Bricanyl

Bricanyl

terbutaline

Manufacturer:

AstraZeneca

Distributor:

Zuellig
/
Four Star
Full Prescribing Info
Contents
Terbutaline sulphate.
Description
Bricanyl turbuhaler is a breath-activated, multiple-dose powder inhaler free from propellant, lubricant, preservative, carrier substances or other additives.
Bricanyl injection also contains the following inactive ingredients: Sodium chloride, HCl (for pH adjustment) and water for injections.
Terbutaline sulphate is 2-(tert-butylamino)-1-(3,5-dihydroxyphenyl)ethanol sulphate.
Action
Pharmacology: Pharmacotherapeutic Group: Selective β2-agonist. ATC Code: R03AC03.
Pharmacodynamics: Terbutaline is an adrenergic agonist which predominantly stimulates β2-receptors, thus, producing relaxation of bronchial smooth muscle, inhibition of the release of endogenous spasmogens, inhibition of edema caused by endogenous mediators, increased mucociliary clearance and relaxation of the uterine muscle.
The tertiary butyl group attached to the terminal nitrogen of the terbutaline molecule is thought to confer selective stimulation of the pulmonary β2-receptors and only relatively minor stimulation of cardiac β1-receptors. The presence of the 2 phenolic hydroxyl groups in the meta positions confers resistance to metabolism by the enzyme catechol-o-methyl transferase.
The active drug is released gradually from Bricanyl prolonged-release tablets, leading to a prolonged bronchodilatation which in clinical trials has been demonstrated for up to 12 hrs.
The potent bronchospasmolytic effect is rapid in onset and reaches a maximum about 30 min after SC injection, 1 hr after aerosol and 2-3 hrs after oral administration. The duration of action is between 4 and 5 hrs.
Inhaled terbutaline acts within a few minutes and has a duration for up to 6 hrs.
Pharmacokinetics: There is a considerable first-pass metabolism in the intestinal wall and in the liver. The bioavailability is around 10%. Maximum plasma concentration of terbutaline is reached within 2-6 hrs, somewhat later after dosing in the evening.
About 20-30% of the metered-dose is deposited in the lungs at a normal inhalation flow rate.
Terbutaline is metabolised mainly by conjugation with sulfuric acid and excreted as the sulphate conjugate. No active metabolites are formed.
Metabolism of terbutaline sulphate which is ingested orally or swallowed following inhalation is principally by conjugation in the GI mucosa. The drug is absorbed unchanged from the respiratory tract and is excreted mainly eg, in the urine. Practically all of an administered dose of terbutaline is eliminated after 72 hrs.
Indications/Uses
Turbuhaler: Bronchial asthma. Chronic bronchitis, emphysema and other lung diseases where bronchospasm is a complicating factor. Intended for short-term management of bronchospasm as well as maintenance therapy.
Turbuhaler/Injection: For relief of bronchospasm in patients with asthma or chronic obstructive pulmonary disease and for acute prophylaxis against exercise-induced asthma or in other situations known to induce bronchospasm.
Injection: Recommended for acute use only.
Dosage/Direction for Use
Turbuhaler: Adults and Children >12 years: 1 inhalation (0.5 mg) as required up to every 4-6 hrs. In severe cases, the single dose may be increased to 3 inhalations (1.5 mg). The total daily dose should not exceed 12 inhalations (6 mg). Children 3-12 yrs: 1 inhalation (0.5 mg) as required up to every 4-6 hrs. In severe cases, the single dose may be increased to 2 inhalations (1 mg). The total daily dose should not exceed 8 inhalations (4 mg).
Injection: Adults and Children >12 years: 0.5 mL SC. Repeat as required up to every 6 hrs.
Dosage should be individualised. Inhaled bronchodilators should be used as required rather than regularly.
If long-term use of terbutaline is proposed, particularly if the patient is asked to take terbutaline in conjunction with other medications, objective pulmonary function testing (eg, by peak flow meter or spirometer) may be useful as part of assessment of the efficacy of treatment.
Children: Dosage schedules for children for oral formulations of terbutaline should be prescribed on a mg/kg basis. The larger safety margins with the dry powder formulation permit a less specific dosage schedule.
Oral administration is indicated in children who are unable to inhale satisfactorily via a metered dose inhaler and who do not have access to a compressor/nebuliser unit.
Bricanyl turbuhaler is suitable for use by children since it is breath-activated and does not require coordination of dose release and inhalation as with use of aerosol inhalers. When prescribing the turbuhaler to young children, it is necessary to ascertain that they can follow the instructions for use as follows.
Administration: Turbuhaler: Directions for Use: Turbuhaler is insipatory flow-driven which means that, when the patient inhales through the mouthpiece, the substance will follow the inspired air into the airway. Follow the instructons given:
1. Unscrew and lift off the cover.
2. Hold the inhaler upright with the grip downwards. Load the inhaler with a dose by turning the grip as far as it will go and then back to the original position.
3. Breathe out. Do not breathe out through the mouthpiece.
4. Place the mouthpiece between your teeth, close your lips and breathe in forcefully and deeply through your mouth. Do not chew or bite hard on the mouthpiece.
5. Before breathing out, remove the inhaler from your mouth. If more than 1 dose has been prescribed, repeat steps 2-5.
6. Replace the cover.
Note: It is important to instruct the patient 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; always replace the cover properly after use; clean the outside of the mouthpiece regularly (weekly) with a dry tissue. Do not use water for cleaning the mouthpiece.
Overdosage
Symptoms: Turbuhaler/Injection: Too frequent administration, as with other sympathomimetic agents, may cause nausea, headaches, changes in blood pressure, anxiety, tension, restlessness, insomnia, tremor, excitement, tonic muscle cramps, palpitations, tachycardia and cardiac arrhythmias. The symptoms and signs are those characteristic of excessive sympathetic stimulation.
Laboratory Findings: Hyperglycaemia and lactacidosis sometimes occur. β2-agonists may cause hypokalaemia as a result of redistribution of potassium, but this usually requires no treatment.
Treatment: Metabolic changes should be corrected. The preferred antidote for overdosage with Bricanyl is a cardioselective β-adrenergic-blocking agent eg, metoprolol (5-10 mg by slow IV injection, repeated if necessary after 5 min). β-blockers should be used with caution in patients with a history of bronchospasm because of the possibility of inducing bronchial obstruction. If the β2-mediated reduction in peripheral vascular resistance significantly contributes to the fall in blood pressure, a volume expander should be given.
Contraindications
Hypersensitivity to sympathomimetic amines or to any of the ingredients of Bricanyl. Prolonged tocolysis.
Special Precautions
Hypokalaemia: Potentially serious hypokalaemia may result from β2-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatments (see Interactions). It is recommended that serum potassium levels are monitored in such situations.
Cardiovascular Diseases and Hyperthyroidism: Caution is advised when terbutaline is administered to patients with thyrotoxicosis.
Diabetes: Due to the hyperglycaemic effects of β2-stimulants, additional blood glucose controls are initially recommended when diabetic patients are commenced on terbutaline.
Terbutaline sulphate has not been approved for and should not be used for acute or maintenance tocolysis (beyond 48-72 hrs). In particular, terbutaline sulphate should not be used for maintenance tocolysis in the outpaitent or home setting.
Patients with chronic asthma who require maintenance therapy with β2-agonists must also have optimal anti-inflammatory treatment with corticosteroids. These patients should be advised to continue taking their anti-inflammatory treatment after starting Bricanyl controlled release tablets even when symptoms reduce. If the symptoms persist or if treatment with β2 agonists needs to be increased, this indicates a worsening in the underlying condition and justifies reassessment of the treatment.
Turbuhaler/Injection: Cardiovascular effects may be seen with sympathomimetic drugs, including Bricanyl. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with β-agonists. Patients with underlying severe heart disease (eg, ischaemic heart disease, arrhythmia or severe heart failure) who are receiving Bricanyl, should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms eg, dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.
Arrhythmogenic Potential: β2-stimulants have an arrhythmogenic potential which must be considered for each patient when receiving treatment for bronchospasm.
Sensitivity to Sympathomimetic Amines: Some patients may be unusually sensitive to β-adrenergic stimulants. Terbutaline should be used with caution when an increased susceptibility to sympathomimetic amines can be expected for instance in other patients with hyperthyroidism not yet adequately controlled.
Pulmonary Conditions: Positive pressure delivery system (IPPB) for respiratory drugs should not be used in pulmonary conditions involving pneumothorax, air cyst or mediastinal emphysema unless special drainage is carried out.
Lack of Response: If the usual dose does not provide the usual relief, a nonresponsive state may be developing. If a previously effective dose lasts less than usual, patients should be instructed to consult a doctor. This could also be the sign of worsening asthma and repeated inhalations of β2-antagonists must then not then delay reassessment of the asthma therapy.
Acute Asthma: If patients with an acute attack of asthma fail to respond to a dry powder inhaler of β2-agonist, they should be advised to follow their personal asthma action plan. Failure to respond to β2-agonists in general can be due to various reasons related to drug administration or the disease itself. Particularly in children ≤5 years and exceptionally in other cases, inspiratory flow through a dry powder inhaler may not be sufficient for optimal drug delivery. If a nonresponse occurs, medical help should be sought while a β2-agonist treatment is continued. In such a situation and if available, a pressurised metered-dose inhaler with spacer should be used. (See Lack of Response in previous text.)
Cardionecrosis: Animal studies suggest that cardionecrotic lesions may occur with high doses of some sympathomimetic amines. On this evidence, it is not possible to exclude myocardial lesions as a possible hazard resulting from long-term treatment.
Impaired Hepatic Function: Hepatic failure has not been shown to influence the metabolism of terbutaline. However, caution should be exercised in patients with impaired liver function.
Impaired Renal Function: As terbutaline is largely excreted in urine, caution should be exercised in patients with renal impairment.
Effects on the Ability to Drive or Operate Machinery: Bricanyl does not affect the ability to drive or use machines.
Use in pregnancy: Pregnancy Category A: No teratogenic effects have been observed in animals or in patients. However, caution is recommended during the 1st trimester of pregnancy.
Oral β2 agonists with slow release must be used with caution in the final stage of pregnancy because of the tocolytic effect.
During pregnancy, serious adverse reactions, including death, have been reported after administration of terbutaline sufate to pregnant women. In the mother, these adverse reactions include increased heart rate, transient hyperglycaemia, hypokalaemia, cardiac arrhythmias, pulmonary edema, and myocardial ischaemia. Increased fetal heart rate and neonatal hypoglycaemia may occur as a result of maternal administration.
Use in lactation: Terbutaline passes over to breast milk but an influence on the child is unlikely with therapeutic doses.
Although terbutaline is secreted into breast milk, and milk concentrations are approximately those in maternal plasma, 2 individual case studies indicate that the infant is likely to receive 0.2-0.7% of the maternal dose (0.4 mcg/kg/day and 0.7 mcg/kg/day, respectively), depending (for example) on the time of feeding in relation to administration of the drug. In the 4 infants studied, this did not result in any signs of β-adrenoceptor stimulation.
Transient hypoglycaemia has been reported in newborn pre-term infants after maternal β2-agonist treatment.
Use In Pregnancy & Lactation
Use in pregnancy: Pregnancy Category A: No teratogenic effects have been observed in animals or in patients. However, caution is recommended during the 1st trimester of pregnancy.
Oral β2 agonists with slow release must be used with caution in the final stage of pregnancy because of the tocolytic effect.
During pregnancy, serious adverse reactions, including death, have been reported after administration of terbutaline sufate to pregnant women. In the mother, these adverse reactions include increased heart rate, transient hyperglycaemia, hypokalaemia, cardiac arrhythmias, pulmonary edema, and myocardial ischaemia. Increased fetal heart rate and neonatal hypoglycaemia may occur as a result of maternal administration.
Use in lactation: Terbutaline passes over to breast milk but an influence on the child is unlikely with therapeutic doses.
Although terbutaline is secreted into breast milk, and milk concentrations are approximately those in maternal plasma, 2 individual case studies indicate that the infant is likely to receive 0.2-0.7% of the maternal dose (0.4 mcg/kg/day and 0.7 mcg/kg/day, respectively), depending (for example) on the time of feeding in relation to administration of the drug. In the 4 infants studied, this did not result in any signs of β-adrenoceptor stimulation.
Transient hypoglycaemia has been reported in newborn pre-term infants after maternal β2-agonist treatment.
Adverse Reactions
Most of the side effects are characteristic of sympathomimetic amines. The incidence and severity of particular adverse reactions depend on the dose, route and rate of administration. An initial dose titration will often reduce adverse reactions. At recommended therapeutic doses, the frequency of adverse reactions is minimal.
Turbuhaler: Most of the reported adverse reactions are characteristic of sympathomimetic amines. The majority of these effects have reversed spontaneously within the 1st 1-2 weeks of treatment.
Urticaria and exanthema may occur.
In children sleep disturbances and behavioural disturbances been observed.
The frequency of adverse reactions is low at the recommended dose. Terbutaline given by inhalation is unlikely to produce significant systemic effects when given in recommended doses. Most of the adverse reactions are characteristic of sympathomimetic amines.
The majority of these effects have reversed spontaneously within the first 1-2 weeks of treatment. (See table.)

Click on icon to see table/diagram/image

Turbuhaler/Injection: More Common Reactions: Commonly observed side effects include tremor, headache, nervousness, increases in heart rate, tonic muscle cramps, hypokalaemia and palpitations.
Less Common Reactions: Cardiovascular: Ectopic beats.
Gastrointestinal: Nausea, vomiting, bad taste, diarrhoea.
General: Sweating.
Musculoskeletal: Muscle twitching, cramps.
Nervous System: Drowsiness, headache, dizziness, sleep disturbance, agitation, hyperactivity, restlessness.
Dermatological: Rash, urticaria, exanthema.
Severe or Life-Threatening Reactions: Cardiac arrhythmias (eg, atrial fibrillation, supraventricular tachycardia and extrasystoles) and myocardial ischaemia have been rarely reported.
Overdose of terbutaline preparations may produce significant tachycardia, arrhythmia and hypotension (see Overdosage).
In rare cases, through unknown mechanisms, drugs for inhalation may cause bronchospasm.
Drug Interactions
Care is recommended if it is proposed to administer terbutaline in concomitant therapy with other sympathomimetic amines as excess sympathetic stimulation may occur.
β-adrenergic-blocking drugs (including eye drops), especially those which are nonselective, may inhibit partly or totally the bronchodilating effect of sympathomimetic bronchodilators and may increase airways resistance in asthmatic patients.
Hypokalaemia may result from β2-agonist therapy and may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics (see Hypokalaemia under Precautions).
Storage
Turbuhaler: Store below 30°C. Replace cap firmly after use.
Injection: Store below 25°C. Protect from light.
Solutions containing terbutaline are sensitive to excessive heat and light. Solutions should not be used if discoloured.
ATC Classification
R03AC03 - terbutaline ; Belongs to the class of adrenergic inhalants, selective beta-2-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases.
R03CC03 - terbutaline ; Belongs to the class of adrenergics for systemic use, selective beta-2-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases.
Presentation/Packing
Turbuhaler 0.5 mg/dose (multidose) x 200 doses. Inj (amp) 0.5 mg/mL x 1 mL x 5's.
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