Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2022 Publisher: Upjohn UK Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, United Kingdom
Hypersensitivity to latanoprost or to any of the excipients listed in section 6.1.
Xalatan may gradually change eye colour by increasing the amount of brown pigment in the iris. Before treatment is instituted, patients should be informed of the possibility of a permanent change in eye colour. Unilateral treatment can result in permanent heterochromia.
This change in eye colour has predominantly been seen in patients with mixed coloured irides, i.e. blue-brown, grey-brown, yellow-brown and green-brown. In studies with latanoprost, the onset of the change is usually within the first 8 months 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 for five years. The effect of increased pigmentation beyond five years has not been evaluated. In an open 5-year latanoprost safety study, 33% of patients developed iris pigmentation (see section 4.8). The iris colour change is slight in the majority of cases and often not observed clinically. The incidence in patients with mixed colour irides ranged from 7 to 85%, with yellow-brown irides having the highest incidence. In patients with homogeneously blue eyes, no change has been observed and in patients with homogeneously grey, green or brown eyes, the change has only rarely been seen.
The colour change is due to increased melanin content in the stromal melanocytes of the iris and not to an increase in number of melanocytes. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery in affected eyes, but the entire iris or parts of it may become more brownish. No further increase in brown iris pigment has been observed after discontinuation of treatment. It has not been associated with any symptom or pathological changes in clinical trials to date.
Neither naevi nor freckles of the iris have been affected by treatment. Accumulation of pigment in the trabecular meshwork or elsewhere in the anterior chamber has not been observed in clinical trials. Based on 5 years clinical experience, increased iris pigmentation has not been shown to have any negative clinical sequelae and Xalatan can be continued if iris pigmentation ensues. However, patients should be monitored regularly and if the clinical situation warrants, Xalatan treatment may be discontinued.
There is limited experience of Xalatan in chronic angle closure glaucoma, open angle glaucoma of pseudophakic patients and in pigmentary glaucoma. There is no experience of Xalatan in inflammatory and neovascular glaucoma or inflammatory ocular conditions. 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.
There are limited study data on the use of Xalatan during the peri-operative period of cataract surgery. Xalatan should be used with caution in these patients.
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.
Reports of macular oedema have occurred (see section 4.8) mainly in aphakic patients, in pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for cystoid macular oedema (such as diabetic retinopathy and retinal vein occlusion). Xalatan should be used with caution in aphakic patients, in pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for cystoid macular oedema.
In patients with known predisposing risk factors for iritis/uveitis, Xalatan can be used with caution.
There is limited experience from patients with asthma, but some cases of exacerbation of asthma and/or dyspnoea were reported in post marketing experience. Asthmatic patients should therefore be treated with caution until there is sufficient experience, see also section 4.8.
Periorbital skin discolouration has been observed, the majority of reports being in Japanese patients. Experience to date shows that periorbital skin discolouration is not permanent and in some cases has reversed while continuing treatment with Xalatan.
Latanoprost may gradually change eyelashes and vellus hair in the treated eye and surrounding areas; these changes include increased length, thickness, pigmentation, number of lashes or hairs and misdirected growth of eyelashes. Eyelash changes are reversible upon discontinuation of treatment.
Xalatan contains benzalkonium chloride, which is commonly used as a preservative in ophthalmic products. From the limited data available, there is no difference in the adverse event profile in children compared to adults. Generally, however, eyes in children show a stronger reaction for a given stimulus than the adult eye. Irritation may have an effect on treatment adherence in children. Benzalkonium chloride has been reported to cause eye irritation, symptoms of dry eyes and may affect the tear film and corneal surface. 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.
Contact lenses may absorb benzalkonium chloride and these should be removed before applying Xalatan but may be reinserted after 15 minutes (see section 4.2).
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 primary congenital glaucoma (PCG), surgery (e.g. trabeculotomy/goniotomy) remains the first line treatment.
Long-term safety in children has not yet been established.
Definitive drug interaction data are not available.
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.
Interaction studies have only been performed in adults.
The safety of this medicinal product for use in human pregnancy has not been established. It has potential hazardous pharmacological effects with respect to the course of pregnancy, to the unborn or the neonate. Therefore, Xalatan should not be used during pregnancy.
Latanoprost and its metabolites may pass into breast milk and Xalatan should therefore not be used in breast-feeding women or breast feeding should be stopped.
Latanoprost has not been found to have any effect on male or female fertility in animal studies (see section 5.3).
Xalatan has minor influence on the ability to drive and use machines. In common with other eye preparations, instillation of eye drops may cause transient blurring of vision. Until this has resolved, patients should not drive or use machines.
The majority of adverse reactions relate to the ocular system. In an open 5-year latanoprost safety study, 33% of patients developed iris pigmentation (see section 4.4). Other ocular adverse reactions are generally transient and occur on dose administration.
Adverse reactions are categorized by frequency as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000), not known (frequency cannot be estimated from the available data).
Rare: Herpetic keratitis*§
Uncommon: Headache*; dizziness*
Very Common: Iris hyperpigmentation; mild to moderate conjunctival hyperaemia; eye irritation (burning grittiness, itching, stinging and foreign body sensation); eyelash and vellus hair changes of the eyelid (increased length, thickness, pigmentation and number of eyelashes)
Common: Punctate keratitis, mostly without symptoms; blepharitis; eye pain; photophobia; conjunctivitis*
Uncommon: Eyelid oedema; dry eye; keratitis*; vision blurred; macular oedema including cystoid macular oedema*; uveitis*
Rare: Iritis*; corneal oedema*; corneal erosion; periorbital oedema; trichiasis*; distichiasis; iris cyst*§; localised skin reaction on the eyelids; darkening of the palpebral skin of the eyelids; pseudopemphigoid of ocular conjunctiva*§
Very Rare: Periorbital and lid changes resulting in deepening of the eyelid sulcus
Uncommon: Angina; palpitations*
Very Rare: Angina unstable
Uncommon: Asthma*; dyspnoea*
Rare: Asthma exacerbation
Uncommon: Rash
Rare: Pruritus
Uncommon: Myalgia*; arthralgia*
Uncommon: Chest pain*
* ADR identified post-marketing
§ ADR frequency estimated using "The Rule of 3"
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.
No information is provided.
In two short term clinical trials (≤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.
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 at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
In vitro studies have shown that precipitation occurs when eye drops containing thiomersal are mixed with Xalatan. If such medicinal products are used, the eye drops should be administered with an interval of at least five minutes.
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