Medications for Allergy

(British Approved Name Modified, rINNM)

Drug Nomenclature

Pharmacopoeias. In Chin, Europe, International, Japan, and US.

European Pharmacopoeia, 6th ed. (Sodium Cromoglicate). A white or almost white, hygroscopic, crystalline powder. Soluble in water practically insoluble in alcohol. Store in airtight containers. Protectfrom light.

The United States Pharmacopeia 31, 2008 (Cromolyn Sodium). A white, odourless, hygroscopic, crystalline powder. Soluble in water insoluble in alcohol and in chloroform. Store in airtight containers.

Adverse Effects

Inhalation ofsodium cromoglicate may cause transient bronchospasm, wheezing, cough, nasal congestion, and irritation of the throat. Nausea, headache, dizziness, an unpleasant taste, and joint pain and swelling have been reported. Other reactions include aggravation of existing asthma, urticaria, rashes, pulmonary infiltrates with eosinophilia, dysuria, and urinary frequency. Severe reactions such as marked bronchospasm, laryngeal oedema, angioedema, and anaphylaxis have been reported rarely. Intranasal use ofsodium cromoglicate may cause transient irritation of the nasal mucosa, sneezing, and occasionally epistaxis. Nausea, skin rashes, and joint pains have occurred when it is taken orally. Transient burning and stinging have occasionally been reported after use ofsodium cromoglicate eye drops.

Formulation. Some of the adverse effects reported with sodium cromoglicate may be due to its formulation: there is a view that some of the irritant effects reported on inhalation may be due to the use of dry powder inhalers. It has also been suggested that in some patients receiving sodium cromoglicate via a nebuliser, hypotonicity of the nebuliser solution may induce bronchospasm, although others consider this debatable. Nausea, bloating, abdominal cramps, and flatulence developed in a 24-year-old lactase-deficient woman 2 hours after the use ofsodium cromoglicate (Intal) inhalation capsules via a turbo-haler for exercise-induced asthma. These symptoms recurred on rechallenge and were attributed to ingestion of lactose contained within the capsules.

Precautions

Sodium cromoglicate has no role in the treatment of acute asthmatic attacks. Withdrawal ofsodium cromoglicate may lead to recurrence of the symptoms of asthma. Should withdrawal be necessary it has been suggested that the dose be reduced gradually over a period of one week patients in whom sodium cromoglicate therapy has permitted a reduction of corticosteroid dosage may require restoration of full corticosteroid cover.

Systemic corticosteroid therapy that has been reduced or stopped in asthmatic patients may need to be reinstated if symptoms increase, during periods of stress such as infection, illness, trauma, or severe antigen challenge, or where airways obstruction impairs inhalation of sodium cromoglicate.

Pharmacokinetics

Sodium cromoglicate is poorly absorbed from the gastrointestinal tract, with a reported bioavailability of only 1%. It has been reported that on inhalation as a fine powder only about 8% of a dose is deposited in the lungs from where it is rapidly absorbed and excreted unchanged in the urine and bile. Less than 7% of an intranasal dose appears to be absorbed. The majority of an inhaled or an intranasal dose is swallowed and excreted unchanged via the gastrointestinal tract. About 0.03% of an ophthalmic dose is reported to be absorbed. The terminal elimination half-life has been reported to be about 20 minutes after intravenous dosage, but the elimination half-life after oral doses or inhalation is about 80 minutes.

A study in patients with exercise-induced asthma concluded that the plasma concentration of cromoglicate was almost certainly not related directly to its protective effect, although another study in asthmatic children given sodium cromoglicate by drypowder inhalation, found both blood concentration and clinical response to be correlated with inhalation technique.

Uses and Administration

Sodium cromoglicate is used for the prevention of allergic reactions. Although its precise mode of action remains uncertain, it is believed to act primarily by preventing release of mediators of inflammation from sensitised mast cells through stabilisation of mast-cell membranes. It has no direct antihistamine or anti-inflammatory action.

Sodium cromoglicate can prevent the asthmatic response to a variety of allergic and non-allergic stimuli. It is used in the management of chronic asthma that cannot be managed with inhaled beta₂ agonists alone it is not used for acute attacks of asthma. Sodium cromoglicate is also used in the prophylaxis and treatment of seasonal and perennial allergic rhinitis and allergic conditions of the eye including acute and chronic allergic conjunctivitis and vernal keratocon-junctivitis. It has been given orally, with dietary restriction, for the prevention of food allergies, and is also used in the treatment of mastocytosis. It is important that the regular use of sodium cromoglicate is maintained, both in the prophylactic control of asthma and in the management of other allergic conditions. Beneficial effects may take several weeks to become established.

In the prophylaxis of asthma, sodium cromoglicate is given by inhalation either as a dry powder, or as a nebulised solution, or from a metered-dose aerosol. The usual dose as dry powder or nebulised solution is 20 mg by inhalation 4 times daily increased, if necessary, to 6 or 8 times daily. Once the asthma has been stabilised it may be possible to reduce the dosage. In different countries, sodium cromoglicate is available in different strengths of metered-dose aerosol. Using a metered-dose aerosol providing 5 mg per inhalation, the usual dose is 10 mg four times daily, increased to 6 to 8 times daily if necessary it may be possible to reduce the dosage to 5 mg four times daily once the asthma has been stabilised. Additional doses as the aerosol or dry powder may be taken before exercise. Metered-dose aerosols providing 1 mg per inhalation are also available. The usual dose is 2 mg four times daily, which can be doubled if necessary. The adequacy of the lower dosage has been questioned (see under Administration, below).

Inhalation of sodium cromoglicate may cause bronchospasm separate inhalation of a beta₂ agonist such as salbutamol a few minutes beforehand should prevent this. Use of a combination product containing a beta₂ agonist is not recommended as this is liable to be used inappropriately for relief of bronchospasm rather than for its prophylactic effect. For the prophylaxis of allergic rhinitis, a 2 or 4% sodium cromoglicate solution can be given as a spray into both nostrils. The 2% spray contains about 2.5 mg per actuation and is given 4 to 6 times daily, and the 4% spray contains about 5 mg per actuation and is given 2 to 4 times daily. Prophylactic treatment for seasonal allergic rhinitis should begin 2 to 3 weeks before exposure to the offending allergen and should continue throughout the season. In allergic conjunctivitis and vernal keratoconjnnctivitis, sodium cromoglicate is used as drops of 2 or 4%, applied 4 to 6 times daily. In food allergy and in mastocytosis, sodium cromoglicate may be given in oral doses of 200 mg four times daily before meals. If satisfactory control is not achieved within 2 to 3 weeks the dosage may be doubled, but should not exceed 40 mg/kg daily a reduction in dosage may be possible once symptoms have been controlled.

For details of doses in children, see Administration in Children below.

Action. Sodium cromoglicate has a range of actions at cellular level that may be important for its protective effect in asthma. It is known as a mast cell stabiliser that inhibits the release of his-tamine and other inflammatory mediators from sensitised mast cells. Other reported actions include a direct effect on airway nerves and antagonism of substance P, which ties up with its inhibition of the effects of platelet activating factor (PAF). There have been a few reports of sodium cromoglicate producing bronchodilatation. However, in practice other drugs with accepted bronchodilating activity are used for this effect in asthma treatment schedules.

Administration. The effectiveness of sodium cromoglicate 2 mg four times daily by metered-dose aerosol inhaler has been reported by controlled studies in adults and children with asthma. However, although sodium cromoglicate 2 mg by inhalation from a metered-dose aerosol was reported to be as effective as 20 mg inhaled as powder, the tenfold difference in dosage has been questioned, and others have reported contrary results. It has been suggested that an aerosol supplying 5 mg per metered dose (see Uses and Administration, above) would be preferable. In a comparison of single-dose pretreatment from metered-dose inhalers, sodium cromoglicate 10 mg (2×5 mg puffs) was as effective as beclometasone dipropionate 200 micrograms in inhibiting bronchial responsiveness to histamine. Care is required if inhaled sodium cromoglicate is given via a spacer device evidence suggests that these may greatly influence the amount of drug delivered, reducing it to one-third of the dose delivered by inhaler actuation in some cases.

Administration in children. Children may be given sodium cromoglicate for prophylactic management of asthma and allergic rhinitis, and in the prophylaxis and treatment of acute and chronic allergic conjunctivitis and vernal keratoconjunctivitis, using adult doses, see Uses and Administration, above. Different countries may have different licensed lower age limits and some inhalation dosage forms are unsuitable in very young children. In food allergy and in mastocytosis, sodium cromoglicate may be given orally to children from 2 years of age. A dose of 100 mg is given four times daily before meals. If satisfactory control is not achieved within 2 to 3 weeks the dosage may be doubled but should not exceed 40 mg/kg daily a reduction in dosage may be possible once symptoms have been controlled. For food allergy, adult doses may be given to children from 14 years of age, and from 13 years for mastocytosis, see above.

Asthma. Sodium cromoglicate is used as a prophylactic agent in the management of chronic asthma, but in practice inhaled corticosteroids are preferred if regular prophylactic treatment is indicated, i.e. if the condition cannot be managed with occasional use of an inhaled short-acting beta₂ agonist alone. Even in children, in whom cromoglicate has tended to be more widely used, inhaled corticosteroids are considered first-line preventers. A systematic review comparing sodium cromoglicate with inhaled corticosteroids found that inhaled corticosteroids were superior in terms of asthma control and lung function for both children and adults with chronic asthma. However, guidelines still specify the use of cromoglicate or nedocromil as a valid alternative to inhaled corticosteroids in some circumstances. Response to treatment with nebulised sodium cromoglicate was found to be age-related in a study of children under 2 years of age with recurrent or persistent wheezy bronchitis and a history of allergic symptoms. It was effective in children of 12 to 24 months of age but not in those below 12 months. Similarly, nebulised sodium cromoglicate was no more effective than placebo in the treatment of a group of 31 infants with persistent wheezing aged under 1 year, and long-term inhalation therapy was ineffective in children aged 1 to 4years.

Cogan’s syndrome. Sodium cromoglicate eye drops improved blurred vision in a patient who had had Cogan’s syndrome for 18 years. Sodium cromoglicate capsules [by mouth] also reduced the frequency of fever attacks in this patient.

Cough. Sodium cromoglicate has been used with modest success by aerosol inhalation to suppress the cough associated with ACE inhibitor therapy in some patients. However, inhalation of nedocromil sodium was not helpful in the treatment of ACE inhibitor induced cough in 6 diabetic patients. A systematic review considered that there was no good evidence to support the use of inhaled cromoglicate or nedocromil in the treatment of non-specific cough in children.

Eczema. Application of a 4% sodium cromoglicate lotion was found to be of benefit in improving symptoms and reducing topical corticosteroid use in a study in children with moderately severe atopic dermatitis.

Food allergy. Oral sodium cromoglicate has been used in the prophylaxis of food allergy reactions. However, efficacy has not been unequivocally established.

Mastocytosis. Mastocytosis is a rare condition characterised by abnormal proliferation of mast cells and their accumulation in body tissues. Signs and symptoms of the disease result from the spontaneous or induced release of mast cell mediators. Mastocytosis occurs in cutaneous or systemic forms, which are further subdivided based on clinical presentation and prognosis. Clinical algorithms and recommendations for diagnosis, treatment, and response criteria have been developed.

• Cutaneous mastocytosis most often manifests as urticaria pigmentosa (disseminated red-brown macules, papules, or plaques) other symptoms include flushing, pruritus, urticaria, blistering, and dermatographism. Mastocytomas may occur as brownish solitary or multiple nodular accumulations of mast cells. In children with cutaneous mastocytosis, symptoms will resolve in about half by adolescence.

• Systemic mastocytosis can involve diverse organs and tissues including the bones, liver, spleen, lymph nodes, haematopoietic system, gastrointestinal tract, and also the skin. General symptoms include fatigue, weight loss, fever, and sweats. Gastrointestinal complaints such as abdominal pain and diarrhoea are common, and some patients may experience malabsorption, steatorrhoea, or peptic ulcer disease. Bone marrow involvement may result in bone pain, osteoporosis, fractures, bone marrow fibrosis, and myeloproliferative and myelodysplastic diseases. Other systemic effects include lymphadenopathy, hepatosplenomegaly, headache and other neuropsychiatric symptoms, syncope, and anaphylactoid reactions.

Avoidance of trigger factors is an important measure in the management of mastocytosis. Such factors include exposure to extremes of cold or heat (hot bath or sunbathing), emotional stress, mechanical irritation (vigorous towel rubbing, massage), infections, alcohol, some drugs (e.g. aspirin, NSAIDs, opioid analgesics, sympathomimetics, polymyxin B, dextran, radiographic dyes), and animal venoms.

Treatment is aimed at relieving symptoms and does not alter the course of the disease. H_rantagonist antihistamines such as hydroxyzine and cyproheptadine are used to provide relief of flushing, pruritus, urticaria, blistering, and abdominal pain. Patients at risk of anaphylactoid reactions should carry adrenaline for self-injection, and those who have repeated reactions should be given prophylactic antihistamines. H₂-antagonist antihistamines such as cimetidine, and proton pump inhibitors such as omeprazole, are used to manage gastrointestinal symptoms, particularly gastritis and peptic ulcer disease. Bisphosphonates may be helpful for osteopenia and bone pain. Sodium cromoglicate is given to manage abdominal pain, nausea, and diarrhoea. It may also provide some relief of headache, neuropsychiatric symptoms, and skin symptoms in some patients. Photochemotherapy using an oral psoralen with ultraviolet A irradiation (PUVA) has been used to reduce cutaneous manifestations of mastocytosis, but urticaria pigmentosa usually recurs within several weeks. Topical PUVA appears to be ineffective. Mastocytomas that cause symptoms may be treated with local PUVA or potent topical corticosteroids. Although surgical removal may be considered, the majority of mastocytomas will involute spontaneously.

Other treatments have also been tried in the treatment of small numbers of patients with aggressive systemic mastocytosis. Mixed results have been reported with the use of interferon alfa. There is a report of ciclosporin with methylprednisolone being used successfully. Imatinib has been used successfully in systemic mastocytosis with associated eosinophilia and with a mutation of the platelet-derived growth factor receptor-α gene on chromosome 4ql 2. Beneficial responses to cladribine have also occurred in a small number of patients with systemic disease.

Rhinitis and conjunctivitis. Many drugs, including sodium cromoglicate, are used in the management of allergic rhinitis and conjunctivitis. There is some evidence that nedocromil or lodoxamide may be more effective than cromoglicate in the management of vernal keratoconjunctivitis.

Preparations

British Pharmacopoeia 2008: Sodium Cromoglicate Eye Drops; Sodium Cromoglicate Powder for Inhalation

The United States Pharmacopeia 31, 2008: Cromolyn Sodium Inhalation Powder; Cromolyn Sodium Inhalation Solution; Cromolyn Sodium Nasal Solution; Cromolyn Sodium Ophthalmic Solution

Proprietary Preparations

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed

Argentina: Claroftal; Clo-5¤; Intal; Klonalcrom; Sificrom¤; Australia: Cromese; Intal; Opticrom; Rynacrom; Vistacrom¤; Austria: Acromax; Aeropaxyn; Allercrom¤; Allergo-COMOD; Coldacrom; Cromal; Cromoglin; Cromophtal; Dilospir¤; Intal; Lomusol; Opticrom¤; Pulmosin¤; Vividrin; Belgium: Lomudal; Lomusol; Opticrom; Vividrin¤; Brazil: Cromabak¤; Cromocato; Cromolerg; Intal; Maxicrom; Opticrom¤; Rilan; Canada: Apo-Cromolyn; Cromolyn; Gen-Cromolyn¤; Intal; Nalcrom; Novo-Cromolyn¤; Opticrom; Rynacrom¤; Solu-Crom; Vistacrom¤; Chile: Oftacon; Czech Republic: Allergo-COMOD; Allergocrom; Cromobene; Cromogen; Cromohexal; Cromolyn; Cusicrom; DNCG; Hay-Crom; Intal; Lecrolyn; Nalcrom; Stadaglicin; Steri-Neb Cromogen; Vividrin; Denmark: Hexacroman; Lecrolyn; Lomudal; Finland: Glinor; Lecrolyn; Lomudal; France: Alerion¤; Allergo-COMOD; Alloptrex; Cromabak; Cromadoses; Cromoptic; Cromosoft; Intercron; Lomudal; Lomusol; Multicrom; Nalcron; Ophtacalm; Opticron; Germany: Acecromol; Alerg; Allergo-COMOD; Allergocrom; Allergoval; Colimune; Crom-Ophtal; Cromo; Cromoglicin-ratiopharm¤; Cromoglicin¤; Cromohexal; Cromol¤; Cromolind; Cromolyn¤; Cromopp; Diffusyl; Dispacromil; DNCG; duracroman; Esirhinol¤; Fenistil¤; Flenid¤; Flui-DNCG; Gelodrin¤; Intal; Logomed Heuschnupfen-Spray¤; Lomupren; Nasivin gegen Heuschnupfen¤; Opticrom; Otriven H¤; Padiacrom; Pentacrom¤; Pentatop; Prothanon cromo¤; Pulbil; Siozwo Allerg; Sofro¤; Stadaglicin¤; Vividrin; Greece: Allergojovis; Allergostop; Allergotin; Botastin; Crolidin¤; Cromabak; Cromo-Pos; Cromolergin UD; Duobetic¤; Erystamine-K; Fluvet¤; Indoprex¤; Iopanchol; Kaosyl; Lomudal; Spaziron; Ufocollyre; Vekfanol; Vividrin; Zineli; Zulboral; Hong Kong: Cromabak; Cusicrom¤; Intal¤; Opticrom¤; Rynacrom M¤; Stadaglicin; Hungary: Cromohexal; Cromolyn; Cusicrom; Intal; Lecrolyn; Opticrom; Stadaglicin; Taleum; India: Cromal; Fintal; Ireland: Cromogen; Hay-Crom; Intal; Nalcrom; Opticrom; Rynacrom; Steri-Neb Cromogen¤; Vividrin; Israel: Cromogen¤; Cromolyn; Cromoptic; Cromunal¤; Cronase; Lomudal; Nalcrom¤; Opticrom; Vicrom; Italy: Acticrom; Cromantal; Cromosan¤; Cronacol¤; Frenal Rinologico¤; Frenal; Gaster¤; Gastrofrenal; Glicacil¤; Lomudal; Lomuspray; Nalcrom; Sificrom; Japan: Intal; Malaysia: Allergocrom; Cusicrom; Intal¤; Opticrom; Stadaglicin; Vividrin¤; Mexico: Alercrom; Cusicrom¤; Exaler; Intal; Maxicrom; Oftacon; Opticrom; Rynacrom; Spralyn; Monaco: Cromedil; Netherlands: Allerg-Abak; Allergocrom¤; Lomudal; Lomusol; Nalcrom; Opticrom; Otrivin hooikoorts; Prevalin; Rynacrom¤; Vividrin; Norway: Lecrolyn; Lomudal; New Zealand: Cromolux; Intal; Nalcrom; Opticrom; Optrex Hayfever Allergy; Rynacrom; Vicrom; Portugal: Croglina; Cromex; Cusicrom; Fenolip; Intal; Opticrom; Rynacrom¤; Russia: Cromohexal (Кромогексал); Cropoz (Кропоз); Hay-Crom (Хай-кром); Ifiral (Ифирал); Intal (Интал); Lecrolyn (Лекролин); South Africa: Cromabak; Cromal¤; Cromogen¤; Cromohexal; Hay-Crom¤; Kiddicrom¤; Lomudal¤; Nalcrom¤; Opticrom¤; Rynacrom¤; Stop-Allerg; Vividrin; Singapore: Cromabak; Cusicrom¤; Intal; Opticrom; Rynacrom; Sificrom; Stadaglicin¤; Vividrin; Spain: Alergocrom; Cromo Asma¤; Cusicrom; Farmacrom; Frenal; Gastrofrenal; Intal¤; Nalcrom¤; Nebulasma; Nebulcrom; Oralcrom¤; Poledin¤; Primover; Renocil; Rinilyn¤; Rinofrenal; Vividrin¤; Sweden: Lecrolyn; Lomudal; Pollyferm; Rinil¤; Switzerland: Allergo-COMOD; Cromabak; Cromodyn; Cromosol ophta; Cromosol UD; Glicinal; Intal Nasal¤; Lomudal; Lomusol; Nalcrom; Novacrom¤; Opticrom; Vividrin; Thailand: Ifiral¤; Intal; Lecrolyn¤; Opticrom¤; Rynacrom; Stadaglicin¤; Vividrin; United Kingdom: Broleze¤; Clariteyes; Clarityn; Cromogen; Cusilyn¤; Hay-Crom; Hayfever Eye Drops; Intal; Nalcrom; Opticrom; Optrex Allergy; Pollenase Allergy; Resiston Two¤; Rynacrom; Vivicrom; Vividrin; Viz-On¤; United States: Crolom; Gastrocrom; Intal; Nasalcrom; Opticrom; Venezuela: Alergocrom; Cromo-Spray; Cromoftal; Maxicrom

Multi-ingredient Preparations

Argentina: Duotec¤; Hyalcrom; Rinogel; Austria: Aarane¤; Allergospasmin¤; Ditec; Lomusol comp¤; Belgium: Lomusol plus Xylometazoline¤; Czech Republic: Allergocrom Kombi; Ditec; Intal Plus; Denmark: Kombicrom¤; Germany: Aarane N; Allergospasmin; Asthmocupin¤; Ditec; Intal compositum¤; Lomupren compositum¤; Vividrin comp¤; Hong Kong: Rynacrom Compound¤; Hungary: Duotec; India: Asthacrom; Ireland: Rynacrom Compound¤; Italy: Cromozil; Frenal Compositum¤; Rinofrenal; Visuglican; Malaysia: Rynacrom Compound¤; Mexico: Aerocrom¤; Netherlands: Cromovist¤; Lomudal Compositum¤; Portugal: Rinoglin¤; Rynacrom Composto¤; Russia: Ditec (Дитек); South Africa: Lomudal Comp¤; Singapore: Rynacrom Compound¤; Spain: Cromoftol¤; Frenal Compositum; Frenal Rinologico¤; Rinofrenal Plus; Switzerland: Aarane; Allergospasmine¤; Lomusol-X; Thailand: Rynacrom Compound¤; United Kingdom: Aerocrom¤; Intal Compound¤; Resiston One¤; Rynacrom Allergy¤; Rynacrom Compound¤

Cromolyn sodium

Cromolyn sodium [Rynacrom(UK), Nasalcrom, Prevalin (Netherlands)] stabilizes mast cells and thereby prevents the degranulation of chemical mediators upon antigen presentation. Intranasal cromolyn ameliorates symptoms such as sneezing, rhinorrhea, and nasal pruritis but lacks efficacy for nasal congestion. Cromolyn is generally less efficacious than intranasal corticos-teroids. Therapy adherence may be problematic, as it necessitates frequent dosing (3 to 4 times daily). However, cromolyn may be safely administered, even to very young children, with negligible side effects. Intranasal cromolyn is now available without prescription. Patients should be advised to initiate therapy with cromolyn before the start of the allergy season or in anticipation of allergen exposure.

Ipratropium bromide

Ipratropium bromide [Atrovent, Apovent] is a well-tolerated topical anti-cholinergic agent that is available in a 0.03% nasal formulation. It is indicated for rhinorrhea associated with allergic and nonallergic perennial rhinitis. (A 0.06% formulation is approved for rhinorrhea associated with the common cold.) This agent quickly and effectively reduces nasal hypersecretion but has no effect on other symptoms of rhinitis such as sneezing and congestion. The most commonly reported adverse effects are nasal dryness and epistaxis. The recommended dose of intranasal ipratropium bromide is 2 sprays per nostril 2 to 3 times daily.

Conclusion

Pharmacotherapy remains the mainstay of management in patients with allergic rhinitis. Given the wide selection of available agents, the ideal regimen should be individualized to reflect disease severity and specific symptoms. Factors such as the potential for side effects, risk for drug interactions, ease of administration, and cost should also be considered. Most importantly, patients should be routinely followed to assess therapeutic response and to monitor for side effects or complications.

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.