Skip to Content

Latanoprost (Ophthalmic)


VA CLASSIFICATION
Primary: OP116

Commonly used brand name(s): Xalatan.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiglaucoma agent (ophthalmic)—

antihypertensive, ocular—

Indications

Accepted

Glaucoma, open-angle (treatment) or
Hypertension, ocular (treatment)—Latanoprost is indicated in the treatment of open-angle glaucoma or ocular hypertension in patients who are intolerant of other intraocular pressure (IOP)–lowering medications or insufficiently responsive (i.e., failed to achieve target IOP after multiple measurements over time) to another IOP-lowering medication {01}. Latanoprost may be used alone or in combination with other antiglaucoma agents {01}.

Acceptance not established
There is limited experience with latanoprost in the treatment of angle-closure, inflammatory, or neovascular glaucoma {01} .


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Latanoprost is a prostaglandin F 2-alpha analog {01}.
Molecular weight—
    432.58 {01}


pH
    Approximately 6.7 {01}.

Mechanism of action/Effect:

Latanoprost is a prostaglandin F 2-alpha analog {01}. It is believed to reduce intraocular pressure by increasing the outflow of aqueous humor {01}. Studies suggest that the main mechanism of action is increased uveoscleral outflow {01}.

Absorption:

Latanoprost is an isopropyl ester prodrug. It is absorbed into the cornea, where it is hydrolyzed by esterases to latanoprost acid, which is biologically active {01}.

Distribution:

Vol D—0.16 ± 0.02 L per kg (L/kg) {01}. Latanoprost acid has been measured in aqueous humor during the first 4 hours and in plasma only during the first hour, following ophthalmic administration {01}.

Biotransformation:

Latanoprost is an isopropyl ester prodrug. It is hydrolyzed by esterases in the cornea to latanoprost acid, which is biologically active {01}. The portion of the latanoprost acid that reaches the systemic circulation is metabolized primarily by the liver to 1,2-dinor and 1,2,3,4-tetranor metabolites by fatty acid beta-oxidation {01}.

Half-life:

The elimination of latanoprost acid from plasma is rapid (half-life 17 minutes) after either ophthalmic or intravenous administration {01}.

Onset of action:

Approximately 3 to 4 hours after administration {01}.

Time to peak concentration:

Peak concentration in the aqueous humor is reached approximately 2 hours after ophthalmic administration {01}.

Time to peak effect:

8 to 12 hours after administration {01}.

Elimination:
    Metabolites are eliminated mainly via the kidneys {01}. Approximately 88 or 98% of the administered dose can be recovered in the urine after ophthalmic or intravenous dosing, respectively {01}.


Precautions to Consider

Carcinogenicity

Latanoprost was not carcinogenic in mice and rats that were administered oral doses of up to 170 mcg per kg of body weight (mcg/kg) a day (approximately 2800 times the recommended maximum human dose) for up to 20 and 24 months, respectively {01}.

Mutagenicity

Latanoprost was not mutagenic in bacteria, mouse lymphoma, or mouse micronucleus tests {01}. In vitro and in vivo studies of unscheduled DNA synthesis in rats were negative {01}. However, in vitro tests using human lymphocytes showed chromosome aberrations {01}.

Pregnancy/Reproduction
Fertility—
In animal studies, latanoprost was not found to have any effect on male or female fertility {01}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done {01}. Risk-benefit should be carefully considered when latanoprost is used during pregnancy {01}.

In rabbits, 4 of 16 dams had no viable fetuses after receiving a dose approximately 80 times the maximum recommended human dose {01}. The highest nonembryocidal dose in rabbits was approximately 15 times the maximum recommended human dose {01}.

FDA Pregnancy Category C {01}.

Breast-feeding

It is not known whether latanoprost or its metabolites are distributed into breast milk {01}. Caution should be exercised when latanoprost is administered to nursing women {01}.

Pediatrics

Appropriate studies on the relationship of age to the effects of latanoprost have not been performed in the pediatric population. Safety and efficacy have not been established {01}.


Geriatrics


No information is available on the relationship of age to the effects of latanoprost in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Thimerosal-containing ophthalmic medications    (precipitation occurs when latanoprost is applied concurrently with thimerosal-containing ophthalmic medications; an interval of at least 5 minutes should elapse between applications of these medications {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Hypersensitivity to latanoprost {01}
» Hypersensitivity to benzalkonium chloride {01}
Risk-benefit should be considered when the following medical problems exist
» Aphakia or
» Macular edema, including cystoid macular edema, risk factors for or
» Pseudophakia    (macular edema, including cystoid macular edema, has been reported during treatment with latanoprost, mainly in patients with aphakia, in patients with pseudophakia who have a torn posterior lens capsule, or in patients with known risk factors for macular edema; latanoprost should be used with caution in these patients {01})


Hepatic function impairment or
Renal function impairment    (studies have not been done in patients with hepatic or renal function impairment; therefore, caution should be used when administering latanoprost in these patients {01})


Iritis or
Uveitis    (latanoprost should be used with caution in patients with active intraocular inflammation [iritis/uveitis] {01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Ophthalmic examinations    (patients should be examined regularly and, depending on the clinical situation, treatment may be stopped if increased brown pigmentation of iris occurs {01})




Side/Adverse Effects

Note: Changes in pigmented tissues may occur with use of latanoprost {01}. Latanoprost may gradually change eye color by increasing the number of melanosomes (pigment granules) in the melanocytes, thereby increasing the amount of brown pigment in the iris {01} . The mechanism of this increased pigmentation is probably not associated with proliferation of the melanocytes, but rather with stimulation of melanin production within the melanocytes of the iris stroma {01}. The long-term effects on the melanocytes, the consequences of potential injury to the melanocytes, and the possibility of deposition of pigment granules to other areas of the eye are not known {01} . The change in iris color occurs slowly and may not be noticeable for several months to years {01} . Patients with mixed-color irides, such as blue-brown, gray-brown, green-brown, or yellow-brown, appear to be predisposed to the iris pigmentation changes {01} . In addition, latanoprost has been reported to cause increased pigmentation of the periorbital tissue (eyelid) {01}. Also, latanoprost may gradually change eyelashes {01}. The changes to the lashes include increased length, thickness, pigmentation, and the number of lashes. {01} Patients should be advised of all the effects listed above and informed that if only one eye is treated with the medication, only one eye will be affected (heterochromia between the eyes) {01} . The changes in pigmentation and eyelash growth may be permanent {01} .
Macular edema, including cystoid macular edema, has been reported during treatment with latanoprost, mainly in patients with aphakia, in patients with pseudophakia who have a torn posterior lens capsule, or in patients with known risk factors for macular edema. It is recommended that latanoprost be used with caution in these patients {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Blurred vision {01}
    
increased length, thickness, pigmentation, and number of eyelashes {01} (longer, thicker, and darker eyelashes)
    
increased pigmentation of iris {01} (increase in brown color in colored part of eye)
    
increased pigmentation of periorbital tissue {01} (darkening of eyelid skin color)
    
punctate epithelial keratopathy {01} (blurred vision, eye irritation, or tearing)

Incidence less frequent
    
Allergic skin reaction {01} ( skin rash)
    
angina pectoris {01} or other chest pain {01}
    
eye pain {01}
    
eyelid crusting, redness, swelling, discomfort, or pain {01}
    
pain in muscles, joints, or back {01}
    
upper respiratory tract infection, cold, or flu {01} (cold or flu symptoms)

Incidence rare
    
Asthma
exacerbation of asthma (cough; difficulty breathing; noisy breathing; shortness of breath; tightness in chest; wheezing){01}
    
conjunctivitis {01} (redness of eye or inside of eyelid)
    
corneal edema and erosions (swelling of the eye){01}
    
diplopia {01} (double vision)
    
discharge from the eye {01}
    
dyspnea (shortness of breath; difficult or labored breathing ; tightness in chest; wheezing){01}
    
intraocular inflammation, such as iritis or uveitis {01} (eye pain, tearing, sensitivity of eye to light, redness of eye, or blurred vision or other change in vision)
    
macular edema, including cystoid macular edema {01} (blurred vision or other change in vision)
    
toxic epidermal necrolysis {01} (fever; pain in muscles; skin rash; sore throat)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Burning of eye {01}
    
conjunctival hyperemia {01} ( redness of eye or inside of eyelid)
    
foreign body sensation {01} (feeling of something in eye)
    
itching of eye {01}
    
stinging of eye {01}

Incidence less frequent
    
Dryness of eye {01}
    
photophobia {01} (increased sensitivity of eyes to light)
    
tearing {01}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
Other than ocular irritation or conjunctival or episcleral hyperemia, the ocular effects of high doses of latanoprost are not known {01}.

Following intravenous doses of 3 mcg per kg of body weight (mcg/kg) in healthy volunteers (which produced mean plasma concentrations that were 200 times the mean plasma concentrations produced by the usual clinical dose), no adverse reactions were observed {01}. However, intravenous doses of 5.5 to 10 mcg/kg caused abdominal pain, dizziness, fatigue, hot flushes, nausea, and sweating {01}.

Treatment of overdose
Treatment of overdose should be symptomatic {01}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Latanoprost (Ophthalmic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to latanoprost, benzalkonium chloride, or any other ingredient in the product {01}



Mutagenicity—
In vitro tests using human lymphocytes showed chromosome aberrations {01}





Breast-feeding—Caution should be exercised when latanoprost is administered to nursing women, since it is not known whether latanoprost or its metabolites are distributed into breast milk {01}
Other medications, especially thimerosal-containing ophthalmic medications
Other medical problems, especially aphakia; macular edema, including cystoid macular edema, risk factors for; and pseudophakia

Proper use of this medication
» Using medication only as directed; not using more of it or using it more often than directed; to do so may increase absorption and the chance of side effects

If physician ordered two different eye drops to be used together, waiting at least 5 minutes between applications of medications to prevent second medication from “washing out” the first one

» Importance of regular visits to physician to check eye pressure during therapy

Removing contact lenses prior to administration of latanoprost; reinserting lenses, if desired, at least 15 minutes after administration

» Proper administration technique; preventing contamination; not touching applicator tip to any surface; keeping container tightly closed

» Proper dosing
Missed dose: Applying as soon as possible; not applying if not remembered until next day; applying regularly scheduled dose

» Proper storage

Precautions while using this medication
» Possibility of iris of eye becoming more brown in color; change in color of iris is usually noticeable within several months to years while using medication; in addition, possibility of the darkening of eyelid skin color; also, possibility of increased length, thickness, pigmentation, and the number of lashes; iris, eyelid, and lash pigmentation and other lash changes may be permanent even if medication is stopped; the color and lash changes will occur only to the eye being treated; if only one eye is treated, there is a possibility of having differently colored eyes and differently appearing eyelashes

Possibility of medication causing eyes to become more sensitive to light than they are normally; wearing sunglasses and avoiding too much exposure to bright light may help lessen discomfort


Side/adverse effects
Signs of potential side effects, especially blurred vision; increased length, thickness, pigmentation, and number of eyelashes; increased pigmentation of iris; increased pigmentation of periorbital tissue; punctate epithelial keratopathy; allergic skin reaction; angina pectoris or other chest pain; eye pain; eyelid crusting, redness, swelling, discomfort, or pain; pain in muscles, joints, or back; upper respiratory tract infection, cold, or flu; asthma or exacerbation of asthma; conjunctivitis; corneal edema and erosions; diplopia; discharge from the eye; dyspnea; intraocular inflammation, such as iritis or uveitis; macular edema, including cystoid macular edema; toxic epidermal necrolysis


General Dosing Information
Latanoprost may be used alone or in combination with other antiglaucoma agents {01}. If more than one ophthalmic medication is used, the medications should be administered at least 5 minutes apart {01}.

Latanoprost contains benzalkonium chloride, which may be absorbed by contact lenses {01}. Contact lenses should be removed prior to administration of latanoprost {01}. Lenses may be reinserted 15 minutes after administration {01}.

Once-daily dosing of latanoprost should not be exceeded {01}. More frequent administration may decrease the intraocular pressure–lowering effect of the medication {01}.


Ophthalmic Dosage Forms

LATANOPROST OPHTHALMIC SOLUTION

Usual adult and adolescent dose
Antiglaucoma agent (ophthalmic)
Antihypertensive, ocular
Topical, to the conjunctiva, 1 drop in the affected eye(s) once a day in the evening {01}.


Usual adult prescribing limits
No more than one dose per day {01}.

Usual pediatric dose
Safety and efficacy have not been established {01}.

Strength(s) usually available
U.S.—


0.005% (50 mcg per mL) (Rx) [Xalatan{01} (benzalkonium chloride 0.02%) (sodium chloride) (sodium dihydrogen phosphate monohydrate) (disodium hydrogen phosphate anhydrous) (water for injection)]

Note: One drop contains approximately 1.5 mcg of latanoprost {01}.


Packaging and storage:
Store the unopened bottle between 2 and 8 °C (36 and 46 °F) {01}, unless otherwise specified by manufacturer. Protect from light {01}.

Stability:
Once the container has been opened, the medication may be stored at room temperature (up to 25 °C [77 °F]) for up to 6 weeks before discarding {01}.

Incompatibilities:
A precipitation occurs when latanoprost is applied concurrently with thimerosal-containing ophthalmic medications; an interval of at least 5 minutes should elapse between applications of these medications {01}.

Auxiliary labeling:
   • For the eye.
   • Keep container tightly closed.



Developed: 06/12/1997
Revised: 04/18/2000



References
  1. Product Information: Xalatan®, latanoprost ophthalmic solution. Pharmacia & Upjohn Company, Kalamazoo, MI (PI revised 12/99) reviewed 4/2000.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Hide