Drugs List

Therapeutic Indications

Uses

Chronic obstructive pulmonary disease
Prevention of exercise-induced bronchospasm
Prophylaxis of bronchial asthma where inhaled corticosteroid is indicated
Symptom relief of broncho-obstruction in asthma when steroids insufficient
Symptom relief of bronchospasm in chronic obstructive pulmonary disease

Contraindications

Children under 6 years

Precautions and Warnings

Children 6 to 12 years
Arterial aneurysm
Breastfeeding
Cardiac arrhythmias
Cardiac disorder
Diabetes mellitus
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hyperthyroidism
Hypertrophic obstructive cardiomyopathy
Hypokalaemia
Idiopathic subvalvular aortic stenosis
Ischaemic heart disease
Lactose intolerance
Long QT syndrome
Occlusive peripheral vascular disorder
Phaeochromocytoma
Pregnancy
Severe decompensated cardiac failure
Severe hypertension
Third degree atrioventricular block
Thyrotoxicosis

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Therapy should not be initiated during exacerbation of asthma
Advise patient dizziness may affect ability to drive or operate machinery
Do not substitute for steroid therapy
Not all available brands are licensed for all indications
Not all available brands are licensed for use in children under 12 years
Not to be used as the sole or main treatment for severe or unstable asthma
Some formulations contain lactose
Check patient is using correct inhaler technique
If frequent need for prophylaxis of exercise induced asthma,review therapy
Monitor serum K+ in patients on high dose steroids/xanthines/diuretics
Monitor serum potassium regularly in patients with severe asthma
CSM (CHM) requests reporting of adverse reactions to cfc-free inhalers
Discontinue at least 12 hours before the start of anaesthesia
Do not withdraw this drug suddenly
Discontinue if paradoxical bronchospasm occurs
Maintain treatment at the lowest effective dose
Advise patient not to exceed stated dose
Advise patient that CFC-free inhalers may have different taste or sensation
Advise patient to continue taking corticosteroid therapy
Patient should seek medical advice if usual relief is diminished

To ensure safe use in the management of chronic asthma, long-acting beta-2 agonists should:

Be added only if regular use of standard-dose inhaled corticosteroids has failed to control asthma adequately;
Not be initiated in patients with rapidly deteriorating asthma;
Be introduced at a low dose and the effect properly monitored before considering dose increase;
Be discontinued in the absence of benefit;
Not to be used for the relief of exercise-induced asthma symptoms unless regular inhaled corticosteroids are also used;
Be reviewed as clinically appropriate: stepping down therapy should be considered when good long-term asthma control has been achieved.

Patients should be advised to report any deterioration in symptoms following initiation of treatment with a long-acting beta-2 agonist.

Pregnancy and Lactation

Pregnancy

Use with caution during pregnancy.

It is not know if formoterol crosses the human placenta. The molecular weight of the dihydrate fumarate salt (about 841), low protein binding, and prolonged elimination half-life suggest that the drug will pass to the embryo and/or foetus. However, the mean steady state plasma concentrations of the drug after twice daily dosing ranged from 4.0 to 8.8 picograms/ml. Thus, very low drug concentrations will be available for placental transfer at the maternal-foetal interface.

The animal data suggests low risk, but the limited human pregnancy experience prevents a more complete assessment of the embryo/foetal risk. However, there is no published evidence that drugs in this class cause developmental toxicity (growth retardation, structural defects, functional/behaviour defects, or death).

Although formoterol has potent tocolytic activity in rodents, this effect has not been studied in humans. Moreover, the systemic bioavailability of the drug after inhalation is probably too low to inhibit uterine activity.

Potential toxic effects of formoterol are maternal hyperglycaemia (especially in diabetics) resulting in newborn hypoglycaemia and maternal pulmonary oedema (especially when used with corticosteroids).

Although published studies of these potential adverse effects from inhaled formoterol have not been located, the reported plasma drug concentrations appear to be too low to cause these toxicities. Because of the availability of extensive human pregnancy experience, either salbutamol or salmeterol would be a better choice if a pregnant woman required an inhaled beta-adrenergic bronchodilator. However, if a non-pregnant woman had a good response to inhaled formoterol, it would be reasonable to continue her on this drug during pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use with caution during breastfeeding

No data is available on formoterol's transfer into human milk, but its extremely low plasma levels (4.0 to 8.8 picograms/ml) would suggest that milk levels would be incredibly low, if even measurable.

It is not likely the amount present in human milk would be clinically relevant to a breastfed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agitation
Angina pectoris
Angioedema
Anxiety
Arrhythmias
Atrial fibrillation
Behavioural disturbances
Blood pressure changes
Bronchospasm
Bronchospasm (paradoxical)
CNS stimulation
Cough
Dizziness
Dry mouth
Dysgeusia
Dyspnoea
Exacerbation of pre-existing asthma
Exanthema
Hallucinations
Headache
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypokalaemia
Hypotension
Insomnia
Muscular cramps
Myalgia
Nausea
Nephritis
Nervousness
Oropharyngeal irritation
Palpitations
Peripheral oedema
Prolongation of QT interval
Pruritus
Rash
Restlessness
Sleep disturbances
Supraventricular tachycardia
Tachycardia
Taste disturbances
Thrombocytopenia
Tremor
Urticaria
Ventricular extrasystoles

Presentation

Inhalation formulations of formoterol fumarate

Drugs List

Therapeutic Indications

Uses

Chronic obstructive pulmonary disease
Prevention of exercise-induced bronchospasm
Prophylaxis of bronchial asthma where inhaled corticosteroid is indicated
Symptom relief of broncho-obstruction in asthma when steroids insufficient
Symptom relief of bronchospasm in chronic obstructive pulmonary disease

Dosage

Adults

Children

Contraindications

Children under 6 years

Precautions and Warnings

Children 6 to 12 years
Arterial aneurysm
Breastfeeding
Cardiac arrhythmias
Cardiac disorder
Diabetes mellitus
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
Hyperthyroidism
Hypertrophic obstructive cardiomyopathy
Hypokalaemia
Idiopathic subvalvular aortic stenosis
Ischaemic heart disease
Lactose intolerance
Long QT syndrome
Occlusive peripheral vascular disorder
Phaeochromocytoma
Pregnancy
Severe decompensated cardiac failure
Severe hypertension
Third degree atrioventricular block
Thyrotoxicosis

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Therapy should not be initiated during exacerbation of asthma
Advise patient dizziness may affect ability to drive or operate machinery
Do not substitute for steroid therapy
Not all available brands are licensed for all indications
Not all available brands are licensed for use in children under 12 years
Not to be used as the sole or main treatment for severe or unstable asthma
Some formulations contain lactose
Check patient is using correct inhaler technique
If frequent need for prophylaxis of exercise induced asthma,review therapy
Monitor serum K+ in patients on high dose steroids/xanthines/diuretics
Monitor serum potassium regularly in patients with severe asthma
CSM (CHM) requests reporting of adverse reactions to cfc-free inhalers
Discontinue at least 12 hours before the start of anaesthesia
Do not withdraw this drug suddenly
Discontinue if paradoxical bronchospasm occurs
Maintain treatment at the lowest effective dose
Advise patient not to exceed stated dose
Advise patient that CFC-free inhalers may have different taste or sensation
Advise patient to continue taking corticosteroid therapy
Patient should seek medical advice if usual relief is diminished

To ensure safe use in the management of chronic asthma, long-acting beta-2 agonists should:

Be added only if regular use of standard-dose inhaled corticosteroids has failed to control asthma adequately;
Not be initiated in patients with rapidly deteriorating asthma;
Be introduced at a low dose and the effect properly monitored before considering dose increase;
Be discontinued in the absence of benefit;
Not to be used for the relief of exercise-induced asthma symptoms unless regular inhaled corticosteroids are also used;
Be reviewed as clinically appropriate: stepping down therapy should be considered when good long-term asthma control has been achieved.

Patients should be advised to report any deterioration in symptoms following initiation of treatment with a long-acting beta-2 agonist.

Pregnancy and Lactation

Pregnancy

Use with caution during pregnancy.

It is not know if formoterol crosses the human placenta. The molecular weight of the dihydrate fumarate salt (about 841), low protein binding, and prolonged elimination half-life suggest that the drug will pass to the embryo and/or foetus. However, the mean steady state plasma concentrations of the drug after twice daily dosing ranged from 4.0 to 8.8 picograms/ml. Thus, very low drug concentrations will be available for placental transfer at the maternal-foetal interface.

The animal data suggests low risk, but the limited human pregnancy experience prevents a more complete assessment of the embryo/foetal risk. However, there is no published evidence that drugs in this class cause developmental toxicity (growth retardation, structural defects, functional/behaviour defects, or death).

Although formoterol has potent tocolytic activity in rodents, this effect has not been studied in humans. Moreover, the systemic bioavailability of the drug after inhalation is probably too low to inhibit uterine activity.

Potential toxic effects of formoterol are maternal hyperglycaemia (especially in diabetics) resulting in newborn hypoglycaemia and maternal pulmonary oedema (especially when used with corticosteroids).

Although published studies of these potential adverse effects from inhaled formoterol have not been located, the reported plasma drug concentrations appear to be too low to cause these toxicities. Because of the availability of extensive human pregnancy experience, either salbutamol or salmeterol would be a better choice if a pregnant woman required an inhaled beta-adrenergic bronchodilator. However, if a non-pregnant woman had a good response to inhaled formoterol, it would be reasonable to continue her on this drug during pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use with caution during breastfeeding

No data is available on formoterol's transfer into human milk, but its extremely low plasma levels (4.0 to 8.8 picograms/ml) would suggest that milk levels would be incredibly low, if even measurable.

It is not likely the amount present in human milk would be clinically relevant to a breastfed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Agitation
Angina pectoris
Angioedema
Anxiety
Arrhythmias
Atrial fibrillation
Behavioural disturbances
Blood pressure changes
Bronchospasm
Bronchospasm (paradoxical)
CNS stimulation
Cough
Dizziness
Dry mouth
Dysgeusia
Dyspnoea
Exacerbation of pre-existing asthma
Exanthema
Hallucinations
Headache
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypokalaemia
Hypotension
Insomnia
Muscular cramps
Myalgia
Nausea
Nephritis
Nervousness
Oropharyngeal irritation
Palpitations
Peripheral oedema
Prolongation of QT interval
Pruritus
Rash
Restlessness
Sleep disturbances
Supraventricular tachycardia
Tachycardia
Taste disturbances
Thrombocytopenia
Tremor
Urticaria
Ventricular extrasystoles

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2013

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Atimos Modulite 12 micrograms. Trinity-Chiesi Pharmaceuticals Ltd. Revised November 2012.

Summary of Product Characteristics: Foradil. Novartis Pharmaceuticals UK Ltd. December 2012.

Summary of Product Characteristics: Formoterol Easyhaler 12 micrograms. Oriorn Pharma (UK) Ltd. Revised September 2011.

Summary of Product Characteristics: Oxis Turbohaler 6. Astra Pharmaceuticals Ltd. Revised August 2010.

Summary of Product Characteristics: Oxis Turbohaler 12. Astra Pharmaceuticals Ltd. Revised August 2010.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 30 June 2017