Instructions for Neladex eye and ear drops, dropper bottle 5 ml
Composition
active ingredients: dexamethasone, neomycin, polymyxin B;
1 ml of the drug contains: dexamethasone - 1 mg; neomycin (in the form of sulfate 5 mg) - 3.5 mg; polymyxin B sulfate - 6000 IU;
Excipients: hydroxypropylmethylcellulose, benzalkonium chloride, disodium edetate, sodium chloride, polysorbate 80, sodium hydroxide or diluted hydrochloric acid, water for injections.
Dosage form
Eye/ear drops, suspension.
Main physicochemical properties: white microdispersed suspension.
Pharmacotherapeutic group
Drugs used in ophthalmology. Corticosteroids in combination with antimicrobial drugs. ATX code S01C A01.
Pharmacological properties
Pharmacodynamics
Neladex is a combination drug with antibacterial and anti-inflammatory effects, containing neomycin, polymyxin B, and dexamethasone.
Neomycin is a broad-spectrum antibiotic from the aminoglycoside group. It has a bactericidal effect by disrupting protein synthesis in the microbial cell. It is active against gram-positive and gram-negative microorganisms, including Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Proteus spp., Shigella spp. It is weakly active against Pseudomonas aeruginosa and streptococci.
Inactive against pathogenic fungi, viruses, anaerobic flora. Resistance of microorganisms to neomycin develops slowly and to a small extent.
Polymyxin B is an antibiotic of polypeptide structure. The mechanism of action is due to the ability to bind to phospholipids of microbial cell membranes, which leads to their destruction. Active against gram-negative microorganisms, including Escherichia coli, Shigella spp., Enterobacter spp., Klebsiella spp., Haemophilus influenzae, Salmonella spp., Bordetella pertussis. Highly active against Pseudomonas aeruginosa. Inactive against Proteus spp., Neisseria spp., obligate anaerobes and gram-positive bacteria.
Vibrio cholerae (except the eltor subtype) and Coccidioides immitis are also sensitive to polymyxin B, but in general fungi are resistant to this antibiotic.
Dexamethasone is a glucocorticoid. It has no mineralocorticoid activity. It has a pronounced anti-inflammatory, antiallergic and desensitizing effect. Dexamethasone actively suppresses inflammatory processes and the release of inflammatory mediators by eosinophils, the migration of mast cells and reduces capillary permeability.
Pharmacokinetics
With topical application of the drug, systemic absorption is low.
Indication
Inflammation of the eye tissues, in which the use of corticosteroids is indicated and there is a superficial bacterial infection or the risk of its development (conjunctivitis, keratitis). Acute and chronic external otitis, acute otitis media without perforation of the eardrum.
Contraindication
Hypersensitivity to the active substances and/or other excipients of the medicinal product; hypersensitivity to other aminoglycosides; keratitis caused by Herpes simplex (the causative agent of herpes simplex); viral diseases of the cornea and conjunctiva (including vaccinia and chickenpox); untreated purulent eye infections; mycobacterial eye infections; untreated parasitic eye infections; fungal eye and ear diseases; viral ear diseases; existing or suspected perforation of the eardrum; tuberculosis; use is contraindicated after uncomplicated removal of a foreign body from the cornea; use is contraindicated in children.
Interaction with other medicinal products and other types of interactions
Concomitant use of topical steroids and topical nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of complications in corneal wound healing.
If more than one ophthalmic agent is applied topically, the interval between their applications should be at least 5 minutes. Eye ointments should be applied last.
In patients taking ritonavir, an increase in dexamethasone plasma concentrations is possible (see section "Special warnings and precautions for use").
CYP3A4 inhibitors (including ritonavir and cobicistat) may decrease dexamethasone clearance, leading to more severe adverse reactions and adrenocortical suppression/Cushing's syndrome. Concomitant use of these agents should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse reactions. Patients should be monitored for systemic corticosteroid adverse reactions if used concomitantly.
Application features
Application in ophthalmology.
Some patients may develop sensitivity to topical aminoglycosides, particularly neomycin. The severity of hypersensitivity reactions may range from local manifestations to generalized reactions such as erythema, pruritus, urticaria, skin rash, anaphylaxis, anaphylactoid reactions, or bullous reactions. If hypersensitivity occurs, the drug should be discontinued.
In addition, topical application of neomycin may cause skin sensitization.
Serious adverse reactions, including neurotoxicity, ototoxicity, and nephrotoxicity, have occurred in patients receiving systemic neomycin therapy or when neomycin was applied topically to open wounds or damaged skin. Nephrotoxicity and neurotoxicity have also been observed with systemic use of polymyxin B. Although these reactions have not been reported following topical ocular administration, the drug should be used with caution when concomitantly administered with systemic aminoglycosides or polymyxin B. Neomycin plasma levels should be monitored.
Prolonged use of topical corticosteroids in the eye may lead to ocular hypertension and/or glaucoma with subsequent damage to the optic nerve, deterioration of visual acuity, the appearance of visual field defects, as well as the formation of posterior subcapsular cataracts. In patients with prolonged use (more than 10 days) of topical corticosteroids in the eye, regular and frequent monitoring of intraocular pressure is necessary. This is especially important in children, since the increase in intraocular pressure caused by the use of corticosteroids may be greater in children and appear earlier than in adults. The risk of increased intraocular pressure and the risk of cataract formation caused by the use of corticosteroids is increased in patients with predisposing factors (for example, in patients with diabetes mellitus).
Visual disturbances may occur with systemic or topical corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should consult an ophthalmologist to determine possible causes, which may include cataracts, glaucoma, or rare conditions such as central serous chorioretinopathy (CSR), which has been reported following the use of systemic or topical corticosteroids.
The use of the drug in the immediate pre- and postoperative period is not recommended, since neomycin may in some cases cause neuromuscular blockade. This effect enhances the effect of skeletal muscle relaxants, which can lead to depression and respiratory arrest.
Corticosteroids may reduce resistance to nonsusceptible bacterial, fungal, parasitic or viral infections and may obscure the detection of such infections by masking the clinical signs of infection.
After intensive or prolonged continuous therapy in susceptible patients, including children and patients receiving ritonavir, Cushing's syndrome and/or adrenal suppression may occur, which is associated with systemic absorption of dexamethasone when used topically in ophthalmology (see section "Interaction with other medicinal products and other types of interactions"). In such cases, treatment should not be stopped abruptly - the dose should be reduced gradually.
In patients with persistent corneal ulceration, the possibility of fungal infection should be considered. If fungal infection occurs, the drug should be discontinued.
As with other antibacterial agents, prolonged use of neomycin and polymyxin may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the drug should be discontinued and alternative therapy instituted.
It is known that in the presence of diseases that lead to thinning of the cornea or sclera, topical corticosteroids may cause perforation. Topical corticosteroids used topically in the eye may slow the healing of corneal wounds. Topical NSAIDs are also known to slow or delay wound healing. Concomitant topical NSAIDs and steroids increase the risk of wound healing problems (see section 4.5).
Topical corticosteroids should never be used for undiagnosed eye redness because their misuse can lead to complete blindness.
To prevent complications of corneal diseases caused by the herpes virus, frequent slit-lamp examinations are recommended.
Topical corticosteroids are ineffective in keratitis caused by mustard gas or Sjögren's keratoconjunctivitis.
Prolonged use of the drug should be avoided as it may lead to increased skin sensitivity and the emergence of resistant microorganisms.
Cushing's syndrome and/or adrenal suppression associated with systemic absorption of ophthalmic formulations of dexamethasone may occur after intensive or long-term continuous therapy in susceptible patients, including children and patients receiving CYP3A4 inhibitors (including ritonavir and cobicistat). In such cases, the drug should be discontinued gradually.
Contact lenses should not be worn during treatment for eye inflammation or infections.
The medicinal product contains benzalkonium chloride, which may cause eye irritation and is known to discolour soft contact lenses. Contact with soft contact lenses should be avoided. However, if in the opinion of the physician contact lens wear is acceptable, the patient should be advised to remove contact lenses before instilling the eye drops and to wait at least 15 minutes before reinserting them.
Before starting the use of the drug, it is necessary to examine the condition of the eardrum (see the section "Adverse reactions"). If the integrity of the eardrum is impaired, the use of the drug is unacceptable, as serious complications are possible (deafness, balance disorders).
Prolonged uncontrolled use of the drug should be avoided, as it may lead to irreversible partial or complete deafness, especially in elderly patients and in patients with impaired renal function. In renal impairment, plasma clearance of neomycin is reduced.
Topical use of antibacterial agents may cause sensitization to the active substances and lead to systemic reactions.
The presence of a corticosteroid does not affect the manifestations of cutaneous allergic reactions to antibiotics, but may change the clinical picture of the allergic reaction.
The use of the medicinal product should be discontinued immediately if skin rashes or other local or systemic manifestations of allergic reactions occur.
Athletes should be warned that this medicine contains an active substance (dexamethasone) which may give a positive reaction during doping control.
If symptoms persist after a 7-day course of treatment, the patient should consult a doctor to review the diagnosis and treatment strategy.
Ability to influence reaction speed when driving vehicles or other mechanisms
During the use of the drug, temporary blurred vision or other visual disturbances may occur, which may affect the ability to drive or use other mechanisms. If blurred vision occurs during instillation, the patient should wait until vision returns to normal before driving or using other mechanisms.
Use during pregnancy or breastfeeding
Pregnancy.
There are limited data from the use of dexamethasone, neomycin, or polymyxin B in pregnant women. Aminoglycoside antibiotics, such as neomycin, cross the placenta after intravenous administration to pregnant women. Preclinical and clinical systemic exposure to aminoglycosides can cause ototoxicity and nephrotoxicity. Neomycin does not cause ototoxicity or nephrotoxicity when used topically at low doses in utero. In a rat study in which neomycin was administered orally at doses up to 25 mg/kg body weight per day, no maternal toxicity, fetotoxicity, or teratogenicity was observed. Prolonged or repeated use of corticosteroids during pregnancy is associated with an increased risk of intrauterine growth retardation. Children whose mothers received significant doses of corticosteroids during pregnancy should be closely monitored for signs of adrenal insufficiency.
Animal studies indicate reproductive toxicity following systemic and ophthalmic administration of dexamethasone. There are no data on the safety of polymyxin B in pregnant animals.
The medicine is not recommended for use during pregnancy.
Breast-feeding.
It is not known whether dexamethasone, neomycin or polymyxin B applied topically to the eye are excreted in human milk. Aminoglycosides are excreted in human milk after systemic administration. There are no data on the excretion of dexamethasone and polymyxin B in human milk. It is unlikely that dexamethasone, neomycin and polymyxin B will be detected in human milk and will not cause clinical effects in the newborn if this medicinal product is administered topically to the woman as appropriate. However, a risk to the breastfed child cannot be excluded. A decision should be made whether to temporarily discontinue breast-feeding during treatment with the medicinal product or to discontinue/abstain from the medicinal product, taking into account the potential benefit of breast-feeding for the child and the benefit of the medicinal product for the woman.
Impact on reproductive function.
There are no data on the effects of neomycin or polymyxin B on reproductive function in men or women.
There are insufficient clinical data to assess the effects of dexamethasone on male and female reproductive function. Dexamethasone did not have a negative effect on reproductive function in rats administered chorionic gonadotropin.
Method of administration and doses
Application in ophthalmology.
The bottle should be shaken well before instillation.
For mild forms of the disease, apply the drug in a dose of 1–2 drops into the conjunctival sac 4–6 times a day.
In severe forms of infections, drops can be used every hour, but not more than 2 days. The frequency of use should be gradually reduced to 2–3 times a day as the patient's condition improves. The duration of treatment is determined by the doctor individually in each individual case.
After instillation, tight eyelid closure or nasolacrimal occlusion is recommended. This reduces systemic absorption of drugs applied to the eye, which reduces the likelihood of systemic adverse reactions.
After opening the bottle for the first time, remove the protective ring, which is intended to control the first opening.
During treatment with eye drops, to prevent microbial contamination, do not touch the eye and eyelids, surrounding areas, or other surfaces with the dropper.
If more than one ophthalmic agent is applied topically, the interval between their applications should be at least 5 minutes. Eye ointments should be applied last.
Application in otology.
Apply the medicine in a dose of 1–5 drops in each ear 2 times a day.
The duration of treatment depends on the nature and severity of the disease and is determined by the doctor. The average duration of treatment is 7 days.
After opening the bottle for the first time, remove the protective ring, which is intended to control the first opening.
Before using the drops, you should warm the bottle by holding it in your hand to avoid the unpleasant sensation associated with getting cold liquid into the ear.
Do not instill under pressure. Tilt your head, drop the required number of drops into your ear and keep your head tilted for a few minutes. In this way, drip each ear.
Patients with impaired liver and kidney function.
No studies have been conducted for this category of patients. However, due to the low systemic absorption of the active substances after topical application of the drug, there is no need for dose adjustment.
Children
The medicine should not be used in children, as safety and efficacy have not been established.
Overdose
Symptoms of drug overdose observed in some patients include punctate keratitis, erythema, increased lacrimation, eyelid edema and itching. Manifestations of overdose may be similar to the side effects observed in some patients. Prolonged intensive use of the drug may lead to systemic adverse reactions.
In case of overdose with topical application, wash excess drug from the eye(s) with warm water. If necessary, carry out symptomatic treatment.
Adverse reactions
The most common adverse reactions observed during clinical trials of dexamethasone/neomycin/polymyxin B sulfate in 0.7-0.9% of patients were ocular discomfort, keratitis, and eye irritation.
Adverse reactions were classified according to frequency as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000). Within each grouping, adverse reactions are presented in order of decreasing seriousness. Adverse reaction data were obtained during clinical trials.
On the part of the organs of vision:
infrequently - keratitis, increased intraocular pressure, eye itching, eye discomfort, eye irritation.
Skin and subcutaneous tissue disorders:
rarely - local exfoliative dermatitis, skin atrophy, telangiectasia, striae, exacerbation of the underlying cause of the pathological skin condition, including eczema.
On the part of the body as a whole and reactions at the injection site:
rarely - reactions at the site of application, including pain, irritation, swelling, burning sensation, rash.
Additional adverse reactions identified during post-marketing surveillance include the following reactions. Frequency cannot be estimated from the available data. Within each system organ class, adverse reactions are presented in order of decreasing seriousness.
On the part of the immune system:
increased sensitivity.
From the nervous system:
headache.
On the part of the organs of vision:
ulcerative keratitis, blurred vision, photophobia, mydriasis, eyelid ptosis, eye pain, eye swelling, foreign body sensation in the eyes, eye hyperemia, increased lacrimation, corneal discoloration.
On the part of the organs of hearing and balance:
vestibular or cochlear ototoxicity in case of disruption of the integrity of the eardrum (see section "Special instructions for use").
Skin and subcutaneous tissue disorders:
Hypersensitivity reactions, including rash, itching, irritation, swelling, redness, contact dermatitis, Stevens-Johnson syndrome.
From the endocrine system:
Cushing's syndrome, adrenal suppression.
Additional adverse reactions that have been observed with the use of dexamethasone and may potentially occur with the use of this medicinal product: dysgeusia, dizziness, conjunctivitis, dry eye syndrome, eyelid margin scaling, decreased visual acuity, corneal erosion.
With intensive use of the drug, the development of systemic adverse reactions is possible.
Some patients may be sensitive to topical aminoglycosides. In addition, topical ophthalmic neomycin may cause skin sensitization (see section 4.4).
Prolonged use of topical corticosteroids in the eye may lead to increased intraocular pressure with subsequent development of glaucoma, optic nerve damage, deterioration of visual acuity and visual field disturbances, as well as the formation of posterior subcapsular cataracts (see section "Special warnings and precautions for use").
Since the medicinal product contains corticosteroids, in the presence of diseases leading to thinning of the cornea or sclera, the risk of perforation after long-term use increases (see section "Special instructions").
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions that occur after the registration of a medicinal product is very important. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.
Expiration date
2 years.
After opening the bottle, use the drug within 1 month.
Storage conditions
Store at a temperature not exceeding 25 °C out of the reach of children.
Packaging
5 ml in a plastic dropper bottle with a screw cap in a cardboard box.
Vacation category
According to the recipe.
Producer
EIP.I.Co., Egypt/ E.I.P.I.Cо., Egypt.
Location of the manufacturer and its business address
Tenth of Ramadan City, First Industrial Area B1, PO box: 149 Tenth, Egypt.
