Loteprednol Etabonate

S01B - Antiinflammatory agents ATC S01BA14 Small molecule approved 1998 Topical Natural product

JFDA label: Lotemax

Mechanism of Action

Agonist of Glucocorticoid receptor — Glucocorticoid receptor agonist

Target	Action	Gene / class
Glucocorticoid receptor efficacy	AGONIST	NR3C1

Indications

Approved

Ophthalmic inflammatory conditions (0.5% suspension)
Postoperative inflammation/pain (0.5% suspension/ointment/gel)
Seasonal allergic conjunctivitis (0.2% suspension)

Contraindications

Source: Lexicomp

Hypersensitivity to loteprednol, other corticosteroids, and any component of the formulation Absolute
fungal diseases of ocular structures Absolute
mycobacterial infection of the eye Absolute
viral diseases of the cornea and conjunctiva (including epithelial herpes simplex keratitis, vaccinia, and varicella) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (2)

Very Common Foreign body sensation · headache

Metabolism and nutrition disorders (1)

Very Common Chemosis

Eye disorders (11)

Very Common Anterior chamber inflammation · blepharitis (Miscellaneous: Papilla ( · blurred vision · Conjunctival hyperemia · corneal edema · epiphora · eye discharge · eye pain · photophobia · visual disturbance · xerophthalmia

General disorders and administration site conditions (1)

Very Common Application site burning

Respiratory, thoracic and mediastinal disorders (1)

Very Common Pharyngitis (1% to 10%:

Dosing

Source: Lexicomp

Seasonal allergic conjunctivitis: Ophthalmic: 0.2% suspension: Instill 1 drop into affected eye(s) 4 times daily. Steroid-responsive inflammatory conditions: Ophthalmic: 0.5% suspension: Instill 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily. During the initial treatment within the first week, the dosing may be increased up to 1 drop every hour. Advise patients not to discontinue therapy prematurely. If signs and symptoms fail to improve after 2 days, re-evaluate the patient. Postoperative inflammation/pain: Ophthalmic: 0.5% ointment: Apply ~1/2 inch ribbon into the conjunctival sac of the affected eye(s) 4 times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period. 0.5% gel, 0.5% suspension: Instill 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.

Warnings & Precautions

Source: Lexicomp

Cataracts

Use of corticosteroids may result in posterior subcapsular cataract formation. Use following cataract surgery may delay healing and increase the incidence of bleb formation.

Corneal thinning

Various ophthalmic disorders, as well as prolonged use of corticosteroids, may result in corneal and scleral thinning. Continued use in a patient with thinning may result in perforation.

Glaucoma

Prolonged use of corticosteroids may result in elevated intraocular pressure (IOP) and/or glaucoma; damage to the optic nerve; and defects in visual acuity and fields of vision. Use with caution in patients with glaucoma; monitor IOP in any patient receiving treatment for ≥10 days.

Immunosuppression

Prolonged use of corticosteroids (including ophthalmic preparations) may increase the incidence of secondary ocular infections (including fungal infections). Acute purulent ocular infections may be masked or exacerbated with use. Fungal infection should be suspected in any patient with persistent corneal ulceration who has received corticosteroids. Disease-related concerns:

Herpes simplex

Corticosteroids should not be used to treat ocular herpes simplex; may exacerbate the severity of the infection. Use extreme caution in patients with history of herpes simplex. Special populations:

Contact lens wearers

Some preparations may contain benzalkonium chloride which may be absorbed by contact lenses. When used for the treatment of seasonal allergic conjunctivitis, wait ≥10 minutes after instilling eye drops before inserting contact lenses; do not wear contacts if eyes are red. Contact lenses should not be worn during treatment with loteprednol ophthalmic gel.

Pediatric

Do not use ointment in children following ocular surgery; may interfere with amblyopia treatment. Other warnings/precautions:

Acute anterior uveitis

More potent steroids may be required for this indication.

Appropriate use

For ophthalmic use only; patients should be re-evaluated if symptoms fail to improve after 2 days. Initial prescription and renewal of medication after 14 days should be made by healthcare provider only after examination with the aid of magnification such as slit lamp biomicroscopy or fluorescein staining (if appropriate). Avoid contamination; do not touch tip of applicator or let tip of applicator touch eye.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in animal reproduction studies following oral administration. The amount of loteprednol absorbed systemically following ophthalmic administration is not known but expected to be

Lactation

Systemic corticosteroids are present in breast milk. The extent of systemic absorption following topical application of the ophthalmic drops is not known. The manufacturer recommends that caution be exercised when administering loteprednol to breastfeeding women.

Monitoring

Clinical pearl	Intraocular pressure (if >10 days of treatment); signs and symptoms of infection

Chemistry & Properties

Formula	C24H31ClO7
Molecular weight	466.96 g/mol
IUPAC name	chloromethyl (8S,9S,10R,11S,13S,14S,17R)-17-ethoxycarbonyloxy-11-hydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-17-carboxylate
CAS	82034-46-6
PubChem CID	444025
InChIKey	`DMKSVUSAATWOCU-HROMYWEYSA-N`
logP	3.92 (XLogP 3.9)
Polar surface area	99.13 Å²
H-bond acceptors / donors	7 / 1
Drug-likeness (QED)	0.49
Lipinski violations	0

SMILES

CCOC(=O)O[C@]1(C(=O)OCCl)CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@@]21C

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C8	Inhibitor	—
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Lotemax	Solution 0.5 %	5 ml pack varies	Petra Drug Store	9.430
Lotemax	Cream 0.5 %	5 g tube pack varies	Petra Drug Store	10.530
Zylet	Solution 0.3 %, 0.5 %	5 ml	Petra Drug Store	11.280