Timod

Package leaflet: Information for the patient

TIMOD 2.5 mg/ml Eye drops, solution, 5 mg/ml Eye drops, solution

Timolol maleate
Please read this leaflet carefully before 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 others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What TIMOD is and what it is used for

TIMOD is an eye drop that contains the active substance timolol maleate and belongs to a group
of medicines called beta-blockers, which work by reducing the pressure inside the
eye.
TIMOD is used in the treatment of:

• Elevated eye pressure (ocular hypertension);
• Chronic open-angle glaucoma: increased eye pressure caused by greater resistance in the outflow pathways;
• Aphakia (absence of the crystalline lens, i.e. the eye's internal lens), eye with glaucoma;
• Narrow iridocorneal angle (iris/the coloured part surrounding the pupil, cornea/the front part of the eye), and episodes in the other eye of closure of the iridocorneal angle, which may be spontaneous or due to medications;
• Pediatric glaucoma, when inadequately controlled with other therapies.

Consult your doctor if you do not feel better or feel worse after the prescribed duration of treatment.

2. What you should know before using TIMOD

Do not use TIMOD

• if you are allergic to timolol maleate, to other closely related chemical substances, or to any of the other ingredients of this medicine (listed in section 6);
• if you suffer from respiratory diseases (asthma, history of asthma, chronic obstructive pulmonary disease, severe bronchial hyperreactivity, allergic rhinitis);
• if you have heart failure not controlled by therapy;
• if you have cardiogenic shock;
• if you have conduction disorders of the heart (second- or third-degree atrioventricular block) in the absence of a pacemaker;
• if you have Prinzmetal's angina (an unusual form of angina caused by spasms of the coronary arteries);
• if you have sinoatrial node dysfunction (sinoatrial node disease, including sinoatrial block);
• if you have a slow heart rate (bradycardia: less than 45–50 beats per minute);
• if you have circulatory disorders (Raynaud’s disease or peripheral circulatory disorders);
• if you have untreated pheochromocytoma (a tumor causing sudden increases in blood pressure);
• if you have low blood pressure (hypotension);
• if you have corneal abnormalities (corneal dystrophies);
• in combination with floctafénine (a non-steroidal anti-inflammatory drug);
• in combination with sultopride (an antipsychotic drug).

Consider the general contraindications for systemic beta-blockers—i.e., those reaching all parts of the body—even though such effects are rare following ocular instillation.

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

Ocular
As with any treatment for glaucoma:

• have regular eye pressure measurements and corneal thickness assessments.

In closed-angle glaucoma, TIMOD alone is not sufficient to reopen the space between the iris and cornea (iridocorneal angle). In such cases, your doctor may prescribe an additional eye drop that constricts the pupil (a miotic agent).

Contact lenses
If you wear contact lenses, you may be at risk of developing intolerance due to reduced tear secretion caused by the beta-blocker.
Avoid wearing contact lenses during treatment with TIMOD.

Cardiovascular disorders
Your doctor will reduce the dosage if your heart rate drops below 50–55 beats per minute at rest, or if you experience symptoms related to slow heart rate (bradycardia), such as shortness of breath or dizziness.

Due to the negative dromotropic effect (slowing of electrical conduction) of beta-blockers, these medicines must be administered with caution if you have conduction disorders (first-degree atrioventricular block, sinoatrial node syndrome) or low blood pressure.

Before starting treatment, your doctor must rule out cardiac dysfunction (heart failure). If you have a history of severe heart disease, you should be closely monitored for signs of possible heart failure.

Metabolic disorders
Use with caution if you have a disturbance in blood water balance (metabolic acidosis).

Pheochromocytoma (adrenal gland tumor) under treatment
To control symptoms caused by the tumor, your doctor will prescribe alpha-blockers in addition to beta-blockers.

Diabetic patients
During the initial phase of treatment, your doctor may advise you to perform self-monitoring of blood sugar levels (glycemic profile). Signs of early low blood sugar (incipient hypoglycemia), such as increased heart rate (tachycardia), awareness of heartbeat (palpitations), and sweating, may be masked by beta-blockers.

Psoriasis (a skin condition characterized by redness and silvery-white scales)
Beta-blockers have been shown to worsen psoriasis. Therefore, if you suffer from this condition, your doctor will advise against using TIMOD.

Allergic reactions
If you are at risk of developing severe allergic (anaphylactic) reactions of any origin—particularly with iodinated contrast agents (used in X-ray imaging), anesthesia, non-steroidal anti-inflammatory drugs (floctafénine), or during allergen desensitization therapy—you should know that beta-blockers may worsen the reaction and make it unresponsive (resistant) to standard doses of adrenaline.

General anesthesia
If you are undergoing anesthesia, inform your doctor or anesthesiologist that you are being treated with beta-blockers.
Your doctor may consider it necessary to discontinue treatment for 48 hours.

Your doctor will advise you not to discontinue systemic (general) beta-blocker treatment:

• if you have coronary insufficiency. Your doctor will recommend continuing treatment up to the time of surgery, due to the risks associated with sudden discontinuation of beta-blockers;
• in emergency situations or when discontinuation is not feasible, your doctor may administer an adequate dose of atropine to prevent excessive vagal stimulation. The anesthesia will be performed using drugs causing minimal cardiac depression, and any blood loss will be appropriately compensated.

For athletes:
The use of this medicine without therapeutic need constitutes doping and may lead to a positive anti-doping test.

Other medicines and TIMOD
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Although the amount of beta-blocker absorbed systemically (into the bloodstream) after ocular instillation is low, the risk of drug interactions remains.

Therefore, consider the interactions observed with systemically administered beta-blockers.

Do not use TIMOD concomitantly with the following medicines, as it is contraindicated:

• Floctafénine (non-steroidal anti-inflammatory drug)
• Sultopride (antipsychotic drug)

Use TIMOD with caution if you are taking the following medicines, as such combinations are not recommended:

• Calcium channel blockers (Bepridil, Diltiazem, Verapamil). Timolol may enhance the effects of Bepridil on the heart's pacemaker, leading to excessive slowing of the heart rate (bradycardia), conduction disturbances (sinoatrial and atrioventricular block, sinus arrest), increased risk of ventricular arrhythmias (torsades de pointes), and heart failure. This combination should only be used under strict medical supervision with ECG monitoring, especially in elderly patients or at the beginning of treatment.

Be cautious when using TIMOD with the following medicines:

• Eye drops. If you are concurrently using eye drops containing adrenaline, regular eye examinations are necessary due to the risk of pupil dilation (mydriasis). Do not use two beta-blocking eye drops simultaneously.
• Amiodarone, a drug used for cardiac rhythm disorders (myocardial contractility, automaticity, conduction disturbances/suppression of compensatory sympathetic mechanisms). If you are taking amiodarone and timolol together, your doctor will closely monitor you via ECG.
• Halogenated inhaled anesthetics. If you are being treated with beta-blockers, inform your anesthesiologist, as the anti-adrenergic effect of beta-blockers may need to be counterbalanced during surgery with drugs having adrenergic-like effects.
• Baclofen, as it may increase the risk of low blood pressure (hypotension), particularly a sudden drop upon standing (orthostatic hypotension). Your doctor will monitor your blood pressure and, if necessary, adjust the dosage of your antihypertensive medication.
• Central antihypertensives, as they may cause a significant increase in blood pressure if therapy is abruptly discontinued. Your doctor will advise against sudden discontinuation and will monitor you closely.
• Insulin and oral hypoglycemic agents. All beta-blockers may mask symptoms of low blood sugar (hypoglycemia), such as palpitations and tachycardia. Especially at the beginning of treatment, perform more frequent self-monitoring of blood glucose levels.
• Lidocaine. Your doctor will perform careful clinical monitoring via ECG and, when possible, measure plasma lidocaine concentrations during combination therapy—even after discontinuation of the beta-blocker. The lidocaine dosage may be adjusted as needed.
• Drugs that may cause torsades de pointes (except sultopride), as they may increase the risk of ventricular arrhythmias, particularly torsades de pointes. Your doctor will perform close clinical monitoring via ECG.
• Propafenone, as it may cause cardiac rhythm abnormalities (myocardial contractility, automaticity) and conduction disturbances (suppression of compensatory sympathetic mechanisms). Close clinical monitoring via ECG is required.
• Urogenital alpha-blockers and antihypertensive alpha-blockers;
• Amifostine;
• Tricyclic antidepressants and neuroleptics, which may increase the risk of low blood pressure, particularly orthostatic hypotension;
• Non-steroidal anti-inflammatory drugs (NSAIDs), as they may reduce the antihypertensive effect;
• Other bradycardic drugs, as they may cause excessive slowing of the heart rate (bradycardia);
• Dihydropyridines, as they may cause hypotension and heart failure in patients with latent or uncontrolled heart failure (due to additive negative inotropic effects reducing excitability);
• Dipyridamole, as it may enhance the antihypertensive effect;
• Pilocarpine, as it may increase the risk of excessive bradycardia (additive bradycardic effects).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Use this medicine only when necessary and under direct medical supervision.

Pregnancy
Although no specific studies have been conducted, ophthalmic timolol solution should only be used during pregnancy after careful medical evaluation.

Breastfeeding
Timolol is excreted in breast milk. During breastfeeding, your doctor will decide whether to discontinue the drug or breastfeeding, due to potential adverse effects on the infant.
Since cases of low blood sugar (hypoglycemia) and slow heart rate (bradycardia) have been reported with beta-blockers that are poorly plasma protein-bound, as a precautionary measure, it is preferable to avoid breastfeeding if treatment is necessary.

Driving and using machines
TIMOD may slightly affect your ability to drive or operate machinery. When driving or using machinery, keep in mind that you may experience visual disturbances (difficulty focusing, double vision, drooping eyelids, frequent mild and transient episodes of blurred vision), and occasionally episodes of dizziness or fatigue.

3. How to use Timod

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.

Treatment may be initiated with the instillation of one drop of TIMOD 2.5 mg/ml eye drops every 12 hours. If the therapeutic response is insufficient, your doctor may increase the dosage by instructing you to administer one drop of TIMOD 5 mg/ml eye drops every 12 hours. If intraocular pressure remains at satisfactory levels, your doctor will advise you to continue treatment with a single daily administration.

Use in children and adolescents
Your doctor will advise you to start treatment with TIMOD 2.5 mg/ml eye drops, instilling one drop into the affected eye every 12 hours, in addition to other antiglaucoma therapy. If a satisfactory therapeutic effect is not achieved, your doctor may increase the dosage by instructing you to administer one drop of TIMOD 5 mg/ml into the affected eye every 12 hours.

If you use more TIMOD than you should
In case of accidental ingestion or overdose of TIMOD, inform your doctor immediately or go to the nearest hospital.
Symptoms you may experience in case of overdose are similar to those seen with systemically administered beta-blockers.

If you forget to use TIMOD
Do not use a double dose to make up for the missed dose.

If you stop using TIMOD
Do not stop treatment with beta-blockers abruptly, especially if you suffer from reduced blood flow to the heart (angina). Sudden discontinuation could cause you to develop a serious heart rhythm disorder (arrhythmia), reduced blood flow (myocardial infarction), or sudden death.
Your doctor will advise you to gradually reduce the dosage over a period of one or two weeks.

If you have any questions 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 everyone experiences them.
If you experience any of the following side effects, inform your doctor:

• Systemic lupus erythematosus (chronic inflammatory disease)
• Signs and symptoms of allergic reactions including a severe allergic reaction (anaphylaxis), swelling (angioedema), red itchy rash (urticaria), skin irritation (erythematous rash).
• Low blood sugar levels (hypoglycaemia).
• Headache (cephalalgia), dizziness, worsening of signs and symptoms of myasthenia gravis (a neuromuscular disease characterized by muscle weakness and fatigue), depression, insomnia, nightmares, decreased sexual desire (libido), impotence.
• Signs and symptoms of eye irritation including mild burning or stinging sensation at the beginning of treatment, eye inflammation (conjunctival hyperaemia), conjunctivitis, inflammation of the eyelid margin (blepharitis), corneal inflammation (keratitis), reduced corneal sensitivity (corneal hypoesthesia), dryness.
• Visual disturbances, including blurred vision, refractive errors (various focusing defects, in some cases due to discontinuation of miotic therapy which stimulates pupil constriction), drooping eyelids (ptosis), double vision (diplopia), choroidal detachment (detachment of the inner membrane of the eye) following filtering surgery (an incisional surgical procedure). In very rare cases, some patients with severe damage to the transparent layer at the front of the eye (cornea) developed cloudy areas on the cornea due to calcium accumulation during treatment.
• Fainting (syncope), awareness of heartbeat (palpitations), arrhythmia, slowed heart rate (bradycardia), low blood pressure (hypotension), heart failure, changes in heart rhythm (atrioventricular block), difficulty walking with calf pain (intermittent claudication), reduced blood flow to extremities (Raynaud's phenomenon, sensation of cold).
• Difficulty breathing (dyspnoea), cough, wheezing (bronchospasm), particularly in patients with pre-existing lung disease.
• Digestive disturbances (dyspepsia), dry mouth sensation (xerostomia), nausea, vomiting, diarrhoea, stomach pain (gastralgia).
• Hair loss (alopecia). Various skin disorders including red itchy rash (urticaria), hypersensitivity reactions, angioedema (angioneurotic oedema), skin irritation and redness (erythematous cutaneous rash), redness with silvery-white scales (psoriasiform rash or worsening of psoriasis).
• Fatigue, lack of energy and weakness (asthenia), chest pain.

In rare cases, antibodies produced by the body against itself (antinuclear antibodies) have been detected, which only exceptionally were associated with clinical symptoms resembling lupus, and which resolved upon discontinuation of treatment.

Reporting of side effects
If you experience any side effect, 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
www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Timod

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
Do not store above 25 °C.
The shelf life after first opening the bottle is 12 weeks.
Do not use this medicine if you notice that the solution is not clear.
The expiry date applies to the product stored in its original intact packaging and kept under proper storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package Contents and Other Information

What TIMOD Contains
TIMOD 2.5 mg/ml Eye Drops, Solution, 5 ml Bottle

• The active substance is timolol maleate. Each ml of eye drops contains 3.42 mg of timolol maleate (equivalent to 2.5 mg of timolol).
• Other components are: monobasic sodium phosphate; dibasic sodium phosphate; water for injections.

TIMOD 5 mg/ml Eye Drops, Solution, 5 ml Bottle

• The active substance is timolol maleate. Each ml of 5 mg/ml eye drops solution contains 6.84 mg of timolol maleate (equivalent to 5 mg of timolol).
• Other components are: monobasic sodium phosphate; dibasic sodium phosphate; water for injections.

Description of the Appearance of TIMOD and Contents of the Package
TIMOD Eye Drops are supplied as a solution, in the following pack sizes:
TIMOD 2.5 mg/ml eye drops, solution: 1 bottle of 5 ml
TIMOD 5 mg/ml eye drops, solution: 1 bottle of 5 ml

Marketing Authorization Holder
VISUFARMA S.p.A.
Via Canino, 21
Rome
Italy

Manufacturer
URSAPHARM, Industriestraße, D-66129 Saarbrücken, Germany