Instructions Aziter eye drops 15mg/g 250mg No. 6
Composition
active ingredient: azithromycin;
1 g of solution contains azithromycin dihydrate - 15 mg, which is equivalent to azithromycin - 14.3 mg.
1 single-dose container (250 mg solution) contains 3.75 mg of azithromycin dihydrate;
excipients: medium chain triglycerides.
Dosage form
Eye drops, solution.
Main physicochemical properties: transparent, colorless or slightly yellow oily liquid, practically free from foreign particles.
Pharmacotherapeutic group
Antibiotics. ATX code: S01A A26.
Pharmacological properties
Pharmacodynamics
Azithromycin is a second-generation macrolide antibiotic belonging to the azalide group.
The mechanism of action of azithromycin is to inhibit bacterial protein synthesis by binding to the 50 S subunit of ribosomes and inhibiting peptide translocation.
Mechanism of resistance.
In general, resistance of different bacterial species to macrolides is attributed to one of three mechanisms: modification of the target cell, inactivation of the antibiotic, or active removal of the antibiotic (efflux) from the cell. Bacteria have different systems for removing substances from the cell. In streptococci, the efflux system is largely controlled by the mef genes, which leads to the formation of limited resistance to macrolides (phenotype M). Modification of the target by methylase, controlled by the erm gene (phenotype MLSB), can lead to cross-resistance to different classes of antibiotics.
Complete cross-resistance to erythromycin, azithromycin, other macrolides and lincosamides, and streptogramin B exists between Streptococcus pneumoniae, group A beta-hemolytic streptococcus, Enterococcus faecalis, and Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA).
Constitutive mutants in inducibly resistant strains with erm (A) or erm (C) can be selected in vitro at their low concentration of 10-7 CFU in the presence of azithromycin.
Limiting concentration. The minimum inhibitory concentrations (MICs) for microorganisms for the indicated indications are presented below (see the "Indications" section).
It should be noted that the MIC breakpoints and in vitro spectrum of activity presented below are applicable for systemic use. Such MICs are not applicable for topical ocular use, taking into account the concentrations achieved in situ and the physicochemical conditions that may affect the overall activity of the antibiotic at the site of application.
EUCAST (European Committee on Antimicrobial Susceptibility Testing) has established the following breakpoints for azithromycin:
Haemophilus influenzae: sensitivity ≤ 0.12 mg/l and resistance > 4 mg/l; Moraxella catarrhalis: sensitivity ≤ 0.5 mg/l and resistance > 0.5 mg/l; Neisseria gonorrhoeae: sensitivity ≤ 0.25 mg/l and resistance > 0.5 mg/l; Staphylococcus spp*: sensitivity ≤ 1.0 mg/l and resistance > 2.0 mg/l; Streptococcus pneumoniae: sensitivity ≤ 0.25 mg/l and resistance > 0.5 mg/l; Streptococcus A, B, C, G: sensitivity ≤ 0.25 mg/l and resistance > 0.5 mg/l.
* spp includes all species of the class.
EUCAST notes that erythromycin can be used to determine the susceptibility of the specified microorganisms to azithromycin.
The prevalence of acquired resistance may vary with location and time for individual species, therefore local information on resistance is necessary, particularly when treating severe infections. Qualified advice may be sought if the local prevalence of resistance is such that the efficacy of the drug in the treatment of at least some types of infections is questionable.
The spectrum of antibacterial activity of azithromycin against bacterial species according to indications:
Usually sensitive species.
Gram-negative aerobes: Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoae1, Haemophilus influenzae$, Haemophilus parainfluenzae$.
Others: Chlamydia trachomatis*.
Species that may acquire resistance.
Gram-positive aerobes:
Staphylococcus aureus (methicillin-resistant and methicillin-susceptible),
Staphylococcus coagulase negative (methicillin-resistant and methicillin-susceptible), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococci viridans, Streptococcus agalactiae, Streptococcus group G.
Resistant species.
Aerobic gram-positive: Corynebacterium spp., Enterococcus faecium.
Aerobic gram-negative: Pseudomonas aeruginosa, Acinetobacter, Enterobacteriaceae.
* Clinical efficacy demonstrated on susceptible strains isolated according to approved indications.
$ Intermediate natural sensitivity.
1 Conjunctivitis caused by Neisseria gonorrhoeae requires systemic treatment (see section "Special instructions").
Information from clinical trials.
Trachomatous conjunctivitis caused by Chlamydia trachomatis.
Mass therapy, treatment and prevention of trachoma with Aziter® (instillation 2 times a day for 3 days) in all population categories (from birth) was evaluated in a phase IV multicenter, open-label, non-comparative study conducted in northern Cameroon (112,000 patients). In a sample of 2,400 children aged ≥ 1 year to < 10 years, the prevalence of active trachoma, which was 31.1% before instillation with Aziter®, decreased to 6.3% after 1 year and to 3.1% in the 2nd and 3rd years.
No serious adverse events were observed in the population treated with the drug.
Purulent bacterial conjunctivitis.
A randomized, blinded study in different geographical areas of Europe, North Africa and India compared Aziter® instilled twice daily for 3 days with tobramycin 0.3% (eye drops) instilled every 2 hours for 2 days, then 4 times daily for 5 days in 1043 patients with purulent bacterial conjunctivitis, including 109 children under 11 years of age, 5 neonates (birth to 27 days) and 38 infants and toddlers (28 days to 23 months).
Clinical recovery within 9 days with Aziter® (87.8%) was not significantly different from the outcome of treatment with tobramycin (89.4%). The microbiological status of recovery with Aziter® was comparable to that with tobramycin therapy.
Children.
The efficacy and safety of Aziter® were demonstrated in the treatment of pediatric patients ≤ 18 years of age in a randomized, blinded, closed-label study comparing Aziter® (instillation 2 times a day for 3 days) with tobramycin (instillation every 2 hours for 2 days, then 4 times a day for 5 days) in 282 children with purulent bacterial conjunctivitis (the subgroup of patients from birth to 24 months included 148 people). Clinical recovery of the most affected eyes by day 3 was significantly higher in the Aziter® group (47%) compared to the tobramycin group (28%). By day 7, 89% of patients receiving Aziter® (instillation 2 times a day for 3 days) were healed, compared to 78% of patients receiving tobramycin. There was no statistical difference between the two study groups in terms of bacteriological status on day 7. Aziter® was well tolerated in all age groups. No new side effects were identified in children. The short duration of treatment with azithromycin 1.5%, the small number of required injections, and the ease of instillation of drops in children were appreciated by both children and their parents.
Pharmacokinetics
Azithromycin was not detected in the blood plasma of patients with bacterial conjunctivitis after administration of Aziter® within the recommended doses (sensitivity limit: 0.0002 μg/ml in plasma). Pharmacokinetic studies in children have not been conducted.
Indication
Aziter® is intended for local antibacterial therapy of conjunctivitis caused by strains sensitive to it, in children from the first days of life and adults, namely:
purulent bacterial conjunctivitis; trachomatous conjunctivitis caused by Chlamydia trachomatis.
Contraindication
Hypersensitivity to azithromycin or other macrolides or to any other component of the drug.
Interaction with other medicinal products and other types of interactions
No specific studies on interactions with Aziter® have been conducted.
Since there is no systemic effect of Azithromycin® eye drops when instilled into the eyes (no significant concentrations of azithromycin are observed in the blood plasma, see the Pharmacokinetics section), none of the interactions of azithromycin with other drugs when administered orally are expected.
In case of concomitant use of other eye drop preparations with Aziter®, a 15-minute interval between applications must be observed, with Aziter® being instilled last.
Application features
The drug is not intended for oral or injectable use, including periocular or intraocular injection.
In case of an allergic reaction, treatment should be discontinued.
The patient should be informed that the drug should not be continued for more than 3 days, even if there are residual signs of bacterial conjunctivitis.
Symptom relief is usually observed within 3 days of use. If there are no signs of improvement after this period, the prescribed treatment should be reviewed.
In cases of bacterial conjunctivitis, contact lenses are not used during the treatment period.
Cases of fulminant hepatitis, which can lead to life-threatening liver failure, have been reported with systemic use of azithromycin. This risk is not expected with topical ocular administration, as systemic exposure to the active substance is clinically insignificant (see section 5.2).
As with erythromycin and other macrolides, rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal); dermatological reactions, including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (rarely fatal), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported. Some of these reactions associated with azithromycin have resulted in recurrent symptoms and have required longer periods of observation and treatment.
In case of allergic reactions, the drug should be discontinued and appropriate symptomatic therapy should be initiated. Physicians should be aware that allergic symptoms may recur after discontinuation of symptomatic therapy.
Childhood.
Comparative efficacy and safety studies of Aziter® eye drops for the treatment of trachomatous conjunctivitis in children under 1 year of age have not been conducted. However, there are no known safety concerns or differences in the pathophysiology of the disease that would preclude its use in children under 1 year of age for this indication, given the clinical experience in children over 1 year of age and the experience of using the drug in children from birth for the treatment of purulent bacterial conjunctivitis.
Use in newborns.
Based on international consensus on eye and genital diseases that can be transmitted to newborns, non-trachomatous (chlamydial) conjunctivitis caused by Chlamydia trachomatis, as well as conjunctivitis caused by Neisseria gonorrhoeae, require systemic treatment.
In neonates and infants under 3 months of age, systemic infections (e.g., pneumonia, Chlamydia trachomatis bacteremia) may be associated with conjunctivitis. In cases of suspicion, a differential diagnosis should be made and systemic treatment should be initiated if necessary.
Aziter® eye drops are not used to prevent bacterial conjunctivitis in newborns.
Ability to influence reaction speed when driving vehicles or other mechanisms
Temporary loss of visual acuity may occur after instillation. In this case, the patient should wait until normal vision returns before driving or operating machinery.
Use during pregnancy or breastfeeding
Since the systemic effects of azithromycin are clinically insignificant, the drug can be used during pregnancy and breastfeeding.
Reproductive function.
Animal data do not indicate any effect of azithromycin on male or female reproductive function. There are no data on human reproductive function. However, since the systemic exposure to azithromycin is not clinically significant, no effect on reproductive function is expected.
Method of administration and doses
The drug is used for instillation into the eyes.
It is necessary for the doctor to provide the patient with recommendations on the proper use of the antibacterial agent.
Adults.
Instill 1 drop into the conjunctival sac 2 times a day, morning and evening. The course of treatment is 3 days.
There is no need to continue treatment for more than 3 days.
Compliance with the dosage is of great importance for the success of treatment.
Elderly patients.
There is no need to adjust the dose.
Application procedure.
Wash your hands, stand or sit comfortably. Pull down the lower eyelid of the affected eye with your finger. Bring the tip of the opened single-dose container as close to the eye as possible, but do not touch the eye. Gently squeeze the container to release one drop into the eye, and release the lower eyelid. Close your eyes and press your finger against the inner corner of the instilled eye for 1 minute. Repeat all of the above steps with the other eye, if your doctor has told you to. Throw away any remaining solution in the single-dose container immediately after use. Do not save it for future use. When using multiple topical ophthalmic products, the products should be used at least 15 minutes apart.
Children
It is used in children from birth. Dosage - as indicated for adults in the section "Method of administration and doses". There is no need to adjust the dose for children (see sections "Features of use" and "Pharmacodynamic properties").
Overdose
The total amount of azithromycin intended to treat both eyes is too small to cause symptoms of overdose if the contents of a single-dose container are administered intravenously or orally.
Adverse reactions
During clinical trials and post-marketing surveillance with Aziter® 15 mg/g, eye drops, solution, the following treatment-related adverse reactions were reported.
Adverse reactions are classified by frequency as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000) and very rare (< 1/10000), unknown (cannot be determined based on available data).
From the immune system.
Uncommon: Quincke's edema*, hypersensitivity reactions.
From the organs of vision (at the injection site).
Common: blurred vision, feeling of eyelids sticking together, foreign body sensation.
Uncommon: conjunctivitis*, allergic conjunctivitis*, keratitis*, eyelid eczema*, eyelid oedema*, eye allergy*, conjunctival hyperaemia, lacrimation increased, eyelid erythema.
Skin and subcutaneous tissue disorders.
Not known (frequency cannot be estimated from the available data): toxic epidermal necrolysis$, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)$, Stevens-Johnson syndrome (SJS)$, exfoliative dermatitis$, acute generalized exanthematous pustulosis (AGEP)$.
* Adverse reactions were not observed during clinical studies of Azithromycin®. These adverse reactions were observed during post-marketing studies of azithromycin. The frequency is calculated using the formula 3/X, where X is the total population involved in all studies and clinical trials, or corresponds to a frequency of 3/879 - "uncommon".
$ extrapolating systemic impact
Children. Clinical studies in pediatrics have shown that the safety profile in children is similar to that in adults. No new adverse reactions have been identified. The safety profile in different pediatric subgroups was also similar (see section 5.1).
Expiration date
36 months.
After first opening the single-dose container, its contents should be used immediately and the single-dose container should be discarded.
Storage conditions
Store at 2°C to 8°C. Store single-dose containers in sachets in order to protect from light.
Keep out of reach of children.
Packaging
250 mg in a single-dose container, 6 single-dose containers in a sachet in a cardboard box.
Vacation category
According to the recipe.
Producer
UNITHER LABORATORY/LABORATOIRE UNITHER.
Location of the manufacturer and its business address
Industrial Zone de la Guerie, COUTANCES CEDEX, 50211, France/ZI de la Guerie, COUTANCES CEDEX, 50211, France.
