Ipratropium-nativ

General characteristics. Structure:

Active ingredient: 0,261 mg of an ipratropiya of bromide monohydrate in terms of an ipratropiya bromide of 0,25 mg.

Excipients: Natrium benzoicum, dinatrium of an edetat a dihydrate (corresponds dinatrium to an edetat), citric acid monohydrate (corresponds to citric acid anhydrous), sodium hydroxide to рН 3,4±0,1, water for injections.

Pharmacological properties:

Pharmacodynamics. Ipratropiya bromide - the bronkhodilatiruyushchy means blocking m-holinoretseptory of smooth muscles of a tracheobronchial tree and overwhelming reflex narrowing of bronchial tubes (bronkhokonstriktion). Having structural similarity to acetylcholine molecule, is his competitive antagonist. Anticholinergics (m-holinoblokatory) prevent increase in intracellular concentration of calcium ions that happens owing to interaction of acetylcholine to the muskarinovy receptors located in unstriated muscles of bronchial tubes. Release of calcium ions happens to the help of secondary intermediaries (mediators) whom ITF (inositol triphosphate) and DAG is among (диациглицерол).

Ipratropiya bromide effectively prevents the narrowing of bronchial tubes resulting from inhalation of cigarette smoke, cold air, effect of various bronkhospazmiruyushchy substances and also the spasm of bronchial tubes connected with influence of a vagus nerve oppresses. At inhalation use has practically no resorptive effect. Bronkhodilatation arising after inhalation a bromide ipratropiya is, mainly, a consequence of local and specific impact of drug on lungs, but not result of its system influence.

After reception the bromide ipratropiya at patients with the bronchospasm caused by a chronic obstructive pulmonary disease is observed the significant improvement of functions of lungs within 15 minutes reaching a maximum in 1-2 hours and remaining till 4-6 o'clock.
 
Pharmacokinetics. Absorption. After inhalation 10-30% of the entered dose a bromide ipratropiya usually get into lungs (depending on a dosage form and a method of inhalation). The most part of a dose is swallowed and comes to digestive tract.

Part of a dose the bromide ipratropiya getting into lungs quickly reaches a system blood-groove (within several minutes).

The general system bioavailability an ipratropiya of the bromide applied inside it is also inhalation, makes 2% and 7-28% respectively proceeding from those data that total renal excretion (within 24 hours) initial connection makes about 46% of size of intravenously entered dose, less than 1% of the size of the dose applied inside and about 3-13% of the size of an inhalation dose a bromide ipratropiya.
Distribution

The kinetic parameters describing distribution a bromide ipratropiya were calculated on the basis of its concentration in a blood plasma after intravenous administration. Bystry two-phase decrease in concentration a bromide ipratropiya in a blood plasma is observed. The seeming distribution volume during a condition of equilibrium concentration (Css) makes primerno176 l (≅2,4 l/kg).

Ipratropiya bromide contacts proteins of a blood plasma (albumine and α-1 an acid glycoprotein) in the minimum degree (less than for 20%).

Ipratropiya the bromide which is quarternary amine does not get through a blood-brain barrier.

Metabolism. After intravenous administration the ipratropiya of bromide about 60% of a dose is metabolized by oxidation, mainly in a liver and is partially excreted with urine. The main metabolites which are removed with urine contact muskarinovy receptors poorly, and are considered as inactive. After inhalation a bromide ipratropiya about 77% of a system available dose are metabolized by hydrolysis of ester communication (41%) and conjugation (36%).

Removal

The elimination half-life (T1/2) during a terminal phase makes about 1,6 hours. The general clearance the bromide ipratropiya - makes 2,3 l/min, and renal clearance — 0,9 l/min.

Total renal excretion within 6 days marked dose isotope including initial connection and all metabolites makes after intravenous administration 72,1%, after intake — 9,3%, and after inhalation use — 3,2%. Excretion through intestines marked dose isotope, makes after intravenous administration 6,3%, after intake — 88,5%, and after inhalation use — 69,4%.

The elimination half-life (T1/2) of initial connection and metabolites at intravenous administration makes about 2-3 hours.

Indications to use:

• Chronic obstructive pulmonary disease (including chronic obstructive bronchitis, emphysema of lungs).
• Bronchial asthma (easy and moderate severity).
• Emphysema of lungs.

Route of administration and doses:

The drug Ipratropium-nativ is intended only for inhalation introduction by inhalation through a mouth by means of the nebulizer. The drug Ipratropium-nativ is not intended for injections or for intake! 20 drops of the drug Ipratropium-nativ (about 1 ml) contain 0,250 mg a bromide ipratropiya, respectively 1 drop of drug contains 0,0125 mg a bromide ipratropiya. The mode of dosing is selected individually. The drug Ipratropium-nativ needs to be used under observation of the doctor only by means of the nebulizer of any design which turns drug solution into an aerosol for inhalations.

As many nebulizers operate only in the presence of a constant flow of air, is not excluded that the sprayed drug will get to the environment. Considering it, the drug Ipratropium-nativ should be used in well aired rooms.

It is not necessary to exceed the recommended daily dose as during an urgent, and maintenance therapy! If treatment does not lead to significant improvement or if the condition of the patient worsens (unexpectedly or quickly an asthma (breath difficulty) amplifies), it is necessary to consult immediately with the doctor. If the doctor it is not appointed differently, the following mode of dosing is recommended.

The supporting treatment: adults (including elderly): on 2,0 ml of the drug Ipratropium-nativ (40 drops = 0,5 mg a bromide ipratropiya) 3 - 4 times a day. The maximum daily dose - 8,0 ml of the drug Ipratropium-nativ (2 mg a bromide ipratropiya).

Acute bronchospasm: adults (including elderly): on 2,0 ml of the drug Ipratropium-nativ (40 drops = 0,5 mg a bromide ipratropiya); repeated inhalations before stabilization of a condition of the patient, an interval are possible between, is defined inhalations by the doctor. Ipratropium-nativ it can be applied together with inhalation β2-адреномиметиками.

For ensuring the correct use of drug, please, attentively read this application instruction. The recommended drug Ipratropium-nativ dose just before use should be diluted with 0,9% chloride sodium solution before achievement of volume of drug of 3-4 ml, to fill in in the nebulizer and to make inhalation. The solution which remained not to reuse, pour out after inhalation.

Speed and duration of inhalation can depend on a method of inhalation and a type of the nebulizer. Duration of inhalation should be controlled on an expenditure of volume of the divorced drug Ipratropium-nativ. When using of the centralized oxygen system solution is better to apply at a flow rate 6 - 8 liters a minute. For inhalations it is recommended to use nebulizers with a tip for a mouth (mouthpiece). When using the nebulizer with a mask, it is necessary to use a mask of the corresponding size.

It is necessary to keep the nebulizer clean.

Features of use:

Use at pregnancy and during breastfeeding. Pregnancy: safety of use a bromide ipratropiya during pregnancy at the person is not established. At appointment a bromide ipratropiya during the possible or confirmed pregnancy it is necessary to consider a ratio of estimated advantage of purpose of drug for mother and possible risk for a fruit. Breastfeeding period: data on penetration a bromide ipratropiya in breast milk are absent. However as many drugs are removed with breast milk, it is necessary to appoint with care an ipratropiya bromide to women during breastfeeding.

It is not recommended to use the drug Ipratropium-nativ for the emergency stopping of an attack of bronchial asthma (as the broncholitic effect develops later, than at β2-адреномиметиков).

At patients with a mucoviscidosis the risk of development of disturbances of motility of digestive tract is increased.

Ipratropium-nativ it can be used for the combined inhalations along with such solutions for inhalations as: Ambroxol, Bromhexine and Fenoterolum.

The drug Ipratropium-nativ contains excipient (stabilizer)
dinatrium эдетат which during inhalation can cause narrowing of a gleam of bronchial tubes; emergence of a bronchospasm at patients with hyperreactivity of respiratory tracts is possible.

After use of the drug Ipratropium-nativ there can be reactions of immediate hypersensitivity what point cases of rash, small tortoiseshell, a Quincke's disease, hypostasis of a throat, a bronchospasm and anaphylactic reactions to.

Patients have to be able to apply Ipratropium-nativ, solution to inhalations correctly. It is not necessary to allow hits of solution in eyes! It is necessary to draw special attention to need of protection of eyes of the patients predisposed to development of glaucoma from drug Ipratropium-nativ hit. In case of any symptom of an attack of closed-angle glaucoma (eye pain, discomfort, indistinct sight, emergence of an aura and color spots before eyes in combination with a conjunctival and corneal hyperemia) it is necessary to begin use of the drops causing narrowing of a pupil and to address immediately the ophthalmologist.

Use of the drug Ipratropium-nativ does not lead to positive takes of doping tests at athletes.

Influence on ability to manage motor transport and other vehicles, for work with moving mechanisms. Data on influence of the drug Ipratropium-nativ on ability to driving of motor transport and to control of mechanisms are absent. In case of development of such side reactions as dizziness, accommodation disturbances, a mydriasis and misting of sight, it is necessary to refrain from driving of motor transport and control of mechanisms, and also from occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Many of the listed undesirable reactions can be a consequence of anticholinergic properties a bromide ipratropiya.

The drug Ipratropium-nativ as well as any inhalation therapy, can cause local irritation. The headache, irritation of a throat, cough, dryness in a mouth, disturbances of motility of digestive tract (including a lock, diarrhea and vomiting), nausea and dizziness were the most frequent side reactions about which it was reported in clinical trials.

Undesirable reactions are distributed according to emergence frequency. For assessment of frequency the following criteria are used: very often (> 1/10); often (from 1/100 to 1/10); infrequently (from 1/1000 to 1/100); seldom (from 1/10000 to 1/1000); very seldom (<1/10000), (including separate messages); frequency is unknown.

Infectious and parasitic diseases: often - grippopodobny symptoms, upper respiratory tract infections; infrequently - infections of urinary tract. Disturbances from immune system: infrequently – hypersensitivity, anaphylactic reactions, a Quincke's disease (Quincke's edema).

Disturbances from a nervous system: often - a headache, dizziness.

Disturbances from an organ of sight: infrequently – sight misting, a mydriasis, increase in intraocular pressure, glaucoma, an acute pain in eyes, emergence of an aura around objects, a conjunctiva hyperemia, cornea hypostasis; seldom - accommodation disturbance.

Disturbances from heart: infrequently - a heart consciousness, supraventricular (supraventricular) tachycardia; seldom - fibrillation of auricles, increase in heart rate.

Disturbances from vessels: frequency is unknown - a lowering of arterial pressure (hypotension).

Disturbances from respiratory system, bodies of a thorax and a mediastinum: often - irritation of a throat, cough, short wind; infrequently – a bronchospasm, a paradoxical bronchospasm, a laryngospasm, throat hypostasis, dryness of a throat, sinusitis.

Disturbances from digestive tract: often – dryness in a mouth, nausea, disturbance of motility of digestive tract; infrequently - diarrhea, a lock, vomiting, dyspepsia, change of flavoring feelings, stomatitis.

Disturbances from skin and hypodermic fabrics: infrequently - rash, an itch; seldom – a small tortoiseshell.

Disturbances from kidneys and urinary tract: infrequently - an ischuria. If any of the side reactions specified in the instruction are aggravated or you noticed any other side reactions which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

At simultaneous use β2-адреномиметики and derivatives of xanthine exponentiate bronkhodilatiruyushchy effect of drug.

The anticholinergic effect amplifies protivoparkinsonichesky means, quinidine, tricyclic antidepressants. At simultaneous use with other anticholinergics the additive action is noted.

Patients with closed-angle glaucoma have to use with extra care the drug Ipratropium-nativ together with inhalation β2-адреномиметиками as the risk of development of a bad attack of glaucoma increases. Ipratropium-nativ, solution for inhalations, it is not necessary to appoint along with inhalation solution of kromoglitsiyevy acid, considering a possibility of precipitation (sedimentation).

Contraindications:

- hypersensitivity to atropine and its derivatives;
- hypersensitivity to an ipratropiya to bromide or to other components of drug;
- age up to 18 years.
 
With care patients Should appoint with care the drug Ipratropium-nativ with such diseases as closed-angle glaucoma, obstruction of urinary tract, a hyperplasia of a prostate and a mucoviscidosis.

Overdose:

Symptoms: specific symptoms of overdose are not revealed. Considering the width of therapeutic action and a local route of administration of the drug Ipratropium-nativ, emergence of any serious anticholinergic symptoms is improbable.

Insignificant manifestations of systemic anticholinergic action, such as dryness in a mouth, accommodation disturbances, increase in heart rate are possible.

Treatment: performing symptomatic therapy.

Storage conditions:

In the place protected from light, at a temperature not above 25 °C. Not to freeze. To store in the place, unavailable to children. A period of validity - 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for inhalations of 0,25 mg/ml. On 20 ml of drug in bottles from dark glass with a polyethylene dropper and the screwing-up polypropylene cover. On 1 bottle with the application instruction place in a cardboard pack.