Rozip - instructions for use, doses, side effects, contraindications

Excipients: Sodium chloride 9,000 mg, sodium edetate 0.500 mg, benzalkonium chloride solution 50% 0.200 mg (based on 100% substance 0.100 mg), hydrochloric acid q. s. up to pH 3.5 - 5.5, water for injection up to 1,000 ml.

Description:

Transparent light yellow or yellow liquid.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

The broad-spectrum antimicrobial agent, a derivative of fluoroquinolone, suppresses bacterial DNA-gyrase (topoisomerases II and IV, responsible for the process of supercoiling the chromosomal DNA around the nuclear RNA, which is necessary for reading the genetic information), disrupts the synthesis of DNA, which leads to a violation of reading information from the chromosomes bacterial cells, which in turn leads to a disruption of the bacterial cell metabolism. As a result, the growth and division of bacteria stop, a rapid death of the bacterial cell occurs.

Ciprofloxacin displays a pronounced antibacterial activity in vitro against a wide range of Gram-positive and Gram-negative microorganisms.

The mechanism of development of resistance

The development of resistance to fluoroquinolones, in particular to ciprofloxacin, is mediated by changes in genes encoding at least one of the following mechanisms:

Change in the structure of target enzymes (DNA gyrase and topoisomerase IV) - enzymes involved in the synthesis of cell DNA;
Violation of the permeability of the cell wall;
Active excretion of the drug from the cell (increased activity of efflux pumps);
Plasmid mediated changes in the work of aminoglycoside 6-N-acetyltransferase.

Ciprofloxacin acts bactericidally on gram-negative organisms during rest and division, on gram-positive microorganisms - only during the fission period. The low toxicity for macroorganism cells is explained by the absence of DNA-gyrase in them.

Against the background of taking ciprofloxacin, there is no parallel development of resistance to antibiotics, differing in chemical structure and mechanism of action, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides,penicillins, cephalosporins, tetracyclines and many other antibiotics.

Minimum inhibitory concentrations

There is no information on the minimum inhibitory concentration of ciprofloxacin when applied as instillations, and therefore the relevant information obtained with the systemic use of fluoroquinolones applies. The clinical significance of these data with the use of ciprofloxacin in the drug form of eye drops is questionable.

According to EUCAST, the minimum inhibitory concentrations for ciprofloxacin are:

Staphylococcus species S ≤1mg / l, R≥1mg / l Streptococcus pneumoniae S ≤ 0.125mg / l, R≥2mg / l Haemophilus influenzae S ≤0.5mg / l, R≥ 0.5mg / l Moraxella catarrhalis S ≤0.5mg / l, R≥ 0.5mg / l Pseudomonas aeruginosa S ≤0.5mg / l, R≥1mg / l

Sensitive to ciprofloxacin:

Corynebacterium accolens,
Corynebacterium auris
Corynebacterium propinquum
Corynebacterium psudodiphtheriticum
Corynebacterium striatum
Staphylococcus aureus (methicillin-sensitive)
Staphylococcus capitis
Staphylococcus epidermidis (methicillin-sensitive)
Staphylococcus hominis
Staphylococcus saprophyticus
Staphylococcus warneri
Streptococcus pneumoniae
Streptococcus viridans
Acinetobacter species
Haemophilus influenzae
Moraxella catarrhalis
Pseudomonas aeruginosa
Serratia marcescens

Conditionally sensitive to ciprofloxacin:

Staphylococcus aureus (resistant to methicillin) Staphylococcus epidermidis (resistant to methicillin) Staphylococcus lugdunensis

Insensitive to ciprofloxacin

Corynebacterium jeikium

Resistance develops very slowly, because on the one hand, after the action of ciprofloxacin are left with persistent microorganisms, and on the other - the bacterial cells do not have the enzymes that inactivate it.

Pharmacokinetics:

Absorption

When topical application is quickly absorbed.

Distribution

The concentration of ciprofloxacin in the blood plasma after instillation into the conjunctiva of 2 drops of 0.3% solution every 2 hours for two days, and then every four hours for 5 days ranged from not quantifiable (<1.0 ng / ml) to 4 , 7 ng / ml. The average maximum concentration of ciprofloxacin in the blood plasma, obtained in this study is about 450 times less than after taking ciprofloxacin inside at a dose of 250 mg.

Ciprofloxacin is widely distributed in the body tissues, the approximate volume of distribution is from 1.7 to 5 l / kg. The connection with plasma proteins is 20-40%.

Metabolism

There is no information on the ways of metabolism of ciprofloxacin.

Elimination

The half-life of plasma is 3-5 hours. Ciprofloxacin and 4 of its metabolites are excreted in urine and feces. Through the kidneys, about two-thirds of the total level of ciprofloxacin in the plasma is eliminated, while a third of the total level of ciprofloxacin is released through the intestine and bile. In patients with impaired renal function, there is a slight increase in the half-life of ciprofloxacin due to extrarenal elimination.Similarly, if there is a disturbance in the liver, the half-life is slightly prolonged.

There is no information on the study of pharmacokinetic properties of ciprofloxacin in its use in children.

Indications:

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

When carrying out ciprofloxacin therapy, the recommendations in the official guidelines for the use of antibacterial drugs should be taken into account.

Contraindications:

Hypersensitivity to the active substance and any of the excipients. Hypersensitivity to quinolones.

Pregnancy and lactation:

Fertility

When carrying out studies of oral forms of ciprofloxacin in animals, no negative effect on fertility was found. Studies of the effects of ciprofloxacin in the form of instillations on fertility in humans have not been conducted.

Pregnancy

There are no data on the use of ciprofloxacin in the medicinal form of eye drops in pregnant women.In animal studies, no results have been obtained that indicate a negative effect of ciprofloxacin on reproductive function. It is expected that the systemic levels of ciprofloxacin when applied in the form of eye drops will be low.

Given the lack of data on the safety of the drug during pregnancy, it is recommended that ciprofloxacin be administered during pregnancy only if the intended benefit of using the drug by the mother exceeds the possible risk to the fetus.

Breastfeeding period

When oral use of ciprofloxacin in women during breastfeeding, it is excreted into breast milk. It is not known whether the blood is excreted ciprofloxacin in breast milk when administered in the form of instillations, but the risk for a child who is breastfed can not be ruled out in this case. Care should be taken when using the drug in women during breastfeeding.

Dosing and Administration:

Ciprofloxacin is applied topically. Do not administer the drug subconjunctivalally or into the anterior chamber of the eye.

With corneal ulcers, the drug should be instilled in the following intervals between instillations (including at night): on the first day - 2 drops every 15 minutes for the first 6 hours, then 2 drops every 30 minutes for the remainder of the day. On the second day of therapy - 2 drops every hour. From the third to the fourteenth day of therapy - 2 drops every 4 hours. If it is necessary to continue therapy for more than 14 days, the choice of dosage regimen should be performed by the attending physician.

In diseases of the anterior segment of the eyeball, the drug should be instilled according to the following scheme: 1 or 2 drops in the affected eye (eye) 4 times a day. In severe infections, the dosing regimen in the first 2 days may include instillations of the drug at 1 or 2 drops every 2 hours during wakefulness.

The duration of therapy with the drug for the indicated indications for use should not exceed 21 days.

Use in the pediatric population

The dosage regimen for therapy in children over the age of 1 year corresponds to that in adults. The efficacy and safety of ciprofloxacin in children aged 0 to 12 years has been confirmed in clinical studies involving 230 children.There was no development of serious adverse events in this group of patients.

Application in renal and hepatic insufficiency

There is no information on the use of ciprofloxacin in patients with concurrent liver and kidney disease.

After applying the drug to reduce the risk of developing systemic adverse reactions, it is recommended to lightly press the finger on the inner corner of the eye to project lacrimal sacs at the inner corner of the eye within 1-2 minutes after instillation of the drug.

Side effects:

In clinical trials, the most common adverse events were discomfort in the eye (in 6% of cases), dysgeusia (in 3% of cases) and precipitates on the cornea (in 3% of cases).

Undesirable reactions obtained during clinical trials and post-marketing surveillance data are grouped according to the following gradation frequency: very often (≥1/10), often (from ≥1 / 100 to <1/10), infrequently (from ≥ 1/1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000), very rarely (<1/10000), with an unknown frequency (the frequency of occurrence can not be established on the basis of available information).In each of the groups, the list of undesirable reactions is made as the frequency of their occurrence decreases.

System of organs	Unwanted phenomenon
Immune system disorders	Rarely: hypersensitivity reactions
Disturbances from the nervous system	Infrequently: a headache. Rarely: dizziness
Disturbances on the part of the organ of sight	Often: precipitates on the cornea, discomfort in the eye, conjunctival hyperemia Infrequent: keratopathy, pinpoint keratitis, corneal infiltrates, photophobia, decreased visual acuity, eyelid edema, blurred vision, eye pain, dry eyes, conjunctival edema and eyelids, itching in the eye, lacrimation, discharge from the eyes, crust formation on the edges of the eyelids , peeling of the skin of the eyelids, hyperemia of the eyelids. Rarely: toxic phenomena from the side of the organ of vision, keratitis, conjunctivitis, corneal epithelial defect, diplopia, decreased corneal sensitivity, asthenopia, barley.
Violations from the organ of hearing and labyrinth	Rarely: pain in the ear.
Disturbances from the respiratory, thoracic and mediastinal organs	Rarely: increased secretion of the paranasal sinuses to be separated by the mucous membrane, rhinitis.
Disturbances from the organs of the digestive system	Often: dysgeusia. Infrequently: nausea. Rarely: abdominal pain, diarrhea.
Disturbances from the skin and subcutaneous fat	Rarely: dermatitis
Disturbances from the musculoskeletal system and connective tissue	With an unknown frequency: disturbances from the ligamentous apparatus

Description of individual groups of unwanted reactions

There were rare cases of development of generalized rash, toxic epidermolysis, exfoliative dermatitis, Stevens-Johnson syndrome and urticaria.

Serious anaphylactic reactions, in rare cases with a fatal outcome, including after the first dose, were noted in patients who received fluoroquinolones orally. Some of these reactions were accompanied by cardiovascular collapse, loss of consciousness, swelling of the larynx and face, tingling sensation, dyspnoea, pruritus and urticaria.

In patients who took fluoroquinolones orally, there were ruptures of tendons of the shoulder joint, tendons of the joints of the hands, Achilles tendon and other tendons, which subsequently required surgical intervention or led to long-term disability.In the course of clinical studies and post-marketing surveillance, there was no evidence of the effects of ciprofloxacin instillations on the state of the musculoskeletal system and connective tissue.

In some cases, with instillations of ciprofloxacin, blurred vision, decreased visual acuity, and a residual amount of the drug on the surface of the cornea.

During the systemic application of quinolones, phototoxicity reactions of moderate and severe severity were noted, however, for ciprofloxacin such reactions are not characteristic.

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. There was no development of serious adverse events in this group of patients.

Overdose:

Data on drug overdose are absent. In case of unpleasant sensations in the eye area, it is recommended to wash eyes with warm water.

Interaction:

Special studies of interaction with the use of ophthalmic forms of ciprofloxacin have not been conducted.Taking into account the low systemic concentration of ciprofloxacin in plasma after instillation into the conjunctival cavity, the interaction between ciprofloxacin used together with drugs is unlikely. In case of joint application with other local ophthalmic preparations, the interval between their use should be at least 5 minutes, with ophthalmic ointments should be used last.

Special instructions:

The experience of clinical use of ciprofloxacin in children younger than 1 year is limited. The use of eye drops of ciprofloxacin in ophthalmia of newborn gonococcal or chlamydial etiology is not recommended due to the lack of information about the use of the drug in this group of patients. Patients with ophthalmic neonates should receive appropriate etiotropic therapy.

When using eye drops of ciprofloxacin, it is necessary to take into account the possibility of rhinopharyngeal passage, which can lead to an increase in the frequency of occurrence and an increase in the degree of bacterial resistance. Serious anaphylactic reactions, in rare cases with a fatal outcome,including after the first dose, were observed in patients who received systemic therapy with fluoroquinolones. Some of these reactions were accompanied by cardiovascular collapse, loss of consciousness, swelling of the larynx and face, tingling sensation, dyspnoea, pruritus and urticaria. Only a few patients had a history of hypersensitivity reactions.

The drug should be discontinued immediately if skin rashes or any other signs of an allergic reaction occur. If hypersensitivity reactions develop, ciprofloxacin may require emergency care, including with the use of artificial ventilation.

With prolonged therapy with antibacterial drugs, excessive growth of non-susceptible microorganisms, including fungal flora, is possible. In case of development of superinfection, additional antibacterial therapy should be prescribed. There are data on cases of inflammation and rupture of tendons in elderly patients with systemic fluoroquinolone use is consonant with glucocorticosteroids, therefore, at the first signs of inflammation of the tendons, the drug should be stopped.

In patients with corneal ulcers, the appearance of white crystalline precipitate, which is the remnants of the drug, was noted. Precipitates do not interfere with the further use of ciprofloxacin and do not affect the therapeutic effect of the drug. The appearance of precipitate is observed in the period from 24 hours to 7 days after the initiation of therapy, and its resorption can occur either immediately after formation, or within 13 days after the initiation of therapy.

The drug contains a preservative benzalkonium chloride, which can be absorbed by contact lenses and cause a change in their color, as well as eye irritation. Before using the drug, contact lenses should be removed and placed back no earlier than 15 minutes after the drug is used.

During the treatment with the drug, wearing contact lenses is not recommended.

The bottle must be closed after each use. Do not touch the tip of the pipette to the eye.

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:

Eye drops, 3 mg / ml.

Packaging:

5 ml and 10 ml into a bottle of low density polyethylene, sealed with a screw cap of low density polyethylene.

1 bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Use within 1 month after opening the vial.

Terms of leave from pharmacies:On prescription

Registration number:LP-003068

Date of registration:02.07.2015

The owner of the registration certificate:Rowecq LimitedRowecq Limited United Kingdom

Manufacturer: & nbsp

AHLCON PARENTERALS, Limited India

Representation: & nbspROUTEC LIMITEDROUTEC LIMITEDUnited Kingdom

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Rozip (Rocip)