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Travoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is expected to increase as long as travoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of travoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known.
Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with IZBA (travoprost ophthalmic solution) 0.003% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. (See PATIENT INFORMATION).
IZBA may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment.
Macular edema, including cystoid macular edema, has been reported during treatment with travoprost ophthalmic solution. IZBA should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.
There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface (See PATIENT INFORMATION).
Use With Contact Lenses
Contact lenses should be removed prior to instillation of IZBA and may be reinserted 15 minutes following its administration.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Two-year carcinogenicity studies in mice and rats at subcutaneous doses of 10, 30, or 100 mcg/kg/day did not show any evidence of carcinogenic potential. However, at 100 mcg/kg/day, male rats were only treated for 82 weeks, and the maximum tolerated dose (MTD) was not reached in the mouse study. The high dose (100 mcg/kg) corresponds to exposure levels over 400 times (for the mouse) and 700 times (for the rat) of the human exposure at the maximum recommended human ocular dose (MRHOD) of 0.03 mcg/kg, based on estimated plasma Cmax for active free acid.
Travoprost was not mutagenic in the Ames test, mouse micronucleus test or rat chromosome aberration assay. A slight increase in the mutant frequency was observed in one of two mouse lymphoma assays in the presence of rat S-9 activation enzymes.
Travoprost did not affect mating or fertility indices in male or female rats at subcutaneous doses up to 10 mcg/kg/day (40 times the MRHOD based on estimated plasma Cmax for active free acid). At 10 mcg/kg/day, the mean number of corpora lutea was reduced, and the post-implantation losses were increased. These effects were not observed at 3 mcg/kg/day (12 times the MRHOD).
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies of IZBA (travoprost ophthalmic solution 0.003%) administration in pregnant women. Malformations were observed in rats at doses that were 1500 times higher the maximum recommended human ocular dose (MRHOD) based on estimated Cmax values for the active free acid. Embryo lethality and decreased fetal/neonate viability were observed in mice at subcutaneous doses 9-fold higher than the MRHOD based on estimated Cmax for the active free acid. IZBA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Travoprost was teratogenic in rats, at an intravenous (IV) dose up to 10 mcg/kg/day (1500 times the MRHOD, evidenced by an increase in the incidence of skeletal malformations as well as external and visceral malformations, such as fused sternebrae, domed head and hydrocephaly. Travoprost did not produce malformations in rats at IV doses up to 3 mcg/kg/day (470 times the MRHOD), or in mice at subcutaneous doses up to 1 mcg/kg/day (9 times the MRHOD). Travoprost produced an increase in post-implantation losses and a decrease in fetal viability in rats at IV doses of 10 mcg/kg/day (1500 times the MRHOD) and in mice at subcutaneous doses of 1 mcg/kg/day (9 times the MRHOD).
In the offspring of female rats that received travoprost subcutaneously from Day 7 of pregnancy to lactation Day 21 at doses of ≥ 0.12 mcg/kg/day (3.2 times the MRHOD), the incidence of postnatal mortality was increased, and neonatal body weight gain was decreased. Neonatal development was also affected, evidenced by delayed eye opening, pinna detachment and preputial separation, and by decreased motor activity.
A study in lactating rats demonstrated that radiolabeled travoprost and/or its metabolites were excreted in milk. It is not known whether this drug or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when IZBA is administered to a nursing woman.
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.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/29/2014
Additional Izba Information
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