Aeronide

Budesonide.

Each actuation contains: Budesonide 200 mcg.

Pharmacology: Pharmacodynamics: Budesonide is a glucocorticosteroid which possesses a high local anti-inflammatory action, with a lower incidence and severity of adverse effects than those seen with oral corticosteroids.
Pharmacokinetics: Absorption: After a single dose of 1 mg budesonide, a peak plasma concentration of 2.6 nmol/L was obtained approximately 20 minutes after nebulization in asthmatic children 4 to 6 years of age. The exposure (AUC) of budesonide following administration of a single 1 mg close of budesonide by nebulization to asthmatic children 4 to 6 years of age is comparable to healthy adults given a single 2 mg close by nebulization. In asthmatic children 4 to 6 years of age, the Total absolute bioavailability (ie, lung + oral) following administration of budesonide inhalation suspension via jet nebulizer was approximately 6% of the labeled dose. The peak plasma concentration of budesonide occurred 10 to 30 minutes after start of nebulization.
Distribution: In asthmatic children 4 to 6 years of age, the volume of distribution at steady-state of budesonide was 3 L/kg, approximately the same as in healthy adults. Budesonide is 85% to 90% bound to plasma proteins, the degree of binding being constant over the concentration range (1 to 100 nmol/L) achieved with, and exceeding, recommended doses. Budesonide showed little or no binding to corticosteroid-binding globulin. Budesonide rapidly equilibrated with concentration independent manner with a blood/plasma ratio of approximately 0.8.
Metabolism: In vitro studies with human liver homogenates have shown that budesonide is rapidly and extensively metabolized. Two major metabolites formed via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4) catalyzed biotransformation have been isolated and identified as 16-hydroxyprednisolone and 6-hydroxybudesonide. Budesonide is primarily cleared by the liver. In asthmatic children 4 to 6 years of age, the terminal half-life of budesonide after nebulization is 2.3 hours, and the systemic clearance is 0.5 L/min, which is approximately 50% greater than in healthy adults after adjustment for differences in weight.
Excretion: Budesonide is excreted in urine and feces in the form of metabolites. In adults, approximately 60% of an intravenous radiolabeled dose was recovered in the urine. No unchanged budesonide was detected in the urine.

For the maintenance treatment of bronchial asthma as prophylactic therapy.

Budesonide 200 mcg is for oral inhalation use only.
General dosing considerations: In all patients, it is desirable to downward-titrate to the lowest effective dose once asthma stability is achieved. The improvement in asthma control following inhaled administration can occur within 2 to 8 days of initiation of treatment, although maximum benefit may not be achieved for 1 to 2 weeks.
The maximum dose in children is 1 mg/day.
Budesonide can be administered once daily either in the morning or in the evening. Gently shake the inhalation suspension using a circular motion before use.
The safety and efficacy of budesonide inhalation suspension when administered in excess of recommended doses have not been established. In children 6 months to 8 years of age should not be administered the excess of the recommended dose.
If deterioration in asthma occurs, the frequency of daily dosing and/or the total dose of budesonide may need to be increased.
Improvement in asthma control following inhaled administration can occur within 24 hours of initiation of treatment, although maximum benefit may not be achieved for 1 to 2 weeks or longer after starting treatment.
Concomitant therapy with oral corticosteroids: For patients who are maintained on chronic oral corticosteroids, the usual maintenance dose should be used concurrently with the initial budesonide therapy. After approximately 1 week, gradual withdrawal of the systemic corticosteroid is started by reducing the daily or alternate daily dose. The next reduction is made after 1 or 2 weeks, depending on the response of the patient. Generally, these decrements should not exceed 25% of the prednisone dose or its equivalent. A slow rate of withdrawal is strongly recommended. During reduction of oral corticosteroids, patients should be carefully monitored for asthma instability, including objective measures of airway function, and for adrenal insufficiency. During withdrawal, some patients may experience symptoms of systemic corticosteroid withdrawal (eg, joint or muscular pain, lassitude, depression) despite maintenance or even improvement in pulmonary function. Such patients should be encouraged to continue with budesonide but should be monitored for objective signs of adrenal insufficiency. If evidence of adrenal insufficiency occurs, the systemic corticosteroid doses should be increased temporarily, and thereafter withdrawal should continue more slowly. During periods of stress or a severe asthma attack, transfer patients may require supplementary treatment with systemic corticosteroids.
Admixture compatibility: The effects of mixing Aeronide 200 mcg with other nebulizable medications have not been adequately assessed. Administer separately in the nebulizer.
Elderly: No dosage adjustment is necessary for elderly patients.
Hepatic function impairment: Exercise caution when administering to patients with hepatic impairment.
Patients not receiving systemic (oral) corticosteroids: Patients who require maintenance therapy of asthma may benefit from treatment with Aeronide 200 suspension at the doses recommended.
For patients who do not respond adequately to the starting dose, consideration should be given to administering the total daily dose as a divided dose if a once-daily dosing schedule was followed. If necessary, higher doses, up to the maximum recommended doses, may provide additional asthma control.
ASTHMA: Children 1 - 8 years of age: Recommended Dosages in Children 1 - 8 years of age: See table.

Click on icon to see table/diagram/image

Dosage adjustment: If once-daily treatment does not provide adequate control of asthma symptoms, the total daily dose should be increased or administered as a divided dose.
Symptomatic children not responding to nonsteroidal therapy (e.g., bronchodilator, mast-cell stabilizer): A starting dose of 250 mcg once daily may also be considered.
Children 7 years of age and above: Recommended dose is 200 to 800 mcg daily in divided into 2 to 4 administrations.
In children with mild to moderate asthma who have not previously received inhale glucocorticosteroids, or who are already controlled on inhaled steroids (e.g. budesonide or beclomethasone dipropionate): 200 to 400 mcg daily may be used in divided into 2 administrations.
During periods of severe asthma, the daily dose can be increased up to 800 mcg.
Adults and children over 12 years of age: Recommended dose is 200 to 1600 mcg daily divided into 2 to 4 administrations.
In less severe cases 200 to 800 mcg daily (200 to 400 mcg may be used in patients with mild to moderate asthma who have not previously received inhaled glucocorticosteroids and up to 800 mcg may be used by patients with mild to moderate asthma already controlled on inhaled steroids e.g. budesonide or beclomethasone dipropionate, administered twice daily).
In more severe cases 800 to 1600 mcg daily. Administration twice daily (morning and evening) is usually sufficient. In severe asthma and during exacerbations some patients may benefit from dividing the daily dose into 3 to 4 administrations per day. In mild asthmatics requiring up to 400 mcg daily for symptom control, the dose could be given once daily in the morning or in the evening. The maintenance dose should be individualised and should be the lowest dose which leaves the patient symptom-free. Recommended doses are 100 to 400 mcg/daily. This may be given as a twice daily dose, or as a once daily dose given in the morning or the evening.

The potential for acute toxic effects following overdose of budesonide inhalation is low. If inhaled corticosteroids are used at excessive doses for prolonged periods, systemic corticosteroid effects such as hypercorticism or growth suppression may occur. In mice the minimal lethal inhalation dose was 100 mg/kg (approximately 410 or 120 times, respectively, the maximum recommended daily inhalation dose in adults or children on a mg/m² basis). In rats there were no deaths at an inhalation dose of 68 mg/kg (approximately 550 or 160 times, respectively, the maximum recommended daily inhalation dose in adults or children on a mg/m² basis). In mice the minimal oral lethal dose was 200 mg/kg (approximately 810 or 240 times, respectively, the maximum recommended daily inhalation dose in adults or children on a mg/m² basis). In rats, the minimal oral lethal dose was less than 100 mg/kg (approximately 810 or 240 times, respectively, the maximum recommended daily inhalation dose in adults or children on a mg/m² basis).
The only harmful effect that follows inhalation of large amounts of the drug over a short period is suppression of hypothalamic-pituitary-adrenal (HPA) function. No special emergency action needs to be taken. Treatment should be continued at the recommended dose to control the asthma.

Hypersensitivity to budesonide or any of the ingredients in its preparations.
Budesonide is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.

Particular care is needed for patients who are transferred from systemically active corticosteroids to inhaled corticosteroids (eg, budesonide) because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of HPA-axis function.
Patients who have been previously maintained on greater than or equal to 20 mg/day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn.
Patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although budesonide may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does not provide the mineralocorticoid activity that is necessary for coping with these emergencies.
During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.
Special caution is necessary in patients with active or quiescent pulmonary tuberculosis, and in patients with fungal or viral infections in the airways.
Non steroid-dependent patients: A therapeutic effect is usually reached within 10 days. In patients with excessive mucus secretion in the bronchi, a short (about 2 weeks) additional oral corticosteroid regimen can be given initially.
Steroid-dependent patients: When transferal from oral steroids to Aeronide 200 suspension is started, the patient should be in a relatively stable phase. A high dose of Aeronide 200 suspension is then given in combination with the previously used oral steroid dose for about 10 days. After that, the oral steroid dose should be gradually reduced (by for example 2.5 milligrams prednisolone or the equivalent each month) to the lowest possible level. In many cases, it is possible to completely substitute Aeronide 200 suspension for the oral steroid.
During transfer from oral therapy to Aeronide 200 suspension, a generally lower systemic steroid action will be experienced which may result in the appearance of allergic or arthritic symptoms such as rhinitis, eczema and muscle and joint pain. Specific treatment should be initiated for these conditions. During the withdrawal of oral steroids, patients may feel unwell in a non-specific way, even though respiratory function is maintained or improved. Patients should be encouraged to continue with Aeronide 200 suspension therapy whilst withdrawing the oral steroid, unless there are clinical signs to indicate the contrary. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases, symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of oral glucocorticosteroids is sometimes necessary.
As with other inhalation therapy, paradoxical bronchospasm may occur, with an immediate increase in wheezing after closing. If a severe reaction occurs, treatment should be reassessed and an alternative therapy instituted if necessary.
Patients who have previously been dependent on oral steroids may, as a result of prolonged systemic steroid therapy, experience the effects of impaired adrenal function. Recovery may take a considerable amount of time after cessation of oral steroid therapy, hence oral steroid-dependent patients transferred to budesonide may remain at risk from impaired adrenal function for some considerable time. In such circumstances, HPA axis functions should be monitored regularly.
Acute exacerbations of asthma may need an increase in the dose of Aeronide 200 mcg or additional treatment with a short course of oral corticosteroid and/or an antibiotic, if there is an infection. The patient should be advised to use a short-acting inhaled bronchodilator as rescue medication to relieve acute asthma symptoms.
If patients find short-acting bronchodilator treatment ineffective or they need more inhalations than usual, medical attention must be sought. In this situation consideration should be given to the need for or an increase in their regular therapy, e.g., higher doses of inhaled budesonide or the addition of a long-acting beta agonist, or for a course of oral glucocorticosteroid.
Prolonged treatment with high doses of inhaled corticosteroids, particularly higher than the recommended doses, may result in clinically significant adrenal suppression.
Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma. It is important, therefore, that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.
It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid, if possible, to the lowest dose at which effective control of asthma is maintained. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.
Reduced liver function may affect the elimination of glucocorticosteroids. The plasma clearance following an intravenous dose of budesonide however was similar in cirrhotic patients and in healthy subjects. After oral ingestion systemic availability of budesonide was increased by compromised liver function due to decreased first pass metabolism. The clinical relevance of this to treatment with the drug is unknown as no data exist for inhaled budesonide, but increases in plasma levels and hence an increased risk of systemic adverse effects could be expected.
In vivo studies have shown that oral administration of ketoconazole and itraconazole (known inhibitors of CYP3A4 activity in the liver and in the intestinal mucosa) causes an increase in the systemic exposure to budesonide. Concomitant treatment with ketoconazole and itraconazole or other potent CYP3A4 inhibitors should be avoided. If this is not possible, the time interval between administration of the interacting drugs should be as long as possible. A reduction in the dose of budesonide should also be considered.

Steroid withdrawal: Particular care is needed for patients who are transferred from systemically active corticosteroids to inhaled corticosteroids (eg, budesonide) because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.
Although budesonide may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does not provide the mineralocorticoid activity that is necessary for coping with these emergencies.
Acute stress/severe asthma attack: During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card and supplementary systemic corticosteroids during periods of stress or a severe asthma attack.
Transfer from systemic steroids: Transfer of patients from systemic corticosteroid therapy to budesonide may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (eg, rhinitis, conjunctivitis, eczema).
Compromised immune system: Patients who are on drugs which suppress the immune system are more susceptible to infection than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults on immunosuppressant doses of corticosteroids. In children or adult patients who have not had these diseases, or who have not been properly vaccinated, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is unknown. The contribution of the underlying disease or prior corticosteroid treatment to the risk is also not known, if exposed, therapy with varicella-zoster immune globulin (VZIG) or pooled IV immunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled IM immunoglobulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
Acute asthma: Budesonide is not indicated for rapid relief of bronchospasm or other acute episodes of asthma.
Bronchospasm: As with other inhaled asthma medications, bronchospasm, with an immediate increase in wheezing, may occur after dosing. If bronchospasm occurs following dosing with budesonide, it should be treated immediately with a fast-acting inhaled bronchodilator. Treatment with budesonide should be discontinued and alternate therapy instituted. Patients should be instructed to contact their physicians immediately when episodes of asthma not responsive to their usual doses of bronchodilators occur during treatment with budesonide. During such episodes, patients may require therapy with oral corticosteroids.
Inhalation suspension: For inhalation use via compressed air driven jet nebulizers only (not for use with ultrasonic devices). Not for injection. Read patient instructions before using. During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal (eg, joint or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.
Systemic corticosteroid effects: Because budesonide is absorbed into the circulation and may be systemically active, particularly at higher doses, suppression of HPA function may be associated when budesonide is administered at doses exceeding those recommended, or when the dose is not titrated to the lowest effected dose. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing budesonide.
Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with these drugs should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.
It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear in a small number of patients, particularly at higher doses. If such changes occur, budesonide should be reduced slowly, consistent with accepted procedures for management of asthma symptoms and for tapering of systemic corticosteroids.
Vision: Rare instances of glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled administration of corticosteroids.
Special risk patients: Inhaled corticosteroids should be used with caution, if all, in patients with active or quiescent tuberculosis infection of the respiratory tract, untreated systemic fungal, bacterial, viral or parasitic infections, or ocular herpes simplex.
Carcinogenesis: Long-term studies were conducted in mice and rats using oral administration to evaluate the carcinogenic potential of budesonide. In a 2-year study in Sprague-Dawley rats, budesonide caused a statistically significant increase in the incidence of gliomas in male rats at an oral dose of 50 mcg/kg (less than the maximum recommended daily inhalation dose in adults and children on a mcg/m² basis.
Mutagenesis: Budesonide was not mutagenic or clastogenic in 6 different test systems: Ames Salmonella/microsome plate test, mouse micronucleus test, mouse lymphoma test, chromosome aberration test in human lymphocytes, sex-linked recessive lethal test in Drosophila melanogaster, and DNA repair analysis in rat hepatocyte culture.
Fertility impairment: In rats, budesonide had no effect on fertility at SC doses up to 80 mcg/kg (less than the maximum recommended daily inhalation dose in adults on a mcg/m² basis). However, it caused a decrease in prenatal viability and viability in the pups at birth and during lactation, along with a decrease in maternal body-weight gain, at SC doses of 20 mcg/kg and above (less than the maximum recommended daily inhalation dose in adults on a mcg/m² basis).
Monitoring: A reduction of growth velocity in children or teenagers may occur as a result of inadequate control of chronic diseases such as asthma or from use of corticosteroids for treatment. Physicians should closely follow the growth of all children taking corticosteroids by any route and weigh the benefits of corticosteroid therapy and asthma control against the possibility of growth suppression.
Use in Children & in the Elderly: No overall differences in safety were observed between these patients and younger patients, and other reported clinical or medical surveillance experience has not identified differences in responses between the elderly and younger patients.

Pregnancy: Pregnancy Category B.
Teratogenic Effects: Budesonide produced fetal loss, decreased pup weights, and skeletal abnormalities at SC doses of 25 mcg/kg/day in rabbits (less than the maximum recommended daily inhalation dose in adults on a mcg/m² basis) and 500 mcg/kg/day in rats (approximately 4 times the maximum recommended daily inhalation dose in adults on a mcg/m² basis). In another study in rats, no teratogenic or embryocidal effects were seen at inhalation doses up 250 mcg/kg/day (approximately 2 times the maximum recommended daily inhalation dose in adults on a mcg/m² basis).
Despite the animal findings, it would appear that the possibility of fetal harm is remote if the drug is used during pregnancy. Nevertheless, because the studies in humans cannot rule out the possibility of harm, budesonide inhalation should be used during pregnancy only if clearly needed.
Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully observed.
Lactation: It is not known whether budesonide is excreted in human milk. Because other corticosteroids are excreted in human milk, caution should be exercised if budesonide is administered to nursing women.

In clinical studies, concurrent administration of budesonide and other drugs commonly used in the treatment of asthma has not resulted in an increased frequency of adverse reactions. The main route of metabolism of budesonide, as well as other corticosteroids, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a potent inhibitor of CYP3A4, the mean plasma concentration of orally administered budesonide increased. Concomitant administration of other known inhibitors of CYP3A4 (eg, itraconazole, clarithromycin, erythromycin) may inhibit the metabolism of, and increase the systemic exposure to, budesonide. Care should be exercised when budesonide is coadministered with long-term ketoconazole and other known CYP3A4 inhibitors.
Omeprazole did not have effects on the pharmacokinetics of oral budesonide, while cimetidine, primarily an inhibitor of CYP1A2, caused a slight decrease in budesonide clearance and a corresponding increase in its oral bioavailability.

Store at temperatures not exceeding 30°C.
Aeronide 200 mcg should be stored upright at controlled room temperature 20° to 25°C (68° to 77°F) and protected from light. Aeronide 200 mcg should not be refrigerated or frozen.

The parts of your inhaler: There are 2 main parts to your inhaler-the metal canister that holds the medicine and the plastic actuator that sprays the medicine from the canister.
The inhaler also has a dust cap that covers the mouthpiece of the actuator.
Do not use the actuator with a canister of medicine from any other inhaler. And do not use with an actuator from any other inhaler.
How to Use your Inhaler: Testing your inhaler: 1. When using the inhaler for the first time, test that it is working. Remove the mouthpiece cover by gently squeezing the sides with your thumb and forefinger and pull apart.
2. To make sure that it works, shake it well, point the mouthpiece away from you and press the canister to release a puff into the air. If you have not used the inhaler for a week or more, release two puffs of medicine into the air.
Using your inhaler: It is important to start to breathe as slowly as possible just before using your inhaler.
1. Stand or sit upright when using your inhaler.
2. Remove the mouthpiece cover. Check inside and outside to make sure that the mouthpiece is clean and free of objects.
3. Shake the inhaler 4 or 5 times to ensure that any loose objects are removed and that the contents of the inhaler are evenly mixed.
4. Hold the inhaler upright with your thumb on the base, below the mouthpiece. Breathe out as far as is comfortable. Do not breathe in again yet.
5. Place the mouthpiece in your mouth between your teeth. Close your lips around it. Do not bite.
6. Breathe in through your mouth. Just after starting to breathe in, press down on the top of the canister to release a puff of medicine. Does this while still breathing in steadily and deeply.
7. Hold your breath, take the inhaler from your mouth and your finger from the top of the inhaler. Continue holding your breath for a few seconds, or as long as is comfortable.
8. If your doctor has told you to take two puffs, wait about half a minute before you take another puff by repeating steps 3 to 7.
9. After use always replace the mouthpiece cover straight away to keep out dust. Replace the cover by firmly pushing and clicking into position.
Cleaning your inhaler: To stop your inhaler blocking, it is important to clean it at least once a week.
To clean your inhaler: Remove the mouthpiece cover.
Do not remove the metal canister from the plastic casing at any time.
Wipe the inside and outside of the mouthpiece and the plastic casing with a dry cloth or tissue.
Replace the mouthpiece cover.
Do not put the metal canister in water.

Antiasthmatic & COPD Preparations

R03BA02 - budesonide ; Belongs to the class of other inhalants used in the treatment of obstructive airway diseases, glucocorticoids.

Rx