Latanoprost

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

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.

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. 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.

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. 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. 8 Undesirable effects a. Summary of the safety profile The majority of adverse events relate to the ocular system.

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 hyperpigm entation; 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 Rash Pruritus 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 disorders 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. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

1.

APO-LATANOPROST (latanoprost) is indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. APO-LATANOPROST may be used for the reduction of intraocular pressure in patients with chronic angle-closure glaucoma who underwent peripheral iridotomy or laser iridoplasty.

3 Pediatrics). 2 Geriatrics Geriatrics: Based on the data submitted and reviewed by Health Canada, there is no overall difference in the safety and efficacy of latanoprost use in the geriatric patient population.

1 Dosing Considerations Contact lenses should be removed prior to the administration of APO-LATANOPROST and may be reinserted 15 minutes after administration (see PATIENT MEDICATION INFORMATION). APO-LATANOPROST may be used concomitantly with other topical ophthalmic products to further lower intraocular pressure.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart. 2 Recommended Dose and Dosage Adjustment The recommended dose for adults, including the elderly (over 60 years of age), is one drop in the affected eye(s) once daily.

The dose of APO-LATANOPROST should not exceed once daily as it has been shown that more frequent administration decreases the IOP lowering effect. Reduction of IOP in humans starts APO-LATANOPROST (Latanoprost Ophthalmic Solution) Page 5 of 31 about 3 to 4 hours after treatment and maximum effect is reached after 8 to 12 hours.

Pressure reduction is maintained for at least 24 hours. 3 Pediatrics). 4 Administration Optimal effect is obtained if APO-LATANOPROST (latanoprost) is administered in the evening. 5 Missed Dose If one dose is missed, treatment should continue with the next dose the following day.

). Skin Eyelid skin darkening, which may be reversible, has been reported in association with the use of latanoprost ophthalmic solution (see 7 WARNINGS AND PRECAUTIONS) APO-LATANOPROST may gradually change eyelashes and vellus hair in the treated eye; these changes include increased length, thickness, pigmentation, the number of lashes or hairs, and misdirected growth of eyelashes.

Eyelash changes are usually reversible upon discontinuation of treatment. 1 Pregnant Women Reproduction studies have been performed in rats and rabbits. In rabbits an incidence of 4 of 16 dams had no viable fetuses at a dose that was approximately 80 times the maximum human dose, and the highest nonembryocidal dose in rabbits was approximately 15 times the maximum human dose (see 16 NON-CLINICAL TOXICOLOGY).

APO-LATANOPROST should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 2 Breast-feeding The active substance in APO-LATANOPROST and its metabolites may pass into breast milk and APO-LATANOPROST should therefore be used with caution in nursing women (see 16 NON- CLINICAL TOXICOLOGY).

3 Pediatrics Pediatrics (< 18 years of age): The safety and efficacy of the use of latanoprost ophthalmic solution in children has not been established; therefore, Health Canada has not authorized an indication for pediatric use. 2 Clinical Trial Adverse Reactions).

2 Clinical Trial Adverse Reactions). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The ocular adverse events and ocular signs and symptoms reported in 5 to 15% of the patients on latanoprost ophthalmic solution in the three 6 month, multi-centre, double-masked, active- controlled trials were blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased iris pigmentation and punctate epithelial keratopathy.

Local conjunctival hyperemia was observed: however, less than 1% of the latanoprost ophthalmic solution treated patients required discontinuation of therapy because of intolerance to conjunctival hyperemia. In addition to the above listed ocular events/signs and symptoms, the following were reported in 1 to 4% of the patients: dry eye, excessive tearing, eye pain, lid crusting, lid edema, lid erythema, lid discomfort/pain and photophobia.

The most common systemic adverse events seen with latanoprost ophthalmic solution were upper respiratory tract infection/cold/flu which occurred at a rate of approximately 4%. Pain in muscle/joint/back, chest pain/angina pectoris and rash/allergic skin reaction each occurred at a rate of 1 to 2%.

3 Less Common Clinical Trial Adverse Reactions The following events were reported in less than 1% of the patients: Eye disorder: conjunctivitis, diplopia, discharge from the eye, retinal artery embolus, retinal detachment, and vitreous hemorrhage from diabetic retinopathy.

5 Post-Market Adverse Reactions APO-LATANOPROST (Latanoprost Ophthalmic Solution) Page 10 of 31 System Organ Class Adverse Drug Reactions Eye disorders Macular oedema including cystoid macular oedema, corneal erosion, punctate keratitis, corneal oedema, uveitis, iritis, pseudopemphigoid of ocular conjunctiva, trichiasis, eyelash and vellus hair changes of the eyelid (increased length, thickness, pigmentation, and number of eyelashes), localised skin reaction on the eyelids, iris cyst, periorbital and lid changes resulting in deepening of the eyelid sulcus, darkening of the palpebral skin of the eyelids Infections and infestations Herpetic keratitis Nervous system disorders Dizziness, headache Gastrointestinal disorders Vomiting, nausea Respiratory, thoracic and mediastinal disorders Acute asthma attacks, asthma aggravation, asthma, dyspnoea Skin and subcutaneous tissue disorders Pruritus 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.

In a long-term observational cohort safety study evaluating hyperpigmentation changes in the eye, 100 paediatric glaucoma patients were followed for up to 10 years: 67 were treated with latanoprost, and 33 were not exposed to prostaglandin analogs (control group).

The proportion of patients with hyperpigmentation was larger in the latanoprost group compared to the control group: iris colour darkening (13% vs 6%), localised iris pigmentation (6% vs 3%), and increase of nevi/freckles of iris, conjunctiva or choroid (12% vs 3%).

5% to 12%) compared to the control group (0%). 1 Pediatrics).

Latanoprost is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

1 INDICATIONS AND USAGE Latanoprost ophthalmic solution is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Latanoprost ophthalmic solution is a prostaglandin F 2α analogue indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

(1)

2 DOSAGE AND ADMINISTRATION The recommended dosage is one drop in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal. The dosage of latanoprost ophthalmic solution should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including latanoprost ophthalmic solution is not recommended.

It has been shown that administration of these prostaglandin drug products more than once daily may decrease the IOP lowering effect or cause paradoxical elevations in IOP. Reduction of the IOP starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours.

Latanoprost ophthalmic solution may be used concomitantly with other topical ophthalmic drug products to lower IOP. In vitro studies have shown that precipitation occurs when eye drops containing thimerosal are mixed with latanoprost ophthalmic solution.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. Contact lenses should be removed prior to the administration of latanoprost ophthalmic solution, and may be reinserted 15 minutes after administration.

One drop in the affected eye(s) once daily in the evening. (2)

4) ] Most common adverse reactions (5-15%) from clinical trials are blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased pigmentation of the iris, and punctate keratitis. gov/medwatch .

1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Latanoprost ophthalmic solution was studied in three multicenter, randomized, controlled clinical trials. Patients received 50 mcg/mL latanoprost ophthalmic solution once daily or 5 mg/mL active-comparator (timolol) twice daily. The patient population studied had a mean age of 65±10 years.

Seven percent of patients withdrew before the 6-month endpoint.

Table 1:

Ocular Adverse Reactions and Ocular Signs/Symptoms Reported by 5-15% of Patients Receiving Latanoprost Symptom/Finding Adverse Reactions (incidence (%)) Latanoprost (n=460) Timolol (n=369) Foreign body sensation 13 8 Punctate keratitis 10 9 Stinging 9 12 Conjunctival hyperemia 8 3 Blurred vision 8 8 Itching 8 8 Burning 7 8 Increased pigmentation of the Iris 7 0 Less than 1% of the patients treated with latanoprost ophthalmic solution required discontinuation of therapy because of intolerance to conjunctival hyperemia.

2 Postmarketing Experience The following reactions have been identified during postmarketing use of latanoprost ophthalmic solution in clinical practice. Because they are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to latanoprost, or a combination of these factors, include: Nervous System Disorders : Dizziness; headache; toxic epidermal necrolysis Eye Disorders : Eyelash and vellus hair changes of the eyelid (increased length, thickness, pigmentation, and number of eyelashes); keratitis; corneal edema and erosions; intraocular inflammation (iritis/uveitis); macular edema, including cystoid macular edema; trichiasis; periorbital and lid changes resulting in deepening of the eyelid sulcus; iris cyst; eyelid skin darkening; localized skin reaction on the eyelids; conjunctivitis; pseudopemphigoid of the ocular conjunctiva.

Respiratory, Thoracic and Mediastinal Disorders :

Asthma and exacerbation of asthma; dyspnea Gastrointestinal Disorders : Nausea; vomiting Skin and Subcutaneous Tissue Disorders : Pruritis Infections and Infestations : Herpes keratitis Cardiac Disorders : Angina; palpitations; angina unstable General Disorders and Administration Site Conditions : Chest pain

4 CONTRAINDICATIONS Known hypersensitivity to latanoprost, benzalkonium chloride, or any other ingredients in this product. Known hypersensitivity to latanoprost, benzalkonium chloride, or any other ingredients in this product. (4)

Catiolanze is indicated for the reduction of elevated intraocular pressure (IOP) in adult patients with open angle glaucoma or ocular hypertension. Catiolanze is indicated for the reduction of elevated IOP in children from 4 years of age and adolescents with elevated IOP and paediatric glaucoma.

Posology Catiolanze may be used in paediatric patients from 4 years old onwards at the same posology as in adults. Recommended therapy is one eye drop in the affected eye(s) once daily. Optimal effect is obtained if Catiolanze is administered in the evening.

The dose of Catiolanze should not exceed once daily since it has been shown that more frequent administration decreases the IOP lowering effect. Missed dose If one dose is missed, treatment should continue with the next dose as normal.

3 Paediatric population The safety of Catiolanze in children aged less than 4 years old has not been established as no data for this formulation (emulsion) are available. 1. Method of administration Ocular use. For single use only. A single-dose container contains enough eye drops liquid to treat both eyes.

As with any eye drops, it is recommended that the lachrymal sac be compressed at the medial canthus (punctal occlusion) for one minute, in order to reduce possible systemic absorption. 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 must be administered at least 5 minutes apart.

5). This medicinal product is a sterile white liquid that does not contain a preservative. The liquid 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 emulsion immediately after first opening the single-dose container and to discard the single-dose after use.

Summary of the safety profile The majority of adverse reactions relate to the ocular system. 4). Other ocular adverse reactions are generally transient and occur on dose administration. Safety data specific for Catiolanze are available from 330 patients.

0%). There were no serious adverse reactions during the studies specific for Catiolanze. Long term safety data are available from a Phase 3 study in which 118 patients received Catiolanze at least for 360 days. The long term safety profile did not differ from that observed during the first 3 months of treatment.

2%). Tabulated list of adverse reactions The table below describes adverse reactions for preserved latanoprost eye drops, solution from clinical trials and postmarketing data. Adverse reactions occurring with a different frequency observed in clinical trials with Catiolanze eye drops emulsion product are labelled in the table with ¥.

The adverse reactions are categorised 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).

System organ class 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 Very rare <1/10 000 Infections and infestations Herpetic keratitis*§ Nervous system disorders Headache*; dizziness* 7 Eye disorders Iris hyperpigmentati on Mild to moderate conjunctival hyperaemia¥ Eye irritation (burning grittiness, itching, stinging, foreign body sensation and abnormal sensation)¥; Punctate keratitis, mostly without symptoms; eye pain; Photophobia; Conjunctivitis* Eyelid oedema¥; eyelash and vellus hair changes of the eyelid (increased length, thickness, pigmentation and number of eyelashes)¥; blepharitis¥; 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; pseudopemphigoid of ocular conjunctiva*§ 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 Gastrointestin al disorders Nausea*; vomiting* Skin and subcutaneous tissue disorder Rash Pruritis Musculoskele tal 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” ¥ADR frequency estimated from studies specific to Catiolanze eye drops emulsion 8 Description of selected adverse reactions No information is provided.

Paediatric population In two short term clinical trials (≤12 weeks), involving 93 (25 and 68) paediatric patients treated with preserved latanoprost eye drops, solution, the safety profile was similar to that in adults and no new adverse events were identified.

1). Adverse events seen more frequently with preserved latanoprost in the paediatric population as compared to adults were nasopharyngitis and pyrexia. Catiolanze was not specifically studied in the paediatric population. 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 national reporting system listed in Appendix V.

1.