Atrodil: composition and form
One inhaled dose contains 21 µg of ipratropium bromide monohydrate, equivalent to 20 µg of ipratropium bromide. It is a metered-dose aerosol in a pressurised canister, made for 200 doses. The canister is not transparent and there is no way to see whether it is already empty — hence all the handling rules, set out in the product information in more detail than for most inhalers.
| When | What to do |
| Before every use | shake the inhaler, but not too vigorously |
| Inhaler new or unused for 3 days or more | shake it and release 2 doses into the air to check it works |
| A second dose is needed straight after | wait at least one minute, shake again and repeat |
| Once a week | take off the cap and canister, rinse the mouthpiece with warm water and let it air-dry |
| 200 doses used up | replace the inhaler even if some liquid is left in the canister |
Every point here has a practical reason. After two hundred doses some solution is still there, but it may no longer deliver a full dose. The mouthpiece is washed so that the medicine does not build up on its walls and block the inhaler, and it is dried in the air only, with no drying devices. The plastic mouthpiece was designed for this aerosol in particular: it must not be used with another aerosol, nor this aerosol with someone else's mouthpiece. The canister is under pressure — it is not forced open and not exposed to temperatures above 50 °C.
How Atrodil works
The product information warns about the speed of action separately, and that matters more than any theory: the onset of action of ipratropium bromide is slower than that of inhaled sympathomimetic bronchodilators. The medicine therefore does not work where an immediate effect is needed. Its mechanism is of a different order: the active substance is a quaternary ammonium derivative with anticholinergic, that is parasympatholytic, properties.
Preclinical studies indicate that, as an antagonist of acetylcholine — the neurotransmitter released from the vagus nerve — the substance inhibits reflexes conducted along that nerve. The chain then descends to the cellular level: anticholinergics prevent a rise in the intracellular concentration of calcium ions, while the effect of acetylcholine on the muscarinic receptors of bronchial smooth muscle is achieved through a second messenger system made up of inositol triphosphate and diacylglycerol. Put simply, the medicine does not stimulate the widening of the bronchi directly: it lifts the command to narrow them.
Indications
There is one indication and it is worded through the medicine's role: it is used as a bronchodilator in the maintenance treatment of bronchospastic states. Two circles of disease are named: chronic obstructive pulmonary disease, taking in chronic bronchitis and pulmonary emphysema, and bronchial asthma.
The key word here is "maintenance". It ties in with what is said about how quickly the effect arrives: the medicine is meant for regular use and for holding the condition steady, not for breaking a sudden attack. That is exactly why the dosing section records separately that with sudden or rapidly worsening breathlessness one must contact a doctor at once rather than increase the number of inhalations.
Administration and dosage
The dose is matched to the individual needs of the patient, who during treatment should remain under a doctor's care. Unless the doctor prescribes otherwise, adults and children over 6 are recommended 2 metered doses four times a day. The recommended daily dose must not be exceeded either in treating acute states or in maintenance treatment, and the overall ceiling is 12 actuations a day. The very appearance of a need to raise the dose is interpreted in the product information unambiguously: it is a sign that other medicines have to be added to the treatment, not that this one should be pushed higher.
When to contact a doctor is set out separately. First, if the treatment brings no noticeable improvement or the condition worsens — then the doctor draws up a new treatment plan. Second, without delay, with sudden or rapidly worsening breathlessness. For children there is an additional condition: information on use in them is insufficient, so the aerosol is used only on a doctor's prescription and under an adult's supervision. And a general remark with which the product information closes the section: correct use has a significant bearing on the effectiveness of treatment, so the inhaler instructions must be read carefully.
Contraindications
There is one prohibition here: hypersensitivity to the active substance, to atropine and its derivatives, or to any excipient. The mention of atropine is not accidental — ipratropium bromide belongs to the same anticholinergic family, and intolerance of one member of that family extends to the others.
Everything else one might expect in this section has been moved to the warnings and worded as caution rather than prohibition: diseases obstructing urinary outflow, a tendency to narrow-angle glaucoma, cystic fibrosis. The difference matters. Those conditions do not rule out prescribing, but they do require the doctor to know about them in advance and to understand what to watch for.
Special warnings and precautions
The fullest part of the section is devoted to the eyes, and the reason lies in how the medicine is given. A few reports are described of eye complications — pupil dilation, raised intraocular pressure, narrow-angle glaucoma, eye pain — after the aerosol came into contact with the eyes; this concerns ipratropium bromide alone as well as its combination with a beta2-adrenoceptor agonist. The signs of acute narrow-angle glaucoma are described so that they can be recognised unaided: pain or discomfort in the eye, blurred vision, a rainbow halo around a light source or altered colour vision together with redness of the eyes from conjunctival congestion and corneal oedema. If any combination of these appears, treatment with pupil-constricting drops is started and a specialist is consulted at once. Prevention is simple: keep the aerosol mist out of the eyes; when it is given through a manually controlled mask the risk is smaller.
The remaining warnings are shorter. Immediate hypersensitivity reactions are possible — rare cases of rash, urticaria, angioedema, swelling of the mucosa of the mouth and throat, bronchospasm and anaphylaxis confirm it. Caution is needed with diseases obstructing urinary outflow, prostatic enlargement or bladder neck narrowing for instance. Patients with cystic fibrosis are more prone to disturbances of gastrointestinal motility, and anticholinergics are given to them with care. As with other inhaled medicines, bronchospasm with a sudden increase in wheezing is possible: a fast-acting inhaled bronchodilator is then given at once, ipratropium is stopped, the patient is reassessed and, if necessary, alternative treatment is started. The composition includes ethanol — 8.42 mg of anhydrous alcohol per metered dose, that is under 100 mg per dose. No studies of the effect on driving have been carried out, but dizziness, accommodation disturbances, pupil dilation and visual disturbances are possible, and if they appear, dangerous activities such as driving are avoided.
Interactions with other medicines
The interactions section of this medicine is one of the shortest and comes down to two thoughts. The first: products acting on beta-adrenoceptors and xanthine derivatives may enhance the bronchodilating action. That is not a warning but a description of compatibility — combining ipratropium with beta2-agonists and theophylline belongs to ordinary practice in obstructive lung disease.
The second thought concerns its own class. No studies of long-term use of ipratropium bromide together with other anticholinergic products have been carried out, and precisely for that reason such long-term combination is not recommended. The wording is worth noting: this is not proven harm but an absence of data from which a cautious conclusion has been drawn. In practice it means that if you already have another anticholinergic prescribed — inhaled or otherwise — the doctor should know about it.
Pregnancy and breastfeeding
The safety of ipratropium bromide in pregnancy has not been established. The decision is therefore taken by weighing it up: one has to consider whether the therapeutic benefits of using the medicine in a confirmed or suspected pregnancy outweigh the potential risk to the fetus. Some ground for calm comes from the preclinical work: studies showed no embryotoxic or teratogenic effect of ipratropium bromide given by inhalation or intranasally at doses well above those recommended in humans.
Whether ipratropium bromide passes into human milk is unknown. The product information holds it unlikely that the substance would reach the infant in any meaningful amount — but still requires caution when using it in breastfeeding women. As for fertility, preclinical studies showed no negative effect, and clinical data on the effect of ipratropium bromide on fertility do not exist.
Adverse reactions
A large share of the adverse reactions can be put down to the anticholinergic properties of the substance, and part of them to the fact that this is an inhaled medicine: like any aerosol it can cause symptoms of local irritation. In clinical trials the most frequently reported were headache, throat irritation, cough, dryness of the oral mucosa, disturbances of gastrointestinal motility including constipation, diarrhoea and vomiting, and also nausea and dizziness.
By system the picture is this. Commonly: headache and dizziness, throat irritation and cough, dry mouth, nausea and disturbed gastrointestinal motility. Uncommonly: hypersensitivity and anaphylactic reactions; on the eye side, blurred vision, pupil dilation, raised intraocular pressure, glaucoma, eye pain, visual halo, conjunctival congestion and corneal oedema; on the cardiac side, palpitations and supraventricular tachycardia; bronchospasm including the paradoxical kind, laryngospasm, swelling of the pharyngeal mucosa and dry throat; diarrhoea, constipation, vomiting, stomatitis and swelling of the mouth; rash, itching, angioedema; urinary retention. Rarely recorded were accommodation disturbances, atrial fibrillation, an accelerated heart rate and urticaria.
Overdose
The manifestations to be expected are few and familiar: dryness of the oral mucosa, accommodation disturbances and an accelerated heart rate. These are mild systemic symptoms of anticholinergic action — the same ones listed among the adverse reactions of ordinary use, only here they are treated as a consequence of exceeding the dose.
Symptoms typical of overdose as such, on the other hand, have not been established, and the explanation follows at once: the medicine has a wide therapeutic range and is given locally. Serious manifestations of anticholinergic action from an overdose are not to be expected. In practice this means that one extra press of the canister calls for no emergency measures — but neither does it cancel the ceiling of 12 actuations a day set in the dosing section.
How to get a prescription for Atrodil online
With this inhaler one mistake is the most common: taking it for a rescue medicine. The onset of action of ipratropium is slower than that of inhaled sympathomimetics, and it is prescribed for maintenance treatment, so the doctor needs to understand what exactly you are relieving with it and what you use during an attack. 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 — chronic obstructive pulmonary disease or bronchial asthma — and list every inhaler you use, the rescue one included. Write how many actuations a day you need now: approaching twelve means the regimen has to be changed, not the dose raised. Be sure to report glaucoma or a predisposition to narrow-angle glaucoma, prostatic enlargement and any difficulty passing urine, cystic fibrosis, intolerance of atropine and its derivatives, pregnancy and breastfeeding. Name separately any other anticholinergic medicines you have been prescribed: their long-term combination with ipratropium is not recommended. And give the child's age if the prescription is for them: the medicine is used from the age of 6 and only under an adult's supervision.
