Fostex: composition and form
Fostex is a pressurised metered-dose inhaler holding two active substances: beclometasone dipropionate, an inhaled corticosteroid, and formoterol fumarate dihydrate, a long-acting beta2-agonist. There are two strengths and they differ only in the steroid dose; the formoterol is the same in both.
| Strength | Metered dose | Delivered dose |
| 100 µg + 6 µg | 100 µg beclometasone, 6 µg formoterol | 84.6 µg beclometasone, 5 µg formoterol |
| 200 µg + 6 µg | 200 µg beclometasone, 6 µg formoterol | 177.7 µg beclometasone, 5.1 µg formoterol |
The difference between the metered and the delivered dose is the difference between what leaves the valve and what leaves the actuator. The inhaler carries a dose counter or a dose indicator: in the 120-dose pack the counter goes down by one with every press; in the 180-dose pack the indicator shows what is left in steps of 20. A new inhaler is bought when the scale reads 20, and the old one is put aside at zero: what remains in the canister may not be enough for a full dose.
How Fostex works
The two active substances work in different ways, and that is the point of the combination: as with other pairings of an inhaled corticosteroid with a beta2-adrenoceptor agonist, their joint action reduces the frequency of asthma exacerbations. The steroid works against inflammation in the airways, the beta2-agonist widens the bronchi, and neither replaces the other.
What is particular to this medicine is the particle size. The beclometasone here distributes through the airways as extrafine particles do, and for that reason acts more strongly than the ordinary form: 100 µg of extrafine beclometasone is equivalent to 250 µg of the larger-particle form. From this follows a practical conclusion that is easy to miss: the total daily dose of beclometasone here should be lower than the customary one, and when a patient is switched from large-particle beclometasone the dose is reduced.
Indications
The main indication is the regular treatment of asthma requiring a combination of an inhaled corticosteroid and a long-acting beta2-agonist. The wording covers two situations: either symptoms are not adequately controlled by a corticosteroid together with an as-needed fast-acting beta2-agonist, or control has already been achieved with both components taken separately. Both strengths are for adults.
The 100 µg + 6 µg strength has a second indication: symptomatic treatment of severe COPD. The group of patients is drawn sharply: a forced expiratory volume in one second below 50% of predicted, repeated exacerbations in the past, and clear symptoms persisting despite regular treatment with long-acting bronchodilators. The 200 µg + 6 µg strength is used in asthma only.
Administration and dosage
The first thing the product information says about doses: the medicine is not intended for the initial period of asthma treatment. The doses of the components are matched to the severity of the disease and, if the combination needed does not coincide with the ready strengths, the beta2-agonist and the corticosteroid are prescribed in separate inhalers. Then a choice is made between two strategies. Maintenance therapy: the medicine is taken regularly, and for relief of symptoms another fast-acting bronchodilator is carried; adults from 18 are given 1 or 2 inhalations twice a day, at most 4 a day. Maintenance and reliever therapy: the same medicine serves both as regular treatment and as the reliever; the maintenance dose is 1 inhalation in the morning and 1 in the evening, an extra one is taken when symptoms appear and, if they persist after a few minutes, one more, up to a maximum of 8 a day.
The second strategy is considered above all in those whose asthma is inadequately controlled or who have had an exacerbation requiring medical attention. If many reliever inhalations are needed, that is a reason to see the doctor and review the maintenance treatment, not to raise their number further. In COPD there is one dose: 2 inhalations twice a day. In older people no adjustment is needed, and there are no data on use in liver or kidney disease. Below 18 it is not recommended: on use under 12 there are no data at all, and for ages 12 to 17 they are limited. It has to be taken every day, even when there are no symptoms, and once control is achieved the dose is gradually lowered to the smallest effective one.
Contraindications
The contraindications section fits into a single line: hypersensitivity to beclometasone dipropionate, to formoterol fumarate dihydrate or to any excipient. There are no further prohibitions — none by age, none by concomitant illness, none by pregnancy.
That does not mean the limits are few. Everything that with other medicines is carried into the contraindications stands here in the warnings section, worded as "use with caution" — from arrhythmias and QTc prolongation to thyrotoxicosis and pulmonary tuberculosis. The difference is practical: such conditions do not close the door to the medicine automatically, but they do require the doctor to know about them before prescribing.
Special warnings and precautions
The first circle of warnings is the heart and metabolism, and it comes from the formoterol. Caution is needed with rhythm disturbances, especially third-degree atrioventricular block and tachyarrhythmia, with subvalvular aortic stenosis, hypertrophic cardiomyopathy, severe heart disease — infarction, ischaemic heart disease, congestive failure — and with obliterative vascular disease and aneurysm. Named separately is a prolonged QTc interval above 0.44 seconds, congenital or drug-induced: formoterol itself can lengthen it. Caution is required in thyrotoxicosis, diabetes, phaeochromocytoma and uncorrected hypokalaemia. Treatment with a beta2-agonist can cause potentially severe hypokalaemia, and the risk rises in severe asthma because of hypoxia. Inhaled formoterol raises blood glucose, so in people with diabetes it is watched closely. If anaesthesia with halogenated agents is planned, the medicine is not taken for at least 12 hours beforehand: otherwise the risk of arrhythmia grows.
The second circle is the steroid one. Inhaled corticosteroids at high doses and over a long time can produce systemic effects: Cushing's syndrome, adrenal suppression, reduced bone density, growth retardation in children, cataract and glaucoma, and less often psychiatric disturbances ranging from anxiety to depression and aggression. Long treatment with high doses can lead to acute adrenal crisis, brought on by trauma, surgery, infection or an abrupt dose reduction; the symptoms are non-specific — loss of appetite, abdominal pain, weight loss, a fall in blood pressure, clouded consciousness, seizures. That is why before planned procedures and in periods of stress an additional systemic corticosteroid is considered. In patients with COPD receiving inhaled corticosteroids, pneumonia is recorded more often, including pneumonia requiring hospital admission; the risk factors are smoking, older age, a low body mass index and severe disease, and its symptoms are easily confused with an exacerbation. Of the practical points: the medicine is suitable neither as first-line treatment nor for prevention before exertion; if paradoxical bronchospasm follows a dose it is stopped at once; after every inhalation the mouth is rinsed with water, which lowers the risk of candidiasis; treatment is not broken off abruptly. The AeroChamber Plus spacer does not increase systemic exposure, and each actuation contains about 7 mg of ethanol.
Interactions with other medicines
Beclometasone is metabolised very rapidly by esterases and without the involvement of cytochrome P450, so almost all the significant interactions run on the formoterol side. The main prohibition is beta-blockers, eye drops included: in asthma they are avoided, and if their use is unavoidable the action of formoterol weakens or disappears altogether. Other beta-adrenergic agents and theophylline, by contrast, add to its effect.
The second group concerns heart rhythm. Quinidine, disopyramide, procainamide, phenothiazines, antihistamines, monoamine oxidase inhibitors and tricyclic antidepressants lengthen the QTc interval and raise the risk of ventricular arrhythmias. L-dopa, L-thyroxine, oxytocin and alcohol worsen the heart's tolerance of beta2-sympathomimetics, and combining them with monoamine oxidase inhibitors and related substances — furazolidone, procarbazine — can raise blood pressure. Anaesthesia with halogenated hydrocarbons is named separately: the risk of arrhythmias is higher with it. The third group concerns potassium: xanthines, steroids and diuretics enhance the hypokalaemic action of beta2-agonists, and hypokalaemia increases the tendency to arrhythmia in people on digitalis glycosides. And a theoretical caveat: because of the ethanol, an interaction is possible in especially sensitive patients taking disulfiram or metronidazole.
Pregnancy and breastfeeding
There are no data in humans. In animal studies high doses of beclometasone were associated with reduced fertility in female rats and with toxicity to the fetus, and when it was combined with formoterol, evidence of harm to reproduction was obtained. There is no experience with the HFA-134a propellant in pregnant women, although in animals it produced no clinically relevant effects on embryonic development. A separate matter is the tocolytic action of beta2-sympathomimetics, that is their ability to relax the uterus: because of it particular caution applies from conception until delivery, and formoterol is not recommended in pregnancy, especially in its late stage and during labour, unless there is no safer alternative. The general conclusion: the medicine is used in pregnancy only if the expected benefit outweighs the possible risk.
Nor are there clinical data on breastfeeding women. No animal studies were done on this, but it should be assumed that beclometasone, like other corticosteroids, passes into breast milk. Whether formoterol passes into it in humans is unknown, though it has been detected in the milk of lactating animals. Use in a breastfeeding woman is considered only where the benefit outweighs the risk, and the decision is taken as a choice: to stop breastfeeding or to stop the treatment.
Adverse reactions
Since the medicine holds two substances, the reactions to expect are those belonging to each of them; no additional effects from their combination have been noted. Commonly there are pharyngitis, oral candidiasis, headache and dysphonia, that is hoarseness, and in patients with COPD pneumonia as well. Uncommonly described are influenza, fungal infections of the mouth and throat, oesophageal and vulvovaginal candidiasis, sinusitis, rhinitis, granulocytopenia, allergic dermatitis, hypoglycaemia and hyperglycaemia, restlessness, tremor, dizziness, palpitations, QTc prolongation and other ECG changes, tachycardia, tachyarrhythmia, atrial fibrillation, flushing, cough, throat irritation, diarrhoea, dry mouth, dyspepsia, difficulty swallowing, nausea, taste disturbance, itching, rash, sweating, urticaria and muscle pain.
The rare reactions are ventricular extrasystoles, angina, paradoxical bronchospasm, angioedema and nephritis. The very rare ones: thrombocytopenia, hypersensitivity reactions with swelling of the lips, face, eyes and throat, adrenal suppression, glaucoma and cataract, breathlessness, worsening of asthma, and growth retardation in children. With unknown frequency, psychomotor hyperactivity, sleep disturbance, anxiety, depression, aggression and behavioural changes have been described, mainly in children.
Overdose
In patients with asthma, inhalation of up to twelve cumulative doses was studied — 1200 µg of beclometasone and 72 µg of formoterol in total. That had no negative effect on vital signs and no serious adverse reactions were seen. An excess of formoterol shows itself in the same way as with other beta2-adrenoceptor agonists: nausea, vomiting, headache, tremor, drowsiness, palpitations, tachycardia, ventricular arrhythmias, QTc prolongation, metabolic acidosis, hypokalaemia and hyperglycaemia.
Treatment is supportive and symptomatic; in severe cases the patient is admitted to hospital. Cardioselective beta-blockers are considered with particular care, because beta-blockade can itself provoke bronchospasm. On the beclometasone side, exceeding the doses can lead to temporary suppression of adrenal function, but that calls for no emergency measures: function returns to normal within a few days, as plasma cortisol levels confirm. Treatment continues with doses that keep symptoms under control; with excessive doses over a long period monitoring may be needed.
How to get a prescription for Fostex online
This inhaler cannot be prescribed "to try": it is not intended for starting asthma treatment and is chosen by what the patient is already using and how much it helps. So what matters to the doctor is which inhalers you use now and how often you reach for the reliever. At e-zdrowie.com you fill in a medical questionnaire, the doctor examines the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and with it any Polish pharmacy will dispense the inhaler.
In the questionnaire give the diagnosis — asthma or COPD — list your current inhalers with their doses, and state how many times a day you have to take reliever inhalations: that is precisely what decides between the two strategies. If you previously took large-particle beclometasone, write down the dose — on switching it is recalculated downwards. Report heart disease and rhythm disturbances, a prolonged QT, hypertension, diabetes, thyroid disease, tuberculosis, pregnancy and breastfeeding. List the medicines separately: beta-blockers, eye drops included, theophylline, diuretics, digitalis glycosides and antidepressants. And mention any operation coming up — before anaesthesia with halogenated agents the medicine is stopped 12 hours in advance.
