Switch from Rx to OTC recommended for Nasalcrom for treatment of allergic rhinitis.

WASHINGTON, D.C.--(BUSINESS WIRE)--Oct. 10, 1996--

The Nonprescription and Pulmonary-Allergy Drugs Advisory Committee to the U.S. Food and Drug Administration (FDA) voted unanimously to recommend that Nasalcrom(R) (cromolyn sodium nasal solution) be switched from prescription (Rx) to over-the-counter (OTC) status.

If cleared by the FDA, Nasalcrom would be the first OTC allergy treatment indicated for prevention as well as treatment of symptoms of allergic rhinitis. Nasalcrom was presented to the FDA by McNeil Consumer Products Co.

More than 40 million Americans -- one out of six -- suffer the misery of allergic rhinitis, which can produce an itchy, runny nose, and nasal congestion and sneezing. Nearly 10 million sufferers are children, who miss an estimated two million days of school, and are impaired on many more, as a result of their allergies. Allergic rhinitis costs Americans an estimated $4 billion each year and can lead to associated illnesses, including otitis media (middle ear infection), asthma attacks and sinusitis.

Nasalcrom 4 percent Nasal Solution was cleared by the FDA for marketing as a prescription drug in 1983. It was developed by Fisons Corp. and is licensed to McNeil Consumer Products Co. for OTC marketing in the U.S. Since its approval, more than 17 million prescriptions have been written for Nasalcrom in the U.S. alone.

The Advisory Committee based its recommendations in part on the safe use of this drug for 13 years as a prescription product, past clinical trials and the results of a recent double-blind, multi-center use study of 1138 subjects, which compared Nasalcrom to placebo. The OTC effectiveness of Nasalcrom was demonstrated in the recent study; moreover, there were no significant differences in adverse events in any category between the Nasalcrom and placebo groups.

The Domino Effect of Allergies

The initial allergic process occurs when a patient is first exposed to an allergic substance, such as ragweed pollen (allergen). Antibodies to the allergen are produced, which bind to mast cells, sensitizing the body to future exposure to the allergen. Subsequent exposure leads to the release of various inflammatory chemicals by the mast cells, including histamine. These chemicals cause allergy symptoms, such as itching, sneezing, runny nose and nasal congestion.

Nasalcrom works differently from antihistamines, which block the action of histamine, and inhaled corticosteroids, which inhibit certain inflammatory processes. Nasalcrom prevents the activation of mast cells and thus helps to turn off the inflammatory cascade and dampen the domino effect of the allergic reaction.

Excellent Safety Profile

The various allergy medications currently available OTC either do not provide adequate relief or have limiting side effects, which inhibit their use by some allergy sufferers. Nasalcrom has an outstanding safety profile, according to Peter S. Creticos, M.D. Medical Director of Asthma and Allergic Diseases at the Johns Hopkins Asthma and Allergy Center. Nasalcrom does not cause the drowsiness that has been associated with antihistamines or the "rebound nasal congestion" linked to nasal decongestant sprays. Moreover, oral decongestants carry labels warning against use in patients with high blood pressure, heart disease, and other conditions. Extensive use has shown that Nasalcrom can be used safely in patients who suffer from these conditions. The medication can be used along with other medications as well.

An important quality of Nasalcrom is that it is topically applied to the nose. There is minimal absorption (seven percent) and that which is absorbed is not metabolized.

Cromolyn sodium nasal solution is registered in more than 80 countries around the globe, and is available without a prescription in more than a dozen of those.

The McNeil Consumer Products Co. is a member of the Johnson & Johnson family of companies and is headquartered in Ft. Washington, Pa. Johnson & Johnson is the world's largest and most comprehensive manufacturer of health care products. -0- Note: The FDA is not bound by recommendations of its advisory committees. The Rx package insert follows, only the molecular diagram is omitted.

Nasalcrom(R) Nasal Solution (cromolyn sodium nasal solution, USP)

DESCRIPTION: Each mL of NASALCROM Nasal Solution (cromolyn sodium nasal solution, USP) contains 40 mg cromolyn sodium in purified water with 0.01% benzalkonium chloride to preserve and 0.01% EDTA (edetate disodium) to stabilize the solution. NASALCROM possesses a natural pH of 4.5-6.5 and negligible titratable acidity.

Chemically, cromolyn sodium is disodium 5,5'-((2-hydroxytrimethylene) dioxy) bis (4-oxo-4H-1-benzopyran-2-carboxylate). The empirical formula is C23H14Na2O11; the molecular weight is 512.34. Cromolyn sodium is a water soluble, odorless, white, hydrated crystalline powder. It is tasteless at first but leaves a slightly bitter aftertaste.

Pharmacologic Category: Mast cell stabilizer/antiallergic.

Therapeutic Category: antiallergic.

After priming the deliver system for NASALCROM, each actuation of the unit delivers a metered spray containing 5.2 mg of cromolyn sodium. The contents of one bottle delivers at least 100 sprays (13 mL bottle) or 200 sprays (26 mL bottle).

CLINICAL PHARMACOLOGY: In vitro and in vivo animal studies have shown that cromolyn sodium inhibits the degranulation of sensitized mast cells which occurs after exposure to specific antigens. Cromolyn sodium inhibits the release of histamine and SRS-A (the slow-reacting substance of anaphylaxis). Rhinitis induced by the inhalation of specific antigens can be inhibited to varying degrees by pretreatment with NASALCROM.

Another activity demonstrated in vitro is the capacity of cromolyn sodium to inhibit the degranulation of non-sensitized rat mast cells by phospholipase A and the subsequent release of chemical mediators. An additional in vitro study showed that cromolyn sodium did not inhibit the enzymatic activity of released phospholipase A on its specific substrate.

Cromolyn sodium has no intrinsic brochodilator or antihistamine activity.

Cromolyn sodium is poorly absorbed from the gastrointestinal tract. After instillation of NASALCROM, less than 7% of the total dose administered is absorbed and is rapidly 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.

INDICATIONS: NASALCROM is indicated for the prevention and treatment of the symptoms of allergic rhinitis.

CONTRAINDICATIONS: NASALCROM is contraindicated in those patients who have shown hypersensitivity to any of the ingredients.

PRECAUTIONS: General: Some patients may experience transient nasal stinging and/or sneezing immediately following instillation of NASALCROM. Except in rare occurrences, these experiences have not caused discontinuation of therapy.

In view of the biliary and renal routes of excretion for cromolyn sodium, consideration should be given to decreasing the dosage or discontinuing the administration of the drug in patients with impaired renal or hepatic function.

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long term studies in mice (12 months intraperitoneal treatment followed by 6 months observation), hamsters (12 months intraperitoneal treatment followed by 12 months observation), and rats (18 months subcutaneous treatment) showed no neoplastic effect of cromolyn sodium.

No evidence of chromosomal damage or cytotoxicity was obtained in various mutagenesis studies.

No evidence of impaired fertility was shown in laboratory animal reproduction studies.

Pregnancy: Pregnancy Category B. Reproduction studies with cromolyn sodium administered parenterally to pregnant mice, rats, and rabbits in doses up to 338 times the human clinical dose produced no evidence of fetal malformations. 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.

Drug Interaction During Pregnancy: Cromolyn sodium and isoproterenol were studied following subcutaneous injections in pregnant mice. Cromolyn sodium alone in doses of 60 to 540 mg/kg (38 to 338 times the human dose) did not cause significant increases in resorptions or major malformations. Isoproterenol alone at a dose of 2.7 mg/kg (90 times the human dose) increased both resorptions and malformations. The addition of cromolyn sodium (338 times the human dose) to isoproterenol (90 times the human dose) appears to have increased the incidence of both resorptions and malformations.

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 NASALCROM is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in pediatric patients below the age of 6 years have not been established.

ADVERSE REACTIONS: The most frequent adverse reactions occurring in the 430 patients included in the clinical trials with NASALCROM were sneezing (1 in 10 patients), nasal stinging (1 in 20), nasal burning (1 in 25), and nasal irritation (1 in 40). Headaches and bad taste were reported in about 1 in 50 patients. Epistaxis, postnasal drip, and rash were reported in less than one percent of the patients. One patient in the clinical trials developed anaphylaxis.

Adverse reactions which have occurred in the use of other cromolyn sodium formulations for inhalation include angioedema, joint pain and swelling, urticaria, cough, and wheezing. Other reactions reported rarely are serum sickness, periarteritic vasculitis, polymyositis, pericarditis, photodermatitis, exfoliative dermatitis, peripheral neuritis, and nephrosis.

DOSAGE AND ADMINISTRATION: The dose for adults and children 6 years and older is one spray in each nostril 3-4 times daily at regular intervals. If needed, this dose may be increased to one spray to each nostril 6 times daily. The patient should be instructed to clear the nasal passages before administering the spray and should inhale through the nose during administration.

In the management of seasonal (pollenotic) rhinitis, and for prevention of rhinitis caused by exposure to other types of specific inhalant allergens, treatment with NASALCROM will be more effective if started prior to expected contact with the offending allergen. Treatment should be continued throughout the period of exposure, i.e., until the pollen season is over or until exposure to the offending allergen is terminated.

In the management of perennial allergic rhinitis, the effects of treatment with NASALCROM may become apparent only after two to four weeks of treatment. The concomitant use of antihistamines and/or nasal decongestants may be necessary during the initial phase of treatment, but the need for this type of medication should diminish and may be eliminated when the full benefit of NASALCROM is achieved.

HOW SUPPLIED: NASALCROM is available in bottles of 13 mL and 26 mL. Each fully assembled unit consists of a pump unit and actuator with cover in position on the bottle of nasal solution. The amount of cromolyn sodium in each bottle is: 13 mL - 520 mg (40 mg/mL); 26 mL - 1040 mg (40 mg/mL).

NDC 0585-0671-03 13 mL bottle (fully assembled unit)

NDC 0585-0671-04 26 mL bottle (fully assembled unit)

NASALCROM should be stored between 15 and 30 degrees Celsius (59 - 86 degrees Fahrenheit). Protect from light.

CAUTION: Federal law prohibits dispensing without prescription.

FISONS Pharmaceuticals

Fisons Corporation

Rochester, NY 14623 U.S.A.

Made in France

NASALCROM, NASALMATIC and FISONS are Registered Trademarks of Fisons plc.

Copyright 1995, Fisons Corporation, Rev. 8/95 RF037E 317-1-188

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