Intal Nebulizer (Sodium Cromoglycate)

INTAL® SPINCAPS® INTAL® NEBULIZER SOLUTION

Rh´ne-Poulenc Rorer

Sodium Cromoglycate

Bronchial Asthma Prophylaxis

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

Sodium cromoglycate inhibits both the immediate and non-immediate bronchoconstrictive reactions to inhaled allergens. Sodium cromoglycate also attenuates bronchospasm caused by exercise, toluene diisocyanate, ASA, cold air, sulfur dioxide and environmental pollutants in some patients.

Sodium cromoglycate has no intrinsic bronchodilator antihistaminic or anti-inflammatory activity.

Indications And Clinical Uses: As an adjunct in the management of intrinsic and extrinsic asthma. It is used on a continuous basis to prevent the symptoms associated with asthma.

Also indicated for use in the prevention of bronchospasm induced by known precipitating factors such as exercise, cold air, allergens, and environmental pollutants.

Contra-Indications: Hypersensitivity to any of its components.

Manufacturers’ Warnings In Clinical States: Sodium cromoglycate has no role in the treatment of an acute attack of asthma, especially status asthmaticus.

Severe anaphylactic reactions can occur after sodium cromoglycate administration. The recommended dosage should be decreased in patients with decreased renal or hepatic function. Sodium cromoglycate should be discontinued if the patient develops eosinophilic pneumonia (or pulmonary infiltrates with eosinophilia).

The number of inhalations per day should be specified to the patient. Regular dosage is important and treatment must not be discontinued abruptly, especially when benefit has been obtained. If troublesome symptoms occur, particularly breathlessness at rest, no benefit is likely to be obtained by increasing the dosage above 8 cartridges or ampuls per day, and the patient should be advised to consult his physician immediately, so that additional measures can be instituted if necessary.

Precautions: Mild throat irritation, coughing and transient bronchospasm may occur. Very rarely, severe bronchospasm associated with a marked fall in pulmonary function has been reported. In such cases treatment should be stopped and should not be reintroduced.

Possible immunologic changes resulting in reactions, such as, polymyositis, pneumonitis and heart failure, urticaria and anaphylaxis have been reported.

Pregnancy: There are no adequate and well-controlled studies in pregnant women. However, during clinical use there have been, to date, no reports of adverse effects on the fetus that could be ascribed to the use of sodium cromoglycate. Nevertheless, as with all medications, caution must be exercised during pregnancy.

Lactation: It is not known whether this drug is excreted in human milk; therefore, caution should be exercised when sodium cromoglycate is administered to a nursing woman, and the attending physician must make a benefit/risk assessment in regard to its use in this situation.

Adverse Reactions: In controlled clinical studies the most frequently reported adverse reactions attributed to sodium cromoglycate treatment were: throat irritation or dryness, bad taste, cough, wheeze and nausea.

Bronchospasm [sometimes severe, associated with precipitous fall in pulmonary function (FEV1)], laryngeal edema (rare), nasal congestion (sometimes severe) and pharyngeal irritation have been reported.

Adverse reactions which occur infrequently and are associated with administration of the drug are: anaphylaxis, angioedema, dizziness, dysuria and urinary frequency, joint swelling and pain, lacrimation, headache, rash, swollen parotid gland, urticaria, pulmonary infiltrates with eosinophilia, substernal burning and myopathy.

The following adverse reactions have been reported as rare events and it is unclear whether they are attributable to the drug: anemia, exfoliative dermatitis, hemoptysis, hoarseness, myalgia, nephrosis, periarteritic vasculitis, pericarditis, peripheral neuritis, photodermatitis, sneezing, drowsiness, nasal itching, nasal bleeding, nasal burning, serum sickness, stomach ache, polymyositis, vertigo and liver disease.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: There have been no reported cases in humans of overdosage of the drug. Symptomatic treatment is suggested should overdosage occur.

Dosage And Administration: Adults and Children: Sodium cromoglycate is used on a continuous basis to prevent the symptoms of asthma and has no role in the treatment of acute attacks.

Intal Spincaps are administered by specially developed inhalers which enable efficient and controlled dosage – 1) the Spinhaler turbo-inhaler and 2) and the Intal Halermatic automatic piercing inhaler.

Intal Nebulizer Solution is recommended for use in a Wright nebulizer or a suitable equivalent operated at an air flow rate of 6 to 8 L/minute and equipped with a suitable face mask.

Initial Treatment: One Spincap or one ampul of Nebulizer Solution 4 times daily at 4 to 6 hourly intervals. In more severe cases, or during periods of high antigen challenge, the interval between doses may be reduced to 3 hours (i.e., up to 8 Spincaps or ampuls daily may be taken).

For protection against bronchospasm induced by exercise, sodium cromoglycate should be used 15 to 30 minutes beforehand.

Maintenance Therapy: When adequate response has been obtained, the frequency of inhalations may be reduced to 1 Spincap or 1 ampul of Nebulizer Solution every 8 to 12 hours (i.e., 2 or 3 Spincaps or ampuls/day). If chest symptoms are troublesome at night, it is important that the final dose be taken, if awakened, during the night.

Patients should be warned against suddenly discontinuing therapy when symptoms have been partially or completely controlled by sodium cromoglycate.

Concomitant Therapy: Other asthma therapy should be continued until clinical improvement permits a progressive reduction in dosage. However, sodium cromoglycate alone may prevent symptoms of mild to moderate asthma, especially in children and young adults.

In severe asthma, particularly in older patients, sodium cromoglycate therapy alone is insufficient to prevent symptoms. In a proportion of such cases, significant improvement can be obtained by combining sodium cromoglycate with corticosteroid therapy, even when inadequate relief is obtained from either drug alone.

In steroid-dependent patients, the addition of sodium cromoglycate to the regimen may permit a slow, progressive and significant reduction in maintenance dose of steroids.

Reduction or Withdrawal of Corticosteroids: The dangers of sudden withdrawal of corticosteroids are well recognized, particularly in steroid-treated patients who have received long-term administration of oral steroids, or ACTH injections.

When the physician attempts to reduce the corticosteroid dosage, it is important that the reduction should be gradual and that close surveillance and frequent examination of the patient is maintained. It should be remembered that the adrenal cortex is suppressed by the administration of oral steroids, and that in both oral steroid and ACTH therapy, the ability of the patient to react to stress is usually impaired. In such patients, acute renal insufficiency and severe asthma can be precipitated by an increase in stress and/or reduction or withdrawal of either steroid or ACTH therapy. In order to identify such a risk in patients who have received long-term steroid therapy and where substantial reduction or complete withdrawal of corticosteroid is contemplated, it is advisable to assess adrenal and pituitary function.

Method of Reducing Steroid Dosage: The reduction in the daily maintenance dose of steroids should be stepwise at a suggested rate equivalent to about 1%/day (e.g., a maintenance dose of 10 mg prednisolone/day is reduced to 9 mg/day after 1 week). The gradual reduction should be continued until either the patient cannot tolerate a further reduction, or it is found possible to withdraw corticosteroids completely.

Note: If troublesome symptoms recur during the period of reduction, the daily dose should be raised immediately. A larger increase in the steroid dose may be essential at times, as a temporary measure, to control a severe relapse induced by antigen challenge, infections or stress. The increased physical or mental activity resulting from subjective improvement can also constitute a stress. When symptoms are brought under control, a progressive reduction may be attempted as before.

Method of Withdrawing ACTH: The same principles apply as discussed above. In practice, either the number of units of ACTH per injection can be reduced, or the interval between injections can be extended (e.g., from 1/day, to 1 on alternate days, to 1 biweekly).

Withdrawal of Sodium Cromoglycate Therapy: As the action of sodium cromoglycate is essentially preventive, continuity of therapy is important in patients who have gained benefit. If, for any reason, sodium cromoglycate is withdrawn, a suggested regimen for withdrawal is to reduce the sodium cromoglycate dosage gradually over a period of 1 week. It should be borne in mind that symptoms of asthma may recur when the drug is discontinued.

Caution: In cases where sodium cromoglycate has permitted a reduction in the maintenance dose of steroids, it is recommended that the steroid dose first be restored to at least the pre-sodium cromoglycate level at the commencement of withdrawal of sodium cromoglycate, followed by slow reduction of the steroid dose to tolerance. This is to avoid risk of acute relapse. It is also recommended that adrenal function be assessed before restoring the pre-sodium cromoglycate steroid dose.

Administration of Spincaps: Administration by inhalation of the contents of a Spincaps cartridge is only possible by the correct use of the Spinhaler or the Intal Halermatic. It is desirable to demonstrate the use of the Spinhaler or the Intal Halermatic to each patient for whom sodium cromoglycate therapy is prescribed. In practice, they are very simple to operate, provided they are used strictly according to the following instructions:

Spinhaler: The Spinhaler turbo-inhaler is essentially a tube-like inhaler in which the movement of the inspired air causes a small propeller to rotate and vibrate at high speed. When a Spincap cartridge is fitted in this device, its gelatin envelope is perforated by moving the grey sleeve of the Spinhaler. During deep and rapid inspiration through the device the contents of the cartridge are dispersed into the inspired air by the action of the propeller. In this way, the drug particles are carried deep into the lungs to the site where their action is required.

The Spinhaler consists of: A tubular body threaded at one end to receive the mouthpiece, and with an air inlet at the other end. The body is fitted with a grey sleeve which can slide from its normal position against the air inlet, to the mouthpiece and back again. The body unscrews from the mouthpiece; The propeller, inside the tubular body which rotates on a stainless steel spindle. It has a slotted cup into which a Spincap can be fitted; The mouthpiece, fitted with a stainless steel spindle.

Loading and Inhaling the Dose: 1. To prepare the Spinhaler for use – hold the appliance vertically with the white mouthpiece downwards and unscrew the body from the mouthpiece.

2. Insert the colored end of the Spincap firmly into the cup on the propeller. Check that the propeller rotates freely.

3. Screw the mouthpiece back into position.

4a. Still holding the Spinhaler vertically (mouthpiece downwards), force the grey sleeve downwards as far as it will go and then back to its original position. (This step may be repeated a second time for optimal piercing.)

4b. The Spincap has now been pierced and the appliance is ready for use.

5. Inhaling Procedure: Hold the Spinhaler well away from your mouth. Breathe out as fully as possible.

6. Now put the mouthpiece of the Spinhaler between your lips with air inlet held slightly upwards. Close your lips, but keep your teeth apart, and draw in a deep breath through the Spinhaler as rapidly as possible. You should hear and feel the high speed vibration made by the rotating propeller.

7. Hold your breath for a few seconds and remove the Spinhaler from your mouth.

8. Breathe out completely, holding the Spinhaler well away from your face. Repeat inhaling procedure several times until the Spincap is empty.

9. Discard Spincap and return Spinhaler to its container.

Note: Patients who experience mild hoarseness following inhalation may benefit by taking a drink of water immediately after using the Spinhaler.

Care of Spinhaler: 1. Brush propeller blades weekly to remove powder and dust.

2. Alternatively, it may be necessary to dismantle the Spinhaler and wash the parts in warm water, including the inside of the shaft (by moving the propeller on and off the spindle underwater).

3. Shake out the excess water, especially from inside the propeller shaft. Allow to dry in a warm place before re-assembly. The Spinhaler will not function properly unless the propeller shaft is clean and dry.

Always handle the Spincap cartridges with clean dry hands and keep the Spinhaler in a dry place at room temperature.

It is advisable to carry the Spinhaler in the container provided. Failure to do so could result in dust and debris entering the apparatus and such foreign matter might then be inhaled when the spinhaler is in use.

Halermatic: The Halermatic, automatic piercing inhaler is an insufflator device used to facilitate the administration of Spincaps.

When a Spincap is fitted in this device its gelatin envelope is perforated automatically when the device is reassembled. During deep and rapid inspiration through the device the contents of the cartridge are dispersed into the inspired air. In this way, the drug particles are carried deep into the lungs to the site where their action is required.

The Halermatic consists of: The body, which contains the Spincap slot, a rotation chamber, and the piercing needles; The mouthpiece, which has air inlets that line up with air inlet channels in the body through which air moves to allow the Spincap to spin within the rotation chamber dispensing the contents of the cartridge into the inspired air. The mouthpiece also has a grid through which the powder must pass on its way into the lungs; The cover, which fits over the mouthpiece protecting the grid and air inlets from dust and debris. The cover has a storage compartment for spincaps. The cover storage compartment is threaded to receive the cap.

How to Load the Halermatic: Cartridges should only be inserted immediately prior to use.

1. Remove the mouthpiece cover and then pull off the mouthpiece.

2. Push a Spincap cartridge firmly down to the bottom of the slot.

3. Slide the mouthpiece back onto the body pushing down slowly as far as it will go. This action pierces the cartridge and lifts it into the rotation chamber – the inhaler is now ready to use.

Note: Step 3 must not be repeated as the cartridge must be pierced once only.

How to use The Halermatic: 1. Breathe out as far as possible holding the device away from the mouth.

2. Tilt the head back and breathe in quickly and steadily through the mouthpiece, keeping the lips closed around it. Be sure not to obstruct the flow of Intal into the lungs with teeth or tongue.

3. Hold your breath to keep the Intal in the lungs as long as possible, remove the device from your mouth and then breathe out.

4. Repeat steps 1 to 3 until all the powder has been inhaled.

5. If the throat becomes dry or irritated, drink a little water before and after inhalation.

6. If there is any difficulty, be sure: the device is clean; the air inlets are not obstructed when breathing in, (e.g., by your fingers); the cartridge is free to rotate. Do not place the cartridge back in the slot if it is already pierced; the cartridge has been pierced. If not, begin again by pushing the cartridge back into the slot.

Cleaning the Halermatic: 1. Brush away powder deposits daily with a brush.

2. When powder deposits build up, wipe away with a lightly dampened cloth.

3. The mouthpiece may be washed separately if necessary. Do not wet the blue-based body of the Halermatic and be sure the mouthpiece grid is dry before reassembling the device.

Spincap cartridges may be carried in the special compartment on the top of the Halermatic, for 1 day only. Ensure that the storage compartment is kept tightly closed to exclude humidity.

Replace the Halermatic every 6 months.

Always handle the Spincap cartridges with clean, dry hands and keep the Halermatic in a dry place at room temperature.

Availability And Storage: Cartridges: Each single dose, yellow/clear, hard gelatin cartridge imprinted Fisons and Intal-p, contains: sodium cromoglycate (micronized) 20 mg. Nonmedicinal ingredients: erythrosine CL 45430, gelatin, iron oxide and quinoline Yellow CL 47005.
Solution: Each mL of sterile solution contains: sodium cromoglycate (micronized) 1% w/v (10 mg/mL). Nonmedicinal ingredients: purified water. Sodium:

INTAL® SPINCAPS® INTAL® NEBULIZER SOLUTION Rh´ne-Poulenc Rorer Sodium Cromoglycate Bronchial Asthma Prophylaxis

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