- epinastine hydrochloride
POM: Prescription only medicine
This information is intended for use by health professionals
Older peopleRelestat has not been studied in older people. Post-marketing safety data from the tablet formulation of epinastine hydrochloride (up to 20 mg once daily) indicates that there are no particular safety issues for older people compared with adult patients. As such, no dosage adjustment is considered to be necessary.
Paediatric populationThe safety and efficacy in children ≥ 12 years has been established in clinical trials. Relestat may be used in adolescents (12 years of age and older) at the same dosage as in adults.The safety and efficacy of Relestat in children aged less than 3 years have not been established. No data are available. There are limited data on the safety in children aged 3-12 years, described in section 5.1.
Patients with hepatic impairmentRelestat has not been studied in patients with hepatic impairment. Post-marketing safety data from the tablet formulation of epinastine hydrochloride (up to 20 mg once daily) indicates that the incidence of adverse reactions was higher in this group compared with adult patients without hepatic impairment. The daily dose of a 10 mg epinastine hydrochloride tablet is more than 100-fold higher than the daily dose following Relestat. In addition, the metabolism of epinastine in humans is minimal (<10%). Therefore, no dosage adjustment is considered to be necessary.
Patients with renal impairmentRelestat has not been studied in patients with renal impairment. Post-marketing safety data from the tablet formulation of epinastine hydrochloride (up to 20 mg once daily) indicate that there are no particular safety issues for patients with renal impairment. As such, no dosage adjustment is considered to be necessary.
Method of AdministrationRelestat is for topical ophthalmic use only.To avoid contamination of the eye or eye drops do not allow the dropper tip to come into contact with any surface.If more than one topical ophthalmic medicinal product is being used, the different medicinal products should be administered at least 10 minutes apart.
PregnancyData on a limited number (11) of exposed pregnancies indicate no adverse effects of epinastine on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3).Caution should be exercised when prescribing to pregnant women.
Breast-feedingEpinastine is excreted in the breast milk of rats, but it is not known if epinastine is excreted in human milk. Due to the lack of experience, caution should be exercised when prescribing to breast-feeding women.
FertilityThere are no adequate data from the use of epinastine on fertility in humans.
Nervous system disordersUncommon: headache
Eye disordersCommon: burning sensation/ eye irritationUncommon: conjunctival/ ocular hyperaemia, eye discharge, eye dryness, eye pruritus, visual disturbance, increased lacrimation*, eye pain*
Respiratory, thoracic and mediastinal disordersUncommon: asthma, nasal irritation, rhinitis
Gastrointestinal disordersUncommon: dysgeusia*Increased lacrimation and eye pain have been identified during postmarketing use of Relestat in clinical practice.
Paediatric populationFrequency, type and severity of adverse reaction in adolescents ≥ 12 years of age are expected to be the same as in adults.There is limited experience in children aged 3-12 years regarding frequency, type and severity of adverse reactions. Adverse reactions reported in phosphate containing eye drops Cases of corneal calcification have been reported very rarely in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.
Mechanism of actionEpinastine is a topically active, direct H1-receptor antagonist. Epinastine has a high binding affinity for the histamine H1-receptor and a 400 times lower affinity for the histamine H2-receptor. Epinastine also possesses affinity for the α1-, α2-, and the 5-HT2 receptor. It has low affinity for cholinergic, dopaminergic and a variety of other receptor sites. Epinastine does not penetrate the blood/brain barrier and, therefore, does not induce side effects of the central nervous system, i.e., it is non-sedative.
Pharmacodynamic effectsFollowing topical eye application in animals, epinastine showed evidence for antihistaminic activity, a modulating effect on the accumulation of inflammatory cells, and mast cell stabilising activity.In provocation studies with allergens in humans, epinastine was able to ameliorate ocular symptoms following ocular antigen challenge. The duration of the effect was at least 8 hours.
Paediatric populationA 6-week, randomised, double-masked, vehicle controlled study (2:1) involving 96 ocular-wise non-symptomatic, healthy children aged 3-12 years, indicated that Relestat was well tolerated and did not identify any significant differences between the groups for any safety variable. Treatment related reactions were conjunctival follicles (6.3% in both epinastine and vehicle-treated subjects) and conjunctival hyperaemia (1.6% of epinastine treated subjects and none in the vehicle group). Safety and efficacy in patients ≥ 12 years has been established in clinical trials.
AbsorptionFollowing administration of one drop of Relestat in each eye twice daily, an average maximum plasma concentration of 0.042 ng/ml is reached after about two hours.
DistributionEpinastine has a volume of distribution of 417 litres and is 64% bound to plasma proteins.
BiotransformationLess than 10% is metabolised.
EliminationThe clearance is 928 ml/min and the terminal plasma elimination half-life is about 8 hours.Epinastine is mainly excreted renally unchanged. The renal elimination is mainly via active tubular secretion.Preclinical studies in vitro and in vivo show that epinastine binds to melanin and accumulates in the pigmented ocular tissues of rabbits and monkeys. In vitro data indicate that the binding to melanin is moderate and reversible.