Treatment of post-operative inflammation following ocular surgery.

Posology
Adults and elderly
One to two drops four times daily beginning 24 hours after surgery and continuing throughout the post-operative period.
The duration of treatment should not exceed 2 weeks.
Paediatric Population
Lotrell should not be used in the paediatric age group until further data become available.

Method of administration
Ocular use
Shake the bottle vigorously before using the eye drops.
This product is sterile when packaged. Patients should be advised not to allow the dropper tip to touch any surface, as this may contaminate the suspension. The bottle should be closed immediately after use.

Lotrell is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures; untreated purulent acute infections which, similar to other infectious diseases, can be masked and worsened by corticoids, 'red eye' with unknown diagnosis and infection caused by amoeba. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to other corticosteroids.

Prolonged use of corticosteroids may result in ocular hypertension or glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision, and in posterior subcapsular cataract formation. Steroids should be used with caution in the presence of glaucoma.
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Prolonged use of corticosteroids may suppress the host response and may increase the possibility 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.
Long term treating with corticosteroids can cause fungal disease. Fungal disease should be considered in the differential diagnosis when a corneal ulcer persists.
Lotrell contains benzalkonium chloride which may cause eye irritation.
In general patients should not wear contact lenses after cataract surgery, unless contact lens wearing is medically indicated.
Contact with soft contact lenses should be avoided. Patients should be advised to remove contact lenses prior to application and wait at least 15 minutes before reinsertion. Known to discolour soft contact lenses.
If signs and symptoms fail to improve after two days, the patient should be re-evaluated. If this product is used for 10 days or longer, intraocular pressure should be monitored.

Since loteprednol etabonate is not detected in plasma following the topical administration of Lotrell, it is not expected to affect the pharmacokinetics of systemically administered medicinal products. However, the low potential of ocular loteprednol etabonate eye drops to increase the intraocular pressure may be adversely affected by systemically administered medicinal products with anticholinergic activity. In patients receiving concomitant ocular hypotensive therapy, the addition of loteprednol etabonate may increase intraocular pressure and decrease the apparent ocular hypotensive effect of these medicinal products.
Concurrent administration of cycloplegics may increase the risk of raised intraocular pressure.
Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweights the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

Pregnancy
For Lotrell no clinical data on exposed pregnancies are available. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown and Lotrell should not be used in pregnancy unless clearly necessary.
Breastfeeding
It is not known whether loteprednol etabonate is excreted in human milk. Excretion of loteprednol etabonate in breast milk has not been investigated in animal studies. Therefore, the use of loteprednol etabonate is contraindicated in lactating women.

No studies on the effects on the ability to drive and use machines have been performed.
If there are any transient effects on vision, the patient should be advised to wait until these subside before driving or operating machinery.

Reactions associated with ophthalmic steroids include elevated intraocular pressure in steroid responsive patients, 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.
Ocular adverse reactions occurring in patients treated with loteprednol etabonate ophthalmic suspension in clinical studies included the following:
All undesirable effects have been classified as follows very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000), or very rare (<1/10,000), not known (cannot be estimated from the available data).

Eye disorders
Common:
Corneal defect, eye discharge, ocular discomfort, dry eye, epiphora, foreign body sensation in eyes, conjunctival hyperaemia and ocular itching.
Uncommon:
Abnormal vision, chemosis, keratoconjunctivitis, conjunctivitis, iritis, eye irritation, eye pain, conjunctival papillae, photophobia and uveitis.
Not known:
Vision blurred (see also section 4.4).
Some of these events were similar to the underlying ocular disease being studied
Non-ocular events possibly related to treatment occurring in patients included:
Infections and infestations
Uncommon:
Pharyngitis
Rare:
Urinary tract infection and urethritis
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rare:
Breast neoplasm
Psychiatric disorders
Rare:
Nervousness
Nervous system disorders
Common:
Headache
Rare:
Migraine, taste perversion, dizziness, paresthesia
Ear and labyrinth disorders
Rare:
Tinnitus
Respiratory, thoracic and mediastinal disorders
Uncommon:
Rhinitis
Rare:
Cough
Gastrointestinal disorders
Rare:
Diarrhoea, nausea and vomiting
Skin and subcutaneous tissue disorders
Rare:
Face oedema, urticaria, rash, dry skin and eczema 

Musculoskeletal and connective tissue disorders
Rare:
Twitching
General disorders and administration site conditions
Common:
Instillation site burning
Uncommon:
Asthenia
Rare:
Chest pain, chills, fever and pain
Investigations
Rare:
Weight gain
In a summation of controlled, randomised studies of individuals treated for 28 days or longer with loteprednol etabonate, the incidence of significant elevation of intraocular pressure (≥10 mmHg) was 2% (15/901) among patients receiving loteprednol etabonate, 7% (11/164) among patients receiving 1% prednisolone acetate and 0.5% (3/583) among patients receiving placebo.

To reports any side effect(s):
• Saudi Arabia
-The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317--2356-2340.
Toll free phone: 19999
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
• Other GCC States:
Please contact the relevant competent authority.

No case of overdose has been reported. Acute overdosage is unlikely to occur via the ophthalmic route.

Pharmacotherapeutic group: Corticosteroid, ATC code: S01BA14 Mechanism of action
Corticosteroids suppress the inflammatory response to inciting agents of mechanical, chemical or immunological nature. No generally accepted explanation of this steroid property has been advanced. Pharmacodynamic effect
Loteprednol etabonate is a new class of corticosteroid with potent antiinflammatory activity designed to be active at the site of action. Its antiinflammatory activity is similar to the most powerful steroid used in ophthalmology but with less intraocular pressure. Animal studies have shown that loteprednol etabonate has a binding affinity to steroid receptors that is 4.3 times greater than dexamethasone. This new class of steroids consists of bioactive molecules whose in-vivo transformation to non-toxic substances can be predicted from their chemistry and knowledge of enzymatic pathways in the body. Cortienic acid is an inactive metabolite of hydrocortisone and analogs of cortienic acid are also devoid of corticosteroid activity. Loteprednol etabonate is an ester derivative of one of these analogs, cortienic acid etabonate. Clinical efficacy and safety
Placebo controlled studies demonstrated that Lotrell is significantly more effective than placebo for the treatment of external ocular inflammation.
Corticosteroids are capable of producing a rise in intraocular pressure in susceptible individuals. In a small study, Lotrell demonstrated a significantly longer time to produce a rise in pressure than did prednisolone acetate. The overall incidence of patients who had an intraocular pressure elevation of ≥10 mm Hg was lower in the Lotrell treated patients. In many patients treated with Lotrell the ultimate rise in intraocular pressure never achieved the levels seen in patients treated with prednisolone acetate. In clinical trials only 2% of all patients had an intraocular pressure elevation of ≥10 mm Hg. In the small percentage of patients who did show a significant rise in intraocular pressure, pressure rapidly returned to normal on discontinuation of the medicinal products. Paediatric population
There are no data available in the paediatric population.

Results from oral and ocular administration of Lotrell in normal volunteers have shown that there are low or undetectable concentrations of either unchanged material or the metabolite. Results from a bioavailability study established that plasma concentrations of loteprednol etabonate following ocular administration of one drop in each eye of Lotrell eight times daily for 2 days or four times daily for 42 days were below the limit of quantitation (1 ng/mL) and detection (500 pg/mL) at all sampling times. In the same study, plasma cortisol concentrations were measured and no evidence of adrenal cortex suppression was observed. All cortisol measurements were within normal range. This study suggests that limited, if any, systemic absorption occurs with Lotrell.

Preclinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and genotoxicity.
Embryotoxicity and teratogenic effects were observed in reproductive toxicity studies in rabbits (delayed ossification, increased incidence of meningocele, abnormal left carotid artery and limb flexures) at oral doses 35 times the maximum daily clinical dose and in rats (decreased foetal body weight and skeletal ossification, absent innominate artery, cleft palate and umbilical hernia) at oral doses greater than 60 times the maximum daily clinical dose.
Mild ocular irritation was noted with both the acute and multidose rabbit ocular studies.

Benzalkonium Chloride
Tyloxapol
Edetate disodium
Glycerol
Povidone K 29/32
Sodium Hydroxide 1N And / or Hydrochloric acid 1N
Water for injection

Not applicable.

2 years

Do not store above 30 °C.
Keep out of reach and sight of children.

Immediate Container: 5 ml fill in 10 ml bottle
Secondary Container: Carton, label with PIL

No special requirements.