CLASSES

Ophthalmic Prostaglandins including Analogs and Receptor Agonists

DEA CLASS

Rx

DESCRIPTION

Ophthalmic analog of prostaglandin F2-alpha
Used for increased intraocular pressure in patients with open-angle glaucoma or ocular hypertension
Associated with increased pigmentation of iris, eyelid, and eyelashes

COMMON BRAND NAMES

Xalatan, Xelpros

HOW SUPPLIED

Latanoprost/Xalatan Ophthalmic Sol: 0.005%
Xelpros Ophthalmic Emulsion: 0.005%

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

1 drop/day per affected eye.

1 drop/day per affected eye.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Latanoprost should be used with caution in patients with hepatic impairment; data are lacking in these patients.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. Latanoprost should be used with caution in patients with renal impairment; data are lacking in these patients.
 
Intermittent hemodialysis
No dosage adjustment is needed.

ADMINISTRATION

Instruct the patient on proper instillation of the eye solution.
Wash hands before and after use.
Remove contact lenses before instilling ophthalmic drops. Lenses may be reinserted 15 minutes after drug administration.
Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch and gently close eyes for 1 to 2 minutes. Do not blink.
Care should be taken to avoid contamination. Do not touch the tip of the dropper to the eye, fingertips, or other surfaces.
Latanoprost may be used concomitantly with other ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart. In vitro studies have shown precipitation occurs when ophthalmic drugs that contain thimerosal are mixed with latanoprost.[63552]
A delivery aid (i.e., Xal-Ease) is available for administering the ophthalmic solution.[41692]

STORAGE

Xalatan:
- During shipment, the product may be maintained at temperatures up to 104 degrees F for a period not exceeding 8 days
- Opened container can be stored for up to 6 weeks at 77 degrees F
- Protect from light
- Store unopened containers in refrigerator (36 to 46 degrees F)
Xelpros:
- During shipment, the product may be maintained at temperatures up to 104 degrees F for a period not exceeding 8 days
- Protect from light
- Store between 36 to 77 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Latanoprost should not be used in patients with closed-angle glaucoma, or inflammatory or neovascular glaucoma. There is limited experience with latanoprost in these patients.

Latanoprost should be used with caution in patients with aphakia, pseudophakic patients with a torn posterior lens capsule, and patients with known risk factors for macular edema. Macular edema, including cystoid macular edema, has been reported during treatment with this drug.

Recipients of latanoprost may experience a gradual increase in pigmentation (i.e., brown coloration) of the iris and periorbital tissue (eyelids), which may not be noticeable for several months to years. Patients who develop increased pigmentation may continue to receive treatment; however, these patients should be examined regularly as they may develop photophobia or be more sensitive to sunlight (UV) exposure. After discontinuing latanoprost, the change in iris color is likely to be permanent, while the pigmentation change in the periorbital tissue may be reversible in some patients. Eyelash changes (i.e., increased length, thickness, pigmentation, the number of lashes or hairs, and misdirected growth of eyelashes) has also been associated with the use of latanoprost. Eyelash changes are usually reversible upon treatment discontinuation. Inform drug recipients of the possibility of iridal and eyelid discoloration, and of the potential for eyelash changes.[41692] [63552]

Latanoprost should be used with caution in patients with active intraocular inflammation (e.g., iritis, uveitis). Use of latanoprost in these patient may exacerbate inflammation.[41692] [63552]

Instruct drug recipients to remove contact lenses before instilling latanoprost ophthalmic drops. Lenses may be reinserted 15 minutes after drug administration. The ophthalmic solution is formulated with the preservative benzalkonium chloride, which may be absorbed by soft contact lenses.[41692] [63552]

The use of multiple dose containers of ophthalmic products has been associated with bacterial keratitis. Inadvertent contamination of the latanoprost containers may increase the risk of infection in ocular surgery patients, or in patients who develop an ocular infection or ocular trauma, including corneal abrasion. If there is any damage to the ocular epithelial surface, latanoprost should be used with caution. Reactivation of herpes simplex keratitis has been reported during latanoprost therapy. Use caution in patients with a history of herpetic keratitis; avoid use in patients with active herpes simplex keratitis due to the potential for exacerbation of inflammation.

No adequate and well-controlled studies have been conducted to evaluate the use of latanoprost during human pregnancy. In animal studies involving rats and rabbits, the administration of intravenous latanoprost (at clinically relevant doses) throughout the period of organogenesis resulted in malformations, embryofetal lethality, and spontaneous abortion. In rabbits, intravenous latanoprost given on gestation days 6 through 18 resulted in post-implantation loss due to late resorption [1.3-times maximum recommended human ophthalmic dose (RHOD)], spina bifida and abortion (32-times RHOD), and total litter loss due to early resorption (324-times RHOD). In rats, intravenous latanoprost given on gestation days 6 through 15 resulted in cleft palate (3.2-times RHOD), brain porencephalic cysts (162-times RHOD), and skeletal anomalies (811-times RHOD). In an observational study involving 11 pregnant women taking latanoprost for glaucoma, there were no congenital anomalies in 9 cases with complete follow-up, 1 case was lost to follow-up, and 1 case experienced an early spontaneous abortion. Limited experience in human pregnancy has not resulted in clinically significant risk to the fetus. A minimal amount of drug reaches systemic circulation after ophthalmic administration, suggesting exposure of the drug to the fetus is low.

According to the manufacturer, it is not known whether latanoprost or its metabolites are excreted in breast milk. Because systemic plasma concentrations of latanoprost are low and the half-life is short after ophthalmic administration, clinically significant amounts of the drug would not be expected to be excreted in breast-milk. To further minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. According to the manufacturer, caution should be exercised when latanoprost is administered during breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

Safety and efficacy of latanoprost have not been established in the pediatric population (i.e., neonates, infants, children, or adolescents).

Latanoprost should be used cautiously in patients with renal disease (e.g., renal failure, renal impairment) or hepatic disease. There have been no studies on safe use in these patients.

ADVERSE REACTIONS

keratitis / Delayed / 1.0-10.0
visual impairment / Early / 4.0-8.0
corneal erosion / Delayed / Incidence not known
uveitis / Delayed / Incidence not known
macular edema / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known

conjunctival hyperemia / Early / 8.0-15.0
blurred vision / Early / 4.0-8.0
blepharitis / Early / 1.0-3.0
photophobia / Early / 2.0-2.0
ocular inflammation / Early / Incidence not known
corneal edema / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known
iritis / Delayed / Incidence not known
dyspnea / Early / Incidence not known
angina / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
palpitations / Early / Incidence not known

ocular pain / Early / 3.0-55.0
ocular irritation / Rapid / 7.0-55.0
foreign body sensation / Rapid / 2.0-13.0
ocular discharge / Delayed / 12.0-12.0
ocular pruritus / Rapid / 5.0-8.0
iridal discoloration / Delayed / 7.0-7.0
lacrimation / Early / 4.0-4.0
blepharedema / Early / 1.0-3.0
xerophthalmia / Early / 3.0-3.0
infection / Delayed / 3.0-3.0
back pain / Delayed / 1.0-1.0
myalgia / Early / 1.0-1.0
musculoskeletal pain / Early / 1.0-1.0
arthralgia / Delayed / 1.0-1.0
rash / Early / 1.0-1.0
skin hyperpigmentation / Delayed / Incidence not known
hypertrichosis / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known
influenza / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
dizziness / Early / Incidence not known
headache / Early / Incidence not known
vomiting / Early / Incidence not known
nausea / Early / Incidence not known

DRUG INTERACTIONS

There are no drug interactions associated with Latanoprost products.

PREGNANCY AND LACTATION

No adequate and well-controlled studies have been conducted to evaluate the use of latanoprost during human pregnancy. In animal studies involving rats and rabbits, the administration of intravenous latanoprost (at clinically relevant doses) throughout the period of organogenesis resulted in malformations, embryofetal lethality, and spontaneous abortion. In rabbits, intravenous latanoprost given on gestation days 6 through 18 resulted in post-implantation loss due to late resorption [1.3-times maximum recommended human ophthalmic dose (RHOD)], spina bifida and abortion (32-times RHOD), and total litter loss due to early resorption (324-times RHOD). In rats, intravenous latanoprost given on gestation days 6 through 15 resulted in cleft palate (3.2-times RHOD), brain porencephalic cysts (162-times RHOD), and skeletal anomalies (811-times RHOD). In an observational study involving 11 pregnant women taking latanoprost for glaucoma, there were no congenital anomalies in 9 cases with complete follow-up, 1 case was lost to follow-up, and 1 case experienced an early spontaneous abortion. Limited experience in human pregnancy has not resulted in clinically significant risk to the fetus. A minimal amount of drug reaches systemic circulation after ophthalmic administration, suggesting exposure of the drug to the fetus is low.

According to the manufacturer, it is not known whether latanoprost or its metabolites are excreted in breast milk. Because systemic plasma concentrations of latanoprost are low and the half-life is short after ophthalmic administration, clinically significant amounts of the drug would not be expected to be excreted in breast-milk. To further minimize the amount of drug that reaches the systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after ophthalmic administration. According to the manufacturer, caution should be exercised when latanoprost is administered during breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

MECHANISM OF ACTION

Latanoprost is a selective agonist at a subtype of prostaglandin receptors known as the FP receptor. By acting on the FP receptor, latanoprost increases the outflow of aqueous humor thereby reducing intraocular pressure. According to the manufacturer, studies in both animals and man suggest that increased uveoscleral outflow is the primary mechanism of action.[41692] [63552]

PHARMACOKINETICS

Latanoprost is administered topically to the eye as an isopropyl ester prodrug. Once in systemic circulation, the biologically active latanoprost acid is primarily metabolized by the liver to the 1,2-dinor and 1,2,3,4- tetranor metabolites via fatty acid beta-oxidation with an elimination half-life of 17 minutes. The metabolites are mainly eliminated by the kidneys, with 88% of the topically administered dose being recovered in the urine.[41692] [63552]
Affected cytochrome P450 isoenzymes: none