Active ingredients: Brinzolamide
AZOPT 10 mg / ml eye drops, suspension
Why is Azopt used? What is it for?
AZOPT contains brinzolamide which belongs to a group of medicines called carbonic anhydrase inhibitors. It lowers the pressure in the eye.
AZOPT eye drops are used to treat high pressure in the eye. This pressure can lead to glaucoma.
If the pressure in the eye is too high, it can damage vision.
Contraindications When Azopt should not be used
Do not use Azopt
- if you have severe kidney problems
- if you are allergic to any of the ingredients of AZOPT.
- if you are allergic to medicines called sulfonamides. Examples include drugs used to treat diabetes and infections as well as diuretics (tablets). AZOPT could cause the same reaction
- if you have too much acidity in your blood (a condition called hyperchloraemic acidosis)
If you have any further questions, please consult your doctor.
Precautions for use What you need to know before taking Azopt
Talk to your doctor or pharmacist before using AZOPT
- if you have kidney or liver problems
- if you have dry eyes or corneal problems
- if you are taking other sulfa drugs
- if you have a specific form of glaucoma in which the pressure inside the eye increases due to deposits blocking the flow of fluid (pseudoexfoliative or pigmentary glaucoma) or a specific form of glaucoma in which the pressure inside the eye increases (sometimes rapidly) because the eye is pushed forward and blocks the flow of fluids (narrow angle glaucoma)
Children and adolescents
AZOPT should not be used by infants, children or adolescents under the age of 18, except on the advice of a doctor.
Interactions Which drugs or foods may change the effect of Azopt
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
If you are taking another carbonic anhydrase inhibitor consult your doctor.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Women of childbearing potential are advised to use effective contraceptive methods during treatment with AZOPT. The use of AZOPT is not recommended during pregnancy or breastfeeding. Do not use AZOPT unless clearly indicated by your doctor.
Ask your doctor or pharmacist for advice before using any medicine.
Driving and using machines
Do not drive or operate machinery until your vision is clear. Your vision may be blurred for some time immediately after using AZOPT.
AZOPT may decrease the ability to perform operations that require mental attention and / or physical coordination. If you experience this symptom, be careful when driving vehicles or using machines.
AZOPT contains benzalkonium chloride
AZOPT contains a preservative (benzalkonium chloride) which can cause eye irritation and is known to discolour soft contact lenses. Contact with soft contact lenses should be avoided. If you wear contact lenses, you should remove them before fitting. application of AZOPT and wait at least 15 minutes after instillation of the dose before reinserting them.
Dose, Method and Time of Administration How to use Azopt: Posology
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Only use AZOPT for your eyes. Do not swallow it and do not inject it.
The recommended dose is 1 drop in the affected eye, twice a day - morning and evening. Use this amount unless your doctor tells you otherwise. Use AZOPT in both eyes only if your doctor tells you to. Use the medicine for as long as your doctor recommends.
- Get AZOPT and a mirror
- Wash your hands
- Shake the bottle and unscrew the cap. After removing the cap, if the safety ring has come loose remove it before using the product.
- Take the bottle in your hand, between your thumb and middle finger, and hold it pointing downwards
- You tilt your head back. Pull the lower lid down with a clean finger, so that a "pocket" is formed between the lid and the eye. Drop a drop of eye drops into the eye.
- Hold the tip of the bottle close to your eye. It may be helpful to look in the mirror
- Do not touch your eye or eyelid, surrounding areas or other surfaces with the bottle tip. It may infect the eye drops
- A light pressure on the base of the bottle will release one drop of AZOPT at a time.
- Do not squeeze the bottle: it has been specially designed so that a slight pressure on the bottom is sufficient
- After using AZOPT, press the corner of the eye near the nose with your finger (figure 3) for at least 1 minute. This prevents AZOPT from spreading to the rest of the body
- If you need to put the drops in both eyes, repeat the steps for the other eye
- Put the cap back on immediately after use
- Finish one bottle before opening the next.
If a drop is missing your eye, try again.
If you are using other eye drops or eye ointments, allow at least 5 minutes between instillation of AZOPT and other eye drops. Ophthalmic ointments should be administered last.
If you forget to use AZOPT
Use a single drop as soon as you remember and then return to your normal instill times. Do not use a double dose to make up for a forgotten dose.
If you stop taking AZOPT
If you stop using AZOPT without consulting your doctor, your eye pressure will not be under control and could lead to loss of vision.
Overdose What to do if you have taken too much Azopt
If you have instilled too much eye drops, immediately wash your eye with lukewarm water. Do not use the drops until it is time for your next dose.
Side Effects What are the side effects of Azopt
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects have been observed with AZOPT
Common side effects (may affect up to 1 in 10 people)
Effects in the eye: blurred vision; eye irritation, eye pain, eye discharge, eye itching, dry eye, abnormal sensation in the eye, red eye.
General side effects: bad taste.
Uncommon side effects (may affect up to 1 in 100 people)
Effects in the eye: sensitivity to light, inflammation or infection of the conjunctiva, eye swelling, itchy red or swollen eyelids, deposits in the eye, glare, burning sensation, growth on the surface of the eye, increased eye pigmentation, eye fatigue, crusting on the edge of the eyelid, increased tearing.
General side effects: decreased heart function, strong heart beat which may be fast or irregular, reduced heart rate, difficulty breathing, shortness of breath, cough, decreased blood count of red blood cells, increased blood chlorine level, dizziness, difficulty in memory, depression, nervousness, decreased emotions, nightmares, generalized weakness, abnormal sensation, fatigue, abnormal feeling, pain, difficulty in movement, decreased sex drive, male sexual difficulty, cold symptoms, chest congestion, infection of the cavities nasal passages, throat irritation, sore throat, increased or decreased sensitivity in the mouth, inflammation of the inside of the esophagus, abdominal pain, nausea, vomiting, stomach upset, frequent defecation, diarrhea, intestinal gas, digestive disturbance, kidney pain , muscle pain, muscle spasms, back pain, nose bleed, nose runny, stuffy nose, sneezing, red skin, abnormal skin sensation, smooth rash or redness with raised bumps, skin tightness, itching, headache, dry mouth, debris in the eye.
Rare side effects (may affect up to 1 in 1000 people)
Effects on the eye: corneal swelling, double or reduced vision, abnormal vision, flashes of light in the visual field, reduced ocular sensation, swelling around the eyes, increased pressure in the eye, damage to the optic nerve.
General side effects: memory impairment, drowsiness, chest pain, upper respiratory tract congestion, sinus congestion, nasal congestion, dry nose, ringing in the ears, hair loss, generalized itching, feeling jittery, irritability, irregular heart rate, generalized weakness, difficulty sleeping, dyspnoea, itchy skin rash.
Not known (frequency cannot be estimated from the available data)
Effects on the eye: eyelid abnormality, vision disturbances, corneal discomfort, eye allergy, decreased growth or number of eyelashes, red eyelid.
General side effects: increased allergy symptoms, decreased sensitivity, tremor, loss or decrease in taste, decreased blood pressure, increased blood pressure, increased heart rate, joint pain, asthma, pain in extremities, redness, inflammation or itching skin, liver function blood test abnormalities, swelling of the extremities, frequent urination, decreased appetite, malaise.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This also applies to any side effects not listed in this leaflet. You can also report side effects directly via the national reporting system. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the bottle and carton after "EXP". The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
The bottle should be discarded four weeks after first opening to prevent infections. Write the date you opened each bottle in the space below and in the space on the bottle label and box. For the 1 bottle pack write only 1 date.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other Information
What AZOPT contains
- The active ingredient is brinzolamide. Each milliliter contains 10 mg of brinzolamide.
- The other ingredients are: benzalkonium chloride, carbomer 974P, edetate disodium, mannitol (E421), purified water, sodium chloride and tyloxapol. Small amounts of hydrochloric acid or sodium hydroxide are added to maintain normal acidity values (pH values).
What AZOPT looks like and contents of the pack
AZOPT is a milky eye drop (suspension) packaged in a 5 ml or 10 ml screw cap plastic bottle (droptainer), or in a pack containing three 5 ml screw cap plastic bottles (droptainer). Not all packs may be on the market.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
AZOPT 10 MG / ML EYE DROPS, SUSPENSION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml of suspension contains 10 mg of brinzolamide.
Excipients:
Each ml of suspension contains 0.1 mg of benzalkonium chloride.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Eye drops, suspension.
White to off-white suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
AZOPT is indicated to reduce high intraocular pressure in cases of:
• ocular hypertension
• open angle glaucoma
as monotherapy in adult patients in whom beta-blockers have proved ineffective or in adult patients in whom beta-blockers are contraindicated, or as add-on therapy to beta-blockers or prostaglandin analogues (see also section 5.1).
04.2 Posology and method of administration
Dosage
When used on its own or as an adjunct therapy, the dosage is one drop of AZOPT in the conjunctival sac of the affected eye (s) twice daily. Some patients may have a better response with one drop three times daily. .
Special populations
Senior citizens
No dose adjustment is necessary in elderly patients.
Hepatic and renal impairment
AZOPT has not been studied in patients with hepatic impairment and is therefore not recommended in such patients.
AZOPT has not been studied in patients with severe renal impairment (creatinine clearance hyperchloraemic acidosis. As brinzolamide and its major metabolite are predominantly excreted by the kidney, AZOPT is contraindicated in such patients (see also section 4.3).
Pediatric population
The safety and efficacy of AZOPT in infants, children and adolescents aged 0-17 years have not been established. Currently available data are described in sections 4.8 and 5.1.
The use of AZOPT is not recommended in infants, children and adolescents.
Method of administration
For ophthalmic use.
Nasolacrimal occlusion or drooping of the eyelid after instillation is recommended. This may reduce the systemic absorption of the ophthalmic drug and result in a reduction of systemic side effects.
Instruct the patient to shake the bottle well before use. After removing the cap, if the safety ring is loose remove it before using the product.
To prevent contamination of the dropper bottle tip and suspension, care should be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle. Instruct patients to keep the bottle tightly closed when not in use.
When AZOPT is used as a substitute for another ophthalmic antiglaucoma agent, discontinue administration of the other agent and initiate AZOPT therapy the next day.
If more than one topical ophthalmic medicinal product is used, the medicinal products should be administered individually at least 5 minutes apart. Ophthalmic ointments should be administered last.
If you miss a dose, continue treatment with the next dose as scheduled. The dose should not exceed one drop three times a day per affected eye.
04.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
• Known hypersensitivity to sulfonamides (see also section 4.4).
• Severe renal insufficiency.
• Hyperchloraemic acidosis (see section 4.2).
04.4 Special warnings and appropriate precautions for use
Systemic effects
AZOPT is a sulphonamide carbonic anhydrase inhibitor and, although administered topically, is absorbed systemically. The same types of adverse reactions that are attributable to sulphonamides may occur with topical administration. If signs of severe reactions occur. or hypersensitivity, discontinue use of this preparation.
Acid / base disturbances have been reported with oral use of carbonic anhydrase inhibitors. Use with caution in patients at risk of renal impairment due to the possible risk of metabolic acidosis (see section 4.2).
The effects of brinzolamide have not been studied in preterm infants (less than 36 weeks gestational age) and in those less than 1 week of age. In patients with immaturity or significant renal tubular abnormalities, brinzolamide can only be given after careful risk assessment because of the possible risk of metabolic acidosis.
Oral carbonic anhydrase inhibitors may reduce the ability to perform tasks that require mental attention and / or physical coordination. AZOPT is absorbed systemically and therefore this may occur with topical administration.
Concomitant therapy
The potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition exists in patients receiving an oral carbonic anhydrase inhibitor and AZOPT. Concomitant administration of AZOPT and oral carbonic anhydrase inhibitors is not has been studied and is not recommended (see also section 4.5).
AZOPT has mainly been evaluated in concomitant administration with timolol in the adjunct therapy of glaucoma. The intraocular pressure (IOP) lowering effect of AZOPT as an adjunct therapy to the prostaglandin analogue travoprost was also investigated. No long-term data are available on the use of AZOPT as add-on therapy to travoprost (see also section 5.1).
There is limited experience with AZOPT in the treatment of patients with pseudoexfoliative or pigmentary glaucoma. Care should be taken in treating these patients and it is
Strict monitoring of intraocular pressure (IOP) is recommended. AZOPT has not been studied in patients with narrow angle glaucoma and its use is not recommended in these patients.
The possible role of brinzolamide on endothelial corneal functions of patients with compromised cornea (particularly in patients with low endothelial cell count) has not been studied.
Patients with contact lenses have not been specifically studied and, in these patients, careful monitoring during use of brinzolamide is recommended, since carbonic anhydrase inhibitors can alter corneal hydration and wear of lenses. contact could increase the risk to the cornea. Close monitoring of patients with corneal compromise such as patients with diabetes mellitus or corneal dystrophies is recommended.
Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and / or toxic ulcerative keratopathy. As AZOPT contains benzalkonium chloride, careful monitoring is required in case of frequent or prolonged use, in patients with dry eye, or corneal compromise.
AZOPT has not been studied in contact lens wearers. AZOPT contains benzalkonium chloride which can cause eye irritation and is known to discolor soft contact lenses. Contact with soft contact lenses should be avoided. Patient should be advised to remove contact lenses prior to surgery. application of AZOPT and wait at least 15 minutes after instilling the dose before reinserting them.
The possibility of a rebound effect after discontinuation of AZOPT treatment has not been studied; the intraocular pressure lowering effect should last for 5-7 days.
Pediatric population
The safety and efficacy of AZOPT in infants, children and adolescents aged 0-17 years have not been established and its use is not recommended in infants, children and adolescents.
04.5 Interactions with other medicinal products and other forms of interaction
No specific drug interaction studies have been conducted with AZOPT. In clinical studies, concomitant use of AZOPT and ophthalmic preparations based on prostaglandin analogues and timolol did not reveal any adverse interactions. The association between AZOPT and miotics or adrenergic agonists has not been evaluated during adjunctive glaucoma therapies.
AZOPT is a carbonic anhydrase inhibitor and although administered topically it is absorbed systemically. Acid / base disturbances have been reported with oral use of carbonic anhydrase inhibitors. The possibility of interaction should be considered in patients receiving AZOPT.
The cytochrome P-450 isoenzymes responsible for the metabolism of brinzolamide include CYP3A4 (the main one), CYP2A6, CYP2C8 and CYP2C9. CYP3A4 inhibitors such as ketoconazole, itraconazole, clotrimazole, ritonavir and troleandomycin may inhibit the metabolism of brinzolamide via CYP3A4. Caution should be exercised if CYP3A4 inhibitors are used concomitantly. However, since elimination is primarily via the kidney, accumulation of brinzolamide is unlikely. Brinzolamide is not an inhibitor of cytochrome P-450 isoenzymes.
04.6 Pregnancy and breastfeeding
Pregnancy
There are no or limited data from the ophthalmic use of brinzolamide in pregnant women. Studies in animals have shown reproductive toxicity following systemic administration (see also section 5.3).
AZOPT is not recommended during pregnancy and in women of childbearing potential who are not using contraceptive measures.
Feeding time
It is unknown whether brinzolamide / metabolites are excreted in human milk following topical ophthalmic administration. Studies in animals have shown excretion of minimal amounts of brinzolamide in breast milk following oral administration.
A risk to the newborns / infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or AZOPT therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility
Animal studies with brinzolamide have shown no effects on fertility. No studies have been performed to evaluate the effect of topical ophthalmic administration of brinzolamide on human fertility.
04.7 Effects on ability to drive and use machines
AZOPT has negligible influence on the ability to drive and use machines.
Temporary blurred vision or other visual disturbances may affect the ability to drive and use machines (see also section 4.8 i). If blurred vision occurs after instillation, the patient should wait for the vision to return. clear before driving or operating machinery.
Oral carbonic anhydrase inhibitors may impair the ability to perform operations that require mental attention and / or physical coordination (see also section 4.4 and section 4.8).
04.8 Undesirable effects
Summary of the safety profile
In clinical trials involving over 2732 patients treated with AZOPT as monotherapy or add-on therapy to timolol maleate 5 mg / ml, the most frequently reported treatment-related adverse reactions were: dysgeusia (6.0%) (bitter taste or unusual, see description below) and temporary blurring on instillation (5.4%) lasting from a few seconds to a few minutes (see also section 4.7).
Table of adverse reactions
The following adverse reactions have been reported with brinzolamide 10 mg / ml eye drops, suspension and are classified according to the following convention: very common (≥1 / 10), common (≥1 / 100 to
Dysgeusia (bitter or unusual taste in the mouth following instillation) was the most frequently reported systemically adverse reaction associated with the use of AZOPT in clinical trials; this is probably due to the passage of the eye drops into the nasopharynx through the nasolacrimal canal. Nasolacrimal occlusion or slight closing of the eyelids after instillation may help reduce the incidence of this effect (see also section 4.2).
AZOPT is a sulphonamide inhibitor of carbonic anhydrase with systemic absorption.
Gastrointestinal, nervous system, haematological, renal and metabolic effects are generally associated with systemic carbonic anhydrase inhibitors. The same type of adverse reactions attributable to oral carbonic anhydrase inhibitors are possible with topical administration.
No unexpected adverse reactions were observed with AZOPT when used as add-on therapy to travoprost. Adverse reactions seen with add-on therapy were observed with each individual active substance.
Pediatric population
In small, short-term clinical trials, adverse reactions were reported in approximately 12.5% of pediatric patients, most of which were local, non-serious ophthalmic reactions, such as conjunctival hyperaemia, eye irritation, ocular discharge and increased lacrimation (see also section 5.1).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. in Appendix V.
04.9 Overdose
No cases of overdose have been reported. Treatment should be symptomatic and supportive. Electrolyte imbalance, development of a state of acidosis and possible effects on the nervous system may occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antiglaucoma and miotic preparations, carbonic anhydrase inhibitors.
ATC code: S01EC04.
Mechanism of action
Carbonic anhydrase is an enzyme found in many tissues in the body, including the eye. Carbonic anhydrase catalyzes the reversible reaction which involves hydration of carbon dioxide and dehydration of carbonic acid.
The inhibition of carbonic anhydrase at the level of the ciliary processes of the eye decreases the secretion of aqueous humor, presumably due to a slowdown in the formation of bicarbonate ions with a consequent reduction in the transport of sodium and fluid. The result is a reduction in intraocular pressure (IOP), a major risk factor in the pathogenesis of optic nerve damage and visual field loss in glaucoma. Brinzolamide, an inhibitor of carbonic anhydrase II (CA-II), the predominant isoenzyme in the eye, with an IC50 in vitro of 3.2 nM and a Ki of 0.13 nM towards CA-II.
Clinical efficacy and safety
The intraocular pressure (IOP) lowering effect of AZOPT as an adjunct therapy to the prostaglandin analogue travoprost was investigated. After an initial 4-week treatment with travoprost, patients with an IOP ≥19 mmHg were randomized to receive additional treatment with brinzolamide or timolol. There was a "further decrease in mean diurnal IOP from 3.2 to 3.4 mmHg for the brinzolamide group and from 3.2 to 4.2 mmHg for the timolol group. There was an" incidence Higher overall of non-serious ocular adverse reactions, mainly related to signs of local irritation, in the brinzolamide / travoprost groups. The events were mild and did not affect the overall study discontinuation rate (see also section 4.8).
A clinical study with AZOPT was conducted in 32 pediatric patients under the age of 6 who were diagnosed with glaucoma or ocular hypertension. Some patients had never undergone ocular hypotonizing therapy while others were already being treated with others. IOP-lowering medicines. The latter did not have to stop therapy until AZOPT monotherapy was initiated.
Among patients who had never undergone ocular hypotonic therapy (10 patients), the efficacy of AZOPT was similar to that observed previously in adult subjects, with reductions of up to 5 mmHg in mean IOP from baseline. patients who were on topical IOP-lowering therapy (22 patients), the mean IOP increased slightly from baseline in the AZOPT group.
05.2 Pharmacokinetic properties
Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its high affinity for carbonic anhydrase II, brinzolamide is extensively distributed in red blood cells and exhibits a long half-life in whole blood (meaning approximately 24 weeks). In humans, the metabolite N-desethyl brinzolamide is formed. which also binds to carbonic anhydrase and accumulates in red blood cells. This metabolite binds primarily to carbonic anhydrase I in the presence of brinzolamide. In plasma, the concentrations of both brinzolamide and N-desethyl brinzolamide are low and generally below the limits of the quantitative analysis (
Plasma protein binding is not high (approximately 60%).Brinzolamide is eliminated primarily by renal excretion (approximately 60%). Approximately 20% of the dose is recovered in the urine as a metabolite. Brinzolamide and N-desethyl-brinzolamide are the major components in the urine, along with higher concentrations. low of the N-desmethoxypropyl and O-desmethyl metabolites.
In an oral pharmacokinetic study, healthy volunteers received brinzolamide 1 mg capsules twice daily for 32 weeks and carbonic anhydrase activity in red blood cells was measured to assess the degree of systemic inhibition of carbonic anhydrase.
RBC saturation of carbonic anhydrase II by brinzolamide was achieved within four weeks (RBC concentrations of approximately 20 μM). N-desethyl brinzolamide accumulated in RBCs reached steady state within 20-28 weeks , with concentrations between 6 and 30 mcM. The inhibition of total carbonic anhydrase activity in steady-state red blood cells was approximately 70-75%.
Subjects with moderate renal impairment (creatinine clearance of 30-60 ml / minute) received 1 mg of brinzolamide orally twice daily for up to 54 weeks. The drug concentration in red blood cells at the fourth week of treatment ranged from approximately 20 to 40 mcM. At steady state, concentrations of brinzolamide and its metabolite in red blood cells ranged from 22.0 to 46.1 and 17.1 to 88.6 mcM, respectively.
The concentration of N-desethyl-brinzolamide in the red blood cells is increased and the activity of the total carbonic anhydrase in the red blood cells is decreased with the reduction of the elimination of creatine, but the concentration of brinzolamide in the red blood cells and the CA-II activity is remained unchanged. In subjects with the highest level of renal dysfunction the inhibition of total carbonic anhydrase activity was higher, although less than 90% at steady state.
In a topical ocular study the steady-state concentrations of brinzolamide in red blood cells were similar to those found in the oral study, but the levels of N-desethyl brinzolamide were lower. Carbonic anhydrase activity was approximately 40-70% of predose levels
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
Developmental toxicity studies in rabbits with oral doses of brinzolamide up to 6 mg / kg / day (125 times the recommended human ophthalmic dose) revealed no effects on fetal development despite significant maternal toxicity. Similar studies in rats. showed slightly reduced ossification of the skull and sternum of fetuses from mothers administered brinzolamide at a dose of 18 mg / kg / day (375 times the recommended ophthalmic dose in humans), but not at doses of 6 mg / kg /day. These results occurred at doses that caused metabolic acidosis with a reduction in maternal body weight growth and fetal weight. A dose-dependent reduction in fetal weight was observed in offspring of mothers who received brinzolamide orally with variable decreases (approximately 5-6%) with 2 mg / kg / day to approximately 14% with 18 mg / day. kg / day. During lactation, the no adverse effect level in offspring was 5 mg / kg / day.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Benzalkonium chloride,
mannitol (e421),
carbomer 974p,
tyloxapol,
edeteate disodium,
sodium chloride,
hydrochloric acid / sodium hydroxide (to adjust the pH)
purified water.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years.
4 weeks after first opening.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Low density opaque polyethylene bottles with polypropylene screw cap of 5 ml and 10 ml.
The following pack sizes are available: pack containing 1 x 5 ml, 3 x 5 ml and 1 x 10 ml.
Not all packs may be on the market.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Alcon Laboratories (UK) Ltd.
Frimley Business Park
Frimley
Camberley
Surrey GU16 7SR
UK.
08.0 MARKETING AUTHORIZATION NUMBER
5 ml bottle: EU / 1/00/129/001 (AIC n.034770014 / E)
10 ml bottle: EU / 1/00/129/002 (AIC n.034770026 / E)
3 bottles of 5 ml: EU / 1/00/129/003
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 9 March 2000
Date of last renewal: March 9, 2005
10.0 DATE OF REVISION OF THE TEXT
D.CCE April 2015
