Cromolyn sodium has been described as a mast-cell stabilizer.
Cromolyn sodium nasal solution is used for self-medication for the symptomatic prevention and treatment of seasonal or perennial allergic rhinitis. Intranasal administration of cromolyn generally provides symptomatic relief of rhinorrhea, nasal congestion, sneezing, and postnasal drip. For optimum symptomatic relief in patients with perennial allergic rhinitis, up to 2-4 weeks of therapy with intranasal cromolyn may be required. Supplemental therapy with topical nasal decongestants and/or oral antihistamines may be necessary until an acceptable clinical response is achieved. Intranasal cromolyn therapy generally does not provide symptomatic relief of eye or throat irritation associated with allergic rhinitis.
Intranasal cromolyn appears to be ineffective in patients with nonallergic rhinitis. Since the intranasal solution of cromolyn must reach the nasal mucosa to be effective, efficacy of the drug in patients with nasal polyps is also unlikely.
Cromolyn sodium ophthalmic solution is used for the symptomatic treatment of certain allergic ocular disorders, including vernal keratoconjunctivitis,205, 208, 213 vernal conjunctivitis205, 208, 213 , and vernal keratitis.205, 208, 213 Cromolyn sodium ophthalmic solution also has been used for the treatment of giant papillary conjunctivitis†. Ophthalmic administration of cromolyn generally provides symptomatic relief of itching, tearing, redness, and discharge within a few days following initiation of therapy; however, up to 6 weeks of therapy may be required for optimum symptomatic relief in some patients.205, 208, 213 Once symptomatic improvement has been established, cromolyn therapy should be continued for as long as needed to sustain improvement.205, 208, 213 If necessary, supplemental therapy with corticosteroids may be used concomitantly with cromolyn sodium ophthalmic solution.205, 208, 213
Users of contact lenses should refrain from wearing lenses during treatment with cromolyn sodium ophthalmic solution.205, 206, 208, 209, 213 (See Cautions: Precautions and Contraindications)
Cromolyn sodium is administered intranasally or topically onto the eye.204, 205, 206 Cromolyn sodium nasal solution is intended for intranasal use only.215 Proper administration of cromolyn sodium is necessary to obtain optimum results, and it is important that the patient receive careful instruction about the particular dosage form employed.204, 210
The manufacturer's instuctions for patients should be consulted for detailed information on how to use the nasal inhaler.204, 215 Parents or care providers must supervise use of cromolyn sodium nasal spray by young children.204, 215 Prior to administration of cromolyn nasal solution, patients should clear their nasal passages by blowing the nose;215 administration of a topical nasal decongestant may be necessary. Prior to initial use or when the inhaler has not been used for several days, the nasal inhaler must be primed by spraying into the air until a fine mist appears.215 Patients should inhale through the nose during administration.215
In the management of allergic ocular disorders, cromolyn sodium is applied topically just inside the lower eyelid of the eye in the form of a solution; patients should avoid applying the solution directly on the cornea.205, 206, 209, 216 To avoid contamination of dropper tip and solution, patients should avoid touching the tip of the dispensing dropper or container to the eye, fingers, or any other surface.206, 209, 216 Patients should be advised that the therapeutic effects of cromolyn sodium ophthalmic solution depend on administration of the drug at regular intervals.205
The nasal inhaler delivers 5.2 mg of cromolyn sodium per metered spray.204 The commercially available preparations deliver about 100 or 200 metered sprays.204
For the symptomatic prevention and treatment of seasonal or perennial allergic rhinitis, the usual initial dosage of cromolyn sodium for adults and children 2 years of age or older is 1 spray in each nostril 3 or 4 times daily given at regular intervals (morning, noon, dinner, bedtime)215 for up to 12 weeks.204, 215 If exposure to allergens cannot be predicted, patients should initiate therapy at the first sign of nasal symptoms.215 For patients with seasonal or perennial rhinitis, therapy should be continued throughout the period of exposure (e.g., until the pollen season is over or contact with allergen has ceased).215 When necessary, dosage may be increased to 1 spray in each nostril 6 times daily.204, 215 In the management of perennial or seasonal rhinitis, symptomatic relief may become apparent after 1-2 weeks of therapy.204, 215
One drop of cromolyn sodium ophthalmic solution contains approximately 1.6 mg of cromolyn sodium.205
For the symptomatic treatment of vernal keratoconjunctivitis, vernal conjunctivitis, or vernal keratitis, the usual dosage of cromolyn sodium ophthalmic solution in adults and children 4 years of age or older is 1 or 2 drops in each eye 4-6 times daily at regular intervals.205, 208, 213 The recommended frequency of administration should not be exceeded.205, 208, 213
Adverse effects reported with use of intranasal cromolyn sodium include sensations of nasal burning and stinging, nasal irritation, and sneezing; sneezing occurs most frequently (about 10% of patients). Transient headache and unpleasant taste in the mouth have been reported less frequently. Epistaxis, postnasal drip, and rash have been reported in less than 1% of patients. In one patient receiving cromolyn sodium nasal solution for 6 weeks, nasal ulcerations, swelling of the tongue and mouth, coughing, and wheezing occurred.
The most frequent adverse effect reported with use of cromolyn sodium ophthalmic solution is transient ocular stinging or burning upon instillation of the drug. Conjunctival injection, dryness around the eyes, eye irritation, styes, and watery, itchy, or puffy eyes have been reported infrequently in patients receiving cromolyn sodium ophthalmic solution, but it is not known whether these effects are directly attributable to the drug.
During toxicity testing of cromolyn in macaque monkeys, proliferative arterial lesions occurred, principally in the kidneys in both treated and untreated animals. The relevance of this effect to toxicity of cromolyn in man is unknown; pending further clinical experience with cromolyn, the possibility of adverse renal effects should be considered.
Precautions and Contraindications
Patients receiving cromolyn intranasally as self-medication for seasonal or perennial allergic rhinitis should be advised that cromolyn must be used at regular intervals to be therapeutically effective. In addition, patients should be advised that the drug will not provide immediate symptomatic relief, but 1-2 weeks of continuous therapy may be required for optimum effects to be achieved in the management of allergic rhinitis.204
Patients with allergies should be instructed to avoid exposure to allergens.215
For maximum therapeutic effect, patients with seasonal or perennial allergic rhinitis receiving intranasal cromolyn as self-medication should be instructed to begin therapy before (e.g., up to 1-2 weeks before), the period of allergenic exposure and to continue therapy at regular intervals during the period of allergenic exposure, with or without the presence of nasal symptoms.204, 215 Patients receiving intranasal cromolyn for self-medication should also be advised that transient nasal stinging and/or sneezing may occur immediately after inhalation of the nasal solution, but that discontinuance of the drug usually is not necessary.204, 215 Patients using intranasal cromolyn sodium for self-medication for the treatment of allergic rhinitis should be advised to discontinue therapy and consult a clinician if symptoms worsen, new symptoms occur, symptoms do not begin to improve within 2 weeks of treatment initiation or if treatment is required for longer than 12 weeks.204, 215
Patients should not use intranasal cromolyn sodium for self-medication for the treatment of sinus infection†, asthma†, or cold symptoms†.204 Patients should discontinue the drug and contact their clinician if shortness of breath, wheezing, hives or swelling of the mouth or throat, or chest tightness occurs.204, 215 Patients considering use of intranasal cromolyn sodium for self-medication should consult a clinician if they have symptoms such as fever, discolored nasal discharge, sinus pain, or wheezing.204
Patients receiving intraocular cromolyn may experience transient stinging or burning sensation after application to the eye.205
Patients should be advised not to wear contact lenses during treatment with cromolyn sodium ophthalmic solution.205, 206, 216 Patients should not use other ocular agents with cromolyn sodium ophthalmic solution unless directed by a clinician.206, 216
Cromolyn sodium is contraindicated in individuals who have shown hypersensitivity to the drug or any ingredient in the commercially available formulations.205, 213
Safety and efficacy of cromolyn sodium given as the nasal solution204 or ophthalmic solution205, 210, 215 have not been established in children younger than 2 or 4 years of age, respectively.
In geriatric patients receiving cromolyn sodium ophthalmic solution, no differences in safety or effectiveness have been observed relative to younger adults.208, 210, 213
Mutagenicity and Carcinogenicity
There was no evidence of carcinogenicity following long-term intraperitoneal or subcutaneous administration of cromolyn in mice, rats, or hamsters.205 There also was no evidence of chromosomal damage or cytotoxicity in mutagenicity studies with the drug.
Pregnancy, Fertility, and Lactation
In animal studies, cromolyn sodium has produced adverse effects on the fetus only in very high parenteral doses also associated with maternal toxicity.205 Healthy infants have been born to women who received cromolyn sodium throughout pregnancy; nevertheless, there is insufficient evidence to establish the safety of cromolyn sodium in pregnancy. Cromolyn sodium should be used during pregnancy only when clearly needed. Pregnant women should consult their clinician prior to initiation of therapy with cromolyn sodium nasal spray.204
There was no evidence of impaired fertility in reproduction studies in animals.205
Since it is not known if cromolyn is distributed into milk in humans, the drug should be used with caution in nursing women.205 Nursing women should consult their clinician prior to initiation of therapy with cromolyn sodium nasal spray.204
Cromolyn appears to act mainly through a local effect on the nasal mucosa and eyes. Cromolyn prevents release of the mediators of type I allergic reactions, including histamine and cysteinyl leukotrienes (slow-reacting substance of anaphylaxis [SRS-A]),214 from sensitized mast cells after the antigen-antibody union has taken place.3, 5, 6, 10, 12, 33 Cromolyn suppresses the IgE-mediated release of substances (e.g., histamine, cysteinyl leukotrienes)214 from mast cells.212 The drug also inhibits type III (late allergic, Arthus) reactions to a lesser extent. The action of cromolyn on the mast cell is not restricted to antigen-evoked secretion, since the drug has also been shown to inhibit secretion induced by other mast cell secretagogues (e.g., the polyamine 48/80). Cromolyn appears to inhibit phospholipase A-induced mast cell degranulation and subsequent release of chemical mediators in vitro.205 However, the enzymatic activity of phospholipase A does not appear to be affected.205 It has been suggested that the drug may block calcium channels in mast cell membranes. It has also been suggested that cromolyn may inhibit histamine release from mast cells by regulating phosphorylation of a specific mast cell protein involved in secretory mechanisms. However, the specific mechanism(s) of action of the drug on mast cells remains to be established.
There is some evidence to indicate that cromolyn may cause hyposensitization that persists after long-term use. Cromolyn has no direct antihistamine, anticholinergic, antiserotonin, or anti-inflammatory properties.205
Less than 7% of an intranasal dose of cromolyn as a solution is absorbed systemically. Cromolyn sodium is only minimally absorbed from the eye following topical administration.205 Drug excretion studies in healthy individuals indicate that approximately 0.03% of an ophthalmic dose of cromolyn as a solution is absorbed systemically.205
The absorption half-life of cromolyn from the lungs is 1 hour.
Following administration as a nasal solution, improvement in allergic rhinitis may take several days; the best effect may not be seen for 1-2 weeks.204 Following instillation of cromolyn sodium ophthalmic solution, improvement in allergic ocular disorders usually is noted in a few days; treatment for up to 6 weeks may sometimes be needed.205, 210
At physiologic pH, cromolyn is mostly ionized. Because both the ionized and free acid form of the drug are highly polar and lipid insoluble, they do not cross most biologic membranes well.
Following IV administration of large doses (up to 540 mg/kg) of cromolyn sodium in animals, the drug crossed the placenta minimally (less than 0.1%). Minimal concentrations (less than 0.001% of a dose) distributed into milk in monkeys following IV administration of cromolyn sodium. It is not known if the drug is distributed into human milk.
The elimination half-life of cromolyn sodium is reported to be 81 minutes.
Cromolyn sodium has been described as a mast-cell stabilizer. Cromolyn sodium occurs as a hygroscopic, white, odorless, crystalline powder which is tasteless at first but has a slightly bitter aftertaste. The drug is soluble in water and insoluble in alcohol. Cromolyn is a dibasic acid with pKa1 and pKa2 of 2.0.
For intranasal use, cromolyn sodium is commercially available as an aqueous solution of the drug; the solution also contains benzalkonium chloride and edetate disodium (EDTA).204 Cromolyn sodium nasal solution has a pH of 4-7. Cromolyn sodium ophthalmic solution is a clear, colorless, sterile solution of the drug in purified water.208, 213 The commercially available ophthalmic solution also contains benzalkonium chloride and edetate disodium and has a pH of 4-7.205, 213
Aqueous solutions of cromolyn sodium are fluorescent at a pH greater than 2.
Cromolyn sodium ophthalmic solution should be protected from direct light and stored at 20-25° or 15-30°C, depending on the manufacturer.205, 206, 208, 209, 213, 216 Cromolyn sodium nasal solution should be stored in tight, light-resistant containers at 20-25°C.204, 215
Cromolyn sodium is stable in solution at pHs ranging from 2-7. The drug is unstable in alkaline solutions, being susceptible to hydrolysis at a pH greater than 7. The drug tends to precipitate out of solution in the presence of calcium or magnesium salts.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Nasal | Solution | 5.2 mg/metered spray* | Cromolyn Sodium Nasal Spray | |
Ophthalmic | Solution | 4%* | Bausch & Lomb | |
Cromolyn Sodium Ophthalmic Solution |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
3. Cox JS. Disodium cromoglycate: a specific inhibitor of reaginic antibody-antigen mechanisms. Nature . 1967; 216:1328-9. [PubMed 6080064]
5. Anon. Disodium cromoglycate. Lancet . 1972; 2:1299.
6. Anon. Disodium cromoglycate in allergic respiratory disease. Br Med J . 1972; 2:159-61. [PubMed 4622784]
10. Falliers CJ. Cromolyn sodium. J Allergy . 1971; 47:298-305. [PubMed 4104162]
12. Orr TS, Cox JS. Disodium cromoglycate, an inhibitor of mast cell degranulation and histamine release induced by phospholipase A. Nature . 1969; 223: 197. [PubMed 4183038]
33. Sheard P, Blair AM. Disodium cromoglycate activity in three in vitor models of immediate hypersensitivity reaction in the lung. Int Arch Allergy Appl Immunol . 1970; 217-24.
204. Pfizer Consumer Healthcare. Nasalcrom®(cromolyn sodium) nasal spray product description. Morris Plains, NJ; 2006,
205. Akorn. Cromolyn sodium ophthalmic solution USP, 4% prescribing information. Somerset, NJ; 1999 May.
206. Akorn. Cromolyn sodium ophthalmic solution USP, 4% information for the patient. Somerset, NJ; 1999 May.
207. Fisons. Opticrom® 4% (cromolyn sodium) ophthalmic solution prescribing information. Bedford, MA; 1984 Jul.
208. Pacific Pharma. Cromolyn sodium ophthalmic solution USP, 4% prescribing information. Irvine, CA; 2004 Sep.
209. Pacific Pharma. Cromolyn sodium ophthalmic solution USP, 4% information for the patient. Irvine, CA; 2004 Sep.
210. Allergan. Opticrom® (cromolyn sodium) ophthalmic solution prescribing information. In: Physicians' desk reference. 55th ed. Montvale, NJ: Medical Economics Company Inc; 2001:518-9.
212. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 2005 Oct. NIH/NHLBI Publication No. 02-3659. Available at: [Web]. Accessed Nov 7,2006.
213. Bausch & Lomb. Crolom® (cromolyn sodium) ophthalmic solution USP 4% prescribing information. Tampa, FL; 2004 Jan.
214. Drazen JM, Israel E, O'Byrne PM. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med . 1999; 340:197-206. [PubMed 9895400]
215. Bausch & Lomb. Cromolyn sodium nasal solution USP patient information. Tampa, FL. Undated.
216. Bausch & Lomb. Crolom® (cromolyn sodium) ophthalmic solution USP 4% information for the patient. Tampa, FL; 2004 Jan.