Instructions for Lotemax eye gel 0.5% bottle 5 g
Composition
active ingredient: loteprednol etabonate;
1 g of gel contains 5 mg of loteprednol etabonate (0.5%);
Excipients: disodium edetate dihydrate, glycerol, propylene glycol, boric acid, polycarbophil, sodium chloride, tyloxapol, sodium hydroxide (2H), benzalkonium chloride, 50% solution (WAK), water for injections.
Dosage form
Eye gel.
Main physicochemical properties: white or almost white gel.
Pharmacotherapeutic group
Drugs used in ophthalmology. Anti-inflammatory drugs. Corticosteroids. Loteprednol. ATC code: S01BA14.
Pharmacological properties
LOTEMAX® (loteprednol etabonate ophthalmic gel) 0.5% contains a sterile topical corticosteroid for ophthalmic use.
Mechanism of action.
Corticosteroids suppress the inflammatory response to a variety of stimuli and are likely to delay or slow healing. They inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, collagen deposition, and scar formation associated with inflammation. Although glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in the modulation of inflammation by glucocorticoid receptors are not clearly established. However, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms.
Pharmacokinetics.
Loteprednol etabonate is lipid soluble and can penetrate cells. Loteprednol etabonate is synthesized by structural modifications of prednisolone-related compounds such that it undergoes a predictable transformation to an inactive metabolite. Based on preclinical in vivo and in vitro metabolic studies, loteprednol etabonate is extensively metabolized to the inactive carboxylic acid metabolites: PJ-91 and PJ-90. The systemic effects of loteprednol etabonate following ocular instillation of LOTEMAX® have not been studied in humans.
Preclinical toxicological data
Carcinogenesis, mutagenesis, impaired fertility
Long-term animal studies to evaluate the carcinogenic potential of loteprednol etabonate have not been conducted. Loteprednol etabonate did not show any evidence of genotoxicity using the in vitro Ames test, the mouse thymidine kinase assay, the human lymphocyte chromosome aberration assay, or the single-dose in vivo mouse micronucleus test.
Administration of loteprednol etabonate to female and male rats at doses ≥25 mg/kg/day (152 times the RHOD based on body surface area, at 100% absorption) prior to and during mating resulted in preimplantation loss and a reduction in the number of live/liveborn offspring. The NOAEL relevant to fertility in rats is 5 mg/kg/day (30 times the RHOD).
Clinical trials
Studies in adult patients
In two randomized, multicenter, double-blind, placebo-controlled, parallel-group studies conducted in 813 patients with postoperative inflammation, LOTEMAX® was more effective than its placebo in reducing anterior chamber inflammation and pain after cataract surgery. The primary endpoints were complete resolution of anterior chamber cells (cell count 0) and freedom from pain at day 8 after surgery.
In these studies, LOTEMAX® had a statistically significantly higher proportion of patients with complete clearance of anterior chamber cells (31% vs. 14-16%) and pain-free at day 8 after surgery (73-76% vs. 42-46%).
Studies in pediatric patients
The safety and efficacy of LOTEMAX® were evaluated in a pediatric study of patients aged birth to 11 years (mean age 3 years) undergoing cataract surgery. Patients were randomized to receive either LOTEMAX® (54 patients) or 1% prednisolone acetate ophthalmic suspension (53 patients) four times daily for 14 days. At day 14, the percentage of patients with complete resolution of anterior chamber inflammation was 57% in the LOTEMAX group and 63% in the prednisolone group.
Indication
LOTEMAX® is a corticosteroid indicated for the treatment of postoperative inflammation and pain relief following ophthalmic surgery.
Contraindication
The drug LOTEMAX® is contraindicated in most viral diseases of the cornea and conjunctiva, in particular epithelial keratitis (tree-like keratitis) caused by the herpes simplex virus, vaccinia, varicella, as well as mycobacterial eye infection and fungal diseases of the eye structures.
Interaction with other medicinal products and other types of interactions
Data is missing.
Application features
Prolonged use of corticosteroids, including LOTEMAX®, may cause glaucoma with optic nerve damage, visual acuity impairment, and narrowing of the visual fields. Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be monitored if this drug is used for 10 days or more.
Cataract
The use of corticosteroids may lead to the formation of posterior subcapsular cataracts.
Slow healing of wounds
The use of steroids after cataract surgery may delay healing and lead to microbial contamination. In diseases that cause thinning of the cornea or sclera, topical corticosteroids may contribute to the development of ulcers. The doctor should make the first prescription and continue the use of the drug only after examining the patient with special devices that allow for a magnified image of the eye, such as slit-lamp examination (biomicroscopy) and, if necessary, with fluorescein staining.
Bacterial infections
Prolonged use of corticosteroids may suppress the immune response and increase the likelihood of secondary ocular infections. In acute purulent ocular diseases, steroids may mask or complicate the course of an existing infection.
Viral infections
The use of corticosteroids in the treatment of patients with a history of herpes simplex requires great caution. The use of ocular steroids may prolong the course and increase the severity of many ocular viral infections (including herpes simplex).
Fungal infections
Fungal infections of the cornea are particularly likely to develop with prolonged topical steroid use. Fungal invasion should be considered in any persistent corneal ulcer for which a steroid has been or is being used. Fungal cultures should be obtained as appropriate.
For contact lens wearers
Patients are not recommended to wear contact lenses during treatment with LOTEMAX®.
Risk of contamination
Patients should be informed that the dropper tip should not touch any surface as this may cause contamination of the gel.
Risk of reinfection
Patients should consult a doctor if pain, redness, itching, or worsening inflammation occurs.
Elderly patients
Overall, no difference in efficacy and safety of the drug was observed between elderly and younger patients.
Children
The safety and efficacy of LOTEMAX® in children have been established. The use of LOTEMAX® in this population is supported by evidence from adequate and well-controlled studies of LOTEMAX® in adults, as well as additional data from safety and efficacy studies in pediatric patients from birth to 11 years of age (see Clinical Studies section).
Use during pregnancy or breastfeeding
Pregnancy
Risk summary
There are no adequate or well-controlled studies of loteprednol etabonate in pregnant women.
Loteprednol etabonate was teratogenic in rabbits and rats when administered orally during pregnancy at clinically relevant doses. Loteprednol etabonate caused malformations when administered orally to pregnant rabbits at doses ≥1.2 times the recommended human ophthalmic dose (RHOD) and when administered to pregnant rats at doses ≥30 times the RHOD. Among pregnant rats given oral doses of loteprednol etabonate during the last trimester of human pregnancy, when lactation occurs, offspring survival was reduced at doses ≥3 times the RHOD. Maternal toxicity was observed in rats at doses ≥304 times the RHOD, and the maternal NOAEL was established at 30 times the RHOD.
The background risk of major birth defects and miscarriage in this population is unknown. However, the background risk of major birth defects in the general US population is 2 to 4%, and the risk of miscarriage is 15 to 20% of clinically recognized pregnancies.
Data
Embryofetal studies were conducted in pregnant rabbits administered loteprednol etabonate by gavage from gestation day 6 to 18, targeting the period of organogenesis. Loteprednol etabonate caused fetal malformations at doses ≥0.1 mg/kg (1.2 times the recommended human ophthalmic dose (RHOD) based on body surface area at 100% absorption). Spinal cord splitting (including meningocele) was observed at doses ≥0.1 mg/kg, and exencephaly and craniofacial malformations were observed at doses ≥0.4 mg/kg (4.9 times the RHOD). At 3 mg/kg (36 times the RHOD), loteprednol etabonate was associated with an increased incidence of left common carotid artery anomalies, limb deformities, umbilical hernia, scoliosis, and delayed bone formation. Abortion and embryofetal lethality (resorption) occurred at doses ≥6 mg/kg (73 times the RHOD). A NOAEL relevant for embryofetal toxicity was not identified in this study. The NOAEL for maternal toxicity in rabbits was 3 mg/kg/day.
Embryofetal studies were conducted in pregnant rats administered loteprednol etabonate by gavage from gestation day 6 to 15, targeting the period of organogenesis. Loteprednol etabonate caused fetal malformations, including absence of brachiocephalic trunk, at doses ≥5 mg/kg (30 times the RHOD); and cleft palate, congenital absence of mandible, cardiovascular malformations, umbilical hernia, decreased fetal body weight, and decreased skeletal ossification at doses ≥50 mg/kg (304 times the RHOD). Embryofetal lethality (resorption) was observed at 100 mg/kg (608 times the RHOD). The NOAEL relevant for embryofetal toxicity in rats is 0.5 mg/kg (3 times the RHOD). Loteprednol etabonate was toxic to the mother (decreased body weight gain) at doses ≥ 50 mg/kg/day. The NOAEL dose causing maternal toxicity is 5 mg/kg.
A peri/postnatal study was conducted in rats administered loteprednol etabonate by gavage from gestation day 15 (beginning of the intrauterine period) to postnatal day 21 (end of lactation). At doses ≥ 0.5 mg/kg (3 times the clinical dose), reduced survival of live-born offspring was observed. Doses ≥ 5 mg/kg (30 times the RHOD) caused umbilical hernia/incompletely formed gastrointestinal tract. Doses ≥ 50 mg/kg (304 times the RHOD) caused maternal toxicity (decreased body weight gain, death), reduced live-born offspring, reduced birth weight, and delayed postnatal development. A NOAEL relevant to embryo-fetal toxicity was not established in this study. The NOAEL dose that has a toxic effect on the mother is 5 mg/kg.
Breast-feeding
There are no data on the presence of loteprednol etabonate in human breast milk, the effects on breastfed infants, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LOTEMAX® and any potential adverse reactions from LOTEMAX® on the breastfed infant.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the effects of the drug on the ability to drive or use machines have been conducted. As with other ophthalmic agents, temporary blurred vision may occur, which may affect the ability to drive or use machines. In such cases, patients should not drive or use machines until their vision clears.
Method of administration and doses
Instill one or two drops of LOTEMAX® into the conjunctival sac of the affected eye four times daily, starting the day after surgery and continuing for the first 2 weeks of the postoperative period.
Method of application:
Before use, turn the closed bottle upside down and shake once to fill the tip with the medication before instilling the medication.
Overdose
Data is missing.
Side effects
Adverse reactions associated with ophthalmic steroids include: increased intraocular pressure, which may be accompanied by rare optic nerve damage, impaired visual acuity and narrowing of the visual fields, and the formation of posterior subcapsular cataracts; delayed wound healing; secondary ocular infection caused by pathogens, including herpes simplex virus; perforation of the eyeball at sites of corneal or sclera thinning.
The most common adverse drug reactions (2-5%) reported during clinical trials were anterior chamber inflammation, eye pain, and foreign body sensation in the eye.
Expiration date
24 months. After first opening - store no more than 28 days.
Storage conditions
Store upright at a temperature not exceeding 25°C. Do not freeze. Keep out of reach of children. After first opening: Store upright at a temperature not exceeding 25°C. Do not freeze.
Incompatibility.
Since there are no compatibility studies, this drug should not be mixed with other medications.
Packaging
5 g of gel in a bottle with a dropper and cap, 1 bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
Bausch & Lomb Incorporated.
Location of the manufacturer and its business address.
8500 Hidden River Parkway Tampa, FL 33637, United States of America
