Xalofree combi

Package leaflet: Information for the patient

Xalofree Combi, 50 micrograms/ml + 5 mg/ml, eye drops, solution
Latanoprostum + Timololum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the 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 eyeball into the bloodstream. Timolol works by reducing the amount of fluid produced in the eye.
Xalofree Combi is used to reduce intraocular pressure in patients with open-angle glaucoma or in patients with ocular hypertension. Both conditions are associated with elevated intraocular pressure and may affect vision. Your doctor will usually recommend using Xalofree Combi if the effect of other medicines has been insufficient.
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 the patient is allergic to latanoprost, timolol, beta-blockers or any of the other ingredients of this medicine (listed in section 6)
• if the patient has or has had breathing problems such as asthma, or severe chronic obstructive bronchitis (a serious lung disease which may cause wheezing, difficulty in breathing and/or long-term cough)
• if the patient has severe heart disease, such as heart failure or heart rhythm disorders
• in patients under 18 years of age.

Warnings and precautions
Before starting treatment, discuss with your doctor if the patient has or has had in the past:

• coronary heart disease (symptoms may include chest pain or tightness, shortness of breath or suffocation), heart failure, low blood pressure,
• heart rhythm disorders, such as slow heartbeat,
• breathing difficulties, asthma or chronic obstructive pulmonary disease (COPD),
• diseases related to poor blood circulation (such as Raynaud's disease or Raynaud's syndrome),
• diabetes, because timolol may mask the subjective and objective symptoms of hypoglycaemia,
• hyperthyroidism, because timol combust may mask the subjective and objective symptoms,
• planned eye surgery (including cataract surgery), or if such surgery has previously been performed,
• eye problems (such as eye pain, eye surface irritation, eye inflammation or blurred vision),
• dry eye,
• if the patient wears contact lenses. The medicine may still be used, but follow the instructions for use with contact lenses given in section 3,
• angina pectoris (especially Prinzmetal's angina),
• severe allergic reactions requiring hospital treatment,
• a history of herpetic keratitis or herpetic keratitis caused by the Herpes Simplex virus (HSV).

Before administering Xalofree Combi eye drops to patients with heart disease, the doctor should ensure that the heart condition is well controlled. During treatment with Xalofree Combi eye drops, the doctor may order additional tests of heart and circulatory function.
In patients with mixed-coloured irises, e.g. blue-brown, grey-brown, green-brown, yellow-brown, the eye colour may gradually change over time due to an increased amount of brown pigment in the iris. Changes in iris colour have been observed rarely in patients with uniformly blue, grey, green or brown eyes. Iris pigmentation changes towards brown are usually slow and often clinically unnoticed for several months or years. If Xalofree Combi eye drops are used in only one eye, a difference in iris colour between the two eyes may become apparent. Iris colour change is considered harmless but is likely to be permanent.
If the patient has mixed-coloured irises or observes a change in iris pigmentation towards brown, the patient should contact their doctor.
Before undergoing surgical procedures, inform the doctor about the use of Xalofree Combi eye drops, as latanoprost and timolol may affect the action of certain anaesthetic drugs.

Children and adolescents
Xalofree Combi must not be used in patients under 18 years of age.

Xalofree Combi and other medicines
Tell your doctor or pharmacist about any medicines (including eye drops) the patient is currently taking or has recently taken, even those not requiring a prescription, as well as any medicines the patient plans to take.
Xalofree Combi may affect the action of other medicines, and other medicines, including other eye drops used in the treatment of glaucoma, may affect Xalofree Combi. Inform your doctor if the patient is taking or plans to take medicines that lower blood pressure, heart medications or medicines used in diabetes treatment.
Inform your doctor if the patient is taking one or more of the following medicines:

• calcium channel blockers (e.g. nifedipine, verapamil or diltiazem), used to treat high blood pressure, angina, heart rhythm disorders or Raynaud's disease
• other medicines used to treat heart rhythm disorders, including amiodarone
• digoxin, a medicine used to treat heart failure or heart rhythm disorders
• quinidine, a medicine used to treat heart diseases and certain types of malaria
• clonidine, a medicine used to treat high blood pressure
• other beta-blocking agents (e.g. medicines used to treat high blood pressure, angina, certain heart rhythm disorders, heart attack, anxiety, migraine, glaucoma or hyperthyroidism), which belong to the same class as timolol and may enhance its effects
• medicines used in the treatment of diabetes
• diuretics (e.g. guanethidine) or medicines that regulate bowel function
• adrenaline (used in the treatment of life-threatening allergic reactions caused by insect bites or stings, food, medicines, latex or other factors)
• antidepressants such as fluoxetine and paroxetine
• prostaglandins, prostaglandin analogues and derivatives (used to stimulate and inhibit smooth muscle contractions, dilate and constrict blood vessels, control blood pressure and modulate inflammatory responses).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Xalofree Combi must not be used during pregnancy.

Breastfeeding
Xalofree Combi must not be used during breastfeeding. Latanoprost and timolol may pass into human milk.

Effect on fertility
Animal studies have shown no effect of latanoprost and timolol on fertility in males or females.

Driving and using machines
Blurred vision may occur for a short time after instillation of the eye drops. If the patient experiences such symptoms, they should not drive or operate machinery until vision clears.

Xalofree Combi contains phosphates
This medicine contains 6.0 mg of phosphates per millilitre of solution. In patients with severe damage to the transparent front part of the eye (cornea), phosphates may very rarely cause corneal clouding due to calcium deposition during treatment.

3. How to use Xalofree Combi

This medicine should always be used exactly as instructed by your doctor. If in doubt, consult your doctor or pharmacist.

Dosage
Adults (including elderly patients)
The recommended dose is: 1 drop in the affected eye(s) once daily.
Do not use this medicine more than once a day, as this may reduce the effectiveness of treatment.

Use of contact lenses

• Remove contact lenses before instilling eye drops. Contact lenses may be reinserted 15 minutes after using Xalofree Combi.

Instructions for using the eye drops
Follow the instructions below to ensure correct use of Xalofree Combi:

1. Wash your hands and then sit or stand comfortably.
2. Remove the cap (Figure 1).
3. Place your thumb on the dosing aid at the top of the bottle and the other fingers on the base. Hold the bottle upside down (Figure 2). Before first use, press the bottle approximately 10 times with the dropper tip pointing downwards to activate the pump mechanism, until the first drop appears.
4. Tilt your head backwards and gently pull down the lower eyelid with your finger to create a "pocket" between the eyeball and the eyelid.
5. Bring the dropper tip as close as possible to the eye without touching it.
6. Press the dosing aid at the top of the bottle and the base simultaneously to release a single drop into the eye, then release the lower eyelid (Figure 3).
7. Close the eye and press gently with your finger on the inner corner of the eye near the nose (Figure 4). Maintain this pressure for one minute, keeping the eye closed.
8. If necessary, instill a drop into the other eye in the same manner.
9. Immediately after use, replace the cap on the bottle tip.

Figure 1. Figure 2. Figure 3. Figure 4.
Only one bottle of medicine should be opened and used at a time. Do not remove the cap until the drops are needed.
Discard the 2.5 ml bottle 30 days after first opening and the 7.5 ml bottle 90 days after first opening to prevent infections. After this time, the patient should use a new bottle.
To better monitor the storage period of the drops after first opening, the patient should record the date of opening on the carton in the space provided for this purpose.

Use with other eye medicines
If Xalofree Combi is used together with other eye medicines, an interval of at least five minutes should be maintained between the administration of each drop. Ointments should be used last.

Overdose of Xalofree Combi
If too many drops are used, eye irritation, tearing, and eye redness may occur. These symptoms should resolve on their own, but if the patient is concerned, they should contact their doctor for advice.
In case of accidental ingestion of the medicine, contact a doctor. If a large amount of Xalofree Combi eye drops is swallowed, symptoms such as malaise, abdominal pain, fatigue, facial flushing, dizziness, and excessive sweating may occur.

Missed dose of Xalofree Combi
If a dose is missed at the usual time, wait until the next scheduled dose. Do not use a double dose to make up for the missed dose.

Stopping Xalofree Combi
This medicine should be used as directed by your doctor, who will decide when treatment should be discontinued. If you intend to stop using Xalofree Combi, consult your doctor first.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine may cause adverse reactions, although not everyone will experience them.
You must stop using this medicine and immediately contact your doctor or the emergency department of the nearest hospital
if the patient experiences (frequency unknown):

• allergic reactions, including urticaria, facial swelling, swelling of the lips, tongue and (or) throat, which may cause difficulty in 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, possibly accompanied by vomiting, dizziness or disturbances of consciousness, as well as balance problems),
• cardiac arrest.

The following are known adverse reactions occurring after administration of a medicine containing
latanoprost and timolol as active substances. If any adverse reactions occur, contact your doctor.
One of the possible adverse reactions is a gradual, permanent change in eye colour.
Xalofree Combi may cause serious disturbances in heart function. Inform the doctor if the patient
notices any changes related to heart rate or heart function, and inform them about the use of this medicine.
Known adverse reactions that may occur after administration of this medicine:
Very common (affects more than 1 in 10 patients):

• gradual change in eye colour due to increased amount of brown pigment in the coloured part of the eye called the iris. This change is more frequently observed in patients whose iris colour is mixed (e.g. blue-brown, grey-brown, yellow-brown or green-brown) than in those with uniformly coloured eyes (blue, grey, green or brown). Changes in eye colour may develop over several years. The change in eye colour may be permanent and significantly more noticeable if only one eye is treated with Xalofree Combi. The change in eye colour appears to be harmless. After discontinuation of this medicine, the change in eye colour does not progress.

Common (affects less than 1 in 10 patients):

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

Uncommon (affects less than 1 in 100 patients):

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

Other adverse reactions
Like other ophthalmic medicines, Xalofree Combi (latanoprost with timolol) is absorbed into the bloodstream. The frequency of systemic adverse reactions after administration of eye drops is lower than with orally or intravenously administered medicines.
Below are adverse reactions reported after administration of the individual components of this medicine (latanoprost and timolol), and which may therefore also occur with Xalofree Combi. Among these adverse reactions are also those observed during use of beta-adrenergic blocking agents (e.g. timolol) in the treatment of eye diseases.
Very common (affects more than 1 in 10 patients):

• changes in eyelashes and eyelid vellus hair (increased amount, length, thickness and darkening).

Common (affects less than 1 in 10 patients):

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

Uncommon (affects less than 1 in 100 patients):

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

Frequency unknown (cannot be estimated from available data):

• development of viral eye infection caused by herpes simplex virus,
• periorbital oedema, iritis and (or) uveitis,
• posterior segment oedema (macular oedema), including cystoid macular oedema,
• corneal oedema and (or) erosion,
• misdirected eyelashes (sometimes leading to eye irritation), development of a double row of eyelashes,
• formation of fluid-filled cysts in the iris (iris cysts),
• changes in the orbit and eyelids resulting in deepening of the eyelid sulcus,
• skin reactions on the eyelids, cicatrizing conjunctivitis,
• darkening of the skin around the eyes,
• choroidal detachment following filtration surgery, which may lead to visual disturbances,
• double vision, decreased corneal sensitivity,
• eyelid ptosis (causing the eyes to be partially closed),
• angina pectoris, palpitations, heart failure, cardiac arrhythmias, bradycardia,
• congestive heart failure (a condition characterized by shortness of breath and swelling of the feet and legs due to fluid accumulation), chest pain,
• oedema (fluid accumulation), decreased arterial blood pressure,
• poor peripheral circulation manifesting as numbness and pallor of fingers and toes, cold hands and feet (Raynaud's phenomenon),
• asthma, worsening of asthma, dyspnoea,
• bronchospasm (mainly in patients with pre-existing bronchial disease), cough, nasal congestion,
• pulmonary fluid accumulation (pulmonary oedema), breathing difficulties (respiratory failure),
• joint pain, muscle pain not caused by physical exertion,
• rash with white-silvery lesions (psoriasiform) or worsening of psoriasis symptoms,
• excessive hair loss,
• low blood sugar levels,
• memory loss, difficulty falling asleep (insomnia), nightmares,
• confusion, hallucinations, anxiety, disorientation, nervousness,
• reduced cerebral blood flow, dizziness,
• exacerbation of myasthenia symptoms (muscle weakness and pain in patients with this condition),
• tingling or numbness in limbs,
• sudden fainting or near-fainting episodes,
• ringing in the ears (tinnitus),
• abdominal pain, diarrhoea, dry mouth sensation, taste disturbances, indigestion,
• sexual dysfunction, decreased libido,
• weakness, fatigue.

Other adverse reactions reported with ophthalmic drops containing
phosphates:
In patients with severe damage to the transparent front part of the eye (cornea), phosphates may, very rarely, cause corneal clouding due to calcium deposits during treatment.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to gather more information on the safety of the medicine.

5. How to store Xalofree Combi

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

• Store Xalofree Combi in a refrigerator (at temperature from 2°C to 8°C). Do not freeze.
• Keep the bottle in the original packaging to protect from light.

After first opening of the bottle:

• There is no need to store the medicine in the refrigerator. Do not store above 25°C. Keep the bottle in the original outer packaging to protect from light.
• 2.5 ml bottle: shelf life after first opening: 30 days. 7.5 ml bottle: shelf life after first opening: 90 days.

Do not use this medicine after the expiry date stated on the carton and bottle. The expiry date refers to the last day of the stated month.
The marking "EXP" on the packaging indicates the expiry date, and "Lot" indicates the batch number.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures 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 millilitre (1 ml) of Xalofree Combi eye drop solution contains 50 micrograms of latanoprost and timolol maleate equivalent to 5 mg of timolol. One drop of the solution contains approximately 1.5 micrograms of latanoprost and 150 micrograms of timolol.
• Other ingredients are: sodium chloride, disodium phosphate, monosodium dihydrogen phosphate monohydrate, polysorbate 80, disodium edetate, sodium hydroxide (for pH adjustment), hydrochloric acid, diluted (for pH adjustment), water for injections.

What Xalofree Combi looks like and contents of the pack
Xalofree Combi is a colourless, clear solution.
The pack consists of an HDPE bottle with a multidose dropper pump, cap (HDPE), and a dosing aid, in a cardboard box.
Each 2.5 ml bottle contains not less than 60 drops.
Each 7.5 ml bottle contains not less than 180 drops.
Pack sizes:
1 bottle of 2.5 ml
1 bottle of 7.5 ml
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation 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