Travoprost Ophthalmic Solution 0.004%

Par Pharmaceutical, Inc.
Par Pharmaceutical, Inc.

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Travoprost Ophthalmic Solution USP, 0.004% safely and effectively. See full prescribing information for Travoprost Ophthalmic Solution USP, 0.004%.Initial U.S. Approval: 2001INDICATIONS AND USAGETravoprost Ophthalmic Solution USP, 0.004% is a prostaglandin analog indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. ( 1)DOSAGE AND ADMINISTRATIONOne drop in the affected eye(s) once daily in the evening. ( 2) DOSAGE FORMS AND STRENGTHSSolution containing 0.04 mg/mL travoprost ophthalmic solution. ( 3) 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) USE IN SPECIFIC POPULATIONSUse 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. ( 8.4)

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 TRAVOPROST OPHTHALMIC SOLUTION 0.004% INDICATIONS AND USAGE
• 2 TRAVOPROST OPHTHALMIC SOLUTION 0.004% DOSAGE AND ADMINISTRATION
• 3 DOSAGE FORMS AND STRENGTHS
• 4 TRAVOPROST OPHTHALMIC SOLUTION 0.004% CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Pigmentation
  • 5.2 Eyelash Changes
  • 5.3 Intraocular Inflammation
  • 5.4 Macular Edema
  • 5.5 Angle-closure, Inflammatory or Neovascular Glaucoma
  • 5.6 Bacterial Keratitis
  • 5.7 Use with Contact Lenses
• 6.1 Clinical Studies Experience
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy Section
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
  • 8.6 Hepatic and Renal Impairment
• 11 TRAVOPROST OPHTHALMIC SOLUTION 0.004% DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis and Mutagenesis and Impairment Of Fertility
• 14 CLINICAL STUDIES
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 Potential for Pigmentation
  • 17.2 Potential for Eyelash Changes
  • 17.3 Handling the Container
  • 17.4 When to Seek Physician Advice
  • 17.5 Use with Contact Lenses
  • 17.6 Use with Other Ophthalmic Drugs
• PRINCIPAL DISPLAY PANEL – 2.5 ML FILL CARTON
• PRINCIPAL DISPLAY PANEL – 5 ML FILL CARTON
• PRINCIPAL DISPLAY PANEL – 2.5 ML FILL CONTAINER
• PRINCIPAL DISPLAY PANEL – 5 ML FILL CONTAINER

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Travoprost Ophthalmic Solution USP, 0.004% is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

2 DOSAGE AND ADMINISTRATION

The recommended dosage is one drop in the affected eye(s) once daily in the evening. Travoprost Ophthalmic Solution USP, 0.004% should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect.

Reduction of the intraocular pressure starts approximately 2 hours after the first administration with maximum effect reached after 12 hours.

Travoprost ophthalmic solution 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 (5) minutes apart.

3 DOSAGE FORMS AND STRENGTHS

Ophthalmic solution containing travoprost 0.04 mg/mL.

4 CONTRAINDICATIONS

None

5 WARNINGS AND PRECAUTIONS

5.1 Pigmentation

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 travoprost ophthalmic solution can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. (see PATIENT COUNSELING INFORMATION, 17.1).

5.2 Eyelash Changes

Travoprost ophthalmic solution 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.

5.3 Intraocular Inflammation

Travoprost ophthalmic solution should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated.

5.4 Macular Edema

Macular edema, including cystoid macular edema, has been reported during treatment with travoprost ophthalmic solution. Travoprost ophthalmic solution 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.

5.5 Angle-closure, Inflammatory or Neovascular Glaucoma

Travoprost ophthalmic solution has not been evaluated for the treatment of angle-closure, inflammatory or neovascular glaucoma.

5.6 Bacterial Keratitis

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 COUNSELING INFORMATION, 17.3).

5.7 Use with Contact Lenses

Contact lenses should be removed prior to instillation of travoprost ophthalmic solution and may be reinserted 15 minutes following its administration.

6.1 Clinical Studies Experience

Because clinical studies 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 practice.

The most common adverse reaction observed in controlled clinical studies with travoprost ophthalmic solution 0.004% 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 studies 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 studies with travoprost ophthalmic solution 0.004% 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.

Nonocular 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.

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy Section

Pregnancy Category C

Teratogenic effects: Travoprost was teratogenic in rats, at an intravenous (IV) dose up to 10 mcg/kg/day (250 times the maximal recommended human ocular dose (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 was not teratogenic in rats at IV doses up to 3 mcg/kg/day (75 times the MRHOD), or in mice at subcutaneous doses up to 1 mcg/kg/day (25 times the MRHOD). Travoprost produced an increase in post-implantation losses and a decrease in fetal viability in rats at IV doses >3 mcg/kg/day (75 times the MRHOD) and in mice at subcutaneous doses >0.3 mcg/kg/day (7.5 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 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.

There are no adequate and well-controlled studies of travoprost ophthalmic solution 0.004% administration in pregnant women. Because animal reproductive studies are not always predictive of human response, travoprost ophthalmic solution should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

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 travoprost ophthalmic solution is administered to a nursing woman.

8.4 Pediatric Use

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.

8.5 Geriatric Use

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

8.6 Hepatic and Renal Impairment

Travoprost ophthalmic solution has been studied in patients with hepatic impairment and also in patients with renal impairment. No clinically relevant changes in hematology, blood chemistry, or urinalysis laboratory data were observed in these patients.

11 DESCRIPTION

•  Travoprost is a synthetic prostaglandin F analogue. Its chemical name is [1R-[1α(Z),2β(1E,3R*),3α,5α]]-7-[3,5Dihydroxy-2-[3-hydroxy-4-[3(trifluoromethyl)phenoxy]-1-butenyl]cyclopentyl]-5heptenoic acid, 1-methylethylester. It has a molecular formula of C₂₆H₃₅F₃O₆ and a molecular weight of 500.55. The chemical structure of travoprost is: