Drug Interactions
No specific drug interaction studies have been conducted. There are no known drug interactions.
Alrex contains benzalkonium chloride which interacts with soft contact lens. See Dosage and Administration, Administration.
Drug-drug, drug-food, drug-herb, and drug-laboratory interactions have not been studied.
Information for the Patient
Alrex
Special Handling Instructions
There is no special handling instruction for Alrex.
Dosage and Administration
One drop instilled into the affected eye(s) four times daily for up to 14 days.
Shake vigorously before using. Instill one drop into the affected eye(s) four times daily.
Alrex should be stored upright between 15-25°C for up to 28 days after first opening.
The preservative in Alrex, benzalkonium chloride, may be absorbed by soft contact lenses, and can discolour soft contact lenses. Therefore, Alrex should not be used while the patient is wearing soft contact lenses. Patients who wear soft contact lenses and whose eyes are not red should wait ten to fifteen minutes after instilling Alrex before they insert their contact lenses.
Patients should be advised not to wear a contact lens if their eye is red. Alrex should not be used to treat contact lens related irritation.
If scheduled dose is missed, patient should be advised to wait until the next dose and then continue as before.
Adverse Reactions
Due to the sample size for each arm of the two phase III studies in SAC, all events captured are greater than 1% of n.
Reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.
In nineteen clinical trials ranging from 1 to 42 days in length, 1209 patients received various concentrations of loteprednol etabonate in topical ocular drops (0.005%, 0.05%, 0.1%, 0.2%, 0.5%). Adverse events related to loteprednol etabonate were generally, mild to moderate, non-serious and did not interrupt continuation in the studies. The most frequent ocular event reported as related to therapy was increased IOP: 6% (77/1209) in patients receiving loteprednol etabonate, as compared to 3% (25/806) in the placebo treated patients.
With the exception of elevations in IOP, the incidence of events in the LE group was similar to, or less than that of the placebo control groups. Itching was reported as related to therapy in 3% of the loteprednol treated eyes, injection, epiphora, burning/stinging other than at instillation, foreign body sensation, and burning/stinging at instillation were each reported for 2% of eyes. The most frequent non-ocular event reported as related to therapy was headache, reported for 1.2% of the loteprednol treated subjects and 0.6% of the placebo treated subjects.
In nineteen clinical trials ranging from 1 to 42 days in length, 1209 patients received various concentrations of loteprednol etabonate in topical ocular drops (0.005%, 0.05%, 0.1%, 0.2%, 0.5%), the most frequent ocular event reported as related to therapy was increased intraocular pressure: 6% (77/1209) in patients receiving loteprednol etabonate, as compared to 3% (25/806) in the placebo population.
Ocular adverse reactions occurring in 5-15% of patients treated with loteprednol etabonate ophthalmic suspension (0.2%-0.5%) in clinical studies included abnormal vision/blurring, burning on instillation, chemosis, discharge, dry eyes, epiphora, foreign body sensation, itching, injection, and photophobia. Other ocular adverse reactions occurring in less than 5% of patients include conjunctivitis, corneal abnormalities, eyelid erythema, keratoconjunctivitis, ocular irritation/pain/discomfort, papillae, and uveitis. Some of these events were similar to the underlying ocular disease being studied.
Non-ocular adverse reactions occurred in less than 15% of patients. These include headache, rhinitis and pharyngitis.
In a summary of controlled, randomized studies of individuals treated for 28 days or longer with loteprednol etabonate, the incidence of significant elevation of intraocular pressure (≥10 mm Hg) was 2% (15/901) among patients receiving loteprednol etabonate and 0.5% (3/583) among patients receiving placebo.
One case of mild cataract has been reported during this time.
Indications and Clinical Use
Alrex should not be used in pediatric patients. The safety and efficacy of Alrex have not been studied in pediatric patients.
Alrex should not be used in geriatric patients. The safety and efficacy of Alrex have not been established in patients >65 years of age.
Overdosage
For management of a suspected drug overdose, CPhA recommends that you contact your regional Poison Control Centre. See the eCPS Directories section for a list of Poison Control Centres.
No cases of overdose have been reported.
Dosage Forms, Composition and Packaging
Loteprednol etabonate ophthalmic suspension 0.2% w/v is supplied in a white low density polyethylene plastic bottle with a white controlled drop tip and a pink polypropylene cap in the following size: 5 mL in a 7.5 mL bottle. Nonmedicinal ingredients: benzalkonium chloride, edetate disodium, glycerin, povidone, purified water and tyloxapol. Hydrochloric Acid and/or Sodium Hydroxide may be added to adjust the pH to 5.4-5.5.
Warnings and Precautions
Alrex should not be used in geriatric patients. The safety and efficacy of Alrex have not been established in patients >65 years of age.
Cortisol and the synthetic analogs of cortisol have the capacity to prevent or suppress the development of the local heat, redness, swelling, and tenderness by which inflammation is recognized. At the microscopic level, they inhibit not only the early phenomena of the inflammatory process (edema, fibrin deposition, capillary dilation, migration of leukocytes into the inflamed area, and phagocytic activity) but also the later manifestations, such as capillary proliferation, fibroblast proliferation, deposition of collagen, and, still later, cicatrisation.
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, or in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay.
Disturbances and suppression of the Hypothalamic-Pituitary-Adrenal (HPA) axis can occur with systemic exposure to corticosteroids. However, given the very low systemic exposure to loteprednol etabonate when using Alrex as directed, these possible effects are not likely. See Action and Clinical Pharmacology.
For ophthalmic use only.
Alrex is indicated as a short-term treatment only (up to 14 days). The initial prescription and renewal of Alrex should be made by a physician only after appropriate ophthalmologic examination is performed. If signs and symptoms fail to improve after two days, the patient should be re-evaluated. If Alrex is used for 10 days or longer, intraocular pressure should be closely monitored. See Ophthalmologic.
Prolonged use of corticosteroids may result in cataract and/or glaucoma formation. Alrex should not be used in the presence of glaucoma or elevated intraocular pressure, unless absolutely necessary and close ophthalmologic monitoring is undertaken. Extreme caution should be exercised, and duration of treatment should be kept as short as possible. See Ophthalmologic.
Alrex should not be used in cases of existing (suspected or confirmed) ocular viral, fungal, or mycobacterial infections. Alrex may suppress the host response and thus increase the hazard of secondary ocular infections. The use of Alrex in patients with a history of herpes simplex requires great caution and close monitoring. See Ophthalmologic.
Alrex contains benzalkonium chloride. See Dosage and Administration.
Alrex has not been studied in pregnant or nursing women, but has been found to be teratogenic in animals. Alrex should not be used in pregnant or nursing women unless the benefits to the mother clearly outweigh the risk to the foetus or the nursing child. See Special Populations.
If Alrex is used for 10 days or longer, intraocular pressure should be monitored. See General.
Glucocorticoids, mostly when systemic exposure occurs, decrease the hypoglycemic activity of insulin and oral hypoglycemics, so that a change in dose of the anti-diabetic drugs may be necessitated. In high doses, glucocorticoids also decrease the response to somatotropin. The usual doses of mineralocorticoids and large doses of some glucocorticoids cause hypokalemia and may exaggerate the hypokalemic effects of thiazides and high-ceiling diuretics. In combination with amphotericin-B, they also may cause hypokalemia. Glucocorticoids appear to enhance the ulcerogenic effects of non-steroidal anti-inflammatory drugs. They decrease the plasma levels of salicylates, and salicylism may occur on discontinuing steroids. Glucocorticoids may increase or decrease the effects of prothrombopenic anticoagulants. Estrogens, phenobarbital, phenytoin and rifampin increase the metabolic clearance of adrenal steroids and hence necessitate dose adjustments. However, given the very low systemic exposure to loteprednol etabonate when using Alrex as directed, these possible effects are not likely. See Action and Clinical Pharmacology.
Alrex should be used as a brief temporary treatment. If Alrex is used for 10 days or longer, intraocular pressure should be closely monitored. The initial prescription and renewal of Alrex should be made by a physician only after appropriate ophthalmologic examination is performed with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. If signs and symptoms fail to improve after two days, the patient should be re-evaluated.
Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Alrex should not be used in the presence of glaucoma or elevated intraocular pressure, unless absolutely necessary and careful and close appropriate ophthalmologic monitoring (including intraocular pressure and lens clarity) is undertaken.
Fungal infections of the cornea are particularly prone to 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.
Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection.
Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution.
Formulations with benzalkonium chloride should be used with caution in soft contact lens wearer. See Dosage and Administration, Administration.
Alrex should not be used in pediatric patients. The safety and efficacy of Alrex have not been studied in pediatric patients.
The effects of Alrex on sexual function and reproduction have not been studied in humans. Treatment of male and female rats with up to 50 mg/kg/day and 25 mg/kg/day of loteprednol etabonate, respectively (1000 and 500 times the Alrex clinical dose), prior to and during mating, was clearly harmful to the rats but did not impair their copulation performance and fertility (i.e., ability of females to become pregnant). However, these doses were highly toxic and had significant toxic effects on the pregnancies, and the survival and development of the offspring. Maternal toxicity, possible occurrence of abnormalities and growth retardation started at 10 times the Alrex clinical dose. See Special Populations, Pregnant Women.
Alrex should not be used in pregnant women, unless the benefit to the mother clearly outweighs the risks to the foetus. Studies in pregnant women have not been conducted. However, studies in animals have shown major reproductive and developmental toxicity when administered orally at ~100 times the Alrex clinical dose. At lower doses (10 times the Alrex clinical dose), maternal toxicity was demonstrated and, although there were no major teratogenic effects, growth retardation and a possible increase in the occurrence of some abnormalities were noted.
Alrex should not be used in lactating women, unless the benefit to the mother clearly outweighs the risks to the nursing infant/child. Studies in lactating women have not been conducted. Systemic steroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.
It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk.
Storage and Stability
Store upright between 15-25°C. Do not freeze. Keep out of reach of children.
Action and Clinical Pharmacology
Results from a bioavailability study in normal volunteers (8 females, 2 males; age range of 19-44 years) established that plasma levels of loteprednol etabonate and Δ1 cortienic acid etabonate (PJ 91), its primary, inactive metabolite, were below the limit of quantitation (1 ng/mL) at all sampling times. The results were obtained following the ocular administration of one drop of 0.5% loteprednol etabonate ophthalmic suspension in each eye 8 times daily for 2 days or 4 times daily for 42 days.
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.
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.
Contraindications
Suspected or confirmed infection of the eye: viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella; untreated ocular infection of the eye; mycobacterial infection of the eye and fungal diseases of ocular structures.
Hypersensitivity to this drug or any ingredient in the formulation or container, or to other corticosteroids. For a complete listing, see Dosage Forms, Composition and Packaging.
