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

An antimicrobial drug for topical use. Azithromycin is a second generation macrolide antibiotic of azalide group. It inhibits protein synthesis in bacteria by binding to 50S-subunit of ribosomes and prevents translocation of peptides.

The mechanism of resistance

There are three mechanisms of resistance for different types of bacteria to macrolides: due to modification of the target of action, modification of the antibiotic or due to active release of the antibiotic from the microbial cell by means of transport systems (efflux). Different efflux systems have been described for bacteria. An important efflux system for Streptococci is encoded by the mef gene and leads to macrolide-limited resistance (M-phenotype). Modification of the target of action controlled by erm encoded methylase (MLSB-phenotype) leads to cross-resistance to different classes of antibiotics.

Cases of cross-resistance to erythromycin, azithromycin, other macrolides and lincosamide and streptogramine B have been described for Streptococcus pneumoniae, β-haemolytic group A 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 10-7COU in the presence of azithromycin.

Borderline value

The following are the minimum inhibitory concentrations (MICs) for microorganisms for these indications.

It should be noted that the borderline MIC values and spectrum of action presented below are for systemic use. These MICs cannot be used for topical treatment with the drug in the form of eye drops due to different concentrations and physicochemical conditions that may affect the overall activity of the drug at the site of action.

According to EUCAST (European Committee on Antibiotic Susceptibility Testing), the following MIC limit values are defined for azithromycin:

Haemophilus influenzaeS ≤ 0.12mg/L and R >4 mg/LMogachella catarrhalisS ≤ 0.5 mg/L and R>0.5 mg/LNeisseria gonorrhoeaeS ≤ 0.25 mg/L and R>0.5 mg/LStarhooloccus spp.S ≤ 1.0 mg/L and R>2.0 mg/LSthealthoccus pneumoniaeS ≤ 0.25 mg/L and R>0.5 mg/LSthealthoccus 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 specified bacterial species to azithromycin.

The incidence of acquired resistance for individual species may vary depending on the geographic region and over time. Therefore, it is advisable to have local information about resistance, especially when treating severe infections. Specialist advice should be sought, if necessary, when the local incidence of resistance is such that the efficacy of the drug, at least for some types of infection, is questionable.

Clinical trial data

• Thoracomatous conjunctivitis caused by Chlamydia trachomatis

. A randomized, double-blind, 2-month comparison study of Azidrop with oral administration of a single dose of azithromycin was conducted to treat active trachoma in 670 children aged 1-10 years. The primary efficacy variable was clinical cure at day 60, i.e., no active trachoma TF0 (according to the simplified WHO trachoma severity classification). At day 60, the rate of clinical cure with Azidrop, administered 1 drop 2 times daily for 3 days, was no lower (96.3%) than with oral azithromycin (96.6%).

The clinical efficacy of Azidrop, administered 1 drop 2 times daily for 3 days, for the treatment and prevention of trachoma in the entire population (from birth) in Northern Cameroon (112,000 subjects) was evaluated in a multicenter, open-label, noncomparative phase IV study. Treatment was administered in 3 periods of 1 year duration. The primary efficacy criterion was the prevalence of active trachoma, i.e., trachomatous follicular inflammation or marked trachomatous inflammation (TF+TI0 or TF+TI+). For the analysis, a clinical evaluation of trachoma was performed each year in 2,400 children aged ≥1 and < 10 years, selected by random cluster sampling. The prevalence of active trachoma (TF+TI0 or TF+TI+) was observed in 31.1% before instillation of Azidrop at “year 0” and decreased to 6.3% (year 1), 3.1% (year 2), and 3.1% (year 3). Overall, no serious adverse reactions to the study drug were observed in the population.

• Purulent bacterial conjunctivitis

A randomized, blinded comparative study of Azidrop, used 1 drop twice daily for 3 days, with tobramycin (eye drops, 0.3%), applied 1 drop every 2 h for 2 days and then 4 times/day for 5 days, to treat purulent bacterial conjunctivitis in 1,043 patients (ITT group), including 109 children under 11 years of age, 5 of whom were newborns (0 to 27 days), 38 infants, and toddlers (28 days to 23 months). According to the protocol, the population (n=471) (RR group), included 16 infants and toddlers and did not include newborns. The clinical trial was conducted in different regions of Europe, North Africa, and India. The primary efficacy variable represented clinical cure at day 9 in the RR group and was defined as 0 points for bulbar conjunctival injection and for purulent discharge. At day 9, the rate of clinical cure with azidrop (87.8%) was no 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 Azidrop in children and adolescents under 18 years of age were demonstrated in a randomized, investigator-masked study comparing tobramycin in 282 study patients diagnosed with purulent bacterial conjunctivitis (including 148 patients in the 0-day-< 24-month subgroup). Patients received either Azidrop (1 drop 2 times daily for 3 days) or tobramycin, eye drops, 0.3% (1 drop every 2 h for 2 days and then 4 times/day for 5 days). The main criterion for efficacy was clinical cure of the more affected eye on day 3 in patients with positive bacteriologic test results on day 0. In patients using Azidrop, clinical cure of the more affected eye on day 3 was superior (47%) to that in patients using tobramycin(28%). At day 7, 89% of patients treated with Azidrop were completely cured, whereas among patients treated with tobramycin, there was a complete cure in 78% of cases.

There were no statistical differences between the treated groups with respect to bacteriological resolution at day 7. Azidrop, administered 1 drop 2 times daily for 3 days, was well tolerated in all age groups in a large group study of children.

The adverse reactions noted in children were also seen in adults; no new adverse reactions were noted in children. Moreover, no age-related clinical problems have been noted. The short duration of therapy with azithromycin (1.5% eye drops), the small number of instillations required, and the ease of instilling the drops in children have been accepted by both children and parents.

Pharmacokinetics

Azithromycin is not detectable in the blood of patients after instillation of Azidrop eye drops for the treatment of bacterial conjunctivitis at the recommended dose (detection limit: 0.0002 µg/ml).

Pharmacokinetic studies have only been performed in adults

Indications

Treatment of conjunctivitis caused by pathogens sensitive to the drug, including Chlamydia trachomatis, in adults and children from 1 year old.

Active ingredient

Composition

1 g eye drops contains:

the active ingredient:

azithromycin dihydrate 15 mg, which corresponds to azithromycin 14.3 mg,

Auxiliary substances:

triglycerides medium-chain to 1 g.

How to take, the dosage

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

If there is no positive change within 3 days of using the drug, a physician should be consulted and the treatment regimen and diagnosis should be reviewed.

Patients in the elderly do not need dose adjustments.

Dose adjustment is not necessary in children.

How to use

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

Patients should follow these instructions:

The solution remaining in the bottle should not be used for the next instillation.

Interaction

There have been no studies of interaction of the drug Azidrop with all specific drugs.

As there are no detectable concentrations of azithromycin in blood plasma when Azidrop eye drops are applied (see section Pharmacokinetics), no interaction is expected with any of the medicinal products that have interacted with azithromycin when administered orally.

Special Instructions

The drug should not be injected or swallowed and should not be administered as peri- and intraocular injections.

In case of an allergic reaction to the drug, treatment should be discontinued.

In case of concomitant treatment with other ophthalmic drugs, Azidrop should be injected last, 15 minutes after instillation of the other drug.

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

Patients with bacterial conjunctivitis should not use contact lenses.

In the background of systemic use of azithromycin, cases of lightning-induced hepatitis have been reported, which may potentially lead to life-threatening liver failure. This risk is not present with ophthalmic use because the systemic effects of the active ingredient are negligible.

Pediatric use

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

The current international guidelines for the treatment of eye and genitourinary tract diseases that are likely to be transmitted to the newborn require systemic therapy for conjunctivitis of non-rhomatous 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 these conditions are suspected, systemic therapy is necessary.

The drug is not intended to prevent bacterial conjunctivitis in infants.

The effect on the ability to drive and operate machinery

The effect on the ability to operate vehicles and machinery has not been studied.

Transient blurring of vision may occur after use of the eye drops. Patients with transient blurred vision after use of eye drops are not recommended to drive vehicles or operate machinery until vision is restored.

Contraindications

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

Side effects

Adverse reactions observed in clinical trials and post-registration studies

Immune system disorders:infrequent (≥1/1000,

Visual system disorders:very common (≥1/10) – ocular discomfort (itching, burning, tingling) after injecting the drug; common (≥1/100,

Adverse reactions observed in post-registration studies

The inclusion of adverse reactions listed is based on post-registration data. Frequency is determined based on 3/X, where X represents the total sample size summed over all relevant clinical trials, which at 3/879 gives the “infrequent” category.

Immune system disorders:infrequent (≥1/1000,

Eye disorders:infrequent (≥1/1000,

The profile of adverse reactions in children is consistent with the adult population, no adverse effects have been identified. The safety profile for different pediatric groups was also identical.

Overdose

There is no information on cases of overdose.

The single-use package contains enough azithromycin to treat both eyes, but not enough to cause adverse reactions after accidental intravenous administration or ingestion of the solution.

Pregnancy use

As the systemic exposure of azithromycin is insignificant, no adverse effects of the drug are expected in pregnancy. The use of the drug Azidrop, eye drops, in pregnant women is possible.

There are limited data that azithromycin is excreted with breast milk, but considering the low doses and low systemic availability the infant dose is very low. Therefore, the use of the drug Azidrop during breastfeeding is acceptable.

The data of animal studies have not confirmed the effect of azithromycin on fertility in men and women. There are no results of studies in humans. Because the systemic effect of azithromycin on the body is insignificant, the effect of the drug on fertility is not expected.

Similarities