Fenoterol
Short acting beta 2 sympathomimetic for asthma and tocolysis
Fenoterol is a short acting β2 sympathomimetic first launched by Boehringer Ingelheim in 1968 as the inhaler Berotec. In pulmonology it has been a rescue bronchodilator in bronchial asthma and chronic obstructive pulmonary disease for decades. In obstetrics fenoterol was also used as a tocolytic agent for temporary suppression of labour. Its role in this indication has declined substantially since the product Partusisten left the German market; the substance is now available only in specialised compounded formulations.
The active substance binds highly selectively to β2 adrenoceptors and relaxes smooth muscle in the bronchi and the uterus. After inhalation the effect begins within a few minutes and lasts four to six hours. As with every short acting β2 agonist (SABA), fenoterol is intended as rescue medication and does not replace anti inflammatory maintenance therapy with inhaled corticosteroids in asthma.
Mechanism of Action
Fenoterol activates β2 adrenoceptors on bronchial smooth muscle. The receptor is G protein coupled; Gs activates adenylate cyclase, which raises cAMP and stimulates protein kinase A. PKA phosphorylates myosin light chain kinase and lowers intracellular calcium. Smooth muscle relaxes, the bronchial lumen widens, airway resistance and work of breathing decrease.
In obstetric use the same signalling pathway is exploited at β2 receptors of the myometrium. Contractile activity wanes, uterine tone falls. This effect is dose dependent and occurs within minutes after intravenous administration. Because β2 receptors are also expressed in blood vessels, skeletal muscle and the heart, typical systemic effects such as tachycardia, tremor and hypokalaemia appear in parallel.
β2 selectivity is relative; at higher doses fenoterol also acts on cardiac β1 receptors. Compared with salbutamol, fenoterol is considered somewhat less selective and clinically more cardiovascularly active. Data from New Zealand in the 1980s suggested increased asthma mortality at high doses, which worldwide led to dose limits and to strict combination regimens with ipratropium bromide.
Indications
- Acute asthma attack: on demand inhalation for rapid bronchodilation
- Maintenance asthma therapy (reliever): rescue medication, not as monotherapy in persistent asthma
- Chronic obstructive pulmonary disease (COPD): widely used in the combination with ipratropium bromide (Berodual)
- Exercise or allergen induced bronchoconstriction: prophylactic use 15 minutes before exposure
- Tocolysis: short term suppression of preterm labour between gestational weeks 22 and 37, as intravenous acute therapy, today often replaced by atosiban
Dosage and Administration
Inhalation in adults and adolescents: 1 to 2 puffs of 100 µg fenoterol as needed, maximum 8 puffs per day. In the combination Berodual one puff contains 50 µg fenoterol plus 20 µg ipratropium bromide. Children from 6 years: 1 puff as needed, titrated under medical supervision.
Intravenous tocolysis: under continuous circulatory and cardiotocographic monitoring in the obstetric unit, individualised to contractions, potassium level and heart rate. Renal impairment: no formal dose adjustment, caution in severe impairment because of hypokalaemia risk. Hepatic impairment: no formal adjustment required. Patients should be trained in inhalation technique; spacers increase lung deposition and reduce oropharyngeal deposition.
Side Effects
Common (1 to 10 percent): fine tremor particularly of the hands, tachycardia, palpitations, headache, restlessness, cough, dryness of the mouth and throat.
Uncommon to rare: hypokalaemia (especially in combination with diuretics or corticosteroids, clinically relevant in severe asthma), paradoxical bronchoconstriction (immediate discontinuation), cardiac arrhythmias, nausea, muscle cramps, allergic skin reactions.
Important in tocolysis: maternal adverse effects such as pulmonary oedema, myocardial ischaemia, hyperglycaemia and hypokalaemia have been reported. Particularly in twin or multiple pregnancies the risk of pulmonary oedema is increased; fluid balance monitoring and potassium control are mandatory.
Interactions
- Other sympathomimetics: additive cardiovascular effects, combination should be avoided
- Beta blockers (propranolol, non selective): antagonism of bronchodilation, avoid combination, use cardioselective β1 blockers when necessary
- Diuretics (loop diuretics, thiazides): enhanced hypokalaemia
- Systemic corticosteroids: enhanced hypokalaemia, potassium monitoring during prolonged combination
- MAO inhibitors and tricyclic antidepressants: enhanced cardiovascular effects
- Inhalation anaesthetics (halothane, enflurane): increased arrhythmia risk, particular caution during the perioperative period
Special Notes
Pregnancy: inhaled fenoterol is acceptable for urgent asthma therapy because uncontrolled bronchoconstriction represents the greater risk to mother and child. Systemic exposure after inhalation is low. Breastfeeding: passage into breast milk is minimal, inhalation is considered compatible.
Cardiovascular comorbidity: in patients with coronary heart disease, severe heart failure, tachyarrhythmias, hypertrophic cardiomyopathy or pheochromocytoma, use only under close medical supervision. Diabetes mellitus: β2 agonists can raise blood glucose; in insulin dependent diabetes more frequent monitoring is advisable.
Monitoring: check potassium in severe asthma and under combination therapy. Rising demand for reliever inhalation indicates loss of control of the underlying disease and requires reassessment of maintenance therapy. High SABA use (more than 3 inhalers per year) is internationally recognised as a marker of poor asthma control.
You might also be interested in
- Formoterol, long acting β2 sympathomimetic with rapid onset
- Budesonide, inhaled corticosteroid for maintenance therapy
- Montelukast, leukotriene receptor antagonist in asthma
- Ambroxol, secretolytic for productive cough
Frequently Asked Questions
How quickly does fenoterol work in an asthma attack?
Bronchodilation begins within one to three minutes, the peak effect is reached after around 30 minutes, and the effect lasts four to six hours. If two puffs do not bring relief, call for medical help as a severe attack may be present.
Why should I use fenoterol only as needed?
Short acting β2 sympathomimetics treat symptoms only, not the underlying airway inflammation. Regular use without anti inflammatory maintenance therapy leads to tolerance, poorer asthma control and, according to large cohort studies, an increased exacerbation rate. The cornerstone of persistent asthma therapy is the inhaled corticosteroid.
What is Berodual and how does it differ from plain fenoterol?
Berodual combines fenoterol with the anticholinergic ipratropium bromide. The two substances act on different regulatory pathways of airway narrowing. The combination is more strongly bronchodilating than either component alone and is used mainly in COPD and in severe acute asthma attacks in the emergency department.
Is fenoterol allowed in pregnancy?
Inhaled use at therapeutic doses is acceptable because untreated asthma poses the greater risk to mother and child. Systemic exposure is low. For tocolysis at higher intravenous doses a strict obstetric indication is required; today atosiban is more commonly used.
Sources
- EMA, European Medicines Agency
- AWMF, National Care Guideline Asthma
- Gelbe Liste, Fenoterol active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
Legal Notice and Disclaimer
The information provided on this page is for general informational purposes only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace consultation with a licensed physician or pharmacist. Medicines should only be taken on medical prescription or via a pharmacy. All information is based on product information and recognised scientific sources published at the time of creation; the manufacturer's current summary of product characteristics is always authoritative. Sanoliste assumes no liability for the completeness, timeliness or accuracy of the information presented. In a medical emergency, call the emergency number 112 (Europe).