4.1. Therapeutic indications

Reduction of elevated intraocular pressure in patients with open angle glaucoma and ocular hypertension.

4.2. Posology and method of administration

Posology

Recommended dosage for adults (including the elderly):

Recommended therapy is one eye drop in the affected eye(s) once daily. Optimal effect is obtained if MONOPOST is administered in the evening.

The dosage of MONOPOST should not exceed once daily since it has been shown that more frequent administration decreases the intraocular pressure lowering effect.

If one dose is missed, treatment should continue with the next dose as normal.

Paediatric population:

No data are available with MONOPOST formulation.

Method of administration

Ocular use.

As with any eye drops, to reduce possible systemic absorption, it is recommended that the lachrymal sac be compressed at the medial canthus (punctal occlusion) for one minute. This should be performed immediately following the instillation of each drop.

Contact lenses should be removed before instillation of the eye drops and may be reinserted after 15 minutes.

If more than one topical ophthalmic medicinal product is being used, the medicinal products should be administered at least five minutes apart.

A single-dose contains enough eye drops solution to treat both eyes.

For single use only.

This medicinal product is a sterile solution that does not contain a preservative. The solution from one individual single dose container is to be used immediately after opening for administration to the affected eye(s). Since sterility cannot be maintained after the individual single dose container is opened, any remaining contents must be discarded immediately after administration.

Patients should be instructed:

- to avoid contact between the dropper tip and the eye or eyelids,

- to use the eye drops solution immediately after first opening the single-dose container and to discard the single-dose after use.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

4.4. Special warnings and precautions for use

Latanoprost 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 latanoprost can be continued if iris pigmentation ensues. However, patients should be monitored regularly and if the clinical situation warrants, latanoprost treatment may be discontinued.

There is limited experience of latanoprost in chronic angle closure glaucoma, open angle glaucoma of pseudophakic patients and in pigmentary glaucoma. There is no experience of latanoprost in inflammatory and neovascular glaucoma, inflammatory ocular conditions, or congenital glaucoma. Latanoprost 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 latanoprost should be used with caution in these conditions until more experience is obtained.

There are limited study data on the use of latanoprost during the peri-operative period of cataract surgery. Latanoprost should be used with caution in these patients.

Latanoprost 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 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). Latanoprost 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, latanoprost 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 latanoprost.

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.

MONOPOST contains macrogolglycerol hydroxystearate (castor oil polyoxyl hydrogenated) which may cause skin reactions. No long-term safety data are currently available on this excipient.

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

Definitive drug interaction data are not available.

There have been reports of paradoxical elevations in intraocular pressure 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.

4.6. Fertility, pregnancy and lactation

Fertility

Latanoprost has not been found to have any effect on male or female fertility in animal studies (see section 5.3).

Pregnancy

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, MONOPOST should not be used during pregnancy.

Breastfeeding

Latanoprost and its metabolites may pass into breast milk and MONOPOST should therefore not be used in breast-feeding women or breast feeding should be stopped.

4.7. Effects on ability to drive and use machines

No studies on the effect of this medicinal product on the ability to drive have been conducted. 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.

4.8. Undesirable effects

a. Summary of the safety profile

The majority of adverse events relate to the ocular system. In an open 5-year latanoprost reference product safety study, 33% of patients developed iris pigmentation (see section 4.4). Other ocular adverse events are generally transient and occur on dose administration.

b. Tabulated list of adverse reactions

The adverse events and their frequencies listed herebelow are those described for the reference product. Adverse events are categorized by frequency as follows: very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥ 1/10,0000 to <1/1,000) and very rare (<1/10,000). Frequency not known (cannot be estimated from the available data).

System Organ Class

Very Common

≥1/10

Common

≥1/100 to <1/10

Uncommon

≥1/1,000 to <1/100

Rare

≥1/10,0000 to <1/1,000

Very Rare

<1/10,000

Infections and infestations

Herpetic keratitis*§

Nervous system disorders

Headache*; dizziness*

Eye disorders

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)

Punctate keratitis, mostly without symptoms; blepharitis; eye pain; photophobia; conjunctivitis*

Eyelid oedema; dry eye; keratitis*; vision blurred; macular oedema including cystoid macular oedema*; uveitis*

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

Periorbital and lid changes resulting in deepening of the eyelid sulcus

Cardiac disorders

Angina; palpitations*

Angina unstable

Respiratory, thoracic and mediastinal disorders

Asthma*; dyspnoea*

Asthma exacerbation

Gastrointestinal disorders

Nausea*; vomiting*

Skin and subcutaneous tissue disorders

Rash

Pruritus

Musculoskeletal and connective tissue disorders

Myalgia*; arthralgia*

General disorders and administration site conditions

Chest pain*

*ADR identified post-marketing

§ADR frequency estimated using “The Rule of 3”

c. Description of selected adverse reactions

No information is provided.

d. Paediatric population

No data are available with Monopost formulation

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

Apart from ocular irritation and conjunctival hyperaemia, no other ocular side effects are known if MONOPOST is overdosed.

If MONOPOST is accidentally ingested the following information may be useful: One single-dose container contains 10 micrograms latanoprost. More than 90% is metabolised during the first pass through the liver. Intravenous infusion of 3 micrograms/kg in healthy volunteers produced mean plasma concentrations 200 times higher than during clinical treatment and induced no symptoms, but a dose of 5.5-10 micrograms/kg caused nausea, abdominal pain, dizziness, fatigue, hot flushes and sweating. In monkeys, latanoprost has been infused intravenously in doses of up to 500 micrograms/kg without major effects on the cardiovascular system.

Intravenous administration of latanoprost in monkeys has been associated with transient bronchoconstriction. However, in patients with moderate bronchial asthma, bronchoconstriction was not induced by latanoprost when applied topically on the eyes in a dose of seven times the clinical dose of MONOPOST.

If overdose with MONOPOST occurs, treatment should be symptomatic.