 90 days.

Do not use Xalofree Combi after the expiry date stated on the carton and bottle. The expiry date refers to the last day of the month stated. The packaging is marked with "EXP" for the expiry date and "Lot" for the batch number. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Xalofree Combi contains

• The active substances are latanoprost and timolol. Each milliliter (1 ml) of Xalofree Combi eye drops solution contains 50 micrograms of latanoprost and timolol maleate, equivalent to 5 mg of timolol. One drop of solution contains approximately 1.5 micrograms of latanoprost and 150 micrograms of timolol.
• The other ingredients are sodium chloride, disodium phosphate, sodium dihydrogen phosphate monohydrate, polysorbate 80, disodium edetate, sodium hydroxide (to adjust pH), hydrochloric acid (to adjust pH), water for injections.

What Xalofree Combi looks like and contents of the pack

Xalofree Combi is a colorless, clear solution. The pack consists of an HDPE bottle with a multidose dropper with a pump, cap (HDPE), and a dosing aid, in a cardboard box. Each 2.5 ml bottle contains at least 60 drops. Each 7.5 ml bottle contains at least 180 drops. Pack size: 1 bottle of 2.5 ml, 1 bottle of 7.5 ml. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Zakłady Farmaceutyczne POLPHARMA S.A., ul. Pelplińska 19, 83-200 Starogard Gdański, tel. +48 22 364 61 01

Manufacturer

Lomapharm GmbH, Langes Feld 5, Emmerthal, Niedersachsen, 31860, Germany

Date of last revision of the package leaflet: