Cromolyn (Nasal)


VA CLASSIFICATION
Primary: NT900

Commonly used brand name(s): Apo-Cromolyn; Children's Nasalcrom; Cromolyn Nasal Solution; Gen-Cromoglycate; Nasalcrom.

Another commonly used name is
sodium cromoglycate . {01} {02} {04}
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Mast cell stabilizer (nasal)—

antiallergic (nasal){15}

Indications

Accepted

Rhinitis, allergic (prophylaxis and treatment)—Cromolyn sodium nasal solution is indicated for the prophylaxis and treatment of the symptoms of perennial and seasonal allergic rhinitis. {01} {03} {06}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    512.34 {11} {14}


pH
    4.5 to 6.5. {06}

Mechanism of action/Effect:

Cromolyn is a mast cell stabilizer that inhibits the Type I immediate hypersensitivity reaction by preventing the antigen-stimulated release of histamine. Cromolyn also prevents the release of leukotrienes and inhibits eosinophil chemotaxis. {03} {05} {06} {07} {08} {15}

In vitroand in vivo animal studies have shown that cromolyn inhibits the degranulation of sensitized mast cells that occurs after exposure to specific antigens. Cromolyn inhibits the release of histamine and SRS-A (slow-reacting substance of anaphylaxis). {06} Some in vitro studies have shown that cromolyn inhibits the degranulation of nonsensitized rat mast cells by phospholipase A and the subsequent release of chemical mediators. {06}


Other actions/effects:

Cromolyn has no intrinsic bronchodilator, antihistaminic, decongestant, or anti-inflammatory action. {01} {06}

Absorption:

Poorly absorbed from the gastrointestinal tract. After instillation of cromolyn nasal solution, less than 7% of the total dose administered is absorbed. {06}

Onset of therapeutic effect

Seasonal allergic rhinitis—Results are usually noticeable in less than 1 week. {10}

Time to peak effect:

Perennial allergic rhinitis—Results are usually noticeable in approximately 1 week; however, in some cases up to 2 to 4 weeks may be required. {03} {05} {06} {08} {15}

Elimination:
    Nasal solution—The portion of the dose that is absorbed (7%) is rapidly {15} excreted unchanged in the bile and urine; the remainder of the dose is expelled from the nose, or swallowed and excreted via the alimentary tract. {06}


Precautions to Consider

Carcinogenicity

Long-term studies with cromolyn in mice (12 months of intraperitoneal treatment followed by 6 months of observation), hamsters (12 months of intraperitoneal treatment followed by 12 months of observation), and rats (18 months of subcutaneous treatment) did not show any neoplastic effect. {06}

Mutagenicity

In various mutagenicity studies, there was no evidence of chromosomal damage or cytotoxicity. {06}

Pregnancy/Reproduction
Fertility—
Animal reproduction studies with cromolyn showed no evidence of impaired fertility. {06}

Pregnancy—
Adequate and well-controlled studies in humans have not been done. {06}



Reproduction studies in mice, rats, and rabbits with cromolyn administered parenterally in doses up to 338 times the human clinical doses showed no evidence of fetal malformations. (Adverse fetal effects [increased resorptions and decreased fetal weight] were noted only at very high parenteral doses that produced maternal toxicity.) {06} {08}

FDA Pregnancy Category B. {06}

Breast-feeding

It is not known whether cromolyn is distributed into breast milk; however, nasal cromolyn reaches very low concentrations in maternal serum. {06} Caution should be exercised when cromolyn is administered to nursing women. Problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of nasal cromolyn have not been performed in the U.S. in children up to 6 years of age (in Canada, up to 5 years of age) {01}. In older children, no pediatrics-specific problems have been documented to date. {08}


Geriatrics


Appropriate studies on the relationship of age to the effects of nasal cromolyn have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date. {08}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Methacholine, for inhalation    (cromolyn may decrease slightly, but inconsistently {09} {12} {13}, the response to methacholine challenge in the diagnosis of bronchial airway hyperreactivity; however, cromolyn generally does not cause false-negative tests {11})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Polyps, nasal    (medication may not be effective if nasal passage obstruction exists; patients need to be observed during treatment {01})


Hepatic function impairment{06}
Renal function impairment{06}
Sensitivity to cromolyn{06}


Side/Adverse Effects

Note: Eosinophilic pneumonia has been reported rarely with cromolyn nasal products. {01}
Although not reported for cromolyn nasal solution, some side/adverse effects that have occurred with cromolyn formulations for inhalation include joint pain and swelling, and, reported rarely, exfoliative dermatitis, heart failure {01}, nephrosis, periarteritic vasculitis, pericarditis, peripheral neuritis, photodermatitis, pneumonitis {01} {06} {08}, polymyositis {01} {06} {08}, and serum sickness.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Anaphylactic reaction{06} (coughing; difficulty in swallowing; hives; itching of skin; swelling of face, lips, or eyelids; wheezing or difficulty in breathing)
    
epistaxis{06} (nosebleeds)
    
skin rash{01}{06}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Burning, stinging, or irritation inside of nose{01}{05}{06}{15}
    
erythema{01} (flushing)
    
increase in sneezing{01}{06}
    
urticaria{01} (hives)

Incidence less frequent
    
Cough{01}
    
headache{01}{06}
    
postnasal drip{06}
    
unpleasant taste{01}{06}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Cromolyn (Nasal) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to cromolyn





Use in children—Safety and efficacy have not been established in the U.S. in children up to 6 years of age (in Canada, up to 5 years of age) {01} {05} {08} {15}


Proper use of this medication
Preventing spread of infection: Not using bottle for more than 1 person

Reading patient directions carefully

Clearing nasal passages before use

For cromolyn nasal solution: Using with a special spray device; wiping nosepiece with a clean tissue and replacing dust cap after use to keep unit clean

» Importance of not using more medication than the amount prescribed

» Using every day in regularly spaced doses in order for medication to work properly; results are usually noticeable in approximately 1 week; however in perennial allergic rhinitis, up to 4 weeks may be required for full benefit

» Proper dosing
Missed dose: Using as soon as possible; using any remaining doses for that day at regularly spaced intervals; not doubling doses

» Proper storage

Precautions while using this medication
» Checking with physician if symptoms do not improve or if condition becomes worse


Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction, epistaxis, and skin rash


General Dosing Information
Prior to administration of cromolyn nasal solution, the nasal passages should be cleared. During administration, patient should inhale through the nose. {05} {06} {15}

In the management of seasonal allergic rhinitis (pollinosis) and for the prevention of rhinitis caused by other types of specific airborne {08} allergens, treatment with nasal cromolyn is more effective if started prior to exposure to the offending allergen. Therapy should be continued throughout the period of exposure (i.e., until the pollen season is over or until the patient is no longer exposed to the offending allergen). {03} {05} {06} {15}

In the management of perennial allergic rhinitis, improvement of condition may not become apparent for up to {08} 2 to 4 weeks. {06} Concurrent use of an antihistamine and/or a nasal decongestant may be necessary during this time; however, the need for these medications should decrease and these medications may be discontinued when the full effect of nasal cromolyn is achieved. {06}

For use of cromolyn sodium nasal solution beyond 12 weeks, consult a physician. {05} {15}


Nasal Dosage Forms

CROMOLYN SODIUM NASAL SOLUTION USP

Usual adult and adolescent dose
Allergic rhinitis, perennial or seasonal (prophylaxis and treatment)
Intranasal, 5.2 mg (1 spray) in each nostril three or four times a day at regular intervals. Dose may be increased to 1 spray in each nostril six times a day. {03} {05} {06} {08} {15}

Note: The following dosage guidelines are used in Canada: Intranasal, 2.6 mg (1 spray) in each nostril six times per day. Dose may be reduced to 1 spray in each nostril every eight to twelve hours, once adequate response is obtained. {01} {08}



Usual adult prescribing limits
5.2 mg in each nostril {03} {05} {06} {08} {15}(2.6 mg in each nostril [Canada] {01}) six times a day.

Usual pediatric dose
Allergic rhinitis, perennial or seasonal (prophylaxis and treatment)
Children up to 6 years of age (in Canada, up to 5 years of age): {08} Safety and efficacy have not been established. {03}

Children 6 years of age (in Canada, 5 years of age) {08} and over: See Usual adult and adolescent dose . {01} {03} {05} {06} {08} {15}


Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


40 mg per mL (5.2 mg per metered spray) (OTC) [Children's Nasalcrom{15} (benzalkonium chloride 0.01%) (edetate disodium 0.01%)] [Nasalcrom{03}{06}{08} (benzalkonium chloride 0.01%) (edetate disodium 0.01%)]

Canada—


20 mg per mL (2.6 mg per metered spray) (Rx) [Apo-Cromolyn{01} (benzalkonium chloride) (edetate disodium) (purified water) (sodium hydroxide)] [Cromolyn Nasal Solution{04}] [Gen-Cromoglycate{02} (benzalkonium chloride) (disodium edetate) (purified water)][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing. {05} {06} {15}

Auxiliary labeling:
   • For the nose.

Note: Include patient instructions when dispensing.
Explain administration technique.


Additional information:
The nasal spray bottle containing 520 mg/13 mL delivers at least 100 sprays. {03} {06}



Revised: 6/04/1999



References
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 34th ed. Ottawa: Canadian Pharmacists Association; 1999. p. 119.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 34th ed. Ottawa: Canadian Pharmacists Association; 1999. p. 724.
  1. PDR Physicians' desk reference for nonprescription drugs. 19th ed. Montvale, NJ: Medical Economics Co Inc; 1998. p. 728-9.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 34th ed. Ottawa: Canadian Pharmacists Association; 1999. p. 424.
  1. Nasalcrom package insert (Pharmacia & Upjohn—US), Rec 3/9/99.
  1. Nasalcrom package insert with patient instructions (Fisons—US), Rev 1/92, Rec 6/93.
  1. Allansmith MR, Ross RN. Ocular allergy and mast cell stabilizers. Surv Ophthalmol 1986 Jan/Feb; 30(4): 229-44.
  1. Panel comments, 12/31/93.
  1. Reed CE, Townley RG. Asthma: classification and pathogenesis. Allergy principles and practice. 2nd ed. St. Louis: The C.V. Mosby Co; 1983. p. 811.
  1. Drug evaluations subscription. Chicago: American Medical Association, Annual 1991: 418.
  1. Methacholine for diagnosis of asthma. Med Lett Drugs Ther 1987 Jun 19; 29(742): 58.
  1. Panel comments, Rec 6/2/87.
  1. Panel comments, Rec 6/19/87.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 198.
  1. Children's Nasalcrom package insert (Pharmacia and Upjohn—US), Rec 4/99.
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