Medications for Allergy

(BANM, US Adopted Name, rINNM)

Drug Nomenclature

Note. Cabastine (rINN) is the racemate of levocabastine.

Pharmacopoeias. In Europe and US.

European Pharmacopoeia, 6th ed. (bevocabastine Hydrochloride). A white or almost white powder. Practically insoluble in water slightly soluble in alcohol and in a 0.2% solution of sodium hydroxide sparingly soluble in methyl alcohol. Protect from light.

The United States Pharmacopeia 31, 2008 (bevocabastine Hydrochloride). Protect from light.

Adverse Effects and Precautions

As for the antihistamines in general. The most common adverse effects reported with levocabastine eye drops are transient stinging and burning of the eyes, urticaria, dyspnoea, drowsiness, and headache. With nasal use headache, nasal irritation, somnolence, and fatigue have been noted. The use of levocabastine nasal spray is not recommended in those with significant renal impairment.

Pharmacokinetics

Levocabastine is absorbed after both nasal and ocular use. Systemic availability has been estimated at 60 to 80% after nasal doses and 30 to 60% after ocular use. However absolute peak plasma concentrations are low. Plasma protein binding is about 55%. An elimination half-life of 35 to 40 hours has been reported for all routes of delivery. Elimination of levocabastine is primarily renal with 70% excreted as unchanged drug and 10% as an inactive acetylglucuronide metabolite the remaining 20% is excreted unchanged in the faeces. Trace amounts of levocabastine have been found in breast milk after ocular and nasal use.

Uses and Administration

Levocabastine, a piperidine derivative, is a long-acting and potent antihistamine with a rapid onset of action. Levocabastine hydrochloride equivalent to 0.05% levocabastine is used topically twice daily as eye drops or as a nasal spray in the treatment of allergic conjunctivitis and rhinitis, respectively, in adults and children aged 9 years and over. The frequency of the dose in both conditions may be increased to 3 or 4 times daily if necessary. In conjunctivitis it is recommended that treatment should be stopped if there is no improvement within 3 days.

Preparations

Proprietary Preparations

Argentina: Histimet

Australia: Livostin

Austria: Livostin

Belgium: Livostin

Brazil: Livostin

Canada: Livostin

Czech Republic: Livostin

Denmark: Livostin

Finland: Livostin

France: Levophta

Germany: Levophta Livocab

Greece: Livostin

Hungary: Livostin

Israel: Livostin

Italy: Levostab Livocab Livostin

Japan: Livostin

Mexico: Livostin

The Netherlands: Livocab

Norway: Livostin

New Zealand: Livostin

Portugal: Livostin

South Africa: Livostin

Spain: Bilina Livocab

Sweden: Livostin

Switzerland: Livostin

Thailand: Livostin

Turkey: Livostin

United Kingdom: Livostin

USA: Livostin

Venezuela: Livostin

It is well-known that people in certain parts of the planet are far more likely to suffer from allergic rhinitis than in other parts, though it is not so clear why that happens. In Denmark, just over one in every 100 visits to a family physician involves seasonal allergic rhinitis, though in Britain the figure is one in 50 and in Australia almost one in 10. The disease is more of an urban than a rural phenomenon, a fact which has led many researchers to point a finger at air pollution as an aggravating condition.

Air pollution may indeed play a role in the increased incidence of this condition, perhaps because gases such as ozone and nitrous oxide are harming epithelial cells, the bloodless surface covering of human tissues, glands, and organs. But one study suggested that the role of air pollution may have been exaggerated. The children of Leipzig, despite breathing the notoriously polluted and sulfur dioxide-laden air of former East Germany, were found to have lower rates of rhinitis than children in the western, alpine city of Munich.

Physicians and rhinologists have traditionally divided allergic patients into those whose symptoms were seasonal and those who suffered all year round. Yet a single patient with a number of seasonal reactions to allergens that peak at different times of year may appear to have a year-round allergy. In any case, an individual with severe perennial symptoms should receive different drug treatments from an individual with mild seasonal symptoms.

For the person who suffers moderate, occasional allergic rhinitis symptoms, there are a variety of pharmacological allies available. Allergen avoidance is, as always, the ideal solution, but it may prove practically impossible for allergy sufferers who have no choice but to share the air they breathe with allergenic pollen. It helps, however, to know when the pollen count of a particular allergenic plant is going to begin climbing, and when it will peak, in order to begin therapy beforehand.

Treatment may include the use of non-sedating oral antihistamines, or topical antihistamines or so-called mast cell stabilizers to the nose and eyes. Mast cells act as receptors for the allergenic pollen, and for the antibody immunoglobulin E which the body uses to defend itself. Its reaction to these signals is to release substances such as histamine that worsen rhinitis symptoms.

Oral antihistamines, which are used to prevent this histamine reaction, offer a number of alternatives in terms of speed of onset and duration of effect for the treatment of milder seasonal rhinitis, available under names such as terfenadine, cetirizine (Zyrtec), astemizole (Hismanal) and acrivastine (Semprex). Topical antihistamines such as levocabastine (Livostin) and azelastine (Astelin), however, are becoming more widely used because their effect can be concentrated on the most affected organ. Topical sodium cromoglycate, long used in treatment of allergic rhinitis symptoms, still has a place today because the absence of significant side effects permits regular use without worry.

Those who suffer from more severe forms of seasonal allergic rhinitis should be treated according to whether they are primarily eye sufferers or primarily nose sufferers. If their symptoms are mostly in the nose, they should receive topical nasal steroids before the beginning of the pollen season to minimize early damage to cells and inflammation, which would release aggravating substances such as histamines and tryptase. Eye treatment may also be necessary for mostly nasal sufferers.

If the eye is the source of most discomfort, choices are limited to the topical use of sodium cromoglycate in conjunction with nasal steroids to lessen general irritation. The only readily-available alternative to that is an oral antihistamine.

Should allergic rhinitis be really severe and treatment beyond the limits of such drugs, the patient will probably need to see a specialist who may, in a crisis, recommend short-term systemic corticosteroids. Immunotherapy may also be considered at this juncture. These more drastic treatments represent the weapons of last resort against seasonal allergic rhinitis at present, but with allergic mechanisms better understood every year, it may not be that way for long.

The eye is one of the most sensitive organs of the body when it comes to manifesting allergic reactions. Airborne allergens can readily reach the ophthalmic conjunctiva, and systemic allergies are often manifested in the ophthalmic tissues. Because of these facts, recognizing and treating ophthalmic allergic conditions remains a major challenge for the clinician.

Inflammation in the eye is the result of numerous interrelated inflammatory pathways

At the recent annual meeting of the American Academy of Allergy, Asthma, and Immunology, Dr. Leonard Bielory of the University of Medicine and Dentistry of New Jersey reviewed the known causes, differential diagnosis, and treatment options for the management of ocular allergic events.

He pointed out several general considerations:

Avoidance of allergens remains the mainstay in the management of any ocular disorder.

Cold compresses provide considerable relief, especially from ocular pruritus. In general, he noted that all ocular medications provide additional subjective relief when refrigerated and applied cold.

Tear substitutes help in the direct removal and dilution of allergens. If these products are inadequate, ointments or time-released tear replacements can be used at night to moisturize the ocular surface during sleep.

Topical decongestants act as vasoconstrictors that are highly effective in reducing ocular redness. However, extended use of topical vasoconstrictors can lead to “rhinitis medicamentosa,” a condition in the eye that is analogous to that observed to result from the overuse of nasal vasoconstrictors. Symptoms can include increased swelling and rebound redness that may persist even after the drops are discontinued. These drugs should not be used in patients with narrow angle glaucoma.

Newer topical antihistamines (i.e., olopatadine (Patanol), levocabastine (Livostin), cromolyn sodium (Nasalcrom), lodoxamide (Alomide)) when applied as single-agent therapy to the eye can effectively reduce redness and itching, but many of the older antihistamines (pyrilamine and pheniramine maleate) provide greater effectiveness when they are applied together with a vasoconstrictor.

Orally administered nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce ocular signs of allergy. Similarly, topically administered NSAIDs such as flurbiprofen (Ansaid), ketorolac (Toradol), and diclofenac (Voltaren) can reduce redness and itching. Other NSAIDs have been developed for the eye (i.e., indomethacin, sulindac, tolmetin), but these have been associated with a low to moderate incidence of burning and stinging.

When topically administered antihistamines, vasoconstrictors, or cromolyn sodium is ineffective, mild topical steroids can be considered. They are highly effective in the treatment of acute and chronic forms of allergic conjunctivitis. However, they are associated with often potentially severe adverse reactions such as increased intraocular pressure, the development of underlying viral infections, and cataract formation. New findings suggest that the transient rise in intraocular pressure that is seen in some persons may be a genetically influenced trait not observed in all persons. Although the effectiveness of various esters of the same corticosteroid base may vary, their ability to increase intraocular pressure remains constant. These drugs should be avoided when herpetic infection may be present in the eye, because the infection can progress rapidly in the presence of a steroid.

Allergic conjunctivitis has been suppressed in animals by the oral administration of an antigen. Whether this will be effective in helping humans has yet to be proven. Oral and intranasal administration of retinal antigens and the S-antigen, as well as the use of crude retinal extracts, has been shown experimentally to inhibit autoimmune uveitis.

Some new therapies that are being investigated include:

• Nedocromil: A potent inhibitor of various allergic inflammatory cells, it can stabilize mast cells and inhibit histamine release more effectively than cromolyn. Is more effective than placebo in improving clinical symptoms of seasonal allergic conjunctivitis. Inhaler under the brand name Tilade; an eye drop under the brand name Alocril; liquid preparations in the UK under the name Rapitil.
• Pentigitide: Also known as human IgE pentapeptide (HEPP), a synthetic peptide that duplicates a five amino acid sequence of the Fc region of the IgE molecule and that has a similarity to the first four amino acids in substance P. It has been reported to be effective in decreasing signs and symptoms of allergic conjunctivitis.
• N-Acetylaspartylglutamic acid (NAAGA): A mast cell stabilizer that may control allergic conjunctivitis.
• Cyclosporine: A cyclic peptide that has immunomodulating activity via actions on interleukin-2 (IL-2). A 2% solution has been shown to decrease signs and symptoms of vernal conjunctivitis. A new carrier (alpha-cyclodextrin) has been recently developed that increases ocular penetration and improves ocular tolerability.
• FK506: May be effective in treating a variety of immune-modulated diseases such as corneal graft rejection, keratitis, scleritis, ocular pemphigoid, and uveitis. It inhibits the generation of cytotoxic lymphocytes and the production of IL-2, IL-3, and gamma-interferon.