Cromolyn is a synthetic mast cell stabilizer. Cromolyn is most often used as a nasal inhalation to treat seasonal allergic rhinitis, or as an ophthalmic solution to treat allergic or vernal conjunctivitis. The oral dosage form has limited therapeutic usage and is approved to treat systemic mastocytosis; the oral dosage form has fared no better than placebo in the treatment of inflammatory bowel disease. Cromolyn has been used as a controller medication for asthma in select patients, but is not a preferred therapy due to a lack of data supporting the effectiveness of cromolyn at reducing exacerbations and improving quality of life versus inhaled corticosteroids. The cromolyn inhaler is no longer available and the drug is marketed only as a nebulized respiratory solution. Although cromolyn has no bronchodilator activity, the drug was found to inhibit antigen-induced bronchospasm. GINA guidelines do not recommend cromolyn use as a maintenance treatment for patients with asthma due to low efficacy. The NAEPP guidelines include cromolyn in combination with "as-needed" short-acting beta-2-receptor agonist (SABA) as an alternative regimen in patients with mild persistent asthma who are unwilling or unable to use ICS but notes that cromolyn products have limited utility in asthma management. Cromolyn is indicated as a preventative for exercise-induced bronchospasm (EIB) or prior to exposure to environmental allergens (e.g., animal danders, toluene diisocyanate, pollutants). Some expert groups state the drug may be considered for use in patients with EIB who continue to have symptoms despite use of short-acting beta-2 agonists. In clinical practice, inhaled corticosteroids or leukotriene receptor antagonists are usually the first-line therapies to be used with SABAs for EIB control. Cromolyn and its many formulations are FDA-approved for use in adults and children as young as 2 years of age. In Europe, cromolyn is known generically as sodium cromoglycate.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Liquid Formulations
Oral concentrate solution (e.g., Gastrocrom)
-The oral ampules of Gastrocrom are for preparation of an oral solution only. Do not use for inhalation or injection.
Preparation and Administration
-Empty the appropriate amount of the ampule(s) into a half glass of water. Stir solution. Do not mix the oral concentrate solution with fruit juice, milk, or food.
-Administer the entire dosage immediately after solution preparation.
-Dosages should be administered at regular intervals at least 30 minutes before meals and at bedtime.
Inhalation Administration
Oral Inhalation Administration
-Instruct patient on proper inhalation technique.
Inhalation solution for nebulization
-Use a power-operated nebulizer with a flow rate of at least 6 to 8 L/minute and equipped with suitable face mask or mouthpiece. Hand-operated nebulizers are NOT appropriate for administration of cromolyn solution for inhalation.
-The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each individual patient.
-Using the 'blow-by' technique (i.e. holding the face mask or open tube near the patient's nose and mouth) is not recommended.
-INCOMPATABILITY: Ipratropium inhalation solutions form a precipitate with cromolyn sodium inhalation solution if mixed in a nebulizer.
Intranasal Inhalation Administration
Nasal spray (Nasalcrom):
-Instruct patient on proper inhalation technique.
-Prime inhaler prior to use.
-The nasal spray for intranasal administration delivers 5.2 mg/spray.
-To avoid the spread of infection, do not use the container for more than one person.
Ophthalmic Administration
-Crolom, Cromoptic, and Opticrom are for ophthalmic use only.
-Instruct patient on appropriate instillation technique.
-Do not to touch the tip of the dropper to the eye, fingertips, or other surface.
Severe anaphylactoid reactions have been reported, though rarely, in association with cromolyn sodium administration.
Respiratory adverse effects have been reported with all formulations of cromolyn sodium. The nebulized oral inhalation has been associated with the development of bronchospasm, throat irritation, cough, nasal congestion, nasal itching, nose bleed, laryngeal edema, swollen parotid gland, angioedema, pulmonary infiltrates with eosinophilia, and hoarseness; administration of a beta-adrenergic bronchodilator can prevent or alleviate these conditions, or withdrawal of cromolyn may be necessary. Reactions reported with the intranasal include nasal irritation (stinging), shortness of breath, chest tightness, and hives or swelling of the mouth or throat. Sneezing, wheezing, and nasal burning have been reported with both the oral nebulized and nasal inhaled formulations. Pharyngitis and dyspnea have been reported with the oral solution. An immediate hypersensitivity reaction to the ophthalmic drops have rarely been reported and include dyspnea as a symptom.
Oral administration, as the oral solution or via nebulization, has been associated with nausea (< 4% with the oral solution), vomiting, diarrhea (< 5% with the oral solution), abdominal pain (2% with the oral solution), flatulence, constipation, dyspepsia, glossitis, and dysphagia. Unpleasant taste, abnormal hepatic function tests, stomatitis, and esophagospasm have also been reported with use of the oral solution.
Oral administration, as the oral solution or via nebulization, has been associated with headache (< 5% with the oral solution) and drowsiness or fatigue. Vertigo has been reported with the nebulized inhalation of cromolyn. Administration of the oral solution has also been associated with insomnia, irritability (2%), malaise, dizziness, postprandial lightheadedness and lethargy, tinnitus, psychosis, anxiety, depression, hallucinations, hypoesthesia, paresthesias, seizures (convulsions), migraine, behavior change, and nervousness.
Oral administration, as the oral solution or via nebulization, has been associated with myalgia (< 4% with the oral solution). Patients receiving the oral solution have reported arthralgia, and stiffness or weakness of the legs. With use of the nebulized inhalation formulation, joint swelling and pain, peripheral neuritis, and polymyositis have been reported.
Use of cromolyn ophthalmic drops can frequently produce ocular irritation (burning, stinging). This effect is generally transient. Less frequently, ophthalmic cromolyn can result in ocular pruritus, watery eyes, dryness or puffiness around the eyes, conjunctival injection, and styes. Lacrimation has been reported with the oral nebulized inhalation formulation.
Oral administration of cromolyn, as the oral solution or via nebulization, has been associated with dysuria and increased urinary frequency. Adverse effects reported with administration of the oral solution include edema, polycythemia, neutropenia, and pancytopenia. The nebulized oral inhalation formulation has been associated with nephrosis, hemoptysis, and anemia.
Cardiovascular adverse reactions have been reported with cromolyn administration. With the oral solution, ventricular tachycardia, atrial tachycardia, premature ventricular contractions (PVCs), chest pain (unspecified), and palpitations have been reported. Periarteritic vasculitis and pericarditis were reported with nebulized oral inhalation administration.
Dermatologic reactions have been reported with cromolyn use. Oral administration, as the oral solution or via nebulization, and ophthalmic administration have been associated with rash (unspecified) (2% with the oral solution). Urticaria has been reported with both the oral solution and oral nebulization. Patients receiving the oral solution have reported flushing, pruritus (< 4%), purpura, lupus-like symptoms, erythema or burning, and photosensitivity. Patients using the orally inhaled nebulizer solution have reported exfoliative dermatitis and photodermatitis.
Cromolyn sodium products are contraindicated in those patients who have shown hypersensitivity to cromolyn sodium. Severe anaphylactic reactions may occur rarely in association with cromolyn sodium use.
The activity of cromolyn sodium acts to prevent asthma symptoms in select patients. It is not a bronchodilator; do not prescribe cromolyn for the treatment of acute bronchospasm; this drug has no role in the treatment of status asthmaticus.
A reduction in the recommended dosage of oral cromolyn sodium should be considered in patients with hepatic disease or renal impairment/renal failure, given the biliary and renal routes of excretion of the drug. However, definitive recommendations for dosage reduction are not provided in the product label.
Patients should not wear contact lenses during treatment with cromolyn sodium ophthalmic solution. In general, users of contact lenses should refrain from wearing lenses while exhibiting the signs and symptoms of vernal keratoconjunctivitis, vernal conjunctivitis, or vernal keratitis. Additionally, cromolyn sodium ophthalmic solution contains benzalkonium chloride as a preservative, which can be absorbed by soft contact lenses.
Cromolyn sodium may be used with caution during pregnancy due to low systemic absorption from the various administration routes. Animal studies have not shown adverse effects on the fetus when cromolyn was administered alone. Cromolyn sodium is considered an alternative therapy to inhaled corticosteroids for mild persistent asthma during pregnancy according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group; however, inhaled corticosteroids are the preferred treatment due to greater efficacy.
It is not known if cromolyn sodium is distributed into breast milk; however, after administration via the oral, nasal, ophthalmic, and inhaled routes only small amounts of drug are absorbed. The manufacturers recommend that the drug be used with caution during breast-feeding. Cromolyn sodium is considered an alternative therapy to inhaled corticosteroids for mild persistent asthma during lactation according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group.
There are limited data are available regarding the safe and effective use of cromolyn sodium products in children and infants less than 2 years of age.
For asthma maintenance treatment as an adjunct:
Respiratory (Inhalation) dosage (inhalation solution):
Adults: 20 mg inhaled by nebulizer 4 times daily. A 4 to 6-week trial may be necessary to determine maximum benefit. Use the lowest effective dose once stable. Usual maintenance dose: 20 mg inhaled by nebulizer 3 times daily. Not recommended for routine use in asthma management due to low efficacy.
Children and Adolescents 2 to 17 years: 20 mg inhaled by nebulizer 4 times daily. A 4 to 6-week trial may be necessary to determine maximum benefit. Use the lowest effective dose once stable. Usual maintenance dose: 20 mg inhaled by nebulizer 3 times daily. Not recommended for routine use in asthma management due to low efficacy.
For exercise-induced bronchospasm prophylaxis or the prevention of bronchospasm induced by other known precipitating factors:
Respiratory (Inhalation) dosage (inhalation solution):
Adults: 20 mg inhaled by nebulizer 10 to 15 minutes before exercise or exposure to other precipitating factors. A mast cell stabilizing agent such as cromolyn before exercise may be considered in persons who continue to have symptoms despite using an inhaled short-acting beta-2 agonist (SABA) before exercise, or in those who require daily (or more frequent) SABA use. In clinical practice, inhaled corticosteroids or leukotriene receptor antagonists are usually the first-line therapies to be used with SABAs for exercise-induced bronchospasm.
Children and Adolescents 2 to 17 years: 20 mg inhaled by nebulizer 10 to 15 minutes before exercise or exposure to other precipitating factors. A mast cell stabilizing agent such as cromolyn before exercise may be considered in persons who continue to have symptoms despite using an inhaled short-acting beta-2 agonist (SABA) before exercise, or in those who require daily (or more frequent) SABA use. In clinical practice, inhaled corticosteroids or leukotriene receptor antagonists are usually the first-line therapies to be used with SABAs for exercise-induced bronchospasm.
For the management of symptoms of seasonal allergies and perennial allergies, including allergic rhinitis and allergic rhinitis prophylaxis:
Nasal dosage (metered spray, e.g., Nasalcrom):
Adults: 1 spray (5.2 mg/spray) in each nostril 3 to 4 times per day; may be increased to 6 times a day if needed. Best if initiated 1 full week before coming into contact with allergens and used every day while in contact with the cause of the allergies (pollen, molds, pets, and dust).
Children and Adolescents 2 years and older: 1 spray (5.2 mg/spray) in each nostril 3 to 4 times per day; may be increased to 6 times a day if needed. Best if initiated 1 full week before coming into contact with allergens and used every day while in contact with the cause of the allergies (pollen, molds, pets, and dust).
For the treatment of allergic ocular disorders such as allergic conjunctivitis, vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis:
Ophthalmic dosage (4% ophthalmic solution):
Adults: 1 to 2 drops in each eye 4 to 6 times daily. Each drop contains approximately 1.6 mg cromolyn sodium.
Children and Adolescents 4 to 17 years: 1 to 2 drops in each eye 4 to 6 times daily. Each drop contains approximately 1.6 mg cromolyn sodium.
For the treatment of systemic mastocytosis:
Oral dosage (e.g., Gastrocrom oral solution):
Adults: 200 mg PO 4 times per day, 30 minutes before meals and at bedtime. If satisfactory control of symptoms is not achieved within 2 to 3 weeks, the dosage may be increased. Max: 40 mg/kg/day PO.
Adolescents: 200 mg PO 4 times per day, 30 minutes before meals and at bedtime. If satisfactory control of symptoms is not achieved within 2 to 3 weeks, the dosage may be increased. Max: 40 mg/kg/day PO.
Children 2 to 12 years: 100 mg PO 4 times per day, 30 minutes before meals and at bedtime. If satisfactory control of symptoms is not achieved within 2 to 3 weeks, the dosage may be increased. Max: 40 mg/kg/day PO.
Infants and Children up to 2 years*: Safety and efficacy have not been established; some clinical data are available. 20 mg/kg/day PO, given in 4 divided doses. May increase after 2 to 3 weeks if symptoms not controlled. Max for those 6 months and older: 40 mg/kg/day PO. Max for term infants up to 6 months: 20 mg/kg/day PO. Reserve use for those under 2 years of age with severe disease for whom the potential benefit clearly outweighs the risks.
Maximum Dosage Limits:
-Adults
40 mg/kg/day PO; 20 mg inhaled via nebulization 4 times per day.
-Geriatric
40 mg/kg/day PO; 20 mg inhaled via nebulization 4 times per day.
-Adolescents
40 mg/kg/day PO; 20 mg inhaled via nebulization 4 times per day.
-Children
2 to 12 years: 40 mg/kg/day PO; 20 mg inhaled via nebulization 4 times per day.
1 year: Safety and efficacy have not been established; 40 mg/kg/day PO is suggested. Safety and efficacy of other routes have not been established.
-Infants
6 to 11 months: Safety and efficacy have not been established; 40 mg/kg/day PO is suggested. Safety and efficacy of other routes have not been established.
1 to 5 months: Safety and efficacy have not been established; 20 mg/kg/day PO is suggested. Safety and efficacy of other routes have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Oral dosage form: The recommended dosage should be decreased in patients with decreased hepatic function, but no specific recommendations are available.
Inhaled, nasal, or ophthalmic dosage forms: No dosage adjustments are needed due to minimal systemic absorption.
Patients with Renal Impairment Dosing
Oral dosage form: The recommended dosage should be decreased in patients with decreased renal function, but no specific recommendations are available.
Inhaled, nasal, or ophthalmic dosage forms: No dosage adjustments are needed due to minimal systemic absorption.
*non-FDA-approved indication
There are no drug interactions associated with Cromolyn Sodium products.
Cromolyn works at the surface of the mast cell to inhibit its degranulation. In vitro and in vivo animal studies have shown that cromolyn sodium inhibits the release of mediators from sensitized mast cells. Cromolyn sodium acts by inhibiting the release of histamine and leukotrienes (SRS-A) from the mast cell. Studies show that cromolyn sodium indirectly blocks calcium ions from entering the mast cell, thereby preventing mediator release. Cromolyn sodium has no intrinsic vasoconstrictor, antihistamine, or glucocorticoid activity. Cromolyn's beneficial effects when inhaled or used nasally or in the eye are largely preventative. Continued use is needed to maintain benefits as a controller medication. Inhaled cromolyn can be used before certain exposures to reduce hyperreactivity to exercise, cold air, or antigenic challenge (e.g., allergens, environmental pollutants). When used orally to manage cutaneous or systemic mastocytosis, use results in a clinically significant improvement in gastrointestinal symptoms (diarrhea, abdominal pain) and some improvement for cutaneous manifestations (e.g., urticaria, pruritus, flushing) and cognitive function.
Cromolyn sodium is administered orally, via nebulization, intranasally, and via ophthalmic route. Very little of the drug is absorbed systemically by any route of administration.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
-Route-Specific Pharmacokinetics
Oral Route
Cromolyn sodium is poorly absorbed from the gastrointestinal tract. No more than 1% of an administered dose is absorbed by humans after oral administration, the remainder being excreted in the feces. Very little absorption of cromolyn sodium was seen after oral administration of 500 mg to each of 12 volunteers. From 0.28% to 0.50% of the administered dose was recovered in the first 24 hours of urinary excretion in 3 subjects. The mean urinary excretion of an administered dose over 24 hours in the remaining 9 subjects was 0.45%.
Inhalation Route
After administration by inhalation, approximately 8% of the total cromolyn sodium dose administered is absorbed and rapidly excreted unchanged, approximately equally divided between urine and bile. The remainder of the dose is either exhaled or deposited in the oropharynx, swallowed and excreted via the alimentary tract.
Other Route(s)
Ophthalmic Route
Minimal systemic absorption occurs after ophthalmic use. Animal studies indicate trace amounts (less than 0.01%) of the cromolyn sodium dose penetrate into the aqueous humor and clearance from this chamber is virtually complete within 24 hours after treatment is stopped. In normal volunteers, analysis of drug excretion indicates that approximately 0.03% of cromolyn sodium is absorbed following administration to the eye.
Intranasal route
As with inhalational use, minimal systemic absorption occurs after intranasal use.