CLASSES
Ocular Anti-Allergics, Mast Cell Stabilizers
Respiratory Mast Cell Stabilizers
Systemic Mast Cell Stabilizers
Topical Nasal Antiallergic Agents
DESCRIPTION
Mast-cell stabilizer; used in adult and pediatric patients 2 years and older
Nasal spray is used for allergic rhinitis; ophthalmic solution used for allergic conjunctivitis; used orall for systemic mastocytosis
Nebulizer solution used for asthma control or exercise-induced bronchospasm, but is not a preferred treatment
COMMON BRAND NAMES
Crolom, Gastrocrom, Intal, Nasalcrom, Nasalcrom Child, Opticrom
HOW SUPPLIED
Crolom/Cromolyn/Cromolyn Sodium/Opticrom Ophthalmic Sol: 4%
Cromolyn/Cromolyn Sodium/Gastrocrom Oral Sol: 5mL, 100mg
Cromolyn/Cromolyn Sodium/Intal Respiratory (Inhalation) Sol: 2mL, 20mg
Nasalcrom Nasal Spray Met: 1actuation, 5.2mg
DOSAGE & INDICATIONS
For use as an adjunct for asthma maintenance.
Nebulized Inhalation dosage (solution for nebulization)
Adults
Inhale 20 mg via nebulizer 4 times per day at regular intervals. A 4 to 6-week trial may be necessary to determine maximum benefit. Once stabilized, reduce to the lowest effective dose. The usual decrease is from 4 to 3 times per day. Not recommended for routine use in asthma management due to low efficacy.
Children and Adolescents 2 years and older
Inhale 20 mg via nebulizer 4 times per day at regular intervals. A 4 to 6-week trial may be necessary to determine maximum benefit. Once stabilized, reduce to the lowest effective dose. The usual decrease is from 4 to 3 times per day. 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.
Oral inhalation dosage (nebulized solution)
Adults
Inhale 20 mg via nebulization not more than 1 hour before anticipated exercise or exposure to other precipitating factors. Effective prophylaxis lasts approximately 1 to 2 hours. For maximum effect, the interval between administration of cromolyn and exposure to the precipitating factor should be as short as possible. The American Thoracic Society states that a mast cell stabilizing agent such as cromolyn before exercise may be considered in patients 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 EIB control.
Children and Adolescents 2 years and older
Inhale 20 mg via nebulization not more than 1 hour before anticipated exercise or exposure to other precipitating factors. Effective prophylaxis lasts approximately 1 to 2 hours. For maximum effect, the interval between administration of cromolyn and exposure to the precipitating factor should be as short as possible. The American Thoracic Society states that a mast cell stabilizing agent such as cromolyn before exercise may be considered in patients 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 EIB control.
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
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.
DOSING CONSIDERATIONS
Hepatic Impairment
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.
Renal Impairment
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.
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.
STORAGE
Crolom:
- Protect from light
- Store between 59 to 77 degrees F
- Store in original container
Gastrocrom:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Protect from light
- Store at controlled room temperature (between 68 and 77 degrees F)
- Store in original package until time of use
Intal:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Discard unused portion. Do not store for later use.
- Protect from light
- Store at controlled room temperature (between 68 and 77 degrees F)
- Store in original package until time of use
Nasalcrom:
- Protect from light
- Store at controlled room temperature (between 68 and 77 degrees F)
Nasalcrom Child:
- Protect from light
- Store between 68 to 77 degrees F
Opticrom:
- Protect from light
- Store between 59 to 77 degrees F
- Store in original container
CONTRAINDICATIONS / PRECAUTIONS
General Information
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.
Acute bronchospasm, status asthmaticus
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.
Hepatic disease, renal failure, renal impairment
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.
Contact lenses
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.
Pregnancy
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.
Breast-feeding
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.
Children, infants
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.
ADVERSE REACTIONS
Severe
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
seizures / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
atrial tachycardia / Early / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
Moderate
dyspnea / Early / Incidence not known
wheezing / Rapid / Incidence not known
glossitis / Early / Incidence not known
constipation / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
psychosis / Early / Incidence not known
depression / Delayed / Incidence not known
hallucinations / Early / Incidence not known
migraine / Early / Incidence not known
neuritis / Delayed / Incidence not known
polycythemia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
hemoptysis / Delayed / Incidence not known
edema / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
dysuria / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
premature ventricular contractions (PVCs) / Early / Incidence not known
palpitations / Early / Incidence not known
erythema / Early / Incidence not known
Mild
diarrhea / Early / 0-5.0
headache / Early / 0-5.0
nausea / Early / 0-4.0
myalgia / Early / 0-4.0
pruritus / Rapid / 0-4.0
abdominal pain / Early / 2.0-2.0
rash / Early / 2.0-2.0
cough / Delayed / Incidence not known
nasal irritation / Early / Incidence not known
throat irritation / Early / Incidence not known
sneezing / Early / Incidence not known
hoarseness / Early / Incidence not known
nasal congestion / Early / Incidence not known
pharyngitis / Delayed / Incidence not known
dyspepsia / Early / Incidence not known
vomiting / Early / Incidence not known
flatulence / Early / Incidence not known
tinnitus / Delayed / Incidence not known
insomnia / Early / Incidence not known
lethargy / Early / Incidence not known
fatigue / Early / Incidence not known
drowsiness / Early / Incidence not known
dizziness / Early / Incidence not known
malaise / Early / Incidence not known
vertigo / Early / Incidence not known
paresthesias / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
ocular irritation / Rapid / Incidence not known
lacrimation / Early / Incidence not known
ocular pruritus / Rapid / Incidence not known
increased urinary frequency / Early / Incidence not known
urticaria / Rapid / Incidence not known
purpura / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
flushing / Rapid / Incidence not known
DRUG INTERACTIONS
There are no drug interactions associated with Cromolyn Sodium products.
PREGNANCY AND LACTATION
Pregnancy
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.
MECHANISM OF ACTION
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.
PHARMACOKINETICS
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
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.