Continuing Education Activity

Cromolyn sodium is a medication used in the management of bronchial asthma, allergic rhinitis, and certain allergic eye conditions such as vernal conjunctivitis, keratitis, and keratoconjunctivitis. It is a mast cell stabilizer. This activity reviews the indications, mechanism of action, and contraindications for cromolyn sodium as adjunctive prophylactic therapy for asthma and other disorders when applicable.

Objectives:

• Identify the mechanism of action and administration of cromolyn sodium.
• Describe the adverse effects and contraindications of cromolyn sodium.
• Review the appropriate monitoring and toxicity of cromolyn sodium.
• Summarize interprofessional team strategies for improving care coordination and communication to advance the management of chronic bronchial asthma, allergic rhinitis, systemic mast cell disease, and allergic eye conditions with cromolyn sodium and improve outcomes.

Indications

Cromolyn sodium is an FDA-approved medication used for prophylaxis of mild to moderate bronchial asthma and adjunctive treatment of allergic rhinitis and systemic mast cell disease (mastocytosis) in both pediatric patients and adults.[1][2] It is not immediate-acting and has no direct bronchodilator effects, and thus does not treat acute attacks of asthma. It is also available as an ophthalmic solution for the symptomatic treatment of certain allergic eye conditions such as vernal conjunctivitis, keratitis, and keratoconjunctivitis.[3] Non-FDA labeled indications include the prevention of serious reactions to foods and the management of inflammatory bowel disease and superior limbic keratoconjunctivitis.[4][5][6][7]

Mechanism of Action

Cromolyn sodium is a mast cell stabilizer that prevents the subsequent release of inflammatory mediators, including histamine and leukotrienes, which cause allergic symptoms and bronchoconstriction.[8][9] It inhibits mast cell degranulation, normally implicated in anaphylaxis following exposure to reactive allergens. Cromolyn sodium differs from antihistamine medications, which reduce the action of histamines following the release from mast cells. Unlike corticosteroids which inhibit the late response of antigen-induced asthmatic reactions, cromolyn sodium inhibits both immediate and late reactions.[10][6]

The bioavailability of cromolyn sodium is 0.5 to 2%, with a half-life of 80 to 90 minutes. This drug is absorbed poorly via oral solution and takes 2 to 6 weeks for onset of action. The effect of cromolyn sodium on mast cells lasts for approximately 6 hours following administration. The majority of the drug (98%) is excreted in the feces unabsorbed, with the remainder excreted in the urine.

Administration

Cromolyn sodium is available as:

• Oral solution of 100 mg/5 mL
• Nasal spray: 5.2 mg/1 actuation
• Ophthalmic solution of 4% (10mL)
• Inhalation solution: 10mg/1mL

FDA-approved clinical indications direct dosing guidelines:

• Asthma prophylaxis
  • Metered-dose inhaler: 2 oral inhalations (800 mcg/spray) 4 times daily at regular intervals, may need to titrate
  • Nebulizer: 20 mg (1 vial) via nebulization four times daily at regular intervals
• Mastocytosis (systemic): empty ampule into a glass of water and drink 30 mins before meals and bedtime
  • Children > 12 years-old and Adults: 200 mg PO four times daily; 30 minutes before meals. May increase to 40 mg/kg/day if control fo symptoms not seen within 2 to 3 weeks
  • Pediatric:
    • < 2 years old: safety and efficacy not established
    • 2 through 12 years old: 100 mg PO four times daily; not to exceed 40 mg/kg/day. Give 30 minutes before meals and at bedtime
• Allergic rhinitis
  • Nasal inhalation: 1 spray/nostril 3 to 6 times/day
• Keratitis/vernal conjunctivitis/vernal keratoconjunctivitis
  • 4+ years old: 1 to 2 drops in each eye 4 to 6 times daily, at regular intervals

Non-FDA Labeled Indications: 

• Food allergy and IBD
  • Children > 12-years-old and Adults: 200 mg PO four times daily; may double dose if inadequate symptom control within 2 to 3 weeks. Do not exceed 400 mg PO four times daily
  • Pediatric
    • < 2 years-old: not recommended
    • 2-12 years-old: 100 mg four times daily initially, may need to increase but do not exceed 40 mg/kg/d 

Adverse Effects

The frequency of adverse effects remains unclear.[11] Adverse effects vary depending on the route of administration.

Adverse events associated with oral solution include nausea, vomiting, diarrhea, abdominal pain, constipation, erythema, photosensitivity, urticaria, and angioedema.

There are reports of nasal congestion, sneezing, nasal itching, nosebleeds, rhinoconjunctivitis, and headaches with the use of cromolyn sodium nasal spray.

Additional adverse effects reported with the inhalation solution, including throat irritation and hoarseness, esophagitis, laryngeal and pharyngeal edema, drowsiness, dizziness, bronchial irritation, pulmonary infiltrates, and cough.

The ophthalmic solution may correlate with transient burning of eyes upon administration, eye dryness, puffiness, irritation, itchiness, rash, and styes.

Pregnancy Category B risk has not been ruled out. It is unknown if cromolyn sodium is excreted in breast milk.[12]

Contraindications

The following are contraindications for the use of cromolyn sodium:

• Hypersensitivity to cromolyn products or components

Monitoring

The clinician should closely monitor kidney and liver function in patients with hepatic or renal insufficiency and begin with a reduced dose. The effects of the medication may increase in patients with these medical conditions, thus increasing the chance of adverse effects. Patients with a history of cardiac arrhythmias or coronary artery disease (CAD) using inhalation solution should undergo cardiac follow up due to the contents of metered-dose inhaler propellants. Regular eye examinations are necessary when using cromolyn sodium ophthalmic solution. For individuals diagnosed with bronchial asthma, symptomatic improvement should have an assessment via pulmonary function tests.

Symptoms may reoccur when tapering or withdrawing the drug.

Toxicity

This drug is poorly absorbed and is low in toxicity. There has been no serious toxicity reported, and a specific toxic dose has not been established. There is not enough research verifying the efficacy or safety of cromolyn sodium use in pediatric patients less than 2-years-old. 

Acute life-threatening reactions have been allergic. In the event of a hypersensitivity reaction, patients should receive treatment with antihistamines with or without beta-agonists, corticosteroids, and epinephrine. In the case of a severe hypersensitivity reaction, oxygen, antihistamines, epinephrine, corticosteroids, as well as ECG monitoring and IV fluids should be administered. No specific labs or testing are necessary unless indicated.

Management of mild to moderate toxicity is symptomatic and supportive. The clinician should correct any significant fluid and or electrolyte abnormalities in patients with vomiting or diarrhea. Severe toxicity is not expected following an overdose but managed with symptomatic and supportive treatment.

Enhancing Healthcare Team Outcomes

Cromolyn sodium is indicated as an adjunctive treatment for a variety of medical conditions and is available as an oral solution, ophthalmic solution, inhalation solution, and nasal spray. Although adverse effects and hypersensitivity reactions to the drug are rare, it is the responsibility of the members of an interprofessional healthcare team, including nurses, pharmacists, and clinicians, to recognize the clinical presentation and provide the appropriate management of potentially life-threatening sequelae if they occur.

In the event a patient has a severe hypersensitivity reaction to cromolyn sodium, the emergency department clinician and nurses must execute an effective, patient-centered treatment plan which includes:

• Withdrawing the offending agent by stopping cromolyn sodium use
• Continual monitoring of the patient for signs and symptoms of anaphylaxis and cardiac arrhythmias
• Starting a peripheral IV and administering fluids
• Administering epinephrine, oxygen, antihistamines, and corticosteroids
• Consulting the pharmacist for thorough medication record review
• Consulting an intensivist for further observation and monitoring in the hospital

Following a hypersensitivity reaction or severe adverse event, a thorough discussion of future drug therapy changes must occur with the health care provider. Through an interprofessional approach, cromolyn sodium can be safely and effectively used in the management of patient care.[13] [Level V]