1. Name Of The Medicinal Product
Bricanyl® Respules® 2.5 mg/ml Nebuliser Solution
2. Qualitative And Quantitative Composition
Terbutaline sulphate 2.5mg/ml.
Each single dose respule contains 2ml (5mg).
For excipients see Section 6.1.
3. Pharmaceutical Form
Nebuliser Solution.
A clear, aqueous, isotonic solution.
4. Clinical Particulars
4.1 Therapeutic Indications
Terbutaline is a selective beta2-adrenergic agonist recommended for the relief of severe bronchospasm in bronchial asthma and in chronic bronchitis and other bronchopulmonary disorders in which bronchospasm is a complicating factor.
4.2 Posology And Method Of Administration
In most patients, the use of terbutaline sulphate, based on the doses below, given 2-4 times daily will be sufficient to relieve bronchospasm. In acute, severe asthma, additional doses may be necessary.
Bricanyl Respules:
Adults: 1 or 2 Respules (5 or 10mg)
Children: (>25kg) 1 Respule (5mg)
Children: (<25kg) use multidose bottles.
Multidose Bottles:
Adults: 0.5 to 1 ml (5 to 10mg) diluted to required nebuliser volume with sterile physiological saline.
Children: 0.2 to 0.5ml (2 to 5mg), see table, diluted to required nebuliser volume with sterile physiological saline.
Table illustrating ml undiluted solution from multidose bottle required for administration to children
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Elderly: Dosage as for adults.
Instructions for use and cleaning are provided in the Patient Information Leaflet which can be found in each pack.
4.3 Contraindications
Bricanyl preparations are contra-indicated in patients with a history of hypersensitivity to any of their constituents.
4.4 Special Warnings And Precautions For Use
Patients should be instructed in proper use and their inhalation technique checked regularly.
If a previously effective dosage regimen no longer gives the same symptomatic relief, the patient should urgently seek further medical advice. Consideration should be given to the requirements for additional therapy (including increased dosages of anti-inflammatory medication). Severe exacerbations of asthma should be treated as an emergency in the usual manner.
As for all beta2-agonists caution should be observed in patients with thyrotoxicosis.
Due to the positive inotropic effect of the beta2-agonists, these drugs should not be used in patients with hypertrophic cardiomyopathy.
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 beta agonists. Patients with underlying severe heart disease (e.g. 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 such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.
Due to the hyperglycaemic effects of beta2-agonists, additional blood glucose controls are recommended initially in diabetic patients.
Potentially serious hypokalaemia may result from beta2-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 section 4.5, Interactions). It is recommended that serum potassium levels are monitored in such situations.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Beta-blocking agents (including eye drops), especially the non-selective ones such as propranolol, may partially or totally inhibit the effect of beta-stimulants. Therefore, Bricanyl preparations and non-selective beta-blockers should not normally be administered concurrently. Bricanyl should be used with caution in patients receiving other sympathomimetics.
Hypokalaemia may result from beta2-agonist therapy and may be potentiated by concomitant treatment with xanthine derivatives, corticosteroids and diuretics (see Section 4.4, Special Warnings and Precautions for use).
4.6 Pregnancy And Lactation
Although no teratogenic effects have been observed in animals or in patients, Bricanyl should only be administered with caution during the first trimester of pregnancy.
Terbutaline is secreted via breast milk, but effect on the infant is unlikely at therapeutic doses.
4.7 Effects On Ability To Drive And Use Machines
None Known
4.8 Undesirable Effects
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.
The frequency of side-effects is low at the recommended doses.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1,000 and <1/100), rare (>1/10,000 and <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
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# A few patients feel tense; this is also due to the effects on skeletal muscle and not to direct CNS stimulation.
^ Reported spontaneously in post-marketing data and therefore frequency regarded as unknown
* In rare cases, through unspecified mechanisms, paradoxical bronchospasm may occur, with wheezing immediately after inhalation. This should be immediately treated with a rapid-onset bronchodilator. Bricanyl therapy should be discontinued and after assessment, an alternative therapy initiated.
4.9 Overdose
i) Possible symptoms and signs
Headache, anxiety, tremor, nausea, tonic cramp, palpitations, tachycardia and arrhythmia. A fall in blood pressure sometimes occurs. Laboratory findings; hypokalaemia, hyperglycaemia and metabolic acidosis sometimes occur.
ii) Treatment
Mild and moderate cases: Reduce the dose.
Severe cases: Gastric lavage, administration of activated charcoal, (where suspected that significant amounts have been swallowed). Determination of acid-base balance, blood sugar and electrolytes, particularly serum potassium levels. Monitoring of heart rate and rhythm and blood pressure. Metabolic changes should be corrected. A cardioselective beta-blocker (e.g. metoprolol) is recommended for the treatment of arrhythmias causing haemodynamic deterioration. The beta-blocker should be used with care because of the possibility of inducing bronchoconstriction: use with caution in patients with a history of bronchospasm. If the beta-mediated reduction in peripheral vascular resistance significantly contributes to the fall in blood pressure, a volume expander should be given.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmaco-therapeutic group: selective beta2-agonist, terbutaline, ATC code: R03A C03.
Terbutaline is a selective beta2-adrenergic stimulant, having the following pharmacological effects:-
i) In the lung: bronchodilation; increase in mucociliary clearance; suppression of oedema and anti-allergic effects.
ii) In skeletal muscle: stimulates Na+/K+ transport and also causes depression of subtetanic contractions in slow-contracting muscle.
iii) In uterine muscle: Inhibition of uterine contractions.
iv) In the C.N.S: Low penetration into the blood-brain barrier at therapeutic doses, due to the highly hydrophilic nature of the molecule.
v) In the C.V.S.: Administration of terbutaline results in cardiovascular effects mediated through beta2-receptors in the peripheral arteries and in the heart e.g. in healthy subjects, 0.25 - 0.5 mg injected s.c., is associated with an increase in cardiac output (up to 85% over controls) due to an increase in heart rate and a larger stroke volume. The increase in heart rate is probably due to a combination of a reflex tachycardia, via a fall in peripheral resistance, and a direct positive chronotropic effect of the drug.
5.2 Pharmacokinetic Properties
Basic parameters have been evaluated in man after i.v. and oral administration of therapeutic doses, e.g.
I.V. single dose
Volume distribution (VSS) - 114L
Total body clearance (CL) - 213 ml/min.
Mean residence time (MRT) - 9.0 h.
Renal clearance (CLR) - 149 ml/min.(males)
Oral dose
Renal clearance (CLR) - 1.925 ml/min. (males)
Renal clearance (CLR) - 2.32 ml/min. (females)
The plasma concentration/time curve after i.v. administration is characterised by a fast distribution phase, an intermediate elimination phase and a late elimination phase.
Terminal half-life t½ has been determined after single and multiple dosing (mean values varied between 16-20 h.).
Bioavailability
Food reduces bioavailability following oral dosing (10% on average) fasting values of 14-15% have been obtained.
Metabolism
The main metabolite after oral dosing is the sulphate conjugate and also some glucoronide conjugate can be found in the urine.
5.3 Preclinical Safety Data
The major toxic effect of terbutaline, observed in toxicological studies in rats and dogs at exposures in excess of maximum human exposure, is focal myocardial necrosis. This type of cardiotoxicity is a well known pharmacological manifestation seen after the administration of high doses of beta2-agonists.
In rats, an increase in the incidence of benign uterine leiomyomas has been observed. This effect is looked upon as a class-effect observed in rodents after long term exposure to high doses of beta2-agonists
6. Pharmaceutical Particulars
6.1 List Of Excipients
Sodium chloride, disodium edetate, hydrochloric acid, water for injections.
6.2 Incompatibilities
None known.
6.3 Shelf Life
36 months
Single dose units in an opened foil envelope should be used within 3 months.
6.4 Special Precautions For Storage
Do not store above 30°C.
Store in the original container.
6.5 Nature And Contents Of Container
Single dose, plastic units (Respules) in cartons of 20 Respules, as 4 strips of 5 units, each wrapped in a foil envelope.
6.6 Special Precautions For Disposal And Other Handling
Bricanyl Respules will not normally require dilution at recommended doses. The pH of Bricanyl Respules is 3-4.5.
If dilution is required use sterile normal saline.
7. Marketing Authorisation Holder
AstraZeneca UK Limited
600 Capability Green
Luton
LU1 3LU
United Kingdom
8. Marketing Authorisation Number(S)
PL 17901/0114
9. Date Of First Authorisation/Renewal Of The Authorisation
7th May 2002 / 12th May 2007
10. Date Of Revision Of The Text
15th January 2010
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