Loteprednol etabonate is an ophthalmic corticosteroid which is an analog of prednisolone, containing a metabolically labile ester in the 17-beta position. Loteprednol was designed to be active at the ocular delivery site with minimal systemic absorption. After application to the eye, loteprednol undergoes a predictable, one-step transformation by hydrolysis to an inactive metabolite. Since loteprednol is metabolized by enzymes in the eye, systemic adverse effects are minimized. Loteprednol has a lower potential to increase intraocular pressure compared to other ophthalmic steroids such as prednisolone and dexamethasone. Loteprednol has been shown to decrease postoperative anterior chamber inflammation in patients who have undergone cataract surgery with intraocular lens implantation. Loteprednol is an alternative corticosteroid for the treatment of uveitis with less potential to cause ocular hypertension but should not be used if more potent corticosteroids are needed as loteprednol 0.5% is less effective than prednisolone 1% in the treatment of acute anterior uveitis. Loteprednol was first approved by the FDA in March 1998. Alrex (0.2% loteprednol ophthalmic suspension) is indicated to relieve seasonal allergic conjunctivitis including bulbar conjunctival injection and itching. Lotemax (0.5% loteprednol ophthalmic suspension) is indicated for the treatment of postoperative ocular inflammation, and steroid responsive ophthalmic diseases including ocular symptoms of acne rosacea, cyclitis, giant papillary conjunctivitis (GPC), iritis, keratitis, and seasonal allergic conjunctivitis. Lotemax ophthalmic gel and ointment are approved for postoperative ocular inflammation and pain. Inveltys (1% ophthalmic suspension) is also approved for postoperative ocular inflammation and pain. Eysuvis (0.25% ophthalmic suspension) is approved for the short-term (up to 2 weeks) treatment of the signs and symptoms of dry eye disease.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
-Loteprednol is administered topically to the eye.
-Wash hands before and after use.
-Do not touch the tip of the dropper or tube to the eye, fingertips, or other surfaces.
-To avoid contamination or the spread of infection, do not use any individual product package for more than 1 person.
-Instruct patient on proper instillation.
Loteprednol ophthalmic suspension:
-Shake well before use (2 to 3 seconds, vigorously).
-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 have the patient gently close eyes for 1 to 2 minutes.
-If another ophthalmic product is to be used concurrently, instruct the patient to wait at least 5 minutes between the instillation of loteprednol and the other ophthalmic medication.
-Contact lenses: Follow the directions for the specific product chosen. For all products, patients should be advised not to wear a contact lens if their eye is red. The patient should not wear contact lenses during product administration. Alert the patient that the preservative in these products may be absorbed by soft contact lenses. Contact lenses may be inserted at least 10 to 15 minutes after administration, depending on the product used. If the eyes are red or the patient has been advised not to wear them, the patient should not insert contact lenses until the drug is discontinued or the physician has approved of their use.
Loteprednol ophthalmic gel:
-Invert closed bottle and shake once to fill tip before instilling drops into the affected eye(s).
-Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch.
-Instill the drop into the pouch.
-Patients should not wear contact lenses during their course of therapy with this ophthalmic gel.
Loteprednol ophthalmic ointment:
-Tilt the head back and pull the lower eyelid down with the index finger to form a pouch.
-Place a small amount (about one-half of an inch) of the ointment into the pouch.
-Have the patient look downward and close eye to spread the ointment.
-Patients should not wear contact lenses during their course of therapy with this ophthalmic ointment.
Reactions associated with ophthalmic steroids include elevated intraocular pressure (ocular hypertension), which may be associated with optic nerve damage, visual acuity and field defects (visual impairment), and perforation of the globe where there is thinning of the cornea or sclera. Loteprednol is associated with a lower incidence of increased IOP compared to prednisolone, a more potent ophthalmic steroid. In large controlled clinical trials of prednisolone acetate 1% compared to loteprednol 0.2% or 0.5% given for 28 days or longer, the incidence of significant elevation of intraocular pressure (IOP of 10 mmHg or more) was 2% for loteprednol vs. 7% for prednisolone and 0.5% for placebo. Among the smaller group of patients in these trials who received loteprednol 0.2%, the incidence was 1% vs. 1% with placebo. Increased IOP may occur in normal and glaucomatous eyes and usually develops 2 to 8 weeks after initiating ophthalmic steroid use. Ocular hypertension is generally reversible 1 to 3 weeks after steroid discontinuation; however, persistent IOP elevation with glaucoma and vision loss has occurred. Intraocular pressure should be monitored if loteprednol ophthalmic is used for longer than 10 days.
Reactions associated with ophthalmic steroids include secondary eye infection. Ophthalmic steroid use, such as with loteprednol, may result in delayed or impaired wound healing of the eye or cornea following injury or surgery. Secondary ocular infection or superinfection may occur from pathogens including viruses such as herpes simplex, fungi, and bacteria. Fungal infections of the cornea may develop during long-term corticosteroid therapy. Fungal invasion should be evaluated in any persistent corneal erosion or ulceration where corticosteroid treatment has been used. Fungal cultures may be needed.
One of the most common adverse drug reactions in the clinical trials with loteprednol eye suspension following eye surgery included ocular pain, reported in 1% of patients, but this side effect may have been the consequence of the surgical procedure. Instillation site ocular pain was also reported by 5% of patients receiving the loteprednol 0.25% suspension for dry eye disease. The most common (2% to 5%) adverse drug reactions reported in the clinical trials for the loteprednol ophthalmic gel following surgery were anterior chamber ocular inflammation, ocular pain, and foreign body sensation. The most common ocular adverse event reported at approximately 25% in subjects in clinical studies with loteprednol eye ointment was anterior chamber ocular inflammation. Other common adverse events, with an incidence of 4% to 5%, were conjunctival hyperemia, corneal edema, and ocular pain. Many of these events may have been the consequence of the surgical procedure. If keratitis of the eye occurs, the corticosteroid should be discontinued. Ocular adverse reactions occurring in 5% to 15% of patients treated with loteprednol etabonate ophthalmic suspension for the treatment of seasonal allergies (0.2% to 0.5% concentrations) included abnormal vision or blurred vision, burning on instillation, chemosis, ocular discharge, dry eyes (xerophthalmia), epiphora, foreign body sensation, ocular pruritus, ocular redness, and photophobia. Other ocular adverse reactions occurring in less than 5% of patients include conjunctivitis, corneal abnormalities, eyelid erythema, keratoconjunctivitis, ocular irritation or discomfort, papillae, and uveitis. Some of these events were similar to the underlying ocular disease being studied.
Long-term ocular administration of corticosteroids, such as loteprednol, over several years has been associated with the formation of posterior subcapsular cataracts. Patients should be monitored for the development of lens opacities during prolonged corticosteroid use. One of the most common adverse drug reactions in the clinical trials with loteprednol eye suspension following eye surgery included posterior capsular opacification, reported in 1% of patients, but this side effect may have been the consequence of the surgical procedure.
Non-ocular adverse effects from ophthalmic loteprednol suspension used in the treatment of ocular allergies occurred in less than 15% of patients and included headache, rhinitis, and pharyngitis. The only non-ocular adverse event occurring at 1% or more during the use of loteprednol ophthalmic ointment was headache (1.5%). Headache was not specifically reported in trials for the ophthalmic gel or suspension for post-surgical use.
Loteprednol should be used with caution in individuals with hypersensitivity to loteprednol etabonate, other corticosteroid hypersensitivity, or to any of the specific ingredients of the chosen ophthalmic formulation.
Loteprednol use is contraindicated in most types of viral infection of the cornea and conjunctiva including herpes simplex virus epithelial keratitis, vaccinia, and varicella, and also in mycobacterial infection of the eye or fungal infection of ocular structures. The use of ocular steroids may prolong the course and exacerbate the severity of an ocular infection. Prolonged use of corticosteroids may suppress the host response and increase the risk of secondary ocular infections. In acute purulent conditions of the eye, steroids may mask infection or enhance existing bacterial infection. Use of ophthalmic corticosteroids in the treatment of patients with a history of herpes simplex requires great caution, as use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Fungal infection of the cornea may develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal cultures should be taken when appropriate.
Use ophthalmic corticosteroids with caution in the presence of glaucoma. Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, as well as defects in visual acuity and fields of vision. If the patient fails to improve within 2 days, reassess therapy. If loteprednol is used for 10 days or longer, monitor for increased intraocular pressure (IOP), even though it may be difficult in children or uncooperative patients. The initial prescription and renewal of the loteprednol medication order beyond 14 days should be made by a physician only after evaluation of the IOP and examination of the patient with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.
Long-term use (several years) of ocular corticosteroids, such as loteprednol, has been associated with the formation of posterior subcapsular (PSC) cataracts. Patients with diabetes mellitus appear to be more susceptible to developing PSC cataracts during ocular steroid use. The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. Loteprednol should be used with caution in patients with a corneal abrasion. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.
Patients who wear contact lenses should be aware that benzalkonium chloride, a preservative in loteprednol preparations, can be absorbed by soft contact lenses. During loteprednol treatment, the patient is advised not to wear soft contact lenses. Patients should not wear any contact lenses when using the ophthalmic gel or ointment preparations. Patients using other products should follow the manufacturer specific instructions regarding if/when contact lenses may be inserted during loteprednol therapy.
There are no adequate and well-controlled studies regarding the use of loteprednol etabonate in pregnant women. In animal studies, orally administered loteprednol etabonate produced teratogenicity at clinically relevant doses in rats and rabbits. Specifically, significant fetal malformations were observed in the offspring of rabbits and rats who received oral doses that were as low as 1.2-times and 30-times, respectively, the recommended human ophthalmic dose (RHOD). Although loteprednol etabonate is not significantly absorbed following ophthalmic administration with plasma concentrations less than 1 ng/mL, the drug should be used during pregnancy only if the potential benefits outweigh the risks of therapy. To minimize the amount of drug that reaches systemic circulation, apply pressure over the tear duct in the corner of the eye for 1 to 2 minutes after ophthalmic administration.
It is unknown if loteprednol etabonate is excreted in human milk, affects milk production, or has an adverse effect on breastfed infants. The drug is not significantly absorbed following ophthalmic administration with plasma concentrations less than 1 ng/mL; therefore, maternal use is not expected to result in fetal exposure. To minimize the amount of drug that reaches systemic circulation, and potentially breast milk, apply pressure over the tear duct in the corner of the eye for 1 to 2 minutes after ophthalmic administration. 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.
For the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis:
Ophthalmic dosage (0.2% loteprednol ophthalmic suspension; e.g., Alrex):
Adults: 1 drop in the affected eye(s) 4 times daily.
For the treatment of steroid responsive ophthalmic diseases including acute allergic conjunctivitis, acne rosacea, giant papillary conjunctivitis (GPC), iritis, keratitis, and cyclitis:
Ophthalmic dosage (0.5% loteprednol ophthalmic suspension; e.g., Lotemax):
Adults: 1 to 2 drops in the affected eye(s) 4 times daily; may increase dose to 1 drop in the affected eye(s) every hour, if needed, for the first week. Reevaluate if no improvement after 2 days. Do not discontinue prematurely.
For use as an alternative corticosteroid for the treatment of uveitis:
Ophthalmic dosage (0.5% loteprednol ophthalmic suspension; e.g., Lotemax):
Adults: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times per day. During the first week, increase up to 1 drop every hour if needed. Care should be taken not to discontinue therapy prematurely. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated. LIMITATIONS OF USE: Lotemax should not be used in patients who require a more potent corticosteroid for uveitis. Lotemax is less effective than prednisolone 1% in the treatment of acute anterior uveitis. Overall, 72% of patients treated with Lotemax experienced resolution of anterior chamber cell by day 28, compared to 87% of patients treated with prednisolone; however, the incidence of patients with clinically significant increases in IOP (i.e., 10 mmHg or more) was 1% with Lotemax versus 6% with prednisolone.
For the treatment of postoperative ocular inflammation after ocular surgery:
Ophthalmic dosage (loteprednol 0.5% ophthalmic suspension; e.g., Lotemax):
Adults: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily, beginning 24 hours after surgery and continuing for 2 weeks after surgery.
Ophthalmic dosage (loteprednol 0.5% ophthalmic gel; e.g., Lotemax):
Adults: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily, beginning 24 hours after surgery and continuing for 2 weeks after surgery.
Infants, Children, and Adolescents: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily, beginning 24 hours after surgery and continuing for 2 weeks after surgery.
Neonates: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily, beginning 24 hours after surgery and continuing for 2 weeks after surgery.
Ophthalmic dosage (loteprednol 0.5% ophthalmic ointment; e.g., Lotemax):
Adults: Apply a small amount (approximately one-half inch ribbon) into the conjunctival sac(s) 4 times daily, beginning 24 hours after surgery and continuing 2 weeks after surgery.
Ophthalmic dosage (loteprednol 1% ophthalmic suspension; e.g., Inveltys):
Adults: Apply 1 to 2 drops into the affected eye(s) twice daily, beginning the day after surgery and continuing for 2 weeks after surgery.
Ophthalmic dosage (loteprednol 0.38% ophthalmic gel; e.g., Lotemax SM):
Adults: Apply 1 drop into the conjunctival sac of the affected eye(s) 3 times daily, beginning 24 hours after surgery and continuing for 2 weeks after surgery.
For the treatment of postoperative ocular pain after ocular surgery:
Ophthalmic dosage (loteprednol 0.5% ophthalmic gel; e.g., Lotemax):
Adults: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily, beginning the day after surgery and continuing for 2 weeks after surgery.
Infants, Children, and Adolescents: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily, beginning the day after surgery and continuing for 2 weeks after surgery.
Neonates: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily, beginning the day after surgery and continuing for 2 weeks after surgery.
Ophthalmic dosage (loteprednol 1% ophthalmic suspension; e.g., Inveltys):
Adults: Apply 1 to 2 drops into the affected eye(s) twice daily, beginning the day after surgery and continuing for 2 weeks after surgery.
Ophthalmic dosage (loteprednol 0.5% ophthalmic ointment; e.g., Lotemax):
Adults: Apply a small amount (approximately one-half inch ribbon) into the conjunctival sac of the affected eye(s) 4 times daily, beginning 24 hours after surgery and continuing 2 weeks after surgery.
Ophthalmic dosage (loteprednol 0.38% ophthalmic gel; e.g., Lotemax SM):
Adults: Apply 1 drop into the conjunctival sac of the affected eye(s) 3 times daily, beginning 24 hours after surgery and continuing for 2 weeks after surgery.
For the treatment of dry eye disease:
Ophthalmic dosage (0.25% ophthalmic suspension):
Adults: 1 to 2 drops in each eye 4 times daily, initially. Reduce dose to 1 to 2 drops in each eye twice daily after 1 to 2 weeks if positive response in signs and/or symptoms and start cyclosporine, then taper or discontinue steroid therapy after 2 to 4 weeks. Consider extending duration to 4 weeks if no response at 2 weeks, especially in patients with moderate to severe disease.
Ophthalmic dosage (0.5% ophthalmic gel*):
Adults: 1 to 2 drops in each eye 4 times daily, initially. Reduce dose to 1 to 2 drops in each eye twice daily after 1 to 2 weeks if positive response in signs and/or symptoms and start cyclosporine, then taper or discontinue steroid therapy after 2 to 4 weeks. Consider extending duration to 4 weeks if no response at 2 weeks, especially in patients with moderate to severe disease.
Ophthalmic dosage (0.5% ophthalmic ointment*):
Adults: 0.5 inch ribbon in each eye 4 times daily, initially. Reduce dose to 0.5 inch ribbon in each eye twice daily after 1 to 2 weeks if positive response in signs and/or symptoms and start cyclosporine, then taper or discontinue steroid therapy after 2 to 4 weeks. Consider extending duration to 4 weeks if no response at 2 weeks, especially in patients with moderate to severe disease.
Maximum Dosage Limits:
-Adults
24 drops/day loteprednol 0.5%, or 8 drops/day loteprednol 0.25%, or 4 drops/day loteprednol 1%, or 4 drops/day loteprednol 0.2%, or 3 drops/day loteprednol 0.38% in each affected eye.
-Geriatric
24 drops/day loteprednol 0.5%, or 8 drops/day loteprednol 0.25%, or 4 drops/day loteprednol 1%, or 4 drops/day loteprednol 0.2%, or 3 drops/day loteprednol 0.38% in each affected eye.
-Adolescents
8 drops/day loteprednol 0.5% gel in each affected eye; safety and efficacy have not been established for other products.
-Children
8 drops/day loteprednol 0.5% gel in each affected eye; safety and efficacy have not been established for other products.
-Infants
8 drops/day loteprednol 0.5% gel in each affected eye; safety and efficacy have not been established for other products.
-Neonates
8 drops/day loteprednol 0.5% gel in each affected eye; safety and efficacy have not been established for other products.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
No dosage adjustment is needed.
Intermittent hemodialysis
No dosage adjustment is needed.
*non-FDA-approved indication
There are no drug interactions associated with Loteprednol products.
Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Corticosteroids are capable of producing a rise in intraocular pressure (IOP). The mechanism by which ophthalmic corticosteroids increase intraocular pressure is not known. Corticosteroids are associated with the presence of extracellular glycosaminoglycans in ocular trabecular cells which have been hypothesized to increase the resistance of aqueous outflow.
Loteprednol is administered topically to the eye. Loteprednol etabonate is lipid soluble and can penetrate into cells. Loteprednol etabonate undergoes a predictable transformation to an inactive metabolite. Based upon in vivo and in vitro preclinical metabolism studies, loteprednol etabonate undergoes extensive metabolism to inactive carboxylic acid metabolites, PJ-91 and PJ-90.
Affected cytochrome P450 isoenzymes: None
-Route-Specific Pharmacokinetics
Other Route(s)
Ophthalmic Route
-Suspension: Limited systemic absorption (less than 1 ng/mL) of loteprednol (0.2%, 0.25%, or 0.5%) occurs following daily administration. Bioavailability data in normal volunteers receiving 0.5% loteprednol etabonate 8-times daily for 2 days or 4-times daily for 42 days demonstrated insignificant plasma concentrations of loteprednol etabonate and its primary carboxylic acid metabolite at all sampling times. In 20 healthy subjects who received 2 drops of the 0.25% ophthalmic suspension 4-times daily for 14 days, the plasma concentrations of loteprednol etabonate were below the limits of quantitation (1 ng/mL) at all time points. Similarly, following twice-daily unilateral topical ocular dosing of 1% ophthalmic suspension for 14 days in healthy subjects, the plasma concentrations of loteprednol etabonate were below the limit of quantitation (less than 1 ng/mL) at all time points.
-Gel: Data from healthy adults receiving 1 drop of the 0.38% gel 3-times daily for 15 days found the mean maximum plasma concentration (Cmax) of loteprednol etabonate on days 1 and 15 to be 0.13 (+/- 0.06) ng/mL and 0.16 (+/- 0.06) ng/mL, respectively. The mean systemic exposures (AUC) were 0.15 (+/- 0.15) hour x ng/mL on day 1 after a single dose and 0.35 (+/- 0.32) hour x ng/mL after the last dose on day 15.
-Ointment: The systemic exposure to loteprednol ophthalmic ointment has not been studied in humans.