Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2017 Publisher: Bausch & Lomb GmbH, Brunsbütteler Damm 165-173, 13581, Berlin, Germany
Pharmacotherapeutic group: Corticosteroid
ATC code: S01BA14
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.
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.
Placebo controlled studies demonstrated that Lotemax 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, Lotemax 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 Lotemax treated patients. In many patients treated with Lotemax 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.
There are no data available in the paediatric population.
Results from oral and ocular administration of Lotemax 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 Lotemax 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 Lotemax.
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.
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