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CROMOLYN AND RELATED AGENTS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Cromolyn is an antiasthmatic agent derived from khellin and extract from a Mediterranean plant. Nedocromil, a pyranoquinoline, is an antiinflammatory agent that blocks the release of mediators of hypersensitivity reactions from mast cells, eosinophils, neutrophils, macrophages, monocytes and platelets.

Specific Substances

    A) CROMOLYN (SYNONYM)
    1) Cromoglycic acid
    2) CAS 16110-51-3
    CROMOLYN SODIUM (SYNONYM)
    1) Disodium cromoglycate
    2) Disodium salt of cromolyn
    3) DSCG
    4) FPL 670
    5) Natrii cromoglicas
    6) Sodium cromoglicate
    7) Sodium cromoglycate
    8) Cromoglicato disodico (Spanish)
    9) CAS 15826-37-6
    NEDOCROMIL CALCIUM (SYNONYM)
    1) FPL-59002KC
    2) CAS 101626-68-0
    NEDOCROMIL SODIUM (SYNONYM)
    1) Disodium 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate
    2) FPL-59002 (nedocromil)
    3) FPL-59002KP (nedocromil sodium)
    4) Nedocromilo sodico
    5) CAS 69049-73-6 (nedocromil)
    6) CAS 69049-74-7 (nedocromil sodium)

    1.2.1) MOLECULAR FORMULA
    1) CROMOLYN SODIUM: C23H14Na2O11
    2) NEDOCROMIL SODIUM: C19H15NNa2O7

Available Forms Sources

    A) FORMS
    1) CROMOLYN
    a) INHALATION: 10 mg/mL (Prod Info cromolyn sodium inhalation solution, 2012).
    b) ORAL SOLUTION: 100 mg/5 mL (Prod Info cromolyn sodium oral solution concentrate, 2013)
    c) NASAL SPRAY: 5.2 mg/actuation (Prod Info Cromolyn sodium nasal spray, 2010).
    d) OPHTHALMIC: 4% ophthalmic solution is available containing 40 mg cromolyn sodium per mL (Prod Info cromolyn sodium 4% ophthalmic solution, 2012).
    2) NEDOCROMIL
    a) OPHTHALMIC SOLUTION: 2% ophthalmic solution is available containing 20 mg of nedocromil sodium per mL (Prod Info ALOCRIL(R) topical ophthalmic solution, 2008).
    b) INHALATION: 210 mg of nedocromil sodium contained in a 16.2 g canister that provides at least 104 metered inhalations is available. Each actuation meters 2 mg of nedocromil sodium from the valve and delivers 1.75 mg nedocromil sodium from the mouthpiece (Prod Info Tilade Inhaler, 2003).
    B) USES
    1) CROMOLYN
    a) Cromolyn is used to treat allergic rhinitis, mastocytosis, vernal keratitis, vernal conjunctivitis, and vernal keratoconjunctivitis. It is also used as a prophylactic agent indicated in treatment of patients with bronchial asthma (Prod Info cromolyn sodium oral solution concentrate, 2013; Prod Info cromolyn sodium 4% ophthalmic solution, 2012; Prod Info cromolyn sodium inhalation solution, 2012; Prod Info Cromolyn sodium nasal spray, 2010).
    2) NEDOCROMIL
    a) OPHTHALMIC SOLUTION: Nedocromil sodium ophthalmic solution is indicated for the treatment of pruritus associated with allergic conjunctivitis (Prod Info ALOCRIL(R) topical ophthalmic solution, 2008).
    b) INHALATION: Nedocromil sodium inhaler has been used as maintenance therapy for the management of mild to moderate asthma in adult and pediatric patients 6-years-old and older (Prod Info Tilade Inhaler, 2003).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Cromolyn is used to treat allergic rhinitis, mastocytosis, vernal keratitis, vernal conjunctivitis, and vernal keratoconjunctivitis. It is also used as a prophylactic agent indicated in treatment of patients with bronchial asthma. Nedocromil sodium ophthalmic solution is indicated for the treatment of pruritus associated with allergic conjunctivitis. Nedocromil sodium inhaler has been used as maintenance therapy for the management of mild to moderate asthma.
    B) PHARMACOLOGY: Cromolyn sodium, an antiinflammatory agent and mast cell stabilizer, prevents bronchoconstriction that manifests early or late in response to an inhaled antigen. It blocks the release of histamine and SRS-A (slow-reacting substance of anaphylaxis) from sensitized mast cells and does not exert any intrinsic vasoconstrictor and glucocorticoid effects. Nedocromil sodium is an antiinflammatory agent that blocks the release of mediators of hypersensitivity reactions from mast cells, eosinophils, neutrophils, macrophages, monocytes and platelets. The drug inhibits the release of histamine from mast cells and beta-glucuronidase from macrophages in bronchoalveolar cells. It does not exert any bronchodilating, antihistaminic, or corticosteroid effects.
    C) EPIDEMIOLOGY: Overdose is rare and serious toxicity has not been reported.
    D) WITH THERAPEUTIC USE
    1) CROMOLYN: The following adverse effects have been reported: ORAL SOLUTION: Nausea, vomiting, diarrhea, abdominal pain, constipation, dyspepsia, flatulence, glossitis, stomatitis, dysphagia, esophagospasm, pruritus, rash, erythema/burning, photosensitivity, urticaria, angioedema, eosinophilia. OPHTHALMIC: Stinging and burning of eyes, allergic reactions (eg, swelling, intense redness, and itching of the eyes), rhinoconjunctivitis, and myositis. NASAL: Nasal congestion, sneezing, nasal itching, nosebleed, nose burning, rhinoconjunctivitis, and headache. INHALATION: Nasal congestion, throat irritation and hoarseness, esophagitis, laryngeal and pharyngeal edema and irritation, drowsiness, headache, dizziness, bronchial irritation, pulmonary infiltrates, cough, and wheezing. Acute, life-threatening reactions (eg, anaphylactoid reaction) have been allergic, rather than toxic, in nature.
    2) NEDOCROMIL: OPHTHALMIC: MOST COMMON: Headache. OTHER EFFECTS: Ocular burning and irritation, taste disturbances, and nasal congestion, conjunctivitis, redness, photophobia. INHALATION: Nedocromil appears to be well-tolerated. MOST COMMON: Taste disturbance. INFREQUENT: Nausea, vomiting, abdominal pain, headache, dizziness, and coughing.
    E) WITH POISONING/EXPOSURE
    1) These agents are poorly absorbed and are low in toxicity. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.
    0.2.20) REPRODUCTIVE
    A) It is unknown whether cromolyn or nedocromil are excreted in breast milk.
    B) Cromolyn and nedocromil are listed as a Pregnancy Category B risk. No well controlled clinical studies have been done in humans.

Laboratory Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with vomiting or diarrhea.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Severe toxicity is not expected after an overdose of cromolyn or nedocromil.
    C) DECONTAMINATION
    1) PREHOSPITAL: These agents are poorly absorbed and are low in toxicity. Gastrointestinal decontamination is not recommended.
    2) HOSPITAL: These agents are poorly absorbed and are low in toxicity. Gastrointestinal decontamination is rarely necessary. Consider activated charcoal if coingestants with significant toxicity are involved.
    D) AIRWAY MANAGEMENTS
    1) Should not be required in these cases.
    E) ANTIDOTE
    1) None.
    F) HYPERSENSITIVITY REACTION
    1) MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
    G) ENHANCED ELIMINATION
    1) Since systemic absorption is minimal, methods to enhance systemic elimination are unlikely to be necessary.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess electrolyte and fluid balance and gastrointestinal function. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    I) PHARMACOKINETICS
    1) Both are poorly absorbed by any route. CROMOLYN: protein binding: approximately 58%. Metabolism: Cromolyn is not metabolized, but is excreted unchanged. Elimination half-life: inhalation: 80 to 90 minutes. NEDOCROMIL: protein binding: approximately 89%. Excretion: approximately 70% of nedocromil is excreted unchanged in the urine. Elimination half-life: inhalation: 1.5 hours.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) TOXICITY: A specific toxic dose has not been established. Significant toxicity is not expected after overdose.
    B) THERAPEUTIC DOSES: CROMOLYN: ADULTS: ORAL INHALATION: 20 mg 4 times daily (nebulizer). NASAL SPRAY: 1 spray/nostril (cromolyn 5.2 mg/spray) 3 to 6 times/day. ORAL SOLUTION: 200 mg 4 times/day 30 minutes before meals and at bedtime. OPHTHALMIC: 1 to 2 drops in each eye 4 to 6 times daily, at regular intervals. NEDOCROMIL: OPHTHALMIC: 1 to 2 drops in each eye twice daily. CHILDREN: CROMOLYN: ORAL INHALATION (2 years and older): 20 mg 4 times/day (nebulizer). ORAL SOLUTION (13 years and older): 200 mg (two 5 mL ampules) 4 times/day 30 minutes before meals and at bedtime. (ages 2 to 12 years): 100 mg (one 5 mL ampule) 4 times daily 30 minutes before meals and at bedtime. (Term to 2 years old): 20 mg/kg/day orally; administered in 4 divided doses. NASAL SPRAY (2 years and older): 1 spray/nostril (cromolyn 5.2 mg/spray) 3 to 6 times/day. OPHTHALMIC (4 years and older): 1 to 2 drops in each eye 4 to 6 times daily, at regular intervals. NEDOCROMIL: OPHTHALMIC (3 years and older): 1 to 2 drops in each eye twice daily.

Clinical Effects

Summary Of Exposure

    A) USES: Cromolyn is used to treat allergic rhinitis, mastocytosis, vernal keratitis, vernal conjunctivitis, and vernal keratoconjunctivitis. It is also used as a prophylactic agent indicated in treatment of patients with bronchial asthma. Nedocromil sodium ophthalmic solution is indicated for the treatment of pruritus associated with allergic conjunctivitis. Nedocromil sodium inhaler has been used as maintenance therapy for the management of mild to moderate asthma.
    B) PHARMACOLOGY: Cromolyn sodium, an antiinflammatory agent and mast cell stabilizer, prevents bronchoconstriction that manifests early or late in response to an inhaled antigen. It blocks the release of histamine and SRS-A (slow-reacting substance of anaphylaxis) from sensitized mast cells and does not exert any intrinsic vasoconstrictor and glucocorticoid effects. Nedocromil sodium is an antiinflammatory agent that blocks the release of mediators of hypersensitivity reactions from mast cells, eosinophils, neutrophils, macrophages, monocytes and platelets. The drug inhibits the release of histamine from mast cells and beta-glucuronidase from macrophages in bronchoalveolar cells. It does not exert any bronchodilating, antihistaminic, or corticosteroid effects.
    C) EPIDEMIOLOGY: Overdose is rare and serious toxicity has not been reported.
    D) WITH THERAPEUTIC USE
    1) CROMOLYN: The following adverse effects have been reported: ORAL SOLUTION: Nausea, vomiting, diarrhea, abdominal pain, constipation, dyspepsia, flatulence, glossitis, stomatitis, dysphagia, esophagospasm, pruritus, rash, erythema/burning, photosensitivity, urticaria, angioedema, eosinophilia. OPHTHALMIC: Stinging and burning of eyes, allergic reactions (eg, swelling, intense redness, and itching of the eyes), rhinoconjunctivitis, and myositis. NASAL: Nasal congestion, sneezing, nasal itching, nosebleed, nose burning, rhinoconjunctivitis, and headache. INHALATION: Nasal congestion, throat irritation and hoarseness, esophagitis, laryngeal and pharyngeal edema and irritation, drowsiness, headache, dizziness, bronchial irritation, pulmonary infiltrates, cough, and wheezing. Acute, life-threatening reactions (eg, anaphylactoid reaction) have been allergic, rather than toxic, in nature.
    2) NEDOCROMIL: OPHTHALMIC: MOST COMMON: Headache. OTHER EFFECTS: Ocular burning and irritation, taste disturbances, and nasal congestion, conjunctivitis, redness, photophobia. INHALATION: Nedocromil appears to be well-tolerated. MOST COMMON: Taste disturbance. INFREQUENT: Nausea, vomiting, abdominal pain, headache, dizziness, and coughing.
    E) WITH POISONING/EXPOSURE
    1) These agents are poorly absorbed and are low in toxicity. Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) CROMOLYN
    a) STINGING AND BURNING of eyes may be seen when cromolyn sodium is instilled into the eyes therapeutically (Prod Info cromolyn sodium ophthalmic solution, 4%, 2002; Ostler, 1982).
    b) CHEMOSIS: An acute chemotic reaction (conjunctival swelling) has been seen with long-term (2 to 3 years) therapeutic use.
    c) Allergic reactions consisting of swelling, intense redness, and itching of the eyes, may occur following therapeutic administration of cromolyn sodium eye drops. Symptoms dissipated when the drug was discontinued for 5 to 7 days (Valdivieso et al, 1998; (Ostler, 1982).
    2) NEDOCROMIL
    a) Ocular irritation, stinging and burning have occurred in 10% to 30% of patients following administration of the 2% ophthalmic solution. Other ocular side effects, including conjunctivitis, redness, and photophobia, have occurred in 1% to 10% of patients using the ophthalmic solution (Prod Info Alocril Ophthalmic Solution, 2002).
    3.4.5) NOSE
    A) WITH THERAPEUTIC USE
    1) CROMOLYN
    a) Nasal congestion, sneezing, nasal itching, nosebleed, and nose burning have been reported with cromolyn usage (Prod Info NASALCROM(R) nasal spray, 2005; Prod Info cromolyn sodium inhalation solution, 2006; Rao, 1975; Block, 1974).
    b) Rhinoconjunctivitis has been reported after therapeutic use in the eyes and nose (Skarpass, 1987).
    2) NEDOCROMIL
    a) Nasal congestion was reported in 10% to 30% of patients using the 2% ophthalmic solution (Prod Info Alocril Ophthalmic Solution, 2002).
    3.4.6) THROAT
    A) WITH THERAPEUTIC USE
    1) CROMOLYN
    a) Throat irritation and hoarseness have been noted with inhalation of disodium cromoglycate (Brown et al, 1981).
    b) Laryngeal and pharyngeal edema and irritation have occurred with use of the capsules used for inhalation (Prod Info cromolyn sodium inhalation solution, 2006).
    2) NEDOCROMIL
    a) TASTE DISTURBANCES: The most frequently observed adverse effect during nedocromil inhalation therapy is a distinctive, unpleasant, or bitter taste, occurring in approximately 11% to 13% of patients (Prod Info Tilade Inhaler, 2003; Greif et al, 1989; Williams, 1989; Goldin & Bateman, 1988; Holgate, 1987; Ayres, 1987; Gonzalez & Brogden, 1987). Unpleasant taste was reported in 10% to 30% of patients using the 2% ophthalmic solution (Prod Info Alocril Ophthalmic Solution, 2002).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) PERICARDITIS
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: CASE REPORT: A single case has been reported of a 46-year-old who was taking cromolyn for 3 months and developed eosinophilia, increased cardiac size, interstitial pulmonary edema, sinus tachycardia, and other signs consistent with pericarditis with cardiac tamponade. This was thought to be a hypersensitivity reaction (Slater, 1978).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) WITH THERAPEUTIC USE
    a) Bronchial irritation may be seen with cromolyn use, and pulmonary infiltrates have been reported in two cases (Lobel, 1972; Burgher, 1974; Paterson, 1976; Cooper, 1970).
    B) BRONCHOSPASM
    1) WITH THERAPEUTIC USE
    a) A number of asthmatic attacks have occurred in patients taking cromolyn (Serup, 1979; Price, 1982).
    C) COUGH
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Cough has been reported with cromolyn sodium inhalation solution (Prod Info cromolyn sodium inhalation solution, 2006).
    b) NEDOCROMIL: Cough has been reported in 7% to 9% of patients receiving inhalational nedocromil therapy (Prod Info Tilade Inhaler, 2003; Williams, 1989; Carrasco & Sepulveda, 1988; Goldin & Bateman, 1988; Lal et al, 1986).
    D) WHEEZING
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Wheezing has been reported with cromolyn sodium inhalation solution (Prod Info cromolyn sodium inhalation solution, 2006).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) DROWSY
    1) WITH THERAPEUTIC USE
    a) Drowsiness has occurred with the use of cromolyn nebulizer solution (Prod Info cromolyn sodium inhalation solution, 2006).
    B) HEADACHE
    1) WITH THERAPEUTIC USE
    a) CROMOLYN
    1) Headache (1 in 50 patients) has been reported with cromolyn sodium nasal solution (Prod Info NASALCROM(R) nasal spray, 2005).
    2) Headache have been reported after use of the capsules for inhalation (Prod Info cromolyn sodium inhalation solution, 2006).
    b) NEDOCROMIL
    1) Headache has been reported with the use of nedocromil (Ayres, 1987; Gonzalez & Brogden, 1987; Greif et al, 1989). This effect has been reported in 8% (severe in 1%) of patients (n=2632) who received inhalations of nedocromil during controlled and open-label clinical trials of 1 to 52 weeks in duration (Prod Info Tilade Inhaler, 2003).
    2) Headache was the most frequently reported adverse effect (40%) associated with the use of the 2% ophthalmic solution (Prod Info Alocril Ophthalmic Solution, 2002).
    C) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Dizziness has been reported after use of the capsules for inhalation (Prod Info cromolyn sodium inhalation solution, 2006).
    b) NEDOCROMIL: Dizziness has been reported in 1% to 2% of patients treated with nedocromil (Gonzalez & Brogden, 1987).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL TRACT FINDING
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Nausea, vomiting, diarrhea, abdominal pain, constipation, dyspepsia, flatulence, glossitis, stomatitis, dysphagia, and esophagospasm have been reported after the use of cromolyn sodium oral solution (Prod Info GASTROCROM(R) oral concentrate, 2006).
    b) CROMOLYN: Esophagitis has been reported with use of the capsules used for inhalation (Israel & Wood, 1979).
    c) NEDOCROMIL: Nausea, vomiting, and abdominal pain have been reported in 4%, 2.5%, and 1.9% of patients (n=2632), respectively, who received nedocromil inhalation during placebo-controlled clinical trials (Prod Info Tilade Inhaler, 2003).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) PAIN IN URETHRA
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Urethral burning was noted in one case of a 15-year-old who was taking 20 mg of cromolyn 4 times a day for 8 days. The burning started 15 to 20 minutes after each treatment and lasted 20 minutes (Block, 1974a).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL TUBULAR DISORDER
    a) ANIMAL STUDIES: Rats given a single IV dose of 750 mg/kg cromolyn or repeated subcutaneous doses of 80 mg/kg for 90 days, developed renal tubular degeneration (Cox et al, 1970).
    b) ANIMAL STUDIES: Monkeys given single doses of 333 mg/kg or greater of cromolyn developed renal tubular damage (degeneration or necrosis of the tubular epithelium). The same was true in monkeys who were given 50 mg/kg of cromolyn which was combined with isoproterenol. Damage only appeared to occur when the concentration of cromolyn in the tubule caused precipitation (Beach et al, 1981).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) EOSINOPHIL COUNT RAISED
    1) WITH THERAPEUTIC USE
    a) Eosinophilia is generally a feature of cromolyn hypersensitivity and is recommended to be followed in patients receiving cromolyn (Slater, 1978).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ITCHING OF SKIN
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Pruritus has rarely been reported after the use of cromolyn sodium oral solution (Prod Info GASTROCROM(R) oral concentrate, 2006).
    B) ERUPTION
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Rash has rarely been reported after the use of cromolyn sodium oral solution (Prod Info GASTROCROM(R) oral concentrate, 2006).
    C) ERYTHEMA
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Erythema/burning has rarely been reported after the use of cromolyn sodium oral solution (Prod Info GASTROCROM(R) oral concentrate, 2006).
    D) PHOTOSENSITIVITY
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Photosensitivity has rarely been reported after the use of cromolyn sodium oral solution (Prod Info GASTROCROM(R) oral concentrate, 2006).
    E) URTICARIA
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Urticaria may be seen as a hypersensitivity reaction to cromolyn (Menon & Das AK, 1977; Sheffer, 1975).
    b) CROMOLYN: Urticaria/angioedema has rarely been reported after the use of cromolyn sodium oral solution (Prod Info GASTROCROM(R) oral concentrate, 2006).
    F) ECZEMA
    1) WITH THERAPEUTIC USE
    a) CROMOLYN: Eczema has been seen in patients taking cromolyn (Fairris, 1984).
    G) CONTACT DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Contact dermatitis has been reported after administration of sodium cromoglycate eyedrops (Kudo et al, 1988).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) MYOSITIS
    1) WITH THERAPEUTIC USE
    a) Myositis has been reported as a side effect of cromolyn therapy (Ostler, 1982; Settipane et al, 1979).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Within 20 minutes of taking a single 20 mg capsule of cromolyn, generalized pruritus, stridor, angioedema, nausea, paresthesias, urticaria, severe bronchospasm, hypotension, sinus tachycardia, and joint pains were seen in a 57-year-old. The patient had a history of bronchial asthma and allergy to grass, pollen, and house dust (Ahmad, 1983).
    b) CASE REPORT: Within one minute of a single inhalation of cromolyn, a 7-year-old patient became cyanotic, hypotensive and suffered cardiopulmonary arrest (Brown et al, 1981).
    B) BRONCHOSPASM
    1) WITH THERAPEUTIC USE
    a) Severe asthmatic reactions have occurred after treatment with cromolyn sodium (Katayama et al, 1996; Serup, 1979; Menon & Das AK, 1977).
    b) CASE REPORT: A fatal bronchoconstriction was associated with 1 capsule of sodium cromoglycate. The patient was an asthmatic and her reaction was thought to be allergic in nature (Leynadier et al, 1985).

Reproductive

    3.20.1) SUMMARY
    A) It is unknown whether cromolyn or nedocromil are excreted in breast milk.
    B) Cromolyn and nedocromil are listed as a Pregnancy Category B risk. No well controlled clinical studies have been done in humans.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    CROMOLYN SODIUMNEDOCROMIL SODIUMBB
    References: Briggs et al, 1998Prod Info Tilade Inhaler, 2003Prod Info Alocril Ophthalmic Solution, 2002
    1) Cromolyn and nedocromil are listed as a Pregnancy Category B risk. No well controlled clinical studies have been done in humans (Prod Info, 1986)(Prod Info Tilade Inhaler, 2003; Prod Info Alocril Ophthalmic Solution, 2002).
    B) ANIMAL STUDIES
    1) In animals given cromolyn parenterally in doses up to 338 times the human clinical dose, no fetal malformations were seen.
    2) Adverse fetal effects such as increased resorptions and decreased fetal weight were noted at doses that were high enough to cause maternal toxicity (Prod Info, 1986).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is unknown if cromolyn or nedocromil are excreted in breast milk (Prod Info, 1986)(Prod Info Tilade Inhaler, 2003; Prod Info Alocril Ophthalmic Solution, 2002).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF EFFECT
    1) Long term studies done in mice, rats, and hamsters did not show neoplastic effects (Prod Info, 1986).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) EOSINOPHILIA is generally a feature of cromolyn hypersensitivity and is recommended to be followed in patients receiving cromolyn (JEF Reynolds , 1990).
    4.1.4) OTHER
    A) OTHER
    1) DERMAL
    a) Patch testing may be beneficial in determining allergenicity to cromolyn (Kudo et al, 1988).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess electrolyte and fluid balance and gastrointestinal function. Patients that remain asymptomatic can be discharged.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities.
    6.3.3.2) HOME CRITERIA/INHALATION
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.3.3) CONSULT CRITERIA/INHALATION
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess electrolyte and fluid balance and gastrointestinal function. Patients that remain asymptomatic can be discharged.

Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) These agents are poorly absorbed and are low in toxicity. Gastrointestinal decontamination is not recommended.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY: These agents are poorly absorbed orally and are low in toxicity. Gastrointestinal decontamination is rarely necessary. Consider activated charcoal only if coingestants with significant toxicity are involved.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) No specific laboratory tests are necessary unless otherwise clinically indicated.
    2) Monitor serum electrolytes in patients with severe vomiting and/or diarrhea.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) ACUTE ALLERGIC REACTION
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) Since systemic absorption is minimal, methods to enhance systemic elimination are unlikely to be necessary.

Range Of Toxicity

Summary

    A) TOXICITY: A specific toxic dose has not been established. Significant toxicity is not expected after overdose.
    B) THERAPEUTIC DOSES: CROMOLYN: ADULTS: ORAL INHALATION: 20 mg 4 times daily (nebulizer). NASAL SPRAY: 1 spray/nostril (cromolyn 5.2 mg/spray) 3 to 6 times/day. ORAL SOLUTION: 200 mg 4 times/day 30 minutes before meals and at bedtime. OPHTHALMIC: 1 to 2 drops in each eye 4 to 6 times daily, at regular intervals. NEDOCROMIL: OPHTHALMIC: 1 to 2 drops in each eye twice daily. CHILDREN: CROMOLYN: ORAL INHALATION (2 years and older): 20 mg 4 times/day (nebulizer). ORAL SOLUTION (13 years and older): 200 mg (two 5 mL ampules) 4 times/day 30 minutes before meals and at bedtime. (ages 2 to 12 years): 100 mg (one 5 mL ampule) 4 times daily 30 minutes before meals and at bedtime. (Term to 2 years old): 20 mg/kg/day orally; administered in 4 divided doses. NASAL SPRAY (2 years and older): 1 spray/nostril (cromolyn 5.2 mg/spray) 3 to 6 times/day. OPHTHALMIC (4 years and older): 1 to 2 drops in each eye 4 to 6 times daily, at regular intervals. NEDOCROMIL: OPHTHALMIC (3 years and older): 1 to 2 drops in each eye twice daily.

Therapeutic Dose

    7.2.1) ADULT
    A) CROMOLYN
    1) ORAL INHALATION: 20 mg 4 times daily (nebulizer) (Prod Info cromolyn sodium inhalation solution, 2012)
    2) NASAL SPRAY: 1 spray/nostril (cromolyn 5.2 mg/spray) 3 to 6 times/day (Prod Info Cromolyn sodium nasal spray, 2010)
    3) ORAL SOLUTION: 200 mg 4 times/day 30 minutes before meals and at bedtime (Prod Info cromolyn sodium oral solution concentrate, 2013)
    4) OPHTHALMIC: 1 to 2 drops in each eye 4 to 6 times daily, at regular intervals (Prod Info cromolyn sodium 4% ophthalmic solution, 2012)
    B) NEDOCROMIL
    1) OPHTHALMIC: 1 to 2 drops in each eye twice daily (Prod Info Alocril Ophthalmic Solution, 2002).
    2) INHALATION: Two inhalations, via a metered-dose inhaler, 4 times daily, providing a total dose of 14 mg per day (Prod Info Tilade Inhaler, 2003).
    7.2.2) PEDIATRIC
    A) CROMOLYN
    1) ASTHMA PROPHYLAXIS
    a) ORAL INHALATION (2 years and older): 20 mg 4 times/day (nebulizer) (Prod Info cromolyn sodium inhalation solution, 2012)
    2) MASTOCYTOSIS
    a) ORAL SOLUTION (13 years and older): 200 mg (two 5 mL ampules) 4 times/day 30 minutes before meals and at bedtime (Prod Info cromolyn sodium oral solution concentrate, 2013)
    b) ORAL SOLUTION (ages 2 to 12 years): 100 mg (one 5 mL ampule) 4 times daily 30 minutes before meals and at bedtime (Prod Info cromolyn sodium oral solution concentrate, 2013)
    3) ALLERGIC RHINITIS
    a) NASAL SPRAY (2 years and older): 1 spray/nostril (cromolyn 5.2 mg/spray) 3 to 6 times/day (Prod Info Cromolyn sodium nasal spray, 2010)
    4) KERATITIS
    a) OPHTHALMIC (4 years and older): 1 to 2 drops in each eye 4 to 6 times daily, at regular intervals (Prod Info cromolyn sodium 4% ophthalmic solution, 2012)
    B) NEDOCROMIL
    1) OPHTHALMIC (3 years and older): 1 to 2 drops in each eye twice daily (Prod Info Alocril Ophthalmic Solution, 2002). Safety and efficacy have not been established for children younger than 3 years of age.
    2) INHALATION: The recommended dosage for pediatric patients 6-years-old or older is 2 inhalations, via a metered-dose inhaler, 4 times daily, which provides a total daily dose of 14 mg (Prod Info Tilade Inhaler, 2003). Safety and efficacy have not been established for children younger than 6 years of age.

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 1000 mg/kg
    2) LD50- (SUBCUTANEOUS)MOUSE:
    a) 4400 mg/kg
    3) LD50- (ORAL)RAT:
    a) >2150 mg/kg
    4) LD50- (SUBCUTANEOUS)RAT:
    a) 6000 mg/kg

Pharmacology Toxicology

Pharmacologic Mechanism

    A) CROMOLYN
    1) Cromolyn inhibits the release of histamine, leukotrienes and other chemicals from mast cells, probably by interfering with calcium transport across the mast cell membrane.
    2) Cromolyn has enhancing activity on IL-2 receptor expression on T cells, on PHA-induced increases, and autologous mixed lymphocyte reaction. It does not affect T3-induced stimulation, IL-2 or interferon production (Ciprandi et al, 1987).
    3) Cromolyn has been shown to be moderately to not effective in treating food allergies in patients with atopic dermatitis (Burks & Sampson, 1988; Ciprandi et al, 1987).
    B) NEDOCROMIL
    1) In vitro studies of nedocromil sodium demonstrate that it inhibits the release of mediators including histamine, leukotriene C4 and prostaglandin D2. It inhibits the release of mediators from various cell types including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets (Prod Info Tilade Inhaler, 2003).
    2) Possessing both antiallergic and antiinflammatory properties, nedocromil is considered a second generation antiasthmatic agent (Gonzalez & Brogden, 1987).

Physicochemical

Physical Characteristics

    A) CROMOLYN SODIUM: A hygroscopic, mostly odorless, white crystalline powder that is soluble in water and is tasteless at first, but may leave a slightly bitter aftertaste (Prod Info cromolyn sodium inhalation solution, 2006; Prod Info GASTROCROM(R) oral concentrate, 2006; Prod Info INTAL(R) INHALER inhalation aerosol, 2005).
    B) NEDOCROMIL SODIUM: A yellow powder that is soluble in water and has an osmolality range of 270 to 330 mOsm/kg (Prod Info ALOCRIL(R) topical ophthalmic solution, 2008; Prod Info TILADE(R) Inhaler, 2003).

Ph

    A) CROMOLYN SODIUM: 4 to 7 (Prod Info cromolyn sodium ophthalmic solution, 4%, 2002)
    B) NEDOCROMIL SODIUM: 4 to 5.5 (Prod Info ALOCRIL(R) topical ophthalmic solution, 2008)

Molecular Weight

    A) CROMOLYN: 468.38
    B) CROMOLYN SODIUM: 512.34 (Prod Info cromolyn sodium inhalation solution, 2006; Prod Info GASTROCROM(R) oral concentrate, 2006; Prod Info INTAL(R) INHALER inhalation aerosol, 2005; Prod Info cromolyn sodium ophthalmic solution, 4%, 2002)
    C) NEDOCROMIL SODIUM: 415.3 (Prod Info ALOCRIL(R) topical ophthalmic solution, 2008; Prod Info TILADE(R) Inhaler, 2003)

References

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