INVELTYS

Ophthalmological Corticosteroids
Ophthalmological Corticosteroids for Dry Eye Disease

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.[44068] [44072] [63470]
 
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.[52303] [63975]
 
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.[44069]

uveitis / Delayed / 0-5.0
keratoconjunctivitis / Early / 0-5.0
ocular hypertension / Delayed / 1.0-2.0
visual impairment / Early / Incidence not known
corneal erosion / Delayed / Incidence not known

ocular inflammation / Early / 5.0-25.0
photophobia / Early / 5.0-15.0
epiphora / Early / 5.0-15.0
blurred vision / Early / 5.0-15.0
corneal edema / Early / 4.0-5.0
conjunctivitis / Delayed / 0-5.0
superinfection / Delayed / Incidence not known
ocular infection / Delayed / Incidence not known
impaired wound healing / Delayed / Incidence not known
cataracts / Delayed / Incidence not known

xerophthalmia / Early / 5.0-15.0
ocular discharge / Delayed / 5.0-15.0
ocular pruritus / Rapid / 5.0-15.0
foreign body sensation / Rapid / 5.0-15.0
pharyngitis / Delayed / 0-15.0
rhinitis / Early / 0-15.0
headache / Early / 1.5-14.0
ocular pain / Early / 1.0-5.0
ocular irritation / Rapid / 0-5.0

Alrex, EYsuVIS, INVELTYS, Lotemax

Rx

Ophthalmic corticosteroid with minimal systemic absorption due to ocular metabolism
Used for seasonal allergic conjunctivitis and steroid responsive ocular diseases (e.g., cyclitis, GPC, iritis, keratitis)
Also used for postoperative ocular pain and inflammation and for the signs and symptoms of dry eye disease

1 drop in the affected eye(s) 4 times daily.

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.

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.

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.

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.

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.

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.

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.

Apply 1 to 2 drops into the affected eye(s) twice daily, beginning the day after surgery and continuing for 2 weeks after surgery.

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.

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.

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.

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.

Apply 1 to 2 drops into the affected eye(s) twice daily, beginning the day after surgery and continuing for 2 weeks after surgery.

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.

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.

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.

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.

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.

No dosage adjustment is needed.

No dosage adjustment is needed.
 
Intermittent hemodialysis
No dosage adjustment is needed.

There are no drug interactions associated with Loteprednol products.

Alrex/EYsuVIS/INVELTYS/Lotemax/Loteprednol Etabonate Ophthalmic Susp: 0.2%, 0.25%, 0.5%, 1%
Lotemax Ophthalmic Ointment: 0.5%
Lotemax/Loteprednol Etabonate Ophthalmic Gel: 0.38%, 0.5%

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.

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.

8 drops/day loteprednol 0.5% gel in each affected eye; safety and efficacy have not been established for other products.

8 drops/day loteprednol 0.5% gel in each affected eye; safety and efficacy have not been established for other products.

8 drops/day loteprednol 0.5% gel in each affected eye; safety and efficacy have not been established for other products.

8 drops/day loteprednol 0.5% gel in each affected eye; safety and efficacy have not been established for other 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

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. [44072] [63470]
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.[63975]
Ointment: The systemic exposure to loteprednol ophthalmic ointment has not been studied in humans.[44069]

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.[44068] [44069] [44072] [52303] [63470] 

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.[44068] [44069] [44072] [52303] [63470] [63975]