Instructions for use Signicef eye drops 0.5%, plastic dropper bottle, 5 ml
Composition
active ingredient: levofloxacin;
1 ml of the drug contains levofloxacin hemihydrate equivalent to levofloxacin 5 mg;
Excipients: benzalkonium chloride, hypromellose, sodium chloride, sodium hydroxide, hydrochloric acid, water for injections.
Dosage form
Eye drops.
main physicochemical properties: clear, light yellow liquid.
Pharmacotherapeutic group
Drugs used in ophthalmology. Levofloxacin. ATX code S01A E05.
Pharmacological properties
Pharmacodynamics.
Levofloxacin is the active ingredient of the drug Signicef - a synthetic broad-spectrum antibacterial agent, a fluoroquinolone of the third generation, the S-enantiomer of ofloxacin. It inhibits bacterial enzymes necessary for replication, transcription, repair and recombination of DNA topoisomerase IV and DNA gyrases (type II topoisomerases), preventing further bacterial reproduction. Active against aerobic gram-positive bacteria.
Antibacterial spectrum of action – susceptibility categories and resistance characteristics according to EUCAST requirements
| Category I: common susceptible species |
| Aerobic Gram-positive microorganisms |
| Staphylococcus aureus (MSSA)* |
| Streptococcus pneumoniae |
| Streptococcus pyogenes |
| Viridans group streptococci |
| Aerobic Gram-negative microorganisms |
| Escherichia coli |
| Haemophilus influenzae |
| Moraxella catarrhalis |
| Pseudomonas aeruginosa | Isolate from public places |
| Other microorganisms |
| Chlamydia trachomatis | When treating patients with chlamydial conjunctivitis, systemic antimicrobial treatment should be administered simultaneously. |
| Category II: species that may cause problems due to acquired resistance |
| Aerobic Gram-positive microorganisms |
| Staphylococcus aureus (MRSA)** | |
| Staphylococcus epidermidis | |
| Aerobic Gram-negative microorganisms |
| Pseudomonas aeruginosa | Isolate from hospitals |
* MSSA – methicillin-sensitive Staphylococcus aureus strains.
** MRSA – methicillin-resistant Staphylococcus aureus strains.
The resistance data presented above are based on the results of a multicenter study of the prevalence of resistance in bacterial isolates collected from patients with ocular infections in Germany. Microorganisms were classified as susceptible to levofloxacin based on in vitro susceptibility and plasma concentrations after systemic therapy. When applied topically to the eye, peak concentrations were achieved in the tear film that were higher than those determined in plasma, but it is not known whether this affects the antibacterial properties of levofloxacin.
Cross-resistance.
Cross-resistance between fluoroquinolones is possible. A single mutation does not result in clinical resistance, but multiple mutations usually result in clinical resistance to all drugs in the fluoroquinolone class. Alterations in outer membrane porins and efflux systems can have broad substrate specificity, be directed against multiple classes of antibacterial agents, and lead to the development of multiple resistance.
MIC (minimum inhibitory concentration) thresholds that allow differentiation of sensitive and moderately resistant microflora from resistant:
Pseudomonas spp., Staphylococcus spp., Streptococcus A,B,C,G: susceptible ≤ 1 mg/l, resistant > 2 mg/l;
Streptococcus pneumoniae: susceptible ≤ 2 mg/l, resistant > 2 mg/l;
Haemophilus influenzae, Moraxella catarrhalis: susceptible ≤ 1 mg/l, resistant > 1 mg/l.
Other pathogenic microorganisms: sensitive ≤ 1 mg/l, resistant > 2 mg/l.
Pharmacokinetics.
Levofloxacin is well retained in the tear film after application. The mean concentrations of levofloxacin in the tear film measured 4 and 6 hours after topical application were 17 μg/mL and 6.6 μg/mL, respectively. Five of the six volunteers studied had concentrations of 2 μg/mL or higher at 4 hours post-dose; four of the six volunteers studied had these concentrations at 6 hours post-dose.
Levofloxacin plasma concentrations were measured in 15 healthy volunteers at various time points during a 15-day course of drug administration. The mean plasma levofloxacin concentration one hour after dosing ranged from 0.86 ng/mL on day 1 to 2.05 ng/mL on day 15. The highest maximum levofloxacin concentration of 2.25 ng/mL was recorded on day 4 after 2 days of dosing every 2 hours (total of 8 doses per day).
Maximum levofloxacin concentrations increased from 0.94 ng/mL on day 1 to 2.15 ng/mL on day 15, which is 1000-fold lower than known concentrations after standard doses of oral levofloxacin.
The concentration of levofloxacin in blood plasma after application to the affected eye is still unknown.
Indication
Topical treatment of ocular infections caused by microorganisms sensitive to levofloxacin.
Contraindication
Hypersensitivity to levofloxacin or other quinolones or to any of the other components of the drug.
Interaction with other medicinal products and other types of interactions
No special studies have been conducted on the interaction of the drug with other medicines.
However, systemic administration of some quinolones has been shown to increase plasma theophylline concentrations, interfere with caffeine metabolism, enhance the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with a transient increase in serum creatinine in patients concomitantly receiving systemic cyclosporine.
Since the maximum concentration of levofloxacin in the blood plasma after application in a therapeutic dose is at least 1000 times lower than those observed after standard doses when administered orally, it is unlikely that clinically significant interactions indicated for systemic drugs can be expected when using Signicef eye drops. In order to avoid possible interactions, in the case of simultaneous topical application of several drugs to the eyes, it is necessary to maintain a 15-minute interval before applying the next drug.
Application features
The drug is not intended for subconjunctival injections and administration directly into the anterior chamber of the eye.
Systemic fluoroquinolones have been associated with serious and sometimes fatal allergic (anaphylactic) reactions, even after a single dose. Some reactions have been accompanied by cardiovascular failure, loss of consciousness, angioedema (including laryngeal, pharyngeal or facial swelling), airway obstruction, dyspnoea, urticaria and pruritus.
Like other fluoroquinolones, levofloxacin is associated with a higher risk of hypersensitivity reactions, even with single use. If hypersensitivity reactions occur, the drug should be discontinued.
In the absence of the expected therapeutic effect during treatment and/or deterioration of the patient's condition, treatment with the drug should be discontinued and other means should be used.
As with other antimicrobial agents, prolonged use of the drug may cause the formation of resistant microflora, including fungal, which requires a change in treatment tactics. According to clinical indications, the patient should undergo additional instrumental examination, for example, using a light slit-lamp biomicroscope, if necessary - with the use of a contrast agent (fluorescein).
Use in elderly patients. There is no need to adjust the dose in elderly patients.
Contact lenses. Patients should generally be advised not to wear contact lenses if they develop symptoms of bacterial conjunctivitis. The product contains benzalkonium chloride as a preservative, which may cause irritation and discoloration of soft contact lenses. Therefore, the patient should remove contact lenses before instillation and wait 15 minutes after instillation before reinserting contact lenses.
Fertility.
Levofloxacin had no effect on fertility or reproduction in rats at oral doses up to 360 mg/kg/day, which is approximately 16,000 times higher than the plasma concentration determined in humans after 8 eye instillations.
Impact on women of reproductive age.
There is no information related to the effects of topical application of levofloxacin 5 mg/ml eye drops on women of reproductive age.
Contraception in men and women.
There is no information related to the effect of topical levofloxacin 5 mg/ml eye drops on contraception in men and women.
Use during pregnancy or breastfeeding
Not used.
Ability to influence reaction speed when driving vehicles or other mechanisms
When using the drug, short-term visual disturbances (loss of image clarity, blurring) are possible, therefore driving a car and working with other mechanisms is possible only after visual clarity is restored.
Method of administration and doses
It is used in children over 1 year of age and adults. During the first 2 days from the onset of the disease, 1–2 drops are instilled into the affected eye(s) every 2 hours up to 8 times a day; then from the 3rd to the 5th day - in the same doses, but the number of applications is reduced to 4 times a day.
The duration of treatment depends on the severity of the lesion, the clinical and bacteriological course of the disease. Usually the treatment period is 5 days.
Method of application.
Tilt your head back, gently pull the lower eyelid of the affected eye with your finger, apply 1–2 drops of the drug and close your eyes. Press the inner edge of the eye with your finger for 1–2 minutes to prevent the drug from entering the tear duct and reduce the possibility of the drug entering the systemic bloodstream. Do not blink. Remove any remaining drug around the eye with a clean tissue, avoiding contact with the eye.
To prevent contamination of the dropper tip, avoid contact with the eyelids or the area around the eye.
When using different topical ophthalmic medications concurrently, the interval between administrations should be at least 15 minutes.
Children
The drug is not used in children under 1 year of age.
Overdose
Symptoms: The amount of levofloxacin in a bottle of eye drops is too small to cause a toxic effect after accidental ingestion. In case of overdose with topical application, an increase in the symptoms of side effects is likely.
Treatment. The drug should be discontinued. Symptomatic therapy: if the drug is applied to the eye(s) - rinse with plenty of water. In case of accidental ingestion, if necessary, the patient should be examined and supportive measures taken.
Side effects
Side effects occur in approximately 10% of patients who use the drug. These reactions are usually mild to moderate in severity, transient in nature, and most often limited to the eye area.
Ophthalmological disorders.
Burning in the eyes, visual disturbances, mucus discharge, temporary deterioration of visual acuity, eye irritation, edema, temporary epithelial complications, corneal epithelial disorders, eyelid opacification, chemosis, conjunctivitis, conjunctival papillary reaction, eyelid edema, ocular discomfort, eye and/or eyelid itching, eye pain, conjunctival injection, conjunctival follicles, dry eye, eyelid erythema and photophobia, blepharitis, keratitis, punctate keratitis, corneal erosion, accommodation disorders, foreign body sensation in the eye, conjunctival discoloration, conjunctival hyperemia, episcleritis, increased tearing.
Corneal deposition was not observed in clinical studies.
Non-ophthalmological disorders.
Allergic reactions (skin rash, urticaria, difficulty breathing, chest tightness, swelling of the mouth, face, lips, tongue), anaphylactic reaction; headache, dizziness, rhinitis, pharyngitis, diarrhea, nausea, dysgeusia, contact dermatitis, decreased sensitivity of the oral cavity, laryngeal edema.
Since the product contains benzalkonium chloride, the active ingredient of this preservative may cause contact eczema and/or irritation.
Expiration date
2 years.
The shelf life after opening the bottle is 1 month.
Storage conditions
Store at a temperature not exceeding 25 °C, protected from light. Do not freeze. Keep out of the reach of children.
Packaging
5 ml in a dropper bottle with a scarifier cap, 1 bottle in a pack.
Vacation category
According to the recipe.
Producer
SENTISS PHARMA PVT. LTD., India / SENTISS PHARMA PVT. LTD., India.
Location of the manufacturer and its business address
Village Khera Nihla, Tehsil Nalagarh, Distt. Solan, Himachal Pradesh, 174 101, India/Village Khera Nihla, Tehsil Nalagarh, Distt. Solan, Himachal Pradesh, 174 101, India.
Applicant
SENTISS PHARMA PVT. LTD., India / SENTISS PHARMA PVT. LTD., India.
Address
212/D-1, Ashirwad Commercial Complex, Green Park, New Delhi, 110016, India.
