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Cromolyn Sodium

Pronunciation

Class: Mast-cell Stabilizers
VA Class: RE100
CAS Number: 15826-37-6

Introduction

Mast-cell stabilizer.c

Uses for Cromolyn Sodium

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

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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.a

Cromolyn Sodium 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: 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
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
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: 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 Sodium

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 solution206 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 Sodium 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.

King Pharmaceuticals discontinued the manufacture of cromolyn sodium oral inhalation aerosol (Intal Inhaler) in 2009.226 FDA states that cromolyn sodium oral inhalation aerosol with chlorofluorocarbon (CFC) propellants will not be manufactured, sold, or dispensed in the US after December 31, 2010.227

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

Cromolyn Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For solution, concentrate (contained in flexible ampuls)

20 mg/mL (100 mg)

Gastrocrom

Azur

Oral Inhalation

Solution, for nebulization

10 mg/mL (20 mg)*

Cromolyn Sodium Inhalation Solution

Intal Nebulizer Solution

King

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 2, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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 vitro models of immediate hypersensitivity reaction in the lung. Int Arch Allergy Appl Immunol. 1970; 217-24.

200. Brandstetter RD, Conetta R, Glazer B. Lactose intolerance associated with Intal capsules. N Engl J Med. 1986; 315:1613-4. [IDIS 224073] [PubMed 3097545]

201. Michet CJ Jr, Rakela J, Luthra HS. Auranofin-associated colitis and eosinophilia. Mayo Clin Proc. 1987; 62:142-4. [IDIS 225178] [PubMed 3807438]

202. Martin DM, Goldman JA, Gilliam J et al. Gold-induce eosinophilic enterocolitis: response to oral cromolyn sodium. Gastroenterology. 1981; 80:1567-70. [IDIS 133653] [PubMed 6785145]

203. Celltech Pharmaceuticals. Gastrocrom (cromolyn sodium) oral concentrate solution prescribing information. Rochester, NY; 2002 Apr.

205. King Pharmaceuticals. Intalinhaler (cromolyn sodium) inhalation aerosol prescribing information. Bristol, TN; 2004 Jul.

206. Aventis. Intal (cromolyn sodium) nebulizer inhalation solution prescribing information. 2Bridgewater, NJ; 2001 Oct.

207. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. 1997 Feb.

208. Kemp JP. Comprehensive asthma management: guidelines for clinicians. J Asthma. 1998; 35:601-20. [PubMed 9860081]

209. Kemp JP. Guidelines update: where do the new therapies fit in the management of asthma? Drugs. 2000; 59(Suppl 1):23-8.

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 NIH website. Accessed Nov 7, 2006.

214. Drazen JM, Israel E, O’Byrne PM. Treatment of athma with drugs modifying the leukotriene pathway. N Engl J Med. 1999; 340:197-206. [IDIS 418266] [PubMed 9895400]

215. King Pharmaceuticals. Intal inhaler (cromolyn sodium) inhalation aerosol information for the patient. Bristol, TN; 2004 Jul.

216. Celltech Pharmaceuticals. Gastrocrom (cromolyn sodium) oral concentrate solution patient instructions. Rochester, NY; 2002 Apr.

221. GlaxoSmithKline. Advair HFA (fluticasone propionate and salmeterol) medication guide. Research Triangle Park, NC; 2006 Jun.

222. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention. Bethesda, MD: National Institutes of Health. 2009 Dec. Available from: . Accessed 2010 Sep 23.

223. National Asthma Education and Prevention Program. Expert panel report III: guidelines for the diagnosis and management of asthma. 2007 Jul. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. Available from NIH website. Accessed Jul 27, 2008.

224. British Thoracic Society/Scottish Intercollegiate Guidelines Network. Guidelines on the management of asthma: a national clinical guideline. London, Eng; British Thoracic Society. 2008 May. Available from BTS website. Accessed Dec 5, 2008.

226. Eric Carter. Dear health care professional letter regarding decision to discontinue the manufacture of Intal Inhaler (cromolyn sodium inhalation aerosol). Cary, NC: King Pharmaceuticals, Inc; 2009 Jul 31. Available from FDA website. Accessed 2010 Oct 14.

227. Food and Drug Administration. Asthma and COPD inhalers that contain ozone-depleting CFCs to be phased out; alternative treatments available. 2010 Apr 13. Available from FDA website. Accessed 2010 Oct 14.

a. AHFS drug information 2003. McEvoy GK, ed. Cromolyn Sodium. Bethesda, MD: American Society of Health-System Pharmacists; 2003:3576-3580.

b. King Pharmaceuticals Inc. Intal Inhaler (cromolyn sodium) inhalation aerosol prescribing information. Bristol, TN; 2005Sep.

c. Azur Pharma Inc. Gastrocrom (cromolyn sodium) oral concentrate prescribing information. New York, NY; 2006 Mar.

d. Azur Pharma Inc. Gastrocrom (cromolyn sodium) oral concentrate patient instructions. New York, NY; 2006 Mar.

e. Dey. Cromolyn Sodium inhalation solution prescribing information. Napa, CA; 2006 Jan.

f. King Pharmaceuticals. Intal inhaler (cromolyn sodium) inhalation aerosol information for the patient. Bristol, TN; 2005 Sep.

g. Dey. Cromolyn Sodium inhalation solution patient instructions. Napa, CA; 2006 Jan.

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