CROMOLYN SODIUM- cromolyn sodium solution 
Mylan Specialty L.P.

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Rx only.

PRESCRIBING INFORMATION

Cromolyn Sodium Inhalation Solution USP

FOR INHALATION USE ONLY—NOT FOR INJECTION

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 is the disodium salt of 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. Cromolyn sodium inhalation solution USP is clear, colorless, sterile and has a target pH of 5.5.

The molecular structure is:

Cromolyn Structural Formula

Each 2 mL vial of cromolyn sodium inhalation solution USP contains 20 mg cromolyn sodium USP in 2 mL of purified water USP.

CLINICAL PHARMACOLOGY

In vitro and in vivo animal studies have shown that cromolyn sodium inhibits sensitized mast cell degranulation which occurs after exposure to specific antigens. Cromolyn sodium acts by inhibiting the release of mediators from mast cells. Studies show that cromolyn sodium indirectly blocks calcium ions from entering the mast cell, thereby preventing mediator release.

Cromolyn sodium inhibits both the immediate and non-immediate bronchoconstrictive reactions to inhaled antigen. Cromolyn sodium also attenuates bronchospasm caused by exercise, toluene diisocyanate, aspirin, cold air, sulfur dioxide and environmental pollutants.

Cromolyn sodium has no intrinsic bronchodilator or antihistaminic activity.

After administration by inhalation, approximately 8% of the total cromolyn sodium dose administered is absorbed and rapidly excreted unchanged, approximately equally divided between urine and bile. The remainder of the dose is either exhaled or deposited in the oropharynx, swallowed and excreted via the alimentary tract.

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 USP 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 USP should be given shortly before exposure to the precipitating factor (see DOSAGE AND ADMINISTRATION).

CONTRAINDICATIONS

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

WARNINGS

Cromolyn sodium inhalation solution USP has no role in the treatment of status asthmaticus.

Anaphylactic reactions with cromolyn sodium administration have been reported rarely.

PRECAUTIONS

General

Occasionally, patients may experience cough and/or bronchospasm following inhalation of cromolyn sodium inhalation solution USP. At times, patients who develop bronchospasm may not be able to continue cromolyn sodium inhalation solution USP administration despite prior bronchodilator administration. Rarely, very severe bronchospasm has been encountered.

Symptoms of asthma may recur if cromolyn sodium inhalation solution USP is reduced below the recommended dosage or discontinued.

Information for Patients

Cromolyn sodium inhalation solution USP is to be taken as directed by the physician. Because it is preventive medication, it may take up to four weeks before the patient experiences maximum benefit.

Cromolyn sodium inhalation solution USP should be used in a power-driven nebulizer with an adequate airflow rate equipped with a suitable face mask or mouthpiece.

Drug stability and safety of cromolyn sodium inhalation solution when mixed with other drugs in a nebulizer have not been established.

For additional information, see Patient Instruction entitled Living a Full Life with Asthma.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long term studies of cromolyn sodium in mice (12 months intraperitoneal administration at doses up to 150 mg/kg three days per week), hamsters (intraperitoneal administration at doses up to 52.6 mg/kg three days per week for 15 weeks followed by 17.5 mg/kg three days per week for 37 weeks), and rats (18 months subcutaneous administration at doses up 75 mg/kg six days per week) showed no neoplastic affects. The average daily maximum dose levels administered in these studies were 192.9 mg/m2 for mice, 47.2 mg/m2 for hamsters and 385.8 mg/m2 for rats. These doses correspond to approximately 330%, 80% and 650% of the maximum daily human dose of 59.2 mg/m2.

Cromolyn sodium showed no mutagenic potential in Ames Salmonella/microsome plate assays, mitotic gene conversion in Saccharomyces cerevisiae and in an in vitro cytogenetic study in human peripheral lymphocytes.

No evidence of impaired fertility was shown in laboratory reproduction studies conducted subcutaneously in rats at the highest doses tested, 175 mg/kg/day (1050 mg/m2) in males and 100 mg/kg/day (600 mg/m2) in females. These doses are approximately 18 and 10 times the maximum daily human dose, respectively, based on mg/m2.

Pregnancy: Pregnancy Category B

Reproduction studies with cromolyn sodium administered subcutaneously to pregnant mice and rats at maximum daily doses of 540 mg/kg (1620 mg/m2) and 164 mg/kg (984 mg/m2), respectively, and intravenously to rabbits at a maximum daily dose of 485 mg/kg (5820 mg/m2) produced no evidence of fetal malformations. These doses represent approximately 27, 16, and 98 times the maximum daily human dose, respectively, on a mg/m2 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.

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 cromolyn sodium inhalation solution USP is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years have not been established.

ADVERSE REACTIONS

Clinical experience with the use of cromolyn sodium inhalation solution USP suggests that adverse reactions are rare events. The following adverse reactions have been associated with cromolyn sodium inhalation solution USP: 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 stomach ache.

In addition, adverse reactions have been reported with cromolyn sodium for inhalation USP 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 USP capsules has been derived from U.S. post-marketing surveillance experience. The following adverse reactions attributed to cromolyn sodium inhalation solution USP, based upon reoccurrence 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.

OVERDOSAGE

There is no clinical syndrome associated with an overdosage of cromolyn sodium. Acute toxicity testing in a wide variety of species has demonstrated an extremely low order of toxicity for cromolyn sodium, regardless of whether administration was parenteral, oral or by inhalation. Parenteral administration in mice, rats, guinea pigs, hamsters and rabbits demonstrated an LD50 in the region of 4000 mg/kg. Intravenous administration in monkeys also indicated a similar order of toxicity. The highest dose administered by the oral route in rats and mice was 8000 mg/kg, 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.

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 vial administered by nebulization four times a day at regular intervals.

Drug stability and safety of cromolyn sodium inhalation solution USP 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 USP therapy is dependent upon its administration at regular intervals, as directed. Cromolyn sodium inhalation solution USP 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 vial 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.

Cromolyn Sodium Inhalation Solution USP Therapy in Relation to Other Treatments for Asthma

Nonsteroidal agents

Cromolyn sodium inhalation solution USP should be added to the patient's existing treatment regimen (e.g., bronchodilators). When a clinical response to cromolyn sodium inhalation solution USP 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 USP may be titrated downward to the lowest level consistent with the desired effect. The usual decrease is from four to three vials 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 vials per day, an increase in the dose of cromolyn sodium inhalation solution USP 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 USP. 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 USP administration, the potential to reduce corticosteroids may nonetheless be present. Thus, gradual tapering of corticosteroid dosage may be attempted. It is important that the dose be reduced slowly, maintaining close supervision of the patient to avoid an exacerbation of asthma.

It should be borne in mind that prolonged corticosteroid therapy frequently causes an impairment in the activity of the hypothalamic-pituitary-adrenal axis and a reduction in the size of the adrenal cortex. A potentially critical degree of impairment or insufficiency may persist asymptomatically for some time even after gradual discontinuation of adrenocortical steroids. Therefore, if a patient is subjected to significant stress, such as a severe asthmatic attack, surgery, trauma or severe illness while being treated or within one year (occasionally up to two years) after corticosteroid treatment has been terminated, consideration should be given to reinstituting corticosteroid therapy. When respiratory function is impaired, as may occur in severe exacerbation of asthma, a temporary increase in the amount of corticosteroids may be required to regain control of the patient's asthma.

It is particularly important that great care be exercised if, for any reason, cromolyn sodium inhalation solution USP is withdrawn in cases where its use has permitted a reduction in the maintenance dose of corticosteroids. In such cases, continued close supervision of the patient is essential since there may be sudden reappearance of severe manifestations of asthma which will require immediate therapy and possible reintroduction of corticosteroids.

HOW SUPPLIED

Cromolyn sodium inhalation solution USP is a colorless solution supplied in a unit-dose plastic vial containing 20 mg cromolyn sodium USP in 2 mL purified water USP. Cards of five vials are placed into a foil pouch. Supplied in cartons as listed below.

NDC 49502-689-61      60 vials per carton.

Storage

Store at 15° to 30°C (59° to 86°F) and protect from direct light. Do not use if solution is discolored or contains a precipitate. Keep out of the reach of children. Store in pouch until time of use.

Rx only.

03-268-22
JAN 06

PHARMACIST:
Patient Instructions.
Please do not remove.

Rev. 1/06

Cromolyn Sodium Inhalation Solution USP
Aqueous solution for nebulization

Rx only.

INSTRUCTIONS FOR USE

Living a Full Life with Asthma

You or your child may be among the millions of Americans who have asthma. For most patients, asthma need not limit your lifestyle, if you closely follow the asthma management plan your doctor provides you. Your doctor has given you this instruction sheet to help you learn more about asthma and ways to control it.

What is Asthma?

Normal Bronchial Tube and Constricted Bronchial Tube

Asthma is a disease that causes patients to have difficulty breathing. Asthma "attacks" occur when the air passages (airways) to the lungs close up, blocking air from passing through. The closing up is caused by two things: 1) the muscles around the airways tighten (constrict) making the airway narrower, and 2) the passage lining swells and produces larger amounts of mucus (a sticky liquid normally found in the airways). This swelling is caused by a certain type of inflammation that can build up in the airways of patients with asthma. Inflammation and the airway sensitivity that results from it cause further attacks to occur.

What Causes These Attacks?

Asthma experts now know that patients with asthma have attacks because their airways are inflamed and overreactive. Their lungs become super-sensitive to certain irritants or "triggers," such as cold dry air, pollen, smoke, or cat dander. In the presence of such triggers, someone with asthma may have an attack, and attacks may occur more often.

Asthma triggers fall into 6 categories:

Substances that cause allergies (pollens, animal dander, molds, house dust, some foods and medicines)
Infections that affect breathing (colds, flu)
Emotional stress (difficult situations at home, school, or work)
Strenuous exercise
Irritating gases (chlorine, perfume, tobacco smoke)
Sudden changes in temperature or humidity

How to Prevent Asthma Attacks

No medicine or procedure will "cure" asthma. The key to asthma relief, therefore, is to prevent attacks and to relieve attack symptoms if they do occur. A successful prevention plan1 will do the following:

Keep your activities, including exercise, at normal levels.
Keep your lungs functioning normally or at a near-normal level.
Prevent symptoms such as coughing or breathlessness that can keep you up at night, or occur in the early morning hours, or after exertion.
Prevent asthma attacks from happening.
Avoid unpleasant or harmful side effects that may result from using asthma medicine.

The best way to prevent asthma attacks is to avoid the triggers that bother you or your child. Try to identify the specific things that cause problems for you - things such as certain foods, house dust, or animal dander. Avoiding these triggers may be difficult or unpleasant. You may need to find a new home for a family pet or remove a carpet or a favorite stuffed toy. Even though these steps are difficult, they may be necessary in order to help prevent asthma attacks.

If house dust is a trigger, remove dust-collections such as feather pillows, mattresses, quilts, and carpets from the bedroom. Mattresses and pillows can be covered with allergen-free covers. If a certain food triggers attacks, keep it out of your diet. Irritants in the air can be reduced by air conditioning, electrostatic air filters, or small-pore (HEPA) filters. Be careful of certain medicines. Aspirin and aspirin-like pain relievers, for example, can trigger attacks in some people and should be avoided if they do.

Other Do's and Don'ts

Anyone with asthma should stick to a healthy, balanced diet, get lots of rest and moderate exercise, and follow these do's and don'ts:

Don't smoke and don't stay in the same room with people that do.
Avoid fresh paint.
Avoid sudden changes of temperature. Don't go in and out of extremely cool air-conditioned buildings during hot weather.
Stay home in extremely cold weather, if possible.
Stay away from people with colds or flu.
Try to avoid emotionally upsetting situations.
Drink lots of liquids.
Don't overdo, but follow a regular exercise plan, including activities that help develop lung capacity.
Don't take any medicine on your own without asking your doctor first.
Take all medicines your doctor prescribes, as much and as often as you are told.
Avoid taking sleeping pills or sedatives, even if asthma keeps you awake. Prop yourself up with extra pillows until your asthma medicine takes effect.
Avoid breathing in insecticides, deodorants, cleaning fluids, chlorine, or other irritating gases.

Asthma Medicines

Preventive Medicine

Your doctor knows that besides relieving an attack when it happens, it is also important to prevent attacks from occurring in the first place. Therefore, he or she has prescribed for you Cromolyn Sodium Inhalation Solution USP, a medicine that prevents asthma attacks by making airways less sensitive to asthma triggers. It works by stabilizing cells in the airway lining called mast cells. During an asthma attack, these cells become unstable and give off chemicals called mediators that cause inflammation and asthma attacks. By preventing mediator release, Cromolyn Sodium Inhalation Solution USP works to prevent asthma attacks.

Bronchodilators:

When someone is having an asthma attack, he or she needs a medicine called a bronchodilator to open up (dilate) the blocked airways in order to relieve the asthma attack. Your doctor may have already prescribed this medicine for you to use at that time.

How Will Cromolyn Sodium Inhalation Solution USP Work for You?

To get the best possible results, follow your doctor's instructions carefully when you first take Cromolyn Sodium Inhalation Solution USP.

Your doctor may tell you to take Cromolyn Sodium Inhalation Solution USP 10 to 15 minutes before you exercise or come into contact with a specific trigger, such as a cat. Usually, however, you will be told to take Cromolyn Sodium Inhalation Solution USP on a regular basis, probably starting at four times a day. It is crucial that you take Cromolyn Sodium Inhalation Solution USP regularly, as often as your doctor recommends, even though you have no asthma symptoms at the time. Cromolyn Sodium Inhalation Solution USP starts working right away, but when you first begin taking it, you may have a lot of inflammation in your airways. Therefore, it may take up to two weeks (or perhaps one month) of regular treatment to bring your asthma under control. Do not stop taking Cromolyn Sodium Inhalation Solution USP or skip any doses without first talking with your doctor.

When you start using Cromolyn Sodium Inhalation Solution USP for the first time, your doctor may ask you to keep a diary showing when you have any symptoms, if and when you have trouble sleeping, how often you wheeze or cough, and other notes to help determine how effective Cromolyn Sodium Inhalation Solution USP will be to help you prevent asthma attacks. Your doctor may also recommend the use of a peak flow meter daily to help you better assess your progress.

While taking Cromolyn Sodium Inhalation Solution USP on a regular basis, you may need to take a bronchodilator-type medicine to treat occasional symptoms or attacks. While taking Cromolyn Sodium Inhalation Solution USP, you should continue taking your other medication until your doctor advises you otherwise.

Care & Storage

Cromolyn Sodium Inhalation Solution USP should be stored between 15°- 30°C (59°- 86°F) and protected from light. Do not use if it contains a precipitate (particles or cloudiness) or becomes discolored. Keep out of the reach of children.

Store in pouch until time of use.

NOTE: In case of difficulty consult your doctor or pharmacist.

Further Information

For more information on asthma ask your doctor.

Provided as an educational service by Dey.

Instructions for the Use of
Cromolyn Sodium Inhalation Solution USP

An aqueous solution for nebulization.

NOT FOR INJECTION

For best results, follow these instructions exactly and observe Care & Storage directions.

Method of Administration

Cromolyn Sodium Inhalation Solution USP is recommended for use in a power driven nebulizer operated at an airflow rate of 6-8 liters per minute and equipped with a suitable face mask or mouth piece. Your doctor will advise on the choice of a suitable nebulizer and how it should be used. Do not use any appliance without consulting your doctor.

Drug stability and safety of Cromolyn Sodium Inhalation Solution USP when mixed with other drugs in a nebulizer have not been established.

Dosage

Nebulization should be carried out four times a day at regular intervals, or as directed by your doctor. Use the contents of a fresh vial each time.

Inhalation

Once the nebulizer has been assembled and contains Cromolyn Sodium Inhalation Solution USP, hold the mask close to the patient's face and switch on the device. The patient should breathe in through the mouth and out through the nose in a normal, relaxed manner. Nebulization should take approximately five to ten minutes.

Exclusive Dey TwistFlex Tops
Open carton by lifting tab as shown.Open carton by lifting tab as shown.
Open foil pouch.Open foil pouch.
Remove a single vial from the strip.Remove a single vial from the strip.
Open the vial by twisting off the TwistFlex™ topOpen the vial by twisting off the TwistFlex top
Squeeze the contents of the vial into the solution container of your nebulizer. Discard the empty vial.Squeeze the contents of the vial into the solution container of your nebulizer. Discard the empty vial.
Place remaining vials back into the foil pouch.Place remaining vials back nito the foil pouch.

03-268-22 PPI
JAN 06


1
Adapted from the National Heart, Lung, and Blood Institute: Guidelines for the Diagnosis and Management of Asthma. National Asthma Education Program, Expert Panel Report, 1991.

        

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CROMOLYN SODIUM 
cromolyn sodium solution
Product Information
Product TypeHUMAN PRESCRIPTION DRUG LABELItem Code (Source)NDC:49502-689
Route of AdministrationRESPIRATORY (INHALATION)DEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
CROMOLYN SODIUM (CROMOLYN) CROMOLYN SODIUM20 mg  in 2 mL
Inactive Ingredients
Ingredient NameStrength
water 
Packaging
#Item CodePackage Description
1NDC:49502-689-6112 in 1 CARTON
15 in 1 POUCH
12 mL in 1 VIAL
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA07420906/29/200906/30/2009
Labeler - Mylan Specialty L.P. (194775557)

Revised: 06/2006
 
Mylan Specialty L.P.