Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2022 Publisher: AstraZeneca UK Limited, 1 Francis Crick Avenue, Cambridge, CB2 0AA, UK
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In the treatment of premature labour Bricanyl is contraindicated in the following conditions:
As for all beta2-agonists caution should be observed in patients with thyrotoxicosis.
Cardiovascular effects may be seen with sympathomimetic drugs, including Bricanyl. There is some evidence from post-marketing data and published literature of myocardial ischaemia associated with beta agonists.
Due to the positive inotropic effect of the beta2-agonists, these drugs should not be used in patients with hypertrophic cardiomyopathy.
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). It is recommended that serum potassium levels are monitored in such situations.
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.
Lactic acidosis has been reported in association with high therapeutic doses of parenteral and nebulised short-acting beta-agonist therapy, mainly in patients being treated for an acute asthma exacerbation (see section 4.8). In patients not adequately responding to acute Bricanyl therapy, consideration should be given to the presence of lactic acidosis as a possible contributing factor to ongoing respiratory symptoms.
Any decision to initiate therapy with Bricanyl should be undertaken after careful consideration of the risks and benefits of treatment.
Treatment should only be carried out in facilities adequately equipped to perform continuous monitoring of maternal and foetal health status. Tocolysis with beta-agonists is not recommended when membranes have ruptured or the cervix dilation is beyond 4 cm.
Bricanyl should be used with caution in tocolysis and supervision of cardiorespiratory function and ECG monitoring, should be performed throughout treatment.
The following monitoring measures must be constantly applied to the mother and, when feasible/appropriate, to the foetus:
Treatment should be discontinued if signs of myocardial ischaemia (such as chest pain or ECG changes) develop.
Bricanyl should not be used as a tocolytic agent in patients with significant risk factors for, or a suspicion of any kind of pre-existing heart disease (e.g. tachyarrhythmias, heart failure, or valvular heart disease; see section 4.3). In premature labour in a patient with known or suspected cardiac disease, a physician experienced in cardiology should assess the suitability of treatment before intravenous infusion with Bricanyl.
An increased tendency to bleeding has been described in connection with cesarean section (give propranolol 1-2 mg i.v.) in patients treated with Bricanyl solution for injection for preterm labour.
As maternal pulmonary oedema and myocardial ischaemia have been reported during or following treatment of premature labour with beta-agonists, careful attention should be given to fluid balance and cardio-respiratory function. Patients with predisposing factors including multiple pregnancies, fluid overload, maternal infection and pre-eclampsia may have an increased risk of developing pulmonary oedema. Administration with a syringe pump as opposed to i.v. infusion will limit risk of fluid overload. If signs of pulmonary oedema or myocardial ischaemia develop, discontinuation of treatment should be considered (see section 4.2 and 4.8).
Increases in maternal heart rate of the order of 20 to 50 beats per minute usually accompany infusion of beta-agonists. The maternal pulse rate should be monitored and the need to control such increases by dose reduction or drug withdrawal should be evaluated on a case by case basis. Generally maternal pulse rate should not be allowed to exceed a steady rate of 120 beats per minute.
Maternal blood pressure may fall slightly during the infusion; the effect being greater on diastolic than on systolic pressure. Falls in diastolic pressure are usually within the range of 10 to 20 mmHg. The effect of infusion on foetal heart rate is less marked, but increases of up to 20 beats per minute may occur.
In order to minimise the risk of hypotension associated with tocolytic therapy, special care should be taken to avoid caval compression by keeping the patient in the left or right lateral positions throughout the infusion.
Administration of beta agonists is associated with a rise of blood glucose. Therefore blood glucose and lactate levels should be monitored in mothers with diabetes and diabetic treatment adjusted accordingly to meet the needs of the diabetic mother during tocolysis (see section 4.5).
Bricanyl should only be administered cautiously to patients suffering from thyrotoxicosis after careful evaluation of the benefits and risks of treatment.
This medicinal product contains less than 1 mmol sodium (23 mg) per ampoule, that is to say essentially ‘sodium-free’.
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.
Owing to the additional antihypertensive effect, there is increased uterine inertia with risk of haemorrhage; in addition, serious ventricular rhythm disorders due to increased cardiac reactivity, have been reported on interaction with halogenated anaesthetics. Treatment should be discontinued, whenever possible, at least 6 hours before any scheduled anaesthesia with halogenated anaesthetics.
Halothane anaesthesia should be avoided during beta2-agonists treatment, since it increases the risk of cardiac arrhythmias. Other halogenated anaesthetics should be used cautiously together with beta2-agonists.
Systemic corticosteroids are frequently given during premature labour to enhance foetal lung development. There have been reports of pulmonary oedema in women concomitantly administered with beta-agonists and corticosteroids.
Corticosteroids are known to increase blood glucose and can deplete serum potassium, therefore concomitant administration should be undertaken with caution with continuous patient monitoring owing to the increased risk of hyperglycaemia and hypokalaemia (see section 4.4).
The administration of beta-agonists is associated with a rise of blood glucose, which can be interpreted as an attenuation of anti-diabetic therapy; therefore individual anti-diabetic therapy may need to be adjusted (see section 4.4).
Owing to the hypokalaemic effect of beta-agonists, concurrent administration of serum potassium depleting agents known to exacerbate the risk of hypokalaemia, such as diuretics, digoxin, methyl xanthines and corticosteroids, should be administered cautiously after careful evaluation of the benefits and risks with special regard to the increased risk of cardiac arrhythmias arising as a result of hypokalaemia (see section 4.4).
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 into breast milk, but any effects on the infant are unlikely at therapeutic doses.
Transient hypoglycaemia has been reported in newborn preterm infants after maternal beta2-agonist treatment.
Bricanyl solution for injection is contraindicated for the treatment of premature labour before the gestational age of week 22 (see section 4.3).
Bricanyl has no or negligible influence on the ability to drive and use machines.
The intensity of the adverse reactions depends on dosage and route of administration. An initial dose titration will often reduce the adverse reactions. 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 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
| System Organ Class (SOC) | Frequency Classification | Adverse Drug Reaction Preferred Term |
|---|---|---|
| Immune System Disorders | Not Known^ | Hypersensitivity reactions including angioedema, bronchospasm, hypotension and collapse |
| Metabolism and Nutritional Disorders | Common | Hypokalaemia (see section 4.4) |
| Rare | Lactic acidosis | |
| Psychiatric Disorders | Not Known^ | Sleep disorder and Behavioural disturbances, such as agitation and restlessness |
| Nervous System Disorders | Very Common | Tremor Headache |
| Cardiac Disorders | Common | Tachycardia Palpitations |
| Not Known^ | Arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia and extrasystoles Myocardial ischaemia (see section 4.4) | |
| Vascular Disorders | Not Known^ | Peripheral vasodilation |
| Respiratory, Thoracic and Mediastinal Disorders | Not Known^ | Paradoxical bronchospasm* |
| Gastrointestinal Disorders | Not Known^ | Nausea Mouth and throat irritation |
| Skin and Subcutaneous Tissue Disorders | Not Known^ | Urticaria Rash |
| Musculoskeletal and Connective Tissue Disorders# | Common | Muscle spasms |
^ 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.
# A few patients feel tense; this is also due to the effects on skeletal muscle and not to direct CNS stimulation.
The most common undesirable effects of Bricanyl are correlated with the betamimetic pharmacological activity and may be limited or avoided by a close monitoring of haemodynamic parameters, such as blood pressure and heart rate, and an appropriate adjustment of the dose. They normally recede upon therapy discontinuation.
| System Organ Class (SOC) | Frequency Classification | Adverse Drug Reaction Preferred Term |
|---|---|---|
| Blood and Lymphatic System Disorders | Not Known^ | An increased tendency to bleeding in connection with caesarean section |
| Immune System Disorders | Not Known^ | Hypersensitivity reactions including angioedema, bronchospasm, hypotension and collapse |
| Metabolism and Nutritional Disorders | Common | Hypokalaemia (see section 4.4)° |
| Rare | Hyperglycaemia° | |
| Rare | Lactic acidosis | |
| Psychiatric Disorders | Not Known^ | Sleep disorder and Behavioural disturbances, such as agitation and restlessness Hyperactivity |
| Nervous System Disorders | Very Common | Tremor Headache |
| Cardiac Disorders | Very Common | Tachycardia° |
| Common | Palpitations° Decrease in diastolic pressure° | |
| Rare | Cardiac arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia and extrasystoles° Myocardial ischaemia (see section 4.4)° | |
| Vascular Disorder | Common | Hypotension (see section 4.4)° |
| Rare | Peripheral vasodilatation° | |
| Respiratory, Thoracic and Mediastinal Disorders | Uncommon | Pulmonary oedema° |
| Not Known^ | Paradoxical bronchospasm* | |
| Gastrointestinal Disorders | Very Common | Nausea |
| Not Known^ | Mouth and throat irritation | |
| Skin and Subcutaneous Tissue Disorders | Not Known^ | Urticaria Rash |
| Musculoskeletal and Connective Tissue Disorders# | Not Known^ | Muscle spasms |
^ Reported spontaneously in post-marketing data and therefore frequency regarded as unknown
° These reactions have been reported in association with the use of short acting beta-agonists in obstetric indications and are considered class effects (see section 4.4).
* 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.
# A few patients feel tense; this is also due to the effects on skeletal muscle and not to direct CNS stimulation.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Bricanyl solution for injection should not be mixed with alkaline solutions, i.e. solutions with a pH higher than 7.0.
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