Tipifree combi

Package leaflet: Information for the patient

Tipifree Combi, 40 micrograms/ml + 5 mg/ml, eye drops, solution
Travoprost + Timolol
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, 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.

Table of contents

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

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

Tipifree Combi eye drops is a combination of two active substances (travoprost and timolol). Travoprost is a prostaglandin analogue that works by increasing the outflow of aqueous humour from the eye, thereby reducing intraocular pressure. Timolol is a beta-blocker that acts by reducing the production of fluid inside the eye. Together, these two substances help lower intraocular pressure.
Tipifree Combi eye drops are used to treat elevated intraocular pressure in adults, including elderly patients. This pressure may lead to the development of a condition called glaucoma.

2. Information before using Tipifree Combi

When not to use Tipifree Combi

• if the patient is allergic to travoprost, prostaglandins, timolol, beta-blocking agents, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has or has previously had respiratory disorders such as: asthma, severe chronic obstructive pulmonary disease [severe lung disease which may cause wheezing, breathing difficulties and (or) long-lasting cough], or other types of respiratory disorders;
• if the patient has severe allergic rhinitis (hay fever);
• if the patient has slow heart rate, heart failure, heart rhythm disorders (irregular heartbeat), or cardiogenic shock (a severe condition characterized by a significant drop in blood pressure leading to multi-organ failure);
• if the surface of the eye is clouded. If any of the conditions listed above apply to the patient, consult a doctor.

Warnings and precautions
Before starting to use Tipifree Combi, discuss with your doctor if any of the following medical conditions are currently present or have occurred in the past:

• coronary heart disease (symptoms may include chest pain or tightness, difficulty breathing, shortness of breath), heart failure, low blood pressure;
• heart rhythm disorders such as slow heartbeat;
• breathing difficulties, asthma, or chronic obstructive pulmonary disease;
• circulatory disorders (such as Raynaud's disease or Raynaud's syndrome);
• diabetes or tendency to spontaneous hypoglycaemia (because timolol may mask symptoms of hypoglycaemia - low blood sugar levels);
• hyperthyroidism (because timolol may mask subjective and objective symptoms of thyroid disease);
• myasthenia (chronic neuromuscular weakness);
• cataract surgery;
• eye inflammation, corneal diseases.

If the patient is to undergo any surgical procedure, inform the doctor about the use of Tipifree Combi, as timolol may alter the effect of certain anaesthetic drugs.
Cases of choroidal detachment after filtration surgery have been reported during administration of drugs reducing aqueous humour production (e.g. timolol, acetazolamide).
If the patient develops any severe allergic reaction (skin rash, redness and itching of the eye) while using Tipifree Combi, regardless of the cause, treatment with adrenaline may not be sufficiently effective. It is therefore important to inform the doctor about the use of Tipifree Combi if the patient is to receive any other treatment.
Tipifree Combi may change the colour of the iris (the coloured part of the eye); this change may be permanent.
Tipifree Combi may increase the length, thickness, colour and (or) number of eyelashes and may cause abnormal hair growth on the eyelids.
Travoprost may be absorbed through the skin and therefore should not be used by pregnant women or women planning to become pregnant. If any amount of the medicine comes into contact with the skin, wash it off immediately.

Children and adolescents
Tipifree Combi is not intended for use in children and adolescents under 18 years of age.

Tipifree Combi and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without prescription.
Tipifree Combi may alter the effect of other concomitantly administered medicines, or these medicines may alter the effect of Tipifree Combi; this also applies to other medicines used in the treatment of glaucoma.
Inform the doctor if the patient is taking or intends to take other medicines that lower blood pressure, used in heart diseases (including quinidine, used in the treatment of heart diseases and certain forms of malaria), antidiabetic medicines or antidepressants such as fluoxetine or paroxetine.
An additive effect, manifesting as hypotension and (or) significant slowing of heart rate, may occur when beta-adrenergic blocking agents in the form of eye drops are used simultaneously with medicines used in heart diseases (such as calcium channel blockers, beta-adrenergic blocking agents, antiarrhythmics including amiodarone, digitalis glycosides, parasympathomimetics or guanethidine).

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor before using this medicine.
Tipifree Combi must not be used during pregnancy unless the doctor considers it necessary. If the patient could become pregnant, she should use appropriate contraceptive methods during treatment with this medicine.
Tipifree Combi must not be used if the patient is breastfeeding. Tipifree Combi may pass into breast milk.

Driving and using machines
For some time after instillation of Tipifree Combi, vision may be blurred. Tipifree Combi may also cause hallucinations, dizziness, nervousness or fatigue in some patients.
Until these symptoms resolve, the patient must not drive or operate machinery.

Tipifree Combi contains macrogolglycerol hydroxystearate 40 and propylene glycol (E 1520)
The medicine may cause skin reactions and skin irritation.

3. How to use Tipifree Combi

This medicine should always be used exactly as directed by the doctor. If in doubt, consult
your doctor or pharmacist.
The recommended dose is one drop into the conjunctival sac of the affected eye or eyes, once daily,
either in the morning or in the evening. The medicine should be used every day at the same time.
Tipifree Combi may be used in both eyes only if so directed by the doctor.
Tipifree Combi should be used only as eye drops.
If other eye drops are used in addition to Tipifree Combi, at least 5 minutes should be left between
instillation of Tipifree Combi and the application of other eye drops.
If the patient wears soft contact lenses, do not instill Tipifree Combi while wearing them. After
instilling the drop, wait 15 minutes before inserting contact lenses.

Instructions for use
Follow the instructions below to properly use Tipifree Combi.

1. Wash your hands and sit or stand comfortably.
2. Remove the protective cap (Figure 1.).
3. Hold the bottle with the tip pointing downwards, placing your thumb on the shoulder of the bottle and the other fingers on the bottom (Figure 2.). Before first use, press the bottle several times—approximately 13 times—until the first drop appears.
4. Tilt your head backward and gently pull down the lower eyelid to form a small pocket between the eye and the eyelid.
5. Position the tip of the bottle close to the eye, without touching it.
6. Do not let the dropper touch the eye, eyelid, surrounding areas, or any other surface. This may contaminate the drops and cause an infection.
7. Hold the bottle as described above (Figure 2.), vertically above the eye, and gently press the pump mechanism to release one drop into the eye, then release the lower eyelid (Figure 3.).
8. Press a finger against the inner corner of the affected eye near the nose (Figure 4.). Hold for 2 minutes, keeping the eye closed.
9. Instill the drop into the other eye if so directed by the doctor.
10. Immediately after use, replace the cap on the bottle tip.
11. If the drop missed the eye, repeat the instillation.

Figure 1. Figure 2. Figure 3. Figure 4.
Only one bottle should be used at a time.
Tipifree Combi should be used for as long as directed by the doctor.

Overdose of Tipifree Combi
If more Tipifree Combi has been used than recommended, rinse the eyes with warm water. Do not
instill any more drops until the next scheduled dose.

Missed dose of Tipifree Combi
If a dose of Tipifree Combi has been missed, continue using the medicine as usual. Do not use a
double dose to make up for the missed dose. The dose administered to the affected eye(s) should
not exceed one drop per day.

Stopping Tipifree Combi treatment
If treatment with Tipifree Combi is stopped without consulting a doctor, intraocular pressure may
not be controlled, which could lead to vision loss.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Usually, you can continue using the eye drops unless the adverse effects are severe.
If you have any concerns, contact your doctor or pharmacist. Do not stop using
Tipifree Combi without consulting your doctor.

Very common adverse effects (occur in more than 1 out of 10 patients)
Eye-related symptoms
Eye redness.

Common adverse effects (occur in less than 1 out of 10 patients)
Eye-related symptoms
Inflammation of the surface of the eye with damage to the eye surface, eye pain, blurred vision,
abnormal vision, dry eye, eye itching, eye discomfort, objective and subjective
symptoms of eye irritation (e.g. burning, stinging).

Uncommon adverse effects (occur in less than 1 out of 100 patients)
Eye-related symptoms
Inflammation of the surface of the eye, eyelid inflammation, conjunctival swelling, increased eyelash growth,
iritis, eye inflammation, light sensitivity, limited vision, eye fatigue, eye allergy, eye swelling, increased tear production, eyelid redness, changes in eyelid colour, skin darkening (around the eye).
General symptoms
Allergic reaction to the active substance, dizziness, headache, increased or decreased
blood pressure, shortness of breath, excessive hair growth, postnasal drip, skin inflammation and itching, slowed heart rate.

Rare adverse effects (occur in less than 1 out of 1,000 patients)
Eye-related symptoms
Thinning (damage) of the eye surface, inflammation of the meibomian glands, rupture
of blood vessels in the eye, crusts on the eyelid margins, abnormal eyelash position,
abnormal eyelash growth.
General symptoms
Nervousness, irregular heartbeat, hair loss, voice disorders, breathing difficulties,
cough, throat irritation, sore throat, chills, abnormal blood test results indicating
liver function abnormalities, urticaria, skin discoloration, excessive thirst, fatigue,
nasal discomfort, blue-green discoloration of urine, pain in hands and feet.

Adverse effects with unknown frequency (frequency cannot be estimated from available data)
Eye-related symptoms
Macular edema, eyelid drooping (giving the impression of half-closed eyes), eye hollowing (eyes appear sunken),
changes in iris colour (coloured part of the eye), corneal disorders.
General symptoms
Rash, heart failure, chest pain, stroke, fainting, depression, asthma,
increased heart rate, tingling or numbness sensation, palpitations, swelling
of lower limbs, taste disturbances.

Additional information:
Tipifree Combi is a combination of two active substances, travoprost and timolol.
Travoprost and timolol (a beta-adrenergic blocking agent), like other ophthalmic medications,
are absorbed into the bloodstream. This may lead to adverse effects similar to those
observed when beta-adrenergic blocking agents are administered orally or by injection.
The frequency of adverse effects after ophthalmic administration is lower than after oral or
injected administration.
The adverse effects listed below include those observed with the entire class of beta-adrenergic blocking agents used in ophthalmology or those observed after the use of travoprost alone:

Eye-related symptoms
Blepharitis, corneal inflammation, retinal detachment after filtration surgery of the layer beneath the retina containing blood vessels, which may lead to vision disturbances, decreased corneal sensitivity, corneal ulceration (damage to the front layer of the eyeball), double vision, conjunctival papillae, eye discharge, swelling around the eyes, eyelid itching, eyelid eversion with redness, eye irritation and excessive tearing, blurred vision (indications of lens opacification), swelling of part of the eye (choroid), eyelid rash, halo vision, decreased eye sensitivity, pigmentation inside the eye, pupil dilation, change in eyelash colour, change in eyelash texture, abnormal visual field.

General symptoms
Ear and labyrinth disorders: dizziness with spinning sensation, tinnitus.
Heart and circulatory system: slowed heartbeat, palpitations, edema (fluid retention),
changes in heart rhythm or rate, congestive heart failure (heart disease causing
shortness of breath and swelling of ankles and legs due to fluid accumulation),
arrhythmia-related disease, heart attack, low blood pressure, Raynaud's syndrome,
coldness in hands and feet, reduced blood flow to the brain.
Respiratory system: bronchoconstriction in the lungs (mainly in patients with pre-existing conditions), nasal discharge or nasal congestion, sneezing (due to allergy), breathing difficulties, nosebleeds, dryness of the nasal mucosa.
Nervous system and general disorders: difficulty falling asleep (insomnia), nightmares, memory loss, hallucinations, loss of strength and energy, anxiety (excessive emotional unease).
Gastrointestinal system: taste disturbances, nausea, indigestion, diarrhea, dry mouth, abdominal pain, vomiting, and constipation.
Allergy: worsening of allergic symptoms, generalized allergic reactions involving skin swelling in areas such as the face and limbs, which may cause airway obstruction and difficulties in swallowing and breathing, localized or generalized rash, itching, severe and sudden life-threatening allergic reaction.
Skin: silver-white rash (resembling psoriasis) or worsening of psoriasis, skin peeling, abnormal hair texture, allergic dermatitis with itchy rash and redness, hair colour changes, loss of eyelashes or eyebrows, itching, abnormal hair growth, skin redness.
Musculoskeletal system: worsening of objective and subjective symptoms of myasthenia gravis (muscle disease), unusual sensations such as chills and tingling, muscle weakness/fatigue, muscle pain not caused by physical exercise, joint pain.
Renal and urinary disorders: difficulty and pain during urination, urinary incontinence.
Reproductive system: sexual dysfunction, decreased libido.
Metabolism: low blood sugar levels, increased prostate-specific antigen (PSA) levels.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 4921 301
Fax: +48 22 4921 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the responsible entity.
By reporting adverse effects, additional information on the safety of the medicine can be collected.

5. How to store Tipifree Combi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and outer packaging
after: EXP. The expiry date refers to the last day of the stated month.
Do not store above 25°C. Store the bottle in the original outer packaging to protect from light.
Do not freeze.
Shelf life after first opening:

• bottle containing 2.5 ml – 30 days;
• bottle containing 7.5 ml – 90 days. The date of opening should be recorded in the space provided on the box. After first opening of the bottle: Do not store above 30°C.

Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Following this advice helps protect the environment.

6. Contents of the pack and other information

What Tipifree Combi contains

• The active substances are travoprost and timolol. Each ml contains 40 micrograms of travoprost and 5 mg of timolol (as timolol maleate).
• Other ingredients are: boric acid; macrogolglycerol hydroxystearate 40; propylene glycol (E 1520); sodium chloride; mannitol; sodium hydroxide (for pH adjustment); purified water.

What Tipifree Combi looks like and contents of the pack
Tipifree Combi is a colourless, clear solution.
The packaging consists of an HDPE bottle with a multi-dose dropper pump (PP, HDPE, LDPE), an HDPE cap, and a dosing aid (PP), 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 sizes:
1 bottle of 2.5 ml
1 bottle of 7.5 ml
Not all pack sizes may be marketed.

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

Manufacturer
Jadran - Galenski Laboratorij d.d.
Svilno 20
51000 Rijeka
Croatia