Xelpros Drug Information

XELPROS (latanoprost ophthalmic emulsion) 0.005% is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. XELPROS is a prostaglandin F 2α analog indicated for reduction of elevated intraocular pressure in patients with open-angle glaucoma, or ocular hypertension.

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 XELPROS should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including XELPROS is not recommended.

It has been shown that administration of these prostaglandin drug products more than once daily may decrease the intraocular pressure (IOP) lowering effect or cause paradoxical elevations in IOP. XELPROS may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.

Contact lenses should be removed prior to the administration of XELPROS, and may be reinserted 15 minutes after administration.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Across multiple clinical trials conducted with XELPROS (latanoprost ophthalmic emulsion) 0.005%, the most frequently reported ocular adverse reactions were eye pain/stinging upon instillation and ocular hyperemia, reported in 55% and 41% of XELPROS treated patients, respectively (Table 1). Less than 1% of patients discontinued therapy because of intolerance to the eye pain/stinging or to the ocular hyperemia.

Table 1. Ocular Adverse Reactions Reported by ≥ 1% of Subjects Receiving XELPROS

Postmarketing Experience

The following reactions have been identified during postmarketing use of topical latanoprost products 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 ophthalmic emulsion or a combination of these factors, include: Nervous System Disorders: Dizziness, headache, toxic epidermal necrolysis Eye Disorders: 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: Pruritus Infections and Infestations: Herpes keratitis Cardiac Disorders: Angina; palpitations; angina unstable General Disorders and Administration Site Conditions: Chest pain

In vitro studies have shown that precipitation occurs when eye drops containing thimerosal are mixed with XELPROS. If such drugs are used, they should be administered at least five minutes apart. The combined use of two or more prostaglandins, or prostaglandin analogs including XELPROS 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. Thimerosal: Precipitation may occur if drugs containing thimerosal are used concomitantly with XELPROS.

Pregnancy Risk Summary There are no adequate and well-controlled studies of XELPROS ophthalmic emulsion in pregnant women to inform drug-associated risks. In animal reproduction studies, intravenous (IV) administration of latanoprost to pregnant rabbits and rats throughout the period of organogenesis produced malformations, embryofetal lethality and spontaneous abortion at clinically relevant doses. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data Animal Data Embryofetal studies were conducted in pregnant rabbits administered latanoprost daily by IV injection on gestation days 6 through 18, to target the period of organogenesis. A no observed adverse effect level (NOAEL) was not established for rabbit developmental toxicity. Spina bifida and abortion occurred at 5 mcg/kg/day (equivalent to 32 times the maximum RHOD).

Total litter loss due to early resorption was observed at doses ≥ 50 mcg/kg/day (324 times the maximum RHOD). Transient signs of maternal toxicity were observed after IV dosing (increased breathing, muscle tremors, slight motor incoordination) at 300 mcg/kg/day (1946 times the maximum RHOD). No maternal toxicity was observed at doses up to 50 mcg/kg/day.

A NOAEL for rat developmental toxicity was not established. Brain porencephalic cyst(s) were observed ≥50 mcg/kg (162 times the maximum RHOD). Skeletal anomalies were observed at 250 mcg/kg (811 times the maximum RHOD).

No maternal toxicity was detectable at 250 mcg/kg/day. Prenatal and postnatal development was assessed in rats. Pregnant rats were administered latanoprost daily by IV injection from gestation day 15, through delivery, until weaning (lactation Day 21).

At 100 mcg/kg/day (324 times the maximum RHOD), maternal deaths and pup mortality occurred.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Known hypersensitivity to latanoprost, or any other ingredients in this product.

Intravenous infusion of up to 3 mcg/kg of latanoprost in healthy volunteers produced mean plasma concentrations 200 times higher than during clinical treatment with XELPROS and no adverse reactions were observed. Intravenous dosages of 5.5 to 10 mcg/kg caused abdominal pain, dizziness, fatigue, hot flashes, nausea, and sweating. If overdosage with XELPROS occurs, treatment should be symptomatic.