Nodofree combi

Package leaflet: Information for the user

Nodofree Combi, 20 mg/ml + 5 mg/ml, eye drops, solution
Dorzolamide + Timolol
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• 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. This medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

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

Nodofree Combi is an ophthalmic medicine in the form of sterile eye drops without preservatives, containing two active substances: dorzolamide and timolol.

• Dorzolamide belongs to a group of medicines called "carbonic anhydrase inhibitors".
• Timolol belongs to a group of medicines called "beta-adrenergic receptor blockers" (beta-blockers). These medicines together reduce intraocular pressure through two different mechanisms.

Nodofree Combi is indicated for the treatment of glaucoma to lower elevated intraocular pressure, when treatment with eye drops containing only a beta-adrenergic receptor blocker is insufficient.

2. Important information before using Nodofree Combi

When not to use Nodofree C

• if the patient is allergic to dorzolamide hydrochloride, timolol maleate, or any of the other ingredients of this medicine (listed in section 6);
• if the patient currently has or has previously had respiratory disorders such as asthma or severe chronic obstructive pulmonary disease (a serious lung condition that may cause wheezing, difficulty breathing, and/or persistent cough);
• if the patient has bradycardia (slow heart rate), heart failure, or cardiac arrhythmias (irregular heartbeat);
• if the patient has severe kidney disease or severe kidney function impairment, or a history of kidney stones;
• if the patient has excessive blood acidification due to accumulation of chloride ions in the body (hyperchloremic acidosis).

If in doubt whether Nodofree Combi can be used, consult a doctor or pharmacist.
Warnings and precautions
Before starting treatment with Nodofree Combi, discuss it with your doctor.
Inform your doctor about all current or past eye conditions and medical disorders, especially if the patient has:

• ischemic heart disease (symptoms include chest pain or pressure, shortness of breath, or a choking sensation), heart failure, or low blood pressure;
• disturbances in heart rate, such as bradycardia;
• breathing difficulties, asthma, or chronic obstructive pulmonary disease;
• conditions related to poor blood circulation (such as Raynaud's disease or Raynaud's syndrome);
• diabetes, because timolol may mask the signs and symptoms of hypoglycemia (low blood sugar);
• hyperthyroidism, because timolol may mask its signs and symptoms;

Before undergoing surgery, inform the attending physician about using Nodofree Combi, as timolol may alter the effects of certain anesthetic drugs. Also inform the doctor about any drug allergies or anaphylactic reactions.
Inform the doctor if the patient experiences muscle weakness or has been diagnosed with myasthenia gravis.
If eye irritation or any new eye problem occurs, such as eye redness or eyelid swelling, consult a doctor immediately.
If the patient suspects that Nodofree Combi is causing an allergic reaction or hypersensitivity (e.g., skin rash, severe skin reaction, skin redness, or itchy eyes), stop using the medicine immediately and contact a doctor without delay.
Inform the doctor if an eye infection occurs, the eye is injured, after eye surgery, or if a reaction occurs accompanied by new or worsening symptoms.
After ocular administration, Nodofree Combi may cause systemic effects.
No studies have been conducted on the use of Nodofree Combi in patients wearing contact lenses. Patients using soft contact lenses should consult their doctor before using Nodofree Combi. Contact lenses must be removed before instilling the drops and may be reinserted at least 15 minutes after administration.

Use in children
Experience with the use of dorzolamide hydrochloride combined with timolol maleate (in a formulation containing a preservative) in infants and children is limited.

Use in elderly patients
In clinical studies, dorzolamide hydrochloride combined with timolol maleate (in a formulation containing a preservative) showed similar effects in elderly and younger patients.

Use in patients with liver function disorders
Inform the doctor about any current or past liver diseases.

Interaction of Nodofree Combi with other medicines
Nodofree Combi may affect the action of other medicines, or other medicines taken by the patient may affect the action of Nodofree Combi. This also applies to other ophthalmic anti-glaucoma medications. Inform the doctor about taking or planning to take antihypertensive drugs, cardiac medications, or antidiabetic agents. Inform the doctor or pharmacist about all medicines currently or recently used, as well as any medicines the patient intends to use. This is particularly important when:

• taking antihypertensive drugs or medications for heart conditions (such as calcium channel blockers, beta-adrenergic receptor antagonists, or digoxin);
• taking medications for cardiac arrhythmias or to restore regular heart rhythm (such as calcium channel blockers, beta-adrenergic receptor antagonists, or digoxin);
• using other eye drops containing beta-blockers;
• taking other carbonic anhydrase inhibitors, such as acetazolamide;
• taking monoamine oxidase inhibitors (MAOIs);
• taking parasympathomimetic (cholinergic) drugs, which may be used to treat urinary disorders. Parasympathomimetic drugs are sometimes also used to restore normal intestinal motility;
• taking opioids such as morphine, used to treat moderate to severe pain;
• taking antidiabetic medications;
• taking antidepressants such as fluoxetine and paroxetine;
• taking chemotherapeutic sulfonamides;
• taking quinidine (a drug used in the treatment of heart conditions and certain forms of malaria).

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Use during pregnancy
Nodofree Combi should not be used during pregnancy.
Use during breastfeeding
This medicine should not be used during breastfeeding. Timolol may pass into human milk. Before taking any medicine during breastfeeding, consult the attending physician.

Driving and operating machinery
No studies have been conducted on the effect on the ability to drive or operate machinery. Some adverse effects associated with the use of Nodofree Combi, such as blurred vision, may affect the ability to drive and/or operate machinery. Patients who feel unwell or experience blurred vision should not drive or operate machinery until these symptoms resolve.

3. How to use Nodofree Combi

This medicine should always be used exactly as directed by the doctor. If in doubt, consult
your doctor or pharmacist.
Your doctor will determine the appropriate dose and duration of treatment.
The recommended dose is one drop into the affected eye(s) in the morning and evening.
If other eye drops are being used in addition to Nodofree Combi, wait at least 10 minutes before
administering the next medicine. Ointments should be applied last.
Do not change the dose of this medicine without first consulting your doctor.
If you have difficulty administering the drops, ask a family member or caregiver for help.
Nodofree Combi is a sterile solution that does not contain preservatives. See section 6

• What Nodofree Combi looks like and contents of the pack

Ensure that no part of the bottle touches the eye or surrounding areas. This could lead to
eye injury as well as bacterial contamination of the bottle, which may result in eye infection
causing serious eye damage or even loss of vision. To avoid possible contamination of the
bottle, wash your hands before using this medicine and avoid contact between the dropper tip
and any surface.

Before instilling eye drops:

• At first use, before administering drops into the eye, the patient should practice using the dropper bottle by slowly squeezing it until one drop is released, away from the eye.
• If the patient is confident they can instill a single drop, they should assume the most comfortable position for instillation (sitting, lying on the back, or standing in front of a mirror).

Instructions for use:

1. Before instilling the medicine, the patient should thoroughly wash their hands.
2. Do not use the medicine if the packaging or bottle is damaged.
3. Before first use, unscrew the cap after ensuring that the tamper-evident ring on the cap is intact. While unscrewing, the patient will feel slight resistance until the ring breaks ( see Figure 1. ).
4. If the tamper-evident ring is loose, remove it before using the medicine, as it may fall into the eye and cause injury.
5. Tilt the head backward and gently pull down the lower eyelid with a finger to form a "pocket" between the eyeball and eyelid ( see Figure 2. ). (Avoid contact between the dropper tip and the eye, eyelids, or fingers.)
6. Instill one drop by gently squeezing the bottle. Squeeze the bottle slowly in the middle section so that a drop enters the patient's eye. Note that there may be a delay of several seconds between squeezing the bottle and the release of the drop. Do not squeeze the bottle too hard ( see Figure 3. ). Patients should consult their doctor, pharmacist, or nurse if they have any doubts about how to use the medicine.
7. Close the eye and press gently on the inner corner of the eye with a finger for about two minutes. This helps prevent the medicine from being absorbed into the rest of the body.
8. Avoid contact between the dropper tip and the eye, eyelids, or fingers.
9. If the doctor has prescribed drops for the other eye, repeat steps 5, 6, and 7.
10. After use and before closing the bottle, to remove any residual liquid from the tip, shake the bottle gently downward without touching the dropper tip to remove any remaining liquid. This is necessary to ensure proper function

for instilling subsequent drops. Immediately after use, tightly recap the bottle ( see Figure

1. 4. ). If the drop misses the eye, repeat the instillation attempt.

Figure 1. Figure 2. Figure 3. Figure 4.
Use of a higher than recommended dose of Nodofree Combi
If too many drops are instilled or if the contents of the bottle are swallowed, symptoms such as
dizziness, breathing difficulties, or a sensation of slowed heart rate may occur. Seek immediate
medical advice from a doctor.
Missed dose of Nodofree Combi
Nodofree Combi should be used exactly as directed by the doctor.
If a dose is missed, administer it as soon as possible. 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.
Stopping treatment with Nodofree Combi
Consult your doctor before stopping treatment with this medicine.
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.
Adverse effects:
If any of the following adverse effects occur, stop using this medicine and seek medical help immediately, as they may be symptoms of an allergic reaction.
Generalised allergic reactions, including subcutaneous swelling, may occur in the facial area and limbs and may cause airway obstruction and difficulty swallowing, breathlessness, urticaria or itchy rash, localised and generalised rash, itching, and severe, sudden and life-threatening allergic reaction.

Treatment with eye drops can generally be continued unless the adverse effects are severe. If concerned, consult a doctor or pharmacist. Do not discontinue treatment with Nodofree Combi without consulting a doctor.

The following adverse effects have been reported during clinical trials or after marketing of the medicine related to dorzolamide hydrochloride and timolol maleate (in preservative-free form), or after administration of one of the active substances:

Very common (occur in more than 1 in 10 patients):

• burning and stinging sensation in the eye, altered taste sensation.

Common (occur in less than 1 in 10 patients):

• redness of the eyes and surrounding skin (eyes), tearing or itching of the eye(s), corneal abrasions (damage to the front layer of the eyeball), swelling and/or irritation of the eyes and surrounding skin (eyes), foreign body sensation in the eye, reduced corneal sensitivity (inability to feel a foreign body in the eye and inability to feel pain), eye pain, dry eyes, blurred vision, headache, sinusitis (feeling of nasal congestion or fullness), nausea, fatigue and feeling of tiredness.

Uncommon (occur in less than 1 in 100 patients):

• dizziness, depression, iritis, visual disturbances, including refractive changes (in some cases due to discontinuation of miotic drugs), bradycardia (slowed heart rate), fainting, dyspnoea (shortness of breath), dyspepsia, kidney stones.

Rare (occur in less than 1 in 1000 patients):

• systemic lupus erythematosus (an autoimmune disease which may cause inflammation of internal organs), tingling or numbness of hands or feet, insomnia, nightmares, memory loss, worsening of objective and subjective symptoms of myasthenia (muscle disorder), decreased libido, stroke, transient myopia which may resolve after discontinuation of the medicine, retinal detachment following filtration surgery of the subretinal vascular layer, which may cause visual disturbances, ptosis (drooping eyelid, with eyelid half-closed), double vision, formation of crusts on the eyelids, corneal oedema (with subjective visual disturbances), low intraocular pressure, tinnitus, hypotension (low blood pressure), cardiac arrhythmias (changes in heart rhythm or rate), congestive heart failure (heart disease characterised by breathlessness and swelling of feet and legs due to fluid accumulation), oedema (fluid accumulation), palpitations (rapid and/or irregular heartbeat), cerebral ischaemia (reduced blood flow to the brain), chest pain, strong heartbeat which may be rapid or irregular (palpitations), myocardial infarction, Raynaud's phenomenon, swelling of hands and feet or cold hands and feet and impaired circulation in upper and lower limbs, leg muscle cramps and/or leg pain while walking (claudication), breathlessness, respiratory failure, rhinitis (nasal inflammation), nosebleeds, bronchoconstriction in the lungs, cough, throat irritation, dry mouth, diarrhoea, contact dermatitis, hair loss, white-silvery rash (psoriasis-like rash), Peyronie's disease (which may lead to penile curvature), allergic reactions such as rash, urticaria, itching, and in rare cases swelling of the lips, eyelids and oral cavity, wheezing or severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Like other medicines administered locally into the eyes, timolol is absorbed into the bloodstream, which may result in adverse effects similar to those observed after oral administration of beta-adrenergic blocking agents. Adverse effects occur less frequently with topical ophthalmic use than with oral or injectable administration of these medicines.

Among the additional adverse effects listed, reactions typical of the therapeutic class of beta-adrenergic blocking agents used in ophthalmic disorders are included:

Not known (frequency cannot be estimated from available data):

• low blood sugar levels, heart failure, cardiac arrhythmias, abdominal pain, vomiting, muscle pain unrelated to physical exertion, sexual dysfunction, hallucinations and foreign body sensation in the eye (feeling that something is in the eye), tachycardia (increased heart rate), increased blood pressure.

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 Reactions to Medicinal Products, 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 effects can also be reported to the marketing authorisation holder.

Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Nodofree Combi

Store below 30°C.
After first opening the bottle – store for 90 days at a temperature below 25°C.
This medicine should be stored in a place out of sight and out of reach of children.
Do not use this medicine after the expiry date stated on the label and on the carton.
The expiry date refers to the last day of the stated month.
The marking on the packaging following the abbreviation "EXP" indicates the expiry date, and following the abbreviation "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 in use. This will help protect the environment.

6. Contents of the pack and other information

What Nodofree Combi contains

• The active substances are dorzolamide and timolol. Each ml contains 20 mg dorzolamide (as dorzolamide hydrochloride 22.26 mg) and 5 mg timolol (as timolol maleate 6.83 mg). Each drop (approximately 35 µl) contains 0.70 mg dorzolamide and 0.18 mg timolol.
• The other ingredients are: hydroxyethylcellulose 6400-11900 mPa·s, mannitol, sodium citrate, sodium hydroxide (for pH adjustment), water for injections.

What Nodofree Combi looks like and contents of the pack
Nodofree Combi is a clear, colourless, slightly viscous solution.
The medicine is available in white 5 ml bottles (LDPE), with a multidose dropper (HDPE) preventing bacterial contamination of the solution, thanks to a system comprising a silicone membrane and filtration of the air drawn into the bottle, with a tamper-evident closure cap made of HDPE, packed in a cardboard box.
Pack sizes:
1 x 5 ml
3 x 5 ml
Not all pack sizes may be marketed.

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

Manufacturer
Rafarm S.A.
Thesi Pousi Xatzi Agiou Louka
Paiania, 190 02
Greece