INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
NYOGEL (EYE GEL)

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

NYOGEL (EYE GEL)

COMPOSITION:
Each g contains:
Timolol maleate         1,37 mg
(Equivalent to 1 mg Timolol base)
Preservative:
Benzalkonium chloride        0,005% m/v

PHARMACOLOGICAL CLASSIFICATION:
A15.4 Ophthalmic preparations - Other

PHARMACOLOGICAL ACTION:
Pharmacodynamic properties
Nyogel gel contains timolol maleate in a gel formulation with the advantages of a reduced concentration of the active ingredient and a longer dosage interval.
Timolol is a non-subtype-selective beta-adrenergic antagonist, which has no intrinsic sympathomimetic activity and no membrane stabilising activity.
Beta-adrenergic antagonists decrease intraocular pressure probably by decreasing the rate of production of aqueous humor by the ciliary body. Timolol maleate reduces intraocular pressure with little or no effect on accommodation or pupil size.
Pharmacokinetic properties
Timolol maleate is subject to first pass metabolism. Protein binding has been reported to be low with low to moderate lipid solubility. A plasma half life of four hours has been reported. It is extensively metabolised in the liver, the metabolites being excreted in the urine with some unchanged timolol. It crosses the placenta and appears in the breast milk.
Topically administered beta-blockers are usually well tolerated, however they are systemically absorbed. It has however been demonstrated clinically that systemic bioavailability of timolol maleate derived from Nyogel gel was lower than comparator aqueous formulations.

INDICATIONS:
Nyogel gel is indicated for the reduction of elevated intraocular pressure in various disorders such as,

-	Ocular hypertension.
-	Chronic open angle glaucoma
-	Aphakic glaucoma
-	Some patients with secondary glaucoma

CONTRA-INDICATIONS:

-	Hypersensitivity to any of the ingredients.
-	Patients with brochospasm and asthma or to those with a history of obstructive airways disease.
-	Heart failure, metabolic acidosis, sinus bradycardia, or partial heart block.
-	In general, beta-blockers should not be given to patients with heart failure, unless it is controlled, even then great care is still necessary.
-	When cardiac function is compromised, orally administered calcium antagonist should not be given in combination with beta-blockers.

Safety in pregnancy and lactation has not been established.

WARNINGS:
As the possibility of adverse effects on corneal permeability and the danger of disruption of the corneal epithelium with prolonged or repeated usage of benzalkonium chloride preserved ophthalmological preparations cannot be excluded, regular ophthalmological examinations is required.
Caution should be exercised in the use of benzalkonium chloride preserved topical medication over an extended period in patients with extensive ocular surface disease.

DOSAGE AND DIRECTIONS FOR USE:
One drop of the gel to be instilled into the affected eye once daily. The Gel should be instilled into the conjunctival cul-de-sac and can be used over a long period of time.
If other eye drops are being used, there must be an interval of at least five minutes between instillations so that the active substance is not washed out. Eye drops should be applied before Nyogel.
As it takes some time to stabilise the effect, it is recommended that the intraocular pressure is checked 3-4 weeks after the start of treatment. The intraocular pressure should also be measured regularly thereafter because the response to timolol may change.
There are no special risks in relation to the treatment of children over 12 years old. Nyogel gel is not recommended for children below the age of 12.
Contact lenses should be removed before application of Nyogel gel and not reinserted earlier than 30 minutes after use.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects
Ophthalmic administration may produce mild local irritation and blurred vision. The blurred vision is generally slight and can last from 1-3 minutes.
Blepharitis, keratitis, decreased corneal sensitivity, visual disturbances, diplopia and ptosis can also occur. Nyogel gel can produce corneal anaesthesia.
Systemic absorption may occur following the use of Nyogel gel. The main systemic effects are associated with the pulmonary, cardiovascular and central nervous system and are as follows.
Cardiovascular side-effects could include, bradycardia, hypotension, heart failure, heart block, syncope, cerebrovascular accident, cerebral ischemia, palpitation, cardiac arrest.
Respiratory side-effects could include bronchospasm, respiratory failure and dyspnoea.
Nervous system side effects could include depression and dizziness.
Other general side-effects could include, headache, dizziness, asthenia, fatigue, chest pain, hypersensitivity reactions including
generalised rash and urticaria, alopecia and nausea. The signs and symptoms of Myasthenia Gravis may increase.
The following side-effects are associated with oral administration of beta-blockers and may occur with topical application of timolol maleate.
Cardiovascular side-effects include atrioventricular block, sinoatrial block, oedema, pulmonary oedema, vasodilation, reduced peripheral circulation leading to coldness of extremities and exacerbating peripheral vascular diseases such as Raynaud’s syndrome.
Respiratory side-effects include pneumonitis, pulmonary fibrosis, pleurisy, rales and cough.
Central nervous system side-effects include, hallucinations, confusion, sleep disturbances including nightmares, nervousness, diminished concentration, increased dreaming, insomnia, somnolence, decreased libido, vertigo and local weakness.
Adverse gastro-intestinal effects include nausea, vomitting, diarrhoea, constipation, abdominal cramping and dyspepsia.
Metabolic changes affecting carbohydrate and lipid metabolism can occur. This could result in hypoglycaemia, hyperglycaemia, and changes in blood concentration of triglycerides and cholesterol.
Sweating and exfoliative dermatitis can occur.
Ocular symptoms may include decreased tear production and soreness.
Haematological reactions include nonthrombocytopenic purpura, thrombocytopenia, and rarely agranulocytosis. Transient eosinophilia can occur.
Other adverse reactions reported with some beta-blockers include a lupus-like syndrome, male impotence, micturition difficulties, sclerosing peritonitis, retroperitoneal fibrosis, arthralgia and tinnitus.
Special Precautions
Since the preparation can cause blurred vision, the influence on the ability to drive a car or to work with machines must be considered. As with other glaucoma preparations a reduced response has been reported in some patients after long term treatment. In general beta-blockers should not be given to patients with heart failure unless the heart failure is controlled. If Nyogel is to be used in these cases the patient must be monitored very carefully.
Caution must be exercised in patients suffering from peripheral vascular disease such as Raynaud’s Phenomenon. Patients with phaeochromocytoma should not receive Nyogel gel without concomitant alpha-adrenoceptor blocking therapy.
Nyogel gel may mask the symptoms of hyperthyroidism and of hypoglycaemia. They may unmask myasthenia gravis. Psoriasis may be aggravated.
Patients with a history of anaphylaxis to an antigen may be more reactive to repeated challenge with the antigen while using Nyogel gel.
Death due to respiratory complications (bronchospasm in asthmatic patients) and cardiac complications (cardiac failure) have been reported with the use of timolol maleate. These are not precluded with the use of Nyogel gel.
If Nyogel gel is to be used in patients already receiving oral beta-blockers, a greater reduction in intraocular pressure as well as systemic side-effects may occur.
In patients with closed-angle glaucoma, efforts should first be made to reopen the iridocorneal angle with a suitable miotic. If Nyogel gel is used to reduce the raised intraocular pressure in angle-closure glaucoma, it should be prescribed together with a miotic.

INTERACTIONS
Since systemic absorption can follow ophthalmic use of beta-blockers, the possibility of interaction occuring with Nyogel gel should also be considered.
Drugs that release catecholamines: It is recommended those patients who are taking medicines that deplete catecholamine reserves e.g. reserpine, in addition to receiving beta-blockers should be monitored closely. Additive effects are possible and lead to hypotension and/or marked bradycardia, which may cause dizziness, syncope or orthostatic hypertension.
Calcium antagonists: As long as cardiac function is normal, orally administered calcium antagonists may be of benefit in combination with beta-blockers. The combination should not be used, however, when cardiac function has been compromised. Intravenously administered calcium channel blockers should be used with caution. If patients who are on oral beta-blockers are also given oral calcium antagonists, there is a potential risk of hypotension, AV conduction disturbances and left ventricular cardiac failure. The nature of the cardiovascular adverse reaction depends on the type of calcium antagonist used. Dihydropyridine derivatives such as nifedipine may lead to hypotension while verapamil and diltiazem tend to cause AV conduction disturbance or left ventricular cardiac failure.
Digitalis: Concomitant use of beta-blocker and digitalis with either diltiazem or verapamil may lead to a prolongation of the AV conduction time.
The response to adrenaline following an anaphylactic reaction may be reduced in patients receiving long term beta-blocker therapy.
Metabolism of beta-blockers can be increased by concomitant treatment with drugs such as barbiturates and rifampicin and decreased with drugs such as cimetidine, erythromycin, fluvoxamine, and hydralazine. Drugs that alter hepatic blood flow also affect metabolism of beta-blockers. For example cimetidine and hydralazine decrease hepatic blood flow and this contributes to a decreased hepatic clearance seen with these drugs.
Anaesthetics that cause myocardial depression, such as ether, cyclopropane, and trichloroethylene should preferably be avoided.
Concomitant use with antiarrhythmic drugs and other drugs affecting cardiac conduction can precipitate bradycardia and heart block.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
The symptoms most likely to be expected with overdosage of a systemic beta-blocker are symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure. Convulsions, coma and respiratory depression can also occur.
The following therapeutic measures should be considered:

1)	Symptomatic bradycardia: To achieve vagal blockage, atropine sulphate is injected intravenously at a dosage of 0,25 to 2 mg. If the bradycardia continues, isoprenaline should be given intravenously. In refractory cases, the insertion of a pacemaker may be required.
2)	Hypotension: Treatment with a sympathomimetic agent that raises the blood pressure e.g. dopamine, dobutamine or noradrenaline. In refractory cases, glucagon has been shown to be beneficial.
3)	Bronchospasm: Give isoprenaline, possibly with aminophylline in addition.
4)	Acute cardiac failure: standard therapy with digitalis, diuretics and oxygen must be started without delay. In refractory cases, intravenous administration is recommended, if necessary followed by glucagon.
5)	Heart block (2nd of 3rd degree): Use isoprenaline or a transvenous cardiac pacemaker.

IDENTIFICATION:
Nyogel gel is an opalescent, odourless gel, free of visible particulate matter.

PRESENTATION:
Transparent five millilitre polyethylene bottle with polyethylene dropper and closure (with safety closure), containing 5 grams of Nyogel gel.

STORAGE INSTRUCTIONS:
Store in a cool place below 25°C and protected from light.
Do not use for more than 30 days after opening.
Keep out of reach of children.

REGISTRATION NUMBER:
36/15.4/0038

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Adcock Ingram Limited
Adcock Ingram Park
17 Harrison Avenue, Bryanston, Ext. 77
Private Bag X69, Bryanston, 2021

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
20/11/2000

Under licence from Novartis Ophthalmics Ltd.

New addition to this site: April 2004
Source: Pharmaceutical Industry
SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2004