loteprednol ophthalmic (Rx)

>10%

Lotemax ointment only

• Anterior chamber inflammation (~25%)

5-15%

Lotemax suspension only

• Abnormal vision/blurring
• Burning on instillation
• Chemosis
• Discharge
• Dry eyes
• Epiphora
• Foreign body sensation
• Itching
• Photophobia

<5%

Lotemax gel

• Anterior chamber inflammation (5%)
• Eye pain (2%)
• Foreign body sensation (2%)

Lotemax suspension only

• Conjunctivitis
• Corneal abnormalities
• Eyelid erythema
• Keratoconjunctivitis
• Ocular irritation/pain/discomfort
• Papillae
• Uveitis

Lotemax ointment

• Conjunctival hyperemia (4-5%)
• Corneal edema (4-5%)
• Eye pain (4-5%)
• Headache (1.5%)

Frequency Not Defined

Inveltys only

• Infrequent optic nerve damage
• Visual acuity and field defects
• Posterior subcapsular cataract formation
• Delayed wound healing
• Secondary ocular infection from pathogens (eg, herpes simplex)
• Perforation of the globe where there is thinning of the cornea or sclera

Contraindications

Hypersensitivity to any component of the formulation

Most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures

Cautions

Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision; use with caution in the presence of glaucoma; if product is used for ≥10 days, monitor intraocular pressure (IOP)

Use of corticosteroids may result in posterior subcapsular cataract formation

Steroid use after cataract surgery may delay healing and increase the incidence of bleb formation; diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids; examine patient prior to initiating or renewing treatment

Prolonged use of corticosteroids may suppress the host response and thus increase the risk of secondary ocular infections; steroids may mask infection or enhance existing infection

Exercise caution with steroid use in patients with a history of herpes; use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (eg, herpes simplex)

Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application; consider fungus invasion in any persistent corneal ulceration where a steroid has been used or is in use; take fungal cultures when appropriate

Do not allow dropper tip to touch any surface, as this may contaminate the suspension

Do not wear contact lenses during therapy

Pregnancy

Inveltys

• Drug is not absorbed systemically following topical ophthalmic administration and maternal use is not expected to result in fetal exposure to drug

Lotemax and Alrex

• There are no adequate and well controlled studies in pregnant women; use during pregnancy only if the potential benefit justifies the potential risk to the fetus

• Animal data

  • Drug shown to be embryotoxic (delayed ossification) and teratogenic (increased incidence of meningocele, abnormal left common carotid artery, and limb flexures) when administered orally to rabbits during organogenesis at a dose of 3 mg/kg/day (35 times the maximum daily clinical dose), a dose which caused no maternal toxicity; no-observed-effect-level (NOEL) for these effects was 0.5 mg/kg/day (6 times the maximum daily clinical dose)
  • Oral treatment of rats during organogenesis resulted in teratogenicity (absent innominate artery at ≥5 mg/kg/day doses, and cleft palate and umbilical hernia at ≥50 mg/kg/day) and embryotoxicity (increased post-implantation losses at 100 mg/kg/day and decreased fetal body weight and skeletal ossification with ≥50 mg/kg/day)
  • Treatment of rats with 0.5 mg/kg/day (6 times the maximum clinical dose) during organogenesis did not result in any reproductive toxicity; loteprednol etabonate was maternally toxic (significantly reduced body weight gain during treatment) when administered to pregnant rats during organogenesis at doses of ≥5 mg/kg/day
  • Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from the start of the fetal period through the end of lactation, a maternally toxic treatment regimen (significantly decreased body weight gain), gave rise to decreased growth and survival, and retarded development in the offspring during lactation; NOEL for these effects was 5 mg/kg/day; no effect on the duration of gestation or parturition when administered orally to pregnant rats at doses up to 50 mg/kg/day during the fetal period

Lactation

Inveltys

• Drug is not absorbed systemically by the mother following topical ophthalmic administration, and breastfeeding is not expected to result in exposure of the child

Lotemax and Alrex

• There are no data on presence of loteprednol etabonate in human milk, effects on breastfed infant, or on milk production; developmental and health benefits of breastfeeding should be considered, along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant
• It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk
• Systemic steroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

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 believed that these proteins control the biosynthesis of potent mediators of inflammation (eg, prostaglandins, leukotrienes) by inhibiting the release of arachidonic acid

Arachidonic acid is released from membrane phospholipids by phospholipase A2

Corticosteroids are capable of producing a rise in IOP

Absorption

Following topical instillation into the conjunctival sac, absorbed into the aqueous humor and minimal systemic absorption occurs

Submicron particles (Lotemax SM) have faster dissolution in tears and twice the penetration into aqueous humor compared with original Lotemax formulation

Metabolism

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

Ophthalmic Administration

Remove contact lenses

Do not to touch the eyelid or surrounding areas with the tip of the bottle/tube

Keep cap on bottle/tube when not in use

Wash hands prior to administering; do not use if tamper evident container compromised

If using other eye drops, advise patient to wait at least 5 minutes between instillation

Ophthalmic suspension (Inveltys, Alrex, Lotemax, Eysuvis): Shake bottle for several seconds before using

Lotemax or Lotemax SM gel: Invert closed bottle and shake once to fill tip before instilling drops

Lotemax ointment: Apply thin ribbon to conjunctival sac; do not wear contact lenses while using this product

Storage

All formulations

• Do not use if tamper-evident overcap seal is not intact
• Store upright at 15-25°C (59-77°F); do not freeze