Prostaglandin analogues

Travatan Z

Approved 21 Sept 2006EyeSolution/drops

Indications

TRAVATAN Z ® (travoprost ophthalmic solution) 0.004% is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. TRAVATAN Z is a prostaglandin analog indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (1)

Contraindications

None. None (4)

Warnings and precautions

Pigmentation: Pigmentation of the iris, periorbital tissue (eyelid), and eyelashes can occur. Iris pigmentation likely to be permanent (5.1)
Eyelash Changes: Gradual change to eyelashes including increased length, thickness and number of lashes. Usually reversible (5.2)

5.1Pigmentation

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 TRAVATAN Z can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.

5.2Eyelash Changes

TRAVATAN Z 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.

At a glance

Brand name: Travatan Z
Active substance: travoprost
Drug class: Prostaglandin analogues
Route: Eye
Dosage form: Solution/drops
Applicant: Sandoz
Status: Prescription
FDA approval: 21 Sept 2006
Application: NDA021994-001
RxCUI: 283809

Indications

Warnings and precautions

Pigmentation: Pigmentation of the iris, periorbital tissue (eyelid), and eyelashes can occur. Iris pigmentation likely to be permanent (5.1)
Eyelash Changes: Gradual change to eyelashes including increased length, thickness and number of lashes. Usually reversible (5.2)

5.1Pigmentation

5.2Eyelash Changes

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

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, TRAVATAN Z 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. Data Animal Data 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 6 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 NOAEL for malformations was 0.3 mcg/kg (2 times the MRHOD, based on estimated plasma C max ).

The maternal 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.

The NOAEL for adverse pregnancy outcomes, low-birth weight and developmental delay was 0.1 mcg/kg (0.6 times the MRHOD, based on estimated plasma C max ). The NOAEL for maternal toxicity was 0.72 mcg/kg (4 times the MRHOD, based on estimated plasma C max ).

Adverse reactions

Most common adverse reaction (30% to 50%) is conjunctival hyperemia (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reaction observed in controlled clinical trials with TRAVATAN and TRAVATAN Z was ocular hyperemia, which was reported in 30% to 50% of patients.

Up to 3% of patients discontinued therapy due to conjunctival hyperemia. Ocular adverse reactions, reported at an incidence of 5% to 10% in these clinical trials, included decreased visual acuity, eye discomfort, foreign body sensation, pain, and pruritus. Ocular adverse reactions, reported at an incidence of 1% to 4% in clinical trials with TRAVATAN or TRAVATAN Z, included abnormal vision, blepharitis, blurred vision, cataract, conjunctivitis, corneal staining, dry eye, iris discoloration, keratitis, lid margin crusting, ocular inflammation, photophobia, subconjunctival hemorrhage, and tearing.

Non-ocular adverse reactions, reported at an incidence of 1% to 5% in these clinical studies, were allergy, angina pectoris, anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold/flu syndrome, depression, dyspepsia, gastrointestinal disorder, headache, hypercholesterolemia, hypertension, hypotension, infection, pain, prostate disorder, sinusitis, urinary incontinence, and urinary tract infections.

6.2Postmarketing Experience

Additional adverse reactions have been identified during postapproval use of TRAVATAN or TRAVATAN Z in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to TRAVATAN or TRAVATAN Z, or a combination of these factors, include: arrhythmia, vomiting, epistaxis, tachycardia, and insomnia.

In postmarketing use with prostaglandin analogs, periorbital and lid changes, including deepening of the eyelid sulcus have been observed.

Travatan Z

Indications

Contraindications

Warnings and precautions

5.1Pigmentation

5.2Eyelash Changes

At a glance

Two medicines in one question?

Travatan Z

Indications

Contraindications

Warnings and precautions

5.1Pigmentation

5.2Eyelash Changes

At a glance

Two medicines in one question?

5.3Intraocular Inflammation

5.4Macular Edema

5.5Angle-closure, Inflammatory or Neovascular Glaucoma

5.6Bacterial Keratitis

5.7Use with Contact Lenses

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information