XALATAN (latanoprost)

Known hypersensitivity to benzalkonium chloride or any other ingredient in this product.

For a complete listing, see the DOSAGE FORMS, COMPOSITION and PACKAGING sections of the product monograph.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

The ocular adverse events and ocular signs and symptoms reported in 5 to 15% of the patients on XALATAN (latanoprost) 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 XALATAN 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 XALATAN 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%.

Less Common Clinical Trial Adverse Drug Reactions (<1%)

The following events were reported in less than 1% of the patients: conjunctivitis, diplopia and discharge from the eye.

During clinical studies, there were extremely rare reports of the following: retinal artery embolus, retinal detachment, and vitreous hemorrhage from diabetic retinopathy.

Post-Market Adverse Drug Reactions

Macular edema, including cystoid macular edema, has been reported during treatment with XALATAN. These reports have mainly occurred in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. XALATAN should be used with caution in these patients. Upon discontinuation of XALATAN treatment, visual acuity has improved, in some cases with concurrent treatment with topical steroidal and non-steroidal anti-inflammatory drugs.

XALATAN has been reported to cause darkening, thickening and lengthening of eye lashes.

Based on spontaneous reports, rare cases of iritis/uveitis and very rare cases of darkening of the palpebral skin have been reported.

The following events, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to XALATAN, or a combination of these factors, have been reported during postmarketing use of XALATAN in clinical practice and in the literature: eyelash changes (increased length, thickness, pigmentation of eyelashes, increased number of eyelashes and vellus hairs on the eyelid, curling of eyelashes, misdirected eyelashes sometimes resulting in eye irritation); eyelid skin darkening: periorbital and lid changes resulting in deepening of the eyelid sulcus; intraocular inflammation (iritis/uveitis); macular edema, including cystoid macular edema; corneal edema and erosions; iris cyst; pseudopemphigoid of ocular conjunctiva; localized skin reaction on the eyelid; photophobia; toxic epidermal necrolysis; infections and infestations: herpetic keratitis; nervous system disorders: dizziness and headache. Those events are reported voluntarily from a population of unknown size; therefore, estimates of frequency cannot be made. Rare cases of asthma, asthma aggravation, acute asthma attack and dyspnoea have been reported. There is limited experience from patients with asthma but latanoprost neither was found to affect pulmonary function when studied in a small number of steroid treated patients suffering from moderate asthma nor was it found to affect the pulmonary function, airway reactivity or β₂-responsiveness when studied in a small number of non-steroid treated asthma patients.

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.

Dosing Considerations

Optimal effect is obtained if XALATAN (latanoprost) is administered in the evening.

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 XALATAN 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 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.

Missed Dose

If one dose is missed, treatment should continue with the next dose the following day.

Administration

Contact lenses should be removed prior to the administration of XALATAN, and may be reinserted 15 minutes after administration (see INFORMATION FOR THE CONSUMER).

Use in combination with other drugs

XALATAN 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.

Mechanism of Action

XALATAN (latanoprost), a prostaglandin F_2α (13,14-dihydro-17-phenyl-18,19,20-trinor-PGF_2α isopropyl ester) analogue, is a selective prostanoid FP receptor agonist which reduces the intraocular pressure by increasing the outflow of aqueous humour. Studies in animals and man indicate that the main mechanism of action is increased uveoscleral outflow.

Glaucoma is a disease with characteristic optic nerve damage and a corresponding visual field defect. Increased intraocular pressure (IOP) is one of the main risk factors. However, disturbances in blood flow may also play a role in some cases. In ocular hypertension, patients may have increased IOP but without changes in the visual field or corresponding optic nerve damage.

Pharmacokinetics

XALATAN is a sterile, isotonic, buffered aqueous solution with a pH of approximately 6.7.

Each mL contains 50 μg of latanoprost, a colourless to slightly yellow oil. Latanoprost is an isopropyl ester prodrug which is well absorbed through the cornea and upon entering the aqueous humour is rapidly and completely hydrolysed to the biologically active acid. Studies in humans indicate that the peak concentration in the aqueous humour is reached about two hours after topical administration.

Following topical administration in monkeys, latanoprost is primarily distributed in the anterior segment, conjunctiva and eyelids with only minute quantities reaching the posterior segment. Reduction of IOP following a single dose in humans starts about 3 to 4 hours following topical administration, and the maximum effect is reached after 8 to 12 hours. Pressure reduction is maintained for at least 24 hours.

There is practically no metabolism of the acid of latanoprost in the eye. The plasma clearance is rapid and occurs in the liver. In humans, the half-life of the biologically active acid in plasma is approximately 17 minutes. In animal studies, the main metabolites were the 1,2-dinor and the 1,2,3,4-tetranor metabolites which exerted only weak or no biologic activity, and were excreted primarily in urine.