Summary of the risk management plan (RMP) for Izba (travoprost)

Transcription

1 EMA/14138/2014 Summary of the risk management plan (RMP) for Izba (travoprost) This is a summary of the risk management plan (RMP) for Izba, which details the measures to be taken in order to ensure that Izba 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 Izba, which can be found on Izba s EPAR page. Overview of disease epidemiology Glaucoma is the second leading cause of global blindness and is the leading cause of irreversible visual loss. Glaucoma is a group of eye conditions resulting in damage to the optic nerve (the nerve that sends signals from the eye to the brain), which may cause loss of vision. Reduction of the pressure inside the eye has been demonstrated to protect against further damage to the optic nerve. By the year 2020 it has been estimated that there will be almost 80 million people in the world with open-angle glaucoma and angle-closure glaucoma. The majority of these individuals will have openangle glaucoma, which is the most common type of glaucoma among Europeans or Africans. Risk factors for open-angle glaucoma include increased age, African ethnicity, family history, increased pressure inside the eye, myopia, and decreased corneal thickness (the cornea is the transparent layer in front of the eye that covers the pupil and iris). Bilateral blindness (blindness in both eyes) from glaucoma has been projected to affect more than 11 million people worldwide by Summary of treatment benefits Travoprost was developed to decrease intra pressure (IOP, pressure inside the eye) in patients diagnosed with open-angle glaucoma (OAG) or hypertension (OHT, when the pressure in the eye is higher than normal). Increased IOP is considered the main risk factor for the progressive loss of vision in patients diagnosed with OAG. In patients diagnosed with OHT, the presence of increased IOP may result in these patients developing OAG. Currently, the only treatment for either OAG or OHT is through the lowering of IOP with the use of medication and/or through surgical procedure(s). 598 patients were treated with travoprost 40 microgram/ml in the 3 studies required for the registration of Travatan (travoprost 40 microgram/ml) and the duration of the studies was from 6 to 12 months: C patients duration 12 months C patients duration 6 months C patients duration 9 months Page 1/5

2 In these studies, patients with OAG or OHT who took travoprost 40 microgram/ml experienced 7-8 mmhg (millimetres of mercury, a measurement of pressure) decreases in IOP. Clinical trial experience involving travoprost at a concentration of 30 microgram/ml (Izba) demonstrated that the IOP-lowering effect (decrease in millimetres of mercury) with travoprost 30 microgram/ml was equivalent to that of travoprost 40 microgram/ml in patients with OAG or OHT. Unknowns relating to treatment benefits Overall, the patients enrolled in clinical trials represent the population that would expect to receive travoprost, with the exception of children, pregnant women or nursing mothers, patients with advanced glaucoma, patients who have been operated for cataracts, patients with a history of active intra inflammation and/or with active intra disease. Summary of safety concerns Important identified risks Risk Preventability Macular oedema Hyperpigmentation (darkening) Hypertrichosis (excessive growth of hair) Iris and uveal inflammations Macular oedema has been reported during treatment with travoprost and other products from the same class. This effect is usually reversible after discontinuation of the medicine. Iris darkening (frequency 1/10) and skin darkening around the eyes (frequency >1/100 to <1/10) have been reported with travoprost. They do not pose a known threat to vision or health. Skin changes seem to be reversible after discontinuation of the medicine. However, iris darkening is often irreversible. Excessive growth of hair is considered as a non-serious and mild effect associated with the use of prostaglandin analogues. Symptomatic iritis (inflammation of the iris) appears to be an uncommon adverse event associated with all prostaglandin analogues. Its course is generally mild and the inflammation resolves upon discontinuation of the medicine with or without antiinflammatory therapy. patients who have undergone cataract surgery or other surgery as well as patients with other risk factors for macular oedema, such as (eye) inflammations, diabetes or hypertension (high blood pressure). If travoprost is used in such patients, patients should check their vision frequently and promptly report any change. In case of macular oedema, the medicine should not be used again, to prevent recurrence. The risk of iris darkening appears to depend on eye colour before treatment. Patients with nonhomogenously blue, grey or hazel irises show greater changes. Caution should be exercised when treating glaucoma only in one eye with prostaglandin analogues (class of medicines to which travoprost belongs). Termination of prostaglandin analogue treatment may reverse this effect but conclusive evidence has not been obtained. Patients who have abnormally positioned eyelashes that grow back toward the eye should be monitored for this complication. Yes, by using travoprost with caution in patients with a history of iritis, or with risk factors for iritis. Reinitiating therapy after an episode of iritis may not be advisable. Page 2/5

3 Risk Preventability Cardiac and vascular disorders (affecting the heart and blood vessels) Respiratory disorders (affecting the airways) Hypersensitivity (allergy) Cardiovascular disorders such as angina pectoris (pains to the chest, jaw and back), bradycardia (slow heart rate), chest pain, hypertension and hypotension (high or low blood pressure) have been reported in association with travoprost administration although they are considered very uncommon. Respiratory disorders such as dyspnoea (difficulty breathing), asthma and worsening of asthma have been associated with the use of prostaglandin analogues. These and other respiratory symptoms have been reported with the use of travoprost. Allergy induced by topical glaucoma treatment is primarily seen in the conjunctiva and around the eye. Serious allergic reactions to travoprost are rare. patients with pre-existing cardiovascular disorders. patients with pre-existing respiratory disorders. patients with hypersensitivity to travoprost or to any of the excipients, or with a tendency to develop allergies and asthma. Also by monitoring for early symptoms. Important potential risks Risk Melanoma (pigmented skin cancer) Corneal damage due to use of preserved eye drops Use during pregnancy and lactation Prostaglandin analogues are well known to cause pigmentary (colour) changes in iris, eyelashes and skin around the eye. The mechanism by which they increase pigment synthesis is uncertain. Melanoma was not seen in the clinical trials for travoprost which studied 6,385 patients and healthy volunteers. Three spontaneous cases of melanoma have been reported to date, two with travoprost and one with the fixed combination of travoprost and timolol. Four cases have been reported in the literature with members of the same pharmaceutical class: one eyelid melanoma associated with bimatoprost (another type of prostaglandin analogue) and one choroidal melanoma and two cutaneous melanomas associated with latanoprost (another type of prostaglandin analogue). However, a direct link between prostaglandin analogue use and development of melanoma has never been documented. Travatan and Izba are indicated to decrease elevated intra pressure in patients with hypertension or open-angle glaucoma. This is a long-term condition where patients are usually exposed to topical medications for life. The presence of a preservative increases the risk of adverse effects on the corneal surface (cell loss and tear film disruption) and the possibility of hypersensitivity reactions. The damage depends on the agent, the posology and the length of treatment. Clinical trials involving Travatan (travaprost 40 microgram/ml) with a duration of up to 5 years as well as postmarketing experience with Travatan (travaprost 40 microgram/ml) have not confirmed an increased frequency of corneal events. Therefore, this is considered only as a potential risk for Izba (travoprost 30 microgram/ml). Animal studies with travoprost have shown reproductive toxicity. Pregnant women, women of childbearing potential and Page 3/5

4 Risk breastfeeding women were excluded from participation in clinical trials. 17 spontaneous cases reporting exposure during pregnancy with associated adverse events have been received. Neither Travatan nor Izba should be used during pregnancy, breastfeeding, or in women of childbearing potential unless they are using adequate contraceptive methods. Missing information Risk Use in population Potential interactions During the development of travoprost (30 or 40 microgram/ml), patients under the age of 18 years have been excluded from participation in clinical trials. Thus, the safety and efficacy of travoprost (30 or 40 microgram/ml) in patients below the age of 18 years have not been established and its use is not recommended in these patients until further data become available. Currently 2 clinical trials are ongoing involving glaucoma patients. No specific pharmacokinetic drug-drug interactions are known for travoprost. Interaction studies have not been performed for Travatan, nor for Izba. 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 Izba can be found on Izba 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 number and title C An open-label, pharmacokinetic and safety study in glaucoma or Objectives To evaluate the steady-state plasma concentrations of Travoprost free acid (AL-5848) following once daily administration of Travoprost Safety concerns /efficacy issue addressed Safety and pharmacokinetics in population Status Ongoing Started Jan 2013 Date for approval of interim or final reports Planned 2014 Page 4/5

5 Study number and title hypertension patients C A 3 month, multicentre, double-masked safety and efficacy study of Travoprost compared to Timolol (0.5% or 0.25%) in glaucoma patients Objectives (preserved with POLYQUAD) in patients with glaucoma or hypertension. To assess the safety in patients with glaucoma or hypertension. To demonstrate that the IOPlowering efficacy (preserved with POLYQUAD) is non-inferior to Timolol Solution (0.5% or 0.25%) in glaucoma patients Safety concerns /efficacy issue addressed Safety and efficacy in population Status Ongoing Started Sept 2012 Date for approval of interim or final reports Planned 2014 Studies which are a condition of the marketing authorisation None of the above studies are conditions of the marketing authorisation for Izba, but they are conditions for the PIP (Paediatric Investigation Plan) application. Summary of changes to the risk management plan over time Not applicable. This summary was last updated in Page 5/5