Cromolyn Sodium

Description

DESCRIPTION The active ingredient of cromolyn sodium inhalation solution, USP is cromolyn sodium, USP. It is an inhaled anti-inflammatory agent for the preventive management of asthma. Cromolyn sodium, USP is chemically designated as disodium 5,5'-[(2-hydroxytrimethylene)dioxy]bis[4-oxo-4 H -1-benzopyran-2- carboxylate]. The molecular formula is C 23 H 14 Na 2 O 11 ; the molecular weight is 512.34. Cromolyn sodium, USP is a water soluble, odorless, white, hydrated crystalline powder. It is tasteless at first, but leaves a slightly bitter after taste. Cromolyn sodium inhalation solution, USP is clear, colorless to pale yellow, sterile, and has a target pH of 5.5. The molecular structure is: Each 2 mL ampule of cromolyn sodium, USP contains 20 mg cromolyn sodium, USP in water for injection, USP. cromolynsodium-structure.jpg

What Is Cromolyn Sodium Used For?

INDICATIONS AND USAGE Cromolyn sodium inhalation solution, USP is a prophylactic agent indicated in the management of patients with bronchial asthma. In patients whose symptoms are sufficiently frequent to require a continuous program of medication, cromolyn sodium inhalation solution, USP is given by inhalation on a regular daily basis (see DOSAGE AND ADMINISTRATION ). The effect of cromolyn sodium inhalation solution is usually evident after several weeks of treatment, although some patients show an almost immediate response. In patients who develop acute bronchoconstriction in response to exposure to exercise, toluene diisocyanate, environmental pollutants, etc., cromolyn sodium inhalation solution should be given shortly before exposure to the precipitating factor (see DOSAGE AND ADMINISTRATION ).

Dosage and Administration

DOSAGE AND ADMINISTRATION For management of bronchial asthma in adults and pediatric patients (two years of age and over), the usual starting dosage is the contents of one ampule administered by nebulization four times a day at regular intervals. Drug stability and safety of cromolyn sodium inhalation solution when mixed with other drugs in a nebulizer have not been established. Patients with chronic asthma should be advised that the effect of cromolyn sodium inhalation solution therapy is dependent upon its administration at regular intervals, as directed. Cromolyn sodium inhalation solution should be introduced into the patient's therapeutic regimen when the acute episode has been controlled, the airway has been cleared and the patient is able to inhale adequately. For the prevention of acute bronchospasm which follows exercise or exposure to cold dry air, environmental agents ( e.g. , animal danders, toluene diisocyanate, pollutants), etc., the usual dose is the contents of one ampule administered by nebulization shortly before exposure to the precipitating factor. It should be emphasized to the patient that the drug is poorly absorbed when swallowed and is not effective by this route of administration. For additional information, see the accompanying leaflet entitled “ Living a Full Life with Asthma” . Cromolyn sodium inhalation solution Therapy in Relation to Other Treatments for Asthma: Non-steroidal agents Cromolyn sodium inhalation solution should be added to the patient's existing treatment regimen ( e.g. , bronchodilators). When a clinical response to cromolyn sodium inhalation solution is evident, usually within two to four weeks, and if the asthma is under good control, an attempt may be made to decrease concomitant medication usage gradually. If concomitant medications are eliminated or required on no more than a prn basis, the frequency of administration of cromolyn sodium inhalation solution may be titrated downward to the lowest level consistent with the desired effect. The usual decrease is from four to three ampules per day. It is important that the dosage be reduced gradually to avoid exacerbation of asthma. It is emphasized that in patients whose dosage has been titrated to fewer than four ampules per day, an increase in the dose of cromolyn sodium inhalation solution and the introduction of, or increase in, symptomatic medications may be needed if the patient's clinical condition deteriorates. Corticosteroids In patients chronically receiving corticosteroids for the management of bronchial asthma, the dosage should be maintained following the introduction of cromolyn sodium inhalation solution. If the patient improves, an attempt to decrease corticosteroids should be made. Even if the corticosteroid-dependent patient fails to show symptomatic improvement following cromolyn sodium inhalation solution administration, the potential to reduce corticosteroids may nonetheless be present. Thus, gradual tapering of corticosteroid...

Side Effects (Adverse Reactions)

ADVERSE REACTIONS Clinical experience with the use of cromolyn sodium suggests that adverse reactions are rare events. The following adverse reactions have been associated with cromolyn sodium: cough, nasal congestion, nausea, sneezing, and wheezing. Other reactions have been reported in clinical trials; however, a causal relationship could not be established: drowsiness, nasal itching, nose bleed, nose burning, serum sickness, and stomachache. In addition, adverse reactions have been reported with cromolyn sodium for inhalation capsules. The most common side effects are associated with inhalation of the powder and include transient cough (1 in 5 patients) and mild wheezing (1 in 25 patients). These effects rarely require treatment or discontinuation of the drug. Information on the incidence of adverse reactions to cromolyn sodium for inhalation capsules has been derived from U.S. postmarketing surveillance experience. The following adverse reactions attributed to cromolyn sodium, based upon recurrence following readministration, have been reported in less than 1 in 10,000 patients: laryngeal edema, swollen parotid gland, angioedema, bronchospasm, joint swelling and pain, dizziness, dysuria and urinary frequency, nausea, cough, wheezing, headache, nasal congestion, rash, urticaria and lacrimation. Other adverse reactions have been reported in less than 1 in 100,000 patients, and it is unclear whether these are attributable to the drug: anaphylaxis, nephrosis, periarteritic vasculitis, pericarditis, peripheral neuritis, pulmonary infiltrates with eosinophilia, polymyositis, exfoliative dermatitis, hemoptysis, anemia, myalgia, hoarseness, photodermatitis, and vertigo. To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA, Inc. at 1-855-839-8195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

Drug Interaction During Pregnancy Cromolyn sodium and isoproterenol were studied following subcutaneous injections in pregnant mice. Cromolyn sodium alone in doses up to 540 mg/kg (approximately 27 times the maximum recommended adult human daily inhalation dose on a mg/m 2 basis) did not cause significant increases in resorptions or major malformations. Isoproterenol alone at a dose of 2.7 mg/kg (approximately 7 times the maximum recommended adult human daily inhalation dose on a mg/m 2 basis) increased both resorptions and malformations. The addition of cromolyn sodium (approximately 27 times the maximum recommended adult human daily inhalation dose on a mg/m 2 basis) to isoproterenol (approximately 7 times the maximum recommended adult human daily inhalation dose on a mg/m 2 basis) appears to have increased the incidence of both resorptions and malformations.

Contraindications

CONTRAINDICATIONS Cromolyn sodium inhalation solution is contraindicated in those patients who have shown hypersensitivity to cromolyn sodium.

Pregnancy and Breastfeeding

Pregnancy Teratogenic Effects Reproduction studies with cromolyn sodium administered subcutaneously to pregnant mice and rats at maximum daily doses of 540 mg/kg and 164 mg/kg, respectively, and intravenously to rabbits at a maximum daily dose of 485 mg/kg produced no evidence of fetal malformations. These doses represent approximately 27, 17, and 98 times, respectively, the maximum recommended adult human daily inhalation dose on a mg/m 2 basis. Adverse fetal effects (increased resorptions and decreased fetal weight) were noted only at the very high parenteral doses that produced maternal toxicity. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when cromolyn sodium is administered to a nursing woman.

Overdosage

OVERDOSAGE There is no clinical syndrome associated with an overdosage of cromolyn sodium. Acute toxicity testing in a wide variety of species has demonstrated that toxicity with cromolyn sodium occurs only with very high exposure levels, regardless of whether administration was parenteral, oral or by inhalation. Parenteral administration in mice, rats, guinea pigs, hamsters, and rabbits demonstrated a median lethal dose of approximately 4000 mg/kg. Intravenous administration in monkeys also indicated a similar pattern of toxicity. The highest dose administered by the oral route in rats and mice was 8000 mg/kg, (approximately 261 and 130 times, respectively, the maximum recommended human daily inhalation dose on a mg/m 2 basis) and at this dose level no deaths occurred. By inhalation, even in long term studies, it proved impossible to achieve toxic dose levels of cromolyn sodium in a range of mammalian species.

How Supplied

HOW SUPPLIED Cromolyn sodium inhalation solution, USP is a clear, colorless to pale yellow solution, practically free from any visible particles supplied in 2mL fill in 3mL BFS (Blow Fill Seal) ampule with twist off cap. Each 2 mL ampule contains 20 mg cromolyn sodium, USP, in water for injection, USP. 2mL fill in 3mL BFS ampule NDC 42571-350-08 Inner Carton of 12 BFS ampules in a PVC Rondo Tray NDC 42571-350-08 Outer Carton of 60 x 2 mL Single-Dose Ampules (5 inner cartons of twelve 2 mL BFS Ampules) NDC 42571-350-09 Outer Carton of 120 x 2 mL Single-Dose Ampules (10 inner cartons of twelve 2 mL BFS Ampules) NDC 42571-350-50 Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Do not use if solution is discolored or contains a precipitate. Retain in rondo tray until time of use. PROTECT FROM LIGHT. Manufactured by: Micro Labs Limited Bangalore-560 099, INDIA. Manufactured for: Micro Labs USA, Inc. Somerset, NJ 08873 Rev.03/2022