4.1. Therapeutic indications

AZYTER 15 mg/g, eye drops, solution in single-dose container is indicated for the local antibacterial curative treatment of conjunctivitis caused by susceptible strains (see sections 4.4 and 5.1):

- Purulent bacterial conjunctivitis in children (aged from birth to 17 years) and adults

- Trachomatous conjunctivitis caused by Chlamydia trachomatis in children (aged from birth to 17 years) and adults (see section 4.4 “Use in neonates”).

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2. Posology and method of administration

Posology

Adult population

Instil one drop in the conjunctival fornix twice a day, morning and evening, during three days.

It is unnecessary to prolong treatment beyond three days.

Adherence to the dosing regimen is important for the success of treatment.

Elderly patients

No dose adjustment is necessary.

Paediatric population

No dose adjustment is necessary (see section 4.4 and 5.1).

Method of administration

Ocular use.

The patient should be advised to:

- thoroughly wash hands before and after the instillation,

- avoid touching the eye or eyelids with the dropper tip of the single-dose container,

- discard the single-dose container after use, and not keep it for subsequent use.

4.3. Contraindications

Hypersensitivity to azithromycin, to any other macrolide or to the excipient listed in section 6.1.

4.4. Special warnings and precautions for use

The eye drops solution should not be injected or be swallowed.

The eye drops solution should not be used for peri- or intra-ocular injection.

In the event of an allergic reaction, the treatment should be discontinued.

The patient should be informed that it is not necessary to continue to instil the eye drops solution after the end of treatment on the third day, even if residual signs of bacterial conjunctivitis remain.

Symptomatic relief occurs generally within 3 days. If there are no signs of improvement after 3 days, diagnosis should be reconsidered.

Contact lenses should not be worn by patients with bacterial conjunctivitis.

With the systemic use of azithromycin cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported. In ophthalmic use, this risk is not relevant since systemic exposure to the active ingredient is negligible (see section 5.2).

Hypersensitivity

As with erythromycin and other macrolides, rare serious allergic reactions, including angioneurotic oedema and anaphylaxis (rarely fatal), dermatologic reactions including acute generalised exanthematous pustulosis (AGEP), Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (rarely fatal) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required a longer period of observation and treatment.

If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted. Physicians should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Paediatric population

Regarding the treatment of trachomatous conjunctivitis, comparative safety and efficacy studies have not been performed with Azyter 15 mg/g eye drops in children younger than one year, but there are no known safety concerns or differences in disease process to exclude its use in children less than one year old in this indication taking into account clinical experience in children older than one year of age in the treatment of trachomatous conjunctivitis and considering Azyter experience in children from birth in the treatment of purulent bacterial conjunctivitis.

Use in neonates

Based on the international consensus on diseases involving the eye and genital tract and susceptible to be transmitted to new-borns, non-trachomatous conjunctivitis caused by Chlamydia trachomatis and conjunctivitis caused by Neisseria gonorrhoeae require a systemic treatment.

In neonates and infants below the age of 3 months systemic infection (eg pneumonia, bacteremia) due to Chlamydia trachomatis may accompany conjunctivitis. In case of suspicion, systemic treatment is required.

This treatment is not intended to be used as prophylactic treatment of bacterial conjunctivitis in newborn infants.

4.5. Interaction with other medicinal products and other forms of interaction

No specific interaction study has been performed with Azyter.

In view of the absence of detectable concentrations of azithromycin in the plasma during the administration of Azyter by ocular instillation (see section 5.2), none of the interactions with other medicinal products described for orally administered azithromycin is expected with use of the eye drops solution.

In the event of concomitant treatment with another eye drops solution, an interval of 15 minutes should be respected between instillation of the two solutions. Azyter should be instilled last.

4.6. Fertility, pregnancy and lactation

Pregnancy

No effect on pregnancy is anticipated, since systemic exposure to azithromycin is negligible. AZYTER can be used during pregnancy.

Breastfeeding

Limited data indicate that azithromycin is excreted in breast milk, but, considering the low dose and the low systemic availability, the doses taken by the new-born are negligible. Consequently, breast feeding is possible during the treatment.

Fertility

Animal data do not suggest an effect of the treatment of azithromycin on male and female fertility. Human data are lacking. However, no effect on fertility is anticipated, since systemic exposure to azithromycin is negligible.

4.7. Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

Vision may be transiently blurred after instillation. In this case, the patient should be advised to avoid driving or using machines until normal vision has been re- established.

4.8. Undesirable effects

During clinical trials and according to post-marketing safety data on Azyter eye drops solution, the following treatment-related signs and symptoms were reported:

Immune system disorders

Uncommon (≥1/1000, <1/100)

Angioedema*, hypersensitivity.

Eye disorders

Very common (≥1/10)

Ocular discomfort (pruritus, burning, stinging) upon instillation.

Common (≥1/100, <1/10)

Blurred vision, sticky eye sensation, foreign body sensation upon instillation.

Uncommon (≥1/1000, <1/100)

Conjunctivitis*, allergic conjunctivitis*, keratitis*, eczema eyelids*, eyelid oedema*, eye allergy*, conjunctival hyperemia, lacrimation increased upon instillation, erythema of the eyelid.

Skin and subcutaneous tissue disorders

Not known (cannot be estimated from the available data)

Toxic epidermal necrolysis#, drug reaction with eosinophilia and systemic symptoms#, Stevens-Johnson syndrome#, dermatitis exfoliative#, acute generalised exanthematous pustulosis (AGEP)#

* adverse event has not been observed during clinical studies with Azyter. Inclusion of adverse event is based on post-marketing data. The frequency has been assigned based on 3/X, with X representing the total sample size summed up across all relevant clinical trials and studies, which is 3/879 resulting in “uncommon”.

# by extrapolation of systemic exposure

Paediatric population

In paediatric clinical trials, the safety profile was similar to that in adults and no new adverse events were identified. The safety profiles in the different paediatric subsets were also similar (see Section 5.1).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

4.9. Overdose

The total amount of azithromycin in a single-dose container, containing a sufficient quantity for treating both eyes, is too small to induce adverse effects after inadvertent intravenous or oral administration.