Bevespi Aerosphere

Bevespi Aerosphere is a prescription medicine used to treat COPD. COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Anoro Ellipta, there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Bevespi Aerosphere crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with the use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Bevespi Aerosphere.

If this medicine gets in your eyes, rinse them with water and call your doctor if you have ongoing eye redness even after rinsing.

Do not use a second form of formoterol (such as Foradil, Dulera, Perforomist, Symbicort) or use a similar other long-acting inhaled bronchodilator such as salmeterol (Advair, Serevent) or arformoterol (Brovana) unless your doctor has told you to.

• Tell all of your health care providers that you take Bevespi Aerosphere. This includes your doctors, nurses, pharmacists, and dentists.
• 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), this medicine may sometimes raise blood sugar. Talk with your doctor about how to keep your blood sugar under control.
• Do not take more of Bevespi Aerosphere 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 this medicine gets in the eyes, rinse with water right away. Call the doctor right away if Bevespi Aerosphere gets in the eyes and blurred eyesight, worsened glaucoma, or eye pain happens.
• If you are 65 or older, use this medicine 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 Bevespi Aerosphere while you are pregnant.

Inhalation Aerosol: Bevespi Aerosphere is a pressurized metered dose inhaler that delivers 9 mcg of glycopyrrolate and 4.8 mcg of formoterol fumarate per inhalation. Two inhalations equal one dose. Bevespi Aerosphere contains 28 or 120 inhalations per canister. The canister has an attached dose indicator and is supplied with a white plastic actuator with an orange dust cap.

. Pregnancy

Teratogenic Effects: 

Pregnancy Category C. There are no adequate and well-controlled trials of Bevespi Aerosphere or its individual components, glycopyrrolate and formoterol fumarate, in pregnant women. Because animal reproduction studies are not always predictive of human response, Bevespi Aerosphere should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking Bevespi Aerosphere.

Glycopyrrolate: There was no evidence of teratogenic effects in rats and rabbits at approximately 18,000 and 270 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults (on a mg/m2 basis at a maternal oral dose of 65 mg/kg/day in rats and at a maternal intramuscular injection dose of 0.5 mg/kg in rabbits).

Single-dose studies in humans found that very small amounts of glycopyrrolate passed the placental barrier.

Formoterol Fumarate: Formoterol fumarate has been shown to be teratogenic, embryocidal, to increase pup loss at birth and during lactation, and to decrease pup weights in rats and teratogenic in rabbits. These effects were observed at approximately 1,500 (rats) and 61,000 (rabbits) times the MRHDID (on a mg/m2 basis at maternal oral doses of 3 mg/kg/day and above in rats and 60 mg/kg/day in rabbits). Umbilical hernia was observed in rat fetuses at approximately 1,500 times the MRHDID (on a mg/m2 basis at maternal oral doses of 3 mg/kg/day and above). Prolonged pregnancy and fetal brachygnathia was observed in rats at approximately 7600 times the MRHDID (on a mg/m2 basis at an oral maternal dose of 15 mg/kg/day in rats). In another study in rats, no teratogenic effects were seen at approximately 600 times the MRHDID (on a mg/m2 basis at maternal inhalation doses up to 1.2 mg/kg/day in rats).

Subcapsular cysts on the liver were observed in rabbit fetuses at an oral dose approximately 61,000 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 60 mg/kg/day in rabbits). No teratogenic effects were observed at approximately 3600 times the MRHDID (on a mg/m2 basis at maternal oral doses up to 3.5 mg/kg/day).

. Labor and Delivery

There are no well-controlled human trials that have investigated the effects of Bevespi Aerosphere on preterm labor or labor at term. Because beta2-agonists may potentially interfere with uterine contractility, Bevespi Aerosphere should be used during labor only if the potential benefit justifies the potential risk.

. Nursing Mothers

It is not known whether Bevespi Aerosphere is excreted in human milk. Because many drugs are excreted in human milk and because formoterol fumarate, one of the active ingredients in Bevespi Aerosphere, has been detected in the milk of lactating rats, caution should be exercised when Bevespi Aerosphere is administered to a nursing woman. Since there are no data from controlled trials on the use of Bevespi Aerosphere by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue Bevespi Aerosphere, taking into account the importance of Bevespi Aerosphere to the mother.

. Pediatric Use

Bevespi Aerosphere is not indicated for use in children. The safety and effectiveness of Bevespi Aerosphere in the pediatric population have not been established.

. Geriatric Use

Based on available data, no adjustment of the dosage of Bevespi Aerosphere in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out.

The confirmatory trials of Bevespi Aerosphere for COPD included 1,680 subjects aged 65 and older and, of those, 290 subjects were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

. Hepatic Impairment

Formal pharmacokinetic studies using Bevespi Aerosphere have not been conducted in patients with hepatic impairment. However, since formoterol fumarate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of formoterol fumarate in plasma. Therefore, patients with hepatic disease should be closely monitored.

. Renal Impairment

Formal pharmacokinetic studies using Bevespi Aerosphere have not been conducted in patients with renal impairment. In patients with severe renal impairment (creatinine clearance of ≤30 mL/min/1.73 m2) or end-stage renal disease requiring dialysis, Bevespi Aerosphere should be used if the expected benefit outweighs the potential risk [see Clinical Pharmacology (12.3)].

Bevespi Aerosphere (glycopyrrolate and formoterol fumarate) Inhalation Aerosol is a pressurized metered-dose inhaler that contains a combination of micronized glycopyrrolate, an anticholinergic, and micronized formoterol fumarate, a long-acting beta2-adrenergic agonist, for oral inhalation. 

Glycopyrrolate is a quaternary ammonium salt with the following chemical name: (RS)-[3-(SR)-Hydroxy-1,1-dimethylpyrrolidinium bromide] α-cyclopentylmandelate. Glycopyrrolate is a powder that is freely soluble in water. The molecular formula is C19H28BrNO3, and the molecular weight is 398.33 g/mol. The structural formula is as follows:

Glycopyrrolate contains two chiral centers (denoted by * in structure above) and is a racemate of a 1:1 mixture of the R,S and S,R diastereomers. The active moiety, glycopyrronium, is the positively charged ion of glycopyrrolate.

Formoterol fumarate has the chemical name N-[2-Hydroxy-5-[(1RS)-1-hydroxy-2-[[(1RS)-2-(4-methoxyphenyl)-1- methylethyl]-amino] ethyl]phenyl] formamide, (E)-2-butenedioate dihydrate. Formoterol fumarate is a powder that is slightly soluble in water. The molecular formula is (C19H24N2O4)2.C4H4O4.2H2O and the molecular weight is 840.91 g/mol. The structural formula is as follows: 

Formoterol fumarate contains two chiral centers (denoted by * in structure above), and consists of a single enantiomeric pair (a racemate of R,R and S,S).

Bevespi Aerosphere is formulated as a hydrofluoroalkane (HFA 134a) propelled pressurized metered dose inhaler containing 28 or 120 inhalations. The canister has an attached dose indicator and is supplied with a white plastic actuator body and mouthpiece with an orange dust cap.

After priming each actuation of the inhaler meters 10.4 mcg of glycopyrrolate (equivalent to 8.3 mcg of glycopyrronium) and 5.5 mcg of formoterol fumarate from the valve which delivers 9 mcg of glycopyrrolate (equivalent to 7.2 mcg of glycopyrronium) and 4.8 mcg of formoterol fumarate from the actuator. The actual amount of drug delivered to the lung may depend on patient factors, such as the coordination between actuation of the device and inspiration through the delivery system. Bevespi Aerosphere also contains porous particles that form a cosuspension with the drug crystals. The porous particles are comprised of the phospholipid, 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC), and calcium chloride. Porous particles and HFA 134a are excipients in the formulation.

Priming Bevespi Aerosphere is essential to ensure appropriate drug content in each actuation. Prime Bevespi Aerosphere before using for the first time. To prime Bevespi Aerosphere, release 4 sprays into the air away from the face, shaking well before each spray.

If the product is not used for more than 7 days re-prime the device. To re-prime Bevespi Aerosphere, release 2 sprays into the air away from the face, shaking well before each spray.

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

Formoterol and glycopyrrolate 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.

Formoterol 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.

Formoterol and glycopyrrolate may also be used for purposes not listed in this medication guide.

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

You should not use this medicine if you are allergic to formoterol or glycopyrrolate. Formoterol and glycopyrrolate is for use only in people with COPD and should not be used to treat asthma.

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

• heart disease;
• high blood pressure;
• liver disease;
• diabetes;
• epilepsy or other seizure disorder;
• glaucoma;
• a thyroid disorder;
• bladder obstruction or other urination problems;
• an enlarged prostate; or
• any food or drug allergies.

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

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

Formoterol and glycopyrrolate is not approved for use by anyone younger than 18 years old.

You should not use Bevespi Aerosphere if you are allergic to formoterol or glycopyrrolate. Bevespi is for use only in people with COPD and should not be used to treat asthma.

To make sure Bevespi Aerosphere is safe for you, tell your doctor if you have:

• heart disease;

• high blood pressure;

• liver disease;

• diabetes;

• epilepsy or other seizure disorder;

• glaucoma;

• a thyroid disorder;

• bladder obstruction or other urination problems;

• an enlarged prostate; or

• any food or drug allergies.

It is not known whether Bevespi Aerosphere will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using Bevespi.

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

Bevespi Aerosphere is not approved for use by anyone younger than 18 years old.

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

Get emergency medical help if you have signs of an allergic reaction to Bevespi Aerosphere: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• wheezing, choking, or other breathing problems after using this medicine;

• new or worsening shortness of breath;

• chest pain;

• fast or irregular heartbeats;

• painful or difficult urination;

• pain or burning when you urinate;

• tremors or feeling nervous;

• blurred vision, tunnel vision, eye pain, or seeing halos around lights;

• high blood sugar - increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or

• low potassium - leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common Bevespi side effects may include:

• cough; or

• urination problems.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to formoterol / glycopyrrolate: inhalation aerosol powder

Along with its needed effects, formoterol / glycopyrrolate may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking formoterol / glycopyrrolate:

• Bladder pain
• bloody or cloudy urine
• chest pain
• cough
• difficult, burning, or painful urination
• frequent urge to urinate
• lower back or side pain

• Blindness
• blurred vision
• decrease in the frequency of urination
• decrease in urine volume
• decreased vision
• difficulty with breathing
• dizziness
• eye pain
• fainting
• headache
• hives or welts, itching, or skin rash
• irregular heartbeat
• nausea or vomiting
• nervousness
• noisy breathing
• pounding in the ears
• recurrent large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• redness of the skin
• slow or fast heartbeat
• tearing
• tightness in the chest

Some side effects of formoterol / glycopyrrolate may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Difficulty with moving
• dry mouth
• fear
• fever
• muscle pain or stiffness
• muscle spasm
• pain in the arms or legs
• pain in the joints
• pain or tenderness around the eyes and cheekbones
• sore throat
• stuffy or runny nose
• unusual tiredness or weakness