4.1. Therapeutic indications

Omidria is indicated in adults for maintenance of intraoperative mydriasis, prevention of intraoperative miosis and reduction of acute postoperative ocular pain in intraocular lens replacement surgery.

4.2. Posology and method of administration

Omidria must be administered in a controlled surgical setting by a qualified ophthalmological surgeon experienced in intraocular lens replacement surgery.

Posology

The recommended dose is 4.0 mL of Omidria concentrate for solution diluted in 500 mL of irrigation solution administered by intraocular irrigation to the affected eye during surgery.

For instructions on dilution of the medicinal product before administration, see section 6.6.

Special populations

Elderly

The elderly population has been studied in clinical studies. No dose adjustment is required.

Renal or hepatic impairment

No formal studies have been conducted with Omidria in patients with renal or hepatic impairment. No dose adjustment or special considerations are anticipated for patients with renal or hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of Omidria in children aged below 18 years have not been established. No data are available.

Method of administration

Intraocular use (after dilution). Single use only.

Omidria has not been evaluated in the absence of standard preoperative mydriatic and anesthetic agents. Preoperative antibiotic, anaesthetics, corticosteroid, mydriatic, and non-steroidal anti-inflammatory drugs (NSAID) eye drops may be administered at the discretion of the treating ophthalmologist.

Before administering the medicinal product

Omidria must be diluted into 500 mL of irrigation solution before use. For dilution instructions, see section 6.6.

The Omidria-containing irrigation solution is intended to be used during the surgical procedure in the same manner that the standard irrigation solution would be used.

4.3. Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

Patients with narrow-angle glaucoma.

4.4. Special warnings and precautions for use

This medicinal product must be diluted before intraocular use.

Omidria is indicated for addition to irrigation solution used during intraocular lens replacement procedures only.

Omidria is not indicated for undiluted use, intravitreal injection, general topical ophthalmic use, or non-ocular systemic use.

The safety and efficacy of Omidria have not been evaluated in patients with a history of uveitis, iris trauma, or alpha-adrenergic antagonist use.

The following warnings and precautions related to topical ophthalmic use of phenylephrine and ketorolac should be considered with the use of Omidria:

Cardiovascular reactions

There have been reports of serious cardiovascular reactions, including ventricular arrhythmias and myocardial infarctions, in patients using ophthalmic phenylephrine. These episodes, some fatal, have usually occurred in patients with pre-existing cardiovascular diseases.

Significant elevations in blood pressure have been reported following instillation of topical ocular phenylephrine. Anticipated systemic exposure is minimal and transient, however, caution should be used in treating patients with poorly controlled hypertension. The risk of blood pressure elevations may be increased in patients requiring prolonged surgery.

Hyperthyroidism and unstable cardiovascular disease should be addressed prior to surgery.

Cross-sensitivity

There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs. There have been reports of bronchospasm or exacerbation of asthma associated with the use of ketorolac ophthalmic solution in patients who either have a known hypersensitivity to acetylsalicylic acid/NSAIDs, or a past medical history of asthma. Therefore, use Omidria with caution in individuals who have previously exhibited sensitivities to these active substances.

Cardiovascular reactions and cross-sensitivity reactions are known to occur with topical ophthalmic use of phenylephrine and ketorolac when used as monotherapy at higher concentration levels than present in Omidria.

The use of Omidria during intraocular lens replacement surgery may cause vision to be temporarily affected. (see section 4.7).

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Intraocular metabolic interactions are unlikely because phenylephrine and ketorolac are removed from the anterior chamber by irrigation during the surgical procedure and by normal aqueous humour circulation postoperatively. The magnitude of the mydriatic effect of Omidria may be altered in patients who concurrently receive medicinal products that can affect pupil size, such as opioids (miotics) or non-sedating antihistamines (mydriatics).

Concomitant use of phenylephrine and atropine may enhance pressor effects and induce tachycardia in some patients. Phenylephrine may potentiate the cardiovascular depressant effects of some inhalation anesthetic medicinal products. In a pharmacokinetic study evaluating Omidria, systemic exposure to each of phenylephrine and ketorolac was minimal and transient. Therefore, no interaction is expected.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

Omidria is not recommended in women of childbearing potential not using contraception.

Pregnancy

There are no or limited amount of data from the use of phenylephrine hydrochloride and/or ketorolac trometamol in pregnant women. Omidria is not recommended during pregnancy.

Breast-feeding

It is unknown whether phenylephrine is excreted in human milk. Ketorolac is excreted in human milk after systemic administration. A risk to the newborns/infants cannot be excluded. Omidria should not be used during breast-feeding.

Fertility

There are no or limited amount of data from the use of phenylephrine hydrochloride and/or ketorolac trometamol on fertility in humans.

4.7. Effects on ability to drive and use machines

Omidria has major influence on the ability to drive and use machines. As vision may be temporarily affected following intraocular lens replacement in patients who receive Omidria, patients should be advised not to drive or use machines until vision is clear. See section 4.8 for further details regarding possible visual disturbances.

4.8. Undesirable effects

Summary of the safety profile

The safety profile of Omidria is based on data from 459 adult patients collected during clinical development obtained in randomised controlled studies. Adverse reactions reported in patients receiving Omidria were typical postoperative findings and most were mild to moderate in intensity and resolved without intervention or any residual effects. The most frequently reported adverse reactions were, eye pain (4.8%), anterior chamber inflammation (3.9%), conjunctival hyperaemia (2.2%), photophobia (1.7%), corneal oedema (1.3%) and inflammation (1.3%). Each of these same findings was reported at a similar frequency in patients receiving placebo.

Following post-marketing exposure to Omidria, primarily in the Unites States of America (USA), there have been very few suspected adverse reactions. The most common adverse reactions are a small number of cases with corneal oedema which were mostly non-serious and self-limiting. The overall safety profile of Omidria on the market is similar to the clinical study experience with this medicinal product.

Tabulated list of adverse reactions

The frequency of adverse reactions is defined 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), not known (cannot be estimated from the available data).

System organ class

Common

Uncommon

Nervous system disorders

Headache.

Eye disorders

Eye pain;

Anterior chamber inflammation;

Conjunctival hyperaemia;

Corneal oedema;

Photophobia.

Ocular discomfort;

Eye inflammation;

Eye irritation;

Conjunctival oedema;

Corneal disorder;

Mydriasis;

Vision blurred;

Visual acuity reduced;

Vitreous floaters;

Eye pruritus;

Eyelid pain;

Foreign body sensation in eyes;

Glare;

Intraocular pressure increased.

Gastrointestinal disorders

Nausea.

General disorders and administration site conditions

Inflammation.

Pain.

Description of specific adverse reactions

Cardiovascular reactions and cross-sensitivity reactions are known adverse reactions associated with topical ophthalmic use of phenylephrine and ketorolac when used as monotherapy at higher concentraton levels than present in Omidria.

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

In case of accidental intracameral injection of the concentrated solution, the anterior chamber should be evacuated immediately and irrigated with standard ophthalmological irrigation solution.

Systemic overdose of phenylephrine may cause a rapid rise in blood pressure. It may also cause headache, anxiety, nausea, and vomiting, and ventricular arrhythmias. In the event of phenylephrine overdose, prompt injection of a rapidly acting alpha-adrenergic blocking agent, such as phentolamine, has been recommended.