Reasons for adding or updating:

• Change to section 2 - Qualitative and quantitative composition
• Change to section 4.2 - Posology and method of administration
• Change to section 4.6 - Fertility, pregnancy and lactation
• Change to section 6.3 - Shelf life
• Change to section 6.5 - Nature and contents of container
• Change to section 6.6 - Special precautions for disposal and other handling
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 11-Apr-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 2 – Updated information relating to excipients of known effect in line with QRD template
Section 4.2 – Updated sub-heading in line with QRD template
Section 4.6 – Minor formating changes
Section 6.3 – Updated shelf life (from months to years) in line with QRD template
Section 6.5 – Updated information in line with QRD template
Section 6.6 – Updated statement regarding disposal of medicinal product in line with QRD template
Section 10 – Updated date of revision of text

Reasons for adding or updating:

• Change to section 1 - Name of the medicinal product
• Change to section 2 - Qualitative and quantitative composition
• Change to section 4.2 - Posology and method of administration
• Change to section 4.3 - Contraindications
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.6 - Fertility, pregnancy and lactation
• Change to section 4.7 - Effects on ability to drive and use machines
• Change to section 4.8 - Undesirable effects
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 4.9 - Overdose
• Change to section 5.2 - Pharmacokinetic properties
• Change to section 6.1 - List of excipients
• Change to section 6.3 - Shelf life
• Change to section 6.6 - Special precautions for disposal and other handling
• Change to section 9 - Date of first authorisation/renewal of the authorisation
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 13-May-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



- section 1 Editorial changes to reflect latest QRD template

- section 2 Editorial changes to reflect latest QRD template and updated sulfate spelling

- section 4.2 Editorial changes to reflect latest QRD template and information on saline added

-section 4.3 Editorial changes to reflect latest QRD template

-section 4.4 Editorial changes to reflect latest QRD template and updated information on glucose and lactate levels

-section 4.5 updated information on Halothane anaesthesia

-section 4.6 Editorial changes to reflect latest QRD template

-section 4.7 Editorial changes to reflect latest QRD template

-section 4.8 Editorial changes to reflect latest QRD template, frequency and term for lactic acidosis has been updated, Hyperactivity has been moved to be listed under psychiatric disorders and repeated information from 4.4 has been removed.

-section 4.9 Editorial changes to reflect latest QRD template

-section 5.2 spelling of sulfate updated

-section 6.1 Editorial changes to reflect latest QRD template

-section 6.3 Editorial changes to reflect latest QRD template

-section 6.6 Editorial changes to reflect latest QRD template

-section 9 Editorial changes to reflect latest QRD template

-section 10 updated revision date

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.2 - Posology and method of administration
• Change to section 4.3 - Contraindications
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.8 - Undesirable effects
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 05-Mar-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



- Section 4.1 Change in premature labour indication as per PRAC recommendation
- Section 4.2 updated posology and method of adminstration information for premature labour as per PRAC recommendation

-Section 4.3 new contraindications for premature labour as per PRAC recommendation

-section 4.4 new information under the tocolysis section as per PRAC recommendation

-Section 4.5 new information on halogenated anaesthetics, corticosteroids, anti diabetics, potassium depleting agents as per PRAC recommendation

-Section 4.8 new side effects added in preterm labour section and change in frequency of some side effects as per PRAC recommendation

-Section 10 Change in revision date

 

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 4.9 - Overdose
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 13-Nov-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4 Information on Lactic acidosis added

Section 4.8 Lactic acidosis added as side effect, AE Reporting statement added, minor editorial changes

Section 4.9 cross reference added

Section 10 Update to "Date of Revision"

Reasons for adding or updating:

• Change to section 4.3 - Contraindications
• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 4.8 - Undesirable Effects
• Change to section 9 - Date of first Authorisation/renewal of the Authorisation
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 30-Mar-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.3

Replacement of paragraph 1:

 

‘Bricanyl solution for injection should not be used as a tocolytic agent in patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease.’

 

Replacement of bullet point:

·         ‘any condition of the mother or foetus in which prolongation of the pregnancy is hazardous, e.g. severe toxaemia, anti-partum haemorrhage, intra-uterine infection, intrauterine infection, severe preeclampsia, abruptio placentae, threatened abortion during the 1^st and 2^nd trimester, or cord compression.’

Addition of last paragraph:

 

‘Bricanyl solution for injection should not be used in patients with a history of hypersensitivity to any of the ingredients.’

Section 4.4

Replacement of text with:

 

‘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.

Tocolysis
Bricanyl should be used with caution in tocolysis and supervision of cardiorespiratory function, including ECG monitoring, should be considered. 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 pre-existing heart disease (see section 4.3, Contraindications).

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.

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.

In treatment of premature labour, hyperglycaemia and ketoacidosis have been found in pregnant women with diabetes after treatment with beta₂-agonists. It may therefore be necessary to adjust the insulin dose when beta₂-agonists are used in the treatment.

Increased tendency to uterine bleeding has been reported in connection with Caesarian section. However, this can be effectively stopped by propranolol 1-2 mg injected intravenously.

Respiratory indications
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.

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.’

Section 4.8

Replacement of text with:

 

‘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 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).

Bronchial asthma. Chronic bronchitis, emphysema and other lung diseases where bronchospasm is a complicating factor.

Frequency Classification	Adverse Drug Reaction
	System Organ Class (SOC)	Preferred term (PT)
Very Common (>1/10)	Nervous System Disorders	Tremor Headache
Common (>1/100, <1/10)	Cardiac Disorders	Tachycardia Palpitations
	Musculoskeletal and Connective Tissue Disorders #	Muscle spasms
	Metabolism and Nutrition Disorders	Hypokalaemia (see section 4.4)
Not Known ^	Cardiac Disorders	Arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia and extrasystoles Myocardial ischaemia (see section 4.4)
	Vascular Disorders	Peripheral vasodilation
	Immune System Disorders	Hypersensitivity reactions including angioedema, bronchospasm, hypotension and collapse
	Gastrointestinal Disorders	Nausea Mouth and throat irritation
	Psychiatric Disorders	Sleep disorder and Behavioural disturbances, such as agitation and restlessness
	Respiratory, Thoracic and Mediastinal Disorders	Paradoxical bronchospasm *
	Skin and Subcutaneous Tissue Disorders	Urticaria Rash

^# 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.

Preterm labour

Frequency Classification	Adverse Drug Reaction
	System Organ Class (SOC)	Preferred term (PT)
Very Common (>1/10)	Cardiac Disorders	Tachycardia
	Nervous System Disorders	Tremor Headache
	Gastrointestinal Disorders	Nausea
Common (>1/100, <1/10)	Cardiac Disorders	Palpitations
	Metabolism and Nutrition Disorders	Hypokalaemia (see section 4.4)
Not Known ^	Blood and Lymphatic System Disorders	An increased tendency to bleeding in connection with caesarean section
	Vascular Disorders	Peripheral vasodilation
	Immune System Disorders	Hypersensitivity reactions including angioedema, bronchospasm, hypotension and collapse
	Cardiac Disorders	Arrhythmias, e.g. atrial  fibrillation, supraventricular  tachycardia and extrasystoles Myocardial ischaemia (see section 4.4)
	Respiratory, Thoracic and Mediastinal Disorders	Symptoms of pulmonary oedema Paradoxical bronchospasm *
	Gastrointestinal Disorders	Mouth and throat irritation
	Psychiatric Disorders	Sleep disorder and Behavioural disturbances, such as agitation and restlessness
	Nervous System Disorders	Hyperactivity
	Metabolism and Nutrition Disorders	Hyperglycaemia Hyperlactacidaemia
	Skin and Subcutaneous Tissue Disorders	Urticaria Rash
	Musculoskeletal and Connective Tissue Disorders #	Muscle spasms

    

# 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.

During treatment of preterm labour, when high doses of Bricanyl are used, diabetic mothers may develop hyperglycaemia and lactacidosis. In these patients glucose and acid-base balance should be carefully monitored. High doses of beta₂-stimulants may cause hypokalaemia as a result of redistribution of potassium. Symptoms of pulmonary oedema have also been reported following treatment of preterm labour, in some cases this has proved fatal. Predisposing factors include fluid overload, multiple pregnancy, pre-existing cardiac disease and maternal infection. Close monitoring of the patient’s state of hydration is essential. If signs of pulmonary oedema develop (e.g. cough, shortness of breath), treatment should be discontinued immediately and diuretic therapy instituted.

An increased tendency to bleeding has been described in connection with caesarean section (give propranolol, 1-2 mg i.v.) in patients treated with Bricanyl for preterm labour.’

Section 9

Change of date:

4^th June 2002 / 12^th May 2007

 

Section 10

Change of date:

30^th March 2009

 

Reasons for adding or updating:

• Change to section 4.4 - Special Warnings and Precautions for Use
• Change to section 4.5 - Interactions with other Medicaments and other forms of Interaction
• Change to section 4.6 - Pregnancy and Lactation
• Change to section 4.8 - Undesirable Effects
• Change to section 4.9 - Overdose
• Change to section 5.3 - Preclinical Safety Data

Reasons for adding or updating:

• Change to section 2 - qualitative and quantitative composition
• Change to section 3 - pharmaceutical form
• Change to section 4.2 - Posology and Method of Administration
• Change to section 4.3 - Contra-indications
• Change to section 4.4 - Special Warnings and Precautions for Use
• Change to section 4.8 - Undesirable Effects
• Change to section 4.9 - Overdose
• Change to section 6.2 - Incompatibilities
• Change to section 6. 4 - Special Precautions for Storage
• Change to section 10 (date of (partial) revision of the text
• Change to section 9 - Date of Renewal of Authorisation

Reasons for adding or updating:

• Change to section 7 - Marketing Authorisation Holder
• Change to section 8 - MA number
• Change to section 9 - Date of Renewal of Authorisation
• Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

• New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC

Reasons for adding or updating:

• No reasons supplied