Azidrop eye drops 15 mg/g 0.25 g vials, 6 pcs.

Composition

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of 1 g of eye drops contains:

Active ingredient:

azithromycin dihydrate 15 mg, which corresponds to the content of azithromycin 14.3 mg,

excipients:

medium-chain triglycerides up to 1 g

. Pharmacological action

 Antimicrobial drug for topical application. Azithromycin is a second-generation macrolide antibiotic from the azalide group. Inhibits bacterial protein synthesis by binding to the 50S subunit of ribosomes and preventing translocation of peptides.

Mechanism of resistance

Three mechanisms of resistance to macrolides are noted for different bacterial species: due to modification of the target of action, modification of the antibiotic, or due to the active release of the antibiotic from the microbial cell using transport systems (efflux). Various efflux systems are described for bacteria. An important efflux system for streptococci is encoded by the mef gene and leads to macrolide-limited resistance (M-phenotype). Target modification controlled by erm-encoded methylase (MLSB-phenotype) leads to cross-resistance to various classes of antibiotics.

Cases of cross-resistance to erythromycin, azithromycin, other macrolides and lincosamide and streptogramin B have been described for Streptococcus pneumoniae, Group A beta-hemolytic streptococci, Enterococcus spp. and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Constitutive mutants in inducibly resistant strains with erm (A) or erm(C) can be isolated in vitro at low frequencies of approximately 10-7 CFU in the presence of azithromycin.

Border value

The minimum inhibitory concentrations (MICS) for micro-organisms for these indications are shown below.

It should be noted that the MIC boundary values and spectrum of action presented below relate to systemic use. These MICS cannot be used in the case of topical treatment with the drug in the form of eye drops due to other concentrations and physico-chemical conditions that may affect the overall activity of the drug at the site of action.

According to EUCAST (European Committee for the Determination of Antibiotic Sensitivity), the following MIC boundary values are defined for azithromycin::

Haemophilus influenzaeS ≤ 0.12 mg/l and R >4 mg/litre Moraxella catarrhalisS ≤ 0.5 mg/l and R>0.5 mg/litre Neisseria gonorrhoeaeS ≤ 0.25 mg/l and R>0.5 mg/litre Staphylococcus spp. S ≤ 1.0 mg/l and R>2.0 mg/litre Streptococcus pneumoniaeS ≤ 0.25 mg/l and R>0.5 mg/litre Streptococcus A, B, C, GS ≤ 0.25 mg/l and R>0.5 mg/l

EUCAST allows the use of erythromycin to determine the sensitivity of other species of these bacteria to azithromycin.

The frequency of acquired resistance for individual species may vary depending on the geographical region and time. In this regard, it is desirable to have local information about resistance, especially in the treatment of severe infections. If necessary, consult a specialist when the local frequency of resistance is such that the effectiveness of the drug, at least in some types of infection, is questionable.

Data from clinical trials

• Trachomatous conjunctivitis caused by Chlamydia trachomatis

A randomized, double-blind,2-month comparative study of Azidrope with a single oral dose of azithromycin for the treatment of active trachoma was conducted in 670 children aged 1-10 years. The main variable efficacy was clinical cure at day 60, i. e. absence of active TF0 trachoma (according to the simplified classification of trachoma severity by WHO). On day 60, the frequency of clinical treatment with Azidrope, applied 1 drop 2 times / day for 3 days, was not lower (96.3%) than with oral azithromycin (96.6%).

The clinical efficacy of Azidrope, administered 1 drop twice daily for 3 days, for the treatment and prevention of trachoma of the entire population (from birth) in Northern Cameroon (112,000 subjects) was evaluated in a multicenter, open-label, non-comparative phase IV study. Treatment was carried out in 3 periods of 1 year duration. The primary efficacy criterion was the predominance of active trachoma, i. e. trachomatous follicular inflammation or severe trachomatous inflammation (TF+TI0 or TF+TI+). For the analysis, a clinical assessment of trachoma was performed each year in 2,400 children aged ≥1 and older. The prevalence of active trachoma (TF+TI0 or TF+TI+) was observed in 31.1% of cases before Azidrope instillation in “year 0” and decreased to 6.3% (1 year),3.1% (2 years) and 3.1% (3 years). In general, no serious adverse reactions to the study drug were observed in the population.

• Purulent bacterial conjunctivitis

A randomized, blind, comparative study of Azidrope, administered 1 drop 2 times/day for 3 days, with tobramycin (eye drops,0.3%), administered 1 drop every 2 hours for 2 days, and then 4 times/day for 5 days, for the treatment of purulent bacterial conjunctivitis in 1043 patients (ITT group), including 109 children under the age of 11 years,5 of whom were newborns (0 to 27 days),38 children and toddlers (from 28 days to 23 months). According to the protocol, the population (n=471) (PP group) included 16 children and toddlers and did not include newborns. The clinical trial was conducted in different regions of Europe, North Africa, and India. The main variable efficacy was clinical cure on day 9 in the PP group and was defined as 0 points for bulbar conjunctiva injection and for purulent discharge. On day 9, the rate of clinical cure with Azidrope (87.8%) was not lower than with tobramycin (89.4%). The microbiological efficacy of azithromycin was comparable to that of tobramycin.

• Children’s population

The efficacy and safety of Azidrope in children and adolescents under 18 years of age were shown in a randomized trial with researcher masking in comparison with tobramycin in 282 study patients diagnosed with purulent bacterial conjunctivitis (including 148 patients in the 0-day subgroup – Patients received either Azidrope (1 drop 2 times a day for 3 days) or tobramycin, eye drops,0.3% (1 drop every 2 hours for 2 days, and then 4 times a day for 5 days). The main criterion for efficacy was the clinical cure of the more affected eye on day 3 in patients with positive bacteriological analysis results on day 0. In patients who used Azidrope, the clinical cure of the more affected eye on day 3 exceeded this indicator (47%) compared to patients who used tobramycin(28%). On day 7,89% of patients treated with Azidrope were completely cured, while among patients treated with tobramycin, complete recovery was observed in 78% of cases.

There were no statistical differences between the treated groups in terms of bacteriological clearance on day 7. Azidrope, applied 1 drop 2 times / day for 3 days, was well tolerated in all age groups in the study of a large group of children.

Adverse reactions reported in children were also detected in adults; no new adverse reactions were detected in children. Moreover, no age-related clinical problems were noted. The short duration of azithromycin therapy (1.5% eye drops), the small number of instillations required, and the ease of instillation of drops in children were taken into account by both children and parents.

Pharmacokinetics

 After instillation of Azidrope eye drops in the treatment of bacterial conjunctivitis at the recommended dose, azithromycin is not detected in the blood of patients (detection limit: 0.0002 mcg / ml).

Pharmacokinetic studies were conducted only in adults

Indications

Treatment of conjunctivitis caused by drug-sensitive pathogens, including Chlamydia trachomatis, in adults and children over 1 year of age.

Use during pregnancy and lactation

 Since the systemic exposure of azithromycin is insignificant, no negative effect of the drug is expected during pregnancy. The use of Azidrope, eye drops, in pregnant women is possible.

There is limited evidence that azithromycin is excreted in breast milk, but given the low doses and low systemic availability, the dose ingested in newborns is extremely low. Thus, the use of the drug Azidrope during breastfeeding is acceptable.

Animal studies have not confirmed the effect of azithromycin on male and female fertility. There are no results of human studies. Since the systemic effects of azithromycin on the body are insignificant, no effect of the drug on fertility is expected.

Contraindications

Individual hypersensitivity to azithromycin and other macrolide antibiotics, as well as components of the drug Azidrope; age less than 1 year.

Side effects

 Adverse reactions that were observed in clinical studies and post-marketing studies

From the immune system:infrequently (≥ 1/1000,

From the side of the visual organ:very often (≥ 1/10) – eye discomfort (itching, burning, tingling) after instillation of the drug; often (≥1/100,

Adverse reactions that were observed in post-marketing studies

The inclusion of these adverse reactions is based on post-marketing data.The frequency is determined based on 3/X, where X is the total sample size summed for all relevant clinical trials, which at 3/879 gives the category “infrequent”.

From the immune system:infrequently (≥1/1000,

From the side of the visual organ:infrequently (≥1/1000,

The profile of adverse reactions in children corresponds to the adult population, and no side effects were detected. The safety profile for different paediatric groups was also identical.

Interaction

Studies of the interaction of Azidrope with all specific drugs have not been conducted.

Due to the lack of detectable plasma concentrations of azithromycin when Azidrope eye drops are instilled (see section Pharmacokinetics), no interaction is expected with any of the drugs that have interacted with azithromycin when administered orally.

How to take, course of administration and dosage

 Adults are instilled 1 drop into the conjunctival sac of the affected eye 2 times / day (morning and evening) for 3 days.

If there is no positive dynamics within 3 days of using the drug, you should consult your doctor and review the treatment regimen and diagnosis.

Elderly patients do not need to adjust the dose.

No dose adjustment is required in children.

Method of application

Eye drops are instilled into the conjunctival sac of the affected eye.

Patients should follow the following guidelines::

• wash your hands thoroughly before instillation of the drug and after the procedure;
• do not touch the eye and eyelid with the tip of the dropper bottle;
• after a single use, the bottle should be discarded along with the remaining residue.

Do not use the remaining solution in the bottle for the next instillation.

Overdose

There is no information about overdose cases.

In a single-use package, azithromycin is contained in an amount sufficient to treat both eyes, but not enough to cause adverse reactions after accidental intravenous administration or oral administration of the solution.

Special instructions

 The drug should not be administered as an injection or swallowed, nor should it be administered as peri – and intraocular injections.

If an allergic reaction to the drug develops, treatment should be discontinued.

With simultaneous treatment with other ophthalmic drugs, Azidrope should be instilled last,15 minutes after instillation of another drug.

The patient should be informed that eye drops should not be instilled after the end of therapy on day 3, even if residual signs of bacterial conjunctivitis persist.

Patients suffering from bacterial conjunctivitis should not use contact lenses.

Cases of fulminant hepatitis, which can potentially lead to life-threatening liver failure, have been reported with systemic use of azithromycin. When using the drug in ophthalmology, such a risk does not exist, since the systemic effect of the Active ingredient is extremely insignificant.

Use in pediatrics

Comparative studies of the efficacy and safety of the drug in trachomatous conjunctivitis in children under 1 year of age have not been conducted. However, taking into account the experience of clinical use in children of this age group with trachomatous conjunctivitis and taking into account the experience of treatment with Azidrope in newborns with purulent bacterial conjunctivitis, there are no concerns about safety and differences in the pathological process that allow us to exclude the use of Azidrope eye drops in children under the age of 1 year for this indication for use.

According to the existing international guidelines for the treatment of diseases of the eyes and genitourinary tract that can be transmitted with a high probability to newborns, systemic therapy is necessary for conjunctivitis of non-trachomatous origin caused by Chlamydia trachomatis and conjunctivitis caused by Neisseria gonorrhoeae.

In newborns and children under 3 months of age, systemic infections (such as pneumonia and bacteremia) caused by Chlamydia trachomatis may be accompanied by conjunctivitis. If such conditions are suspected, systemic therapy is necessary.

The drug is not intended for the prevention of bacterial conjunctivitis in newborns.

Influence on the ability to drive motor vehicles and manage mechanisms

The effect on the ability to drive vehicles and mechanisms has not been studied.

After applying eye drops, temporary blurring of vision may occur. Patients who experience temporary blurred vision after applying eye drops are not recommended to drive vehicles or work with mechanisms until vision is restored.

Form of production

Eye drops.

Storage conditions

Store at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf life

18 months

Active ingredient

Azithromycin

Conditions of release from pharmacies

By prescription

Dosage form

eye drops

Purpose

Children as prescribed by a doctor, Pregnant women as prescribed by a doctor, Adults as prescribed by a doctor, Nursing mothers as prescribed by a doctor

Indications

Eye Infections, Conjunctivitis

Weight

Weight: 24 gr.