Ultibro 110/50

Glycopyrronium Bromide (Ultibro 110/50) Breezhaler is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).

Maintenance Treatment of COPD

Indacaterol (Ultibro 110/50) is a long-acting beta2-agonist indicated for long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Important Limitations of Use

Indacaterol (Ultibro 110/50) is not indicated to treat acute deteriorations of chronic obstructive pulmonary disease.

Indacaterol (Ultibro 110/50) is not indicated to treat asthma. The safety and effectiveness of Indacaterol (Ultibro 110/50) in asthma have not been established.

Treating peptic ulcers in combination with other medicines. It may also be used for other conditions as determined by your doctor.

Glycopyrronium Bromide (Ultibro 110/50) is an anticholinergic. It works by blocking the activity of a certain substance (acetylcholine) in the body, which decreases stomach acid secretion.

Indacaterol (Ultibro 110/50) is used to treat air flow blockage and prevent worsening of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. COPD is a long-term lung disease that causes bronchospasm (wheezing or difficulty with breathing).

Indacaterol (Ultibro 110/50) is a long-acting bronchodilator. Bronchodilators are medicines that are breathed in through the mouth to open up the bronchial tubes (air passages) in the lungs. They relieve cough, wheezing, shortness of breath, and troubled breathing by increasing the flow of air through the bronchial tubes.

Indacaterol (Ultibro 110/50) is available only with your doctor's prescription.

The recommended dose is the inhalation of the content of one capsule once daily using the Glycopyrronium Bromide (Ultibro 110/50) Breezhaler inhaler.

Glycopyrronium Bromide (Ultibro 110/50) Breezhaler is recommended to be administered, at the same time of the day each day. If a dose is missed, the next dose should be taken as soon as possible. Patients should be instructed not to take more than one dose in a day.

Special Populations: Elderly: Glycopyrronium Bromide (Ultibro 110/50) Breezhaler can be used at the recommended dose in elderly patients (≥75 years).

Renal Impairment: Glycopyrronium Bromide (Ultibro 110/50) Breezhaler can be used at the recommended dose in patients with mild to moderate renal impairment. In patients with severe renal impairment or end stage renal disease requiring dialysis Glycopyrronium Bromide (Ultibro 110/50) Breezhaler should be used only if the expected benefit outweighs the potential risk.

Hepatic Impairment: No studies have been conducted in patients with hepatic impairment. Glycopyrronium is predominantly cleared by renal excretion and therefore no major increase in exposure is expected in patients with hepatic impairment.

Paediatric population: There is no relevant use of Glycopyrronium Bromide (Ultibro 110/50) Breezhaler in the paediatric population (<18 years) in the indication COPD.

Administration: For inhalation use only. The capsules must be administered only using the Glycopyrronium Bromide (Ultibro 110/50) Breezhaler inhaler. The capsules must not be swallowed. Patients should be instructed on how to administer the product correctly.

For instructions on use of the medicinal product before administration, see section Cautions for Usage.

Adults: The recommended dosage of Indacaterol (Ultibro 110/50) is the once-daily inhalation of the content of one 150-mcg capsule using the Indacaterol (Ultibro 110/50) inhaler. The dosage should only be increased on medical advice.

Once-daily inhalation of the content of one 300-mcg capsule, using the Indacaterol (Ultibro 110/50) inhaler, has been shown to provide additional clinical benefit to some patients eg, with regard to breathlessness, particularly for patients with severe COPD. The maximum dose is 300 mcg once daily.

Special Populations: No dosage adjustment is required for geriatric patients, patients with mild and moderate hepatic impairment, or renally impaired. No data is available for subjects with severe hepatic impairment.

Indacaterol (Ultibro 110/50) should not be used in patients <18 years.

Administration: Indacaterol (Ultibro 110/50) capsules must be administered only by the oral inhalation route and only using the Indacaterol (Ultibro 110/50) inhaler. Indacaterol (Ultibro 110/50) capsules must not be swallowed.

Indacaterol (Ultibro 110/50) should be administered at the same time of the day each day. If a dose is missed, the next dose should be taken at the usual time the next day.

Indacaterol (Ultibro 110/50) capsules must always be stored in the blister and only removed immediately before use. Instructions on how to use the Indacaterol (Ultibro 110/50) inhaler are provided in Cautions for Usage.

Patients should be instructed on how to administer the product correctly. Patients who do not experience improvement in breathing should be asked if they are swallowing the medicine rather than inhaling it.

See also:
What is the most important information I should know about Glycopyrronium Bromide (Ultibro 110/50)?

Hypersensitivity. Glaucoma; obstructive uropathy; obstructive GI diseases; intestinal atony; paralytic ileus; pyloric stenosis; myasthenia gravis. Unstable CV status in acute haemorrhage. Injectable not recommended in new borns ≤1 mth if benzyl alcohol is present in the preparation.

See also:
What is the most important information I should know about Indacaterol (Ultibro 110/50)?

This medication may increase the risk of asthma-related death. It is critical that you use only the prescribed dose of this medicine and follow all patient instructions for safe use of the medication.

Before you use this medicine, tell your doctor if you have heart disease, high blood pressure, coronary artery disease, a heart rhythm disorder, seizures, diabetes, a thyroid disorder, or lactose intolerance.

Do not take an Indacaterol (Ultibro 110/50) capsule by mouth. It is for use only in the Neohaler device.

Call your doctor right away if your symptoms do not improve, or if they get worse while using Indacaterol (Ultibro 110/50). Tell your doctor if any of your medications do not seem to work as well in preventing attacks.

Do not stop using Indacaterol (Ultibro 110/50) without your doctor's advice. Your asthma symptoms may get worse after you stop using the medication.

Use Glycopyrronium Bromide (Ultibro 110/50) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Glycopyrronium Bromide (Ultibro 110/50) by mouth with or without food.
• If you miss a dose of Glycopyrronium Bromide (Ultibro 110/50), take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Glycopyrronium Bromide (Ultibro 110/50).

Use Indacaterol (Ultibro 110/50) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Indacaterol (Ultibro 110/50) comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Indacaterol (Ultibro 110/50) refilled.
• Indacaterol (Ultibro 110/50) is for inhalation only. Do NOT swallow the capsule.
• Store Indacaterol (Ultibro 110/50) in the original blister in a dry place. Do not remove the capsule from the blister or the foil until right before use. Be sure your hands are completely dry before you handle the capsules.
• If a second capsule is exposed to the air when you are removing a capsule for use, it must be discarded. Do not save the capsule for later.
• Use the new inhaler device that comes with each refill. Do not reuse an old inhaler. Do not use Indacaterol (Ultibro 110/50) with a different kind of inhaler. Do not use a different medicine with Indacaterol (Ultibro 110/50)'s inhaler. Do not try to use a spacer device with Indacaterol (Ultibro 110/50).
• To prepare the device for use, remove the inhaler cover and tilt the mouthpiece to open the inhaler. Place a capsule in the capsule chamber in the base of the inhaler. Do NOT place a capsule in the mouthpiece of the inhaler. Close the mouthpiece fully; you should hear a click as it fully closes.
• Hold the inhaler upright and press both buttons at the same time. You should hear a click as the capsule is pierced. Do NOT press the buttons more than once. Release the buttons.
• Before placing the inhaler in your mouth, breathe out fully. Do NOT exhale into the device for any reason. Keep the inhaler level, with the buttons to the left and the right (not up and down). Place the mouthpiece in your mouth and close your lips around it. Breathe in quickly, steadily, and as deeply as you can. Do not press the piercing buttons.
• As you breathe in through the inhaler, you should hear a whirring noise as the capsule spins around inside the inhaler. If you do not hear a whirring noise, the capsule may be stuck. If this occurs, open the inhaler and loosen the capsule by tapping the base of the device. Do NOT push the buttons again. Then, repeat the inhalation process. If you are not sure if you are receiving your dose correctly, contact your doctor or pharmacist.
• After breathing in your dose, remove the inhaler from your mouth. Continue to hold your breath for as long as possible. Then, breathe out slowly.
• After you use Indacaterol (Ultibro 110/50), open the inhaler to see if any powder is still in the capsule. If any powder remains in the capsule, close the inhaler. Repeat the inhalation process. Most people are able to empty the capsule in 1 or 2 inhalations.
• After you have taken your dose, open the inhaler, remove the capsule, and throw it away. Do not leave a used capsule in the inhaler. Close the mouthpiece and replace the cover.
• Rarely, very small pieces of the gelatin capsule may get past the screen and enter your mouth. It is not harmful if these pieces are swallowed or inhaled. To avoid this, store Indacaterol (Ultibro 110/50) properly, remove the capsules from the blister right before use, and pierce each capsule only once.
• Never wash the mouthpiece or any part of the inhaler. Keep it dry and always store it in a dry place. Do NOT try to take the inhaler apart.
• Use Indacaterol (Ultibro 110/50) on a regular schedule to get the most benefit from it.
• If you miss a dose of Indacaterol (Ultibro 110/50), use it as soon as possible. Do not use more often than 1 time every 24 hours.

Ask your health care provider any questions you may have about how to use Indacaterol (Ultibro 110/50).

Indacaterol (Ultibro 110/50) is used to treat adults having difficulty in breathing due to a lung disease known as COPD (chronic obstructive pulmonary disease).

See also:
What other drugs will affect Glycopyrronium Bromide (Ultibro 110/50)?

The co-administration of Glycopyrronium Bromide (Ultibro 110/50) Breezhaler with inhaled anticholinergic-containing drugs has not been studied and is therefore, like for other anticholinergics, not recommended.

In a clinical study in healthy volunteers, cimetidine, an inhibitor of organic cation transport which is thought to contribute to the renal excretion of glycopyrronium, increased total exposure (AUC) to glycopyrronium by 22% and decreased renal clearance by 23%. Based on the magnitude of these changes, no clinically relevant drug interaction is expected when Glycopyrronium Bromide (Ultibro 110/50) Breezhaler is co-administered with cimetidine or other inhibitors of the organic cation transport.

Concomitant administration of Glycopyrronium Bromide (Ultibro 110/50) Breezhaler and orally inhaled indacaterol, a β2-adrenergic agonist, under steady state conditions of both drugs did not affect the pharmacokinetics of either medicinal product.

See also:
What other drugs will affect Indacaterol (Ultibro 110/50)?

Drugs Known to Prolong QTc Interval: Indacaterol (Ultibro 110/50), as other β₂-adrenergic agonists, should be administered with caution to patients being treated with monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants or drugs known to prolong the QT interval, as any effect of these on the QT interval may be potentiated. Drugs known to prolong the QT interval may increase the risk of ventricular arrhythmia.

Sympathomimetic Agents: Concomitant administration of other sympathomimetic agents (alone or as part of combination therapy) may potentiate the undesirable effects of Indacaterol (Ultibro 110/50).

Hypokalemia: Concomitant treatment with methylxanthine derivatives, steroids or nonpotassium-sparing diuretics may potentiate the possible hypokalemic effect of β₂-adrenergic agonists.

Beta-Adrenergic Blockers: Beta-adrenergic blockers may weaken or antagonize the effect of β₂-adrenergic agonists. Therefore, Indacaterol (Ultibro 110/50) should not be given together with β-adrenergic blockers (including eye drops) unless there are compelling reasons for their use. Where required, cardioselective β-adrenergic blockers should be preferred, although they should be administered with caution.

Metabolic and Transporter Based Drug Interaction: Inhibition of the key contributors of Indacaterol (Ultibro 110/50) clearance, CYP3A4 and P-gp, has no impact on safety of therapeutic doses of Indacaterol (Ultibro 110/50). Drug interaction studies were carried out using potent and specific inhibitors of CYP3A4 and P-gp (ie, ketoconazole, erythromycin, verapamil and ritonavir). Verapamil was used as the prototypic inhibitor of P-gp and resulted in 1.4- to 2-fold increase in AUC and 1.5-fold increase in C_max. Co-administration of erythromycin with Indacaterol (Ultibro 110/50) resulted in an increase of 1.4- to 1.6-fold for AUC and 1.2-fold for C_max. Combined inhibition of P-gp and CYP3A4 by the very strong dual inhibitor ketoconazole caused a 2-fold and 1.4-fold increase in AUC and C_max, respectively. Concomitant treatment with ritonavir, another dual inhibitor of CYP3A4 and P-gp, resulted in a 1.6- to 1.8-fold increase in AUC whereas C_max was unaffected. Taken together, the data suggest that systemic clearance is influenced by modulation of both P-gp and CYP3A4 activities and that the 2-fold AUC increase caused by the strong dual inhibitor ketoconazole reflects the impact of maximal combined inhibition. The magnitude of exposure increases due to drug interactions does not raise any safety concerns given the safety experience of treatment with Indacaterol (Ultibro 110/50) in clinical trials of up to 1 year at doses 2- to 4-fold the recommended therapeutic doses.

Indacaterol (Ultibro 110/50) has not been shown to cause drug interactions with co-medications. In vitro investigations have indicated that Indacaterol (Ultibro 110/50) has negligible potential to cause metabolic interactions with medications at the systemic exposure levels achieved in clinical practice.

Incompatibilites: Not applicable.

See also:
What are the possible side effects of Glycopyrronium Bromide (Ultibro 110/50)?

Applies to glycopyrrolate: oral solution, oral tablet

As well as its needed effects, glycopyrrolate (the active ingredient contained in Glycopyrronium Bromide (Ultibro 110/50)) may cause unwanted side effects that require medical attention.

Major Side Effects

If any of the following side effects occur while taking glycopyrrolate, check with your doctor immediately:

More common:

• Body aches or pain
• chills
• constipation
• cough
• decrease in the frequency of urination
• decrease in urine volume
• difficulty in passing urine (dribbling)
• difficulty with breathing
• ear congestion
• feeling of warmth
• fever
• headache
• loss of voice
• nasal congestion
• painful urination
• redness of the face, neck, arms, and occasionally, upper chest
• runny nose
• sneezing
• sore throat
• unusual tiredness or weakness

• Abdominal or stomach discomfort or pain
• abdominal or stomach distension
• chest pain
• confusion
• convulsions
• dizziness
• dry heaves
• dry mouth
• fainting
• increase in heart rate
• lightheadedness
• pain or tenderness around the eyes and cheekbones
• rapid breathing
• shortness of breath or troubled breathing
• stuffy nose
• sunken eyes
• thirst
• tightness in the chest
• vomiting
• wheezing
• wrinkled skin

If any of the following symptoms of overdose occur while taking glycopyrrolate, get emergency help immediately:

• low blood pressure
• muscle weakness
• trouble breathing

Minor Side Effects

Some glycopyrrolate side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

Less common:

• Altered mood
• anxiety
• attack, assault, or force
• bloated
• change in taste
• chapped lips
• crying
• dry skin
• dry tongue
• excess air or gas in the stomach or intestines
• full feeling
• hyperventilation
• irregular heartbeats
• irritability
• loss of taste
• moaning
• nervousness
• pain
• paleness of the skin
• passing gas
• rash
• restlessness
• shaking
• trouble with sleeping
• uncontrolled eye movements

See also:
What are the possible side effects of Indacaterol (Ultibro 110/50)?

Long-acting beta) percent predicted of 54%. The mean age of patients was 64 years, with 47% of patients aged 65 years or older, and the majority (88%) was Caucasian.

In these six clinical trials, 48% of patients treated with any dose of Indacaterol (Ultibro 110/50) reported an adverse reaction compared with 43% of patients treated with placebo. The proportion of patients who discontinued treatment due to adverse reaction was 5% for Indacaterol (Ultibro 110/50)-treated patients and 5% for placebo-treated patients. The most common adverse reactions that lead to discontinuation of Indacaterol (Ultibro 110/50) were COPD and dyspnea.

The most common serious adverse reactions were COPD exacerbation, pneumonia, angina pectoris, and atrial fibrillation, which occurred at similar rates across treatment groups.

Table 1 displays adverse drug reactions reported by at least 2% of patients (and higher than placebo) during a 3 month exposure at the recommended 75 mcg once daily dose. Adverse drug reactions are listed according to MedDRA (version 13.0) system organ class and sorted in descending order of frequency.

Table 1: Number and frequency of adverse drug reactions greater than 2% (and higher than placebo) in COPD patients exposed to Indacaterol (Ultibro 110/50) 75 mcg for up to 3 months in multiple dose, controlled trials

In these trials the overall frequency of all cardiovascular adverse reactions was 2.5% for Indacaterol (Ultibro 110/50) 75 mcg and 1.6% for placebo during a 3 month exposure. There were no frequently occurring specific cardiovascular adverse reactions for Indacaterol (Ultibro 110/50) 75 mcg (frequency at least 1% and greater than placebo).

Additional adverse drug reactions reported in greater than 2% (and higher than on placebo) in patients dosed with 150, 300 or 600 mcg for up to 12 months were as follows:

• Musculoskeletal and connective tissue disorders: muscle spasm, musculoskeletal pain
• General disorders and administration site conditions: edema peripheral
• Metabolism and nutrition disorder: diabetes mellitus, hyperglycemia
• Infections and infestations: sinusitis, upper respiratory tract infection

Cough experienced post-inhalation

In the clinical trials, health care providers observed during clinic visits that an average of 24% of patients experienced a cough on at least 20% of visits following inhalation of the recommended 75 mcg dose of Indacaterol (Ultibro 110/50) compared to 7% of patients receiving placebo. The cough usually occurred within 15 seconds following inhalation and lasted for no more than 15 seconds. Cough following inhalation in clinical trials was not associated with bronchospasm, exacerbations, deteriorations of disease or loss of efficacy.

Clinical Trials Experience in Asthma

In a 6-month randomized, active controlled asthma safety trial, 805 adult patients with moderate to severe persistent asthma were treated with Indacaterol (Ultibro 110/50) 300 mcg (n=268), Indacaterol (Ultibro 110/50) 600 mcg (n=268), and salmeterol (n=269), all concomitant with inhaled corticosteroids, which were not co-randomized. Of these patients, there were 2 respiratory-related deaths in the Indacaterol (Ultibro 110/50) 300 mcg dose group. There were no deaths in the Indacaterol (Ultibro 110/50) 600 mcg dose group or in the salmeterol active control group. Serious adverse reactions related to asthma exacerbation were reported for 2 patients in the Indacaterol (Ultibro 110/50) 300 mcg group, 3 patients in the Indacaterol (Ultibro 110/50) 600 mcg group, and no patients in the salmeterol active control group.

In addition, a two-week dose-ranging trial was conducted in 511 adult patients with mild persistent asthma taking inhaled corticosteroids. No deaths, intubations, or serious adverse reactions related to asthma exacerbation were reported in this trial.

Postmarketing Experience

The following adverse reactions have been identified during worldwide post-approval use of Indacaterol (Ultibro 110/50), the active ingredient in Indacaterol (Ultibro 110/50). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are: tachycardia/heart rate increase/palpitations, pruritus/rash and dizziness.

Each capsule contains Glycopyrronium Bromide (Ultibro 110/50) 63 mcg equivalent to glycopyrronium 50 mcg.

Each delivered dose (the dose that leaves the mouthpiece of the Glycopyrronium Bromide (Ultibro 110/50) Breezhaler inhaler) contains Glycopyrronium Bromide (Ultibro 110/50) 55 mcg equivalent to glycopyrronium 44 mcg.

Glycopyrronium Bromide (Ultibro 110/50) Breezhaler also contains the following excipients: Capsule: Lactose monohydrate, magnesium stearate. Capsule Shell: Hypromellose, purified water, carrageenan, potassium chloride, FDC yellow 6 (110 sunset yellow FCF).

Each 150-mcg capsule contains Indacaterol (Ultibro 110/50) maleate 194 mcg equivalent to Indacaterol (Ultibro 110/50) 150 mcg. The delivered dose (the dose that leaves the mouthpiece of the Indacaterol (Ultibro 110/50) inhaler) is equivalent to Indacaterol (Ultibro 110/50) 120 mcg.

Each 300-mcg capsule contains Indacaterol (Ultibro 110/50) maleate 389 mcg equivalent to Indacaterol (Ultibro 110/50) 300 mcg. The delivered dose (the dose that leaves the mouthpiece of the Indacaterol (Ultibro 110/50) inhaler) is equivalent to Indacaterol (Ultibro 110/50) 240 mcg.

It also contains the following excipients: Lactose monohydrate and gelatin.