Ciprofloxacin-Optic, eye drops 0.3% 5 ml

Pharmacotherapeutic group: antimicrobial agent – fluoroquinolone

ATX code: S01AX13

Pharmacological properties

Pharmacodynamics
A broad-spectrum antimicrobial agent, a fluoroquinolone derivative, inhibits bacterial DNA gyrase (topoisomerases II and IV, responsible for the process of superspiralization of chromosomal DNA around nuclear RNA, which is required for the reading of genetic information); disrupts DNA synthesis, bacterial growth and division; causes pronounced morphological changes (including cell wall and membranes) and rapid death of the bacterial cell.
Bactericidal on Gram-negative organisms during quiescence and fission (as it affects not only DNA-gyrase, but also causes lysis of cell wall), on Gram-positive microorganisms – only during fission.
Low toxicity to macroorganism cells is explained by the absence of DNA-gyrase in them. Against the background of ciprofloxacin use there is no parallel development of resistance to other antibiotics which do not belong to gyrase inhibitors group and this makes it highly effective against bacteria which are resistant to, for example, aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Ciprofloxacin is sensitive to Gram-negative aerobic bacteria: enterobacteriaceae (Escherichia coli, Salmonella spp, Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvei, Edwardsiella tarda, Providencia spp, Morganella morganii, Vibrio spp., Yersinia spp.), other Gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigeoides, Campylobacter jejuni, Neisseria spp.); some intracellular pathogens (Legionella pneumophila, Brucella spp, Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium diphtheria); Gram-positive aerobic bacteria: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalac-tiae).

Most methicillin-resistant staphylococci are also resistant to ciprofloxacin. The sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) is moderate (high concentrations are required for their suppression).
Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides are resistant to the drug. It is ineffective against Treponema pallidum.
Resistance develops very slowly because, on the one hand, after the action of ciprofloxacin there are almost no persistent microorganisms, and on the other hand, bacterial cells have no enzymes that inactivate it.

Mechanisms of resistance development
The development of resistance to fluoroquinolones, particularly to ciprofloxacin, is mediated by changes in genes encoding at least one of 4 mechanisms:
1. Changes in the structure of target enzymes (DNA-gyrase and topoisomerase IV) – enzymes involved in cellular DNA synthesis;
2. Disruption of cell wall permeability;
3. Active drug withdrawal from the cell (increased efflux pump activity);
4. Plasmid-mediated changes in aminoglycoside 6-N-acetyltransferase activity.

Pharmacokinetics

Absorption
It is rapidly absorbed when applied topically.

Distribution
The plasma concentration of ciprofloxacin after instillation into the conjunctiva of 2 drops of 0.3% solution every 2 hours for 2 days and then every 4 hours for 5 days ranged from unquantifiable (< 1.0 ng/mL) to 4.7 ng/mL. The mean maximum plasma concentration of ciprofloxacin obtained in this study was approximately 450 times lower than after oral ciprofloxacin doses of 250 mg.
Ciprofloxacin is widely distributed in body tissues, with approximately 1.7 to 5 L/kg of distribution. Binding to plasma proteins is 20-40 %.

Metabolism
There is no information about the ways of metabolism of ciprofloxacin.

Elimation
The half-life from plasma is 3-5 hours. Ciprofloxacin and its four metabolites are excreted with urine and feces. About 2/3 of the total level of ciprofloxacin in plasma is eliminated through the kidneys, while 1/3 of the total level of ciprofloxacin is excreted through the intestine and with the bile. In patients with impaired renal function a slight increase in the elimination half-life of ciprofloxacin is observed due to extrarenal routes of elimination. Similarly, in patients with hepatic impairment the elimination half-life is slightly prolonged.
There are no data on the study of pharmacokinetic properties of ciprofloxacin in children.

There are no data on the study of pharmacokinetic properties of ciprofloxacin in children.

Indications

Active ingredient

Composition

Active substance:

ciprofloxacin hydrochloride – 3.49 mg, in terms of ciprofloxacin – 3.0 mg

Auxiliary substances:

dinatrium edetate dihydrate (trilon B) – 0.4 mg,

sodium chloride – 9 mg,

benzalkonium chloride – 0.2 mg,

Sodium hydroxide solution 1 M – to pH 3.5-5.5,

Purified water – up to 1.0 ml

How to take, the dosage

Interaction

There have been no specific studies of interactions with ocular dosage forms of ciprofloxacin.

In view of the low systemic plasma concentration of ciprofloxacin after conjunctival instillation, interactions between co-administered drugs with ciprofloxacin are unlikely. If co-administered with other topical ophthalmic drugs, the interval between applications should be at least 5 minutes, and eye ointments should be used last.

Ciprofloxacin-Optik solution is not compatible with drug solutions having pH values of 3-4 that are physically or chemically unstable.

Special Instructions

Contraindications

Side effects

In clinical trials, the most frequently reported adverse events were ocular discomfort (in 6% of cases), dysgeusia (in 3% of cases), and corneal precipitates (in 3% of cases).

The adverse reactions from clinical trials and post-marketing surveillance data are grouped according to the following frequency of occurrence gradation: Very common (≥1/10), common (≥1/100 to < 1/10), infrequent (≥1/1000 to < 1/100), rare (≥1/10000 to < 1/1000), very rare (< 1/10000), with unknown frequency (incidence cannot be determined based on available data). In each group, the reactions are listed in decreasing order of occurrence.

Organ system

Undesirable events

Immune system disorders

Rare: hypersensitivity reactions.

Nervous system disorders

Infrequent: headache.

Rarely: dizziness.

Visual disorders

Often: Corneal precipitates, ocular discomfort, conjunctival injection.

Infrequent: Keratopathy, pitting keratitis, corneal infiltrates, photophobia, decreased visual acuity, eyelid edema, blurred vision, pain in the eye, feeling dry in the eye, swelling of the conjunctiva and eyelids, lacrimation, discharge from the eye, crust formation on the eyelid edges, peeling of eyelid skin, eyelid hyperemia.

Rarely: toxic effects on the eye, keratitis, conjunctivitis, corneal epithelial defect, diplopia, decreased corneal sensitivity, asthenopia, barley.

Hearing organ and labyrinth disorders

Rarely: ear pain.

Respiratory, thoracic and mediastinal disorders

Rare: Increased secretion of mucous membrane discharge of the paranasal sinuses, rhinitis.

Digestive system disorders

Often: dysgeusia.

Infrequent: nausea.

Rarely: abdominal pain, diarrhea.

Skin and subcutaneous fatty tissue disorders

Rare: dermatitis.

Musculoskeletal and connective tissue disorders

With unknown frequency: ligamentous system disorders.

Description of individual groups of adverse reactions

Rare cases of generalized rash, toxic epidermolysis, exfoliative dermatitis, Stevens-Johnson syndrome and urticaria have been reported.

Serious anaphylactic reactions, in rare cases with fatal outcome, including after the first dose, have been reported in patients receiving oral fluoroquinolones. Some of these reactions have been accompanied by cardiovascular collapse, loss of consciousness, swelling of the larynx and face, tingling sensation, dyspnea, itching and urticaria.

In patients taking oral fluoroquinolones, there have been tears of the shoulder tendon, hand tendon, Achilles tendon and other tendons, which subsequently required surgery or resulted in long-term disability. No effect of ciprofloxacin instillations on the musculoskeletal system and connective tissue has been noted in clinical studies and postmarketing surveillance.

In individual cases, ciprofloxacin instillations have resulted in blurred vision, decreased visual acuity and residual amount of drug on the corneal surface.

In systemic use of quinolones, moderate to severe phototoxicity reactions have been reported, but these reactions are not characteristic of ciprofloxacin.

The profile of adverse reactions in the pediatric population

The efficacy and safety of ciprofloxacin in children aged 0 to 12 years has been confirmed in clinical studies involving 230 children. No serious adverse events were noted in this group of patients.

Overdose

Similarities