Each metered dose contains 200 micrograms of budesonide.
Excipients/Inactive Ingredients: Frenolyn 200 contains lactose monohydrate.
Pharmacotherapeutic group: Inhalation drugs for obstructive airway diseases. ATC Code: RO3B A02.
Pharmacology: Pharmacodynamics: Budesonide is a glucocorticosteroid with a high local anti-inflammatory effect.
The precise mechanism of action of glucocorticosteroids in the treatment of asthma is not fully understood. Anti-inflammatory actions, such as inhibited release of inflammatory mediators and inhibition of cytokine-mediated immune response are probably important. The activity of budesonide measured as its affinity for glucocorticosteroid receptors is approx. 15 times higher than that of prednisolone.
Budesonide has anti-inflammatory effects shown as reduced bronchial obstruction during both the early and the late phase of an allergic reaction.
Budesonide has been shown to decrease airway reactivity to histamine and methacholine in hyperreactive patients.
Studies have shown that the earlier budesonide treatment is initiated after the onset of asthma, the better lung function can be expected.
Studies in healthy volunteers with budesonide have shown dose-related effects on plasma and urinary cortisol. At recommended doses, budesonide causes significantly less effect on the adrenal function than prednisolone 10 mg, as shown by ACTH tests.
In children over the age of 3 years, no systemic effects have been detected with doses up to 400 micrograms per day. In the range 400 - 800 micrograms per day biochemical signs of a systemic effect may occur. With daily doses in excess of 800 micrograms such signs are common.
Asthma, like inhaled corticosteroids, can delay growth.
However, studies in children and adolescents who were treated with budesonide for a long period (up to 13 years) show that the patients reach the expected adult height.
Inhalation therapy with budesonide is effective in preventing exercise-induced asthma.
Pharmacokinetics: Absorption: Inhaled budesonide is rapidly absorbed. The peak plasma concentration is reached within 30 minutes after inhalation. In studies, the average deposition in the lungs after inhalation via different devices has been shown to be 25-35% of the metered dose. The systemic bioavailability is approximately 38% of the metered dose.
Distribution and metabolism: Plasma protein-binding is approx. 90%. The volume of distribution is approx. 3l/kg.
Budesonide undergoes an extensive degree (approximately 90%) first pass metabolism in the liver to metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide.
Elimination: Budesonide is eliminated through metabolism, catalysed primarily by the enzyme CYP3A4. The metabolites are excreted in the urine in unchanged or conjugated form. Only negligible amounts of unchanged budesonide are recovered in the urine. Budesonide has a high systemic clearance (approx. 1.2l/min), and the plasma half-life after intravenous administration is on average of 4 hours.
The pharmacokinetics of budesonide is proportional to the dose at relevant dosages.
The pharmacokinetics of budesonide in children and in patients with impaired renal function is unknown.
Exposure to budesonide may be increased in patients with hepatic disease.
Indicated for patients with bronchial asthma who require maintenance treatment with glucocorticosteroids for control of the underlying airway inflammations.
The dosage of Frenolyn Miat-Haler is individual. Initially, of the beginning of inhaled corticosteroid therapy, for therapy during periods of severe asthma or when scaling down or withdrawing oral corticosteroids the dosage should be: Children 5 - 7 years: 200 - 400 micrograms daily divided into 2 - 4 administrations.
Children 7 years and more: 200 - 800 micrograms daily divided into 2 - 4 administrations.
Adults: 200 - 1600 micrograms daily divided into 2 - 4 administrations, (less severe cases 200 - 800 micrograms daily, more severe cases 800 - 1600 micrograms daily).
Administration twice daily (morning and evening) is usually sufficient.
The maintenance dose is individual and should be the lowest possible. When the maintenance dose is 400 micrograms or lower the dose can be given once daily. The dose may then be given in the morning or in the evening. If deterioration of asthma occurs, the frequency of dosing and the daily dose should be increased.
Following a single dose, an effect may be expected after a few hours. The full therapeutic effect is only achieved after a few weeks of treatment. Treatment with Frenolyn Miat-Haler is prophylactic therapy with no demonstrated effect on acute disorders.
In patients in whom an increased therapeutic effect is desired, in general, an increase of the Frenolyn Miat-Haler dose is to be recommended in preference to combination treatment with corticosteroids because of the lower risk of systemic side effects.
Patients dependent on oral steroids: When transfer from oral steroids is initiated the patient must be in a relatively stable condition. A high dose of Frenolyn is given in combination with the previous used oral steroid dose for 10 days. After that, the oral dose should be gradually reduced by e.g. 2.5 mg prednisolone or equivalent per month to the lowest possible level. The oral steroid can often be discontinued entirely.
There is no experience of treatment in patients with impaired hepatic or renal function. Since budesonide is predominantly eliminated through hepatic metabolism, increased exposure may be expected in patients with severe cirrhosis of the liver.
Acute overdose with Budesonide, even in high doses, is not expected to cause any clinical problems. If used chronically in high doses, systemic effects of glucocoticosteroids such as hypercortisolism and adrenal suppression can occur.
Hypersensitivity to the active substance, budesonise, or to any of the excipients (see Description).
Active pulmonary tuberculosis.
Visual disturbance: Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Special care is needed in patients with lung tuberculosis and fungal or viral infections.
Children who are on immunosuppressant drugs are more susceptible to infections than healthy children. Chicken pox and measles, for example, can have a more serious or fatal course in children on immunosuppressant corticosteroids. In such children, or in adults who have not had these diseases, particular care should be taken to avoid exposure. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chicken pox develops, treatment with antiviral agents may be considered. If, however, a viral upper respiratory infection is present, the patient should adhere to the regular asthma medication. In patients who are known to deteriorate rapidly when they have viral respiratory infection, a short course of oral corticosteroid therapy should be considered.
Clinical studies have shown that viral infections cause significantly less problems in patients who are on regular treatment of topical glucocorticosteriods.
In order to minimise the risk of Candida infections in the oral cavity and throat, the patient should be instructed to rinse the mouth with water after each dose administration.
Concomitant treatment with ketoconazole and itraconazole or other potent CYP3A4 inhibitors should be avoided (see Interactions). If this is not possible, the time interval between administration of the interacting drugs should be as long as possible.
Particular care is needed in patients transferring from oral glucocorticosteroids, since they may remain at risk of impaired adrenal function for a considerable time. Patients who have required high dose emergency glucocorticosteroid therapy or prolonged treatment at the highest recommended dose of inhaled glucocorticosteroids, may also be at risk. These patients may exhibit signs and symptoms of adrenal insufficiency when exposed to severe stress. Additional systemic glucocorticosteroid cover should be considered during periods of stress or elective surgery.
During the transfer from oral steroid therapy to budesonide, patients may experience the return of previous symptoms such as and joint pain. In these cases a temporary increase of the oral steroid dose may sometimes be necessary. If, in isolated cases, fatigue, headache, nausea, vomiting or similar symptoms occur, a generally unsatisfactory effect of the steroid should be suspected.
Replacement of systemic steroid treatment by budesonide sometimes reveals allergies, e.g. rhinitis and eczema, that were previously controlled by the systemic treatment.
Regular monitoring of growth is recommended in children and adolescents receiving long-term treatment with corticosteroids, irrespective of the administration form. The benefits of corticosteroid treatment must be placed in relation to possible risks of inhibition of growth. 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. Budesonide is not indicated for rapid relief of bronchospasm. Budesonide is therefore not suitable as sole therapy for the treatment of status asthmasticus or other acute exacerbations of asthma where intensive measures are required.
If patients find short-acting bronchodilator treatment ineffective or they need more inhalations than usual, medical attention must be sought. This indicates a worsening of the underlying conditions and warrants a reassessment of the therapy. Acute exacerbations of asthma may need complementary treatment with a short oral steroid regimen.
Decreased liver function may affect the ability to eliminate budesonide.
This product also contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose - galactose malabsorption should not take this medicine.
Warning for sportsmen: Sportsmen need to know that the medicine contains an active ingredient that gives positive results at an antidopping test.
Effects on ability to drive and use machines: Frenolyn is not known to have any effects on the ability to drive and use machines.
Pregnancy: Data from approximately 2,000 pregnancies have not revealed any increased risk of malformations as a result of treatment with budesonide. Animal studies have shown that glucocorticosteroids can induce malformations, but this is judged not to be relevant for humans with the recommended dosage.
During pregnancy the aim must be the lowest effective dose of budesonide while taking account of the risk of a worsening of the asthma.
Lactation: Budesonide is excreted in breast milk. However, at therapeutic doses of budesonide no effects on the suckling child are anticipated. Budesonide can be used during breast feeding.
Up to 10% of patients treated may be expected to experience adverse reactions of a local nature. (See table.)
Click on icon to see table/diagram/image
On account of the risk of Candida infections in the oropharynx the patient must rinse the mouth with water after every dose.
In isolated cases, signs or symptoms of systemic glucocorticoid effects may occur, including adrenal hypofunction.
No clinically relevant interactions with other agents for asthma are known.
Ketoconazole 200 mg once daily increased the plasma concentrations of budesonide (3 mg in a single dose) on average six-fold when administered concomitantly. When ketoconazole was administered 12 hours after budesonide, the concentration was increased on average three-fold. Information about this interaction is lacking for inhaled budesonide, but markedly increased plasma levels are also expected in such cases. The combination should be avoided since data to support dose recommendations are lacking.
If this is not possible, the time interval between administration of ketoconazole and budesonide should be as long as possible. A reduction of budesonide dose must also be considered.
Other potent inhibitors of CYP3A4, i.e. itraconazole are also cause a marked increase in the plasma levels of budesonide.
Instructions for correct use of Miat-Haler: Miat-Haler is inspiratory flow-driven which means that, when the patient inhales through the mouthpiece, the substance will follow the inspired air into the airways.
Note: It is important to instruct the patient: To carefully read the instructions for use: "How to use Frenolyn Miat-Haler".
To breathe in forcefully and deeply through the mouthpiece to ensure that an optimal dose is delivered to the lungs.
Never to breathe out through the mouthpiece.
To rinse the mouth out with water after inhaling the prescribed dose to minimise the risk of oropharyngeal thrush.
It is possible that the patient will not taste or perceive any medicine when Frenolyn Miat-Haler is used; this is because such a small amount of substance is dispensed.
Incompatibilities: Not applicable.
Do not store above 25°C.
Do not refrigerate or freeze.
Keep the container tightly closed.
In order to protect from moisture, always replace the inhaler in the outer case, and screw closed immediately after every use.
Shelf life: 36 months.
Once opened the inhaler can be used within 6 months.
How to use FRENOLYN Miat-Haler: The FRENOLYN Miat-Haler inhaler is packed in an aluminium blister in the outer carton. You should not open the blister or remove the inhaler from it until you need to use the inhaler. Open the aluminium blister and discard it. The FRENOLYN Miat-Haler inhaler may rattle when you shake it, this does not mean anything is wrong; it is part of the mechanism. The inhaler is easy to use, provided you follow the instructions. Your doctor or pharmacist should have shown you how to use it but if you are unsure, you should ask him/her.
The Miat-Haler consists of two pieces, as shown: It is a light grey, except for the cap, which is dark brown.
STEP 1: Hold the Miat-Haler upright. Unscrew the inhaler by rotating anticlockwise, keeping the brown top in the upright position and remove it from the protective case.
Note: If the inhaler is not kept upright, a warning signal in the Inhaler will generate a rattling noise, reminding you to keep the Inhaler in the right position. If you hear the rattling noise repeat the operation keeping the Inhaler upright.
STEP 2: Be sure that the △ shaped notch on the body is aligned with the △ notch on the top.
If the notches are not aligned, turn the Inhaler until the notches are aligned.
Press the brown top and release. The dose is now ready for administration.
Note: At this stage the desired dosage of active is prepared for intake and ready for the next step (inhalation).
Attention: Proceed immediately to the next step. Do not interrupt the sequence at this stage.
STEP 3: Breathe out gently, before bringing the Inhaler to your mouth. Place the Inhaler mouthpiece between your lips (with the inhaler still kept in the upright position) and breathe in as deeply as possible. Remove the inhaler from your mouth and hold breath for a few seconds before breathing out.
You can repeat step 3 to be sure you have taken your entire dose.
Note: A subtle sweet taste of the powder inhaled can be felt, that confirms you have inhaled the dose. You may not notice any taste in your mouth when using FRENOLYN Miat Haler, but you will still have received the correct dose.
Attention: After taking your dose, you should rinse your mouth out with water, and/or clean your teeth. This will reduce the risk of you getting "thrush" (a yeast infection) in your mouth.
You should wipe the mouthpiece with a clean dry tissue after each use.
STEP 4: Place the inhaler in the protective case and screw closed rotating clockwise.
Notice: If you need to take another inhalation, you should repeat steps 1-4 again.
Attention: Always place the inhaler back in its protective case after every use; this is necessary for the preparation of the next dose.
Replacing your Frenolyn: As your inhaler becomes nearly empty, a red band will begin to appear in the small window on the right hand side of the device. When it is empty, after the labeled number of doses has been used, the red band will fill the window. The brown top will not depress, as it will lock to stop you using an empty inhaler.
You should see your doctor for a replacement prescription when you first see the red band appear.
R03BA02 - budesonide ; Belongs to the class of other inhalants used in the treatment of obstructive airway diseases, glucocorticoids.
Powd for inhalation 200 mcg/dose x 100 doses x 1's.