TRAVADROP

Travoprost is a synthetic isopropyl ester prodrug of a prostaglandin F2alpha (F2α) analogue and selective FP prostanoid receptor agonist.

It is used to decrease intraocular pressure in open-angle glaucoma and ocular hypertension.

Unlike other prostaglandin analogues, travoprost demonstrates full agonism and high selectivity at the prostanoid receptor, reporting a higher efficacy in reducing intraocular pressure and a reduced risk for developing off-target side effects.

Travoprost is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. 7, 6, 8 It is also used in pediatric patients aged two months to less than 18 years.

Travoprost demonstrates preferential affinity and full agonist activity for the prostaglandin FP receptor in the nanomolar range.

Travoprost shows no significant affinity for other prostanoid or non-prostanoid receptors.

Travoprost-induced reduction of intraocular pressure is observed about two hours after administration, and the maximum effect is reached after 12 hours.

Significant lowering of intraocular pressure can be maintained for periods exceeding 24 hours with a single dose.

Following ophthalmic administration, travoprost is absorbed through the cornea.

In many patients in multiple-dose pharmacokinetic studies, the plasma concentrations of the free acid were below 0.01 ng/mL, which was the quantitation limit of the assay.

In these studies, the mean plasma C max of travoprost free acid was 0.018 ± 0.007 ng/mL (ranging from 0.01-0.052 ng/mL), and the T max was about 30 minutes.

No information is available.

Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid.

Systemically, travoprost free acid is metabolized to inactive metabolites via beta-oxidation of the α (carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13, 14 double bond. 4, 7 Hover over products below to view reaction partners Travoprost Travoprost free acid.

The elimination of travoprost free acid from plasma is rapid.

The levels of travoprost free acid were generally below the limit of quantification within one hour after dosing.

Less than 2% of the topical ocular dose of travoprost was excreted in the urine within 4 hours as the travoprost free acid.

The terminal elimination half-life of travoprost free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the mean half-life of 45 minutes.

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No cases of overdose have been reported for travoprost, as overdose from topical or ophthalmic administration is not likely to occur.

Overdose from topical administration should be responded to with flushing of the eyes with lukewarm water.

Treatment of an oral overdose should be symptomatic and supportive.

The recommended dosage is one drop in the affected eye(s) once daily in the evening.

Travoprost ophthalmic solution (ionic buffered solution) should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the IOP lowering effect.

Reduction of the

IOP starts approximately 2 hours after the first administration with maximum effect reached after 12 hours.

Travoprost ophthalmic solution (ionic buffered solution) may be used concomitantly with other topical ophthalmic drug products to lower IOP.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart.

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

Travoprost ophthalmic solution

USP, (ionic buffered solution) 0.004% is a clear colorless, sterile, aqueous solution of travoprost, USP (0.04 mg/mL).

Travoprost ophthalmic solution, USP (ionic buffered solution) is supplied as a 2.5 mL or 5 mL solution in a 5 mL natural colored low density polyethylene bottle with a turquoise, high density polyethylene, tamper evident screw cap and a low density polyethylene nozzle. 2.5 mL fill NDC 0378-9651-32 carton of one bottle 5 mL fill NDC 0378-9651-50 carton of one bottle Storage: Store at 2° to 25°C (36° to 77°F).

After opening, travoprost ophthalmic solution, USP (ionic buffered solution) can be used until the expiration date on the bottle.

There are no adequate and well-controlled studies in pregnant women to inform a drug-associated risk.

In animal reproduction studies, subcutaneous (SC) administration of travoprost to pregnant mice and rats throughout the period of organogenesis produced embryo-fetal lethality, spontaneous abortion, and premature delivery at potentially clinically relevant doses.

Advise pregnant women of a potential risk to a fetus.

Because animal reproductive studies are not always predictive of human response, travoprost should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

An embryo-fetal study was conducted in pregnant rats administered travoprost once daily by SC injection from gestation day (GD) 6 to 18, to target the period of organogenesis.

At 10 mcg/kg (60 times the maximum recommended human ocular dose [MRHOD], based on estimated plasma C max ), travoprost was teratogenic in rats, evidenced by an increase in the incidence of skeletal malformations as well as external and visceral malformations, including fused sternebrae, domed head and hydrocephaly.

Travoprost caused post-implantation loss at 10 mcg/kg. The no observed adverse effect level (NOAEL) for post-implantation loss was 3 mcg/kg (18 times the MRHOD, based on estimated plasma C max ).

The maternal

NOAEL was 10 mcg/kg. An embryo-fetal study was conducted in pregnant mice administered travoprost once daily by SC injection from GD to 11, to target the period of organogenesis.

At 1 mcg/kg (6 times the MRHOD, based on estimated plasma C max ), travoprost caused postimplantation loss and decreased fetal weight.

The no observed adverse effect level (NOAEL) for malformations was 0.3 mcg/kg (2 times the MRHOD, based on estimated plasma C max ).

NOAEL was 1 mcg/kg. Pre/postnatal studies were conducted in rats administered travoprost once daily by subcutaneous injection from GD 7 (early embryonic period) to postnatal Day 21 (end of lactation period).

At doses of greater than or equal to 0.12 mcg/kg/day (0.7 times the MRHOD, based on estimated plasma C max ), adverse pregnancy outcomes (embryo-fetal lethality, abortion, and early delivery), low-birth weight and developmental delays were observed.

NOAEL for adverse pregnancy outcomes, low-birth weight and developmental delay was 0.1 mcg/kg (0.6 times the MHROD, based on estimated plasma C max ).

NOAEL for maternal toxicity was 0.72 mcg/kg (4 times the MHROD, based on estimated plasma C max ).

Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.