Signicef^® (Drops) Instructions for Use

Marketing Authorization Holder

Sentiss Pharma, Pvt. Ltd. (India)

ATC Code

S01AE05 (Levofloxacin)

Active Substance

Levofloxacin (Rec.INN registered by WHO)

Dosage Form

Signicef®

Eye drops 0.5%: dropper bottle 5 ml 1 pc.

Dosage Form, Packaging, and Composition

Eye drops in the form of a clear, light yellow solution.

Excipients : benzalkonium chloride – 0.1 mg, hypromellose – 2 mg, sodium chloride – 9 mg, sodium hydroxide – q.s., hydrochloric acid – q.s., purified water – up to 1 ml.

5 ml – dropper bottles made of polyethylene (1) – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group for topical use in ophthalmology

Pharmacotherapeutic Group

Drugs used in ophthalmology; antimicrobials; fluoroquinolones

Pharmacological Action

Levofloxacin is the L-isomer of the racemic drug substance ofloxacin. The antibacterial activity of ofloxacin is primarily attributed to the L-isomer. As an antibacterial drug of the fluoroquinolone class, Levofloxacin inhibits DNA gyrase and topoisomerase IV, disrupts DNA supercoiling and cross-linking of breaks, inhibits DNA synthesis, and causes profound morphological changes in the cytoplasm, cell wall, and membranes of bacteria.

The in vitro activity of levofloxacin is approximately twice that of ofloxacin against members of the Enterobacteriaceae family, Pseudomonas aeruginosa, and gram-positive microorganisms. The drug is active against gram-negative aerobes such as Branhamella (Moraxella) catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, gram-positive aerobes, such as Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes. Other microorganisms sensitive to levofloxacin include Chlamydia trachomatis.

The maximum concentration of levofloxacin achieved when using 5 mg/ml eye drops is more than 100 times greater than the minimum inhibitory concentration (MIC) value of levofloxacin for susceptible microorganisms.

Pharmacokinetics

After instillation into the eye, Levofloxacin is well retained in the tear film. The concentration of levofloxacin in the tear fluid after a single dose (1 drop) quickly reaches high levels and remains above the MIC for most sensitive ocular pathogens (less than or equal to 2 µg/ml) for at least 6 hours. Studies in healthy volunteers have shown that the mean concentrations of levofloxacin in the tear film, measured at 4 and 6 hours after topical application, were 17.0 µg/ml and 6.6 µg/ml, respectively. In 5 out of 6 subjects, levofloxacin concentrations were 2 µg/ml and above 4 hours after instillation. In 4 out of 6 subjects, this concentration persisted 6 hours after instillation.

The mean plasma concentration of levofloxacin 1 hour after application ranged from 0.86 ng/ml on day 1 to 2.05 ng/ml. The C_max of levofloxacin in plasma, equal to 2.25 ng/ml, was detected on day 4 after 2 days of drug application every 2 hours up to 8 times/day. The C_max of levofloxacin achieved on day 15 is more than 1000 times lower than the concentrations observed after oral administration of standard doses of levofloxacin.

Indications

For adults and children aged 1 year and older for

• Treatment of infections of the eye adnexa and anterior segment caused by flora susceptible to levofloxacin;
• Prevention of complications after surgical and laser eye operations.

ICD codes

Dosage Regimen

Instill 1-2 drops into the affected eye(s) every 2 hours, up to 8 times per day while awake, during the first 2 days of treatment.

Reduce the frequency to 4 times per day from day 3 to day 5.

Follow the prescribed duration of the treatment course, which is typically 5 days.

For surgical prophylaxis, follow the specific regimen prescribed by the surgeon, which may involve instillation prior to and following the procedure.

Do not allow the dropper tip to contact any surface, including the eye, to avoid contamination of the solution.

If using more than one type of ophthalmic drop, maintain an interval of at least 15 minutes between instillations.

After administration, keep the eye closed for 1-2 minutes and apply gentle pressure to the lacrimal sac at the inner corner of the eye to minimize systemic absorption.

Discard the container and any remaining solution 4 weeks after first opening the bottle.

Adverse Reactions

From the organ of vision common (1-10%) – decreased visual acuity and appearance of mucous strands; rare (0.1-1%) – blepharitis, chemosis, conjunctival papillae, eyelid edema, eye discomfort, eye burning and itching, visual impairment, eye pain, conjunctival hyperemia, mucous discharge, conjunctival folliculosis, dry eye syndrome, eyelid erythema, contact dermatitis, photophobia.

Other rare (0.1-1%) – allergic reactions, headache, rhinitis.

Contraindications

• Hypersensitivity to levofloxacin or other quinolones;
• Pregnancy;
• Breastfeeding period;
• Children under 1 year of age.

With caution

Children and adolescents under 18 years of age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Pediatric Use

Contraindicated for use in children under 1 year of age. The drug should be used with caution in children and adolescents under 18 years of age.

Special Precautions

This product must not be administered subconjunctivally or into the anterior chamber of the eye.

When using other ophthalmic products simultaneously, the interval between instillations should be at least 15 minutes.

Effect on ability to drive vehicles and operate machinery

This product does not significantly affect the ability to drive vehicles and operate machinery. Immediately after instillation, temporary blurred vision may occur. It is not recommended to drive vehicles or engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions until visual clarity is restored.

Drug Interactions

Since the C_max of levofloxacin in plasma after instillation into the eye is at least 1000 times lower than after oral administration of standard doses, interactions with other drugs characteristic of systemic use are clinically insignificant.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.