VI.2 Elements for a public summary VI.2.1 Overview of disease epidemiology
The term ocular hypertension usually refers to any situation in which the pressure inside the eye, called intraocular pressure, is higher than normal. Normal eye pressure ranges from 10-21 mm Hg (millimeters of mercury). Patients with ocular hypertension should be observed more closely than the general population for the onset of glaucoma.
Recent data on people with ocular hypertension from the Ocular Hypertension Treatment Study have shown that they have an average estimated risk of 10% of developing glaucoma over 5 years.
This risk may be decreased to 5% (a 50% decrease in risk) if eye pressure is lowered by medications or laser surgery. However, the risk may become even less than 1% per year because of significantly improved techniques for detecting glaucomatous damage.
Glaucoma is the second important cause of blindness in the world (after cataracts) and the primary cause of blindness among African-Americans. Open-angle glaucoma is the most common type of glaucoma among populations of European or African descent, whereas angle-closure glaucoma is more common among populations of Asian descent. It is estimated that there are 44.7 million people with open-angle glaucoma worldwide in 2010, and that this number will increase to 58.6 million in 2020.
The Barbados Eye Study found ocular hypertension present more frequently in women. Mean intraocular pressure (IOP) slowly increases with growing. Age older than 40 years is considered a risk factor for the development of ocular hypertension and primary open-angle glaucoma (POAG).
Pseudoexfoliation syndrome occurs when a flaky, dandruff-like material peels off the outer layer of the lens of the eye. It is also associated with secondary open-angle glaucoma.
Frequency of pseudoexfoliation syndrome in Europe was found to be 4.7% in England, 6.3% in Norway, 4% in Germany, 1.1% in Greece, and 5.5% in France. In a U.S. population, the Framingham Eye Study revealed an increase in the occurrence of pseudoexfoliation syndrome with age (0.6 percent in 52- to 64-year-olds, rising to 5 percent in 75- to 85-year-olds). However, pseudoexfoliation syndrome is rarely seen before age 50 years and is more common in females than in males.
VI.2.2 Summary of treatment benefits
Dorzolamide is a carbonic anhydrase inhibitor. Many studies have been performed, following first marketing authorisation of dorzolamide eyes drop solution on 1995 to evaluate safety and efficacy of it use as monotherapy and/or as adjunctive treatment.
As monotherapy, dorzolamide treatment reduces intra ocular pressure (IOP) by 18-26%. However, if it is used as an adjunctive therapy (e.g. to beta-blockers such as timolol), brings about additional 13-21% lowering of IOP
Dorzolamide reduces efficiently the ocular pressure comparing to other agents such as beta blockers and brimonidine. Therefore it may be used as additive to multiple topical anti-glaucoma agents (e.g.
as adjunctive treatment to latanoprost, a prostaglandin analogue)
In glaucoma patients who were intolerant to systemic carbonic anhydrase inhibitors, dorzolamide offers similar efficacy and better tolerability. It does not produce acid-base or electrolyte disturbances & severe systemic adverse events associated with oral carbonic anhydrase inhibitors.
[Dorzolamide] 20 mg/ml eye drops solution does not contain preservative. Thus, there is no risk of eye irritation that may occur due to the preservative itsself.
VI.2.3 Unknowns relating to treatment benefits
In the SmPC of [Dorzolamide] 20 mg/ml eye drops solution is stated that has not been studied invery young children less than 36 weeks gestational age and less than 1 week of age. Patients with significant renal tubular immaturity should only receive dorzolamide after careful consideration of the risk benefit balance because of the possible risk of metabolic acidosis.
Dorzolamide has not been studied in patients with acute angle-closure glaucoma.
VI.2.4 Summary of safety concerns
Important identified risks
Risk What is known Preventability
Safety concern in lay language
(medical term)
Brief summary in lay language
Whether risk can be
minimised or mitigated, and how
Administration in patients with severe kidney problems or hyperchloraemic acidosis (Use in patients with severe renal impairment (creatinine clearance < 30 ml/min) or hyperchloraemic acidosis)
Dorzolamide and its metabolite are excreted predominantly by the kidney.
In patient with severe kidney disease dorzolamide and its metabolite cannot be fully eliminated. In addition in case of hyperchloremic acidosis (is a form of metabolic acidosis) there is often an increased urine anion gap, due to the kidney's inability to secrete ammonia.
Dorzolamide should not be used in patients with severe kidney problems or hyperchloraemic acidosis
Disease of the surface layer of the eye with sore eye and blurred vision
(Corneal oedema and irreversible corneal decompensation)
Corneal oedema is manifested by blurred vision or visual disturbances (halos or rainbows around streetlights, headlights and other bright lights at night). If corneal edema progresses, symptoms may include blisters that form on the surface of the eye.
These can rupture and become painful, and also cause sensitivity to light.
Treatment should immediately discontinued and a physician should be advised as the disorder can eventually cause corneal nerves to rupture, resulting in severe pain
Disturbance in the acid/alkali balance (pH) of the blood
(Systemic adverse effects including urolithiasis)
Because dorzolamide is a topical carbonic anhydrase inhibitor used for the treatment of glaucoma and is
absorbed systemically, patients with a prior history of
kidney stones may be at increased risk of urolithiasis while using dorzolamide due to acid-base disturbances
In patients with group of risk, particular attention during treatment with dorzolamide is recommended. The concomitant administration of dorzolamide and oral carbonic anhydrase inhibitors is not recommended
Problem in the surface layer of the eye, eye surgery
(Choroidal detachment)
The choroid is the pigmented, highly vascular layer of the globe lying between the sclera (on the outside) and the retina (on the inside). The choroid can be subject to inflammatory
Management of eyes with chronic or recurrent choroidal detachment should include stopping all forms of aqueous suppressant therapy and
treating endogenous
disorders (often in conjunction with the retina), tumour formation and a number of other disorders.
Causes of choroidal detachment include a low intraocular pressure associated with eye surgery, blunt trauma, inflammatory diseases (e.g., scleritis), intraocular tumours, uveal effusion syndrome, and treatment with acetazolamide.
inflammation vigorously.
Occurrence of conjunctivitis (redness and irritation of the eye[s]), swelling of the eye or eyelids, skin rash, or itching in and around the eye
(Eye irritation including conjunctivitis, eyelid reactions)
Common adverse event (affecting less than 1 in 10 people): inflammation or swelling of the surface layer of the eye(s) and possible inflammation of the eyelid(s) and/or skin around the eye(s), watering or itching of the eye(s), blurred vision, have been reported.
Risk increased following long- term treatment with drug.
Ophthalmologist evaluate the risks and benefits of ophthalmic medications before initiating therapy, identify the minimum dosages necessary to achieve a therapeutic benefit, and monitor patients for local and systemic adverse effects
Concomitant administration of dorzolamide with other drugs such as acetazolamide, or a sulfa drug
(Drug combination dorzolamide and oral carbonic
anhydrase inhibitors)
There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and dorzolamide.
Systmeic side effecst includes bitter taste, gastrointestinal
disorders, headaches, dizziness, depression, fatigue,
urticaria, pruritus
The concomitant administration of dorzolamide
and oral carbonic anhydrase inhibitors is not recommended.
Important potential risks
Risk What is known (Including reason why it is considered a potential risk)
Eye infection (including
bacterial keratitis) or injury Bacterial keratitis is an infection and inflammation of the cornea that cause pain, reduced vision, light sensitivity and tearing or discharge from the eye that can, in severe cases cause loss of vision. Most bacteria only produce keratitis once the integrity of epithelium is compromised, such as following corneal abrasion or prolonged contact lens wear.
Improperly handled of ocular solution can become contaminated by common bacteria. In addition eye traumatism by erroneous handling of the container may result in eye infection. Patient should follows specific instructions for use included in the PIL of the product
Medication error Overdosage
Only limited information is available with regard to human overdose by accidental or deliberate ingestion of dorzolamide hydrochloride.
Symptoms
The following have been reported with oral ingestion:
somnolence; topical application: nausea, dizziness, headache, fatigue, abnormal dreams, and dysphagia.
Treatment
Treatment should be symptomatic and supportive. Electrolyte imbalance, development of an acidotic state, and possible central nervous system effects may occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
Lack of product efficacy Deterioration of patient vision Sulphonamide-associated
severe hypersensitivity reactions (including Stevens- Johnson syndrome and toxic epidermal necrolysis)
Dorzolamide belong to sulphonamides (a large group of drugs used to treat bacterial infections), and although administered topically, is absorbed systemically. Therefore the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration.
Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.
Sensitization may recur when a sulfonamide is readministered
irrespective of the route of administration Missing information
Risk What is known
Use in pregnant and breast- feeding women
Pregnancy:
Dorzolamide should not be used during pregnancy.
No adequate clinical data in exposed pregnancies are available.
Developmental toxicity studies with dorzolamide hydrochloride in rabbits at oral doses of ≥ 2.5 mg/kg/day revealed malformations of the vertebral bodies. These malformations occurred at doses that caused metabolic acidosis (a disruption of the body's acid/base balance) with decreased body weight gain in dams and decreased fetal weights.
Lactation:
It is not known whether dorzolamide is excreted in human milk.
In a study of dorzolamide hydrochloride in lactating rats, decreases in body weight gain of 5 to 7% in offspring at an oral dose of 7.5 mg/kg/day were seen during lactation. A slight delay in postnatal development (incisor eruption, vaginal canalization and eye openings), secondary to lower fetal body weight, was noted. Dorzolamide should not be used during lactation. If treatment with dorzolamide is required, then lactation is not recommended.
Use in patients with hepatic impairment
Dorzolamide has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients.
Use in patients with acute angle-closure glaucoma
The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents that reduce ocular pressure. Dorzolamide has not been studied in patients with acute angle-closure glaucoma.
Use in patients wearing contact lenses
Dorzolamide has not been studied in patients wearing contact lenses.
Use in paediatric patients Dorzolamide has not been studied in patients less than 36 weeks gestational age and less than 1 week of age. Patients with significant renal tubular immaturity should only receive dorzolamide after careful consideration of the risk benefit balance because of the possible risk of metabolic acidosis.
VI.2.5 Summary of risk minimisation measures by safety concern
All medicines have a Summary of Product Characteristics (SmPC) which provides physicians, pharmacists and other health care professionals with details on how to use the medicine, the risks
and recommendations for minimising them. An abbreviated version of this in lay language is provided in the form of the package leaflet (PL). The measures in these documents are known as routine risk minimisation measures.
This medicine has no additional risk minimisation measures.
VI.2.6 Planned post authorisation development plan Not applicable
VI.2.7 Summary of changes to the risk management plan over time
Version Date Safety concerns Change
1.0 29.10.2015 Important identified risks
●Hypersensitivity reaction to sulphonamides (including Stevens-Johnson syndrome and toxic epidermal
necrolysis)
●Use in patients with severe renal impairment (creatinine clearance < 30 ml/min) or hyperchloraemic acidosis
●Corneal edema and irreversible corneal decompensation
●Systemic adverse effects including urolithiasis
●Choroidal detachment
●Eye irritation including
conjunctivitis, eyelid reactions
Important potential risks
●Usage of medicinal product longer than 28 days after first opening the container
Missing information
●No adequate clinical studies in pregnant and
Initial version
breast-feeding women
●No studies in patients with hepatic impairment
●No studies in patients with acute angle-closure
glaucoma
●No studies in patients with the concomitant
administration of dorzolamide and oral carbonic anhydrase inhibitors
●No studies in patients wearing contact lenses
●Exposure in paediatric patients
1.0 14.06.2016 Important identified risks
●Use in patients with severe renal impairment (creatinine clearance < 30 ml/min) or hyperchloraemic acidosis
●Corneal edema and
irreversible corneal
decompensation
●Systemic adverse effects including urolithiasis
●Choroidal detachment
●Eye irritation including
conjunctivitis, eyelid reactions
●Drug combination dorzolamide and oral
carbonic anhydrase inhibitors
Important potential risks
●Eye infection (including bacterial keratitis) or injury
●Medication error
●Sulphonamide-associated
severe hypersensitivity
Implementation of day 70 and day 100 comments on the RMP
reactions (including Stevens-Johnson syndrome
and toxic epidermal necrolysis)
Missing information
●Use in pregnant and breast-feeding women
●Usein patients with hepatic impairment
●Use in patients with acute angle-closure glaucoma
●Use in patients wearing contact lenses
●Use in paediatric patients
