1.    NAME OF THE MEDICINAL PRODUCT

Ocufen

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Flurbiprofen sodium 0.03% w/v

For the full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Eye drops, solution

4    CLINICAL PARTICULARS

4.1 Therapeutic indications

Ocufen is indicated for

1)    the inhibition of intraoperative miosis. Ocufen does not have intrinsic mydriatic properties and does not replace mydriatic agents.

2)    the management of post-operative and post-laser trabeculoplasty inflammation in the anterior segment of the eye in patients in whom steroid therapy is not recommended.

4.2. Posology and Method of Administration

Posology:

Adult dosage: For the inhibition of intraoperative miosis, 1 drop is instilled every half hour starting 2 hours before surgery. The final drop should be given not less than 30 minutes before surgery.

To control post-operative and post-laser trabeculoplasty inflammation the dosing regimen above should be followed. Beginning twenty-four hours after surgery, one drop is administered four times daily for at least one week after laser trabeculoplasty or for two to three weeks after other surgery.

Paediatric population:

The safety and efficacy of Ocufen in children has not been established. Elderly population:

There is no specific advice for the elderly.

Method of administration:

Ocufen is administered topically by instillation into the conjunctival sac.

In accordance with standard practice, other topical medication should not be co-administered with Ocufen. When administering other topical medications, a minimum interval of 5 minutes between instillations is recommended.

4.3. Contra-indications

Hypersensitivity to the active substance or to any of the excipients.

Ocufen is contra-indicated in epithelial herpes simplex keratitis (dendritic keratitis).

The potential exists for cross-sensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs. Ocufen is contra-indicated in individuals who have previously exhibited sensitivities to these drugs.

With non-steroidal anti-inflammatory drugs, there exists the potential for increased bleeding due interference with thromobocyte aggregation. The use of Ocufen is contra-indicated in patients with known haemostatic defects or who are receiving other medications which may prolong bleeding time.

Ocufen is contra-indicated for intraocular use during surgical procedures.

As with all non-steroidal anti inflammatory drugs, Ocufen is contraindicated in the third trimester of pregnancy.

4.4    Special warnings and precautions for use

Wound healing may be delayed with the use of Ocufen.

There have been reports that Ocufen may cause an increased bleeding tendency of ocular tissues in conjunction with surgery.

Patients with a history of herpes simplex keratitis should be monitored closely.

4.5    Interaction with other medicinal products and other forms of interaction

Although clinical studies with acetylcholine chloride and animal studies with acetylcholine chloride or carbachol revealed no interference, and there is no known pharmacological basis for an interaction, there have been reports that acetylcholine chloride and carbachol have been ineffective when used in some surgical patients treated with Ocufen.

4.6. Fertility, Pregnancy and Lactation

Pregnancy:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately

1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, Ocufen should not be given unless clearly necessary.

If Ocufen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

-    cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

-    renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; the mother and the neonate, at the end of pregnancy, to:

-    possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

-    inhibition of uterine contractions resulting in delayed or prolonged labour. Consequently, Ocufen is contraindicated during the third trimester of pregnancy. Breast-feeding:

In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

It is unknown whether flurbiprofen/metabolites are excreted in human milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Ocufen therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

4.7. Effects on Ability to Drive and Use Machines

Transient blurred vision can result after instillation. If this occurs, the patient should wait until the vision clears before driving or using machinery.

Undesirable effects

The following adverse reactions were reported during the use of Ocufen in clinical studies.

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) adverse reactions are presented according to MedDRA System organ class

Eye disorders:

Very common: Eye irritation, eye pain, Hyphema*

Additionally, the following adverse reactions have been identified during post marketing experience;

Eye disorders:

Not known: eye haemorrhage*, mydriasis (prolonged mydriasis), ocular hyperaemia.

* see section 4.4 for further information.

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:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

4.9. Overdose

Overdose by the topical ophthalmic route will not ordinarily cause acute problems. If accidentally ingested, treatment should be symptomatic.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Pharmacotherapeutic group: Antiinflammatory agents, non-steroids ATC code: S01BC04

Flurbiprofen sodium is a non steroidal anti inflammatory agent which inhibits prostaglandin synthesis by inhibition of the cyclo-oxygenase enzyme.

Ophthalmic surgery causes prostaglandin release, with the effect that prostaglandin-mediated miosis may occur.

Treatment with Ocufen prior to surgery has been shown to inhibit intra-operative miosis and it is believed that this is brought about by inhibition of ocular prostaglandin release.

The sympathetic nervous system is not affected by this mechanism and acetylcholine-induced miosis has not been found to be inhibited in clinical trials.

Prostaglandins have also been shown to be mediators of certain kinds of intraocular inflammatory processes. In studies performed on animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humour barrier, vasodilation, increased vascular permeability, leukocytosis and increased intraocular pressure.

5.2    Pharmacokinetic properties

Flurbiprofen concentrations of 213 ng/ml in aqueous humour have been reported following half hourly treatment for two hours preceding surgery.

5.3. Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in the Summary of Product Characteristics.

6.    PHARMACEUTICAL PARTICULARS

6.1.    List of Excipients

Liquifilm (polyvinyl alcohol)

Potassium chloride

Sodium chloride

Sodium citrate dihydrate

Citric acid monohydrate

Sodium hydroxide or

Hydrochloric acid (for pH adjustment)

Purified water

6.2.    Incompatibilities

Not applicable

6.3    Shelf life

The shelf life is 24 months for the unopened vial. The vial should be discarded after a single dose.

6.4    Special precautions for storage

Store at or below 25°C.

6.5    Nature and contents of container

Clear, plastic unit dose vial, each containing 0.4 ml of solution.

6.6    Special precautions for disposal

Each vial of Ocufen should be used for a single dose and discarded after use.

7    MARKETING AUTHORISATION HOLDER

Allergan Ltd.

Marlow International The Parkway Marlow

Bucks SL7 1YL United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 00426/0069

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

28/06/1991 / 16/05/2005

10 DATE OF REVISION OF THE TEXT

20/05/2014