1. Name Of The Medicinal Product
Teoptic 2% w/v Eye Drops, Solution
2. Qualitative And Quantitative Composition
Carteolol hydrochloride 2% w/v
Excipients: Benzalkonium chloride 0.005%.
For the full list of excipients, see Section 6.1
3. Pharmaceutical Form
Eye drops solution.
A clear, colourless solution.
4. Clinical Particulars
4.1 Therapeutic Indications
For the reduction of intraocular pressure e.g. in ocular hypertension, chronic open angle glaucoma, some secondary glaucomas.
4.2 Posology And Method Of Administration
Adults: Initially one drop of 1% eye drops instilled twice daily in each affected eye. If the clinical response is not adequate the dosage may be altered to one drop of 2% eye drops twice daily in each affected eye.
Elderly: There is no indication that dosage needs to be modified for the elderly.
Children: Safety and effectiveness of carteolol has not been established.
Nasolacrimal occlusion or closing the eyelids after drug instillation can reduce the systemic absorption. This may result in a decrease in systemic adverse events and an increase in local activity. It is recommended that the period of occlusion is five minutes in duration.
The dispenser remains sterile until the original closure is broken. Patients must be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures as this may contaminate the solution.
If the patients IOP is not at a satisfactory level with this regimen, concomitant treatment with other IOP lowering drugs may be considered.
If more than one medication needs to be instilled in the eye, an interval of at least 5 minutes between application of the different medicinal products must be allowed.
4.3 Contraindications
The carteolol eye drops are contraindicated in patients:
- with unsatisfactorily controlled cardiac insufficiency, sinus bradycardia, second- or third-degree atrioventricular block, and or cardiogenic shock (these diseases or symptoms may be exacerbated).
- with symptoms or a history of bronchospasm including bronchial asthma or severe chronic obstructive pulmonary disease (these diseases or symptoms may be exacerbated).
- known hypersensitivity to carteolol hydrochloride or to any of the excipients
4.4 Special Warnings And Precautions For Use
Like other topically applied ophthalmic drugs, carteolol hydrochloride may enter the systemic circulation and systemic effects or systemic adverse effects seen with oral beta-blockers may occur.
Carteolol eye drops must be administered with caution in the following patients:
- Patients with right heart failure due to pulmonary hypertension
- Patients with congestive heart failure. Cardiac failure should be adequately controlled before beginning therapy with carteolol. Patients with a history of severe cardiac disease should be watched for signs of cardiac failure.
- Patients with sick sinus syndrome, Prinzmetal's angina, untreated phaeochromocytoma, severe peripheral circulatory disturbances (Raynaud disease), and hypotension
- Patients with unsatisfactorily controlled diabetes mellitus. Careful monitoring of blood glucose levels is required during therapy.
- Patients with diabetic ketoacetosis or metabolic acidosis.
- Patients with hyperthyroidism
- Patients with myasthenia gravis. Beta-adrenergic blockade may potentiate muscle weakness related to certain myasthenic symptoms, such as diplopia, ptosis and generalised weakness.
Severe prolonged hypotension has been observed in some patients after administration of systemic beta-blockers during anaesthesia.
In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires constricting the pupil with a miotic.
Carteolol has little or no effect on the pupil. When carteolol is used to reduce intraocular pressure in angle-closure glaucoma it must be used with a miotic and not alone.
Risk from anaphylactic reactions: While taking beta-blockers, patients with a history of atropy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge with such allergens, either accidental, diagnostic or therapeutic [55]. Such patients may be unresponsive to the usual dose of adrenaline used to treat anaphylactic reactions.
As with any glaucoma treatment, regular examination of the intraocular pressure and cornea is recommended.
Eye drops are not for injection. They should never be injected subconjunctivally, nor should they be directly introduced into the anterior chamber of the eye.
The carteolol eye drops contain benzalkonium chloride as a preservative.
Therefore, the medicament should not be used while wearing soft contact lenses. The lenses must be removed before application of the drops and not reinserted earlier than 15 minutes after use.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
The effect on intraocular pressure or the known effects of systemic betablockade may be exaggerated when carteolol is given to patients already receiving an oral beta-blocking agent. The response of these patients should be closely observed.
A drug in the same pharmacological class as carteolol, ophthalmic timolol maleate has been shown to potentiate the mydriatic effect of adrenaline when combined.
As carteolol may be absorbed systemically the following interactions as those seen with oral betablockers may occur:
- Carteolol may potentially add to the effects of oral calcium antagonists such as verapamil, and diltiazem, to induce congestive heart failure or cardiac conduction disturbances such as bradycardia and AV block.
- Digitalis glycosides, parasympathomimetics: association with betablockers may increase auriculoventricular conduction time.
- Class I anti-arrhythmic drugs (e.g. disopyramide, quinidine) and amiodarone: may have potentiating effect on atrial-conduction time and induce negative inotropic effect.
If a supplementary ophthalmic medication is used, there must be an interval of at least five minutes between the administration of the two products.
4.6 Pregnancy And Lactation
Teoptic eye drops have not been studied in human pregnancy and lactation.
Use during pregnancy is therefore contraindicated. In animal studies, orally administered carteolol has been shown to penetrate the breast milk and the use of Teoptic eye drops in lactating mothers should therefore be at the discretion of the physician.
4.7 Effects On Ability To Drive And Use Machines
As with any other eye medication, should a patient experience any disturbance of vision, dizziness or syncope following instillation of carteolol eye drops, driving and the operation of machinery must be avoided until vision has returned to normal.
4.8 Undesirable Effects
Ocular: Signs and symptoms of eye irritation including eye pain, eye pruritus, ocular hyperaemia, sensation of foreign body, dry eyes, burning and stinging.
Sensitivity to light (photophobia), conjunctival discharge, conjunctivitis, blepharitis, keratitis, vision blurred, conjunctival hyperaemia, oedema and decreased corneal sensitivity. Ptosis has been observed in other topical beta blockers.
Cardiovascular: Bradycardia, chest pain, atrioventricular block, syncope and palpitations. Cerebrovascular accident has been observed in other topical beta blockers.
Respiratory: Dyspnoea and asthma attacks. Respiratory and cardiac reactions, including death due to bronchospasm in patients with asthma have been reported.
Skin: Hypersensitivity reactions, including localised and generalised rash.
Isolated cases of urticaria, alopecia, psoriasiform-like lesions or exacerbation of psoriasis have been reported. There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic receptor blocking drugs.
Other: Headache, discomfort, malaise, dizziness, nausea and bitter taste. weakness, sinusitis and depression.
4.9 Overdose
No specific information on emergency treatment of overdose in humans is available. Should accidental ocular overdose occur, the eyes should be flushed with water or saline solution.
The most common signs and symptoms to be expected following overdose with a beta-adrenergic receptor blocking agent include dizziness, headache, shortness of breath, symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure.
In case of overdose standard medical treatment can be administered.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group:Antiglaucoma preparations and miotics, beta blocking agents. ATC code: S0lED05
Carteolol is a non-selective beta-adrenergic blocking agent with associated intrinsic sympathomimetic activity (ISA) and without significant membrane stabilizing activity. It has been shown that beta blocking agents with ISA affect cardiac output, heart rate at rest, peripheral vascular resistance and consequently peripheral circulation less than beta blocking agents without ISA.
Carteolol reduces normal and elevated intraocular pressure whether or not accompanied by glaucoma.The exact mechanism of the ocular hypotensive effect of beta-blockers has not been definitely demonstrated. However, it appears that ophthalmic beta-adrenergic blocking agents mainly act by reducing aqueous humor production.
Given topically twice daily in controlled clinical trials, carteolol eye drops effectively reduced IOP in patients with glaucoma or ocular hypertension. No significant effects were noted on corneal sensitivity in healthy subjects or tear secretion or pupil size.
Administration of carteolol to the eyes of animals and healthy individuals has shown that carteolol increases the iris tissue blood velocity in the treated eye of rabbits and may increase tissue blood flow in the human optic nerve head.
Whereas topical nonselective beta-adrenergic blockers decrease serum HDL and worsen the total cholesterol/HDL ratio, beta-blockers with intrinsic sympathomimetic activity appear to have a lesser effect.
5.2 Pharmacokinetic Properties
A single ocular instillation of 14C-labelled carteolol hydrochloride 2% solution into rabbit eyes demonstrated that carteolol penetrates the cornea quickly. The highest concentration levels were found in the cornea, iris, anterior sclera, ciliary body and conjunctiva 30 to 60 minutes after dosing but declined rapidly to 5 to 10% of the maximum level after 8 hours.
CYP2D6 mediated 8-hydroxylation is the only cytochrome P450 catalyzed metabolic reaction of carteolol . Carteolol has neither stimulatory nor inhibitory effects on CYP1A2, 2C9, 2C19, 2E1, and 3A4 activities. 8- Hydroxycarteolol was estimated to be more potent than carteolol in lowering IOP both in rabbits and in monkey. No data is available on metabolism after ocular application of carteolol in human.
One drop of a 2% carteolol hydrochloride solution was instilled in each eye of healthy volunteers. Approximately 16% of the dose was excreted in the urine as unchanged compound during the first 24 hours after instillation. The urinary elimination half-life was about 5 hours. The plasma level of carteolol hydrochloride after topical administration in the eye was below the detection limit (5ng/mL).
5.3 Preclinical Safety Data
Preclinical data reveal no special hazard for humans based on conventional studies of acute and repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.
6. Pharmaceutical Particulars
6.1 List Of Excipients
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6.2 Incompatibilities
None known.
6.3 Shelf Life
Unopened: 24 months
Opened: 28 days
6.4 Special Precautions For Storage
Do not store above 25°C.
6.5 Nature And Contents Of Container
1 X 5ml polyethylene dropper bottle
3 X 5ml polyethylene dropper bottle
6.6 Special Precautions For Disposal And Other Handling
None stated.
7. Marketing Authorisation Holder
Laboratories Thea
12 Rue Louis-Bleriot
Z.I Du Brezet
63017 Clermont-Ferrand Cedex 2
France
8. Marketing Authorisation Number(S)
PL 20162/0008
9. Date Of First Authorisation/Renewal Of The Authorisation
6 December 2001
10. Date Of Revision Of The Text
22 June 2009
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