Tsiproneks eye/ear drops 0.3% dropper bottle 5 ml

Instructions for use Tsiproneks eye/ear drops 0.3% dropper bottle 5 ml

Composition

active ingredient: ciprofloxacin;

1 ml of solution contains 3 mg of ciprofloxacin in the form of ciprofloxacin hydrochloride monohydrate 3.5 mg;

Excipients: mannitol (E 421); sodium acetate, trihydrate; glacial acetic acid; disodium edetate; benzalkonium chloride, solution; purified water.

Dosage form

Eye and ear drops, solution.

Main physicochemical properties: almost colorless light yellow or light green transparent liquid.

Pharmacotherapeutic group

Means for use in ophthalmology and otology. Antimicrobial agents. ATX code S0ZA A07.

Pharmacological properties

Pharmacodynamics

Mechanism of action

Ciprofloxacin hydrochloride is a quinolone antibiotic. The bactericidal action of quinolones, which mainly affects bacterial DNA synthesis, is expressed by inhibiting DNA gyrase.

Ciprofloxacin has high in vitro activity against most gram-negative microorganisms, including Pseudomonas aeruginosa. It is also effective against aerobic gram-positive microorganisms, such as staphylococci and streptococci.

Sensitivity to microorganisms

Ophthalmic use

Ciprofloxacin has been shown to be active against most strains of the following organisms in both in vitro studies and clinical use in ocular infections.

Aerobic gram-positive microorganisms:

Staphylococcus aureus (including both methicillin-susceptible and methicillin-resistant strains);

Staphylococcus epidermidis;

Staphylococcus spp., other coagulase-negative Staphylococcus spp., including S. haemolyticus and S. hominis;

Corynebacterium spp.;

Streptococcus pneumoniae;

Viridans Group Streptococcus.

Aerobic Gram-negative microorganisms:

Acinetobacter spp.;

Haemophilus influenzae;

Pseudomonas aeruginosa;

Moraxella spp. (including M. catarrhalis)

Application in otology

Ciprofloxacin has high in vitro activity against most aerobic Gram-negative microorganisms, including Pseudomonas aeruginosa. It is also effective against aerobic Gram-positive microorganisms, such as staphylococci and streptococci. As shown in Table 1, ciprofloxacin exhibits a broad spectrum of in vivo activity (MIC90S ≤2 μg/ml) against pathogenic microorganisms isolated from patients with acute otitis externa.

Table 1

Ciprofloxacin is also active against pathogenic microorganisms isolated from patients with acute otitis media using tympanostomy tubes.

Table 2

Limit values of diameters of zones of inhibition of growth of microorganisms

Ophthalmic use

Ciprofloxacin has been shown to be active in vitro against most strains of the following microorganisms; however, the clinical significance of these findings in ophthalmic infections is unknown. The safety and efficacy of ciprofloxacin in the treatment of corneal ulcers or conjunctivitis caused by these microorganisms have not been established in adequate and well-controlled clinical trials.

The following bacteria are considered susceptible when assessed using systemic zone inhibition diameter breakpoints. However, the relationship between systemic in vitro zone inhibition diameters and ophthalmic efficacy has not been established. Ciprofloxacin exhibits in vitro minimum inhibitory concentrations (MICs) of 1 μg/mL or less (systemic zone inhibition diameter breakpoints) against the majority (90%) of the following ocular pathogens.

Aerobic gram-positive microorganisms:

Bacillus species.

Aerobic Gram-negative microorganisms:

Acinetobacter calcoaceticus;

Enterobacter aerogenes;

Escherichia coli;

Haemophilus parainfluenzae;

Klebsiella pneumoniae;

Neisseria gonorrhoeae;

Proteus mirabilis;

Proteus vulgaris;

Serratia marcescens.

Others

Peptococcus spp., Peptostreptococcus spp., Propionibacterium acnes and Clostridium perfringens are susceptible microorganisms.

Some strains of Burkholderia cepacia and Stenotrophomonas maltophilia are resistant to ciprofloxacin, as are some anaerobic bacteria, especially Bacteroides fragilis.

Other information

The minimum bactericidal concentration (MBC) usually does not exceed the MIC by more than a factor of 2.

Application in otology

Ciprofloxacin has been shown to be active in vitro against most strains of the following microorganisms, but the clinical relevance of these findings in ear infections is unknown. The safety and efficacy of ciprofloxacin in the treatment of acute otitis externa caused by these microorganisms have not been established in adequate and well-controlled clinical trials.

The following bacteria are considered susceptible when assessed using systemic zone inhibition breakpoints. However, the relationship between in vitro systemic zone inhibition breakpoints and otic efficacy has not been established. Ciprofloxacin exhibits in vitro MICs of 1 μg/mL or less (systemic zone inhibition breakpoints) against most (90%) strains of the following pathogens.

Aerobic gram-positive microorganisms:

Bacillus species;

Corynebacterium species;

Enterococcus faecalis;

Staphylococcus aureus;

Staphylococcus epidermidis;

Staphylococcus caprae;

Staphylococcus capitis;

Staphylococcus haemolyticus;

Streptococcus pneumoniae;

Viridans Group Streptococcus.

Aerobic Gram-negative microorganisms:

Achromobacter xylosoxidans subsp. hulosoxidans;

Acinetobacter baumanii;

Acinetobacter junii;

Acinetobacter Iwoffi;

Acinetobacter radioresistant;

genospecies of Acinetobacter 3;

Citrobacter freundii;

Citrobacter koseri;

Enterobacter aerogenes;

Enterobacter cloacae;

Escherichia coli;

Haemophilus influenzae;

Klebsiella oxytoca;

Klebsiella pneumoniae;

Moraxella catarrhalis;

Proteus mirabilis;

Pseudomonas stutzeri;

Serratia marcescens.

Ciprofloxacin has also been shown to be active in vitro against most strains of the following microorganisms that cause otitis media.

Aerobic gram-positive microorganisms:

Staphylococcus aureus;

Staphylococcus epidermidis;

Streptococcus pneumoniae.

Aerobic Gram-negative microorganisms:

Escherichia coli;

Haemophilus influenzae;

Moraxella catarrhalis;

Pseudomonas aeruginosa.

Resistance to ciprofloxacin usually develops slowly. However, parallel resistance has been observed within this group of gyrase inhibitors.

Bacterial susceptibility studies revealed that most of the microorganisms resistant to ciprofloxacin were also resistant to other fluoroquinolones. The frequency of isolation of strains with acquired resistance to ciprofloxacin was low.

Due to its specific mode of action, there is no cross-resistance between ciprofloxacin and other antibacterial agents with different chemical structures, such as beta-lactam antibiotics, aminoglycosides, tetracyclines, macrolides and peptides, as well as sulfonamides, trimethoprim and nitrofuran derivatives. Thus, microorganisms resistant to these drugs may be sensitive to ciprofloxacin.

Pharmacokinetics

Ciprofloxacin is well absorbed after topical application to the human eye. Ciprofloxacin concentrations found in the tear film, cornea, and anterior chamber of the eye are ten to several hundred times higher than the MIC90 for susceptible ocular pathogens.

Systemic absorption of ciprofloxacin after topical ocular administration is low. Plasma ciprofloxacin levels after 7 days of topical administration ranged from unquantifiable (<1.25 ng/ml) to 4.7 ng/ml. The mean maximum plasma ciprofloxacin concentration obtained after topical ocular administration was approximately 450-fold lower than that observed after a single oral dose of ciprofloxacin, 250 mg.

In children with otorrhea using a tympanostomy tube or with a perforated eardrum, topical application of ciprofloxacin to the ear resulted in unquantifiable plasma ciprofloxacin concentrations with a detection limit of 5 ng/mL. In animals, ciprofloxacin was distributed in plasma and middle ear fluid after intramuscular injection and was absorbed into the inner ear after topical application to the middle ear.

The systemic pharmacokinetic properties of ciprofloxacin are well studied.

Ciprofloxacin is well distributed in body tissues, with tissue levels usually higher than plasma levels. The volume of distribution at steady state is 1.7-2.71 l/kg. Serum protein binding is 16-43%. The serum half-life of ciprofloxacin is 3-5 hours. After oral administration of a single dose of 250 to 750 mg in adult patients with normal renal function, 15-50% of the dose is excreted in the urine as unchanged drug and 10-15% as metabolites within 24 hours. Both ciprofloxacin and its four primary metabolites are excreted in the urine and feces. The renal clearance of ciprofloxacin is usually 300-479 ml/min. Approximately 20-40% of the dose is excreted in the feces as unchanged drug and metabolites within 5 days.

Indication

Corneal ulcers and superficial infections of the eye(s) and its adnexa caused by strains of bacteria susceptible to ciprofloxacin.

Acute otitis externa, as well as acute otitis media with the use of drainage through a tympanostomy tube, caused by strains of bacteria sensitive to ciprofloxacin.

Contraindication

Hypersensitivity to ciprofloxacin or to other quinolones, or to any of the components of the drug.

Interaction with other medicinal products and other types of interactions

Since ciprofloxacin has low systemic concentrations when applied topically to the eye or otitis, interactions with other drugs are unlikely. If several topical eye medications are used simultaneously, wait at least 5 minutes between their applications. Ophthalmic ointments should be applied last.

Application features

For ophthalmic use only.

General

Serious and sometimes fatal (anaphylactic) hypersensitivity reactions have been reported in patients receiving quinolone therapy, some after the first dose. Some reactions have been associated with cardiovascular failure, loss of consciousness, tinnitus, swelling of the throat or face, dyspnea, urticaria, and pruritus. Only a few patients have experienced hypersensitivity reactions.

Serious cases of acute hypersensitivity to ciprofloxacin may require emergency treatment. Oxygen therapy and airway patency should be instituted as clinically indicated.

Ciprofloxacin should be discontinued at the first sign of skin rash or any other sign of a hypersensitivity reaction.

As with all antibacterial agents, prolonged use may result in overgrowth of antibiotic-resistant bacterial strains or fungi. In the event of superinfection, appropriate therapy should be administered.

Tendonitis and rupture are possible with systemic therapy with fluoroquinolones, including ciprofloxacin, especially in elderly patients and in patients receiving concomitant corticosteroids. Therefore, treatment with Ciprofloxacin eye/ear drops should be discontinued at the first sign of tendonitis.

Eye drops

Clinical experience with the use of the drug in children under 1 year of age, especially newborns, is quite limited.

Ciprofloxacin eye drops are not recommended for use in neonates with gonococcal or chlamydial neonatal blenorrhea, as it has not been evaluated in this category of patients. Neonates with neonatal blenorrhea should receive treatment appropriate to their condition.

When using Cipronex® eye drops, the risk of the drug entering the nasopharynx should be taken into account, which may lead to the emergence and spread of bacterial resistance.

In patients with corneal ulcers and frequent use of eye drops containing ciprofloxacin, white ocular precipitates (drug residues) were observed, which disappeared after discontinuation of the eye drops. The appearance of precipitates does not preclude further use of the eye drops and does not have a negative impact on the course of the disease. Precipitates were observed from 24 hours to 7 days after the start of therapy. Complete disappearance of precipitates occurs immediately or within 13 days after the start of therapy.

Ciprofloxacin eye drops contain benzalkonium chloride, which may cause irritation and discolouration of soft contact lenses.

It is not recommended to wear contact lenses while treating an eye infection.

Therefore, patients should be advised not to wear contact lenses during treatment with Ciprofloxacin eye drops. If patients are permitted to wear contact lenses, they should be removed before instillation of the eye drops and wait at least 15 minutes before reinsertion.

Ear drops

The efficacy and safety of the drug in children under 1 year of age have not been evaluated.

Although there are very limited data in patients under 1 year of age treated for acute otitis externa, there are no differences in the course of the disease in this patient population that would preclude the use of this medicinal product. Based on the very limited data, the physician prescribing the medicinal product to children under 1 year of age should weigh the clinical benefits of use against the known and possibly unknown risks. The safety and efficacy of Ciprofloxacin® have not been studied in the presence of a perforated eardrum, therefore it should be used with caution in patients with known or suspected perforation of the eardrum, or in cases where there is a risk of perforation of the eardrum.

If signs and symptoms of the disease do not disappear after a week of using the drug, it is recommended to re-evaluate the treatment regimen.

Photosensitivity reactions of varying degrees have been reported in patients receiving systemic quinolones. Since this medicinal product is administered topically, photosensitivity reactions are unlikely.

When instilling into the ear, frequent medical monitoring should be carried out to allow for timely implementation of other therapeutic measures.

Use during pregnancy or breastfeeding

Reproductive function

Studies to assess the effects on reproductive function with topical application of Cipronex® have not been conducted.

There are no adequate data from the use of Ciprofloxacin in pregnant women. Animal studies do not indicate direct harmful effects with respect to reproductive toxicity.

It is advisable to avoid using the drug during pregnancy.

Breast-feeding

Ciprofloxacin has been detected in breast milk after oral administration. It is not known whether ciprofloxacin is excreted in breast milk after topical application to the eye or ear. Ciprofloxacin should be used with caution in nursing women.

Ability to influence reaction speed when driving vehicles or other mechanisms

This medicine has no or negligible influence on the ability to drive or use machines. Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs during instillation, the patient should wait until the vision clears before driving or using machines.

There are no data on the effect of Cipronex® ear drops on the ability to drive or use machines.

Method of administration and doses

Application in ophthalmology

Adults, including elderly patients, and children

Corneal ulcers

Ciprofloxacin should be administered at the following intervals, including at night:

on the 1st day, instill 2 drops into the conjunctival sac(s) of the affected eye(s) every 15 minutes for the first 6 hours, then 2 drops every 30 minutes for the first day;

on the 2nd day, instill 2 drops into the conjunctival sac(s) of the affected eye(s) every hour;

From day 3 to day 14, instill 2 drops into the conjunctival sac(s) of the affected eye(s) every 4 hours.

In case of corneal ulcer, treatment may last more than 14 days; the dosage regimen and duration of treatment are determined by the doctor.

Bacterial superficial infections of the eye and its adnexa

The standard dose is 1-2 drops in the conjunctival sac(s) of the affected eye(s) 4 times daily.

For severe infections, the dose may be 1-2 drops every 2 hours for the first two days during the daytime.

Usually, treatment lasts 7-14 days.

After instillation, tight eyelid closure or nasolacrimal occlusion is recommended. This reduces systemic absorption of the drug administered into the eye, which reduces the likelihood of systemic side effects.

In case of concomitant therapy with other topical ophthalmic drugs, an interval of 10-15 minutes should be observed between their use.

Children

The dosage for children over 1 year of age is the same as for adults.

As a result of a clinical study of the use of the drug in newborns and children under one month of age, it was found that Cipronex® is clinically and microbiologically effective for the treatment of bacterial conjunctivitis in this category of patients when used 3 times a day for 4 days.

Patients with impaired liver and kidney function

The use of Ciprofloxacin® in this category of patients has not been studied.

Precautions for use

To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas, or other surfaces with the tip of the dropper bottle.

Application in otology

Dosage

Adults, including elderly patients

For adults, the dose is 4 drops of Ciprodex® into the ear canal 2 times a day.

For patients requiring the use of ear plugs, the dose can be doubled only for the first use (i.e. 6 drops for children and 8 drops for adults).

In general, the duration of treatment should not exceed 5-10 days. In some cases, treatment can be extended, but in this case it is recommended to check the sensitivity of the local flora.

In case of concomitant therapy with other topical medications, an interval of 10-15 minutes should be observed between their application.

Children

The dose is 3 drops of Cipronex® in the ear canal 2 times a day. The safety and efficacy of Cipronex® have been studied in children aged 1 to 12 years. The safety and efficacy of the drug in children under 1 year of age have not been established.

Patients with impaired liver and kidney function

The use of Ciprofloxacin® in this category of patients has not been studied.

Precautions for use

The external auditory canal should be thoroughly cleaned. To prevent vestibular stimulation, it is recommended to administer a solution at room temperature or body temperature.

The patient should be in a lying position on the opposite side of the affected ear. It is advisable to stay in this position for 5-10 minutes. Also, after local cleaning, a moistened gauze or hygroscopic cotton swab can be inserted into the ear canal for 1-2 days, but it must be moistened to be saturated with the drug 2 times a day.

To prevent contamination of the dropper tip and solution, care must be taken not to touch the auricle or external ear canal, surrounding areas, or other surfaces with the tip of the dropper bottle.

Children

Eye drops

Use in children from birth (see section "Special instructions for use").

Ear drops

Use for children over 1 year of age.

Safety and effectiveness in children under 1 year of age have not been established.

Overdose

Given the characteristics of this drug, intended for external use, no toxic effect is expected when used in ophthalmology/otology at recommended doses, as well as in the event of accidental ingestion of the contents of one bottle.

Side effects

The following adverse reactions are classified as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (<1/10000) or not known (frequency cannot be estimated from the available data). Within each grouping, adverse reactions are presented in order of decreasing seriousness. Data on adverse reactions were obtained during clinical trials and during the post-marketing period.

Side effects observed after the use of Ciprofloxacin® in the eye

Adverse reactions reported with the use of Ciprofloxacin® in the ear

Table 2

Description of the listed adverse reactions

Reactions such as (generalized) rash, toxic epidermolysis, exfoliative dermatitis, Stevens-Johnson syndrome and urticaria have occurred very rarely with topical application of fluoroquinolones.

In isolated cases, blurred vision, decreased visual acuity, and signs of drug residue have been observed when ciprofloxacin was applied to the eye.

Rarely, the components of the product may cause a hypersensitivity reaction when applied to the ear. However, as with any substance applied to the skin, there is always the possibility of an allergic reaction to any of the components of the product (for Cipronex® ear drops only).

Serious and in some cases fatal (anaphylactic) hypersensitivity reactions, sometimes after the first dose, have been reported in patients receiving systemic quinolone therapy. Some reactions have been associated with cardiovascular collapse, loss of consciousness, tingling, swelling of the throat or face, dyspnea, urticaria, and pruritus.

In patients receiving systemic fluoroquinolones, tendon ruptures of the shoulder, hand, Achilles tendon, or other tendons requiring surgical repair or resulting in long-term disability have been reported. Studies and post-marketing experience with systemic fluoroquinolones indicate that the risk of such ruptures may be increased in patients receiving corticosteroids, especially in the elderly, and in patients with high tendon loads, including the Achilles tendon. To date, clinical and post-marketing data have not demonstrated a clear association between the use of Ciprofloxacin and musculoskeletal and connective tissue adverse reactions.

In patients with corneal ulcers, frequent use of Ciprofloxacin® has been associated with the development of a white precipitate in the eye (residue of the drug), which disappeared after further use. The presence of a precipitate does not require discontinuation of Ciprofloxacin® and does not have a negative impact on the clinical picture of the recovery process.

Expiration date

3 years. Do not use after the expiry date stated on the packaging.

The shelf life of the drug after first opening is 4 weeks.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

5 ml of the drug in a 5 ml polyethylene dropper bottle with a cap with a warranty ring. 1 bottle in a cardboard box.

Vacation category

According to the recipe.

Producer

Warsaw Pharmaceutical Works Polfa SA.

Address

22/24 Karolkowa Str., 01-207 Warsaw, Poland.

Applicant

Pharmaceutical Works “POLPHARMA” SA

The location of the applicant and the address of its place of business.

19, Pelplinska Str., 83-200 Starogard Gdanski, Poland.