Summary of the risk management plan (RMP) for Simbrinza (brinzolamide/brimonidine tartrate)

Transcription

1 EMA/339377/2014 Summary of the risk management plan (RMP) for Simbrinza (brinzolamide/brimonidine tartrate) This is a summary of the risk management plan (RMP) for Simbrinza, which details the measures to be taken in order to ensure that Simbrinza 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 Simbrinza, which can be found on Simbrinza s EPAR page. Overview of disease epidemiology Simbrinza is used to reduce intra-ocular pressure (pressure inside the eye) in adults with ocular hypertension (high intra-ocular pressure) or in those with an eye condition known as open-angle glaucoma. Glaucoma as well as other causes of high pressure in the eye increase the risk of damage to the retina and the optic nerve that sends signals from the eye to the brain. This can result in serious vision loss and even blindness. Glaucoma is the second leading cause of blindness and is the leading cause of irreversible visual loss. Treating glaucoma and ocular hypertension by reducing the pressure inside the eye has been demonstrated to protect against further damage to the optic nerve. It has been estimated that by the year 2020 there will be almost 80 million people in the world that are affected by either open-angle glaucoma or angle-closure glaucoma. The majority of these people will have open-angle 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 (short-sightedness), and decreased corneal thickness (the cornea is the transparent layer in front of the eye that covers the pupil and iris). Blindness in both eyes from glaucoma is expected to affect more than 11 million people worldwide by Summary of treatment benefits Simbrinza contains two active substances brinzolamide and brimonidine tartrate and is used when treatment with one single agent does not lower eye pressure enough. A clinical study involving 560 patients showed that Simbrinza reduced intra-ocular pressure (IOP) more effectively than either brinzolamide or brimonidine alone. Another clinical study showed that the effect of Simbrinza is comparable to the effect of brinzolamide and brimonidine added together. Unknowns relating to treatment benefits Simbrinza has not been studied in patients under 18 years and in pregnant or breastfeeding women. Simbrinza has also not been studied in patients with severe liver or kidney impairment, cardiovascular Page 1/5

2 disease, and those with other forms of glaucoma or eye disease or taking antidepressants. The benefit of Simbrinza in these patients is unknown. Elderly patients were included in the main clinical trials and no differences were observed between them and other adult patients. Summary of safety concerns Important identified risks Risk Preventability Hypersensitivity/ eye allergy/ anaphylaxis (severe allergic reaction)/ severe skin reactions Central nervous system depression in children Heart and circulatory disorders Corneal oedema (swelling of the thin, transparent Eye allergy has been reported when using brimonidine alone and may be delayed for up to 15 months after treatment is started and may be associated with a loss of control of intraocular pressure. Skin reactions and other more serious allergic reactions might also occur. Symptoms of central nervous system depression like slow heart rate, shallow breathing or cessation of breathing, hypotension (low blood pressure), low body temperature, low heart rate, drowsiness, sleepiness and even coma have been reported in the literature in association with brimonidine eye drops in children. Children younger than 6 years and weighing less than 20 kg may be at greatest risk. Brimonidine can cause fatigue (tiredness) and reduce blood pressure at rest. There have been isolated and reversible cases of corneal oedema reported in the literature with the use Patients should be asked about any previous history of eye-drop allergies or dry eye and should be monitored for early symptoms like conjunctivitis, red eyes, eyelid swelling, redness around the eye and breathing difficulties. Simbrinza should not be used in patients with allergies or hypersensitivity to any of the active substances, to other medicines of the same class, or to any of the excipients (inactive ingredients) Simbrinza must not be used in newborns and infants under the age of 2 years and is not recommended in children or adolescents. These effects can be prevented by prescribing Simbrinza with caution in patients with severe or unstable and uncontrolled heart or circulatory disease, cerebral or coronary insufficiency (insufficient blood supply to the brain or heart), tendency to develop pale or blue fingers, dizziness or faintness on standing up, and small blood vessels that become inflamed and swollen. This effect can be prevented by appropriate selection of patients, avoiding use in high risk patients, such Page 2/5

3 Risk Preventability covering over the eye) and/or corneal decompensation Metabolic acidosis (increase acid levels in blood) and/or kidney impairment of brinzolamide applied directly onto the eye. Carbonic anhydrase inhibitors (medicines that work in a similar way to brinzolamide) have been reported to cause metabolic acidosis in patients with kidney function impairment. as those with sensitive corneas, those who wear contact lenses, those who suffer from diabetes or corneal diseases, and those who have a history of eye surgery. Simbrinza should not be used in patients with acidosis and/or with severe kidney impairment or in patients with conditions which can lead to acidosis (e.g patients with kidney disease and elderly patients with reduced kidney function). Important potential risks Risk Damage to the corneal epithelium due to use of eye drops containing preservatives Patients with open-angle glaucoma and ocular hypertension are usually required to use eye drops for life. The presence of a preservative in eye drops increases the risk of both adverse effects on the corneal surface and the possibility of allergic reactions. The extent of the damage depends on, among other factors, the type of eye drops used, and the frequency and duration of use. Accidental overdose/ingestion in children Several reports of serious adverse effects following accidental ingestion of brimonidine by children have been published. After an accidental overdose, the children experienced symptoms of central nervous system depression like slow heart rate, shallow breathing or cessation of breathing, hypotension, low body temperature, low heart rate, drowsiness, sleepiness, and even coma, and all of them required admission to intensive care. They completely recovered after intensive care, mostly within 6-24 hours. Children younger than 6 years and weighing less than 20 kg are at greatest risk. Missing information Risk Use in pregnant women There are no or limited data from the use of Simbrinza in pregnant women. Animal studies have shown that Brinzolamide may interfere with normal fetal development, following systemic administration. Oral administration of brimonidine did not indicate direct harmful effects on reproduction. In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. Page 3/5

4 Risk Use by breastfeeding mothers Long-term safety of Simbrinza No studies have been carried out in breastfeeding women. It is not known whether Simbrinza is excreted in human milk. In animal studies, minimal levels of brinzolamide were detected in breast milk following oral administration. Most glaucoma patients receive long-term medical treatment. It is known that long-term eye drop use may cause damage to the eye surface, mainly due to the preservatives in the eye drops. Brimonidine can also cause eye allergy that may take months to occur but with symptoms generally similar to those of an immediate allergic reaction. 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 Simbrinza can be found on Simbrinza 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) Objectives Safety concerns /efficacy issue addressed Status Planned date for submission of (interim and) final results M Evaluate the additional IOP lowering effect with Simbrinza when used as an adjunct to travoprost (thrice daily dosing) Efficacy of Simbrinza in an adjunctive setting with a prostaglandin analogue (PGA) Started Planned Q M Evaluate the additional IOP lowering effect with Simbrinza when used as an adjunct to a PGA (thrice daily dosing) Efficacy of Simbrinza in an adjunctive setting with a PGA Started Planned Q M Evaluate the 24-hour intra-ocular pressure lowering of Simbrinza Nocturnal intraocular pressure control Started Planned Q Page 4/5

5 Study/activity (including study number) Objectives Safety concerns /efficacy issue addressed Status Planned date for submission of (interim and) final results (thrice daily dosing) 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 Page 5/5