Drug class: Mast-cell Stabilizers
CAS number: 15826-37-6

Medically reviewed by Drugs.com on Jun 24, 2024. Written by ASHP.

Introduction

Mast-cell stabilizer.^c

Uses for Cromolyn (Systemic, Oral Inhalation)

Asthma

Prevention of bronchial asthma symptoms.^{205 206 207 222}

Has been used as an alternative to low-dose inhaled corticosteroids in patients with mild persistent asthma, but is less effective and generally not preferred as initial therapy.^{222 223 224}

Not effective for treatment of acute attacks of asthma, especially status asthmaticus.^{205 206} (See Acute Bronchospasm under Warnings/Precautions.)

Prevention of Bronchospasm

Prevention of exercise-induced bronchospasm or that induced by exposure to other known precipitating factors (e.g., cold dry air, allergens, sulfur dioxide, toluene diisocyanate, environmental pollutants).^{205 e} Less effective than orally inhaled β₂-adrenergic agonists in preventing exercise-induced bronchospasm.^a

Systemic Mastocytosis

Symptomatic treatment of systemic mastocytosis (designated an orphan drug by US FDA for this use).^{a 203} Improves diarrhea, abdominal pain, pruritus, whealing, flushing, cognitive dysfunction, headaches, nausea, vomiting, and urticaria.^{a 203} Efficacy appears similar to chlorpheniramine maleate plus cimetidine in reducing the signs and symptoms of mastocytosis.²⁰³

Food Allergy

Has been used for the prophylactic management of food allergy^{† [off-label]}.^a

Cromolyn (Systemic, Oral Inhalation) Dosage and Administration

General

Asthma

• Initiate oral inhalation therapy after acute asthma has been controlled, the airway is clear, and the patient is able to inhale adequately.^{206 b}

• When oral inhalation is added to existing therapy, initially do not change dosage of concurrent antiasthmatic agents (e.g., inhaled β₂-adrenergic agonist or inhaled corticosteroid).^{206 b} When a response to therapy is evident, gradually reduce the dosage of concurrent agents.^{206 b} (See Concomitant Corticosteroid Therapy under Cautions.)

Administration

Administer orally or via oral inhalation.^{b c e} Do not inject oral concentrate or use for oral inhalation therapy.^{c d}

Administer at regular intervals.^{205 206 d}

Oral Administration

Oral Concentrate

Dilute just prior to administration; empty the contents of the ampul(s) into a glass of water and stir.^{203 d}

Administer as a diluted solution; patient should drink all of the resultant solution.^{203 d}

Do not mix solution with fruit juice, milk, or food.^a

Administer 30 minutes before meals and at bedtime.^{c d}

Oral Inhalation

Oral Inhalation Aerosol

Prime aerosol inhaler (aerosol preparation for oral inhalation no longer commercially available in US²²⁶ ) prior to first use and after a period of nonuse by pressing once (i.e., actuating) on the top of the metal canister.^f

Canister should be at room temperature prior to use;^{205 f} shake well prior to actuation.^f

Patient should exhale slowly and completely and place the mouthpiece of the inhaler well into the mouth with the lips closed around it.^f Tilt inhaler upward and head backward and then inhale deeply through the mouth while actuating the inhaler.^f Remove inhaler from the mouth, hold breath for a few seconds, and then exhale slowly.^f Repeat if a second inhalation is necessary.^f

Avoid spraying into the eyes.^{205 f}

Clean inhaler by removing the canister from the inhaler and cleaning the plastic mouthpiece with warm water.^f

Discard canister after the labeled number of actuations.^{205 f}

Prevention of bronchospasm: Administer 10–15 minutes but ≤60 minutes before anticipated exercise or exposure to another precipitating factor.²⁰⁵

Solution for Nebulization

Administer oral inhalation solution by nebulization using a power-operated nebulizer with an adequate flow rate and suitable face mask.^{206 g} Do not use hand-operated nebulizers.^a

Administer by nebulization for young children who have difficulty using the oral aerosol inhaler (no longer commercially available in US²²⁶ ).²⁰⁵

Safety and stability of oral inhalation solution when mixed with other drugs in the nebulizer not established.^{206 g}

Prevention of bronchospasm: Administer 10–15 minutes before anticipated exercise or exposure to another precipitating factor.^{e g}

Dosage

Available as cromolyn sodium; dosage expressed in terms of the salt.^{203 205}

Unless otherwise stated, the dosage of cromolyn sodium via aerosol inhalation (aerosol preparation for oral inhalation no longer commercially available in US²²⁶ ) is expressed as the amount delivered from the mouthpiece of the inhaler per metered spray.^b The oral aerosol inhaler delivers approximately 1 mg from the valve and 800 mcg per metered spray from the mouthpiece.^b The 8.1- or 14.2-g canister delivers at least 112 or 200 metered sprays, respectively.^{b f}

Pediatric Patients

Systemic Mastocytosis

Oral

Full-term neonates and infants <2 years of age^{† [off-label]}: Initially, 20 mg/kg daily in 4 divided doses.^a (See Pediatric Use under Cautions.)

Children 2–12 years of age: Initially, 100 mg 4 times daily.^{203 d}

Children ≥13 years of age: Initially, 200 mg 4 times daily.^{203 d}

Dosage may be increased after 2–3 weeks, according to clinical response.²⁰³

Reduce dosage to minimum effective level when an adequate response is achieved.²⁰³

Food Allergy† [off-label]

Oral

Children 2–14 years of age: Initially, 100 mg 4 times daily 15–20 minutes before meals has been used.^a If satisfactory control of symptoms is not achieved within 2–3 weeks, may double dosage but should not exceed 40 mg/kg daily.^a

Reduce dosage to minimum effective level when an adequate response is achieved.^a

Children 2–14 years of age requiring occasional therapy (e.g., when avoidance of allergenic foods cannot be assured): 100 mg about 15 minutes before meal suggested.^a Optimal dosage must be individualized.^a

Asthma

Oral Inhalation

Aerosol inhalation (no longer commercially available in US²²⁶ ) in children ≥5 years of age: 1.6 mg (2 inhalations) 4 times daily.^{205 f} Lower dosage may be effective, especially in younger patients.^{205 f} Following stabilization, gradually reduce the frequency of administration from 4 to 3 and then 3 to 2 times (2 inhalations per dose) daily.^b

Inhalation solution for nebulization in children ≥2 years of age: 20 mg 4 times daily at regular intervals.²⁰⁶ Following stabilization, gradually reduce the frequency of administration from 4 to 3 times daily.²⁰⁶

If control deteriorates at a reduced dosage (<4 doses daily), with or without concurrent agents at a reduced dosage, may need to increase the dosage of cromolyn sodium and reinitiate or increase the dosage of concurrent agent.^{205 206}

Prevention of Bronchospasm

Oral Inhalation

Aerosol inhalation (no longer commercially available in US²²⁶ ) in children ≥5 years of age: 1.6 mg (2 inhalations) 10–15 minutes but ≤60 minutes before anticipated exercise or exposure to precipitating factor.^{205 f}

Inhalation solution for nebulization in children ≥2 years of age: 20 mg 10–15 minutes before anticipated exercise or exposure to precipitating factor.^{206 e g}

Adults

Systemic Mastocytosis

Oral

Initially, 200 mg 4 times daily.²⁰³ Dosage may be increased after 2–3 weeks, according to clinical response.²⁰³ Reduce dosage to minimum effective level when an adequate response is achieved.²⁰³

Food Allergy† [off-label]

Oral

Initially, 200 mg 4 times daily given 15–20 minutes before meals has been used.^a If satisfactory control of symptoms not achieved within 2–3 weeks, may double dosage.^a

Reduce dosage to minimum effective level when an adequate response is achieved.^a

Adults requiring occasional therapy (e.g., when avoidance of allergenic foods cannot be assured): 200 mg about 15 minutes before meal suggested.^a Optimal dosage must be individualized.^a

Asthma

Oral Inhalation

Aerosol inhalation (no longer commercially available in US²²⁶ ): 1.6 mg (2 inhalations) 4 times daily.²⁰⁵ Following stabilization, gradually reduce the frequency of administration from 4 to 3 and then 3 to 2 times daily.^b

Inhalation solution for nebulization: 20 mg 4 times daily.^{206 e} Following stabilization, gradually reduce the frequency of administration from 4 to 3 times daily.²⁰⁶

Prevention of Bronchospasm

Oral Inhalation

Aerosol inhalation (no longer commercially available in US²²⁶ ): 1.6 mg (2 inhalations) 10–15 minutes but ≤60 minutes before anticipated exercise or exposure to precipitating factor.^{205 b}

Inhalation solution for nebulization: 20 mg 10–15 minutes before anticipated exercise or exposure to precipitating factor.^{206 e g}

Prescribing Limits

Pediatric Patients

Systemic Mastocytosis

Oral

Infants <6 months age^{† [off-label]}: Maximum 20 mg/kg daily.²⁰³

Children ≥2 years of age: Maximum 40 mg/kg daily.²⁰³

Asthma

Oral Inhalation

Children ≥5 years of age: Maximum 1.6 mg 4 times daily via metered-dose aerosol (no longer commercially available in US²²⁶ ).²⁰⁵

Adults

Asthma

Oral Inhalation

Maximum 1.6 mg 4 times daily via metered-dose aerosol (no longer commercially available in US²²⁶ ).²⁰⁵

Special Populations

Hepatic Impairment

Systemic Mastocytosis

Reduce oral dosage.²⁰³

Asthma/Bronchospasm

Reduce aerosol inhalation (no longer commercially available in US²²⁶ ) dosage.²⁰⁵

Renal Impairment

Systemic Mastocytosis

Reduce oral dosage.²⁰³

Asthma/Bronchospasm

Reduce aerosol inhalation (no longer commercially available in US²²⁶ ) dosage.²⁰⁵

Geriatric Patients

Oral concentrate: Initiate dosage at the low end of the dosing range.²⁰³ (See Geriatric Use under Cautions.)

Cautions for Cromolyn (Systemic, Oral Inhalation)

Contraindications

• Known hypersensitivity to cromolyn sodium or any ingredient in the formulations.^{203 205 206}

Warnings/Precautions

Warnings

Acute Bronchospasm

Cromolyn is not a bronchodilator and has a slow onset of action; metered-dose aerosol (no longer commercially available in US²²⁶ ) or solution for oral inhalation should not be used for relief of acute bronchospasm, especially status asthmaticus.^{205 206}

Bronchospasm, rarely severe, and/or cough reported following oral inhalation.²⁰⁵ Cromolyn may need to be discontinued despite administration of a bronchodilator.²⁰⁵

Concomitant Corticosteroid Therapy

In corticosteroid-dependent asthmatic patients receiving cromolyn sodium for several weeks, make an attempt to gradually reduce the dosage of corticosteroids even if symptomatic improvement in asthma is not observed.^{206 b} Monitor patients closely during such dosage reduction to avoid exacerbation of asthma.^{206 b}

Monitor patients closely when discontinuing cromolyn therapy in patients in whom the dosage of corticosteroid therapy has been reduced.^{206 b} Exacerbations of asthma may require immediate therapy and an increase in corticosteroid dosage.^{206 b}

Eosinophilic Pneumonia

Discontinue if eosinophilic pneumonia or pulmonary infiltrates with eosinophilia occurs.²⁰⁵

CAD or Cardiac Arrhythmia

Metered-dose aerosol inhalation (no longer commercially available in US²²⁶ ) contains fluorocarbon propellants; use not recommended in patients with CAD or a history of cardiac arrhythmia.²⁰⁵

Sensitivity Reactions

Severe anaphylactic reactions reported.^{205 203}

Specific Populations

Pregnancy

Category B.^{205 203}

Lactation

Not known whether cromolyn is distributed into milk.^{205 203 206} Use with caution;^{205 203 206} weigh the potential benefits to the mother against the potential risks to the infant when considering therapy.^b

Pediatric Use

Use with caution in pediatric patients.^{203 205} Consider benefits versus risks of long-term therapy.^b

Safety and efficacy of cromolyn sodium given as the oral concentrate,²⁰³ oral inhalation aerosol (no longer commercially available in US²²⁶ ),²⁰⁵ or oral inhalation solution^{206 e} not established in children <2, <5, or <2 years of age, respectively.

Treatment of systemic mastocytosis in full-term neonates and infants <2 years of age is recommended only if disease is severe and incapacitating and if benefits clearly outweigh risks.²⁰³

Geriatric Use

Oral concentrate: Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^c Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.²⁰³

Aerosol inhalation (no longer commercially available in US²²⁶ ): Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^b

Common Adverse Effects

Oral concentrate: Headache, diarrhea.²⁰³

Aerosol inhalation (no longer commercially available in US²²⁶ ): Irritation or dryness of the throat, bad taste, cough, wheezing, nausea.²⁰⁵

Solution for oral inhalation: Nasal congestion, cough, sneezing, wheezing, nausea.^{206 e}

Cromolyn (Systemic, Oral Inhalation) Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract; about 1% or less is absorbed following an oral dose.^c

Approximately 8% absorbed following oral inhalation.^{205 e}

Onset

Oral inhalation: Improvement usually occurs within the first 2–4 weeks; some patients show immediate response.^{205 206 b e g}

Oral concentrate: Beneficial effects on systemic mastocytosis apparent ≤2–6 weeks of therapy.^c

Duration

Oral concentrate: Exacerbation of signs and symptoms of systemic mastocytosis occur within 2–3 weeks after discontinuance of the drug.^c

Distribution

Extent

Does not cross most biologic membranes well.^a

Minimally crosses the placenta (<0.1%) and minimally distributed into milk (<0.001% of a dose) in animals.^a

Elimination

Elimination Route

Oral concentrate: ≥98% of a dose is excreted in feces as unabsorbed drug; ≤0.5% of a dose is excreted in urine.^{a 203 c}

Oral inhalation: Absorbed fraction rapidly excreted unchanged in urine and bile with approximately equal proportions being excreted via each route.^{206 b e} Remainder of dose exhaled or deposited onto oropharynx, swallowed, and excreted in feces.^{206 b e}

Half-life

81 minutes.^a

Stability

Storage

Oral

Oral Concentrate

15–30°C; protect from light.^{203 d} Store ampules in foil pouch until ready for use.^{203 d} Do not use solution if a precipitate is present or solution becomes discolored.^{c d}

Oral Inhalation

Aerosol/Solution for Inhalation

Aerosol (no longer commercially available in US²²⁶ ): 15–30°C.^{205 b} Do not puncture aerosol canisters, use or store near heat or open flame, expose to temperatures >42°C, or place into fire or incinerator for disposal.^b

Inhalation solution: 20–25 or 15–30°C, depending on manufacturer.^{206 e}

Actions

• Inhibits degranulation of sensitized mast cells.^{205 203 206} Inhibits release of mediators of type I allergic reactions, including histamine and cysteinyl leukotrienes (e.g., slow-reacting substance of anaphylaxis [SRS-A]²¹⁴ from sensitized mast cells after exposure to antigens.^{a 3 5 6 10 12 33 205 203}

• May block calcium channels in mast cell membranes.^{206 b}

• No direct antihistamine, anticholinergic, antiserotonin, anti-inflammatory, bronchodilator, or corticosteroid-like properties.^{203 205 206 a e}

• Following oral inhalation, acts mainly through a local effect on the lung mucosa.^a

Advice to Patients

• Importance of providing patient a copy of manufacturer’s patient information.^{205 203}

• Importance of clinicians instructing patients about proper use of the drug, including proper administration of the particular dosage form employed.^{203 205 206 215}

• Importance of advising patients that oral inhalation solution should not be taken orally (i.e., swallowed) and is not effective for bronchial asthma when taken by this route.^{206 e}

• Importance of administration of the drug at regular intervals.^{b c d}

• Importance of taking only as prescribed; do not change dosage or duration of therapy unless otherwise instructed by clinician.^{b d}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{205 203}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{205 203}

• Importance of informing patients of other important precautionary information.^{205 203} (See Cautions.)

Preparations

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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