Ultibro Brizhaler, 50 mcg+110 mcg 30 pcs

Chronic Obstructive Pulmonary Disease, Bronchospasm, Bronchial Asthma

– Maintenance therapy of bronchial conduction disorders in patients with chronic obstructive pulmonary disease.

Active ingredient

Glycopyrronium bromide, Indacaterol

Composition

Excipients:

Lactose monohydrate – 24.9 mg,

Magnesium stearate – 0.037 mg.

Composition of the capsule:

Hypromellose – 45.59 mg,

water – 2.7 mg,

carrageenan – 0.42 mg,

sodium chloride – 0.18 mg,

dye sunset yellow (E110) – 0.12 mg.

Ink composition:

shellac, iron oxide black dye, propylene glycol, sodium hydroxide.

How to take, the dosage

Each pack of Cibri® Brizhaler® contains:

– one inhalation device – Brizhaler®;

– blister packs of inhalation powder capsules.

Powder inhalation capsules must not be taken orally!

The Brizhaler® inhalation device in the pack is for use with the product capsules only.

The Brizhaler® Inhaler is only to be used with the capsules in the pack.

Do not use the product capsules with any other inhalation device and in turn do not use the Brizhaler® to inhale other medications.

The Brizhaler® should be discarded after 30 days of use.

How to use the inhaler

1. Remove the lid.

2. Open the Breechhaler®. To open the inhaler, hold it firmly by the base and tilt the tip.

3. To prepare the capsule: Separate one blister from the blister pack by tearing along the perforations; take one blister and remove the protective film to release the capsule; do not squeeze the capsule through the protective film.

4. Remove the capsule: Keep the capsules in the blister and remove only immediately before use; wipe hands dry and remove the capsule from the blister. Do not swallow.

5.5 Insert capsule into Breechhaler®: Place capsule into the capsule chamber; never put capsule directly into the mouthpiece.

6. Close the Breechhaler®: Close the inhaler firmly; you will hear a “click” when it is fully closed.

7. To pierce the capsule: Hold the Brizhaler® upright with the mouthpiece facing up and press both buttons fully down at the same time; you will hear a “click” when the capsule is pierced; do not press the buttons more than once to pierce the capsule.

8. Fully release the buttons on both sides of the Breezehaler® inhaler.

9. Breathe out: Always exhale completely before inserting the mouthpiece into your mouth; never blow into the mouthpiece.

10. To inhale the medication: hold the Brizhaler® in your hand so that the buttons are on the left and right (not the top and bottom); place the Brizhaler® inhaler mouthpiece in your mouth and press your lips tightly around it; take quick, even, deepest breaths. Do not press the buttons of the piercing device.

If the patient inhales through the inhaler, they should hear a rattling sound as the capsule rotates in the chamber and the powder is atomized. This might make a sweet aftertaste in the mouth.

If there is no rattling sound, it may mean that the capsule is stuck in the chamber of the inhaler. If this happens, open the inhaler and gently release the capsule by tapping on the base of the device. To release the capsule, do not press the buttons to pierce the capsule. If necessary, repeat steps 9 and 10.

12. Hold your breath: if a characteristic sound appears when you inhale, you should hold your breath as long as possible (to avoid discomfort), and at the same time take the mouthpiece out of your mouth. After that you should exhale. Open the Brizhaler® and see if there is any powder left in the capsule. If there is powder left in the capsule, close the Brizhaler® and repeat steps 9-12. In most cases, the capsule will empty in 1 or 2 inhalations. Some patients have a cough for a short time after inhalation. If there is no cough, the patient should not worry. If there is no powder left in the capsule, then the patient has received a full dose of the drug.

13. Withdraw the empty capsule: When the daily dose of Cibri®Brischaler® has been taken, tilt the mouthpiece, remove the empty capsule by tapping on the inhaler and throw it away. Close the mouthpiece of the Brizhaler® inhaler and close the Brizhaler® cap. Do not store capsules in the Brizhaler® inhaler.

Do not swallow capsules with inhalation powder.

Use only the Brizhaler® in the package.

The capsules should be stored in a blister and removed just before use.

Never insert the capsule into the mouthpiece of a Brizhaler® inhaler. Do not press the piercing device more than once.

Never blow into the mouthpiece of the Brizhaler® inhaler.

Always pierce the capsule before inhaling.

Do not wash Brizhaler®. Keep it dry. Do not disassemble Brizhaler®.

When starting a new pack of this medicine, always use the new Brizhaler® in the pack to inhale the capsules.

Do not store the capsules in the Brizhaler® inhaler.

Always store the blister packs of capsules and Brizhaler® in a dry place.

In very rare cases, a small amount of capsule contents may enter the mouth when inhaled or swallowed; this does not matter.

If the capsule has been punctured more than once, there is an increased risk of it breaking.

How to clean Brizhaler®

The Brizhaler® should be cleaned once a week. Wipe the mouthpiece inside and outside with a clean, dry cloth. Never use water to clean the Brizhaler® inhaler. Keep it dry.

Interaction

The concomitant use of glycopyrronium bromide and inhaled indacaterol, a beta2-adrenoceptor agonist, does not affect the pharmacokinetics of either drug.

In clinical studies in healthy volunteers, cimetidine, an inhibitor of organic cation transporters that affect renal clearance of glycopyrronium bromide, increased total exposure (AUC) of glycopyrronium bromide by 22% and decreased renal clearance by 23%.

Based on these indications, no clinically significant interactions are expected when Cibri® Brizhaler® is used concomitantly with cimetidine or other cation transporter inhibitors.

In vitro studies have shown that Cibri® Brizhaler® probably does not affect the metabolism of other drugs.

Inhibition or induction of metabolism of glycopyrronium bromide does not result in significant changes in the systemic exposure of the drug.

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Special Instructions

Cibri® Brizhaler® is not recommended for the management of acute episodes of bronchospasm.

Hypersensitivity reactions

Cases of immediate hypersensitivity reactions have been reported after the use of Cibri® Brizhaler®. If there are signs of an allergic reaction including angioedema (including difficulty in breathing or swallowing, swelling of the tongue, lips and face), urticaria or skin rash, the drug should be discontinued and alternative therapy should be chosen.

Paradoxic bronchospasm

As with other inhaled therapies, use of Cibri®BrizHaler® may result in paradoxic bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs, the use of Cibri® Brizhaler® should be discontinued immediately and alternative therapy should be used.

M-choline-blocking effects

As with other m-choline-blocking drugs, Cibri®Brizhaler® should be used with caution in patients with closed-angle glaucoma or urinary retention.

Patients should be informed of the signs and symptoms of an acute attack of closed-angle glaucoma and the need to discontinue use of Cibri®Brizhaler® and immediately inform their physician if any of these signs or symptoms develop.

Severe renal impairment

Patients with impaired renal function (GFR less than 30 mL/min/1.73 m2), including those with end-stage disease requiring hemodialysis, require close monitoring for possible adverse drug reactions.

The drug Cibri® Brizhaler® is intended for the maintenance treatment of patients with COPD.

Due to the fact that the general population of COPD is significantly dominated by patients over 40 years of age, spirometric confirmation of the diagnosis of COPD is required when using the product in patients younger than 40 years of age.

Influence on driving and operating ability

The drug Cibri® Brizhaler® has no adverse effect on driving and operating ability.

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Contraindications

– hypersensitivity to glycopyrronium bromide or any other component of the drug;

– childhood and adolescence under 18 years of age;

– concomitant use with inhaled drugs containing other m-cholinoblockers;

– galactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose).

With caution

Closed angle glaucoma, diseases accompanied by urinary retention, severe renal insufficiency (GFR below 30 ml/min/1.73 m2), including terminal renal failure requiring hemodialysis (Cibri® Brizhaler® should only be used if the expected benefit exceeds the potential risk); unstable CHD, history of myocardial infarction, heart rhythm disorders, QTc interval prolongation (QT corrected > 0.44 s).

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Side effects

The safety profile of Cibri® Brizhaler® is characterized by symptoms associated with m-cholin-blocking effects, including dry mouth (2.2%), while other GI effects and signs of urinary retention were infrequent.

Unwanted drug reactions related to local tolerance of the drug included pharyngeal irritation, nasopharyngitis, rhinitis and sinusitis. At the recommended doses, Cibri® Brizhaler® has no effect on BP and HR.

The safety and tolerability of Cibri® Brizhaler® was studied when used in 1,353 patients with COPD at the recommended dose of 50 mcg once daily. Of these, 842 patients were treated for at least 26 weeks and 351 for at least 52 weeks.

Determine the frequency of adverse drug reactions: very frequently (≥1/10); frequently (≥1/100, <1/10); infrequently (≥1/1000, <1/100); rarely (≥1/10 000, 1/1000); very rarely (<1/10 000).

Infectious and parasitic diseases:often – nasopharyngitis; infrequently – rhinitis, cystitis.

Metabolic disorders: infrequent – hyperglycemia.

Mental side:often – insomnia.

Nervous system disorders:often – headache; infrequently – hypoesthesia.

Cardiovascular system disorders:infrequent – atrial fibrillation, palpitations.

Respiratory system, thorax and mediastinum:infrequent – sinus congestion, productive cough, pharyngeal irritation, nasal bleeding.

From the digestive system:often – dry mouth, gastroenteritis; infrequently – dyspepsia, dental caries.

Skin and subcutaneous tissue: infrequently – skin rash.

Muscular system disorders:infrequent – pain in the extremities, pain in the skeletal muscles of the chest.

Since the urinary system:often – urinary tract infection; infrequently – dysuria, urinary retention.

General disorders: infrequent – fatigue, asthenia.

In a 12-month clinical trial, the following additional adverse events were identified that occurred more frequently with Cibri® Brizhaler® compared to placebo: nasopharyngitis (9.0% vs. 5.6%), vomiting (1.3% vs. 0.7%), muscle pain (1.1% vs. 0.7%), neck pain (1.3% vs. 0.7%), and diabetes (0.8% vs. 0%).

Unwanted drug reactions reported in post-marketing studies and from the literature: Since data are reported voluntarily from a population of uncertain size, it is not possible to determine their frequency (frequency unknown) – Angioedema.

In patients older than 75 years, the incidence of urinary tract infections and headache was higher with Cibri®Brischaler® than in the placebo group (3.0% versus 1.5% and 2.3% versus 0%, respectively).

If any of the above side effects worsen or any other side effects occur, the patient should inform the physician.

Overdose

There are no data on overdose of Cibri® Brizhaler®.

In patients with COPD, regular inhalation administration of Cibri®Brizhaler® at a total dose of 100 and 200 mcg once daily for 28 days was well tolerated. Acute intoxication in case of accidental swallowing of Cibri® Brizhaler® capsule is unlikely due to low bioavailability of glycopyrronium bromide when administered orally (approximately 5%).

. Plasma Cmax and total systemic exposure following IV administration of 150 mcg glycopyrronium bromide (equivalent to 120 mcg glycopyrronium) in healthy volunteers were approximately 50 and 6 times higher, respectively, than the plasma Cmax and total systemic exposure in equilibrium achieved when using Cibri® Brizhaler® inhaled at the recommended dose (50 mcg 1 time/day). No signs of overdose were detected.

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