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Loteprednol Etabonate

Class: Corticosteroids
VA Class: OP300
Chemical Name: 17-(ethyl carbonate) chloromethyl 11β,17-dihydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate
Molecular Formula: C24H31ClO7
CAS Number: 82034-46-6
Brands: Alrex, Lotemax, Zylet

Introduction

Synthetic nonfluorinated corticosteroid.1 2 3 4 5 6 7 8 9 10 11 16 17

Uses for Loteprednol Etabonate

Allergic Conjunctivitis

Symptomatic relief of seasonal allergic (hay fever, pollinosis) conjunctivitis.1 2 10 12 17 19

Inflammatory Ocular Disorders

Symptomatic relief of corticosteroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe (i.e., allergic conjunctivitis, acne rosacea keratitis, superficial punctate keratitis, herpes zoster keratitis, iritis, and cyclitis.1 8 9 10 11 17 Use in conjunction with appropriate anti-infective therapy in some cases of conjunctival infection, when the benefits of reducing edema and inflammation outweigh the risks associated with use of topical corticosteroids.1

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Loteprednol etabonate 0.5% less effective than prednisolone acetate 1% in the management of anterior uveitis.1 29

Postoperative Ocular Inflammation

Treatment of postoperative ocular inflammation following ocular surgery.1 27 28

Bacterial Ophthalmic Infections

Used in fixed combination with tobramycin in certain bacterial ocular infections.31

Loteprednol Etabonate Dosage and Administration

General

  • For seasonal allergic rhinitis, do not use for >2 weeks.26

  • For inflammatory ocular disorders, do not discontinue therapy prematurely.1

  • When used in fixed combination with tobramycin, do not discontinue prematurely.31

  • Reevaluate patient if ocular signs and symptoms fail to improve after 2 days of therapy.1 2 26 31

  • Monitor intraocular pressure (IOP) in patients receiving therapy for ≥10 days.1 2 31

Administration

Ophthalmic Administration

Apply topically to the eyes as an ophthalmic suspension.1 2 8 9 10 11 12

In fixed combination with tobramycin, apply topically to the eyes as an ophthalmic suspension.31

Shake suspension vigorously prior to use.1 2 30 31

Avoid contamination of the dropper tip.1 2

Dosage

Available as loteprednol etabonate; dosage expressed in terms of the salt.1 2

Adults

Seasonal Allergic Conjunctivitis
Ophthalmic

1 drop of a 0.2% suspension in the affected eye(s) 4 times daily.2

Inflammatory Ocular Disorders
Ophthalmic

1 or 2 drops of a 0.5% suspension in the affected eye(s) 4 times daily.1 8 9 10 11 During initial treatment (within the first week), may increase dosage up to 1 drop every hour.1 When improvement occurs, decrease frequency of application.1 26 30

Postoperative Ocular Inflammation
Ophthalmic

1 or 2 drops of a 0.5% suspension to the eye(s) undergoing surgery 4 times daily beginning 24 hours after surgery and continuing for 2 weeks after surgery.1 27 28

Bacterial Ophthalmic Infections
Ophthalmic

Loteprednol etabonate and tobramycin ophthalmic suspension: 1 or 2 drops in the affected eye(s) every 4–6 hours.31 During the initial 24–48 hours, dosing may be increased to every 1–2 hours.31 When improvement occurs, decrease frequency of application.31

Cautions for Loteprednol Etabonate

Contraindications

  • Viral diseases of the cornea and conjunctiva (e.g., epithelial herpes simplex keratitis [dendritic keratitis], vaccinia, varicella), mycobacterial infection of the eye, and fungal diseases of ocular structures.1 2 31

  • Known hypersensitivity to loteprednol, other corticosteroids, or any ingredient in the formulations.1 2 31

Warnings/Precautions

Warnings

Ocular Effects

Risk of glaucoma (with damage to optic nerve), defects in visual acuity and fields of vision, and posterior subcapsular cataract formation with prolonged use of corticosteroids.1 2 31 Use with caution in the presence of glaucoma.1 2 31 Marked elevation in IOP (≥10 mm Hg) reported with loteprednol use; incidence lower than that reported with prednisolone acetate.1 2 31

In conditions causing thinning of the cornea or sclera, perforations reported with use of topical corticosteroids.1 2 31

Corticosteroid use after cataract surgery may delay healing and increase incidence of bleb formation.1 2 31

Immunosuppressive Effects

Risk of secondary ocular infection with prolonged use of corticosteroids.1 2 31

In acute purulent ocular conditions, corticosteroids may mask infection or exacerbate existing infection.1 2 31

Risk of prolongation or exacerbation of ocular viral infections (e.g., herpes simplex) with ophthalmic corticosteroids.1 2 31 Use with extreme caution in patients with history of herpes simplex.1 2 31

General Precautions

Use of Fixed Combination

Observe the usual precautions associated with tobramycin therapy when loteprednol is used in fixed combination with tobramycin.31

Evaluation of Ocular Condition

Initial prescription or renewal of medication order beyond 14 days should be provided only after examination of the patient with the aid of magnification (e.g., slit lamp biomicroscopy, fluorescein staining where appropriate).1 2 31

Fungal Infections

Long-term local corticosteroid application associated with development of fungal infections of the cornea.1 2 31 Consider fungus invasion in patients with persistent corneal ulceration who have or are receiving corticosteroid therapy; obtain fungal cultures when appropriate.1 2 31

Specific Populations

Pregnancy

Category C.1 2 31

Lactation

Not known whether distributed into human milk following topical application to the eye.1 2 31 Systemic corticosteroids distributed into human milk and may suppress growth, interfere with endogenous corticosteroid production, and cause other adverse effects.1 2 31 Use with caution.1 2 31

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 2 26 31

Common Adverse Effects

Abnormal/blurred vision, burning on instillation, chemosis, discharge, dry eyes, epiphora, foreign body sensation, itching, injection, photophobia.1 2

Adverse systemic events include headache, rhinitis, and pharyngitis.1 2

Loteprednol Etabonate Pharmacokinetics

Absorption

Bioavailability

Limited systemic exposure following topical application to the eye; plasma concentrations usually are undetectable.1

Onset

In clinical studies in patients with seasonal allergic conjunctivitis, improvement in ocular itching and bulbar conjunctival injection occurred within 2 hours following initiation of therapy.2 12 17 19

In clinical studies in patients with contact lens-associated giant papillary conjunctivitis, improvement in papillae, conjunctival injection and itching, and lens intolerance was evident within 1 week of therapy.1 8 9 11 17

Duration

In patients with seasonal allergic conjunctivitis, improvement in ocular itching and bulbar conjunctival injection persisted through day 14 of therapy.2

In patients with contact lens-associated giant papillary conjunctivitis, improvement in papillae, conjunctival injection and itching, and lens intolerance persisted for up to 6 weeks while therapy was continued.1 8 9 11 17

Elimination

Metabolism

Undergoes extensive metabolism to inactive carboxylic acid metabolites.1 2

Stability

Storage

Ophthalmic

Suspension

Upright at 15–25°C.1 2 31 Do not freeze.1 2 31

Actions

  • Corticosteroids inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.1 2 31

  • Corticosteroids may induce phospholipase A2 inhibitory proteins; these proteins may inhibit release of arachidonic acid and, thus, control biosynthesis of potent mediators of inflammation (e.g., prostaglandins, leukotrienes).1 2 31

Advice to Patients

  • Importance of learning and adhering to proper administration techniques to avoid contamination of the tip of the suspension container.1 2 31

  • Consult a clinician if pain, redness, itching, or inflammation worsens.1 2 31

  • Importance of not wearing soft contact lenses during treatment with Lotemax or Zylet (benzalkonium chloride preservative may be absorbed by the lenses).1 31

  • Importance of removing soft contact lenses prior to administration of each dose of Alrex.2 Delay reinsertion for 10 minutes after administration if eyes are not red; do not wear contact lenses if eye(s) are red.2 Not indicated for contact lens-related irritation.2

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 2 31

  • Importance of informing patients of other important precautionary information.1 2 31 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Loteprednol Etabonate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Suspension

0.2%

Alrex (with benzalkonium chloride and povidone)

Bausch & Lomb

0.5%

Lotemax (with benzalkonium chloride and povidone)

Bausch & Lomb

Loteprednol Etabonate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Suspension

0.5% with Tobramycin 0.3%

Zylet (with benzalkonium chloride and povidone)

Bausch & Lomb

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 24, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Bausch & Lomb Pharmaceuticals, Inc. Lotemax (loteprednol etabonate) ophthalmic suspension 0.5% prescribing information. Tampa, FL; 2005 May.

2. Bausch & Lomb Pharmaceuticals, Inc. Alrex (loteprednol etabonate) ophthalmic suspension 0.2% prescribing information. Tampa, FL; 1998 Mar.

3. Hochhaus G, Chen LS, Ratka A et al. Pharmacokinetic characterization and tissue distribution of the new glucocorticoid soft drug loteprednol etabonate in rats and dogs. J Pharm Sci. 1992; 81:1210-15. [PubMed 1491342]

4. Loftsson T, Bodor N. The pharmacokinetics and transdermal delivery of loteprednol etabonate and related soft steroids. Adv Drug Delivery Rev. 1994; 14:293-9.

5. Bodor N, Wu WM, Murakami T et al. Soft drugs 19. Pharmacokinetics, metabolism and excretion of a novel soft corticosteroid, loteprednol etabonate, in rats. Pharm Res. 1995; 12:875-9. [PubMed 7667193]

6. Druzgala P, Wu WM, Bodor N. Ocular absorption and distribution of loteprednol etabonate, a soft steroid, in rabbit eyes. Curr Eye Res. 1991; 10:933-7. [PubMed 1959381]

7. Anon. Corticosteroids. In: Zimmerman TJ, Kooner KS, Sharir M et al, eds. Textbook of ocular pharmacology. Philadelphia: Lippincott-Raven; 1997:620-6.

8. Asbell P, Howes J. A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. CLAO J. 1997; 23:31-6. [PubMed 9001768]

9. Friedlaender MH, Howes J for the Loteprednol etabonate Giant Papillary Conjunctivitis Study Group I. A double-masked, placebo-controlled evaluation of the efficacy and safety of loteprednol etabonate in the treatment of giant papillary conjunctivitis. Am J Ophthalmol. 1997; 123:455-64. [IDIS 383467] [PubMed 9124242]

10. Dell SJ, Shulman DG, Lowry GM et al, for the Loteprednol Allergic Conjunctivitis Study Group. Am J Ophthalmol. 1997; 123:791-7. (IDIS 387183)

11. Bartlett JD, Howes JF, Ghormley NR et al. Safety and efficacy of loteprednol etabonate for treatment of papillae in contact lens-associated giant papillary conjunctivitis. Curr Eye Res. 1993; 12:313-21. [PubMed 8319490]

12. Dell SJ, Lowry GM, Northcutt JA et al. A randomized, double-masked, placebo-controlled parallel study of a 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol. 1998; 102: 251-5. [IDIS 412946] [PubMed 9723669]

13. Novack GD, Howes J, Crockett RS et al. Changes in intraocular pressure during long-term use of loteprednol etabonate. J Glaucoma. 1998; 7: 266-9. [PubMed 9713785]

14. Bodor N, Bodor N, Wu WM. A comparison of intraocular pressure elevating activity of loteprednol etabonate and dexamethasone in rabbits. Curr Eye Res. 1992; 11:525-30. [PubMed 1505197]

15. Bartlett JD, Horwitz B, Laibovitz R et al. Intraocular pressure response to loteprednol etabonate in known steroid responders. J Ocul Pharmacol. 1993; 9:157-65. [PubMed 8345288]

16. Bodor N. Design of novel soft corticosteroids. Curr Probl Dermatol. 1993; 21:11-9. [PubMed 8299363]

17. Anon. Loteprednol etabonate. Drugs Future. 1997; 22:1086-90.

18. Howes JF, Baru H, Vered M et al. Loteprednol etabonate: comparison with other steroids in two models of intraocular inflammation. J Ocul Pharmacol. 1994; 10:289-93. [PubMed 8207332]

19. Schulman DG, Lothringer LL, Rubin JM et al. A randomized, double-masked, placebo controlled , parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis. Ophthalmology. 1999; 106:362-9. [IDIS 422861] [PubMed 9951491]

20. Ciprandi G, Buscaglia S, Cerqueti PM et al. Drug treatment of allergic conjunctivitis: a review of the evidence. Drugs. 1992; 43:154-76. [IDIS 360840] [PubMed 1372215]

21. Friedlaender MH. Current concepts in ocular allergy. Ann Allergy. 1991; 67:5-10,13. [IDIS 312766] [PubMed 1859041]

22. Trocme SD. Medical therapy for ocular allergy. Mayo Clin Proc. 1992; 67:557-65. [IDIS 296611] [PubMed 1359206]

23. 137. Reviewers’ comments (personal observation) Reviewers’ comments (personal observation) ketorolac tromethamine ophthalmic solution.

24. Tinkelman DG, Rupp G, Kaufman H et al. Double-masked, paired-comparison clinical study of ketorolac tromethamine 0.5% ophthalmic solution compared with placebo eyedrops in the treatment of seasonal allergic conjunctivitis. Surv Ophthalmol. 1993; 38(Suppl): 133-140. [PubMed 8236004]

25. Ballas Z, Blumenthal M, Tinkeman DG et al. Clinical evaluation of ketorolac tromethamine 0.5% ophthalmic solution for the treatment of seasonal allergic conjunctivitis. Surv Ophthalmol. 1993; 38(Suppl): 141-8.

26. Reviewers’ comments (personal observations).

27. The Loteprednol Etabonate Postoperative Inflammation Study Group 2. A double-masked, placebo-controlled evaluation of 0.5% loteprednol etabonate in the treatment of postoperative inflammation. Ophthalmology. 1998; 105:1780-6. [IDIS 413091] [PubMed 9754192]

28. Stewart R, Horwitz B, Howes J et al. Double-masked, placebo-controlled evaluation of loteprednol etabonate 0.5% for postoperative inflammation. Loteprednol Etabonate Post-operative Inflammation Study Group 1. J Cataract Refract Surg. 1998; 24:1480-9. [PubMed 9818338]

29. Loteprednol Etabonate US Uveitis Study Group. Controlled evaluation of loteprednol etabonate and prednisolone acetate in the treatment of acute anterior uveitis. Am J Ophthalmol. 1999; 127:537-44. [IDIS 428957] [PubMed 10334346]

30. Bausch & Lomb, Tampa, FL: Personal communication.

31. Bausch & Lomb Pharmaceuticals, Inc. Zylet (loteprednol etabonate 0.5% and tobramycin 0.3%) ophthalmic suspension prescribing information. Tampa, FL; 2004 Dec.

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