Overview:
Latanoprost belongs to the class of prostaglandin F2 alpha analogs. Due to its efficiency in lowering IOP, easy once-daily dosing, and generally good safety profile, prostaglandins are frequently chosen as the primary treatment for glaucoma. The United States Food and Drug Association (FDA) approved the fixed-dose combination of Netarsudil/Latanoprost in March 2019 to treat open-angle glaucoma and ocular hypertension. This formulation combines the benefits of both medications to provide a comprehensive approach to managing these conditions. By staying informed about Latanoprost's properties and collaborating effectively, the healthcare team can ensure the best possible outcomes for patients with ocular hypertension or open-angle glaucoma.
How Does Latanoprost Work?
Latanoprost, a prostaglandin analog, reduces intraocular pressure (IOP) in the eyes by enhancing aqueous humor outflow through the uveoscleral pathway and reducing resistance in the trabecular meshwork. This dual action helps regulate IOP levels, making it an effective treatment for ocular hypertension and open-angle glaucoma. Latanoprost protects the optic nerve and prevents vision loss associated with elevated IOP in these conditions by promoting fluid drainage and relaxing ocular muscles.
Uses:
Latanoprost is primarily used to treat conditions associated with elevated intraocular pressure (IOP) in the eyes. It is commonly prescribed for the following purposes:
Open-angle Glaucoma: Latanoprost is used to lower IOP in individuals diagnosed with open-angle glaucoma, the most common form of glaucoma. Open-angle glaucoma is characterized by the drainage angle between the iris and cornea remaining open. Still, inadequate fluid outflow results in elevated intraocular pressure (IOP) and the possibility of optic nerve damage.
Ocular Hypertension: Elevated IOP without optic nerve injury or changes to the visual field is referred to as ocular hypertension, which can eventually raise the chance of developing glaucoma. Latanoprost may be prescribed to individuals with ocular hypertension to lower IOP and reduce the risk of glaucoma progression.
Dosage:
Latanoprost is available in two dosage forms and strengths. The first is an ophthalmic solution containing 0.005 % (2.5 mL). The second option is a preservative-free ophthalmic solution with 0.005 % Latanoprost, supplied in single-dose containers.
Warning:
Macular Edema - Warnings and precautions for using this medication include the risk of macular edema, including cystoid macular edema. Additionally, caution is advised in cases of active intraocular inflammation (e.g., iritis/uveitis), as this medication may exacerbate inflammation and is generally not recommended for use in such patients.
Herpetic Keratitis - This medication should be provided with caution to patients who have a history of herpetic keratitis, and it should be avoided in situations of active herpes simplex keratitis since it may reactivate the infection and exacerbate inflammation. When applying the medication, contact lenses should be removed, and they can be reinserted at least 15 minutes later to prevent any potential interactions or adverse effects.
Bacterial Keratitis - There is a risk of bacterial keratitis resulting from inadvertent contamination of multidose ophthalmic solutions, so proper hygiene and medication handling are essential.
Gradual Changes - This medication may cause gradual changes in eyelashes and vellus hair, such as increased thickness, length, pigmentation, number of lashes, or misdirected growth of eyelashes, which are usually reversible upon discontinuation. Long-term use of this medication may permanently change eyelid skin, the brown pigmentation of the iris, and eyelashes. Patients should be informed about the possibility of increased pigmentation, and those who develop noticeably increased iris pigmentation should continue treatment and undergo regular examinations.
For Patients:
Learn About Open-angle Glaucoma:
What Is Open-Angle Glaucoma?
Increased intraocular pressure can harm the optic nerve and cause vision loss in a group of disorders known as glaucoma. However, not all glaucoma cases are linked to elevated intraocular pressure; some, known as normal pressure glaucoma, exhibit similar optic nerve and visual field damage. Glaucoma is further classified into open-angle and closed-angle types, each having primary or secondary causes. It is distinguished by an open anterior chamber angle, particular changes in the optic nerve head, and a progressive loss of peripheral vision followed by a loss of central vision that results in blindness. While intraocular pressure (IOP) is a significant risk factor for OAG, it is not always present, and some individuals with chronically elevated IOP may remain asymptomatic. Asymmetry in the disease's presentation may occur depending on the underlying cause. It is vital to understand that elevated intraocular pressure is not mandatory for glaucomatous optic nerve damage, and the correlation between IOP and the disease is not absolute.
What Causes Open-Angle Glaucoma?
To comprehend the cause of open-angle glaucoma, it is essential to grasp the process of aqueous humor formation and drainage. The ciliary body in the eye's posterior chamber continuously produces aqueous humor, which then flows into the anterior chamber. Most of its drainage occurs through the trabecular meshwork, while a smaller portion exits through the uveoscleral pathway. Although the drainage angle between the iris and cornea is open, there is increased resistance to fluid drainage within the trabecular meshwork in primary open-angle glaucoma. This blockage causes a gradual rise in eye pressure, leading to optic nerve damage and gradual visual loss. Secondary open-angle glaucoma may have various underlying causes but is less common than primary open-angle glaucoma.
How to Treat Open-Angle Glaucoma?
The primary objectives in the treatment of open-angle glaucoma are twofold:
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To prevent the progression of optic nerve head changes.
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To avoid the deterioration of the visual field.
The concept of target IOP was introduced to achieve these goals. Target IOP represents the upper limit of intraocular pressure (IOP) below which it is estimated that the visual field and the parameters related to the optic nerve head and retinal nerve fiber layer (RNFL) will remain stable, and the patient's quality of life will not be compromised. By maintaining the IOP below the target IOP, visual impairment and the risk of disease progression can be minimized.
Learn More About Latanoprost:
Before Starting Latanoprost:
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Before using Latanoprost, inform the doctor and pharmacist about any allergies to Latanoprost or other drugs.
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Provide details about prescription and nonprescription medications being taken, including vitamins.
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Notify the doctor about any eye inflammation and liver or kidney disease history.
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In the case of pregnancy, planning to become pregnant, or breastfeeding, inform the doctor.
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If pregnancy occurs while using Latanoprost, contact the doctor promptly.
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For scheduled surgeries, including dental procedures, inform the doctor or dentist about Latanoprost.
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Adequate communication with healthcare providers ensures safety and helps manage potential interactions or complications.
How to Use Latanoprost?
Latanoprost eye drops are used as prescribed by the doctor. Typically, one drop is applied to the affected eye(s) once daily in the evening. If using other topical eye medications with Latanoprost, ensure a minimum of five minutes between each medication administration. Pay close attention to the directions on the prescription label, and if anything is unclear, ask the doctor or pharmacist to explain it.. Use Latanoprost precisely as directed, neither more nor less, and not more frequently than the doctor prescribes.
To apply the eye drops correctly, follow these steps:
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Wash hands thoroughly with soap and water.
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Use a mirror or have someone else administer the drops to the eye.
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Ensure the dropper's end is not chipped or cracked.
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Avert putting the eye or any other surface in contact with the dropper.
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Keep the dropper tip down at all times to prevent contamination of the remaining contents in the bottle.
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Lie down or tilt the head back.
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Hold the bottle, placing the dropper as close to the eyelid as possible without touching it.
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Use the remaining fingers to brace against the cheek or nose.
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Pull down the lower eyelid to form a pocket with the opposite hand's index finger.
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Administer the prescribed number of drops into the eye. Avoid placing the drops directly on the eyeball, as it may cause stinging.
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Close the eye and gently press on the lower lid with the finger for two to three minutes to ensure the medication stays in the eye. Do not blink.
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Immediately replace and tighten the cap without wiping or rinsing it off.
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Use a clean tissue to wipe off any excess liquid from the cheek. Rewash hands.
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If glaucoma symptoms persist, such as eye pain or blurred vision, after using the medication for a few days, contact the doctor for further guidance.
Look out for the Side Effects:
The main adverse effects of Latanoprost encompass eyelid edema, blurred vision, dry eyes, itching, redness, and changes in the growth and pigmentation of the eyelashes, iris, and eyelids.
Hypertrichosis: An increase in the thickness, length, and number of eyelashes is observed with Latanoprost use. While some patients find this change beneficial from a cosmetic perspective, unilateral occurrence can be undesirable. The eyelash changes are typically reversible upon discontinuation of the drug due to the stimulation of the hair cycle's growth phase.
Conjunctival Hyperemia: This side effect is commonly observed in 5 % to 15 % of patients, more frequently than in those treated with Timolol. Latanoprost with preservatives, such as benzalkonium chloride, may reduce goblet cell density. The redness typically appears within two to three days of starting the topical treatment, diminishes within a month, and is generally mild with continued use.
Intraocular Inflammation: Latanoprost may worsen intraocular inflammation (uveitis) and should be avoided in cases of actively inflamed eyes.
Pigmentation: Latanoprost causes increased melanin in the melanocytes, resulting in pigmentation changes. The increase in iris pigmentation usually occurs within one year of therapy and continues as long as the drug is used. Patients should be informed about the possibility of iris color changes, which may be more evident if Latanoprost is used in only one eye. Iris pigmentation is more common in light-colored eyes but may also occur in dark or brown eyes. Darkening of the iris may occur in up to 10 % of cases. The pigmentation of periocular tissue can be reduced by removing excess latanoprost drops from around the eye.
Macular Edema: Latanoprost may initiate or exacerbate macular edema, including cystoid macular edema (CME). Patients with aphakia and pseudophakia with open posterior capsules are at higher risk of developing CME. Prostaglandin analogs (PGA) associated with CME can be managed by discontinuing the PGA. For pseudophakic CME, the most commonly used treatment strategy involves suppressing postsurgical inflammation using topical nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids, either alone or in combination.
Reactivation of Herpetic Keratitis: Latanoprost may lead to the reactivation of herpetic keratitis. Patients with active herpetic keratitis should avoid using Latanoprost. Contaminated multidose vials of Latanoprost may cause bacterial keratitis in patients with corneal epithelial defects or other corneal diseases.
Superficial Punctate Keratopathy: Latanoprost (Benzalkonium) preservative can damage the ocular surface, resulting in reduced tear break-up time and superficial punctate keratopathy. Preservative-free tafluprost has been noted to cause less ocular surface toxicity.
For Doctors
Indication:
Latanoprost ophthalmic is indicated to treat glaucoma. It is a condition characterized by increased pressure in the eye that can lead to progressive vision loss, as well as ocular hypertension, which also causes elevated eye pressure. Belonging to the prostaglandin analogs class, Latanoprost facilitates the drainage of natural eye fluids, thereby reducing the pressure within the eye.
Pharmacology:
Mechanism of Action:
Prostaglandin synthesis occurs within the cell from arachidonic acid, a 20-carbon molecule. Arachidonic acid can be metabolized into leukotrienes (LT) by lipoxygenases or converted into cyclic endoperoxides by cyclooxygenases. Eicosanoids exert their effects through various receptors, such as DP (prostaglandin D), EP (prostaglandin E), FP (prostaglandin F), IP (prostaglandin I or prostacyclin receptor), and TP (prostaglandin T). Among these receptors, the FP receptor exists in type A (full-length variant) and type B (spliced variant), both acting as G-protein coupled receptors. The FP receptors are found in multiple ocular tissues, including ciliary smooth muscles.
Latanoprost, a prostaglandin F2-alpha analog (FP receptor agonist), enhances the uveoscleral outflow of the aqueous humor. Other prostaglandin F2 alpha analogs, like Travoprost and Tafluprost, work through the exact mechanism of action. Proposed mechanisms of action include relaxation of ciliary smooth muscles, cytoskeletal alterations leading to changes in cell shape, and remodeling of the extracellular matrix of the uveoscleral pathway through increased matrix metalloproteinases. In cultured ciliary smooth muscles, PG F2 alpha and Latanoprost were observed to reduce collagen I, III, and IV, hyaluronans, fibronectin, and laminin while increasing matrix metalloproteinases 2 and 3 and plasmin. In animal models, topical PGF2 alpha reduced the expression of TIGR (trabecular meshwork inducible glucocorticoid response gene) or MYOC (myocilin).
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Absorption: Latanoprost is absorbed through the cornea, and the isopropyl ester of Latanoprost undergoes hydrolysis by the cornea to form the biologically active acid. Studies in men have shown that the peak concentration of Latanoprost in the aqueous humor is reached approximately two hours after topical administration. The aqueous humor's medication concentration peaks within two hours of using the eye drop. The drug begins to reduce intraocular pressure (IOP) after three to four hours of administration, and its maximum IOP-lowering effect is observed eight to 12 hours after use. The IOP-lowering effect lasts more than 24 hours, allowing for once-daily dosing.
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Metabolism: Latanoprost is classified as an isopropyl ester prodrug. Within the cornea, esterases facilitate the prodrug hydrolysis, converting it into the biologically active acid form. Once in the systemic circulation, the liver metabolizes Latanoprost into 1,2-dinner and 1,2,3,4-tetranor compounds through fatty acid β-oxidation.
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Elimination: Latanoprost is swiftly eliminated from human plasma with a half-life (t1/2) of 17 minutes after intravenous and topical administration. The systemic clearance rate is seven mL/min/kg. After undergoing hepatic β-oxidation, the metabolites are primarily excreted through the kidneys.
Dosage and Administration:
Latanoprost is available as a 0.005 % colorless ophthalmic solution. Unopened bottles should be stored under refrigeration between two to eight degrees Celsius (36 to 46 degrees Fahrenheit), and during shipping, they can be exposed to temperatures up to 40 degrees Celsius (104 degrees Fahrenheit) for a maximum of eight days. The bottle can be kept open for six weeks at a temperature of up to 25 degrees Celsius (77 degrees Fahrenheit). Using the medication more than once daily may reduce its intraocular pressure (IOP) lowering effect or cause a paradoxical IOP rise, likely due to subsensitivity at the FP receptors. Latanoprost can be used with other antiglaucoma agents, but there should be a minimum gap of five minutes between administering different eye drops. Contact lenses should not be reinserted within 15 minutes after applying the eye drop. The average IOP reduction with Latanoprost is approximately 30 % to 35 %. Clinical studies have shown that once-daily Latanoprost effectively reduces IOP either alone or when combined with a twice-daily dose of Timolol. In combination with Timolol, the dosage remains once daily.
Contraindications:
As per the product labeling, Latanoprost should not be used in patients with a known hypersensitivity to the drug or its components. The components of the eye drop formulation include the active ingredient Latanoprost and inactive ingredients such as benzalkonium chloride (preservative), monobasic sodium phosphate, sodium chloride, and dibasic sodium phosphate.
Drug Interactions:
Latanoprost can potentially interact with other medications, leading to changes in its efficacy, safety, or both. Some notable drug interactions of Latanoprost include:
Other Prostaglandin Analogs: Concurrent use of multiple prostaglandin analogs for glaucoma treatment may result in reduced effectiveness or an increased risk of adverse effects. Avoid using more than one prostaglandin analog at the same time.
Beta-Blockers: When Latanoprost is used with beta-blockers, it may further reduce intraocular pressure. However, the combination should be used cautiously, especially in patients with certain heart conditions or respiratory disorders.
Alpha-Adrenergic Agonists: Combination therapy with Latanoprost and alpha-adrenergic agonists may provide additive effects in reducing intraocular pressure. However, careful monitoring is necessary, as both medications can cause systemic side effects like changes in blood pressure and heart rate.
Carbonic Anhydrase Inhibitors: Co-administration of carbonic anhydrase inhibitors and Latanoprost may lead to additional intraocular pressure reduction. However, these combinations may also increase the risk of adverse effects on ocular surfaces.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs): The concomitant use of Latanoprost with NSAIDs may reduce the intraocular pressure-lowering effect of Latanoprost.
Systemic Prostaglandin Inhibitors: Medications that inhibit the synthesis of prostaglandins, such as NSAIDs and certain pain relievers, may also reduce the effectiveness of Latanoprost.
CYP2D6 Inhibitors: Latanoprost's metabolism may be affected by medications that block CYP2D6, changing the amount of the medicine in the body.
Latanoprost Preservative-Free Formulation: The preservative-free formulation of Latanoprost may be preferred in patients with sensitivity or allergies to preservatives commonly found in eye drops.
Other Specifications:
- Patients With Renal Impairment: The manufacturer's labeling does not include guidance on dosage adjustments for patients with renal impairment.
- Pregnancy Considerations: Prostaglandins, including Latanoprost, can stimulate smooth muscle in the uterus, leading to contractions. When Latanoprost was given intravenously to pregnant rabbits and rats throughout organogenesis at clinically relevant doses, animal studies demonstrated an increased risk of termination or preterm delivery. Adequate and well-controlled studies regarding Latanoprost ophthalmic solution in pregnant women are lacking, and the associated risks for the fetus are uncertain. Due to the theoretical risk of increased uterine tone and premature labor, other medication classes should be chosen to treat glaucoma during pregnancy. Latanoprost is categorized as FDA Category C for pregnancy.
- Patients With Hepatic Impairment: The manufacturer's labeling does not provide specific information about dosage adjustments for patients with hepatic impairment.
- Breastfeeding Considerations: Limited information is available on the use of Latanoprost during breastfeeding. The drug has a short half-life, making it unlikely to reach significant levels in breast milk and cause adverse effects in breastfed infants. To minimize the amount of drug reaching breast milk after using eye drops, patients should be advised to apply pressure to the tear duct at the corner of the eye for one minute or more and then remove any excess solution with an absorbent tissue.
