Ipramol Steri-Neb (Solution) Instructions for Use

Marketing Authorization Holder

NORTON HEALTHCARE, Limited (United Kingdom)

Manufactured By

IVAX Pharmaceuticals UK, Limited (United Kingdom)

ATC Code

R03AL02 (Salbutamol and Ipratropium bromide)

Active Substances

Ipratropium bromide (Rec.INN registered by WHO)

Salbutamol (Rec.INN registered by WHO)

Dosage Form

Ipramol Steri-Neb

Inhalation solution 200 mcg+1 mg/1 ml: amp. 2.5 ml 20 or 60 pcs.

Dosage Form, Packaging, and Composition

Inhalation solution from colorless to pale yellow, clear.

Excipients: sodium chloride – 22.5 mg, hydrochloric acid – to pH 3.5, water for injection – 2.5 ml.

2.5 ml – polyethylene ampoules, welded together in the form of a block (5) – laminated foil (4) – cardboard packs.
2.5 ml – polyethylene ampoules, welded together in the form of a block (5) – laminated foil (12) – cardboard packs.

Clinical-Pharmacological Group

Bronchodilator drug

Pharmacotherapeutic Group

Combined bronchodilator agent (m-cholinergic blocker + selective beta2-adrenomimetic)

Pharmacological Action

A combined drug with a pronounced bronchodilatory effect due to the action of its components, ipratropium bromide and salbutamol.

Ipratropium bromide is an anticholinergic agent. It blocks m-cholinergic receptors of the smooth muscles of the tracheobronchial tree (mainly large and medium bronchi), suppresses reflex bronchoconstriction, and reduces the secretion of the respiratory tract mucous membrane glands. Having a structural similarity to the acetylcholine molecule, it is its competitive antagonist. It effectively prevents bronchoconstriction caused by inhalation of cigarette smoke, cold air, the action of various bronchospastic agents, and also relieves bronchospasm associated with the influence of the vagus nerve.

Salbutamol is a beta₂-adrenomimetic that acts on the smooth muscles of the airways, causing its relaxation and preventing bronchospasm. It reduces airway resistance and increases vital lung capacity. It prevents the release of histamine, leukotrienes, prostaglandin D₂, and other biologically active substances from mast cells. In recommended therapeutic doses, it does not have a negative effect on the cardiovascular system and does not cause an increase in blood pressure. To a lesser extent compared to other drugs in this group, it has a positive chronotropic and inotropic effect. It causes dilation of the coronary arteries.

Simultaneous inhalation of ipratropium bromide and salbutamol has a simultaneous local effect on m-cholinergic receptors and β₂-adrenergic receptors in the lungs, resulting in an enhanced bronchodilatory effect. Systemic absorption during simultaneous inhalation of ipratropium bromide and salbutamol does not increase.

Pharmacokinetics

Ipratropium bromide

Absorption

Rapidly absorbed after inhalation, but systemic bioavailability is less than 10% of the administered dose.

Distribution and Elimination

Plasma protein binding (mainly to albumin and glycoprotein) – 9%. 46% of the drug is excreted by the kidneys. Ipratropium bromide does not cross the blood-brain barrier.

Salbutamol

Absorption

Salbutamol is rapidly and completely absorbed after inhalation. C_max of salbutamol in blood plasma is observed after 3 hours.

Distribution and Metabolism

Plasma protein binding – 10%. Salbutamol crosses the blood-brain barrier, creating concentrations approximately equal to 5% of the concentration in blood plasma.

It undergoes presystemic metabolism in the liver and intestinal wall.

Elimination

T_1/2 is 3-7 hours. It is excreted by the kidneys, mainly unchanged (30% of the dose within 24 hours) and as an inactive phenol sulfate metabolite within 72 hours, and with bile.

Indications

• Bronchospastic syndrome in patients with COPD and bronchial asthma.

ICD codes

Dosage Regimen

The drug is administered by inhalation using nebulizer inhalers or a system for non-invasive lung ventilation in the mode of positive airway pressure.

Adults (including elderly patients) and children over 12 years are prescribed 1 ampoule with a sterile solution 3-4 times/day as an inhalation using a nebulizer.

Technique for using the drug

1. Prepare the nebulizer according to the manufacturer’s instructions.

2. Separate the Steri-Neb (ampoule with sterile solution) from the block by twisting and pulling it.

3. Holding the ampoule vertically with the cap upwards, break off the cap.

4. Squeeze the solution into the nebulizer reservoir.

5. Use the nebulizer according to the manufacturer’s instructions.

The solution remaining unused in the nebulizer chamber should be discarded. Thoroughly wash the nebulizer.

Adverse Reactions

Nervous system disorders common (>1/100, <1/10) – headache; uncommon (>1/1000, <1/100) – dizziness, excessive fatigue, tremor, paresthesia, insomnia, nervousness; rare (>1/10,000, <1/1000) – coordination disorders, mental and psychotic disorders such as dysphoria, memory impairment, fear, depression.

Cardiovascular system disorders common (>1/100, <1/10) – palpitations, tachycardia; uncommon (>1/1000, <1/100) – increased systolic blood pressure, arrhythmia; rare (>1/10,000, <1/1000) – decreased systolic blood pressure.

Digestive system disorders common (>1/100, <1/10) – dry mouth, nausea; uncommon (>1/1000, <1/100) – vomiting, taste perversion, diarrhea.

Respiratory system disorders common (>1/100, <1/10) – cough, dysphonia; rare (>1/10,000, <1/1000) – nasal congestion, stridor, paradoxical bronchospasm, dyspnea.

Sensory organ disorders common (>1/100, <1/10) – accommodation disturbance (if the drug gets into the eyes); rare (>1/10,000, <1/1000) – if it gets into the eyes, increased intraocular pressure, acute eye pain, visual acuity impairment, mydriasis, scleral injection, conjunctival hyperemia, angle-closure glaucoma are possible.

Musculoskeletal system disorders uncommon (>1/1000, <1/100) – tremor; rare (>1/10,000, <1/1000) – myalgia, muscle cramps, muscle weakness, arthralgia.

Urinary system disorders common (>1/100, <1/10) – urinary retention, dysuria.

Metabolism disorders rare (>1/10,000, <1/1000) – hypokalemia, hyperglycemia.

Dermatological reactions rare (>1/10,000, <1/1000) – alopecia, sweating.

Allergic reactions rare (>1/10,000, <1/1000) – angioedema of the tongue, lips, face, skin rash (including urticaria, up to giant urticaria), laryngospasm, bronchospasm, itching, anaphylactic shock.

Contraindications

• Hypertrophic obstructive cardiomyopathy;
• Tachyarrhythmia;
• First trimester of pregnancy;
• Children under 12 years of age;
• Hypersensitivity to salbutamol, ipratropium bromide, atropine or their derivatives.

With caution angle-closure glaucoma, urinary tract obstruction (including due to prostatic hyperplasia), severe organic cardiovascular diseases, pheochromocytoma, hyperthyroidism, inadequately controlled diabetes mellitus, cystic fibrosis, recent myocardial infarction, second and third trimesters of pregnancy, lactation period (breastfeeding).

Use in Pregnancy and Lactation

It is not recommended to prescribe the drug during the second and third trimesters of pregnancy and during breastfeeding, except in cases where the expected benefit to the mother outweighs any possible risk to the fetus and infant. Contraindicated in the first trimester of pregnancy.

Pediatric Use

Contraindicated in children under 12 years of age. For children over 12 years of age, the drug is prescribed as 1 ampoule with a sterile solution 3-4 times/day as an inhalation using a nebulizer.

Geriatric Use

For elderly patients, as for adults, the drug is prescribed as 1 ampoule with a sterile solution 3-4 times/day as an inhalation using a nebulizer.

Special Precautions

To avoid overdose, it is not recommended to exceed the maximum allowable daily dose.

Patients should be instructed on the correct use of Ipramol Steri-Neb with a nebulizer and warned about the inadmissibility of getting the solution into the eyes.

In patients with bronchial asthma or moderate forms of COPD, symptomatic treatment may be preferable to regular use.

It is necessary to additionally analyze the addition or intensification of anti-inflammatory therapy to control airway inflammation in patients with bronchial asthma and steroid-dependent forms of COPD.

Regular use of beta₂-adrenomimetics in high doses, including as part of Ipramol Steri-Neb, to control symptoms of bronchial obstruction may worsen the course of the disease. With increasing bronchial obstruction, simply increasing the dose of Ipramol Steri-Neb above the recommended level for a long period of time is inappropriate and even dangerous. To prevent life-threatening deterioration in the course of the disease, the patient’s treatment plan should be reviewed, and in particular, the adequacy of anti-inflammatory therapy with corticosteroids.

When using an inhalation solution based on ipratropium bromide together with beta₂-adrenomimetics, cases of acute angle-closure glaucoma have rarely occurred. Pain or discomfort in the eyes, blurred vision, the appearance of a halo characteristic of glaucoma combined with reddening of the eyes from conjunctival edema to corneal edema may be signs of the development of acute angle-closure glaucoma. If these symptoms do not disappear, it is necessary to start treatment with miotics in the form of eye drops and immediately undergo an examination by a specialist.

The patient should be explained that in case of acute, rapidly worsening shortness of breath or a clear decrease in response to the drug, it is necessary to consult a doctor.

Treatment with beta₂-adrenomimetics can lead to significant hypokalemia. Particular caution should be exercised in cases of severe airway obstruction, since concomitant treatment with xanthine derivatives, diuretics and corticosteroids may contribute to the occurrence of hypokalemia. Hypokalemia may lead to an increased risk of arrhythmia in patients receiving digoxin. In addition, hypoxia may exacerbate the effect of hypokalemia on heart rhythm. In such situations, it is recommended to check serum potassium concentration.

In patients with cystic fibrosis, Ipramol Steri-Neb should be prescribed with caution due to the possible appearance of symptoms of gastrointestinal motility disorders. Such patients should be warned to inform the doctor about any changes in gastrointestinal function.

If larger doses than recommended are required to relieve symptoms of bronchial obstruction (or bronchospasms), the patient’s treatment plan should be reviewed.

Use in pediatrics

Data on the use of Ipramol Steri-Neb in children under 12 years of age are not available.

Effect on ability to drive vehicles and mechanisms

Data on the effect on the ability to drive vehicles and/or other mechanisms are not available. However, given the possibility of developing side effects from the central nervous system, during treatment with Ipramol Steri-Neb, caution should be exercised when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms of ipratropium bromide overdose are unlikely due to low systemic absorption after inhalation or oral administration, so all overdose symptoms are mainly associated with the systemic action of salbutamol. Symptoms of salbutamol overdose may include headache, nausea, vomiting, angina pectoris, arterial hypertension, arterial hypotension, hypokalemia, hyperglycemia, tachycardia, arrhythmia, chest pain, tremor, hyperemia, anxiety, hallucinations and dizziness.

Treatment is symptomatic, including the administration of cardioselective beta-blockers. However, it should be taken into account that these drugs may increase bronchospasm.

Drug Interactions

Concomitant use of additional beta₂-adrenomimetics, corticosteroids, anticholinergic agents and xanthine derivatives may enhance the bronchodilatory effect of Ipramol Steri-Neb on the airways and cause severe side effects. With concomitant treatment with beta-blockers, a significant decrease in the effectiveness of the drug may be observed.

MAO inhibitors and tricyclic antidepressants may enhance the beta-adrenergic effect of salbutamol and lead to a sharp decrease in blood pressure.

Inhalation anesthesia with anesthetic substances containing halogenated hydrocarbons, for example, halothane, trichloroethylene and enflurane, may exacerbate the side effects of beta₂-adrenomimetics on the cardiovascular system, so careful monitoring of patients is required. As an alternative, the use of Ipramol Steri-Neb can be discontinued before surgery.

Theophylline and other xanthines increase the likelihood of tachyarrhythmias.

Ipramol Steri-Neb, due to the hypokalemic effect of salbutamol, may enhance the effect of CNS stimulants, increase the likelihood of glycoside intoxication, and enhance the cardiotropic effect of thyroid hormones.

A possible increase in heart rate and blood pressure while taking Ipramol Steri-Neb may necessitate dose adjustment of antihypertensive and antianginal drugs.

Diuretics and corticosteroids enhance the hypokalemic effect of salbutamol.

Anticholinergic drugs increase the risk of increased intraocular pressure.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature not exceeding 25°C (77°F), do not freeze.

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

IPOL-RU-00007-DOC

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.