Xalatan Eye 1 mL Solution

u2022 Reduction of elevated intraocular pressure in patients with open angle glaucoma, chronic angle closure glaucoma and ocular hypertension.

u2022 In children less than 3 years of age, XALATAN can be initiated prior to other corrective procedures and may be continued if therapeutic response is adequate.

Posology

Use in adults (including the elderly)

One drop in the affected eye(s) once daily. Optimal effect is obtained if XALATAN is administered in the evening. The dosage of XALATAN should not exceed once daily since it has been shown that more frequent administration decreases the intra-ocular pressure lowering effect.

If one dose is missed, treatment should continue with the next dose as normal. Reduction of the intraocular pressure starts about three to four hours after administration and maximum effect is reached after 8 to 12 hours. Pressure reduction is maintained for at least 24 hours. XALATAN may be used concomitantly with other classes of topical ophthalmic medicines to lower intraocular pressure. If more than one topical ophthalmic medicine is being used, the medicines should be used at least five minutes apart. Contact lenses should be removed before instillation of the eye drops and may be reinserted after fifteen minutes.

Paediatric population

XALATAN eye drops may be used in paediatric patients at the same posology as in adults. No data are available for preterm infants (less than 36 weeks gestational age). Data in the age group < 1 year (4 patients) are limited (see section 5.1).

Method of administration

For ophthalmic use.

u2022 Known hypersensitivity to latanoprost, benzalkonium chloride or to any of the excipients of XALATAN (listed in section 6.1).

u2022 Pregnancy and lactation (see section 4.6).

XALATAN may gradually increase the brown pigment of the iris. The eye colour change is due to increased melanin content in the stromal melanocytes of the iris, rather than to an increase in number of melanocytes. Typically, brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. The change in iris colour is mild in the majority of cases and may not be detected clinically. The increase in iris pigmentation in one or both eyes has been documented predominantly in patients who have mixed coloured irides that contain the colour brown at baseline. Neither naevi nor freckles of the iris have been affected by treatment. No accumulation of pigment in the trabecular meshwork or elsewhere in the anterior chamber has been observed in clinical trials. In a clinical trial designed to assess iris pigmentation over five years, there was no evidence of adverse consequences due to increased pigmentation even when administration of XALATAN continued. Intraocular pressure (IOP) reduction was similar in patients regardless of the development of increased iris pigmentation. Therefore, treatment with XALATAN can be continued in patients who develop increased iris pigmentation. These patients should be examined regularly and, depending on the clinical situation, treatment may be stopped. Onset of increased iris pigmentation occurs within the first year of treatment, rarely during the second or third year, and has not been seen after the fourth year of treatment. The rate of progression of iris pigmentation decreases with time and is stable by five years. The effects of increased pigmentation beyond five years have not been evaluated. During clinical trials, the increase in brown iris pigment has not been shown to progress further upon discontinuation of treatment, but the resultant colour change may be permanent. Eyelid skin darkening, which may be reversible, has been reported in association with the use of XALATAN. XALATAN may gradually change eyelashes and vellus hair in the treated eye; these changes include increased length, thickness, pigmentation, and number of lashes or hairs and misdirected growth of eyelashes. Eyelash changes are reversible upon discontinuation of treatment. The potential for heterochromia exists for patients receiving unilateral treatment. Macular oedema, including cystoid macular oedema, has been reported during treatment with XALATAN. These reports have mainly occurred in aphakic patients, in pseudophakic patients with torn posterior lens capsule, or in patients with known risk factors for macular oedema. Caution is recommended when using XALATAN in these patients. There is limited experience with XALATAN in the treatment of inflammatory neovascular, angle closure congenital or pigmentary glaucoma and also in pseudophakic patients with open angle glaucoma. Therefore, it is recommended that XALATAN should be used with caution in these conditions until more experience is obtained. XALATAN has no or little effect on the pupil but there is no experience in acute attacks of closed angle glaucoma. Therefore, it is recommended that XALATAN should be used with caution in these conditions until more experience is obtained. XALATAN is hydrolysed in the cornea. The effect of continued administration of XALATAN in the corneal epithelium has not been fully evaluated. There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. XALATAN should be used with caution in patients with a history of herpetic keratitis and should be avoided in cases of active herpes simplex keratitis and in patients with a history of recurrent herpetic keratitis specifically associated with prostaglandin analogues. Patients must not let the tip of the dispensing container contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. XALATAN has not been studied in patients with renal or hepatic impairment and should therefore be used with caution in such patients. Asthma There is limited experience in patients with asthma, but cases of asthma, asthma aggravation, acute asthma attack, coughing and dyspnoea have been reported. Benzalkonium chloride XALATAN contains benzalkonium chloride, which may be absorbed by contact lenses. Benzalkonium chloride has been reported to cause eye irritation, symptoms of dry eyes and may affect the tear film and corneal surface. XALATAN should be used with caution in dry eye patients and in patients where the cornea may be compromised. Patients should be monitored in case of prolonged use. As the possibility of adverse effects on the corneal permeability and the danger of disruption of the corneal epithelium with prolonged or repeated usage of benzalkonium chloride-preserved ophthalmological preparations cannot be excluded, regular ophthalmological examination is required. Caution should be exercised in the use of benzalkonium chloride-preserved topical medicine over an extended period in patients with extensive ocular surface disease. Paediatric population Efficacy and safety data in the age group < 1 year (4 patients) are very limited (see section 5.1). No data are available for preterm infants (less than 36 weeks gestational age). In children from 0 to < 3 years old that mainly suffer from PCG (Primary Congenital Glaucoma), surgery (e.g. trabeculotomy/goniotomy) remains the first line treatment, as these children, prior to surgery for congenital glaucoma, respond poorly to XALATAN treatment. Long-term safety in children has not yet been established.

XALATAN is effective as monotherapy. The intraocular pressure-reducing effect of XALATAN has been shown to be additive to that of beta-adrenergic antagonists (timolol). In short-term studies (up to 2 weeks) the effect of XALATAN was additive in combination with adrenergic agonists (dipivefrin), and oral carbonic anhydrase inhibitors (acetazolamide) and at least partly additive with cholinergic agonists (pilocarpine). In case of combined therapy, eye drops should be administered with an interval of at least five minutes. There have been reports of paradoxical elevations in IOP following the concomitant ophthalmic administration of two prostaglandin analogues. Therefore, the use of two or more prostaglandins, prostaglandin analogues, or prostaglandin derivatives is not recommended.

Pregnancy

The use of XALATAN in pregnancy is contraindicated. XALATAN has potential hazardous pharmacological effects with respect to the course of pregnancy, to the unborn or the neonate, and should therefore not be used in pregnancy (see section 4.3).

Breastfeeding

The safety in lactation has not been established. Mothers treated with XALATAN should not breastfeed their infants (see section 4.3).

Instillation of eye drops may cause transient blurring of vision. Until this has resolved, patients should not drive or use machines.

Summary of the safety profile

Most undesirable effects observed relate to the ocular system. XALATAN has caused increased pigmentation of the iris (see section 4.4). Macular oedema including cystoid macular oedema has been reported during XALATAN treatment, mainly in patients with aphakia and pseudophakia with torn posterior lens capsule or anterior chamber lenses.

Systemic events

The most common systemic adverse events seen with XALATAN were:

• Upper respiratory tract infections.
• Colds and flu.
• Pain in muscles, joints, back pain.
• Chest pain and angina pectoris has also been reported.

Tabulated summary of adverse reactions

The tables below contain side effects categorised as follows utilising the incidence rates: Very common ( u2265 1/10); common ( u2265 1/100 to < 1/10); uncommon ( u2265 1/1 000 to < 1/100); rare ( u2265 1/10 000 to < 1/1 000); very rare ( < 1/10 000).

Clinical trials

MedDRA system organ class Frequency Side effects

Eye disorders Very common Iris hyperpigmentation, eye irritation (burning, grittiness, itching, stinging and foreign body sensation)

Common Blepharitis, eye pain, eyelid oedema, mild to moderate conjunctival hyperaemia, punctate keratitis mostly without symptoms

Cardiac disorders Uncommon Angina

Skin and subcutaneous tissue disorders Common Rash

Rare Pruritus

Post-marketing surveillance

MedDRA system organ class Side effects

Infections and infestations Herpetic keratitis

Nervous system disorders Dizziness, headache

Eye disorders Eyelash and vellus hair changes of the eyelid (increased length, thickness, pigmentation, and number of eye lashes), conjunctivitis, blurred vision, iritis, uveitis, keratitis, macular oedema including cystoid macular oedema, corneal oedema, corneal erosion, trichiasis, periorbital oedema, photophobia, periorbital and lid changes resulting in deepening of the eyelid sulcus, localised skin reaction on eyelids, darkening of palpebral skin of the eyelids, iris cyst, pseudopemphigoid of ocular conjunctiva

Cardiac disorders Palpitations, unstable angina

Respiratory, thoracic and mediastinal disorders Asthma, dyspnoea, asthma aggravation, acute asthma attacks

Gastrointestinal disorders Nausea, vomiting

Musculoskeletal and connective tissue disorders Myalgia, arthralgia

General disorders and administration site conditions Chest pain

Cases of corneal calcification have been reported very rarely in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas.

Paediatric population

In two short-term clinical trials (u2264 12 weeks) involving 93 (25 and 68) paediatric patients, the safety profile was similar to that in adults and no new adverse events were identified. The short-term safety profiles in the different paediatric subsets were also similar (see section 5.1). Adverse events seen more frequently in the paediatric population as compared to adults are nasopharyngitis and pyrexia.

In overdose, side effects will be exacerbated and exaggerated (see section 4.8). Apart from ocular irritation and conjunctival hyperaemia, no other ocular side effects are known if XALATAN is overdosed. Intravenous infusion of 5,5 u2013 10 u03bcg/kg in healthy volunteers caused nausea, abdominal pain, dizziness, fatigue, hot flushes and sweating. If overdosage with XALATAN occurs, treatment should be symptomatic and supportive.