Active ingredients: Netilmicin, Dexamethasone
NETILDEX 3 mg / ml / 1 mg / ml eye drops, solution
Netildex package inserts are available for packs:- NETILDEX 3 mg / ml / 1 mg / ml eye drops, solution
- NETILDEX 3 mg / ml / 1 mg / ml eye gel
Indications Why is Netildex used? What is it for?
What is Netildex and what is it for
Netildex contains two active ingredients: netilmicin and dexamethasone.
- Netilmicin is an antibiotic with bactericidal activity.
- Dexamethasone is a corticosteroid that reduces inflammation.
Netildex is used in adults to reduce inflammation and to kill bacteria in eyes that are swollen, irritated and likely to become infected with bacteria.
What you need to know before using Netildex
Netildex can be used in adults, including the elderly.
It is not recommended for people under 18 years of age.
Contraindications When Netildex should not be used
You do not use Netildex:
- if you are allergic to netilmicin, dexamethasone, antibiotics known as aminoglycosides or any of the other ingredients of this medicine (listed in section 6);
- if your doctor has told you that your eye pressure is too high;
- if you think you have a "viral or fungal intra- or extraocular infection;
- if you have, or have had in the past, a "viral infection of the eye" caused by herpes simplex virus (HSV);
- if your doctor has told you that you have an 'eye infection' caused by bacteria known as mycobacteria.
If you are not sure whether you should use Netildex, ask your doctor or pharmacist.
Precautions for use What you need to know before taking Netildex
Talk to your doctor or pharmacist before using Netildex.
Use in children and adolescents
Netildex is not recommended for use in children and adolescents (birth to 18 years of age).
For external use only.
Use Netildex only on the surface of the eye. This medicine should not be injected or swallowed.
If the problem with your eye (s) has not improved within a few days of starting treatment, please report it to your doctor. He / She may change your treatment.
If you are using Netildex for a long time:
- the pressure in your eye could increase and damage the optic nerve and cause vision problems. If you use Netildex for more than 15 days your eye pressure should be checked regularly by your doctor;
- could develop cataracts;
- healing processes could be slowed down;
- your body, following a lowering of the immune defenses, may not effectively fight other types of infections in your eye, in particular infections of a fungal and viral nature;
- purulent infections of the eye, with the use of corticosteroids, may worsen or it may be more difficult to identify the type of bacteria causing the infection;
- in diseases that cause thinning of the ocular surface, the use of corticosteroids could cause perforations of the cornea and of the "white part" of the eye (sclera);
- you may develop allergies to the antibiotic in the eye drops.
Before using Netildex tell your doctor if:
- have glaucoma or cases of glaucoma in the family;
- have cornea problems;
- you are taking other medications containing phosphates. Your doctor will check your cornea at regular intervals;
- wear contact lenses. You can use Netildex, but follow the instructions for contact lens wearers in section 3.
Interactions Which drugs or foods can modify the effect of Netildex
Netildex may interact with other medicines. Tell your doctor or pharmacist if you are taking or have recently taken any other eye drops or other medicines, including non-prescription medicines. You can use Netildex with other eye drops, but you must follow the instructions in section 3.
In particular, tell your doctor or pharmacist if you know you are taking:
- any other antibiotic, in particular polymyxin B, colistin, viomycin, streptomycin, vancomycin and cephaloridin. The use of other antibiotics at the same time as Netildex could increase the risk of kidney problems, hearing problems or repercussions on the activity of the antibiotics administered in combination with Netildex;
- cisplatin, an anticancer drug;
- diuretics (medicines that reduce water retention) such as ethacrynic acid and furosemide;
- anticholinergic drugs (drugs that block glandular secretion), such as atropine.
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.
Use in pregnancy
It is preferable not to use Netildex in pregnancy unless your doctor considers it necessary.
Use while breastfeeding
You shouldn't use Netildex if you are breastfeeding.
Driving and using machines
While using Netildex your vision may become blurred for a short time. If this happens, do not drive or use machines until your vision is clear again.
Netildex multidose eye drops contain a preservative called benzalkonium chloride.
This preservative may cause eye irritation or ocular surface changes. It can be absorbed by contact lenses and is known to discolour soft contact lenses. Therefore, avoid contact between this medicine and soft contact lenses.
Dose, Method and Time of Administration How to use Netildex: Posology
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Dose
The recommended dose is one drop in the infected eye four times a day or as directed by a doctor.
Do not change the dose of the eye drops without consulting your doctor.
Use in children and adolescents
Netildex is not recommended for use in children and adolescents (birth to 18 years of age).
Contact lens wearers
If you wear contact lenses, you must remove them before using Netildex multidose eye drops.
After administering Netildex, wait 15 minutes before putting your contact lenses back in.
If you are to use Netildex with soft contact lenses you should use Netildex eye drops in single-dose containers without preservative.
If you use Netildex with other eye drops
Wait at least 10 minutes between administering Netildex and other eye drops.
Instructions for Use
Multi-dose eye drops
Make sure the bottle is intact.
- Wash your hands and sit comfortably.
- Screw the cap tightly until the bottle is perforated. Unscrew the cap.
- Bring your head back.
- Use your fingers to gently pull down the lower lid of the affected eye.
- Turn the bottle upside down and place the bottle tip close to the eye, but without touching it. Do not touch the eye or eyelid with the dropper tip.
- Gently squeeze the bottle so that only one drop goes into his eye, then release the lower lid.
- Close the eye and press a finger against the corner of the affected eye near the nose. Hold for 2 minutes.
- Repeat in the other eye if your doctor has told you to.
- Put the cap back on the bottle.
Single-dose eye drops
Make sure that the single-dose container is intact.
- Wash your hands and get seated or in a comfortable position.
- Separate the single-dose container from the strip.
- Open by turning the top without pulling.
- Tilt your head back.
- Gently pull down the lower lid of the affected eye with your fingers.
- Invert the single-dose container and place the tip of the single-dose container close to the eye, but without touching it. Do not touch the eye or eyelid with the tip of the single-dose container.
- Press the single-dose container so that only one drop is administered, then release the lower lid.
- Close the eye and press a finger against the corner of the affected eye near the nose. Hold for 2 minutes.
- Repeat in the other eye if your doctor has told you to.
- Discard after use.
Netildex single-dose eye drops should be used immediately after opening. After administration, the single-dose container and unused content should be discarded.
If you handle the drops incorrectly, it can be contaminated with bacteria that can lead to eye infections. Using contaminated eye drops can cause serious eye damage and subsequent loss of vision
Overdose What to do if you have taken an overdose of Netildex
If you use more Netildex than you should
If you use more eye drops than you should it is unlikely that it will cause you any problems. Apply your next dose as normal.
If you ingest the entire contents of a multidose container of Netildex, you should consult your doctor immediately, as undesirable effects may occur.
If you forget to use Netildex
Do not use a double dose to make up for a forgotten dose. If you forget to use the drops at the usual time, wait until the next dose time and apply the dose as normal.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist
Side Effects What are the side effects of Netildex
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Possible side effects due to dexamethasone are:
- increased eye pressure after 15-20 days of application if you have glaucoma or are predisposed to it;
- cataract formation following prolonged treatments;
- development or aggravation of viral infections caused by herpes simplex virus (HSV) or fungal in nature;
- delayed healing.
In all these cases it is advisable to suspend the treatment and resort to adequate therapy.
Possible side effects due to netilmicin:
The most common side effect with the use of netilmicin is hypersensitivity. This is manifested by redness of the conjunctiva, burning and itching. These phenomena can occur in less than 3% of patients treated and are possible even after the use of other aminoglycoside antibiotics.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. 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 carton and bottle label after EXP.
The expiry date refers to the last day of that month.
Store at a temperature below 30 ° C.
Netildex multidose eye drops:
After first opening, do not use this bottle for more than 28 days. When you are not using Netildex multidose eye drops, keep the bottle inside the outer carton in order to protect it from light.
Netildex single-dose eye drops:
The product does not contain preservatives. After administration the single-dose container and unused content should be discarded.
Do not throw away 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.
Composition and pharmaceutical form
What Netildex contains:
The active substances are dexamethasone 1 mg / ml (as dexamethasone sodium phosphate) and netilmicin 3 mg / ml (as netilmicin sulfate).
The other ingredients are:
Netildex multidose eye drops:
sodium citrate, monobasic sodium phosphate monohydrate, disodium phosphate dodecahydrate, benzalkonium chloride, purified water.
Netildex single-dose eye drops:
sodium citrate, monobasic sodium phosphate monohydrate, disodium phosphate dodecahydrate, purified water.
Description of the appearance of Netildex and contents of the package
Netildex is a clear, colorless and slightly viscous solution.
Netildex multidose eye drops
One bottle containing 5 ml of Netildex eye drops, solution.
Netildex single-dose eye drops:
Five single-dose containers of 0.3 ml of Netildex eye drops, solution wrapped in an aluminum sachet.
Packs of 15 or 20 single-dose containers.
Not all pack sizes may be marketed.
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
NETILDEX 2 MG / ML 1 MG / ML EYE DROPS, SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains:
Netilmicin sulphate 4.55 mg, equal to Netilmicin 3 mg.
Dexamethasone Disodium Phosphate 1.32 mg, equivalent to Dexamethasone 1 mg.
Excipients with a known effect (multidose product): Benzalkonium chloride 0.05 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Eye drops, solution.
Clear and colorless, slightly viscous solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
NETILDEX is indicated in inflammatory states of the anterior segment of the eye, postoperative and otherwise, in the presence or at risk of bacterial infection.
04.2 Posology and method of administration
Adults (including the elderly)
Instill in the conjunctival sac of the affected eye a drop of eye drops 4 times a day or according to medical prescription.
When using nasolacrimal occlusion or eyelid closure for 2 minutes, systemic absorption is reduced.
This can lead to a decrease in systemic side effects and an increase in local activity.
Pediatric population
The safety and efficacy of NETILDEX in children and adolescents less than 18 years of age has not yet been established.
No data are available.
In pediatric patients, the product should only be administered after a careful risk-benefit assessment and under close medical supervision.
Method of administration
Multidose container
Make sure the bottle is intact before use.
1. Wash your hands and get seated or in a comfortable position.
2. Screw the cap tightly until the bottle pierces, then unscrew the cap.
3. Tilt your head back.
4. Gently pull down the lower lid of the affected eye with your fingers.
5. Invert the bottle and place the tip of the bottle close to the eye, but without touching it.
Do not touch the eye or eyelid with the dropper tip.
6. Gently squeeze the bottle so that only one drop is delivered, then release the lower lid.
7. Close the eye and press a finger against the corner of the affected eye near the nose. Hold for 2 minutes.
8. Repeat in the other eye as prescribed by the doctor.
9. Put the cap back on the bottle.
Single-dose container
Make sure that the single-dose container is intact before use.
1. Wash your hands and get seated or in a comfortable position.
2. Separate the single-dose container from the strip.
3. Open by turning the top without pulling.
4. Tilt your head back.
5. Gently pull down the lower lid of the affected eye with your fingers.
6. Invert the single-dose container and place the tip of the single-dose container close to the eye, but without touching it.
Do not touch the eye or eyelid with the tip of the single-dose container.
7. Press the single-dose container so that only one drop is delivered, then release the lower lid.
8. Close the eye and press a finger against the corner of the affected eye near the nose. Hold for 2 minutes.
9. Repeat in the other eye according to medical prescription.
10. Discard after use.
NETILDEX single-dose eye drops should be used immediately after opening.
After administration, the single-dose container and unused content should be discarded.
Precautions to be taken before handling or administering the medicinal product.
If contact lenses are worn, they should be removed prior to instillation of the multidose eye drops and can be reapplied after 15 minutes (see section 4.4).
Patients should be advised that the eye drops, if handled incorrectly, can be contaminated with bacteria that can lead to eye infections. Using contaminated eye drops can cause serious eye damage and subsequent loss of vision.
If more than one topical ophthalmic drug is used, they should be administered at least ten minutes apart.
04.3 Contraindications
Hypersensitivity to the active substances, to aminoglycoside antibiotics or to any of the excipients listed in section 6.1.
The product contains corticosteroids and is therefore contraindicated in patients suffering from:
1) intraocular hypertension,
2) herpetic keratitis or other eye infections caused by Herpes simplex,
3) viral diseases of the cornea and conjunctiva,
4) fungal infections of the eye,
5) mycobacterial eye infections.
04.4 Special warnings and appropriate precautions for use
When prescribing NETILDEX, official guidelines for the appropriate use of antibacterial agents should be considered.
NETILDEX is for ophthalmic use only and must not be administered orally, subconjunctival or introduced into the anterior chamber.
During treatments lasting more than 15 days, it is advisable to regularly check the intraocular pressure.
Prolonged use could lead to ocular hypertension / glaucoma resulting in damage to the optic nerve and defects in visual acuity and visual field.
Prolonged use of corticosteroids could cause:
1) onset of posterior subcapsular cataract,
2) delayed wound healing,
3) reduction of immune capacities with a consequent increase in the risk of secondary ocular infections, in particular of a fungal or viral nature.
In purulent infections of the eye, administration of corticosteroids can mask or aggravate the infection. In diseases causing thinning of the cornea or sclera it has been reported that the use of topical corticosteroids can cause corneal or scleral perforation.
Hypersensitivity to topical aminoglycosides may occur in some patients. If this occurs, discontinue use.
This product contains dexamethasone and should be used with caution in patients with glaucoma and should be carefully considered in patients with a family history of this disease.
This product contains phosphates which can lead to corneal deposits or corneal opacity when administered topically. It should be used with caution in patients with compromised cornea and in cases where the patient is receiving multiple therapy with other phosphate-containing ocular drugs (see section 4.5).
In the event that, within a few days, no improvement in the clinical picture is obtained or if phenomena of hypersensitivity or irritation occur, the treatment must be suspended and adequate therapy must be used.
NETILDEX multidose eye drops contain benzalkonium chloride, which is commonly used as a preservative in ophthalmic products. Benzalkonium chloride has been reported to cause punctate keratopathy and / or toxic ulcerative keratopathy and eye irritation. Close monitoring is required in the case of frequent or prolonged use of Netildex, or in conditions where the cornea is compromised.
Regular checks should be made if NETILDEX eye drops are used multidose in patients with previous corneal abnormalities, or use NETILDEX single-dose eye drops without preservative.
Use of contact lenses
NETILDEX eye drops multidose contains benzalkonium chloride, which is known to discolor soft contact lenses.
Soft contact lenses can also absorb benzalkonium chloride and must be removed before administering Netildex multidose eye drops, but can be re-applied after 15 minutes (see section 4.2).
If necessary, you can consider concurrent use of NETILDEX in single-dose containers without preservative and soft contact lenses.
Pediatric population
NETILDEX is not recommended for children and adolescents (see paragraph 4.2).
04.5 Interactions with other medicinal products and other forms of interaction
No interaction studies have been performed with NETILDEX.
Below is information on each of the active components.
Netilmicin:
No significant drug interactions have been reported with the use of netilmicin in eye drops.
The simultaneous administration of other potentially nephrotoxic and ototoxic antibiotics (including topical, especially if intracavitary) can increase the risk of these effects.
An increased potential nephrotoxicity of some aminoglycosides has been reported following subsequent or concomitant administration of other potentially nephrotoxic substances, such as cisplatin, polymyxin B, colistin, viomycin, streptomycin, vancomycin, other aminoglycosides and some potent cephalosporins (cephaloridin) or diuretics. such as ethacrynic acid and furosemide for the repercussions on the kidney.
Concomitant or subsequent administration of these drugs with netilmicin should be avoided.
In vitro, the combination of an aminoglycoside with a beta-lactam antibiotic (penicillins or cephalosporins) can cause significant reciprocal inactivation. Even when an aminoglycoside and a penicillin-like antibiotic have been administered through two different routes, a reduction in "half-life or plasma levels of the aminoglycoside in patients with renal insufficiency and in some patients with normal renal function."
Dexamethasone:
In patients predisposed to acute narrow-angle glaucoma, the risk of increased intraocular pressure associated with prolonged corticosteroid therapy is more likely to occur with concomitant use of anticholinergic drugs, particularly atropine and related compounds.
The risk of corneal deposits or corneal opacity is more likely to occur in patients with compromised cornea on polypharmacy with other phosphate-containing ocular medications.
04.6 Pregnancy and lactation
Use in pregnancy
There are no clinical data on the safe use of NETILDEX in pregnant women.
Animal studies have shown teratogenic activity of dexamethasone. It is preferable to avoid the use of NETILDEX during pregnancy.
Feeding time
There is insufficient information on the excretion of dexamethasone or netilmicin or their metabolites in breast milk following ocular administration.
A risk to the newborns / infants cannot be excluded.
NETILDEX should not be used while breastfeeding.
04.7 Effects on ability to drive and use machines
NETILDEX moderately affects the ability to drive and use machines. Instillation of eye drops may cause transient blurring of vision. Until this has resolved, patients should not drive or operate machinery.
04.8 Undesirable effects
Possible side effects following the use of NETILDEX can be attributed to the corticosteroid component, the anti-infective component or their combination.
Possible side effects due to dexamethasone are:
1) increase in intraocular pressure after 15-20 days of topical application in predisposed patients or glaucomatosis,
2) formation of posterior subcapsular cataract following prolonged treatments,
3) development or aggravation of Herpes simplex or fungal infections,
4) delayed healing.
In all these cases it is advisable to suspend the treatment and resort to adequate therapy.
Possible side effects due to netilmicin:
The most common side effect with the topical use of netilmicin is hypersensitivity. This manifests itself with conjunctival hyperemia, burning and itching. These phenomena can occur in less than 3% of treated patients and are possible even after topical use. of other aminoglycoside antibiotics.
04.9 Overdose
No cases of overdose have been reported.
In the event that the entire contents of a multidose container of NETILDEX (containing 5 mg dexamethasone) side effects may occur. In this case, consult your doctor immediately.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Combination anti-inflammatory and anti-infective agents, Combination corticosteroids and anti-infectives, ATC Code: S01C A01
NETILDEX contains two active substances: dexamethasone and netilmicin.
Dexamethasone:
Mechanism of action
Dexamethasone is a corticosteroid with an intense anti-inflammatory activity equal to 25 times that of hydrocortisone. Like all corticosteroids, it acts mainly by inhibiting the release of arachidonic acid, which is the main precursor of the most important mediators of the process. phlogistic, such as prostaglandins and leukotrienes. The efficacy of dexamethasone for the treatment of inflammatory conditions of the eye is well established.
Pharmacodynamic effects
The anti-inflammatory effect of corticosteroids is expressed through the suppression of the vascular adhesion molecules of endothelial cells and the expression of cytokines. This determines a reduced expression of pro-inflammatory mediators and the suppression of the adhesion of circulating leukocytes to the vascular endothelium, preventing their migration into the inflamed ocular tissues.
Dexamethasone is characterized by marked anti-inflammatory activity and reduced mineralocorticoid activity compared to some other steroids, and is one of the most potent anti-inflammatory agents.
Netilmicin:
• Mechanism of action
Netilmicin is a powerful broad-spectrum aminoglycoside antibiotic with a rapid bactericidal effect. It exerts its main effect by interfering with the synthesis and assembly of proteins of the bacterial cell at the level of the 30S subunit.
In this combination netilmicin offers antibacterial protection against sensitive bacteria.
• Pharmacodynamic effects:
Table 1 provides MICs at the breakpoint, distinguishing between susceptible and resistant organisms, based on EUCAST data.
The prevalence of resistance may vary geographically and with time for selected species and information on local resistance is desirable, particularly when treating severe infections. If necessary, when the local prevalence of resistance is such that the utility of the agent in some types of infections is questionable, expert advice is advised. The following information provides only a rough guide on the likelihood that bacteria are sensitive to netilmicin in NETILDEX.
Breakpoint definitions that classify isolates as susceptible or resistant are useful in predicting the clinical efficacy of antibiotics that are administered systemically. However, when the antibiotic is administered topically in very high concentrations directly to the site of infection, the definitions at the breakpoint are not applicable. Most isolates that would be classified as resistant to the systemic breakpoint are successfully treated topically.
In some European countries, the frequency of overall resistance to aminoglycosides can reach 50% of all staphylococci.
Table 1 MIC Species-related clinical breakpoints (EUCAST 2012)
Notes: S = Sensitive. R = Resistant. ECOFF = Common epidemiological cut-off value for resistance surveillance.
IE = Lack of sufficient evidence that the species in question is a good target for therapy with this drug. NR = Not Reported.
In vitro studies have shown that netilmicin is active against most strains of common ocular pathogens and against skin saprophytic flora. Table 2 provides a list of netilmicin susceptibility levels for a total of 767 bacterial isolates from clinical eye samples collected in France (FR), Germany (DE), Italy (IT), Poland (PL), Slovak Republic (SK) , Spain (ES) and United Kingdom (UK), demonstrating the general level of sensitivity of ocular flora bacteria to the antibiotic.
Table 2 In vitro sensitivity data to netilmicin from European isolates
Other information:
Cross-resistance between aminoglycosides (e.g. gentamicin, tobramycin and netilmicin) is due to the specificity of the modifications of the enzymes adenyltransferase and acetyltransferase. However, cross-resistance varies among aminoglycoside antibiotics due to the different specificity of the various modifying enzymes. The most common mechanism of acquired resistance to aminoglycosides is the inactivation of the antibiotic by enzymes that modify the encoded plasmids and transposons.
05.2 Pharmacokinetic properties
Dexamethasone:
• Absorption
After instillation into the conjunctival sac, dexamethasone reaches therapeutic intraocular concentrations. Maximal concentrations in the cornea and aqueous humor are reached within 1-2 hours. The plasma half-life of dexamethasone is approximately 3 hours.
• Distribution:
Following topical ocular administration of NETILDEX, the systemic distribution of dexamethasone is low.
After one drop of NETILDEX in each eye four times a day for two consecutive days, the peak plasma levels of dexamethasone after the last topical administration range from 220 to 888 picograms / ml (mean 555 & plumn; 217 pg / ml ).
• Metabolism:
After ocular administration, dexamethasone sodium phosphate undergoes a hydrolysis reaction catalyzed by enzymes of the tear film and the cornea and is partially converted to the fat-soluble form dexamethasone alcohol.
• Elimination:
Dexamethasone is extensively eliminated in the form of metabolites.
Netilmicin:
• Absorption
Like all other aminoglycosides, netilmicin is a poorly lipophilic molecule, therefore, after topical ocular application, it penetrates poorly into the anterior chamber of the eye.
• Distribution:
Studies conducted on humans have shown that after a single topical administration netilmicin reaches concentrations in tears of: 256 mcg / ml after 5 minutes, 182 mcg / ml after 10 minutes, 94 mcg / ml after 20 minutes and 27 mcg / ml after 1 hour.
• Metabolism:
Topically administered ocular netilmicin is not metabolised.
• Elimination:
As with other aminoglycoside antibiotics, netilmicin is eliminated unchanged primarily by the kidney.
05.3 Preclinical safety data
Non-clinical safety data are mainly derived from the bibliography.
Dexamethasone
The toxicity of dexamethasone is common to that of other cortisones and has been studied in several animal species after systemic administration. Acute toxicity and hepatic toxicity were observed. Dexamethasone inhibits skin carcinogenesis and the synthesis of DNA, RNA and proteins in the mouse epidermis.
Dexamethasone has the same general teratogenic action as cortisone and neural tube closure defects have been reported in rabbits and a greater potential to produce cleft palate than hydrocortisone.
In studies in rats after dermal application, no adverse effects on fetuses were reported. In monkeys treated with 10 mg / kg daily for 22-50 days, cranio bifidus and congenital cutaneous aplasia have been reported.
Dexamethasone has been shown to cross the placenta and induce a variety of malformations in laboratory animals. Treatment of pregnant baboons with dexamethasone resulted in a significant drop in maternal serum cortisol concentrations at all stages of pregnancy, which rapidly returned to normal concentrations after termination of treatment. At any stage of gestation, progesterone concentrations are not affected by dexamethasone. After administration of dexamethasone, the serum concentrations of estradiol, testosterone and androstenedione remained unchanged. Toxicity due to dexamethasone has been reported following topical ocular instillation in rabbits of dexamethasone alcohol and dexamethasone-21-tert-butyl acetate. Dose-dependent changes were detected with respect to a) infiltration of liver glycogen lipids, b) hepatic dropsy changes, c) vacuolation and multifocal hepatic necrosis, d) atrophy of Peyer's plaques of the intestine, e) atrophy of the white pulp of spleen; and f) atrophy of the adrenal cortex. No pathological changes were found in the other tissues examined (brain, heart, lungs, thyroid, kidney, pancreas, gonads, gallbladder, skeletal muscles, urinary bladder and eye).
Netilmicin
It is known that the aminoglycoside class of antibiotics can potentially cause significant nephrotoxic and ototoxic effects, some of which may be irreversible. Fertility, teratogenicity and postnatal studies on netilmicin in rats and rabbits did not provide any significant element of netilmicin toxicity, particularly after ocular administration.
In an ocular tolerance study in rabbits, no conjunctival and corneal or fundus lesions were observed and ocular reflexes were not altered.
Fixed combination
Results similar to those summarized above for each active substance were found in studies with the fixed combination in rabbits.
Val ut a t i o n e d e l r i sc h i o a m b i e nt a l e
The calculation of the predicted environmental concentration (PEC) of surface water for dexamethasone and netilmicin was based on a maximum human dose of eight drops of the drug in a 24 hour period.
Each drop contains 0.0608 mg of dexamethasone and 0.114 mg of netilmicin. The calculated values of PEC Surface Water resulting from the administration of the eye drops, for dexamethasone and netilmicin, respectively, are 0.000304 mcg / l and 0.000456 mcg / l. These values are below the action limit of 5% (0.01 mcg / l) and therefore it is not likely that the amount of dexamethasone and netilmicin in normal use of the product poses a risk to the aquatic environment.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Multi-dose eye drops:
Sodium citrate
Monobasic sodium phosphate monohydrate
Disodium phosphate dodecahydrate
Benzalkonium chloride
Purified water
Single-dose eye drops:
Sodium citrate
Monobasic sodium phosphate monohydrate
Disodium phosphate dodecahydrate
Purified water
06.2 Incompatibility
Not applicable.
06.3 Period of validity
Multi-dose eye drops:
2 years
After first opening: 28 days.
Single-dose eye drops
2 years
The product does not contain preservatives. After administration, the single-dose container must be disposed of even if only partially used.
06.4 Special precautions for storage
Multi-dose and single-dose eye drops:
Store at a temperature below 30 ° C. Store in the original container.
For storage conditions after first opening of the medicinal product, see section 6.3.
06.5 Nature of the immediate packaging and contents of the package
Multidose container
5ml white low density polyethylene bottle.
Single-dose container
Single-dose containers in low density polyethylene (LDPE) in aluminum sachet of 5 containers.
Packs of 15 or 20 single-dose containers.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions for disposal.
07.0 MARKETING AUTHORIZATION HOLDER
S.I.F.I. S.p.A. - Via Ercole Patti, 36 - 95025 Lavinaio - Aci S. Antonio (CT) - Italy
08.0 MARKETING AUTHORIZATION NUMBER
NETILDEX 3 mg / ml / 1 mg / ml eye drops, 5 ml solution: 036452011
NETILDEX 3 mg / ml / 1 mg / ml eye drops, solution 15 single-dose containers: 036452023
NETILDEX 3 mg / ml / 1 mg / ml eye drops, solution 20 single-dose containers: 036452035
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: March 2006
Date of latest renewal: November 2012
10.0 DATE OF REVISION OF THE TEXT
November 2013
