Instructions for use Ciprofloxacin eye/ear drops 0.3% bottle 5 ml
Composition
active ingredient: ciprofloxacin;
1 ml of solution contains 3 mg of ciprofloxacin;
Excipients: benzalkonium chloride; disodium edetate (Trilon B); sodium chloride; purified water.
Dosage form
Eye and ear drops.
Main physicochemical properties: clear liquid with a greenish-yellowish tint.
Pharmacotherapeutic group
Means for use in ophthalmology and otology. Antimicrobial agents. ATX code S0ZA A07.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
Ciprofloxacin is an antimicrobial drug from the quinolone class. The bactericidal effect 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, both in vitro and in 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, Streptococcus viridans group.
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 the table below, ciprofloxacin demonstrates a broad spectrum of in vivo activity (MIC90S ≤2 μg/ml) against pathogenic microorganisms isolated from patients with acute otitis externa in recent clinical studies.
| Type of bacteria | Isolates N = | IPCmin (μg/ml) | IPC50 (μg/ml) | IPC90 (μg/ml) | MICmax (μg/ml) |
| Pseudomonas aeruginosa | 1089 | 0.03 | 0.13 | 0.25 | 16 |
| Staphylococcus aureus | 221 | 0.13 | 0.50 | 1.0 | 128 |
| Staphylococcus epidermidis | 257 | 0.06 | 0.25 | 0.50 | 128 |
| Staphylococcus caprae | 75 | 0.13 | 0.50 | 0.50 | 2.0 |
| Enterococcus faecalis | 53 | 0.50 | 1.0 | 2.0 | 4.0 |
| Enterobacter cloacae | 45 | 0.004 | 0.016 | 0.032 | 0.25 |
Ciprofloxacin is also active against pathogenic microorganisms isolated from patients with acute otitis media with the use of tympanostomy tubes.
| Type of bacteria | Isolates N = | IPCmin (μg/ml) | IPC50 (μg/ml) | IPC90 (μg/ml) | MICmax (μg/ml) |
| Streptococcus pneumoniae | 197 | 0.25 | 1.0 | 2.0 | 8.0 |
| Staphylococcus aureus | 134 | 0.06 | 0.25 | 1.0 | >128 |
| Pseudomonas aeruginosa | 132 | 0.03 | 0.25 | 0.50 | 128 |
| Haemophilus influenzae | 122 | 0.004 | 0.008 | 0.016 | 0.25 |
| Staphylococcus epidermidis | 103 | 0.06 | 1.0 | 64 | 64 |
| Moraxella catarrhalis | 37 | 0.008 | 0.03 | 0.06 | 0.06 |
| Escherichia coli | 15 | 0.008 | 0.03 | 128 | >128 |
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 breakpoints. However, the relationship between in vitro systemic zone inhibition breakpoints and ophthalmic efficacy has not been established. Ciprofloxacin exhibits in vitro MICs of 1 μg/mL or less (systemic zone inhibition 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.
Insensitive
Some strains of Burkholderia cepacia and Stenotrophomonas maltophilia are resistant to ciprofloxacin, as are some anaerobic bacteria, especially Bacteroides fragilis.
Other
The minimum bactericidal concentration (MBC) usually does not exceed the MIC by more than a factor of 2.
Ciprofloxacin has been shown to be active in vitro against most strains of the following microorganisms; however, 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, Streptococcus of the Viridans group.
Aerobic gram-negative microorganisms: Achromobacter xylosoxidans subsp. khulosoxidans, Acinetobacter baumanii, Acinetobacter junii, Acinetobacter Iwoffi, Acinetobacter radioresistans, genospecies 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 generally develops slowly. However, parallel resistance has been observed within this group of gyrase inhibitors.
It has been confirmed that most microorganisms resistant to ciprofloxacin are also resistant to other fluoroquinolones. In clinical studies, 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 sensitive ocular pathogens.
Systemic absorption of ciprofloxacin after topical ocular administration is low. Plasma levels of ciprofloxacin after seven days of topical administration ranged from unquantifiable (<1.25 ng/ml) to 4.7 ng/ml. The mean maximum plasma concentration of ciprofloxacin obtained after topical ocular administration was approximately 450-fold lower than that observed after a single oral dose of ciprofloxacin of 250 mg.
In children with otorrhea with a tympanostomy tube or with a perforated eardrum, plasma ciprofloxacin concentrations were not quantifiable after topical otitis media with ciprofloxacin, with a detection limit of 5 ng/mL. In chinchillas, ciprofloxacin was distributed in plasma and middle ear fluid after intramuscular injection and was absorbed into the inner ear after topical otitis media.
The systemic pharmacokinetic properties of ciprofloxacin are well studied.
Ciprofloxacin is well distributed in body tissues, with tissue levels generally 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 single oral doses ranging from 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 generally 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 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 otolaryngology, 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
The drug is intended for topical use (in the conjunctival sac or in the external auditory canal).
Eye drops
Clinical experience in children under 1 year of age, especially newborns, is quite limited.
The use of the drug is not recommended in newborns with neonatal blenorrhea of gonococcal and chlamydial origin, as it has not been evaluated in this category of patients. Newborns with neonatal blenorrhea should receive treatment appropriate to their condition.
When using the drug, the risk of getting into the nasopharynx should be taken into account, which may contribute to the emergence and spread of bacterial resistance.
In patients with corneal ulcers, frequent use of eye drops containing ciprofloxacin has been associated with the appearance of white ocular precipitates (drug residues), which disappear after discontinuation of the eye drops. The appearance of precipitates does not preclude continued use of the eye drops and does not have a negative impact on the course of the disease.
It is not recommended to wear contact lenses while treating an eye infection.
Ear drops
The efficacy and safety of use in children under 1 year of age have not been evaluated.
When instilling into the ear, frequent medical monitoring should be carried out to allow for timely implementation of other therapeutic measures.
General features
Serious and sometimes fatal (anaphylactic) hypersensitivity reactions have been reported in patients receiving quinolone therapy, some after the first dose. Some reactions were accompanied by cardiovascular failure, loss of consciousness, tinnitus, swelling of the throat or face, dyspnea, urticaria, and pruritus. Only a few of these had a history of hypersensitivity reactions.
Serious cases of acute hypersensitivity to ciprofloxacin may require emergency treatment. Oxygen therapy and airway patency should be administered 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 of ciprofloxacin may result in overgrowth of non-susceptible bacterial strains or fungi. In the event of superinfection, appropriate therapy should be instituted.
Tendonitis and rupture have been reported with systemic fluoroquinolone therapy, including ciprofloxacin, particularly in the elderly and in patients receiving concomitant corticosteroids. Therefore, ciprofloxacin treatment should be discontinued at the first sign of tendonitis.
The medicinal product contains benzalkonium chloride, which may cause irritation. Contact with soft contact lenses should be avoided (remove contact lenses before using the eye drops and do not reinsert them until 15 minutes after instillation). Benzalkonium chloride discolours soft contact lenses. Therefore, patients should be advised not to wear contact lenses during treatment with the eye drops.
When applied externally, benzalkonium chloride may cause skin reactions.
Use during pregnancy or breastfeeding
Reproductive function
Studies to evaluate the effects on reproductive function with topical application of ciprofloxacin have not been conducted.
Pregnancy
There are no 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 medicine during pregnancy.
Breast-feeding
Ciprofloxacin has been found 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. Caution should be exercised when used in nursing mothers.
The ability to influence the reaction speed when driving or working with other mechanisms
The drug has no or negligible influence on the ability to drive or use machines. Temporary blurred vision or other visual disturbances may impair 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 is no data on the effect of ear drops on the ability to drive or use other mechanisms.
Method of administration and doses
Application in ophthalmology
Dosage
Use in adolescents and adults, including elderly patients
Corneal ulcers
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.
Typically, treatment lasts 7–14 days.
After instillation, tight eyelid closure or nasolacrimal occlusion is recommended. This reduces systemic absorption of drugs 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 applications.
Use in children
The dosage for children over 1 year of age is the same as for adults.
Ciprofloxacin is known to be clinically and microbiologically effective for the treatment of bacterial conjunctivitis in neonates and infants under 1 month of age when administered 3 times daily for 4 days.
Use in liver and kidney dysfunction
The use of ciprofloxacin in this category of patients has not been studied.
Method of application
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
Use in adults, including elderly patients
For adults, the dose is 4 drops of the drug into the ear canal twice 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 may 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.
Use in children
The dose is 3 drops of the drug in the ear canal twice a day. The safety and efficacy of ciprofloxacin have been studied in children aged 1 to 12 years. The safety and efficacy in children under 1 year of age have not been established.
Use in liver and kidney dysfunction
The use of ciprofloxacin in this category of patients has not been studied.
Method of application
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 supine 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
It is known that the safety and efficacy of eye drops were determined in 230 children aged 0 to 12 years. No serious adverse reactions associated with the use of the drug were reported in this category of patients.
Ear drops
It is known that the safety and efficacy of the ear drops were determined in 193 children aged 1 to 12 years. No serious adverse reactions associated with the use of the drug were reported in this category of patients.
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 effects are 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 according to frequency of occurrence as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), or unknown 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
Infections and infestations: rare: stye, rhinitis.
On the part of the immune system: rare: hypersensitivity.
Ophthalmological disorders: common: corneal deposits, ocular discomfort, ocular hyperaemia; uncommon: keratopathy, corneal infiltrates, corneal discolouration, photophobia, visual acuity reduced, eyelid oedema, blurred vision, eye pain, dry eye, eye swelling, eye itching, foreign body sensation in the eye, lacrimation increased, eye discharge, eyelid margin scaling, eyelid exfoliation, conjunctival oedema, eyelid erythema; uncommon: ocular toxicity, punctate keratitis, keratitis, conjunctivitis, corneal dysfunction, corneal epithelial defect, diplopia, ocular hypoaesthesia, asthenopia, eye irritation, eye inflammation, conjunctival hyperaemia.
On the part of the organs of hearing: rare: ear pain.
Respiratory, thoracic and mediastinal disorders: rare: hypersecretion of the paranasal sinuses.
Gastrointestinal: Infrequent: nausea; Rare: diarrhea, abdominal pain.
Skin and subcutaneous tissue disorders: rare: dermatitis.
General disorders and administration site conditions: rare: drug intolerance.
Laboratory tests: isolated: deviations from the norm of laboratory test results.
Adverse reactions reported with ciprofloxacin in the ear
Nervous system: infrequent: tearfulness, headache.
From the side of the organs of hearing and labyrinth: infrequent: ear pain, ear congestion, otorrhea, ear itching; frequency unknown: ringing in the ears.
Skin and subcutaneous tissue disorders: uncommon: dermatitis.
General disorders and administration site conditions: uncommon: hyperthermia.
Description of selected 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 medicine may cause a hypersensitivity reaction when used in 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 medicine (applies to ear drops only).
Serious and in some cases fatal (anaphylactic) hypersensitivity reactions, sometimes after the first dose, have occurred in patients receiving systemic quinolone therapy. Some reactions have been accompanied by cardiovascular collapse, loss of consciousness, tingling, swelling of the throat or face, dyspnea, urticaria, and pruritus.
Tendon ruptures of the shoulder, hand, Achilles tendon, or other tendons requiring surgical repair or resulting in long-term disability have been reported in patients receiving systemic fluoroquinolones. Studies and post-marketing experience with systemic fluoroquinolones suggest that the risk of such ruptures may be increased in patients receiving corticosteroids, particularly 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 (drug residue), which disappeared after continued use. The presence of the precipitate does not require discontinuation of the drug and does not adversely affect the clinical course of the recovery process.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Do not refrigerate.
Keep out of reach of children.
Packaging
5 ml or 10 ml in a bottle with a dropper cap in a box.
Vacation category
According to the recipe.
Producer
Limited Liability Company "Research Plant "GNTSLS".
Limited Liability Company "PHARMEX GROUP".
Address
Ukraine, 61057, Kharkiv region, Kharkiv city, Vorobyovy street, building 8.
(Limited Liability Company "Research Plant "GNTSLS")
Ukraine, 08301, Kyiv region, Boryspil city, Shevchenko st., building 100.
(Limited Liability Company "PHARMEX GROUP")
