Minims Prednisolone Sodium Phosphate 0.5% w / v

1. Name Of The Medicinal Product

Minims Prednisolone Sodium Phosphate

2. Qualitative And Quantitative Composition

Clear, colourless, sterile eye drops containing Prednisolone Sodium Phosphate Ph. Eur. 0.5% w/v.

3. Pharmaceutical Form

Sterile single-use eye drop.

4. Clinical Particulars

4.1 Therapeutic Indications

Non-infected inflammatory conditions of the eye.

4.2 Posology And Method Of Administration

Adults and the elderly

One or two drops applied topically to the eye as required.

Children

At the discretion of the physician.

4.3 Contraindications

Use is contraindicated in viral, fungal, tuberculous and other bacterial infections.

Prolonged application to the eye of preparations containing corticosteroids has caused increased intraocular pressure and therefore the drops should not be used in patients with glaucoma.

In children, long-term, continuous topical corticosteroid therapy should be avoided due to possible adrenal suppression.

4.4 Special Warnings And Precautions For Use

Care should be taken to ensure that the eye is not infected before Minims Prednisolone is used.

Systemic absorption may be reduced by compressing the lacrimal sac at the medial canthus for a minute during and following the instillation of the drops. (This blocks the passage of drops via the naso-lacrimal duct to the wide absorptive area of the nasal and pharyngeal mucosa. It is especially advisable in children.).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Corticosteroids are known to increase the effects of barbiturates, sedative hypnotics and tricyclic antidepressants.

They will, however, decrease the effects of anticholinesterases, antiviral eye preparations and salicylates.

4.6 Pregnancy And Lactation

Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal development and although the relevance of this finding to human beings has not been established, the use of Minims Prednisolone during pregnancy should be avoided.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Prolonged treatment with corticosteroids in high dosage is occasionally associated with cataract.

The systemic effects of steroids are possible following the use of Minims Prednisolone, but are, however, unlikely due to the reduced absorption of topical eye drops.

4.9 Overdose

As Minims are single dose units, overdose is unlikely to occur.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

The actions of corticosteroids are mediated by the binding of the corticosteroid molecules to receptor molecules located within sensitive cells. Corticosteroid receptors are present in human trabecular meshwork cells and in rabbit iris ciliary body tissue.

Prednisolone, in common with other corticosteroids, will inhibit phospholipase A2 and thus decrease prostaglandin formation.

The activation and migration of leucocytes will be affected by prednisolone. A 1% solution of prednisolone has been demonstrated to cause a 5.1% reduction in polymorphonuclear leucocyte mobilisation to an inflamed cornea. Corticosteroids will also lyse and destroy lymphocytes. These actions of prednisolone all contribute to its anti-inflammatory effect.

5.2 Pharmacokinetic Properties

The oral availability, distribution and excretion of prednisolone is well documented. A figure of 82 ± 13% has been quoted as the oral availability and 1.4 ± 0.3ml/min/kg as the clearance rate. A half life of 2.1 - 4.0 hours has been calculated.

With regard to ocular pharmacokinetics, prednisolone sodium phosphate is a highly water soluble compound and is almost lipid insoluble. Therefore, theoretically it should not penetrate the intact corneal epithelium. Nevertheless, 30 minutes after instillation of a drop of 1% drug, corneal concentrations of 10µg/g and aqueous levels of 0.5µg/g have been attained. When a 0.5% solution was instilled in rabbit eyes every 15 minutes for an hour, an aqueous concentration of 2.5µg/ml was measured. Considerable variance exists in the intraocular penetration of prednisolone depending on whether the cornea is normal or abraded.

It can be seen that only low levels of prednisolone will be absorbed systemically, particularly where the cornea is intact.

Any prednisolone which is absorbed will be highly protein-bound in common with other corticosteroids.

5.3 Preclinical Safety Data

The use of prednisolone in ophthalmology is well-established. Little specific toxicology work has been reported, however, the breadth of clinical experience confirms its suitability as a topical ophthalmic agent.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Disodium edetate

Disodium dihydrogen phosphate

Sodium chloride

Sodium hydroxide for pH adjustment

Purified water

6.2 Incompatibilities

None known.

6.3 Shelf Life

15 months

6.4 Special Precautions For Storage

Store below 25°C. Do not freeze. Protect from light.

6.5 Nature And Contents Of Container

A sealed conical shaped polypropylene container fitted with a twist and pull off cap. Each Minims unit is overwrapped in an individual polypropylene/paper pouch. Each container holds approximately 0.5ml of solution.

6.6 Special Precautions For Disposal And Other Handling

Each Minims unit should be discarded after a single use.

7. Marketing Authorisation Holder

Chauvin Pharmaceuticals Ltd

106 London Road

Kingston-upon-Thames

Surrey

KT2 6TN

8. Marketing Authorisation Number(S)

PL 0033/0091

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of Grant: 11.3.81

10. Date Of Revision Of The Text

September 2006