Prostaglandin Analog

Xalatan

Approved 5 Jun 1996EyeSolution/drops

Indications

XALATAN is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. XALATAN is a prostaglandin F 2α analogue indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. ( 1 )

Contraindications

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

XALATAN 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 latanoprost 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 latanoprost, 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. Beyond 5 years the effects of increased pigmentation are not known [see Clinical Studies (14.2) ] . 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 XALATAN can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.

5.2Eyelash Changes

At a glance

Brand name: Xalatan
Active substance: latanoprost
Pharmacologic class: Prostaglandin Analog
Route: Eye
Dosage form: Solution/drops
Applicant: Upjohn
Status: Prescription
FDA approval: 5 Jun 1996
Application: NDA020597-001

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 of XALATAN 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 [see Data ] . 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 2 to 4%, and of miscarriage is 15 to 20% of clinically recognized pregnancies. Data Animal Data 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.

Adverse reactions

The following adverse reactions were reported in postmarketing experience and are discussed in greater detail in other sections of the label:

Iris pigmentation changes [see Warnings and Precautions (5.1) ]
Eyelid skin darkening [see Warnings and Precautions (5.1) ]
Eyelash changes (increased length, thickness, pigmentation, and number of lashes) [see Warnings and Precautions (5.2) ]
Intraocular inflammation (iritis/uveitis) [see Warnings and Precautions (5.3) ]
Macular edema, including cystoid macular edema [see Warnings and Precautions (5.4) ] Most common adverse reactions (5-15%) from clinical trials are blurred vision, burning and stinging, conjunctival hyperemia, foreign body sensation, itching, increased pigmentation of the iris, and punctate keratitis. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) 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, the adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. XALATAN was studied in three multicenter, randomized, controlled clinical trials. Patients received 50 mcg/mL XALATAN once daily or 5 mg/mL active-comparator (timolol) twice daily.

The patient population studied had a mean age of 65±10 years. Seven percent of patients withdrew before the 6-month endpoint. Table 1: Ocular Adverse Reactions and Ocular Signs/Symptoms Reported by 5-15% of Patients Receiving Latanoprost Symptom/Finding Adverse Reactions (Incidence (%)) Latanoprost (n=460) Timolol (n=369) Foreign body sensation 13 8 Punctate keratitis 10 9 Stinging 9 12 Conjunctival hyperemia 8 3 Blurred vision 8 8 Itching 8 8 Burning 7 8 Increased pigmentation of the iris 7 0 Less than 1% of the patients treated with XALATAN required discontinuation of therapy because of intolerance to conjunctival hyperemia.

Table 2: Adverse Reactions That Were Reported in 1-5% of Patients Receiving Latanoprost Adverse Reactions (Incidence (%)) Latanoprost (n=460) Timolol (n=369) Ocular Events/Signs and Symptoms Excessive tearing 4 6 Eyelid discomfort/pain 4 2 Dry eye 3 3 Eye pain 3 3 Eyelid margin crusting 3 3 Erythema of the eyelid 3 2 Photophobia 2 1 Eyelid edema 1 3 Blepharitis 1 3 Systemic Events Upper respiratory tract infection/nasopharyngitis/influenza 3 3 Myalgia/arthralgia/back pain 1

0.5 Rash/allergic skin reaction 1 0.3

6.2Postmarketing Experience

The following reactions have been identified during postmarketing use of XALATAN in clinical practice. Because they are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to XALATAN, or a combination of these factors, include: Nervous System Disorders: Dizziness; headache; toxic epidermal necrolysis Eye Disorders: Eyelash and vellus hair changes of the eyelid (increased length, thickness, pigmentation, and number of eyelashes); keratitis; corneal edema and erosions; intraocular inflammation (iritis/uveitis); macular edema, including cystoid macular edema; trichiasis; periorbital and lid changes resulting in deepening of the eyelid sulcus; iris cyst; eyelid skin darkening; localized skin reaction on the eyelids; conjunctivitis; pseudopemphigoid of the ocular conjunctiva.

Respiratory, Thoracic and Mediastinal Disorders: Asthma and exacerbation of asthma; dyspnea Gastrointestinal Disorders: Nausea; vomiting Skin and Subcutaneous Tissue Disorders: Pruritis Infections and Infestations: Herpes keratitis Cardiac Disorders: Angina; palpitations; angina unstable General Disorders and Administration Site Conditions: Chest pain

Xalatan

Indications

Contraindications

Warnings and precautions

5.1Pigmentation

5.2Eyelash Changes

At a glance

Two medicines in one question?

Xalatan

Indications

Contraindications

Warnings and precautions

5.1Pigmentation

5.2Eyelash Changes

At a glance

Two medicines in one question?

5.3Intraocular Inflammation

5.4Macular Edema

5.5Herpetic Keratitis Reactivation

5.6Bacterial Keratitis

5.7Contact Lens Use

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information