Epinastine

Article Author:
Mawra Jha
Article Editor:
Majid Moshirfar
Updated:
6/5/2020 9:07:42 PM
PubMed Link:
Epinastine

Indications

Epinastine belongs to the class of second-generation antihistamines and is also a mast cell stabilizer. It also shows anti leukotriene, anti-PAF, and anti-bradykinin activities, which provide additional anti-allergic activities. Antihistamines and mast cell stabilizers have been used to manage various allergic conditions for many years.

Currently, epinastine is FDA approved to treat:

Allergic conjunctivitis - Allergic conjunctivitis is an umbrella term that includes[1][2]:

  1. Perennial allergic conjunctivitis (PAC) 
  2. Seasonal allergic conjunctivitis (SAC)
  3. Vernal keratoconjunctivitis (VKC) 
  4. Atopic keratoconjunctivitis (AKC) 

Epinastine is used in many countries to treat the following conditions as well:

  • Chronic urticaria[3]
  • Psoriasis vulgaris[3]
  • Allergic Rhinitis[3]
  • Atopic Dermatitis[4]

The chemical structure of epinastine is a benzazepine, which is 6,11-dihydro-5H-dibenzo[b,e]azepine in which the azepine ring merges with the side of 4,5-dihydro-1H-imidazole-2-amine. It is a member of benzazepine and guanidines. It is solid at room temperature, and the melting point is 205 to 208 degrees Celsius.

Mechanism of Action

Epinastine acts through various pathways to decrease inflammation. It acts as:

  1. a) Mast cell stabilizer:-Mast cells, when activated, promote IgE mediated allergic reactions. Epinastine causes the cessation of degranulation of mast cells by stabilizing them to reduce the inflammation.[1] Mast cell stabilizers act via altering the outcome of delayed chloride channels in the cellular membrane, which is essential for the degranulation of mast cells.
  1. b) Anti-histamine:-Inflammatory conditions have been very well known to be associated with the activation of histamine receptors. Histamine is known to increase the permeability of the vessels as a result of which fluid exudates into the interstitial space. The vascular phase is followed by the cellular phase and sets of an inflammatory cascade. Drugs that block the effects of histamine by competitively inhibiting histamine at its receptors or by behaving as inverse agonists are known as anti-histamines. It prevents the binding of histamine to H1 and H2 receptors.[5]

 c) It ceases the release of pro-inflammatory mediators, and hence inflammatory response does not progress.

Administration

The drug is available as epinastine hydrochloride eye drops, as oral epinastine tablets, and in the form of syrup for the management of various diseases.

Eye Drops

Epinastine has shown superiority to placebo in the management of various manifestations of allergic conjunctivitis. It is used topically as eye drops for allergic conjunctivitis.

Topical mast cell stabilizers and antihistamines are effective in providing relief in allergic conjunctivitis without any systemic absorption. Patients can use it throughout the allergy season. It shows the onset of action within 3 minutes, and the action lasts for over 8 hours.[6]

It can be used as one drop in each eye twice daily.[7]

In the USA, only the topical ophthalmic drops are an approved dose form.

Oral Tablets

Clinicians can prescribe this drug for patients with allergic conditions in the form of oral tablets at a dose of 10 to 20 mg once daily.[8]

Syrup:

Epinastine is also available in the form of syrup for the pediatric age group. The clinician should adjust dosing for pediatric patients.[8]

Adverse Effects

Epinastine is a safe and well-tolerated drug. It is used topically as an eye drop, and it does not cause any systemic side effects.[9] However, it can cause a burning sensation in the eyes, hyperemia, increased lacrimation, folliculitis, and pruritus.

It is unable to cross the blood-brain barrier, and hence it doesn’t cause any adverse effects related to the central nervous system. There is no diffusion at the central nervous system because of its polarity and cationic charge at the ph of the physiological state.[10]

It has no cardiotoxic effects.[3]

Epinastine is not teratogenic, even at high doses in the animal model[3]. However, there is not enough data from human clinical trials, and hence, it should be used in pregnancy only if the use justifies the benefit as compared to potential risk.

Contraindications

Epinastine is contraindicated in patients who have allergy/sensitivity to epinastine. Epinastine should be administered only after a test dose.

Use in specific cases:

  • Pregnancy 

Epinastine is a pregnancy category C drug. However, it should be used in pregnant patients judiciously.

  • Breastfeeding Mothers

Studies have shown that epinastine gets transferred into breastmilk, but the resulting infant serum levels are minimal. Nonetheless, breastfeeding mothers must consult a physician before administering epinastine.

  • Pediatric Population

The safety of the drug has not been established in patients below two years of age. The medication should have the dose adjusted according to the patient's body weight in the pediatric age group above two years.

  • Geriatric Population 

No such difference in the dose has been reported for geriatric patients. However, the clinician should obtain a thorough liver function and kidney function tests before prescribing epinastine.

Monitoring

Pharmacokinetic

Epinastine is a powerful anti-allergic drug which has antihistaminic properties. In addition to that, epinastine also shows anti leukotriene, anti-PAF, and anti-bradykinin activities, which provide additional anti-allergic activities.[3]

Plasma concentration at steady state is approximately 5.96 to 6.04 ng/ml.[10]

Epinastine is categorized as a second-generation antihistamine as it can not cross the blood-brain barrier. There is no diffusion at the central nervous system because of its polarity and cationic charge at the ph of the physiological state. Since it doesn’t cross the blood-brain barrier, it has no CNS effects and does not cause sedation in patients.

The duration of onset of epinastine is approximately 180 seconds and lasts for about 8 hours when administered as an eye drop.

Monitoring

Physicians should educate the patients about the course of therapy, potential adverse/side effects, and steps to take in case of an adverse event. Patients should be monitored via regular checkups to assess the relief in their symptoms. Patient compliance with the prescription should be ensured and encouraged. Drug dose should be adjusted as needed based on regular checkups and thorough examination. 

Toxicity

There are no reported cases of overdose with epinastine to date. However, in case of an overdose, the institution and health care providers must act promptly to ensure airway patency and that there is no circulatory collapse. 

Enhancing Healthcare Team Outcomes

Anti-histamines have been the mainstay for the treatment of allergic conditions. Epinastine is a mast cell stabilizer as well as an anti-histaminic, which the FDA has approved for topical use to relieve various allergic conditions. Since epinastine does not possess any CNS toxicity, it is superior to other anti-histamines with sedative properties. An accurate diagnosis is necessary before prescribing epinastine. Any clinician can prescribe epinastine, and the patient must be monitored regularly for adverse outcomes. Patients should be encouraged to follow the treatment plan; this requires a team effort from the clinicians, nursing staff, and pharmacists, coordinating efforts and communicating across interprofessional lines to improve and enhance patient care outcomes.


References

[1] Ben-Eli H,Solomon A, Topical antihistamines, mast cell stabilizers, and dual-action agents in ocular allergy: current trends. Current opinion in allergy and clinical immunology. 2018 Oct;     [PubMed PMID: 30020258]
[2] La Rosa M,Lionetti E,Reibaldi M,Russo A,Longo A,Leonardi S,Tomarchio S,Avitabile T,Reibaldi A, Allergic conjunctivitis: a comprehensive review of the literature. Italian journal of pediatrics. 2013 Mar 14;     [PubMed PMID: 23497516]
[3] Tasaka K, Epinastine: An update of its pharmacology, metabolism, clinical efficacy and tolerability in the treatment of allergic diseases. Drugs of today (Barcelona, Spain : 1998). 2000 Nov;     [PubMed PMID: 12845334]
[4] Fraunfelder FW, Epinastine hydrochloride for atopic disease. Drugs of today (Barcelona, Spain : 1998). 2004 Aug     [PubMed PMID: 15510239]
[5] Maciel-Guerra H,Penha MÁ,Jorge MFS,Libório RDS,Carrijo ACNDA,Parise-Fortes MR,Miot HA, Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil. Anais brasileiros de dermatologia. 2018 Mar;     [PubMed PMID: 29723372]
[6] Friedlaender MH, Epinastine in the management of ocular allergic disease. International ophthalmology clinics. 2006 Fall;     [PubMed PMID: 17060794]
[7] Whitcup SM,Bradford R,Lue J,Schiffman RM,Abelson MB, Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis. Clinical therapeutics. 2004 Jan;     [PubMed PMID: 14996515]
[8] Sarashina A,Tatami S,Yamamura N,Tsuda Y,Igarashi T, Population pharmacokinetics of epinastine, a histamine H1 receptor antagonist, in adults and children. British journal of clinical pharmacology. 2005 Jan;     [PubMed PMID: 15606439]
[9] Pradhan S,Abhishek K,Mah F, Epinastine: topical ophthalmic second generation antihistamine without significant systemic side effects. Expert opinion on drug metabolism     [PubMed PMID: 19630694]
[10] Jeong SH,Jang JH,Cho HY,Lee YB, Pharmacokinetic Comparison of Epinastine Using Developed Human Plasma Assays. Molecules (Basel, Switzerland). 2020 Jan 3;     [PubMed PMID: 31947890]