Combinil, eye and ear drops 5ml

Composition

Active ingredients:

dexamethasone 1 mg,

ciprofloxacin (in the form of hydrochloride) 3 mg;

Auxiliary substances:

benzalkonium chloride,

hydroxypropyl betadex,

disodium edetate,

mannitol,

hydrochloric acid (up to pH 4.0),

d/i water.

Pharmacological action

A drug with an antibacterial and anti-inflammatory effect for topical use in ophthalmology and ENT practice. Therapeutic effect of the drug Combination is due to the antibacterial effect of ciprofloxacin and the anti-inflammatory effect of dexamethasone.

Ciprofloxacin is an antibacterial drug from the group of fluoroquinolones, has a wide spectrum of action, has a bactericidal effect. The drug inhibits the enzyme DNA gyrase of bacteria, as a result of which DNA replication and synthesis of bacterial cell proteins are disrupted. Ciprofloxacin acts both on multiplying microorganisms and on dormant ones. Active against gram-negative microorganisms: Esherichia coli, Salmonella spp., Shigella spp., Proteus spp. (indole-positive and indole-negative), Morganella morganii, Citrobacter spp., Klebsiella spp., Enterobacter spp., Vibrio spp., Campylobacter spp., Hafnia spp., Providencia stuartii, Haemophilus influenzae, Pasteurella multocida, Pseudomonas spp., Gardnerella spp., Legionella pneumophila, Neisseria spp., Moraxella catarrhalis, Acinetobacter spp., Brucella spp., Chlamydia spp. ;gram-positive microorganisms:  Staphylococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, corynebacterium diphtheriae, Listeria monocytogenes.

Dexamethasone is a synthetic corticosteroid. When applied topically, the therapeutic activity of dexamethasone is due to its anti-inflammatory, anti-allergic and antiproliferative effects. It reduces capillary permeability and proliferation, local exudation, cellular infiltration, phagocytic activity, collagen deposition and fibroblast activity, and inhibits the formation of scar tissue. Thus, dexamethasone reduces the main symptoms of inflammation.

Pharmacokinetics

When used in ophthalmology, ciprofloxacin penetrates well into various eye tissues, with the exception of the lens. Cmax occurs within 30 minutes, the highest concentration is observed in the moisture of the anterior chamber. Systemic reabsorption is observed. However, the concentration of the drug substance reached in the blood is significantly lower than the detection limit and has no clinical significance. Dexamethasone, after instillation in the conjunctival sac, penetrates well into the corneal epithelium and conjunctiva; at the same time, therapeutic concentrations are achieved in the watery moisture of the eye; with inflammation or damage to the mucous membrane, the penetration rate increases.

When used in otorhinolaryngological practice with the introduction of a fixed combination of ciprofloxacin and dexamethasone into the auditory canal, Cmax for ciprofloxacin is 1.55 ng/l, and for dexamethasone 0.86 ng/l. T1 / 2 of ciprofloxacin is 2.9 hours, dexamethasone is 2.8 hours.

Hydroxypropyl betacyclodextrin, which is part of the drug as an auxiliary component, contributes to the long-term preservation of the Active ingredient on the anterior surface of the eye, thereby increasing the effectiveness and duration of the drug’s action.

Indications

Infectious and inflammatory diseases of the eye and its appendages:

• acute and subacute conjunctivitis;
• keratitis;
• anterior uveitis;
• blepharitis and other inflammatory diseases of the eyelids;
• prevention and treatment of infectious complications after injuries to the eye and its appendages and during operations on the eyeball.

Infectious and inflammatory diseases of the ear:

• acute otitis externa;
• acute otitis media with a tympanic membrane shunt;
• acute otitis media with granulations and otorrhea in the presence of a tympanic membrane shunt.

Use during pregnancy and lactation

Kombinil is not recommended for children under 18 years of age, pregnant women and during lactation.

Contraindications

• herpetic keratitis and other viral lesions of the cornea and conjunctiva;
• tuberculosis of the eyes;
• fungal eye lesions;
• viral infections of the ear canal;
• perforation of the eardrum;
• children under 18 years of age;
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to active substances or to any of the auxiliary ingredients of the drug.

Side effects

From the side of the visual organ: corneal infiltrates, burning, redness, itching of the eyes, conjunctivitis, keratitis, periocular edema, foreign body feeling in the eye, photophobia, blurred vision, dry eye, eyelid edema, conjunctival hyperemia, glaucoma and optic nerve damage, decreased visual acuity and narrowing of the visual fields, cataract formation, secondary infection (fungal and bacterial), corneal thinning and/or perforation of the eyeball.

From the side of the organ of hearing: discomfort and pain in the ear, itching in the ear, ear congestion.

Others: facial edema, delayed wound healing, taste perversions, skin rash.

Interaction

Systemic absorption with topical application is insignificant, so the probability of drug interactions is extremely low.

Inducers, inhibitors, and substrates of liver enzymes. Drugs that inhibit the activity of cytochrome P 4503A4 (CYP3A4) (barbiturates, phenytoin, carbamazepine, rifampicin) may increase corticosteroid metabolism. Drugs that induce CYP3A4 activity (ketoconazole, macrolides) can potentially cause an increase in plasma corticosteroid levels. Dexamethasone is a moderate inducer of CYP3A4. Co-use with drugs metabolized by CYP3A4 (erythromycin) may increase their clearance, reducing the concentration in plasma.

When ciprofloxacin is combined with other antimicrobial drugs (beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole), synergy is usually observed; it can be successfully used in combination with azlocillin and ceftazidime for infections caused by Pseudomonas spp. ; with mezlocillin and other beta-lactam antibiotics — for streptococcal infections; with isoxazolylpenicillins and vancomycin — for staphylococcal infections; with metronidazole and clindamycin — for anaerobic infections.

It can be successfully used in combination with azlocillin and ceftazidime for infections caused by Pseudomonas spp.

With mezlocillin and other beta-lactam antibiotics – for streptococcal infections.

With isoxazolylpenicillins and vancomycin – for staphylococcal infections.

With metronidazole and clindamycin – for anaerobic infections.

How to take, course of use and dosage

For bacterial inflammatory diseases of the eye and its appendages

,1-2 drops are instilled into the conjunctival sac every four to six hours. For the first 24 to 48 hours, installations can be made every two hours.

For bacterial inflammatory diseases of the ear

,4 drops into the external auditory canal of the affected ear twice a day for 7 days. Do not change the position of the head for 60 seconds to fully penetrate the drug into the auditory canal.

Course of treatment: acute bacterial conjunctivitis, blepharitis-from 5 to 14 days. With keratitis – 2-4 weeks. For the prevention of inflammatory diseases after surgical interventions with perforation of the eyeball-from 5 days to 1 month.

If the drug is used for more than 10 days, the patient’s intraocular pressure should be monitored.

Overdose

Symptoms: local-the appearance of pinpoint keratitis, erythema, increased lacrimation, swelling and itching of the eyelids. There are no data on systemic manifestations of overdose.

Treatment: there is no specific antidote. You should wash your eyes with water, cancel the drug and prescribe symptomatic therapy.

Special instructions

Bacterial inflammatory diseases of the ear

Before applying ear drops, the external ear canal should be sanitized (rinse and dry the external ear canal).

Before instilling the drug in the external ear canal, warm it to body temperature, holding it in your hands for 1-2 minutes.

It is necessary to lie on your side or tilt your head back to facilitate instillation. Drop the specified amount of drops into the external ear canal. Allow the drops to drain into the external ear canal by pulling the earlobe down and back. Keep your head tilted back for about 2 minutes. You can put a cotton turunda in the external ear canal.

Bacterial inflammatory diseases of the eye and its appendages

Prolonged use can lead to increased intraocular pressure, followed by damage to the optic nerve, reduced visual acuity and fields of vision, and the formation of posterior subcapsular cataracts.

When using the drug Kombinil-Duo for more than 10 days, it is necessary to monitor intraocular pressure.

In acute purulent eye infections, corticosteroids can worsen or mask the symptoms of the disease.

Prolonged use of the drug can reduce the immune response and lead to the development of a secondary eye infection.

Patients using contact lenses should remove them before instilling the drug and put them back on only after 20 minutes, since the preservative contained in the drug can have an adverse effect on the eye tissue.

The bottle must be closed after each use.

Do not touch the tip of the pipette to the eye.

Influence on the ability to drive vehicles and mechanisms

After using the drug, visual clarity may decrease, so immediately after instillation, it is not recommended to drive a car and engage in activities that require increased attention and speed of psychomotor reactions.

Form of production

Eye and ear drops.

Storage conditions

In a dark place, at a temperature not exceeding 25 °C (do not freeze)

Shelf life

2 years

Active ingredient

Ciprofloxacin, Dexamethasone

Conditions of release from pharmacies

By prescription

Dosage form

eye drops