Overall, both oral inhaled cromolyn and nedocromil are well tolerated with minimal side effects. The side effects reported with cromolyn include: throat irritation, cough, nasal congestion, mild bronchospasm, urticaria, angioedema, anaphylaxis, anaphylactoid reaction, and pulmonary infiltration with eosinophilia (PIE), cardiac tamponade and eosinophilia, dysuria, dermatitis, and myositis (155). One patient experienced a near-death exacerbation as he tried to use DSCG during an asthma attack (156).

The adverse effects of intranasal cromolyn include: sneezing, nasal burning or stinging (3). It has been reported that ocular cromolyn can result in contact dermatitis, allergic conjunctivitis, and chemosis (157,158). A 63-year-old male treated with DSCG ophthalmic solution developed allergic conjunctivitis and IgE antibodies to DSCG were demonstrated in serum by RAST (158).

Anti-CS antibodies have been documented by intracutaneous and RAST testing (159-161). Furthermore, Sheffer et al. (162) reported increased lymphocyte proliferation and elevated production of migration inhibition factor in response to cromolyn stimulation and increased serum immunoglobulin G binding of cromolyn in one patient with PIE compared to cromolyn-tolerant patients.

Drug interactions have not been documented with cromolyn. Overall, cromolyn can be used safely in elderly patients with hypertension, heart disease, seizure disorders, or prostate disease. Cromolyn is classified as category B in pregnancy. Patients who will benefit from intranasal cromolyn include: children >2 years, elderly patients, patients with comorbidities, patients reluctant to take medications, patients and athletes who undergo drug monitoring to avoid corticosteroids (3).

In general, nedocromil is well tolerated with a good safety record. On the other hand, nedocromil has been associated with an unpleasant taste, nausea, and vomiting (3).

There has been a concern with growth rate and the use of ICS in children. A recent study compared bone mineral density in children on fluticasone propionate (FP) versus nedocromil for two years (163). No significant difference in growth was observed between the groups; adjusted mean growth rates were 6.1 cm/yr with FP and 5.8 cm/yr with nedocromil (163).

Both cromolyn and nedocromil have no effect on normal host defense, no known teratogenic effects, and do not influence the development of neoplastic disease (164,165). A 10-year follow-up study with cromolyn showed no adverse effects (101).

In summary, both cromolyn and nedocromil can be useful as adjuvant therapy in the treatment of asthma. Their benefits have been seen in a reduction in ED visits and hospitalizations for asthma, and a decrease in allergen/exercise-induced bronchospasm and frequency of prednisone use. Furthermore, cromolyn has been useful in the treatment of allergic rhinitis and allergic conjunctivitis, with occasional use in other systemic diseases.

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