Instructions Cytomoxan eye drops 0.5% bottle 5 ml
Composition
active ingredient: moxifloxacin;
1 ml of drops contains 5.45 mg of moxifloxacin hydrochloride (calculated as 100% anhydrous substance), which is equivalent to 5 mg of moxifloxacin;
Excipients: sodium chloride, boric acid, 1 M hydrochloric acid solution, sodium hydroxide, water for injections.
Dosage form
Eye drops.
Main physicochemical properties: clear liquid from yellow to yellow-green.
Pharmacotherapeutic group
Agents used in ophthalmology. Antibacterial agents. Fluoroquinolones. Moxifloxacin. ATX code S01A E07.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
Moxifloxacin, a fourth-generation fluoroquinolone, inhibits DNA gyrase and topoisomerase IV, which are essential for bacterial DNA replication, repair, and recombination.
Mechanism of resistance
Resistance to fluoroquinolones, including moxifloxacin, usually occurs due to chromosomal mutations in the genes encoding DNA gyrase and topoisomerase IV. In Gram-negative bacteria, resistance to moxifloxacin can occur due to mutations in the mar (multidrug resistance) and qnr (quinolone resistance) gene systems. Cross-resistance with beta-lactams, macrolides and aminoglycosides is unlikely due to differences in the mode of action.
Limit values
The European Committee on Antibiotic Susceptibility Testing (EUCAST) has established the following minimum inhibitory concentration (MIC) breakpoints (mg/L):
| · Staphylococcus species | S ≤ 0.5, R > 1 |
| · Streptococcus A, B, C, G | S ≤ 0.5, R > 1 |
| · Streptococcus pneumoniae | S ≤ 0.5, R > 0.5 |
| · Haemophilus influenzae | S ≤ 0.5, R > 0.5 |
| · Moraxella catarrhalis | S ≤ 0.5, R > 0.5 |
| · Enterobacteriaceae | S ≤ 0.5, R > 1 |
| · non-specific | S ≤ 0.5, R > 1 |
In vitro breakpoints are used to predict the clinical efficacy of moxifloxacin when administered systemically. These breakpoints may not be acceptable when the drug is administered topically to the eye, as higher concentrations are used with topical administration and local physical/chemical conditions may affect the activity of the drug at the site of administration.
Sensitivity
The prevalence of acquired resistance may vary geographically and over time for the relevant species of microorganisms, therefore it is desirable to have local information on the resistance of microorganisms, especially when treating severe infections.
If necessary, specialist advice should be sought if the local prevalence of resistance is such that the activity of moxifloxacin, at least against some types of infections, is questionable.
| Sensitive species | Conditionally resistant species | Resistant microorganisms |
Aerobic gram-positive microorganisms: Corynebacterium species, including: Corynebacterium diphtheriae, Staphylococcus aureus (methicillin-sensitive), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans group. Aerobic Gram-negative microorganisms: Enterobacter cloacae, Haemophilus influenzae, Klebsiella oxytoca, Moraxella catarrhalis, Serratia marcescens. Anaerobic microorganisms: Propriobacterium acnes. Other microorganisms: Chlamydia trachomatis. | Aerobic gram-positive microorganisms: Staphylococcus aureus (methicillin-resistant), Staphylococcus, coagulase-negative species (methicillin-resistant). Aerobic Gram-negative microorganisms: Neisseria gonorrhoeae Other microorganisms: Missing. | Aerobic Gram-negative microorganisms: Pseudomonas aeruginosa. Other microorganisms: Missing. |
Preclinical safety data
In preclinical studies, effects following topical ocular administration were observed only at doses significantly in excess of the maximum human dose, indicating little relevance to clinical use.
As with other quinolones, moxifloxacin has also been shown to be genotoxic in vitro in bacterial and mammalian cells. A threshold level for genotoxicity can be suggested, as at much higher concentrations these effects may result in interactions with bacterial gyrase and topoisomerase II in mammalian cells. In vivo studies, despite high doses of moxifloxacin, no evidence of genotoxicity was found. Thus, therapeutic doses for humans provide an adequate level of safety. No signs of carcinogenicity were observed in preclinical studies in rats.
Unlike other quinolones, moxifloxacin did not demonstrate any phototoxic or photogenotoxic properties in extensive in vitro and in vivo studies.
After topical application of moxifloxacin in the form of eye drops, it was absorbed into the systemic circulation. Plasma concentrations of moxifloxacin were determined in 21 male and female subjects who received topical instillation of the drug into both eyes 3 times a day for 4 days. The mean statistical maximum concentration (Cmax) and the concentration-time curve (AUC) in plasma were 2.7 ng/ml and 41.9 ng h/ml, respectively. These values are approximately 1600 and 1200 times lower than the mean Cmax and AUC, respectively, reported after oral administration of therapeutic doses of moxifloxacin, which were 400 mg. The half-life of moxifloxacin from plasma is 13 hours.
Indication
Topical treatment of bacterial conjunctivitis caused by moxifloxacin-sensitive strains of bacteria.
For information on the appropriate use of antibacterial agents, see official guidelines.
Contraindication
Hypersensitivity to the active substance, other quinolones or to any of the components of the drug.
Interaction with other medicinal products and other types of interactions
Interaction studies with other medicinal products have not been conducted. Interactions with other medicinal products are unlikely, since moxifloxacin has low systemic concentrations when applied topically to the eye. If several topical ophthalmic medicinal products are administered simultaneously, the interval between their administration should be at least 5 minutes. Eye ointments should be applied last.
Application features
- For ophthalmic use only. Not for injection. Cytomoxan® eye drops should not be administered by subconjunctival injection or directly into the anterior chamber of the eye.
- Serious, sometimes fatal, hypersensitivity (anaphylactic) reactions have been reported in patients receiving systemic quinolone therapy, sometimes after the first dose. Some reactions have been associated with cardiovascular failure, loss of consciousness, angioedema including laryngeal, pharyngeal and facial swelling, airway obstruction, dyspnoea, urticaria and pruritus.
- If an allergic reaction to Cytomoxan® eye drops occurs, the drug should be discontinued. Serious acute hypersensitivity reactions to moxifloxacin or any component of this medicinal product may require emergency treatment. If clinically indicated, airway patency should be restored and oxygen therapy should be administered.
- As with other antibiotics, prolonged use of Cytomoxan® eye drops may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, treatment should be discontinued and appropriate therapy instituted.
- With systemic therapy with fluoroquinolones, including moxifloxacin, inflammation and tendon rupture may occur, especially in elderly patients, as well as with simultaneous use with corticosteroids. At the first signs of tendon inflammation, treatment with Cytomoxan® eye drops should be discontinued.
- It is not recommended to wear contact lenses during treatment of eye inflammation/infections.
- The drug is not prescribed to children under 2 years of age for the treatment of eye diseases caused by Chlamydia trachomatis, as its effect has not been studied in this category of patients. Children over 2 years of age with eye diseases caused by Chlamydia trachomatis should receive appropriate systemic treatment. Newborns should receive appropriate systemic treatment in case of eye lesions caused by Chlamydia trachomatis or Neisseria gonorrhoeae.
Use during pregnancy or breastfeeding
Reproductive function
No studies have been conducted on the effects of Cytomoxan® eye drops on human reproductive function when used topically.
No adverse reactions on the reproductive function of men or women have been reported during the use of moxifloxacin hydrochloride eye drops.
Pregnancy
Since there are no adequate and well-controlled studies of the drug in pregnant women, Cytomoxan® should not be used during pregnancy, except in cases where the expected benefit of using the drug for the mother outweighs the potential risk to the fetus.
Breastfeeding period
It is not known whether moxifloxacin or its metabolites are excreted in human milk. Animal studies have shown low levels of oral moxifloxacin excretion. Cytomoxan® should be administered with caution to breastfeeding women.
Ability to influence reaction speed when driving vehicles or other mechanisms
Cytomoxan®, eye drops, 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.
Method of administration and doses
For ophthalmic use.
Adults, including elderly patients
Instill 1 drop into the affected eye(s) 3 times a day.
Usually the condition improves within 5 days, after which the treatment should be continued for another 2-3 days. If no improvement is observed within 5 days of treatment, a doctor should be consulted for clarification of the diagnosis and/or treatment. The duration of treatment depends on the severity of the disease and the clinical and bacteriological picture of the course of the disease.
Children
There is no need for dose adjustment for this category of patients.
Patients with impaired liver and kidney function
There is no need for dose adjustment for this category of patients.
To prevent contamination of the dropper tip and contents of the bottle, care should be taken not to touch the eyelids, surrounding areas, or other surfaces with the dropper tip.
To prevent absorption of drops through the nasal mucosa, especially in newborns and children, occlusion of the nasolacrimal duct for 2–3 minutes after application of the drops is recommended.
Not for injection. Cytomoxan® should not be administered by subconjunctival injection or directly into the anterior chamber of the eye.
Children
In clinical studies, moxifloxacin hydrochloride eye drops were found to be safe in children, including neonates. Two adverse reactions were reported in patients under 18 years of age: eye irritation and eye pain (incidence 0.9%). See also section "Special warnings and precautions for use".
Overdose
Given the characteristics of the drug, no toxic effect is expected in case of overdose when applying the drug to the eye or in case of accidental swallowing of the contents of one vial.
Adverse reactions
In clinical studies, the most common adverse reactions were eye pain and eye irritation, occurring in approximately 1-2% of patients.
The following adverse reactions observed during clinical trials with moxifloxacin hydrochloride eye drops are classified as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000). Within each grouping, adverse reactions are presented in order of decreasing seriousness.
| Organ system | Adverse reactions according to MedDRA (version 15.1) |
| From the circulatory and lymphatic system | Rare: decreased hemoglobin level. |
| From the nervous system | Uncommon: headache. Rare: paresthesia. |
| From the organs of vision | Common: eye pain, eye irritation. Uncommon: punctate keratitis, dry eye syndrome, conjunctival haemorrhage, conjunctival hyperaemia, ocular hyperaemia, ocular pruritus, abnormal ocular sensitivity, eyelid oedema, ocular discomfort. Rare: corneal epithelial defect, corneal disorder, corneal discoloration, conjunctivitis, blepharitis, eye swelling, eyelid pain, conjunctival edema, blurred vision, decreased visual acuity, asthenopia, eyelid disorder, eyelid erythema. |
| Respiratory, thoracic and mediastinal disorders | Rare: nasal discomfort, pharyngolaryngeal pain, foreign body sensation (in the throat). |
| From the digestive system | Uncommon: dysgeusia. Rare: vomiting. |
| Liver and biliary tract disorders | Rare: increased alanine aminotransferase, increased gamma-glutamyltransferase. |
Additional adverse reactions have been identified during post-marketing surveillance. It is not possible to estimate their frequency. Within each system organ class, adverse reactions are presented in order of decreasing seriousness.
| Organ system | Adverse reactions according to MedDRA (version 15.1) |
| On the part of the immune system | Increased sensitivity. |
| From the nervous system | Dizziness. |
| From the organs of vision | Ulcerative keratitis, keratitis, increased lacrimation, photophobia, eye discharge. |
| From the side of the cardiovascular system | Rapid heartbeat. |
| Respiratory, thoracic and mediastinal disorders | Dyspnea. |
| From the digestive system | Nausea. |
| Skin and subcutaneous tissue disorders | Erythema, itching, rash, urticaria. |
Tendon inflammation and rupture may occur with systemic use of fluoroquinolones. Studies and post-marketing experience with systemic quinolones indicate 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 (see section 4.4).
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
3 years. Shelf life after opening the bottle is 28 days.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
5 ml per bottle. 1 bottle per pack.
Vacation category
According to the recipe.
Producer
JSC "Farmak".
Location of the manufacturer and address of its place of business.
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
