Rocip (Drops) Instructions for Use

Marketing Authorization Holder

Medical Leasing-Consulting, LLC (Russia)

Manufactured By

Dalkhimpharm, JSC (Russia)

ATC Code

S01AE03 (Ciprofloxacin)

Active Substance

Ciprofloxacin (Rec.INN registered by WHO)

Dosage Form

Rocip

Eye drops 3 mg/1 ml: 5 ml or 10 ml bottle with dropper inserts

Dosage Form, Packaging, and Composition

Eye drops as a clear, light yellow or yellow liquid.

Excipients : sodium chloride – 9 mg, sodium edetate – 0.5 mg, benzalkonium chloride solution 50% – 0.2 mg (calculated as 100% substance – 0.1 mg), hydrochloric acid – q.s. to pH 3.5-5.5, water for injections – up to 1 ml.

5 ml – polymer bottles (1) with dropper caps – cardboard packs.
10 ml – polymer bottles (1) with dropper caps – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group for topical use in ophthalmology and ENT practice

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

Broad-spectrum antimicrobial agent, a fluoroquinolone derivative.

It inhibits bacterial DNA gyrase (topoisomerases II and IV, responsible for the supercoiling process of chromosomal DNA around nuclear RNA, which is necessary for reading genetic information), disrupts DNA synthesis, growth, and division of bacteria; causes pronounced morphological changes (including of the cell wall and membranes) and rapid death of the bacterial cell.

It acts bactericidally on gram-negative organisms during both the resting and division phases (as it affects not only DNA gyrase but also causes lysis of the cell wall), and on gram-positive microorganisms – only during the division phase.

Low toxicity for the cells of the macroorganism is explained by the absence of DNA gyrase in them. During the administration of ciprofloxacin, parallel development of resistance to other antibiotics not belonging to the group of gyrase inhibitors does not occur, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines, and many other antibiotics.

The following are sensitive to ciprofloxacin: gram-negative aerobic bacteria enterobacteria (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 shigelloides, Campylobacter jejuni, Neisseria spp.), some intracellular pathogens (Legionella pneumophila, Brucella spp., Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium diphtheriae); gram-positive aerobic bacteria Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Most staphylococci resistant to methicillin 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).

Resistant to the drug: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Ineffective against Treponema pallidum.

Resistance develops extremely slowly because, on the one hand, after the action of ciprofloxacin, practically no persisting microorganisms remain, and on the other hand, bacterial cells lack enzymes that inactivate it.

Pharmacokinetics

When applied topically, it is rapidly absorbed. The concentration of ciprofloxacin in blood plasma 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 values not amenable to quantitative assessment (<1.0 ng/ml) to 4.7 ng/ml. The mean C_max of ciprofloxacin in blood plasma obtained in this study is approximately 450 times lower than after oral administration of ciprofloxacin at a dose of 250 mg. The binding of ciprofloxacin to plasma proteins is 20-30%; the active substance is present in the blood plasma mainly in a non-ionized form. Ciprofloxacin is freely distributed in body tissues and fluids. The V_d in the body is 2-3 L/kg. The concentration of ciprofloxacin in tissues significantly exceeds the concentration in blood serum. It is metabolized in the liver. Four metabolites of ciprofloxacin can be detected in the blood in small concentrations: diethylciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3), formylciprofloxacin (M4), three of which (M1-M3) exhibit antibacterial activity in vitro comparable to the antibacterial activity of nalidixic acid. The in vitro antibacterial activity of metabolite M4, present in smaller quantities, more closely corresponds to the activity of norfloxacin. Ciprofloxacin is eliminated from the body mainly by the kidneys through glomerular filtration and tubular secretion; a small amount – through the gastrointestinal tract. Renal clearance is 0.18-0.3 L/h/kg, total clearance is 0.48-0.60 L/h/kg. Approximately 1% of the administered dose is excreted in the bile. Ciprofloxacin is present in bile in high concentrations. In patients with unchanged renal function, T_1/2 is usually 3-5 hours. In case of impaired renal function, T_1/2 increases.

Indications

In ophthalmology: treatment of corneal ulcers and infections of the anterior segment of the eyeball and its appendages caused by bacteria sensitive to ciprofloxacin in adults, newborns (0 to 27 days), infants and toddlers (28 days to 23 months), children (2 to 11 years) and adolescents (12 to 18 years).

In otorhinolaryngology: external otitis, treatment of postoperative infectious complications.

ICD codes

Dosage Regimen

For ophthalmic use, instill one to two drops into the affected eye(s).

For acute bacterial conjunctivitis, apply every two hours while awake for two days, then every four hours while awake for the next five days.

For bacterial corneal ulcers, instill one drop every fifteen minutes for the first six hours, then one drop every thirty minutes for the remainder of the first day.

On the second day, apply one drop hourly.

From days three through fourteen, instill one drop every four hours.

For otitis externa, instill two to three drops into the affected ear two to three times daily.

Prior to administration, warm the bottle by holding it in the hand for one to two minutes.

Lie down or tilt the head sideways for ear instillation.

Maintain the position for several minutes after application.

The recommended treatment duration is typically seven to ten days.

Do not extend use beyond fourteen days without medical reevaluation.

Avoid allowing the dropper tip to contact the eye, ear, or any other surface to prevent contamination.

Close the bottle tightly immediately after use.

If using other topical ophthalmic or otic medications, maintain an interval of at least five minutes between applications.

Apply eye ointments last.

Discontinue use and consult a physician if symptoms worsen, if no improvement is seen within a few days, or if a rash or other signs of an allergic reaction appear.

Adverse Reactions

Immune system disorders hypersensitivity reactions.

Nervous system disorders uncommon – headache; rare – dizziness.

Eye disorders: common – corneal precipitates, eye discomfort, conjunctival injection; uncommon – keratopathy, punctate keratitis, corneal infiltrates, photophobia, decreased visual acuity, eyelid edema, blurred vision, eye pain, dry eye sensation, conjunctival and eyelid edema, lacrimation, eye discharge, crusting on eyelid margins, eyelid skin scaling, eyelid hyperemia; rare – toxic phenomena from the organ of vision, keratitis, conjunctivitis, corneal epithelial defect, diplopia, decreased corneal sensitivity, asthenopia, stye.

Ear and labyrinth disorders : rare – ear pain.

Respiratory, thoracic and mediastinal disorders rare – increased secretion of sinus mucosa discharge, rhinitis.

Gastrointestinal disorders : common – dysgeusia; uncommon – nausea; rare – abdominal pain, diarrhea.

Skin and subcutaneous tissue disorders rare – dermatitis.

Musculoskeletal and connective tissue disorders frequency unknown – disorders of the ligamentous apparatus.

Contraindications

Hypersensitivity to ciprofloxacin and to other quinolones.

With caution

Cerebral atherosclerosis, cerebrovascular accident, convulsive syndrome – due to the risk of developing adverse reactions from the central nervous system.

Use in Pregnancy and Lactation

There are no data on the safety of topical use of ciprofloxacin during pregnancy, so its use is justified only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

When taken orally, Ciprofloxacin is excreted in human breast milk. It is not known whether Ciprofloxacin is excreted in breast milk with topical use, however, the risk to the breastfed infant in this case cannot be excluded. Caution is required if used during lactation.

Pediatric Use

The drug is approved for use in children and adolescents under 18 years of age.

Geriatric Use

The drug is approved for use in elderly patients.

Special Precautions

Use should be discontinued if any signs of hypersensitivity appear. The patient should be informed that if conjunctival hyperemia persists or increases for a long time after application of the drops, then the use of the drug should be discontinued and a doctor should be consulted.

Effect on ability to drive vehicles and operate machinery

After application of the eye drops, a decrease in the clarity of visual perception is possible, therefore, immediately after instillation, it is not recommended to drive a car and engage in activities requiring increased attention and speed of psychomotor reactions.

Drug Interactions

Taking into account the low systemic concentration of ciprofloxacin in plasma after instillation into the conjunctival cavity, interaction between drugs used concomitantly with ciprofloxacin is unlikely.

In case of concomitant use with other topical ophthalmic drugs, the interval between their applications should be at least 5 minutes, with eye ointments to be applied last.

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.