CARTEOL 1 % Eye Drops Solution Bottle/3ml

Eye drops in solution.
Dropper bottle of 3 mL. Box of 1.

For 100 mL:
Carteolol hydrochloride: 1 g

Excipients with known effect:

This medicinal product contains 0,15 mg of benzalkonium chloride and 4,2 mg of phosphates per unit volume of 3 mL (see sections Warnings and precautions and Adverse effects).

Excipients:

• Intraocular hypertension.
• Chronic open-angle glaucoma.

Dosage

The eye drops are available in two strengths, 1 % and 2 %.

In adults

The recommended dose is one drop 2 times a day (morning and evening) in the affected eye. It is recommended to start treatment by instilling one drop of carteolol eye drops in the lowest strength into the affected eye, 2 times a day (morning and evening).

If efficacy is insufficient (see below), switch to a more concentrated eye drop solution.

Paediatric population

The use of these eye drops is not recommended in children and adolescents due to the lack of safety and efficacy data.

Method of administration

Ophthalmic use.

• To administer the treatment, instil one drop into the eye while looking upwards and gently pulling the lower eyelid down, close the eye for a few seconds,
• With the eye closed, carefully wipe away the excess,
• Replace the cap on the bottle after each use.

In a number of cases, the daily administration of a single drop of carteolol eye drops may be sufficient, particularly when intraocular pressure has been maintained at satisfactory levels.

The ophthalmologist may, if deemed necessary, combine carteolol eye drops with one or more other antiglaucoma treatments (topical and/or systemic).

Concomitant eye drops must be administered at least 15 minutes before CARTEOL.

Systemic absorption may be reduced by nasolacrimal occlusion or by closing the eyelids for 2 minutes. This method may help reduce systemic adverse effects and increase local efficacy.

However, normalisation of intraocular pressure with carteolol eye drops sometimes requires several weeks; therefore, evaluation of the treatment should include measurement of intraocular pressure and examination of the cornea at the start of treatment and, consequently, regularly after a treatment period of approximately 4 weeks.

Switching from a previous treatment

When carteolol eye drops are to take over from another anti-glaucoma eye drop, the latter eye drop must be stopped at the end of a full day of treatment, and carteolol eye drops must be administered the following day at a rate of one drop in the affected eye twice a day.

In case of insufficient efficacy, a more concentrated eye drop should be used.

If carteolol eye drops are to be substituted for several associated anti-glaucoma agents, the withdrawals should concern only one medicine at a time.

When myotic eye drops are substituted by carteolol eye drops, a refraction examination may prove necessary once the effects of the myotics have disappeared.

The medical prescription will be accompanied by monitoring of intraocular pressure, especially when starting treatment.

The contraindications of systemically administered beta-blockers should be kept in mind, although systemic effects of beta-blockers are only observed exceptionally after ocular instillation:

• Hypersensitivity to the active substance or to any of the excipients listed in section Composition.
• Conditions associated with bronchial hyperreactivity, in particular asthma or a history of asthma, and severe chronic obstructive bronchopneumopathy.
• Heart failure.
• Cardiogenic shock.
• Second- and third-degree atrioventricular blocks not controlled by a pacemaker.
• Sinus node disease (including sino-atrial block).
• Sinus bradycardia.
• Untreated pheochromocytoma.

Ocular

• Other beta-blocking agents:
  The effect on intraocular pressure or the known effects of systemic beta-blockers may be increased when topical beta-blocker is administered to patients already receiving a systemic beta-blocker. The response of these patients should be closely monitored. The use of two topical beta-blockers is not recommended (see section Interactions).
• Where this eye drop is administered to reduce intraocular pressure in patients with angle-closure glaucoma, a myotic must be associated.
  In effect, in these patients, the immediate objective of treatment is the reopening of the angle, which requires the use of a myotic in order to obtain pupillary constriction, carteolol having little or no effect on the pupil.
• Choroidal detachments have been observed after glaucoma filtration surgery with the administration of treatments that reduce aqueous humor secretion (e.g., timolol, acetazolamide).
• Contact lens wearers:
  • There is a risk of contact lens intolerance due to decreased tear secretion, generally related to beta-blockers:
  • This medicine contains benzalkonium chloride.
  • Benzalkonium chloride may deposit on soft contact lenses and alter their colour; therefore, this eye drop must not be used in the presence of soft lenses. Contact lenses must be removed before instillation of the drops and must not be reinserted before a minimum period of 15 minutes after use of this eye drop.
• Benzalkonium chloride is known to cause eye irritation, dry eye syndrome symptoms, and may affect the tear film and corneal surface. Should be used with caution in patients with dry eye and those at risk of corneal damage.
  The patients should be monitored in case of prolonged use.
• A decrease in sensitivity to carteolol may appear after prolonged treatment. In long-term treatments, the absence of therapeutic escape should be checked every year.

Corneal diseases

Ophthalmic beta-blockers may cause ocular dryness. Patients with corneal diseases should be treated with caution.

General

As with other topical ophthalmic medicinal products, cartéolol hydrochloride is absorbed into the systemic circulation. Due to the presence of a beta-adrenergic component, cartéolol hydrochloride, cardiovascular and pulmonary adverse reactions and other adverse reactions identical to those seen with systemically administered beta-adrenergic blocking agents may occur. The frequency of systemic adverse reactions after ophthalmic administration is lower than after systemic administration. To reduce systemic absorption, see section Dosage and administration.

Athletes

Athletes are advised that this medicine contains an active substance that may cause a positive reaction in tests carried out during anti-doping controls.

Discontinuation of treatment

Never abruptly interrupt systemic beta-blocker treatment, particularly in patients with angina: sudden withdrawal may lead to serious cardiac rhythm disorders, myocardial infarction or sudden death.

The dose should be reduced gradually, i.e. over one to two weeks.

Cardiac disorders

In patients with cardiovascular diseases (for example, coronary artery disease, Prinzmetal's angina and heart failure) or hypotension, beta-blocker treatment must be carefully evaluated and treatment with other active substances should be considered. In these patients, monitoring should be carried out to look for signs of worsening of these conditions or adverse reactions.

Due to their negative dromotropic effect, beta-blockers should be prescribed with caution to patients with first-degree atrioventricular block.

Bradycardia

If the heart rate falls below 50-55 beats per minute at rest and the patient presents symptoms related to bradycardia, the dose should be reduced.

Vascular disorders

Patients with severe peripheral circulatory disorders (i.e. severe forms of the disease or Raynaud's syndrome) should be treated with caution.

Respiratory disorders

In asthmatic patients, respiratory manifestations, including death from bronchospasm, have been reported following administration of certain ophthalmic beta-blockers.

CARTEOL should be administered with caution in patients with mild to moderate chronic obstructive pulmonary disease (COPD) and should only be administered if the benefit appears to outweigh the risk.

Hypoglycaemia/Diabetes

Beta-blockers should be administered with caution in patients prone to spontaneous hypoglycaemia or in patients with unstable diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycaemia.

Pheochromocytoma

The use of beta-blockers in the treatment of hypertension due to treated pheochromocytoma requires close monitoring of blood pressure.

Elderly patients, patients with renal and/or hepatic impairment

In these at-risk subjects, and when a beta-blocker eye drop is co-administered with a systemic beta-blocker, dose adjustment is often necessary.

Psoriasis

Worsening of the disease has been reported under beta-blocker treatment; the indication should be weighed carefully.

Allergic/anaphylactic reactions

During beta-blocker therapy, patients with a history of atopy or severe anaphylactic reaction to a range of allergens may be more reactive to repeated exposure to these allergens. In patients at risk of a severe anaphylactic reaction, whatever its origin, in particular floctafenine, iodinated contrast media, during the use of anaesthetic products or during desensitisation treatments, beta-blocker treatment may lead to an aggravation of the reaction and resistance to treatment with adrenaline (epinephrine) at usual doses.

Surgical anesthesia

Beta-blockers used in ophthalmology may block the effects of systemic beta-agonist agents such as adrenaline (epinephrine). The anaesthetist should be informed when the patient is receiving cartéolol hydrochloride.

• If discontinuation of treatment is deemed necessary, a suspension of 48 hours is considered sufficient to allow the return of sensitivity to catecholamines.
• In some cases beta-blocker treatment cannot be interrupted:
  • In patients with coronary insufficiency, it is desirable to continue treatment until surgery, given the risk associated with abrupt withdrawal of beta-blockers,
  • In case of emergency or inability to stop, the patient must be protected from vagal predominance by sufficient premedication with atropine, repeated as needed.
  • Anesthesia should use agents that are as little myocardial depressant as possible, and blood losses must be compensated.

Thyrotoxicosis

Beta-blockers may mask the signs of hyperthyroidism.

Beta-blockers may mask certain signs of thyrotoxicosis, particularly cardiovascular signs.

Interactions with other medicinal products

The combination of CARTEOL eye drops in solution is not recommended with diltiazem, fingolimod, ozanimod and verapamil (see section Interactions).

Excipients with known effect

Benzalkonium chloride, monosodium phosphate dihydrate, disodium phosphate dodecahydrate.

This medicine contains 0,15 mg of benzalkonium chloride and 4,2 mg of phosphates per unit volume of 3 mL.

No specific interaction study has been carried out with carteolol hydrochloride.

1°) Eye drops in solution

Mydriasis has occasionally been reported when ophthalmic beta-blockers and adrenaline (epinephrine) were used concomitantly.

Therefore, ophthalmological monitoring is necessary in case of concomitant treatment with an eye drop containing adrenaline (risk of mydriasis).

When several topical ophthalmic medicines are used, the administrations of medicines must be spaced by at least 15 minutes. Ophthalmic ointments must be administered last.

2°) Other medicines

Although the amounts of beta-blockers passing into the systemic circulation are low after ocular instillation, the risk of drug interactions exists.

Therefore, the interactions observed with beta-blockers administered systemically should be taken into account.

Bradycardic medicinal products

Many medicines may cause bradycardia. This is notably the case for class Ia antiarrhythmics, beta-blockers, certain class III antiarrhythmics, certain calcium antagonists, digoxin, pilocarpine, anticholinesterases, etc.

Combinations not recommended (see section Warnings and precautions)

+ Diltiazem

Disorders of automaticity (excessive bradycardia, sinus arrest), disorders of sino-atrial and atrioventricular conduction, and cardiac failure.

Such a combination should only be made under close clinical and ECG monitoring, particularly in elderly subjects or at the start of treatment.

+ Fingolimod

Potentiation of bradycardic effects that may have fatal consequences. Beta-blockers are all the more at risk as they prevent adrenergic compensatory mechanisms.

Clinical monitoring and continuous ECG for 24 hours following the first dose.

+ Ozanimod

Potentiation of bradycardic effects which may have fatal consequences. Beta-blockers are all the more at risk as they prevent adrenergic compensation mechanisms.

Clinical monitoring and continuous ECG for at least 6 hours.

+ Verapamil

Automaticity disorders (excessive bradycardia, sinus arrest), sino-atrial and atrioventricular conduction disorder and heart failure.

Such a combination should only be made under close clinical and ECG monitoring, particularly in elderly subjects or at the start of treatment.

Associations requiring precautions for use

+ Amiodarone

Automaticity and conduction disorders (suppression of compensatory sympathetic mechanisms).

Clinical monitoring and ECG.

+ Halogenated volatile anaesthetics (desflurane, halothane, isoflurane, methoxyflurane, sevoflurane)

Reduction of compensatory cardiovascular reactions by beta-blockers. Beta-adrenergic inhibition may be reversed during surgery by beta-mimetics.

As a general rule, do not stop beta-blocker treatment and, in any case, avoid abrupt withdrawal. Inform the anaesthetist of this treatment.

+ Central antihypertensives (clonidine, guanfacine, methyldopa, moxonidine, rilmenidine) Significant increase in blood pressure in case of abrupt discontinuation of treatment with the central antihypertensive.

Avoid abrupt withdrawal of treatment with the central antihypertensive. Clinical monitoring.

+ Glinides (nateglinide, repaglinide)

All beta-blockers may mask certain symptoms of hypoglycaemia: palpitations and tachycardia.

Inform the patient and reinforce blood glucose self-monitoring, especially at the beginning of treatment.

+ Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin)

All beta-blockers may mask certain symptoms of hypoglycaemia: palpitations and tachycardia.

Inform the patient and reinforce blood glucose self-monitoring, especially at the beginning of treatment.

+ Insulin

All beta-blockers may mask certain symptoms of hypoglycaemia: palpitations and tachycardia.

Inform the patient and reinforce blood glucose self-monitoring, especially at the start of treatment.

+ Lidocaine

With intravenous lidocaine: increased plasma concentrations of lidocaine with possible neurological and cardiac adverse effects (decreased hepatic clearance of lidocaine).

Clinical monitoring, ECG and possibly monitoring of plasma lidocaine concentrations during the combination and after discontinuation of the beta-blocker. Adjust the lidocaine dosage if necessary.

+ Propafenone

Disorders of contractility, automaticity and conduction (suppression of compensatory sympathetic mechanisms).

Clinical monitoring and ECG.

+ Substances liable to cause torsades de pointes

(amiodarone, amisulpride, arsenic trioxide, chloroquine, chlorpromazine, citalopram, cocaine, crizotinib, cyamemazine, disopyramide, domperidone, dronedarone, droperidol, erythromycin, escitalopram, flupentixol, fluphenazine, halofantrine, haloperidol, hydroquinidine, hydroxychloroquine, hydroxyzine, levomepromazine, lumefantrine, mequitazine, methadone, moxifloxacin, pentamidine, pimozide, pipamperone, piperaquine, pipotiazine, quinidine, sotalol, spiramycin, sulpiride, tiapride, toremifene, vandetanib, vincamine, zuclopenthixol)

Increased risk of ventricular rhythm disorders, in particular torsades de pointes.

Clinical and electrocardiographic monitoring during the combination.

+ Hypoglycaemic sulfonylureas (glibenclamide, gliclazide, glimepiride, glipizide)

All beta-blockers may mask certain symptoms of hypoglycaemia: palpitations and tachycardia.

Inform the patient and reinforce blood glucose self-monitoring, especially at the start of treatment.

Associations to be taken into account

+ Non-steroidal anti-inflammatory drugs (NSAIDs)

(aceclofenac, mefenamic acid, niflumic acid, tiaprofenic acid, alminoprofen, celecoxib, dexketoprofen trometamol, diclofenac, etodolac, etoricoxib, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, meloxicam, morniflumate, nabumetone, naproxen, nimesulide, parecoxib, piroxicam, rofecoxib, sulindac, tenoxicam)

Reduction of the antihypertensive effect (inhibition of vasodilatory prostaglandins by NSAIDs).

+ Alpha-blockers for urological use (alfuzosin, doxazosin, prazosin, silodosin, tamsulosin, terazosin)

Increased hypotensive effect, increased risk of orthostatic hypotension.

+ Alpha-blocking antihypertensives (doxazosin, prazosin, urapidil)

Increased hypotensive effect, increased risk of orthostatic hypotension.

+ Other bradycardic agents

(acebutolol, ambenonium, amiodarone, atenolol, betaxolol, bisoprolol, carvedilol, celiprolol, clonidine, crizotinib, digoxin, diltiazem, disopyramide, donepezil, dronedarone, esmolol, fampridine, fingolimod, galantamine, hydroquinidine, ivabradine, labetalol, levobunolol, mefloquine, metoprolol, midodrine, nadolol, nebivolol, neostigmine, pasireotide, pilocarpine, pindolol, propranolol, pyridostigmine, quinidine, rivastigmine, sotalol, tertatolol, thalidomide, timolol, verapamil)

Risk of excessive bradycardia (additive effects).

+ Beta-2-mimetics (bambuterol, indacaterol, olodaterol, salbutamol, terbutaline, vilanterol)

Risk of reciprocal reduced efficacy through pharmacodynamic antagonism.

+ Dihydropyridines

(amlodipine, clevidipine, felodipine, isradipine, lacidipine, lercanidipine, manidipine, nicardipine, nifedipine, nimodipine, nitrendipine)

Hypotension, cardiac failure in patients with latent or uncontrolled heart failure (additive negative inotropic effects). The beta-blocker may also minimise the reflex sympathetic reaction brought into play in case of excessive haemodynamic repercussions.

+ Dipyridamole

With dipyridamole given by injection: increased antihypertensive effect.

+ Medicinal products causing orthostatic hypotension

(alfuzosin, alimemazine, alizapride, amantadine, amifostine, amisulpride, amitriptyline, amoxapine, apomorphine, aripiprazole, avanafil, baclofen, bromocriptine, chlorpromazine, clomipramine, clozapine, cyamemazine, isosorbide dinitrate, dosulepin, doxazosin, doxepin, droperidol, entacapone, flupentixol, fluphenazine, haloperidol, imipramine, isosorbide, levodopa, levomepromazine, levosimendan, lisuride, loxapine, maprotiline, metopimazine, molsidomine, nicorandil, olanzapine, oxomemazine, paliperidone, penfluridol, perindopril, pimozide, pipamperone, pipotiazine, piribedil, pramipexole, prazosin, promethazine, propericiazine, quetiapine, rasagiline, riociguat, risperidone, ropinirole, rotigotine, selegiline, sildenafil, silodosin, sulpiride, tadalafil, tamsulosin, terazosin, tiapride, tolcapone, trimipramine, trinitrine, vardenafil, vortioxetine, zuclopenthixol)

Risk of increased hypotension, in particular orthostatic hypotension.

The systemic passage of beta-blockers administered by the ocular route is lower than by the general route but nevertheless real.

Pregnancy

There are no relevant data concerning the use of carteolol hydrochloride in pregnant women.

Carteolol hydrochloride must not be used during pregnancy except in cases of absolute necessity. To reduce systemic absorption, see section Dosage and administration.

Epidemiological studies have not revealed a malformative effect, but have shown a risk of intra-uterine growth retardation when beta-blockers are administered by the oral route. In addition, signs and symptoms of a beta-blocking effect (for example: bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the newborn when beta-blockers were administered up to delivery. If CARTEOL is administered up to delivery, the newborn must be closely monitored during the first days of its life.

Breast-feeding

Beta-blockers are excreted in breast milk. However, at the therapeutic doses of carteolol hydrochloride contained in the eye drops, it is unlikely that the quantity passing into breast milk would be sufficient to cause clinical symptoms of beta-blockers in the infant. To reduce systemic absorption, see section Dosage and administration.

Transient visual discomfort may be felt after instillation of CARTEOL. In this case, the patient is advised not to drive or use machines until normal vision returns.

Like other topically applied ophthalmic medicines, this beta-blocker eye drop solution is absorbed into the systemic circulation and may therefore induce undesirable effects similar to those observed with systemically administered beta-blockers. The incidence of systemic drug-related undesirable effects is lower after ophthalmic administration than after systemic administration. The undesirable effects mentioned include those observed with the class of ophthalmic beta-blockers.

The following undesirable effects have been reported with carteolol eye drop solution either during clinical trials or after marketing.

Adverse effects are classified according to their frequency, as follows:

Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1 000 to < 1/100), Rare (≥ 1/10 000 to < 1/1 000), Very rare (< 1/10 000) and Frequency not known (cannot be estimated from the available data).

Additional adverse effects have been observed with ophthalmic beta-blockers and may occur with CARTEOL.

Immune system disorders:

Frequency not known: Systemic allergic reactions including angioedema, urticaria, localised and generalised rash, pruritus, anaphylactic reaction.

Metabolism and nutrition disorders:

Frequency not known: Hypoglycaemia.

Psychiatric disorders:

Frequency not known: Insomnia, depression, nightmares, decreased libido.

Nervous system disorders:

Common: Dysgeusia.

Uncommon: Vertigo.

Frequency not known: Syncope, cerebrovascular accident, cerebral ischaemia, worsening of signs of myasthenia gravis, paraesthesia, headache, amnesia.

Eye disorders:

Common: Signs and symptoms of ocular irritation (for example burning), ocular pain (for example stinging), ocular pruritus, increased lacrimation, ocular hyperaemia), conjunctival hyperaemia, conjunctivitis, keratitis.

Frequency not known: Blepharitis, blurred vision, choroidal detachment after filtering surgery (see section Warnings and precautions), ocular hypoaesthesia, dry eye, corneal erosion, ptosis, diplopia. Refractive disorder (due to discontinuation of miotic treatment in certain cases).

A few very rare cases of corneal calcification have been reported in association with the use of drops containing phosphates in some patients with severely damaged corneas.

Cardiac disorders:

Frequency not known: Bradycardia, palpitations, arrhythmia, congestive heart failure, atrioventricular block, cardiac arrest, cardiac failure.

Vascular disorders:

Frequency not known: Hypotension, Raynaud's syndrome, cold extremities, intermittent claudication.

Respiratory, thoracic and mediastinal disorders:

Frequency not known: Bronchospasm (mainly in patients with pre-existing bronchospastic disease), dyspnoea, cough.

Gastrointestinal disorders:

Frequency not known: Nausea, dyspepsia, diarrhoea, dry mouth, abdominal pain, vomiting.

Skin and subcutaneous tissue disorders:

Frequency not known: Alopecia, psoriasiform dermatitis, worsening of psoriasis, rash.

Musculoskeletal and connective tissue disorders:

Uncommon: Myalgia, muscle cramps

Frequency not known: Systemic lupus erythematosus.

Reproductive system and breast disorders:

Frequency not known: Sexual dysfunction, erectile dysfunction.

General disorders and administration site conditions:

Frequency not known: Asthenia/fatigue, chest pain, oedema.

Investigations:

Rare: Appearance of antinuclear antibodies.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr.

Although the amounts of beta-blockers passing into the systemic circulation are low after ocular instillation, the risk of overdose must be kept in mind.

The experience of overdose by the ocular route is limited.

In case of accidental ocular overdose, rinse the eyes with a sterile sodium chloride solution at 9 mg/mL (0,9 %).

In case of accidental oral ingestion or misuse, the symptoms and management are modelled on those of a systemic beta-blocker overdose.

Pharmacotherapeutic class: Beta-blocking agent, ATC code: S01ED05.

General

Carteolol is a non-cardioselective beta-blocker, with partial agonist activity [moderate intrinsic sympathomimetic activity (ISA)] and a non-significant membrane-stabilising effect (local anaesthetic or quinidine-like).

Ocular

• Carteolol hydrochloride in eye drops lowers intraocular pressure, whether or not associated with glaucoma.
• It reduces intraocular hypertension by decreasing aqueous humour secretion. Its activity appears about 20 minutes after instillation, reaches its maximum between 1 and 2 hours, and is still present after 24 hours.
• Stability of the hypotensive effect over time: the effect may remain constant for one year;
• As with all beta-blockers, a decrease in sensitivity to carteolol hydrochloride nevertheless remains possible, particularly after longer treatment.
• There is practically no change in pupil diameter or accommodation. Therefore, no accommodative spasm or change in visual acuity is observed.

Like other beta-blocker eye drops, the carteolol contained in CARTEOL can pass into the general circulation.

Preclinical data from conventional safety pharmacology, repeated-dose toxicity, genotoxicity or carcinogenicity tests did not reveal any particular risk in humans.

In reproductive toxicity studies, embryotoxicity was demonstrated at high oral doses, corresponding to systemic exposure levels considered sufficiently high compared with the systemic exposure associated with clinical use of CARTEOL eye drops. Carteolol did not show teratogenic properties in reproduction studies.

It has been reported that, in rats, carteolol hydrochloride can cross the placental barrier and is weakly excreted in milk.

Before opening : 18 months

After opening : 15 days

Store at a temperature not exceeding 25 °C.

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

List I

Marketing authorisation (AMM)

CIP 3400934380792 (Fl/3ml).

Price:

3,27 euros (Fl/3ml).

Social security reimbursement at 65%. Collective.