Summary of the risk management plan (RMP) for Omidria (phenylephrine / ketorolac)

EMA/368070/2015 Summary of the risk management plan (RMP) for Omidria (phenylephrine / ketorolac) This is a summary of the risk management plan (RMP) for Omidria, which details the measures to be taken in order to ensure that Omidria is used as safely as possible. For more information on RMP summaries, see here. This RMP summary should be read in conjunction with the EPAR summary and the product information for Omidria, which can be found on Omidria s EPAR page. Overview of disease epidemiology Omidria is used in adults during intraocular lens replacement (ILR) surgery to keep the pupil dilated (widened) and prevent its contraction, and to reduce eye pain after surgery. During ILR, the lens is removed and replaced by an artificial lens. There are two diseases potentially requiring ILR: cataract and refractive errors. A cataract is a clouding of the lens in the eye that affects vision. Mostly this occurs due to increased age. Cataracts are very common in older people. Cataracts occur in 50% of people between the age of 65-74, and in 70% of people over age of 75. Other causes are injury, hereditary diseases, radiation, the intake of certain drugs (e.g., anti-inflammatory medicines like steroids) or an underlying disease, such as diabetes. Refractive errors are vision problems that happen when the shape of the eye is abnormal and light rays are not focused on the retina. The most common types of refractive errors are nearsightedness (myopia), farsightedness (hyperopia), focus problems caused by the cornea (astigmatism) and the inability to focus close up due to age (presbyopia). About 94,000 ILR procedures were conducted in Western Europe in 2013 in patients with refractive errors, and this number is expected to increase to 120,000 by 2019. Summary of treatment benefits Omidria contains the active substances phenylephrine and ketorolac. The efficacy and safety of Omidria was evaluated in two clinical studies involving a total of 821 adults. Patients received either Omidria or placebo (a dummy treatment), and effectiveness was measured using the change in diameter of the pupil by the end of the surgery, and how much eye pain patients felt soon after surgery. Pupil widening was maintained in the Omidria-treated patients while the placebo-treated groups experienced progressive narrowing of the pupil during the course of the surgery. Patients treated with Omidria reported an average pain score of around 4, compared with around 9 for those given placebo. Unknowns relating to treatment benefits Studies with Omidria involved mainly healthy older patients without serious known health risks at the time of surgery (such as heart disease, liver disease, kidney disease, psychiatric disease, diseases Page 1/5

affecting the lung, certain forms of autoimmune diseases). Furthermore, pregnant and breastfeeding women were excluded. However, as Omidria is applied to the eye and treatment consists of two applications at most (one for each eye), the potential exposure to the rest of the body is minimal; therefore, the effects in other patient groups are expected to be similar. Summary of safety concerns Important identified risks Risk Preventability Allergy in patients who are allergic to aspirin and other painkillers called nonsteroidal antiinflammatory drugs (NSAIDs), or who have asthma (hypersensitivity or cross sensitivity to aspirin/nsaids, or a past medical history of asthma) Narrow-angle glaucoma Ketorolac (one of the components of Omidria) belongs to the class of NSAIDs and patients who have had an allergic reaction following use of an NSAID are likely to also be allergic to Omidria (this is known as cross-sensitivity). NSAIDs, including ketorolac, can cause asthma flareups or bronchospasm (sudden contraction of the airways, which can cause difficulty breathing). This has been reported in patients allergic to aspirin/nsaids and in asthma patients given Omidria. Narrow-angle glaucoma is a condition in which the pressure inside the eye increases rapidly because fluid cannot drain out. It may be caused by the shape of the eye, but it can also be triggered by certain medicines which dilate the pupil such as phenylephrine, one of the two active ingredients of Omidria. Omidria should be used with caution in individuals who have already shown hypersensitivity to acetylsalicylic acid (aspirin) or other NSAIDs, because one of the active substances in Omidria, ketorolac, belongs to this class of medicines. Omidria must not be used in patients known to be allergic to ketorolac. Omidria must not be used in patients with pre-existing narrow-angle glaucoma. Important potential risks Risk Wrong method of administration (medication error) Omidria is only administered to patients by a physician during eye surgery, therefore the risk of medication errors is considered to be very low. However, as with any medication, theoretically there are some errors that could occur regarding the application of Omidria. Also, Omidria could be mistaken for a different medicine that only contains phenylephrine and is also used during eye surgery. Medication errors were not reported during the studies to develop and license the medicine. To help prevent wrong methods of administration, the packaging of Omidria is designed to be different from that of other phenylephrine products that can be Page 2/5

Risk used during eye surgery. Furthermore, clear instructions on the correct use of Omidria are included in the product information. Problems with the heart or the blood vessels in patients with a history of heart disease or raised blood pressure and/or overactive thyroid glands (cardiovascular reactions in patients with pre-existing cardiovascular disease and/or hyperthyroidism) Build-up of fluid in the transparent layer in front of the eye that covers the pupil and iris resulting in swelling (corneal oedema) One of the active ingredients of Omidria, phenylephrine, can increase blood pressure because it causes the blood vessels to narrow. There have been reports of serious side effects on the heart including irregular heart beat and heart attack, or increases in blood pressure, following use of phenylephrine on the eye. These episodes have usually occurred in patients with pre-existing heart disease or raised blood pressure. However, as it is expected that very little phenylephrine enters the rest of the body from a single use of Omidria during ILR (because it is given as a very diluted irrigation solution that is washed in and over the eye), any effects on the body will be minimal and short-lived. Healthcare professionals should use caution when treating patients with poorly controlled hypertension. Hyperthyroidism and unstable cardiovascular disease should be treated before surgery. The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. After cataract surgery, fluid may build up and this can lead to swelling of the cornea (corneal oedema). This in turn can lead to blurred vision and potentially permanent corneal damage. Risk factors for developing swelling of the cornea include old age, complicated/repeat eye surgery, and pre-existing defects to the cornea. In addition ketorolac as well as other anti-inflammatory medicines and phenylephrine, the other active substance in Omidria, have also been reported to cause fluid build-up in the cornea. However, any build-up of fluid after cataract surgery usually resolves completely without any long term complications. In clinical trials, patients receiving Omidria experienced only mild to moderate build-up of fluid in the cornea and all reported events were reversible. Missing information Risk Use in children No data are available on the safety and efficacy of Omidria in children. Omidria is only indicated for use in adults. Use in patients with certain diseases which were excluded from the clinical studies (patients with connective tissue disease, inflammation of the eyes, injury of the iris, infection of the eye) People with certain pre-existing diseases were excluded from the clinical studies with Omidria because these diseases might have affected the evaluation of the effect of Omidria and might have interfered with the surgery. There is nothing that indicates that Omidria would not be safe or effective in these patient groups but because they have not been studied and exposed to Omidria in the clinical trial programme so far, evidence is lacking. Page 3/5

Risk Lack of long-term data on injury to the inner lining of the cornea (lack of longterm data on corneal endothelial injury) The cornea, the front part of the eye, is transparent and therefore without any blood vessels. The inner lining of the cornea is responsible for providing the necessary nutrients to the cornea without the help of blood vessels. Injury to this cell layer could, for example, result in corneal oedema. Ketorolac, one of the components of Omidria, has rarely been reported to cause corneal damage. However, no established mechanism for this is known. During the clinical studies with Omidria, there has been no evidence that Omidria causes damage to the inner part of the cornea. However, these studies have not yet provided enough data on long-term safety and more details on the effect of Omidria on these cells are needed. Influence of Omidria on the occurrence of thickening and swelling of the macula of the eye after eye surgery (influence on the incidence of cystoid macular oedema) Thickening and swelling of the macula (the yellow central area of the eye) due to fluid collection, called macular oedema, can occur in two forms: diabetic (caused by diabetes) or cystoid. The so-called cystoid macular oedema can have several causes, including cataract surgery. It usually develops within 1-3 months after the surgery. In general, cystoid macular oedema after cataract surgery happens in 0.1-2.3% of cases. So far, the occurrence in the clinical trial programme with Omidria is within this range, and the occurrence in the clinical trial programme is comparable between surgeries where Omidria was used and those where it was not used. However, the data available up to date is limited and further information will be collected to make sure that Omidria does not have a negative influence and does not lead to an increased risk of developing a cystoid macular oedema after cataract surgery. Summary of risk minimisation measures by safety concern All medicines have a summary of product characteristics (SmPC) which provides physicians, pharmacists and other healthcare professionals with details on how to use the medicine, and also describes the risks and recommendations for minimising them. Information for patients is available in lay language in the package leaflet. The measures listed in these documents are known as routine risk minimisation measures. The SmPC and the package leaflet are part of the medicine s product information. The product information for Omidria can be found on Omidria s EPAR page. This medicine has no additional risk minimisation measures. Planned post-authorisation development plan List of studies in post-authorisation development plan Study/activity (including study number) OMS302-ILR-007 Objectives To evaluate the effect of Omidria Safety concerns /efficacy issue addressed Status Planned date for submission of (interim and) final results General safety in Started September 2017 Page 4/5

Study/activity (including study number) Objectives Safety concerns /efficacy issue addressed Status Planned date for submission of (interim and) final results Phase 3 Randomized, double-masked, phenylephrinecontrolled study of the effect of Omidria (OMS302) in young children on pupil diameter and acute postoperative pain in children aged 0 to 3 years this population September 2014 OMS302-ILR-008 Phase 2 Randomized, double-masked, placebo-controlled study of the effect of Omidria (OMS302) in adolescents (PIP Number: 1361472175116) To evaluate the effect of Omidria on pupil diameter and acute postoperative pain in children aged 13 to 17 years General safety in this population Planned to start Q1 2016 March 2017 Studies which are a condition of the marketing authorisation None of the above studies are conditions of the marketing authorisation. Summary of changes to the risk management plan over time Not applicable. This summary was last updated in 07-2015. Page 5/5