Utibron Neohaler

Glycopyrrolate is an anticholinergic. Indacaterol is a bronchodilator. These medications work by relaxing muscles in the airways to improve breathing.

Glycopyrrolate and indacaterol is a combination medicine used to prevent airflow obstruction or bronchospasm in people with COPD (chronic obstructive pulmonary disease).

This medicine is not for use in treating asthma.

Indacaterol may increase the risk of death in people with asthma, but the risk in people with COPD is not known. Talk with your doctor about your individual risk.

Glycopyrrolate and indacaterol may also be used for purposes not listed in this medication guide.

You should not use this medicine if you are allergic to glycopyrrolate or indacaterol.

Glycopyrrolate and indacaterol is not a rescue medicine. It will not work fast enough to treat a bronchospasm attack.

Indacaterol may increase the risk of death in people with asthma, but the risk in people with COPD is not known. Glycopyrrolate and indacaterol is not for use in treating asthma.

You should not use this medicine if you are allergic to glycopyrrolate, indacaterol, or milk proteins. Glycopyrrolate and indacaterol is for use only in people with COPD and should not be used to treat asthma.

To make sure glycopyrrolate and indacaterol is safe for you, tell your doctor if you have:

• heart disease;
• high blood pressure;
• liver or kidney disease;
• narrow-angle glaucoma;
• an enlarged prostate;
• a bladder obstruction or other urination problems;
• diabetes;
• a thyroid disorder;
• seizures; or
• allergy to milk proteins.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether glycopyrrolate and indacaterol passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Glycopyrrolate and indacaterol is not approved for use by anyone younger than 18 years old.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Glycopyrrolate and indacaterol inhalation powder (Utibron Neohaler) is packaged in capsules that come with a special inhaler device. Each time you use the medicine, load a capsule into the device and click the mouthpiece closed. Push the buttons on the side of the device to pierce the capsule and release the medicine into the inhalation chamber. You may need 2 inhalations to get the full dose from 1 capsule.

Do not swallow the Utibron capsule or place it in your mouth. The capsule is for use only with the Neohaler inhalation device.

The usual dose of this medicine is 1 capsule twice daily. Follow your doctor's dosing instructions very carefully.

Use this medicine at the same time each day, even if you feel well.

Glycopyrrolate and indacaterol is not a rescue medicine. It will not work fast enough to treat a bronchospasm attack. Use only a fast-acting inhalation medicine for a sudden attack. Tell your doctor if any of your medicines seem to stop working as well in controlling your COPD.

Seek medical attention if your breathing problems do not improve, or if your symptoms get worse quickly.

Use glycopyrrolate and indacaterol regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely. Always use the new Neohaler device that comes with this medicine.

You should not stop using glycopyrrolate and indacaterol unless your doctor tells you to. Stopping suddenly may make your condition worse.

Store at room temperature away from moisture and heat. Keep the capsules in the blister pack until it is time for your dose. Remove only one capsule each time you use the medicine. Do not push a capsule through the foil or you may damage the capsule.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include blurred vision, chest pain, fast or pounding heartbeats, severe headache, tremors, muscle cramps, vomiting, little or no urination, drowsiness, or feeling restless.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Do not use more than 2 capsules in one 24-hour period.

Utibron Neohaler is a prescription medication used to treat chronic obstructive pulmonary disease (COPD).

It is a single product containing 2 products: indacaterol and glycopyrrolate. 

Indacaterol belongs to a group of drugs called long-acting beta2-adrenergic agonist (LABA). Glycopyrrolate belongs to a group of drugs called anticholinergics. Together these work to help the muscles around the airways in your lungs stay relaxed to prevent symptoms such as wheezing, cough, chest tightness, and shortness of breath.

This medication is available in capsule form to use with a specially designed inhaler. The capsules are inserted into the neohaler and inhaled twice a day.

Do not swallow Utibron capsules. Instead, using the Utibron Neohaler, the capsule is punctured, and the powder inside the capsule is inhaled into the lungs. 

Common side effects of Utibron Neohaler include sore throat and runny nose, high blood pressure, and back pain.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Anticholinergics such as umeclidinium, tiotropium, ipratropium, and aclidinium
• LABA medicines such as formoterol, salmeterol, vilanterol, indacaterol, and olodaterol)
• Beta blockers such as metoprolol (Toprol XL, Lopressor), carvedilol (Coreg), bisoprolol (Zebeta), betaxolol (Kerlone), nebivolol (Bystolic), propranolol (Inderal)
• Monoamine oxidase inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), selegiline (Emsam, Eldepryl, Zelapar), rasagiline (Azilect)
• Tricyclic antidepressants such as trimipramine (Surmontil), amitriptyline (Elavil), nortriptyline (Pamelor, Aventyl), protriptyline (Vivactil), and clomipramine (Anafranil)
• Diuretics such as acetazolamide (Diamox), amiloride (Midamor), bumetanide (Bumex), chlorothiazide (Diuril), chlorthalidone (Thalitone), ethacrynic acid (Edecrin), furosemide (Lasix), hydrochlorothiazide (Microzide, HCTZ), metolazone (Zaroxolyn), torsemide (Demadex), triamterene (Dyrenium, Dyazide, Maxzide)
• Medications that can prolong the QTc interval such as:
  • certain antiarrhythmic medications such as procainamide, sotalol (Betapace), quinidine, dofetilide (Tikosyn), amiodarone (Nexterone, Pacerone, Cordarone), ibutilide (Corvert)
  • certain fluoroquinolone antibiotics such as levofloxacin (Levaquin), ciprofloxacin (Cipro), gatifloxacin (Zymar), moxifloxacin (Avelox)
  • certain macrolide antibiotics such as clarithromycin (Biaxin) and erythromycin (EES)

This is not a complete list of Utibron Neohaler drug interactions. Ask your doctor or pharmacist for more information.

• It is used to treat COPD (chronic obstructive pulmonary disease).
• This medicine is not to be used to treat intense flare-ups of shortness of breath. Use a rescue inhaler. Talk with the doctor.

• Tell all of your health care providers that you take Utibron Neohaler. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• Do not get Utibron Neohaler powder in your eyes. Side effects like eye pain or redness, blurred eyesight, or other eyesight problems may happen. Call your doctor right away if you have any of these signs.
• Call your doctor right away if your breathing problems get worse, if your rescue inhaler does not work as well, or if you need to use your rescue inhaler more often.
• If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
• Check your blood sugar as you have been told by your doctor.
• Do not take more of this medicine or use it more often than you have been told. Deaths have happened when too much of this type of drug has been taken. Talk with your doctor.
• If you are 75 or older, use Utibron Neohaler with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Utibron Neohaler is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Utibron Neohaler or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Utibron Neohaler. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

     Asthma-Related Death [see Boxed Warning]

• Data from a large, placebo-controlled U.S. study in asthma patients showed that LABAs may increase the risk of asthma-related death. Data are not available to determine whether the rate of death in patients with COPD is increased by LABAs.
• A 28-week, placebo-controlled U.S. study comparing the safety of another LABA (salmeterol) with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol versus 3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34). The increased risk of asthma-related death is considered a class effect of the LABAs, including indacaterol, one of the ingredients in Utibron Neohaler.
• No study adequate to determine whether the rate of asthma-related death is increased in patients treated with Utibron Neohaler has been conducted. The safety and efficacy of Utibron Neohaler in patients with asthma have not been established. Utibron Neohaler is not indicated for the treatment of asthma.

     Deterioration of Disease and Acute Episodes

Utibron Neohaler should not be initiated in patients with acutely deteriorating or potentially life-threatening episodes of COPD. Utibron Neohaler has not been studied in patients with acutely deteriorating COPD. The initiation of Utibron Neohaler in this setting is not appropriate.

Utibron Neohaler should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Utibron Neohaler has not been studied in the relief of acute symptoms, and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.

When beginning Utibron Neohaler, patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief of acute respiratory symptoms. When prescribing Utibron Neohaler, the healthcare provider should also prescribe an inhaled, short-acting beta2-agonist and instruct the patient on how it should be used. Increasing inhaled beta2-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated.

COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If Utibron Neohaler no longer controls the symptoms of bronchoconstriction; the patient’s inhaled, short-acting beta2-agonist becomes less effective; or the patient needs more inhalation of short-acting beta2-agonist than usual, these may be markers of deterioration of disease. In this setting, a re-evaluation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dose of Utibron Neohaler beyond the recommended dose is not appropriate in this situation.

     Excessive Use of Utibron Neohaler and Use with Other Long-Acting Beta2-Adrenergic Agonists

As with other inhaled drugs containing beta2-adrenergics, Utibron Neohaler should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using Utibron Neohaler should not use another medicine containing a LABA for any reason [see Drug Interactions (7.1)].

     Paradoxical Bronchospasm

As with other inhaled medicines, Utibron Neohaler can produce paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs following dosing with Utibron Neohaler, it should be treated immediately with an inhaled, short-acting bronchodilator; Utibron Neohaler should be discontinued immediately and alternative therapy instituted.

     Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions have been reported after administration of indacaterol or glycopyrrolate, the components of Utibron Neohaler. If signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of tongue, lips and face), urticaria, or skin rash, Utibron Neohaler should be discontinued immediately and alternative therapy instituted. Utibron Neohaler should be used with caution in patients with severe hypersensitivity to milk proteins.

     Cardiovascular Effects

Indacaterol, like other beta2-agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms. If such effects occur, Utibron Neohaler may need to be discontinued. In addition, beta-agonists have been reported to produce ECG changes, such as flattening of the T-wave, prolongation of the QTc interval, and ST segment depression, although the clinical significance of these findings is unknown.

Therefore, Utibron Neohaler should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

     Coexisting Conditions

Utibron Neohaler, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to sympathomimetic amines. Doses of the related beta2-agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.

     Worsening of Narrow-Angle Glaucoma

Utibron Neohaler should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

     Worsening of Urinary Retention

Utibron Neohaler should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

     Hypokalemia and Hyperglycemia

Beta2-adrenergic agonists may produce significant hypokalemia in some patients, which has the potential to produce adverse cardiovascular effects [see Clinical Pharmacology (12.2)]. The decrease in serum potassium is usually transient, not requiring supplementation. Inhalation of high doses of beta2-adrenergic agonists may produce increases in plasma glucose.

In patients with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant treatment [see Drug Interactions (7.2)], which may increase the susceptibility for cardiac arrhythmias.

In 2 clinical trials of 12-weeks duration evaluating Utibron Neohaler in subjects with COPD, there was no evidence of a treatment effect on serum glucose or potassium.

     Pregnancy

Teratogenic Effects: Pregnancy Category C

There are no adequate and well-controlled studies with Utibron Neohaler or its individual components, indacaterol and glycopyrrolate, in pregnant women. Animal reproduction studies were conducted with individual components, indacaterol and glycopyrrolate. Because animal reproduction studies are not always predictive of human response, Utibron Neohaler should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physician if they become pregnant while taking Utibron Neohaler.

Indacaterol: Indacaterol was not teratogenic in Wistar rats and New Zealand rabbits at approximately 340 and 770 times, respectively, the MRHD in adults (on an AUC basis at maternal subcutaneous doses up to 1 mg/kg/day in rats and rabbits).

Glycopyrrolate: Glycopyrrolate was not teratogenic in Wistar rats or New Zealand White rabbits at approximately 1400 and 530 times, respectively, the MRHD in adults (on an AUC basis at maternal inhaled doses up to 3.83 mg/kg/day in rats and up to 4.4 mg/kg/day in rabbits).

Non-teratogenic Effects:

Indacaterol: There were no effects on perinatal and postnatal developments in rats at approximately 110 times the MRHD in adults (on an AUC basis at maternal subcutaneous doses up to 0.3 mg/kg/day).

Glycopyrrolate: There were no effects on perinatal and postnatal developments in rats at approximately 1100 times the MRHD in adults (on an AUC basis at maternal subcutaneous doses up to 1.88 mg/kg/day).

     Labor and Delivery

There are no adequate and well-controlled human trials that have investigated the effects of Utibron Neohaler during labor and delivery. Because beta-agonists may potentially interfere with uterine contractility, Utibron Neohaler should be used during labor only if the potential benefit justifies the potential risk.

In human parturients undergoing Caesarean section, 86 minutes after a single intramuscular injection of 0.006 mg/kg glycopyrrolate, umbilical plasma concentrations were low.

     Nursing Mothers

Utibron Neohaler: It is not known whether Utibron Neohaler is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when Utibron Neohaler is administered to a nursing woman. Since there are no data from well-controlled human studies on the use of Utibron Neohaler by nursing mothers, based on the data for the individual components, a decision should be made whether to discontinue nursing or to discontinue Utibron Neohaler, taking into account the importance of Utibron Neohaler to the mother.

Indacaterol: It is not known whether indacaterol is excreted in human breast milk. Indacaterol (including its metabolites) have been detected in the milk of lactating rats.

Glycopyrrolate: It is not known whether glycopyrrolate is excreted in human breast milk. Glycopyrrolate (including its metabolites) have been detected in the milk of lactating rats and reached up to 10-fold higher concentrations in the milk than in the blood of the dam.

     Pediatric Use

Utibron Neohaler is not indicated for use in children. The safety and efficacy of Utibron Neohaler in pediatric patients have not been established.

     Geriatric Use

Based on available data, no adjustment of Utibron Neohaler dosage in geriatric patients is warranted. Utibron Neohaler can be used at the recommended dose in elderly patients 75 years of age and older.

Of the total number of subjects in clinical studies of Utibron Neohaler, 45% were aged 65 and older, while 11% were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

     Renal Impairment

Based on the pharmacokinetic characteristics of its monotherapy components, Utibron Neohaler can be used at the recommended dose in patients with mild to moderate renal impairment. In patients with severe renal impairment (estimated GFR less than 30 mL/min/1.73 m2) or end-stage renal disease requiring dialysis, Utibron Neohaler should be used if the expected benefit outweighs the potential risk since the systemic exposure to glycopyrrolate may be increased in this population [see Clinical Pharmacology (12.3)].

     Hepatic Impairment

Based on the pharmacokinetic characteristics of its monotherapy components, Utibron Neohaler can be used at the recommended dose in patients with mild to moderate hepatic impairment. Studies in subjects with severe hepatic impairment have not been performed [see Clinical Pharmacology (12.3)].

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Asthma-Related Death

Inform patients that LABAs, such as indacaterol, one of the active ingredients in Utibron Neohaler, increase the risk of asthma-related death. Utibron Neohaler is not indicated for the treatment of asthma.

Not for Acute Symptoms

Inform patients that Utibron Neohaler is not meant to relieve acute symptoms of COPD and extra doses should not be used for that purpose. Advise them to treat acute symptoms with a rescue inhaler such as albuterol. Provide patients with such medicine and instruct them on how it should be used [see Warnings and Precautions (5.2)].

Instruct patients to seek medical attention immediately if they experience any of the following:

• Symptoms get worse
• Need for more inhalations than usual of their rescue inhaler

Patients should not stop therapy with Utibron Neohaler without physician/healthcare provider guidance since symptoms may recur after discontinuation.

Do Not Use Additional Long-Acting Beta2-Agonists

Instruct patients to not use other medicines containing a LABA. Patients should not use more than the recommended twice-daily dose of Utibron Neohaler [see Warnings and Precautions (5.3)].

Instruct patients who have been taking inhaled, short-acting beta2-agonists on a regular basis to discontinue the regular use of these products and use them only for the symptomatic relief of acute symptoms.

Paradoxical Bronchospasm

Inform patients that Utibron Neohaler can produce paradoxical bronchospasm. Advise patients that if paradoxical bronchospasm occurs, patients should discontinue Utibron Neohaler.

Risks Associated with Beta2-Agonist Therapy

Inform patients of adverse effects associated with beta2-agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness. Instruct patients to consult a physician immediately should any of these signs or symptoms develop [see Warnings and Precautions (5.6)].

Worsening of Narrow-Angle Glaucoma

Instruct patients to be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop [see Warnings and Precautions (5.8)].

Worsening of Urinary Retention

Instruct patients to be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination). Instruct patients to consult a physician immediately should any of these signs or symptoms develop [see Warnings and Precautions (5.9)].

Instructions for Administering Utibron Neohaler

It is important for patients to understand how to correctly administer UTIBRON capsules using the NEOHALER device [see Instructions for Use]. Instruct patients that UTIBRON capsules should only be administered via the NEOHALER device and the NEOHALER device should not be used for administering other medications. Remind patients that the contents of UTIBRON capsules are for oral inhalation only and must not be swallowed.

Instruct patients always to store UTIBRON capsules in sealed blisters and to only remove 1 UTIBRON capsule immediately before use or it may not be as effective. Instruct patients to discard unused additional UTIBRON capsules that are exposed to air (i.e., not intended for immediate use).

Inform patients to use 1 inhalation of Utibron Neohaler orally twice-daily (1 capsule in the morning and 1 capsule in the evening) at the same time every day.

Inform patients that if they miss a dose of Utibron Neohaler, they should use their next capsule at the usual time. Instruct patients to not use 2 capsules at one time and to not use more than 2 capsules in a day.

Distributed by:
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936

© Novartis

T2017-10
January 2017

PRINCIPAL DISPLAY PANEL

NDC 0078-0664-19

UTIBRONTM NEOHALER®

(indacaterol and glycopyrrolate) inhalation powder

27.5 mcg / 15.6 mcg per capsule

60 Capsules

FOR ORAL INHALATION ONLY

Do not swallow the UtibronTM capsules

UtibronTM capsules are for use with the Neohaler® Inhaler only

PHARMACIST: Dispense with Medication Guide enclosed.

Rx only

Novartis