XALATAN

Latanoprost is a prodrug analog of prostaglandin F2 alpha that is used to treat elevated intraocular pressure (IOP).

It was initially approved by the

FDA in 1998.

Latanoprost is the first topical prostaglandin

F2 alpha analog used for glaucoma treatment.

It has been found to be well-tolerated and its use does not normally result in systemic adverse effects like other drugs used to treat elevated intraocular pressure, such as Timolol.

Another benefit latanoprost is that it can be administered once a day.

Latanoprost is indicated for the reduction of elevated intraocular pressure in patients who have been diagnosed with open-angle glaucoma or ocular hypertension. 6, 10, 11 It is available as monotherapy or in a with netarsudil 9 or timolol.

In Canada, latanoprost is also indicated to treat elevated intraocular pressure due to angle-closure glaucoma that has been treated with peripheral iridotomy or laser iridoplasty.

Latanoprost effectively decreases intraocular pressure by increasing uveoscleral outflow.

A decrease in intraocular pressure has been measured within 3–4 hours post-administration, reaches a maximum decrease at 8–12 hours, and can be maintained for a period of 24 hours.

A note on eye and periorbital changes Between 3-10% of patients taking latanoprost have experienced iris pigmentation after about 3-4 months of latanoprost use. 1, 2 Patients should be notified of this risk before initiating treatment.

It may occur in both patients with light-colored irides (green-brown or blue/grey-brown) or dark-colored (brown) irides, but is less pronounced in the latter group.

This drug may also cause other ocular effects including infrequent conjunctival hyperemia, pigmentation of periocular tissues, eyelash changes, hypertrichosis, and ocular irritation. 3, 6.

This drug is rapidly absorbed in the cornea as an isopropyl ester prodrug and is then activated by the process of hydrolysis.

A small amount of this drug is systemically absorbed.

Cmax of latanoprost in the systemic circulation is reached after 5 minutes and is measured to be 53 pg/mL.

Cmax in the aqueous humor is attained within 2 hours after administration. 3, 6 and has been estimated to be 15-30 ng/mL.

The volume of distribution of latanoprost is 0.16 ± 0.02 L/kg. The activated acid form of latanoprost can be measured in aqueous humor in the initial 4 hours post-administration, and it is measured in the plasma only for 1 hour following ophthalmic administration.

This drug is more lipophilic than its parent prostaglandin and easily penetrates the cornea.

It has been shown to cross the placenta in rats.

After corneal uptake, this prodrug is hydrolyzed and activated by esterases to become a pharmacologically active drug.

The small portion of this drug that is able to reach the circulation is found to be metabolized by the liver to the 1,2-dinor and 1,2,3,4-tetranor metabolites through fatty acid beta-oxidation. 2, 3, 6 Hover over products below to view reaction partners Latanoprost Latanoprost acid 1, 2 Dinor Latanoprost Acid + 1,2,3,4 Tetranor Latanoprost Acid.

After hepatic beta-oxidation, the metabolites of latanoprost are primarily found to be excreted by the kidneys.

About 88% of the latanoprost dose is recovered in the urine after topical administration. 2, 6 About 15% of a dose is reported to be excreted in the feces.

The elimination half-life of latanoprost from the plasma is about 17 minutes. 3, 6 The elimination half-life of latanoprost from the eye is estimated at 2–3 hours.

The systemic clearance of latanoprost is 7 mL/min/kg.

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The oral

LD50 in the rat is > 50 mg/kg.

An overdose of latanoprost is not expected to result in dangerous patient outcomes, however, conjunctival or episcleral hyperemia may occur.

An intravenous infusion of 3 μg/kg of latanoprost in healthy volunteers led to mean plasma concentrations 200 times higher than a normally administered therapeutic dose and no adverse effects were noted.

One study suggested that an overdose of latanoprost leads to cystoid macular edema after a large, unintended overdose.

This resolved within 4 weeks after 4 weeks following treatment with nepafenac 0.3% eye drops in addition to oral acetazolamide.

Contact the local poison control center for updated guidance on managing a latanoprost overdose.

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

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 to 4 hours after administration and the maximum effect is reached after 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 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.

Latanoprost ophthalmic solution is a clear, isotonic, buffered, preserved colorless solution of latanoprost 50 mcg/mL (0.005%).

It is supplied as a 2.5 mL solution in a 5 mL clear low density polyethylene bottle with a clear polyethylene dropper tip, a turquoise high density polyethylene screw cap, and a tamper-evident ring between the bottle and cap. 2.5 mL fill, 50 mcg/mL (0.005%): Package of 1 bottle: NDC 68083-609-01 Storage: Protect from light.

Store unopened bottle(s) under refrigeration at 2°C to 8°C (36°F to 46°F).

During shipment to the patient, the bottle may be maintained at temperatures up to 40°C (104°F) for a period not exceeding 8 days.

Once a bottle is opened for use, it may be stored at room temperature up to 25°C (77°F) for 6 weeks.

There are no adequate and well-controlled studies of latanoprost ophthalmic solution administration 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.

However, the background risk in the U.S. general population of major birth defects is to 4%, and of miscarriage is to 20% of clinically recognized pregnancies.

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.

Post-implantation loss due to late resorption was shown as doses ≥0.2 mcg/kg/day (equivalent to 1.3 times the maximum recommended human ophthalmic dose [RHOD], on a mg/m 2 basis, assuming 100% absorption).

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. Embryofetal studies were conducted in pregnant rats administered latanoprost daily by IV injection on gestation days 6 through 15, to target the period of organogenesis.

A NOAEL for rat developmental toxicity was not established.

Cleft palate was observed at 1 mcg/kg (equivalent to 3.2 times the maximum RHOD, on a mg/m 2 basis, assuming 100% absorption).

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).

No adverse effects on rat offspring were observed at doses up to 10 mcg/kg/day (32 times the maximum RHOD, on a mg/m 2 basis, assuming 100% absorption).

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

Safety and effectiveness in pediatric patients have not been established.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.