Combinil, eye and ear drops 5 ml

A drug with antibacterial and anti-inflammatory action for local application in ophthalmology and ENT practice. The therapeutic effect of Combinil is due to the antibacterial action of ciprofloxacin and anti-inflammatory action of dexamethasone.

Ciprofloxacin is an antibacterial drug from the group of fluoroquinolones, has a broad spectrum of action and has a bactericidal effect. The drug inhibits bacterial enzyme DNA-gyrase, as a consequence of which DNA replication and synthesis of bacterial cell proteins are disrupted. Ciprofloxacin acts both on multiplying microorganisms and on those which are in the dormant stage.

It is 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, Chlamydia spp.; Gram-positive microorganisms: Staphylococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, Cynebacterium diphtheriae, Listeria monocytogenes.

Dexamethasone is a synthetic GCS. 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, cell infiltration, phagocytic activity, collagen deposition and fibroblast activity, inhibits scar tissue formation. Thus, dexamethasone reduces the main symptoms of inflammation.

Pharmacokinetics

When used in ophthalmology, ciprofloxacin penetrates well into various tissues of the eye except for 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 drug concentration reached in the blood is well below the detection limit and is not clinically relevant. Dexamethasone penetrates well into the corneal epithelium and conjunctiva after injection into the conjunctival sac; therapeutic concentrations are reached in the aqueous humor of the eye; the rate of penetration increases with inflammation or mucosal damage.

When used in otorhinolaryngologic practice when a fixed combination of ciprofloxacin and dexamethasone is administered into the ear canal, the Cmax for ciprofloxacin is 1.55 ng/L and for dexamethasone 0.86 ng/L. The T1/2 of ciprofloxacin is 2.9 h and that of dexamethasone is 2.8 h.

The excipient hydroxypropyl betacyclodextrin promotes prolonged storage of the active substance on the anterior surface of the eye, thus increasing the effectiveness and duration of action of the drug.

Indications

Infectious and inflammatory diseases of the eye and its appendages:

Infectious and inflammatory diseases of the ear:

Active ingredient

Composition

Active ingredients:

dexamethasone 1 mg,

ciprofloxacin (in the form of hydrochloride) 3 mg;

Associating agents:

benzalkonium chloride,

hydroxypropyl betadex,

dinatrium edetate,

mannitol,

hydrochloric acid (to pH 4.0),

d/water.

How to take, the dosage

In bacterial inflammatory diseases of the eye and its appendages

1 to 2 drops are instilled into the conjunctival sac every four to six hours. For the first 24 to 48 hours, the instillation may be every two hours.

For bacterial inflammatory ear disease

4 drops into the external auditory canal of the affected ear twice a day for 7 days. Do not change the head position for 60 seconds to allow full penetration of the product into the auditory canal.

The course of treatment: for acute bacterial conjunctivitis, blepharitis – from 5 to 14 days. For keratitis it should be used for 2 – 4 weeks. For prophylaxis of inflammatory diseases after surgical operations 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.

Interaction

Systemic absorption when applied topically is negligible, so the likelihood of drug interactions is extremely low.

Hepatic enzyme inducers, inhibitors and substrates. Drugs that inhibit the activity of cytochrome P4503A4 (CYP3A4) (barbiturates, phenytoin, carbamazepine, rifampicin) may increase the metabolism of corticosteroids. Drugs that induce CYP3A4 activity (ketoconazole, macrolides) may potentially cause increased plasma levels of corticosteroids.

Dexamethasone is a moderate inducer of CYP3A4. Co-administration with drugs metabolized with CYP3A4 (erythromycin) may increase their clearance, reducing plasma concentrations.

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

Can be successfully used in combination with azlocillin and ceftazidime in infections caused by Pseudomonas spp.

With meslocillin and other beta-lactam antibiotics in streptococcal infections.

With isoxazolylpenicillins and vancomycin – in staphylococcal infections.

With metronidazole and clindamycin – in anaerobic infections.

Special Instructions

In case of bacterial inflammatory diseases of the ear

Before using the ear drops, sanation of the external auditory canal (rinsing and drying of the external auditory canal) should be performed.

The product should be warmed to body temperature by holding it in your hands for 1-2 minutes before injecting it into the external auditory canal.

Lie on your side or with your head tilted back to make it easier to inject. Drip the indicated 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. A cotton turunda may be placed in the ear canal.

In bacterial inflammatory diseases of the eye and its appendages

Long-term use can lead to increased intraocular pressure with consequent damage to the optic nerve, decreased visual acuity and fields of vision, and formation of a posterior subcapsular cataract.

Intraocular pressure should be monitored when using Combinyl-Duo for more than 10 days.

In acute purulent eye infections, corticosteroids may worsen or mask disease symptoms.

Long-term use of the drug may decrease the immune response and lead to the development of a secondary infection of the eye.

Patients who wear contact lenses should remove them before putting the medication in and only wear them again after 20 minutes, because the preservative in the medication may have an adverse effect on the eye tissue.

The bottle should be closed after each use.

Do not touch the pipette tip to the eye.

Impact on ability to drive vehicles and mechanisms

Development of visual perception may decrease after the use of the drug; therefore, immediately after injection it is not recommended to drive vehicles and engage in activities requiring increased attention and quick psychomotor reactions.

Contraindications

Side effects

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

Hearing organ: discomfort and pain in the ear, itching in the ear, congestion.

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

Overdose

Symptoms: local – occurrence of pitting keratitis, erythema, increased lacrimation, edema and itching of the eyelids. There are no data on systemic manifestations of overdose.

Treatment: there is no specific antidote. The eyes should be flushed with water, the drug should be withdrawn and symptomatic therapy should be prescribed.

Pregnancy use

Combinil is not recommended for children under 18 years of age, pregnant and lactating women.